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The hidden curriculum of unspoken professional expectations negatively impacts medical student interest in surgery. Medical student mentorship and early surgical exposure have been shown to demystify the hidden curriculum. Although residents and faculty play a vital role, near-peer mentorship may aid in uncovering the hidden curriculum and promoting medical student interest in surgery, especially for those learners who are underrepresented in medicine. We developed and implemented a formalized near-peer mentorship program composed of quarterly small group Surgical Peer Teacher led lessons and one-on-one Surgical Support Team mentorship meetings covering surgical curriculum topics for medical students at an academic medical school. This structured near-peer mentorship model provides a mechanism to demystify surgical culture, increase early access to surgical mentorship, and develop mentorship skills amongst students. This program aims to uncover the surgical hidden curriculum to improve surgical career support and interest among medical students with less exposure and access to physician role models. This longitudinal mentorship model is student-run and can be easily adapted to enhance existing support models at medical schools. Future studies will evaluate utilization, impact on surgical specialty interest, and efficacy in demystifying the surgical hidden curriculum.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

The identification of lattice multiphases in TiO2 nanocrystals is studied by high resolution transmission electron microscope and electron diffraction patterns. Based on the spectroscopic analysis using soft x-ray absorption and resonant inelastic soft x-ray scattering, it is believed that the oxygen vacancies at the interface exhibit structural distortion of the TiO68−cluster around the defect site as for the multiphase lattice. We elucidate that the extra 3d electrons nearby induce the inelastic scattering features with the excitation energy dependence owing to different energy relaxation processes, a characteristic of the electron-phonon coupling or the nature of the electron-hole pair at the intermediate state. The manifold dd excitations driven by the strong interaction between Ti-3d and O-2p electrons are noticeably rich, coexisting on both Ti and O sites. This sophisticated experiment can advance the perspective of nanocomposite TiO2 for various interactions of surface Ti3+ in applications of future devices.

Yan-Bin Liu,1 Li-Juan Zuo,2 Ya-Chao Liu,1 Yan-Ping Li,1 Yun-Chao Xin,1 Hong-Yan Zhang,3 Li-Yuan Hou4 1Department of ENT & HN Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 2Department of Endocrine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 3Departmentof Psychiatry, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 4Department of Nuclear Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of ChinaCorrespondence: Yan-Bin Liu, Department of ENT & HN Surgery, The First Affiliated Hospital of Hebei North University, No. 12, Changqing Street, Qiaoxi District, Zhangjiakou, Hebei, 075000, People’s Republic of China, Email liuyanbin19830524@163.comObjective: This study aimed to design a standard method of psychological intervention and evaluate the effect of such psychological intervention against the psychological distress of differentiated thyroid cancer (DTC) patients in the treatment with radioactive iodine.Methods: The enrolled patients were randomly divided into the intervention group and the control group. Both the patients in the 2 groups received the routine nursing care, while the patients in the intervention group also received the additional standard psychological interventions. The questionnaires including patient health questionnaire-9 (PHQ-9), generalized anxiety disorder 7-item (GAD-7), cancer fatigue scale (CFS) and positive and negative affect schedule (PANAS) were used to assess psychological status. These questionnaires were performed at week 0 (T0), week 8 (T1, immediately after the last time of intervention) and week 24 (T2, 16 weeks after the intervention).Results: PHQ-9, GAD-7, CFS and Negative Affect (NA) scores measured at T1 and T2 in the intervention group were significantly lower than those in the control group (P < 0.001). And intervention group also had higher positive affect (PA) scores at T1 and T2 (P < 0.001). Furthermore, the changes of PHQ-9, GAD-7, CFS, PA and NA scores from T0 to T1 and T0 to T2 were more evident in the intervention group than in the control group.Conclusion: Psychological intervention could significantly improve psychological distress of DTC patients in the treatment with radioactive iodine.Keywords: differentiated thyroid cancer, radioactive iodine, psychological intervention, psychological distress, mood

At the Fermilab Tevatron proton-antiproton (pp¯) collider, high-mass electron-neutrino (eν) pairs are produced predominantly in the process pp¯→W(→eν)+X. The asymmetry of the electron and positron yield as a function of their pseudorapidity constrain the slope of the ratio of the u- to d-quark parton distributions versus the fraction of the proton momentum carried by the quarks. This paper reports on the measurement of the electron-charge asymmetry using the full data set recorded by the Collider Detector at Fermilab in 2001-2011 and corresponding to 9.1 fb-1 of integrated luminosity. The measurement significantly improves the precision of the Tevatron constraints on the parton-distribution functions of the proton. Numerical tables of the measurement are provided.

IntroductionThe impact of COVID-19 on surgical education has been profound, and clinical learning experiences transitioned to virtual formats. This study investigated the impact of virtual experiences created to facilitate learning during the pandemic for medical students.MethodsWe performed a cohort study to determine the perceived clinical preparedness for medical students enrolled in the preclinical surgery pilot course, surgical Extended Mastery Learning Rotation (EMLR), and longitudinal surgical clerkship (LC). The preclinical surgery pilot course took place before COVID-19 disruptions, and the EMLR and LC experiences took place virtually. Specialty choice was examined in the EMLR and LC cohorts. Performance on the NBME surgical assessments was analyzed among students enrolled in the traditional clerkship and pandemic-disrupted courses and compared to national data using a two-sample t-test.ResultsCompared to preclinical students, EMLR and LC students demonstrated improvements in their perceived surgical clerkship readiness. After the 3-week EMLR course, in the setting of completing only one-third of the clerkship year, students had an average NBME Surgical Self-Assessment Exam score of 72 (SD 12), comparable to the national average of 71 (SD 9) p = 0.33. The average shelf exam score for students (N = 24) enrolled in the traditional clerkship (block 1), prior to COVID-19, disruptions was 66 (SD 9) compared to an average score of 69 (SD 9) for the longitudinal clerkship students (N = 20) that took the shelf exam later in the year (p = 0.36). COVID-19 disruptions did not affect specialty choice. All LC students have decided on a specialty; 50% nonsurgical and 50% surgical. From the EMLR cohort, 36% and 38% plan to pursue surgical and nonsurgical specialties, respectively, with 26% still undecided.ConclusionsCourses were well-liked and will be implemented in future clerkships. Surgical educators demonstrated flexibility and creativity in the development of the EMLR. Despite COVID-19 disruptions, medical students made progress in their clinical skills and foundational science knowledge. COVID-19 disruptions did not appear to impact specialty choice.

X-ray crystallography is the gold standard to resolve conformational ensembles that are significant for protein function, ligand discovery, and computational methods development. However, relevant conformational states may be missed at common cryogenic (cryo) data-collection temperatures but can be populated at room temperature. To assess the impact of temperature on making structural and computational discoveries, we systematically investigated protein conformational changes in response to temperature and ligand binding in a structural and computational workhorse, the T4 lysozyme L99A cavity. Despite decades of work on this protein, shifting to RT reveals new global and local structural changes. These include uncovering an apo helix conformation that is hidden at cryo but relevant for ligand binding, and altered side chain and ligand conformations. To evaluate the impact of temperature-induced protein and ligand changes on the utility of structural information in computation, we evaluated how temperature can mislead computational methods that employ cryo structures for validation. We find that when comparing simulated structures just to experimental cryo structures, hidden successes and failures often go unnoticed. When using structural information in ligand binding predictions, both coarse docking and rigorous binding free energy calculations are influenced by temperature effects. The trend that cryo artifacts limit the utility of structures for computation holds across five distinct protein classes. Our results suggest caution when consulting cryogenic structural data alone, as temperature artifacts can conceal errors and prevent successful computational predictions, which can mislead the development and application of computational methods in discovering bioactive molecules.

Devastating Japan in October 2019, Supertyphoon (STY) Hagibis was an important typhoon in the history of the Pacific. A striking feature of Hagibis was its explosive rapid intensification (RI). In 24 h, Hagibis intensified by 100 knots (kt; 1 kt ≈ 0.51 m s-1), making it one of the fastest-intensifying typhoons ever observed. After RI, Hagibis's intensification stalled. Using the current typhoon intensity record holder, i.e., STY Haiyan (2013), as a benchmark, this work explores the intensity evolution differences of these two high-impact STYs. We found that the extremely high prestorm sea surface temperature reaching 30.5°C, deep/warm prestorm ocean heat content reaching 160 kJ cm-2, fast forward storm motion of ∼8 m s-1, small during-storm ocean cooling effect of ∼0.5°C, significant thunderstorm activity at its center, and rapid eyewall contraction were all important contributors to Hagibis's impressive intensification. There was 36% more air-sea flux for Hagibis's RI than for Haiyan's. After its spectacular RI, Hagibis's intensification stopped, despite favorable environments. Haiyan, by contrast, continued to intensify, reaching its record-breaking intensity of 170 kt. A key finding here is the multiple pathways that storm size affected the intensity evolution for both typhoons. After RI, Hagibis experienced a major size expansion, becoming the largest typhoon on record in the Pacific. This size enlargement, combined with a reduction in storm translational speed, induced stronger ocean cooling that reduced ocean flux and hindered intensification. The large storm size also contributed to slower eyewall replacement cycles (ERCs), which prolonged the negative impact of the ERC on intensification.

Ya-Chun Liao,1 Yao-Ting Huang,2,&ast; Chien-Hao Tseng,1 Chia-Wei Liu,1 Po-Yu Liu1,3,4,&ast; 1Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Computer Science and Information Engineering, National Chung Cheng University, Chiayi, Taiwan; 3Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung, Taiwan; 4Genome Center for Infectious Diseases, Taichung Veterans General Hospital, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Po-Yu Liu, Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Xitun District, Taichung, Taiwan, Tel +886-4-2359-2525, Fax +886-4-2359-5046, Email pyliu@vghtc.gov.twPurpose: Burkholderia cepacia complex (Bcc) is a known significant opportunistic pathogen causing morbidity and mortality, particularly in those with cystic fibrosis, chronic granulomatous disease, or immunocompromising host. Mortality of Bcc bloodstream infections among non-cystic fibrosis patients remained high. The antibiotic treatment for Bcc infection is quite challenging due to its intrinsic resistance to most antibiotics, and the resistance to carbapenems was the biggest concern among them. We aimed to realize the mechanism of carbapenem resistance in Bcc.Patients and Methods: Ten strains of Bcc were identified by the MALDI-TOF MS, and the drug susceptibility test was using VITEK 2 system. The Burkholderia cepacia complex genomes were sequenced via Nanopore GridIon. We also downloaded another ninety-five strains of Bcc from the National Center for Biotechnology Information database to evaluate the divergence between carbapenem-resistance and carbapenem-sensitive strains.Results: The genetic organization between carbapenem-sensitive and carbapenem-resistant strains of Bcc showed no difference. However, in the carbapenem-sensitive strain, E151V substitution in PenR was detected. In addition, a novel specific OXA family subgroup, blaOXA-1043 in Burkholderia cenocepacia was discovered.Conclusion: The E151V substitution in PenR may be associated with carbapenem-sensitive in Bcc. Moreover, the V151E mutation in PenR may be related to the activation of PenB, leading to Bcc resistance to carbapenems. Besides, a novel OXA family subgroup, blaOXA-1043, was found in Burkholderia cenocepacia, which differs from the previous OXA family.Keywords: Burkholderia cepacia complex, Burkholderia cenocepacia, carbapenem-resistant, whole-genome sequencing

Yu Lee,1 Pao-Yen Lin,1 Yu-Chi Huang,1 Nien-Mu Chiu,1 Chi-Fa Hung,1 Liang-Jen Wang2 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanCorrespondence: Liang-Jen Wang, Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial, Hospital, No. 123, Ta-Pei Road, Kaohsiung City, Taiwan, Tel +886-7-7317123 ext. 8753, Fax +886-7-7326817, Email wangliangjen@gmail.comObjective: Depressive disorder significantly impacts patients’ daily living activities and quality of life. Caregivers of patients with depression may also suffer from psychological distress related to the chronic burden of caring for the patient’s mood changes. The purpose of this study was to evaluate the morbidity and associated factors of depression in caregivers of patients with depressive disorder.Methods: In this study, we used a cross-sectional design with consecutive sampling. Study subjects were recruited from the psychiatric outpatient clinic of a medical center from August 2021 to June 2022. Caregivers of depressive disorder patients were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale (HADS), Suicide Assessment Scale (SAS), Stigma Scale of the Explanatory Model Interview Catalogue (EMIC), and Family APGAR Index.Results: Of the 120 caregivers that completed the study, 59.2% (n=71) were females. The most common psychiatric diagnosis was depressive disorders (25.8%), followed by anxiety disorders (17.5%) and insomnia disorder (15.8%); 54.2% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, we found that anxiolytics/hypnotics use (OR=5.58; 95% CI, 1.84– 16.96; p< 0.01), higher suicide risk (SAS) (OR=1.10; 95% CI, 1.05– 1.16; p< 0.001), and lower family support (APGAR scores) (OR=0.82; 95% CI, 0.71– 0.94; p< 0.01) were three significant associated factors.Conclusion: Depression was the most prevalent psychiatric diagnosis in caregivers of patients with depressive disorder. Early psychiatric diagnosis for caregivers of patients with depression is crucial to offering suitable support and treatment and may improve caregivers’ quality of life.Keywords: depression, morbidity, associated factor, caregiver

Ya Xin Zhang,1– 3,&ast; Zhi Yuan Shen,1– 3,&ast; Yi Cun Jia,1– 3 Xin Guo,1– 3 Xiao Su Guo,1– 3 Yuan Xing,1– 3 Shu Juan Tian1– 3 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei Hospital, Xuanwu Hospital, Capital Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu Juan Tian; Yuan Xing, Department of Neurology, The First hospital of Hebei Medical University, Shijiazhuang, Hebei, 050030, People’s Republic of China, Email jtian72@126.com; leaf_trunks@163.comBackground and Purpose: The aim of this study was to explore the relationship between functional prognosis and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic inflammatory response index (SIRI) in patients with acute ischemic stroke (AIS) at discharge.Methods: A total of 861 patients with AIS were enrolled between January 2019 and December 2021. Blood cell counts were collected on admission. Logistic regression analysis was performed to assess the relationship between NLR, PLR, LMR, SIRI and adverse functional outcomes (modified Rankin scale score of 3– 6) at discharge. We also used receiver operating characteristic (ROC) curves to estimate the overall ability of NLR, PLR, LMR and SIRI to judge short-term functional outcomes. Associations between NLR, PLR, LMR, and SIRI with length of hospital stay were analyzed by Spearman correlation test.Results: A total of 194 patients (22.5%) had poor functional outcomes at discharge. Multivariate logistic regression analysis showed that NLR (odds ratio [OR], 1.060; 95% confidence interval [CI] 1.004– 1.120, P=0.037), PLR (OR, 1.003; 95% CI 1.000– 1.005, P=0.018), LMR (OR, 0.872; 95% CI 0.774– 0.981, P=0.023) and SIRI (OR, 1.099; 95% CI 1.020– 1.184, P=0.013) were independent factors for poor functional outcome. The odds ratios of the highest versus lowest quartiles of NLR, PLR and SIRI were 2.495 (95% CI 1.394– 4.466), 1.959 (95% CI 1.138– 3.373) and 1.866 (95% CI 1.106– 3.146), respectively. The odds ratio of the lowest versus highest quartile of LMR was 2.300 (95% CI 1.331– 3.975). The areas under the curve (AUCs) of the NLR, PLR, LMR, and SIRI to discriminate poor functional prognosis were 0.644, 0.587, 0.628, and 0.651, respectively. NLR, LMR, and SIRI were related with the length of hospital stay (P< 0.05).Conclusion: NLR, PLR, LMR, and SIRI were associated with functional outcome at discharge in AIS patients. NLR, LMR and SIRI were related to hospitalization days in patients with AIS.Keywords: acute ischemic stroke, short-term functional outcome, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic inflammatory response index

Yi-Chun Hsiao,1,&ast; Pei-Yi Shen,1,&ast; Li-Ting Wong,2 Ming-Cheng Chan,3,4 Wen-Cheng Chao3– 6 1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 5Big Data Center, Chung Hsing University, Taichung, Taiwan; 6Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Wen-Cheng Chao, Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung City, 40705, Taiwan, Email cwc081@hotmail.comObjective: Absolute lymphocyte count (ALC) has been implicated with short-term outcomes in a number of diseases, and we aimed to investigate the association between week-one ALC and long-term mortality in patients who were admitted to the medical intensive care units (ICUs).Methods: We enrolled patients who were admitted to the medical ICUs at the Taichung Veterans General Hospital, a referral centre located in central Taiwan, between 2015 and 2020 to conduct this retrospective cohort study. The outcome of interest was long-term all-cause mortality, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the association. Furthermore, we employed propensity score-matching (PSM) and weighting techniques, consisting of inverse probability of treatment weighting (IPTW) and covariate balancing propensity score (CBPS), to confirm the association between ALC and mortality.Results: A total of 5722 critically ill patients were enrolled, and the one-year mortality was 44.8%. The non-survivor group had a lower ALC (1549, 1027– 2388 vs 1948, 1373– 2743 counts/μL, p< 0.01) compared with those in the survivor group. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.091, 95% CI 1.050– 1.134). Propensity score-based analyses demonstrated the robust association, with adjHRs in the original, PSM, IPTW, and CBPS populations of 1.327 (95% CI 1.224– 1.438), 1.301 (95% CI 1.188– 1.424), 1.292 (95% CI 1.186– 1.407), and 1.297 (95% CI 1.191– 1.412), respectively. Sensitivity analyses further showed that the association between low ALC and mortality existed in a dose-response manner.Conclusion: We found that low ALC was associated with long-term mortality in critically ill patients; further studies are warranted to validate and translate these findings into clinical utility.Keywords: absolute lymphocyte counts, critical illness, mortality, long-term outcome, propensity score

Xulin Liao,1,2 Chu Qi Li,1 Qian Min Ge,1 Li Ying Tang,3 Ting Su,4 Qiu Yu Li,1 Yi Cong Pan,1 Hui Ye Shu,1 Li Juan Zhang,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China; 4Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USACorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comPurpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients.Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity.Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients’ anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus.Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.Keywords: herpes zoster keratitis, resting-state functional magnetic resonance imaging, brain activity patterns, brain region, the percent amplitude of fluctuation

Yang-Chun Du,1,2,&ast; Dan Jiang,3,&ast; Ji Wu1 1Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Ultrasound, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning, 530021, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, No. 6 of Shuangyong Road, Qingxiu District, Nanning, 530021, People’s Republic of China, Tel +86 13978862109, Email gxnnwuji@163.comBackground: The presence and extent of severity of esophageal varices (EV) in patients with liver cirrhosis (LC) are predicted using noninvasive clinical, biochemical, and imaging parameters. The aim of this study was to investigate the accuracy of noninvasive predictors of EV, such as the platelet count-to-spleen diameter ratio (PSR), platelet count-to-spleen volume ratio (PSVR), spleen size (SZ), and a combination of these markers in determining the severity of EV in patients with cirrhosis.Methods: We recruited 82 inpatients with LC from the Department of Gastroenterology at the First Affiliated Hospital of Guangxi Medical University between January 2018 and December 2019 for this diagnostic investigation. All patients underwent endoscopy, ultrasound, computed tomography, and routine laboratory investigations. For the study, we evaluated and compared the diagnostic accuracy of PSR, PSVR, SZ, and their combinations.Results: There were significant differences in the area under the receiver operating characteristic (ROC) curve (AUC) in the prediction of severe and moderate/severe EV for all the variables. PSR+PSVR had the highest AUC at 0.735 (95% CI: 0.626– 0.826) and 0.765 (95% CI: 0.659– 0.852) for predicting severe and moderate/severe EV, respectively. There were statistically significant differences in the AUCs (95% CI) for PSR, PSVR, and PSR+PSVR in predicting the existence of EV. As per the overall model quality chart, the combination of PSR+PSVR was the best indicator for detecting the presence of EV (AUC, 0.696; 95% CI: 0.584– 0.792).Conclusion: In our study, we found that these noninvasive parameters could predict the extent of severity of EV in patients with LC. We anticipate the use of a combination of PSR + PSVR to emerge as the superior indicator as studies progress.Keywords: esophageal varices, liver cirrhosis, noninvasive predictors, platelet count-to-spleen diameter ratio, platelet count-to-spleen volume ratio, spleen size

Yin-Han Wang,1 Tsung-Ming Yang,2,3 Ming-Szu Hung,2– 4 Yu-Ching Lin,2– 4 Tien-Pei Fang,1,3 Tzu-Tzu Kuo,5,&ast; Mark D Griffiths,6 Chung-Ying Lin7– 10,&ast; 1Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 3Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 4Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Division of Respiratory Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 6International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 7Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Tel +886-6-2353535 ext. 5106, Fax +886-6-2367981, Email cylin36933@gmail.com Tzu-Tzu Kuo, Division of Respiratory Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan, Email ed101231@gmail.comPurpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties.Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA).Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06).Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.Keywords: adherence, confirmatory factor analysis, COPD, psychometrics

Introduction: Compartment syndrome complicating intramedullary nailing of closed tibia fractures has been described as early as the 1980s, but currently remains less described in literature compared to compartment syndrome directly following trauma. This study aims to review this potentially disabling complication and highlight the importance of timely diagnosis and management of compartment syndrome following fracture fixation, not just after fracture itself, via a review of three cases. Material and methods: A retrospective study of a series of three cases was conducted. The type of fracture, wait time to fixation, surgery duration, reaming, size of nail implant used, tourniquet time, and surgical technique were recorded. Time to diagnosis of compartment syndrome, compartment pressure if available, extent of muscle necrosis, reconstructive procedures performed, and post-operative complications were analysed. Results: The three cases following high-energy trauma from road traffic accidents presented from January to May 2010. Compartment syndrome was diagnosed clinically for all cases, between one to six days post-operatively and supported by elevated compartment pressure measurements in two of the three cases. Conclusion: This study advocates thorough clinical monitoring and maintaining strong clinical suspicion of compartment syndrome in patients even after intramedullary nail fixation of tibial shaft fractures to achieve timely limb- salvaging intervention. While intercompartmental pressure can be used to aid in diagnosis, we do not advise using it in isolation to diagnose compartment syndrome. Tendon transfer improves functional mobility and provides a good result in patients with severe muscle damage, while skin grafting sufficient in patients with minimal muscle damage

Yu Hsia,1,2 Maharajan Sivasubramanian,1 Chia-Hui Chu,1 Yao-Chen Chuang,1,3 Yiu-Kay Lai,2 Leu-Wei Lo1 1Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan; 2Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan; 3Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, TaiwanCorrespondence: Leu-Wei Lo, Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Zhunan, Taiwan, Tel +886-37-206-166 Ext 37115, Fax +886-37-586-440, Email lwlo@nhri.edu.tw Yiu-Kay Lai, Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, 300044, Taiwan, Tel +866-35-742-745, Email lslyk@life.nthu.edu.twBackground: Cancer multidrug resistance (MDR) is an important factor that severely affects the chemotherapeutic efficacy. Among various methods to bypass MDR, usage of cytokines, such as tumor necrosis factor alpha (TNFα) is attractive, which exerts antitumor effects of immunotherapeutic response and apoptotic/proinflammatory pathways. Nevertheless, the challenges remain how to implement targeted delivery of TNFα to reduce toxicity and manifest the involved signaling mechanism that subdues MDR.Methods: We synthesized a multifunctional nanosytem, in which TNFα covalently bound to doxorubicin (Dox)-loaded pH-responsive mesoporous silica nanoparticles (MSN) through bi-functional polyethylene glycol (TNFα-PEG-MSN-Hydrazone-Dox) as a robust design to overcome MDR.Results: The salient features of this nanoplatform are: 1) by judicious tailoring of TNFα concentration conjugated on MSN, we observed it could lead to a contrary effect of either proliferation or suppression of tumor growth; 2) the MSN-TNFα at higher concentration serves multiple functions, besides tumor targeting and inducer of apoptosis through extrinsic pathway, it inhibits the expression level of p-glycoprotein (P-gp), a cell membrane protein that functions as a drug efflux pump; 3) the enormous surface area of MSN provides for TNFα functionalization, and the nanochannels accommodate chemotherapeutics, Dox; 4) targeted intracellular release of Dox through the pH-dependent cleavage of hydrazone bonds induces apoptosis by the specific intrinsic pathway; and 5) TNFα-PEG-MSN-Hydrazone-Dox (MSN-Dox-TNFα) could infiltrate deep into the 3D spheroid tumor model through disintegration of tight junction proteins. When administered intratumorally in a Dox-resistant mouse tumor model, MSN-Dox-TNFα exhibited a synergistic therapeutic effect through the collective performances of TNFα and Dox.Conclusion: We hereby develop and demonstrate a multifunctional MSN-Dox-TNFα system with concentration-tailored TNFα that can abrogate the drug resistance mechanism, and significantly inhibit the tumor growth through both intrinsic and extrinsic apoptosis pathways, thus making it a highly potential nanomedicine translated in the treatment of MDR tumors.Graphical Abstract: Keywords: cytokine cancer therapy, tumor necrosis factor alpha, mesoporous silica nanoparticle, pH-responsive controlled release, intrinsic/extrinsic apoptosis pathways, cancer multidrug resistance

Yu-Chen Lin,1 Wei-Yang Lee2 1Department of Psychiatry, Veteran General Hospital-Taichung, Taichung, 407, Taiwan, Republic of China; 2Department of Psychiatry, Cheng Gung Memorial Hospital, Taoyuan City, 333, Taiwan, Republic of ChinaCorrespondence: Wei-Yang Lee, Department of Psychiatry, Cheng Gung Memorial Hospital, Linkou, No. 5, Fuxing St., Guishan District, Taoyuan City, 333, Taiwan, Republic of China, Tel +886 988067722, Email wayne2859750@gmail.comPurpose: Caregivers’ responses have an impact on children’s emotional and behavioral development. The inability of caregivers to perceive their own emotions affects their responses to children. This study aims to examine the relationship between a mother’s difficulties in emotional expression and children’s emotional and behavioral disorders.Patient and Methods: A total of 78 cases, aged between 3 and 15 years old, were included in this study. The mothers completed the Taiwan version of the “Toronto Alexithymia Scale” (TAS) and “Children’s Behavior Checklist” (CBCL) questionnaires, which served as research tools. TAS consists of three factors: difficulty in distinguishing emotions (Factor 1, F1), difficulty in expressing feelings (Factor 2, F2), and an externally oriented thinking style (Factor 3, F3). CBCL represents a child’s behavior profile. The Mann–Whitney test and correlation analyses were used for follow-up analysis.Results: Our analysis revealed that F1, F2, F3, and total scores of TAS (TAS-Total) correlate positively with the somatic complaint subscale of CBCL (F1: p = 0.003; F2: p = 0.002; F3: p = 0.034, TAS-Total p=0.002). Additionally, TAS-F1 was positively correlated with the internalizing problems subscale of CBCL (p = 0.020) and the withdrawn (WD) subscale of CBCL (p = 0.044). We also found a significant association between TAS-F1 and WD of CBCL in boys alone (p = 0.022). However, we observed a negative association between TAS-F3 and the social problems subscale of CBCL in boys alone (p = 0.038).Conclusion: Mothers with alexithymic features are more likely to have children who internalize emotions, leading to withdrawal and somatic expression. Boys tend to exhibit withdrawal traits associated with internalization. This study provides initial evidence of a partial correlation between maternal alexithymia and children’s emotional and behavioral disorders, emphasizing the importance of investigating caregivers’ emotional traits for a better understanding of children’s development in the future.Keywords: maternal alexithymia, childhood behavioral disturbance, external and internal problem, children’s behavior checklist, Toronto alexithymia scale

Ching Su,1 I-Ting Tsai,1,2 Chung-Hsu Lai,2,3 Kuo-Hsuan Lin,1 Chia‐Chi Chen,2,4 Yin-Chou Hsu1,2,5– 7 1Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 4Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 5School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 6School of Medicine for International Student, I-Shou University, Kaohsiung, Taiwan; 7Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yin-Chou Hsu, Department of Emergency Medicine, E-Da Hospital, No. 1, Yida Road, Jiao-Su Village, Yan-Chao District, Kaohsiung City, 82445, Taiwan, Tel +886-7-615-0011, Fax +886-7-615-5352, Email yinchou0406@gmail.comPurpose: Klebsiella pneumoniae is an important causative pathogen of nosocomial infections, resulting in poor prognosis owing to its hypervirulence and antibiotic resistance. A simplified quicker version of the Pitt bacteremia score (PBS) (qPitt) for acute illness severity measurement was developed recently. The goal of this study was to explore the prognostic value of qPitt in patients with K. pneumoniae infection.Patients and Methods: Demographic information and management strategies were retrospectively collected from the records of all adult patients who visited the emergency department between January 1, 2021, and December 31, 2021, with culture-positive K. pneumoniae. The qPitt score was calculated based on: temperature < 36°C, systolic blood pressure ≤ 90 mmHg or vasopressor administration, respiratory rate ≥ 25 times/min or need of mechanical ventilation, altered mental status, and cardiac arrest event. The 30-day mortality prediction abilities of the qPitt were compared with the PBS, the sequential organ failure assessment (SOFA), and the quick sequential organ failure assessment (qSOFA) using receiver operating characteristic curves.Results: Data from 867 patients (57.8% men) with a mean age of 66.9 were compiled. The 30-day mortality rate of the enrolled patients was 13.4%, and the area under the curve (AUC) of the scoring systems were as follows: SOFA, 0.91 (95% confidence interval [CI]=0.89– 0.93), qPitt, 0.87 (95% CI=0.84– 0.89), PBS, 0.87 (95% CI=0.85– 0.89), and qSOFA, 0.73 (95% CI=0.70– 0.76). The AUC of qPitt was significantly higher than that of qSOFA (p< 0.01) and similar to that of PBS (p=0.65).The qPitt also demonstrated excellent mortality discrimination ability in non-bacteremic patients, AUC= 0.85 (95% CI=0.82– 0.88).Conclusion: The qPitt revealed excellent 30-day mortality prediction ability and also predicted mortality in non-bacteremic patients with K. pneumoniae infection. Clinicians can use this simplified scoring system to stratify patients earlier and initiate prompt treatment in high-risk patients.Keywords: Klebsiella pneumoniae, organ dysfunction scores, bacteremia, prognosis

Jian-Jun Xi,1,&ast; Yu Cao,1,&ast; Ruo-Yu He,1 Jian-Kang Zhang,2 Yan-Mei Zhao,1 Qiao Tong,1 Jian-Feng Bao,1 Yi-Chen Dong,3 Rang-Xiao Zhuang,1 Jin-Song Huang,1 Yongping Chen,4 Shou-Rong Liu1 1Department of Pharmacy, Hangzhou Xixi Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2School of Medicine, Zhejiang University City College, Hangzhou, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Wenzou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongping Chen, Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325025, People’s Republic of China, Email 13505777281@163.com Shou-Rong Liu, Department of Infectious Diseases, Hangzhou Xixi Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310023, People’s Republic of China, Email lsr85463990@126.comObjective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents.Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed.Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 μM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice.Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.Graphical Abstract: Keywords: glycosylation, silibinin derivatives, solubility, anti-proliferative activity

Sheng-Te Hung,1 Yi-Chen Cheng,2 Chieh-Chen Wu,2 Chun-Hsien Su1,2 1Graduate Institute of Sports Coaching Science, College of Kinesiology and Health, Chinese Culture University, Taipei, 111396, Taiwan; 2Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei, 111396, TaiwanCorrespondence: Chun-Hsien Su, Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, 55, Hwa-Kang Road, Shilin Distract, Taipei City, 111396, Taiwan, Tel +886-2-28610511 ext.45001, Fax +886-2-28617084, Email chsu@ulive.pccu.edu.twAbstract: This review examines the impact of physical activity, nutrition, and sleep evaluations on the physical wellness (PW) and overall well-being of older individuals. A comprehensive search was conducted in databases like PubMed, Google Scholar, and EBSCO Information Services. The search spanned from January 2000 to December 2022, resulting in 19,400 articles, out of which 98 review articles met the inclusion criteria. Through the analysis of these articles, key characteristics of the literature were summarized, and opportunities to enhance the practical application of physical activity (PA), nutrition, and sleep evaluations in the daily lives of older persons were identified. Regular physical activity is crucial for older persons to maintain their physical, mental, and emotional well-being and prevent age-related health issues. Older persons have specific nutritional needs, including increased protein, vitamin D, calcium, and vitamin B12 intake. Poor sleep quality in older persons is associated with negative health outcomes such as cognitive decline, physical disability, and mortality. This review emphasizes the significance of considering physical wellness as a fundamental element for achieving holistic well-being in older persons and highlights the importance of physical activity, nutrition, and sleep evaluations in improving their overall health and well-being. By understanding and implementing these findings, we can enhance the quality of life and promote healthy aging in older persons.Keywords: wellness, healthy aging, physical activity, nutrition, sleep

Jia Xin Fan,1,2,&ast; Ya Chen Hu,1,2,&ast; XinXin Chen,1,2,&ast; YuMei Li2 1School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YuMei Li, Department of Nursing, Shanghai Pulmonary Hospital, Tongji University, No. 507 Zheng Min Road, Shanghai, 200433, People’s Republic of China, Tel +86 13917922290, Fax +86 021-65115006-2185, Email 1500179@tongji.edu.cnPurpose: This study investigated the experience of oncology nurses caring for chemotherapy-induced peripheral neuritis patients.Patients and Methods: Through phenomenological research method, 11 nurses in a tertiary hospital in Shanghai were interviewed using face-to-face semi-structured interviews. Data analysis was conducted with the thematic analysis approach.Results: This analysis revealed the experiences of oncology nurses in caring for patients with CIPN and identified three themes: 1) stress in the nursing of CIPN (inadequate knowledge of CIPN among oncology nurses, oncology nurses’ CIPN nursing skills need to be improved, negative emotions of oncology nurses at work); 2) environmental dilemmas in nursing of CIPN (lack of effective care norms, busy schedules, doctors pay little attention to CIPN); 3) oncology nurses’ desire to improve their knowledge of CIPN to meet care needs.Conclusion: Based on the perspective of oncology nurses, the care dilemma of CIPN is mainly influenced by individual and environmental factors. It is recommended to enhance the attention of oncology nurses to CIPN, set specific and feasible training courses, explore CIPN assessment tools that meet our clinical practice, and construct CIPN care programs to improve CIPN clinical care ability and reduce patient suffering.Keywords: lung cancer, nursing experience, qualitative research, qualitative study

Yong-Pyo Lee,1,&ast; Sang Eun Yoon,2,&ast; Junhun Cho,3 Young Hyeh Ko,3 Dongryul Oh,4 Yong Chan Ahn,4 Won Seog Kim,2,5 Seok Jin Kim2,5 1Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Seok Jin Kim, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Korea, Tel +82-2-3410-1766, Fax +82-2-3410-1754, Email kstwoh@skku.eduBackground: Primary testicular lymphoma is a rare type of non-Hodgkin lymphoma, mostly of the diffuse large B cell lymphoma (DLBCL). Although a consensus on standard treatment has been established, unresolved issues remain, such as recurrence in the central nervous system (CNS).Methods: We retrospectively analyzed the clinical characteristics and survival outcomes of 65 testicular DLBCL patients according to clinical settings and treatment modalities.Results: The median age of the patients in our study was 65 years, and two-thirds of them had disease limited to one testis. There was no right or left lateralization of testicular involvement. Over a median follow-up of 53.9 months (95% confidence interval 34.0– 73.7 months), patients with stage I disease and a low international prognostic index score showed better survival outcomes than those in other categories. Orchiectomy, six cycles of chemotherapy, and radiation therapy (RT) to the contralateral testis demonstrated survival benefits, whereas CNS prophylaxis therapy did not reduce CNS recurrence. During the follow-up period, the survival curves showed continuous decline, mostly due to disease progression. CNS recurrence was observed in 15% of patients, and parenchymal involvement was dominant. However, no factors were associated with CNS recurrence in our analyses. Although our molecular analyses were performed in a small number of patients, MYD88, CD79B, and PIM1 mutations were frequent.Conclusion: In our study, treatment with orchiectomy, six cycles of immunochemotherapy, and contralateral RT was effective. However, because CNS prophylaxis is an essential part of testicular DLBCL management, better treatment strategies than intrathecal therapy are required.Keywords: testis, diffuse large B cell lymphoma, central nervous system, survival outcome

Kuan-Pei Lin,1 Ting-Kuang Yeh,1,2 Yu-Chuan Chuang,1 Li-An Wang,1 Yun-Ching Fu,3,4,&ast; Po-Yu Liu1,4– 6,&ast; 1Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Genomic Center for Infectious Diseases, Taichung Veterans General Hospital, Taichung, Taiwan; 3Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yun-Ching Fu; Po-Yu Liu, Taichung Veterans General Hospital, No. 1650, Section 4, Taiwan Blvd, Xitun District, Taichung City, 40705, Taiwan, Tel +886-4-2359-2525 ext.3110, Fax +886-4-2359-5046, Email yunchingfu@gmail.com; pyliu@tcvgh.gov.twAbstract: Infective endocarditis is a potentially fatal condition, and identifying the pathogen is crucial to optimizing antibiotic treatment. While a blood culture takes time and may yield negative results, it remains the gold standard for diagnosis, blood culture-negative endocarditis, which accounts for up to 20% of infective endocarditis cases, poses a clinical challenge with increasing mortality. To better understand the etiology of blood culture-negative infective endocarditis, we reviewed non-culture-based strategies and compared the results. Serology tests work best in limited pathogens, such as Coxiella burnetii and Bartonella infections. Most of the pathogens identified by broad-range PCR tests are Streptococcus spp, Staphylococcus spp and Propionibacterium spp. adding specific real-time PCR assays to the systematic PCR testing of patients with blood culture-negative endocarditis will increase the efficiency of diagnosis. Recently, metagenomic next-generation sequencing has also shown promising results.Keywords: endocarditis, diagnosis, serology, PCR, metagenomic sequencing, Streptococcus

Kai-Ming Jhang,1,&ast; Wen-Fu Wang,1,2,&ast; Yu-Ching Cheng,3,&ast; Yu-Chun Tung,4,&ast; Shao-Wei Yen,5 Hsin-Hung Wu3,6,7 1Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 3Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 4Department of Pharmacy, Taichung Veterans General Hospital Puli Branch, Nantou, Taiwan; 5Department of Information Management, National Changhua University of Education, Changhua, Taiwan; 6Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 7Faculty of Education, State University of Malang, Malang, East Java, Indonesia&ast;These authors contributed equally to this workCorrespondence: Hsin-Hung Wu, Email hhwu@cc.ncue.edu.twPurpose: The purpose of this study was to find care need combinations for dementia patients with multiple chronic diseases and their caregivers.Patients and Methods: A cross-sectional study was conducted with 83 patients who had multiple chronic diseases. Variables from patients included age, gender, severity of clinical dementia rating, feeding, hypnotics, mobility, getting lost, mood symptoms, and behavioral and psychological symptoms. Moreover, 26 types of care needs were included in this study. The Apriori algorithm was employed to first identify care need combinations and then to find the relationships between care needs and variables from dementia patients with multiple chronic diseases.Results: Six rules were generated for care need combinations. Four care needs could be formed as a basic care need bundle. Moreover, two additional care needs could be added to provide a wider coverage for patients. In the second stage, 93 rules were found and categorized into three groups, including 2, 6, and 28 general rules with support of 30% but less than 40%, 20% but less than 30%, and 10% but less than 20%, respectively. When the support value is 10% but less than 20%, more variables from patients were found in rules which help the dementia collaborative care team members provide tailor-made care need bundles.Conclusion: Four basic care needs were social resources referral and legal support (Care (1)), drug knowledge education (Care (3)), memory problem care (Care (5)), and fall prevention (Care (8)). Besides, disease knowledge education (Care (2)) and hypertension care (Care (16)) were frequent unmet needs in this specific population. Moreover, care for the mood of the caregiver (Care (11)) should be considered especially in dementia patients with preserved ambulatory function or with symptoms of hallucination. The collaborative care team should pay more attention to those care needs when assessing this specific population.Keywords: multiple chronic diseases, care need, dementia, dementia collaborative care team, Apriori algorithm

ABSTRACTPurpose International studies document that lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI+) patients face significant health disparities. Studies exploring the attitudes, knowledge, preparedness and comfort levels of healthcare students towards LGBTQI+ health have been conducted in the United States, United Kingdom and Malaysia. This study aims to investigate stigma in healthcare for LGBTQI+ patients in Singapore, and possible upstream factors within medical education.Methods This mixed-methods study adopts a convergent parallel design. The Health Stigma and Discrimination Framework was referenced to devise in-depth interviews with representatives from 13 LGBTQI-affirming non-governmental organisations, analysed through thematic analysis. 320 clinical medical students were surveyed about attitudes, knowledge, comfort, preparedness, and perceived importance of/towards LGBTQI+ health, analysed via descriptive statistics and multivariate regression.Results Prevailing stigma in Singaporean society against LGBTQI+ individuals is exacerbated in healthcare settings. Doctors were cited as unfamiliar or uncomfortable with LGBTQI+ health, possibly from lack of training. Among medical students surveyed, the median composite attitudes, comfort and preparedness index was 3.30 (Interquartile Range (IQR) = 0.50), 3.17 (IQR = 0.83), 2.50 (IQR = 1.00) respectively. Only 12.19% of students answered all 11 true-false questions about LGBTQI+ health correctly.Conclusion Medical students in Singapore have scored sub-optimally in their knowledge and preparedness towards LGBTQI+ health, while interpersonal and structural stigma in healthcare towards LGBTQI+ people in Singapore negatively affects health and wellbeing. These findings are an impetus to improve medical training in this area. High scores among medical students in attitudes, comfort and perceived importance of LGBTQI+ topics demonstrate that there is space for LGBTQI+ health in the local medical education curriculum. Curricular interventions can prioritise content knowledge, communication skills and sensitivity.

We have used angle-dependent soft x-ray absorption spectroscopy (XAS) at the O K edge and first-principles calculations to investigate the electronic structures of iridate-based superlattices (SrIrO3)m/(SrTiO3) (m=1, 2, 3, and ∞). We focus on the pre-edge Ir 5d t2g-O 2p orbital hybridization feature in the XAS spectra. By varying the measurement geometry relative to the incident photon polarization, we are able to extract the dichroic contrast and observe the systematic increase in the anisotropy of Ir 5d orbitals as m decreases. First-principles calculations elucidate the orbital anisotropy coming mainly from the enhanced out-of-plane compression of IrO6 octahedra in the SrIrO3 layers that are adjacent to the inserted SrTiO3 layers. As m decreases, the increased volume fraction of these interfacial SrIrO3 layers and their contact with the SrTiO3 layers within the (SrIrO3)m/(SrTiO3) supercell lead to enhanced orbital anisotropy. Furthermore, the tilt and rotation of IrO6 octahedra are shown to be essential to understand the subtle orbital anisotropy in these superlattices, and constraining these degrees of freedom will give an incorrect trend. Our results demonstrate that the structural constraint from the inserted SrTiO3 layers, in addition to other electronic means such as polar interface and charge transfer, can serve as a knob to control the orbital degree of freedom in these iridate-based superlattices.

PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.ResultsWe randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Several thousand core-collapse supernovae (CCSNe) of different flavors have been discovered so far. However, identifying their progenitors has remained an outstanding open question in astrophysics. Studies of SN host galaxies have proven to be powerful in providing constraints on the progenitor populations. In this paper, we present all CCSNe detected between 2009 and 2017 by the Palomar Transient Factory. This sample includes 888 SNe of 12 distinct classes out to redshift z ≈ 1. We present the photometric properties of their host galaxies from the far-ultraviolet to the mid-infrared and model the host-galaxy spectral energy distributions to derive physical properties. The galaxy mass function of Type Ic, Ib, IIb, II, and IIn SNe ranges from 105 to 1011.5 M o˙, probing the entire mass range of star-forming galaxies down to the least-massive star-forming galaxies known. Moreover, the galaxy mass distributions are consistent with models of star-formation-weighted mass functions. Regular CCSNe are hence direct tracers of star formation. Small but notable differences exist between some of the SN classes. Type Ib/c SNe prefer galaxies with slightly higher masses (i.e., higher metallicities) and star formation rates than Type IIb and II SNe. These differences are less pronounced than previously thought. H-poor superluminous supernovae (SLSNe) and SNe Ic-BL are scarce in galaxies above 1010 M o˙. Their progenitors require environments with metallicities of < 0.4 and < 1 solar, respectively. In addition, the hosts of H-poor SLSNe are dominated by a younger stellar population than all other classes of CCSNe. Our findings corroborate the notion that low metallicity and young age play an important role in the formation of SLSN progenitors.

PurposeCurrent FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging.Experimental designMen with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety.ResultsA total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8-80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers).ConclusionsPerformance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.See related commentary by True and Chen, p. 3512.

Nonlinear wave mixing in solids with ultrafast x-rays can provide insight into complex electronic dynamics of materials. Here, tabletop-based attosecond noncollinear four-wave mixing (FWM) spectroscopy using one extreme ultraviolet (XUV) pulse from high harmonic generation and two separately timed few-cycle near-infrared (NIR) pulses characterizes the dynamics of the Na+ L2,3 edge core-excitons in NaCl around 33.5 eV. An inhomogeneous distribution of core-excitons underlying the well-known doublet absorption of the Na+ Γ point core-exciton spectrum is deconvoluted by the resonance-enhanced nonlinear wave mixing spectroscopy. In addition, other dark excitonic states that are coupled to the XUV-allowed levels by the NIR pulses are characterized spectrally and temporally. Approximately

We perform a comprehensive analysis of both the chemical and correlated electronic structure reconstruction of rhombohedral CrX3 (X=Br, Cl, I) van der Waals bulk crystals. Using the generalized gradient approximation (GGA) plus dynamical mean-field theory we explicitly demonstrate the importance of local dynamical correlations for a consistent understanding of emergent Kondo quasiparticles and Mott localized electronic states, showing the interplay between material-dependent one-electron GGA line-shape and multiorbital electronic interactions. To probe the correlated paramagnetic electronic state we performed x-ray absorption spectroscopy measurements for CrCl3 and CrBr3 bulk crystals. Our correlated many-body study is relevant to understanding the electronic structure reconstruction of paramagnetic Cr-trihalide crystals and should be widely applicable to other van der Waals magnetic materials.

We present the first Hubble diagram of superluminous supernovae (SLSNe) out to a redshift of two, together with constraints on the matter density, ωM, and the dark energy equation-of-state parameter, w(p/ρ). We build a sample of 20 cosmologically useful SLSNe I based on light curve and spectroscopy quality cuts. We confirm the robustness of the peak-decline SLSN I standardization relation with a larger data set and improved fitting techniques than previous works. We then solve the SLSN model based on the above standardization via minimization of the χ2 computed from a covariance matrix that includes statistical and systematic uncertainties. For a spatially flat Λ cold dark matter (ΛCDM) cosmological model, we find $\Omega{\rm M}=0.38^{+0.24}_{-0.19}$, with an rms of 0.27 mag for the residuals of the distance moduli. For a w0waCDM cosmological model, the addition of SLSNe I to a 'baseline' measurement consisting of Planck temperature together with Type Ia supernovae, results in a small improvement in the constraints of w0 and wa of 4 per cent. We present simulations of future surveys with 868 and 492 SLSNe I (depending on the configuration used) and show that such a sample can deliver cosmological constraints in a flat ΛCDM model with the same precision (considering only statistical uncertainties) as current surveys that use Type Ia supernovae, while providing a factor of 2-3 improvement in the precision of the constraints on the time variation of dark energy, w0 and wa. This paper represents the proof of concept for superluminous supernova cosmology, and demonstrates they can provide an independent test of cosmology in the high-redshift (z > 1) universe.

Po-Ming Chow,1 Yao-Chi Chuang,2 Karina Chin Po Hsu,3 Yuan-Chi Shen,2 Shih-Ping Liu1 1Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 2Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Medical Affairs Department, Former Employee of Astellas Pharma Taiwan, Inc., Taipei, TaiwanCorrespondence: Shih-Ping Liu, Department of Urology, National Taiwan University Hospital and College of Medicine, No. 7, Chung Shan South Road, Taipei, 10002, Taiwan, Tel +886 2 2312-3456 ext. 62135, Fax +886 2 2321-9145, Email spliu@ntuh.gov.twBackground: Stress urinary incontinence (SUI) is common among adult women with negative effects on psychosocial well-being, mental health, and health-related quality of life. The purpose of the research is to determine if SUI in women is a factor implicated in changes in health-related quality of life (HRQoL) in both physical and mental health domains and in work difficulties.Methods: Data of women 40 years or older from a cross-sectional, population-based, internet survey were examined post-hoc. The effect of SUI frequency on HRQoL (SF12 score), in physical and mental health domains, was assessed. In addition, multivariate and univariate analyses were used to show the influence of SUI on HADS (Hospital Anxiety and Depression Scale) depression score and HADS anxiety score. The effects of demographic factors and physical ailments and SUI on work difficulties were similarly analyzed using multivariate logistic regression.Results: A total of 4208 women with mean age of 60 were included in the analysis. The more frequent SUI episodes were associated with a greater reduction of HRQoL in both physical and mental health domains. In addition, both multivariate and univariate analyses showed that SUI could be correlated with a negative effect on HADS anxiety score (OR 1.617, CI 1.335– 1.958, p=0.000) and HADS depression score (OR 1.263, CI 1.044– 1.527, p=0.016). Univariate analyses suggested that work difficulties were correlated with SUI. Available data revealed that many sufferers, including up to 40% of individuals with SUI frequency rating 1 (less than once a month) to 3 (a few times a week), failed to seek treatment.Conclusion: SUI, common in women ≥ 40 years of age, impairs quality of life in both physical and mental health domains. SUI is an independent risk factor for anxiety and depression and has been linked to significant work dysfunctions.Trial Registration: This study is registered at ClinicalTrials.gov: NCT02618421 (Date of registration: December 1, 2015).Keywords: stress urinary incontinence, quality of life, China, South Korea, Taiwan

Lipid miscibility phase separation has long been considered to be a central element of cell membrane organization. More recently, protein condensation phase transitions, into three-dimensional droplets or in two-dimensional lattices on membrane surfaces, have emerged as another important organizational principle within cells. Here, we reconstitute the linker for activation of T cells (LAT):growth-factor-receptor-bound protein 2 (Grb2):son of sevenless (SOS) protein condensation on the surface of giant unilamellar vesicles capable of undergoing lipid phase separations. Our results indicate that the assembly of the protein condensate on the membrane surface can drive lipid phase separation. This phase transition occurs isothermally and is governed by tyrosine phosphorylation on LAT. Furthermore, we observe that the induced lipid phase separation drives localization of the SOS substrate, K-Ras, into the LAT:Grb2:SOS protein condensate.

Rachel Campbell,1 Madeleine T King,1 Martin R Stockler,2 Yeh Chen Lee,2– 4 Felicia T Roncolato,2,5 Michael L Friedlander3,4 1University of Sydney, Faculty of Science, School of Psychology, Sydney, NSW, Australia; 2University of Sydney, NHMRC Clinical Trials Centre, Sydney, NSW, Australia; 3School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Prince of Wales and Royal Hospital for Women, Sydney, NSW, Australia; 5MacArthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, NSW, AustraliaCorrespondence: Rachel Campbell, University of Sydney, Room 325, Brennan-Maccallum Building, Sydney, NSW, 2006, Australia, Tel +61 2 8627 7631, Email r.campbell@sydney.edu.auAbstract: Patient-reported outcomes (PROs) provide a valid, standardized way of assessing symptoms, adverse events and the subjective benefit of treatment from the patient’s perspective. Assessment of PROs is critical in ovarian cancer due to the high morbidity of the disease and its treatments. Several well-validated PRO measures are available to assess PROs in ovarian cancer. Their inclusion in clinical trials can provide evidence on the benefits and harms of new treatments based on patients’ experiences to guide improvements in clinical practice and health policy. Aggregate PRO data collected in clinical trials can be used to inform patients about likely treatment impacts and assist them to make informed treatment decisions. In clinical practice, PRO assessments can facilitate monitoring of a patient’s symptoms throughout treatment and follow-up to guide their clinical management; in this context, an individual patient’s responses can facilitate communication with their treating clinician about troublesome symptoms and their impact on their quality of life. This literature review aimed to provide clinicians and researchers with a better understanding of why and how PROs can be incorporated into ovarian cancer clinical trials and routine clinical practice. We discuss the importance of assessing PROs throughout the ovarian cancer disease and treatment trajectory in both clinical trials and clinical practice, and provide examples from existing literature to illustrate the uses of PROs as the goals of treatment change in each setting.Keywords: ovarian cancer, patient-reported outcomes, clinical trials, clinical practice

Elsa Vitale,1 Rocco Mea,2 Yun-Chen Chang3,4 1Centre of Mental Health Modugno, Local Health Authority Bari, Bari, Italy; 2Cardiovascular Department, San Carlo Hospital, Potenza, Italy; 3School of Nursing and Graduate Institute of Nursing, China Medical University, Taichung, Taiwan; 4Nursing Department, China Medical University Hospital, Taichung, TaiwanCorrespondence: Yun-Chen Chang, School of Nursing and Graduate Institute of Nursing, China Medical University, No. 100, Section 1, Jingmao Road, Beitun District, Taichung, 406040, Taiwan, Tel +886 983503901, Email lisacow@mail.cmu.edu.twBackground: The nursing essential mission was to satisfy patients’ and caregivers’ essential health-relating demand, thanks to communicational, interventional, assistance and helping skills through an appropriate approach which best satisfied both patients and their caregivers. To assess any differences in nursing-home care quality perceived levels both by patients and caregivers.Methods: A cohort observational study was conducted from November 2022 to January 2023 using an online anonymous questionnaire for both patients and caregivers who received nursing-home care service.Results: A total of 677 patients (43.4%) and caregivers (56.6%) were enrolled. Most interviewees benefited from the nursing-home care service less than 12 months (p = 0.014). Quality perceptions did not significantly vary from patients and caregivers (p > 0.05) for all the items proposed, with the exception of the nursing listening skills which was better assessed by caregivers than patients (p = 0.034).Conclusion: Patients and caregivers perceived an average quality of nursing-home care, giving particular importance to some nursing skills, such as listening skills. The general quality of nursing care was however satisfying. Findings suggested more incisive action from health-care nurses to improve quality of nursing-home care and both patient and caregiver satisfaction.Keywords: caregiver, home-care, nursing, patient, quality

Wyatt M Corbin,1 Carter J Payne,2,3 Hamed Momeni-Moghaddam,4 Yasmyne C Ronquillo,2 Phillip C Hoopes Snr,2 Majid Moshirfar2,5,6 1Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA; 2Hoopes Vision Research Center, Hoopes Vision, Draper, UT, USA; 3Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Rehabilitation Sciences Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; 5Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 6Utah Lion’s Eye Bank, Murray, UT, USACorrespondence: Majid Moshirfar, Hoopes Vision Research Center, Hoopes Vision, 11820 S. State St. Ste. 200, Draper, UT, 84020, USA, Tel +1 801 568-0200, Fax +1 801 563-0200, Email cornea2020@me.comAbstract: Increasing popularity and utility of epithelial thickness mapping (ETM) in keratorefractive surgery screening may begin to inappropriately devalue the use of tomography. An increasing body of research suggests that the interpretation of ETM based solely on the corneal resurfacing function may be insufficient to screen and select patients for refractive surgery. ETM and tomography are complementary and, when used together, may provide the safest and most optimal tools for keratorefractive surgery screening.Keywords: corneal tomography, corneal topography, corneal epithelial map, SMILE, LASIK, PRK

Dai Gong, Qiong Tang, Li-Juan Yan, Xiao-Min Ye, Yi-Can Yang, Li Zou, Qing Ji, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, Hunan, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 Changjiang Road, Tianyuan District, Zhuzhou, Hunan, 412007, People’s Republic of China, Tel/Fax +86 13873317331, Email wenxianglianwxl@126.comBackground: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air.Case Description: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary.Conclusion: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.Keywords: gene test, primary ciliary dyskinesia, reduced ciliary clearance function, short stature

Chanda Simfukwe,1 Young Chul Youn,1 Min-Jae Kim,2 Joonki Paik,2 Su-Hyun Han1 1Department of Neurology, Chung-Ang University College of Medicine, Seoul, South Korea; 2Department of Image, Chung-Ang University, Seoul, South KoreaCorrespondence: Young Chul Youn; Su-Hyun Han, Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea, Email neudoc@cau.ac.kr; freesu84@cau.ac.krPurpose: Electroencephalogram (EEG) signals give detailed information on the electrical brain activities occurring in the cerebral cortex. They are used to study brain-related disorders such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Brain signals obtained using an EEG machine can be a neurophysiological biomarker for early diagnosis of dementia through quantitative EEG (qEEG) analysis. This paper proposes a machine learning methodology to detect MCI and AD from qEEG time-frequency (TF) images of the subjects in an eyes-closed resting state (ECR).Participants and Methods: The dataset consisted of 16,910 TF images from 890 subjects: 269 healthy controls (HC), 356 MCI, and 265 AD. First, EEG signals were transformed into TF images using a Fast Fourier Transform (FFT) containing different event-rated changes of frequency sub-bands preprocessed from the EEGlab toolbox in the MATLAB R2021a environment software. The preprocessed TF images were applied in a convolutional neural network (CNN) with adjusted parameters. For classification, the computed image features were concatenated with age data and went through the feed-forward neural network (FNN).Results: The trained models’, HC vs MCI, HC vs AD, and HC vs CASE (MCI + AD), performance metrics were evaluated based on the test dataset of the subjects. The accuracy, sensitivity, and specificity were evaluated: HC vs MCI was 83%, 93%, and 73%, HC vs AD was 81%, 80%, and 83%, and HC vs CASE (MCI + AD) was 88%, 80%, and 90%, respectively.Conclusion: The proposed models trained with TF images and age can be used to assist clinicians as a biomarker in detecting cognitively impaired subjects at an early stage in clinical sectors.Keywords: neurodegenerative diseases, electroencephalography, supervised machine learning, regression analysis

IntroductionThe growing adoption of social media (SoMe) by the scientific community has cemented the role of SoMe in information dissemination and engagement of academic work. The objective of this study is to evaluate the relationship between traditional and alternative SoMe metrics of urology journals.MethodsUrology journals listed on the SCImago Journal & Country Rank (SJR) electronic portal were selected and data pertaining to traditional metrics were collected. Official SoMe platforms of eligible journals were identified and indicators of online activity were recorded. Correlations between traditional metrics (SJR, h-index, and Scopus CiteScore) and social metrics were performed via Spearman rank-order correlation.ResultsOf 107 journals, 54.2% of journals had at least one form of SoMe presence. The median SJR (0.535 versus 0.334, P = 0.005), h-index (34 versus 20, P = 0.001), and Scopus CiteScore (3.25 versus 2.20, P = 0.014) were significantly higher among journals with SoMe networks. All 3 traditional indicators demonstrated strong global correlations with various Twitter-based metrics (rs = 0.428 to 0.571). In particular, SoMe journals with more than 3000 citations in the previous 3 years also displayed very strong correlations between all 3 traditional metrics and alternative social metrics (rs = 0.714 to 0.821).ConclusionsJournals with SoMe presence had significantly higher traditional metric values (SJR, h-index, and CiteScore) compared to journals without SoMe presence. Strong, positive correlations between citation-based and alternative social metrics were also observed. Alternative social metrics may be harnessed as supplemental indicators of a journal’s scientific impact.

Zhen-Hua Li,1,&ast; Jie Wang,1,&ast; Xin Cheng,1,&ast; Yi-Cheng Mao,1 Kang-Di Zhang,1 Wen-Jie Yu,1 Ying-Qing Li,1 Kai Huang,1,2 Kun Ding,1 Xiao-Jing Yang,1 Cheng-Yang Hu,3 Xiu-Jun Zhang1,4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Hospital Infection Prevention and Control, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Humanistic Medicine, School of Humanistic Medicine, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Center for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Yang Hu; Xiu-Jun Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Tel/Fax +86 551 65167031 ; +86 551 65169635, Email cy.hu@ahmu.edu.cn; zhangxiujun@ahmu.edu.cnBackground: There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them.Methods: A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model.Results: PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (β = – 0.22, SE = 0.051, 95% CI: – 0.27, – 0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = – 0.16, 95% CI: – 0.20, – 0.13, P < 0.05).Conclusion: During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.Keywords: left-behind experience, COVID-19, psychology, mental health

Ashleigh Barrett-Young,1 Wickliffe C Abraham,1 Carol Y Cheung,2 Jesse Gale,3 Sean Hogan,1 David Ireland,1 Ross Keenan,4– 6 Annchen R Knodt,7 Tracy R Melzer,6,8,9 Terrie E Moffitt,7,10 Sandhya Ramrakha,1 Yih Chung Tham,11,12 Graham A Wilson,13 Tien Yin Wong,12,14 Ahmad R Hariri,7 Richie Poulton1 1Department of Psychology, University of Otago, Dunedin, New Zealand; 2Department of Ophthalmology and Visual Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong; 3Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand; 4Department of Radiology, Christchurch Hospital, Christchurch, New Zealand; 5Pacific Radiology Group, Christchurch, New Zealand; 6New Zealand Brain Research Institute, Christchurch, New Zealand; 7Department of Psychology and Neuroscience, Duke University, Durham, NC, USA; 8Department of Medicine, University of Otago, Christchurch, New Zealand; 9School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand; 10Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 11Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, Singapore; 12Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 13Department of Medicine, University of Otago, Dunedin, New Zealand; 14Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Ashleigh Barrett-Young, Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Email Ashleigh.barrett-young@otago.ac.nzPurpose: The retina has potential as a biomarker of brain health and Alzheimer’s disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort.Participants and Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI).Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities.Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.Keywords: optical coherence tomography, retina, Alzheimer’s, magnetic resonance imaging, brain aging

Miao Zhang, Jing Liu, Yu-Chen Pan, Hui-Li Liu, Jing Shu, Xiao-Ming Wu, Yang Yang Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaCorrespondence: Jing Liu, Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Tel +86 010 59616889, Email liujing2893@126.comObjective: The aim of this study was to analyze the prevalence of vaginal flora and drug resistance in bacterial vaginitis among girls.Methods: A total of 3099 girls (0– 10 years old) with vaginitis who visited the Beijing Children’s Hospital from January 2020 to December 2021 were included in the present study. The clinical data, results of bacterial culture of vaginal secretions, and drug sensitivity reports of the subjects were collected and analyzed.Results: Of the 3099 girls with vaginitis, 399 girls had a positive bacterial culture of vaginal secretions. Nineteen types of bacteria were cultured from the vaginal secretions of these 399 girls, with a total of 419 strains. The top three infective bacteria were Haemophilus influenzae (127 strains, 30.31%), Staphylococcus aureus (66 strains, 15.75%), and Streptococcus agalactiae (32 strains, 7.64%). Additionally, 20 girls were simultaneously infected with two types of bacteria. Staphylococcus aureus, Group G Streptococcus, Haemophilus parainfluenzae, and Pseudomonas aeruginosa more frequently occurred in mixed infections. The number and bacterial detection rate among school-age girls were higher than those of preschool-age girls. We found seasonal variation in infection rates, and vaginitis among girls was higher in summer. Recurrence of vaginitis in girls was not related to the type of pathogenic bacteria in the infection. Drug sensitivity analyses showed that the resistance rates of clindamycin and erythromycin were generally high, 70– 100%. After the coronavirus disease 2019 outbreak, the resistance rates of some antibiotics had decreased to varying degrees.Conclusion: Improving the understanding of vaginal flora and drug resistance in girls with vaginitis will facilitate the selection of highly effective and sensitive antibacterial drugs and reduce the production of drug-resistant strains.Keywords: drug sensitivity analysis, girls, pathogenic bacteria, vaginitis

Ping-Ying Chang,1,2 Jian-Hong Chen,1– 3 Hui-Wen Cheng,1 Yen-Chin Wang4 1Department of Psychiatry, Chang-Gung Medical Foundation Keelung Chang-Gung Memorial Hospital, Keelung, Taiwan, Republic of China; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 3Doctoral Program for Transnational Sport Management and Innovation, National Taiwan Sport University, Taoyuan, Taiwan, Republic of China; 4Department of Psychiatry, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan, Republic of ChinaCorrespondence: Jian-Hong Chen, Email psydr.jc@gmail.comObjective: Prevention, de-escalation, and management of violence in the acute psychiatric ward is essential. Few studies have focused on differences in the duration of high-violence risk between different profiles of high-violence risk. This study aimed to analyze the data of high-violence patients and duration of high-violence risk to provide a new perspective on violence prevention, de-escalation and management.Methods: This retrospective observational cohort study included 171 patients who were treated in the acute psychiatric ward of Keelung Chang Gung Memorial Hospital between January 2016 and June 2020, and who were assessed daily as having high violence risk. All patient data were collected from electronic hospital records (eg, age, gender, diagnosis, violence history, self-harm history, and admission condition (involuntary admission, discharged against medical advice). Between-group differences in disease severity, use of antipsychotics and benzodiazepine, and duration of high violence risk were analyzed using regression analysis.Results: Only patients’ age was significantly associated with duration of high-violence risk (P = 0.028), making it predictive of longer duration of high-violence risk. In patients with schizophrenia spectrum disorder or bipolar disorder, higher severity was significantly associated with longer duration of high-violence risk (P = 0.007, P = 0.001, respectively).Conclusion: Only age is a predictor of longer duration of violence risk in psychiatric patients, although higher severity is associated with higher violence risk. Study results may help management and healthcare staff better understand how quickly or slowly violence risk will decrease and may improve efficient use of healthcare resources and individualized patient-centered care.Keywords: acute psychiatric ward, predictor, risk assessment, severity, violence risk

Ya-Chun Chu,1,2,&ast; Hsu-Wei Fang,2,3,&ast; Yu-Yi Wu,1 Yu-Jun Tang,1 Erh-Hsuan Hsieh,1 YiZhou She,4 Che-Yi Chang,1 I-Chan Lin,5,6 Yin-Ju Chen,1,7– 9 Guei-Sheung Liu,1,10– 12 Ching-Li Tseng1,8,9,13 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan; 4School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan; 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 7Department of Radiation Oncology, Taipei Medical University Hospital, Taipei City, Taiwan; 8International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9Center for Precision Medicine and Translational Cancer Research, Taipei Medical University Hospital, Taipei City, Taiwan; 10Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; 11Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia; 12Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; 13Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan&ast;These authors contributed equally to this workCorrespondence: Ching-Li Tseng, Tel +886 2 2736 1661 (ext. 5214), Email chingli@tmu.edu.twBackground: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis.Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery.Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV’s cornea.Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.Graphical Abstract: Keywords: gp91 peptide, gelatin, nanoparticles, ocular retention, control release, corneal neovascularization, eye drops

Ning-Ping Foo,1,2 Yang Chien Tun,3 Che Chao Chang,4,5 Hung-Lin Lin,3 Cheng-Hsin Cheng,2,4,&ast; Hao-Yu Chuang4,6,&ast; 1Department of Emergency, An Nan Hospital, China Medical University, Tainan, 70965 Taiwan; 2Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, 71101 Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, 40447 Taiwan; 4Department of Neurosurgery, An Nan Hospital, China Medical University, Tainan, 70965 Taiwan; 5Neurophysiology Laboratory, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, 70101 Taiwan; 6Department of Neurosurgery, China Medical University Beigang Hospital, Beigang, Yunlin County, 65152 Taiwan&ast;These authors contributed equally to this workCorrespondence: Cheng-Hsin Cheng; Hao-Yu Chuang, Department of Neurosurgery, An-Nan Hospital, China Medical University, No. 66, Sec. 2, Changhe Road, Annan District, Tainan City, Taiwan, Tel +886-6-3553111, Email u701018.tw@yahoo.com.tw; sn232099@gmail.comObjective: This study aimed to evaluate the functional outcomes of lumboperitoneal (LP) shunt for the treatment of non-obstructive hydrocephalus.Methods: We retrospectively studied the clinical surgical results of 172 adult patients with hydrocephalus who underwent LP shunt surgery between June 2014 and June 2019. Data regarding the following were collected: pre- and postoperative symptom status, third ventricle width changes, Evans index, and postoperative complications. Additionally, the baseline and follow-up Glasgow Coma Scale (GCS) score, Glasgow Outcome Scale (GOS), and Modified Rankin Scale (mRS) scores were investigated. All patients were followed up for ≥ 12 months using clinical interview and braining imaging using computed tomography (CT) scan or magnetic resonance imaging (MRI).Results: Majority of patients presented with normal pressure hydrocephalus as the etiology of their disease (48.8%), followed by cardiovascular accident (28.5%), trauma (19.7%), and brain tumor (3%). The mean GCS, GOS, and mRS improved postoperatively. The average period from symptomatic onset to surgery was 402 days. The average width of the third ventricle on CT scan or MRI was 11.43 mm preoperatively and 10.8 mm postoperatively (P< 0.001). The Evans index improved from 0.258 to 0.222 after operation. The symptomatic improvement score was 7.0, with a complication rate of 7%.Conclusion: Significant improvement was observed in the functional score and brain image after LP shunt placement. Moreover, the satisfaction with symptomatic improvement after surgery remains high. LP shunt operation is a viable alternative in the treatment of non-obstructive hydrocephalus due to the low complication rate, fast recovery, and high satisfaction.Keywords: clinical outcome, complication, lumboperitoneal shunt, non-obstructive hydrocephalus