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Jui-Jen Chang,1,2,* Yi-Chen Wang,3,4,* Shu-Hui Yang,5,6 Ju-Yu Wu,7 Ming-Wei Chang,8 Hui-Min David Wang5,9– 11 1Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40447, Taiwan; 2Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40447, Taiwan; 3Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung City, 802, Taiwan; 4Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 807, Taiwan; 5Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, 402, Taiwan; 6Bachelor Program of Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan; 7Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, 402, Taiwan; 8Nanotechnology and Integrated Bioengineering Centre, University of Ulster, Belfast, BT15 1AB, Northern Ireland, UK; 9Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 10Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 404, Taiwan; 11Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan*These authors contributed equally to this workCorrespondence: Hui-Min David Wang, Graduate Institute of Biomedical Engineering, National Chung Hsing University, No. 145, Xingda Road, South Dist, Taichung City, 402, Taiwan, Tel +886-4-22840733#651 ; +886-935753718, Email davidw@dragon.nchu.edu.twBackground: Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer.Methods: Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion.Results: In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported.Conclusion: Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug. Keywords: melanoma, astaxanthin, nanoparticle

Julia J Chang,1 Adam Hain,2 Chrysoula Dosiou,1,* Neil Gesundheit1,* 1Division of Endocrinology, Metabolism, and Gerontology, Department of Medicine, Stanford School of Medicine, Stanford, California; 2Office of Medical Education, Stanford School of Medicine, Stanford, California*These authors contributed equally to this workCorrespondence: Julia J Chang, Stanford School of Medicine, 300 Pasteur Dr., Room S025, Stanford, CA, 94305, Tel +1 650-724-2474, Fax +1 (248) 720-4461, Email jchang89@stanford.eduBackground: The COVID-19 pandemic and a movement away from traditional lecture-based learning have increased the use of online flipped classroom (FC) and active learning models in medical education. The Community of Inquiry (CoI) framework for online learning may be used to evaluate the effectiveness and strengths of the online FC model compared with other learning formats.Methods: An observational survey study was conducted to measure medical student and facilitator perceptions of an online FC endocrinology tutorial compared with online lecture experiences. For the tutorial, students were instructed to watch short, pre-recorded lecture videos on thyroid pathophysiology prior to class. During class, small groups of students were paired with a faculty facilitator in online Zoom rooms for case discussion. Students were surveyed using the CoI framework to assess elements of cognitive, social, and teaching presence between the two online learning modalities. Facilitators were also surveyed. Survey questions were rated on a 5-point Likert scale.Results: Fifty-three out of 92 students (58% response rate) and seven out of eight facilitators (88% response rate) completed surveys. In general, students felt that online FC learning improved cognitive, teaching, and social presence compared with online lecture. Areas of cognitive presence (mean score 3.9 ± 1.0 SD), such as stimulating curiosity and applying concepts, were highly rated. Certain elements of social presence (3.6 ± 0.9) and teaching presence (3.7 ± 0.9), such as expression of emotion and communication of expectations, garnered lower ratings. All surveyed facilitators felt that online FC was more effective and enjoyable to teach than online lectures but did not feel it was superior to in-person instruction.Conclusion: Medical students and facilitators viewed an online FC tutorial in endocrinology positively. Most, but not all, areas of the CoI framework were enhanced with the online FC tutorial compared with online lecture-based learning.Keywords: flipped classroom, online learning, community of inquiry, small group learning

Miao Cai,1 Echu Liu,2 Ruihua Zhang,3 Xiaojun Lin,4,5 Steven E Rigdon,1 Zhengmin Qian,1 Rhonda Belue,2 Jen-Jen Chang1 1Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO, 63104, USA; 2Department of Health Management and Policy, College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO, 63104, USA; 3School of Management, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, People’s Republic of China; 4West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China; 5West China Research Center for Rural Health Development, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of ChinaCorrespondence: Ruihua ZhangSchool of Management, Chengdu University of Traditional Chinese Medicine, 1166 Liutaidadao, Chengdu 610075, Sichuan, People’s Republic of ChinaEmail zhangruihua@cdutcm.edu.cnObjective: Earlier comorbidity measures have been developed or validated using the North American population. This study aims to compare five Charlson or Elixhauser comorbidity indices to predict in-hospital mortality using a large electronic medical record database from Shanxi, China.Methods: Using the primary diagnosis code and surgery procedure codes, we identified four hospitalized patient cohorts, hospitalized between 2013 and 2017, in Shanxi, China, as follows: congestive heart failure (CHF, n=41,577), chronic renal failure (CRF, n=40,419), diabetes (n=171,355), and percutaneous coronary intervention (PCI, n=39,097). We used logistic regression models and c-statistics to evaluate the in-hospital mortality predictive performance of two multiple comorbidity indicator variables developed by Charlson in 1987 and Elixhauser in 1998 and three single numeric scores by Quan in 2011, van Walraven in 2009, and Moore 2017.Results: Elixhauser comorbidity indicator variables had consistently higher c-statistics (0.824, 0.843, 0.904, 0.853) than all other four comorbidity measures, across all four disease cohorts. Moore’s comorbidity score outperformed the other two score systems in CHF, CRF, and diabetes cohorts (c-statistics: 0.776, 0.832, 0.869), while van Walraven’s score outperformed all others among PCI patients (c-statistics: 0.827).Conclusion: Elixhauser comorbidity indicator variables are recommended, when applied to large Chinese electronic medical record databases, while Moore’s score system is appropriate for relatively small databases.Keywords: comorbidity, Charlson, Elixhauser, administrative data, China

Chang-Min Chung,1,2 Hui-Wen Cheng,2 Jung-Jung Chang,2 Yu-Sheng Lin,2 Ju-Feng Hsiao,2 Shih-Tai Chang,1 Jen-Te Hsu2,31School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, 2Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, 3Department of Medicine, College of Medicine, Chang Gung University, Taoyuan County, TaiwanBackground: Resistant hypertension (RH) is a common clinical condition associated with increased cardiovascular mortality and morbidity in older patients. Several factors and conditions interfering with blood pressure (BP) control, such as excess sodium intake, obesity, diabetes, older age, kidney disease, and certain identifiable causes of hypertension are common in patients resistant to antihypertensive treatment. Arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), is increasingly recognized as an important prognostic index and potential therapeutic target in hypertensive patients. The aim of this study was to determine whether there is an association between RH and arterial stiffness. Methods: This study included 1,620 patients aged ≥65 years who were referred or self-referred to the outpatient hypertension unit located at a single cardiovascular center. They were separated into normotensive, controlled BP, and resistant hypertension groups. Home BP, blood laboratory parameters, echocardiographic studies and baPWV all were measured. Results: The likelihood of diabetes mellitus was significantly greater in the RH group than in the group with controlled BP (odds ratio 2.114, 95% confidence interval [CI] 1.194–3.744, P=0.010). Systolic BP was correlated in the RH group significantly more than in the group with controlled BP (odds ratio 1.032, 95% CI 1.012–1.053, P=0.001). baPWV (odds ratio 1.084, 95% CI 1.016–1.156, P=0.015) was significantly correlated with the presence of RH. The other factors were negatively correlated with the existence of RH.Conclusion: In patients aged ≥65 years, the patients with RH have elevated vascular stiffness more than the well controlled hypertension group. baPWV increased with arterial stiffness and was correlated with BP levels. Strict BP control is necessary to prevent severe functional and structural vascular changes in the course of hypertensive disease.Keywords: arterial stiffness, brachial-ankle pulse wave velocity, resistant hypertension

Jin-bin Han,1,2 Feng Sang,3 Jin-jia Chang,1,4 Yong-qiang Hua,1,2 Wei-dong Shi,1,2 Li-hua Tang,1,2 Lu-ming Liu1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3The Center for AIDS Research of the First Affiliated Hospital of Henan University of TCM, Zhengzhou, 4Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China Objective: Overexpression of the sonic hedgehog (SHH) signaling pathway is an essential characteristic of pancreatic cancer stem cells (PCSCs) and arsenic trioxide (ATO) is described as a SHH inhibitor. This study evaluates whether ATO has the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins. Methods: Cell counting kit-8 and flow cytometry were used for analyzing apoptosis in cells in vitro. The animal model was an athymic nude mouse model bearing subcutaneous xenografts of SW1990 pancreatic cancer cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry were used for tumor tissue analysis. The interaction between Gli1 and ATO was examined by a confocal system and an ultraviolet absorption spectrum assay. Results: ATO induced apoptosis in pancreatic cancer cells, especially CD24+CD44+ cells in vitro. Combination treatment of ATO and low dose gemcitabine inhibited tumor growth by 60.9% (P = 0.004), and decreased the expression of CD24, CD44, and aldehyde dehydrogenase 1 family, member A1 significantly in vivo. ATO changed the structure of the recombinant Gli1 zinc finger peptides in a cell-free condition and the binding action of ATO to recombinant Gli1 was observed in cultured pancreatic cancer cells. Conclusion: ATO may have the potential to inhibit viability of PCSCs via binding to SHH-Gli proteins in vitro and in vivo. Keywords: pancreatic cancer, stem cells, gemcitabine, arsenic trioxide, sonic hedgehog, Gli

Natural environments are characterized by variable wind that can pose significant challenges for flying animals and robots. However, our understanding of the flow conditions that animals experience outdoors and how these impact flight performance remains limited. Here, we combine laboratory and field experiments to characterize wind conditions encountered by foraging bumblebees in outdoor environments and test the effects of these conditions on flight. We used radio-frequency tags to track foraging activity of uniquely identified bumblebee (Bombus impatiens) workers, while simultaneously recording local wind flows. Despite being subjected to a wide range of speeds and turbulence intensities, we find that bees do not avoid foraging in windy conditions. We then examined the impacts of turbulence on bumblebee flight in a wind tunnel. Rolling instabilities increased in turbulence, but only at higher wind speeds. Bees displayed higher mean wingbeat frequency and stroke amplitude in these conditions, as well as increased asymmetry in stroke amplitude-suggesting that bees employ an array of active responses to enable flight in turbulence, which may increase the energetic cost of flight. Our results provide the first direct evidence that moderate, environmentally relevant turbulence affects insect flight performance, and suggest that flying insects use diverse mechanisms to cope with these instabilities.

This article examines the quantitative interrelations between sectoral composition of public spending and equilibrium (in)determinacy in a two-sector real business cycle model with positive productive externalities in investment. When government purchases of consumption and investment goods are set as constant fractions of their respective sectoral output, we show that the public-consumption share plays no role in the model's local dynamics, and that a sufficiently high public-investment share can stabilize the economy against endogenous belief-driven cyclical fluctuations. When each type of government spending is postulated as a constant proportion of the economy's total output, we find that there exists a trade-off between public consumption versus investment expenditures to yield saddle-path stability and equilibrium uniqueness. (JEL E32, E62, O41).

Purpose: This study was designed to investigate potential discrepancies between the depth and width of the mandibular denture anterior lingual flange and the alveolingual sulcus and to measure the changes in retention when flange lengths were modified to optimal dimensions in a sample population of elderly edentulous subjects. Materials and Methods: The anterior lingual flange and alveolingual sulcus were measured in 66 randomly selected elderly Taiwanese denture patients. The length and width of corresponding regions of the anterior lingual flange and alveolingual sulcus were compared. Mandibular denture retention was recorded and compared prior to and following modification of the anterior lingual flange with border molding. Results: A significant statistical difference existed between the mean anatomical dimensions of the alveolingual sulcus and the corresponding denture flanges. Following functional border molding, the mean retention of the mandibular denture increased in a statistically significant manner. Conclusion: The discrepancies between the anterior lingual denture flange and alveolingual sulcus dimensions appeared to significantly diminish mandibular denture retention and reinforce the value of proper flange extensions in the sublingual region. Int J Prosthodont 2011;24:460-464. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pathogenesis of and risk factors for hepatic flare (HF) after the initiation of hepatitis B virus (HBV)-active antiretroviral therapy (ART) in HIV/HBV-coinfected individuals is not well understood. METHODS: We studied HF in ART-naive HIV/HBV-coinfected individuals in Thailand ([Formula: see text]) who were beginning HBV-active ART as part of a prospective clinical trial. HF was defined as an alanine aminotransferase (ALT) level>5 times the upper limit of normal or >200 IU/L higher than that at baseline. Immune mediators (interleukin [IL]-18, IL-2, IL-6, IL-8, IL-10, soluble CD26 [sCD26], sCD30, sCD8, CXCL-10, CCL-2, tumor necrosis factor-alpha, interferon [IFN]-gamma, and IFN-alpha) and activated NK cells were quantified. RESULTS: HBV DNA and ALT levels at baseline were higher in patients with HF (n=8) than in patients without HF (n=28) (P=.01). After the initiation of ART, CXCL-10 levels remained elevated in patients with HF but decreased in patients without HF (P<.01). sCD30 levels increased and were significantly higher at week 8 in patients with HF (P<.05). There was a positive correlation between levels of ALT and levels of CXCL-10, sCD30, CCL-2, and IL-18 at week 8 (the time of peak ALT level) but not at other time points. CONCLUSION: Elevated HBV DNA and ALT levels before the initiation of HBV-active ART are risk factors for HF. The pathogenesis of HF after the initiation of HBV-active ART is probably consistent with immune restoration disease. Copyright © 2009 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the effect of bilateral reaching, with/without inertial loading on the unaffected arm, on hemiparetic arm motor control in stroke. METHODS: Twenty unilateral stroke patients were recruited. A three-dimensional optical motion capture system was used to measure the movement trajectory of the hemiparetic arm while performing three tasks: affected limb reaching forward; two-limb reaching forward; and two-limb reaching forward with inertia loading of 25% upper limb weight on the unaffected limb, respectively. Kinematical parameters were utilized to quantify the reaching performance of the affected arm. RESULTS: No matter whether loading was applied on the unaffected arm or not, the bilateral reaching task did not significantly facilitate smoother and faster movement. Furthermore, during bilateral reaching task with/without loading on the unaffected arm, stroke patients showed slower movement, lower maximal movement velocity, feedback control dominant and discontinuous movements in the affected arm than the same task with unilateral reaching. Subjects showed the greatest active upper extremity range of motion in proximal joints during the bilateral reaching task without unaffected arm loading. The amount of trunk movement also increased during bilateral reaching either with or without loading on the unaffected arm. Patients with moderate upper extremity motor impairment performed more discontinuous movements and less active elbow range of motion during bilateral reaching tasks; however, those with mild upper extremity motor impairment performed smoother movements and demonstrated greater active elbow range of motion during bilateral reaching tasks. CONCLUSIONS: Bilateral reaching tasks with/without loading on the unaffected arm could be considered as adding challenges during motor control training. Training with bilateral arm movements may be considered as a treatment strategy, and can be incorporated in stroke rehabilitation to facilitate greater arm active movement and improve motor control performance in the affected arm. [ABSTRACT FROM AUTHOR]

PURPOSE: To report prevalence of adolescent victimization and delinquency recidivism as well as to assess the association between repeat victimization and delinquency recidivism in a large, population-based sample of high school seniors. METHODS: A nationally representative sample of the Monitoring the Future Project (about 17,000 high school seniors from 1996 to 1999) was analyzed as a pooled sample. The analysis was based on self-reported measures of ten different types of delinquent behaviors including violent and property offenses. Other measures included in the analysis are victimization and information about sociodemographic (e.g,. geographic region, parental education, number of parents in the home) and lifestyle (e.g., grade from average, truancy, work experience, religious commitment) characteristics. Pairwise and multivariate methods were used to examine the risk association between repeat victimization and delinquency recidivism. RESULTS: From 1996 to 1999, a downward trend was observed for most types of delinquent behaviors: recidivism among seniors except for hitting instructors/supervisors, damaging school property, and car theft. For the same study period, the prevalence of victimization recidivism was also on the decline except for injury with a weapon and physical threats. Repeat victimization was found to be significantly associated with delinquency recidivism. Other risk factors more frequently associated with delinquency recidivism included gender, race, drug use, poor school performance, truancy, risk-seeking, and conflicts with parents. CONCLUSIONS: The present study showed a significant association between repeat victimization and delinquent recidivism; it identified characteristics of adolescent at risk of repetitive delinquent behaviors, which could be used for planning intervention strategies. [ABSTRACT FROM AUTHOR]

As providers, insurers, and physicians partner for market share, nurse leaders' responsibilities change To ensure nursing's bright future, leaders must understand the corporate, consumer, and legal trends affecting the marketplace. [ABSTRACT FROM AUTHOR]

The article examines the effect of maternal depressive symptoms on child problem behavior trajectories and how the father's involvement may modify this association. It assesses maternal self-reports of child internalizing and externalizing behaviors repeatedly using a modified Child Behavior Checklist. Linear growth curve models reveals that the adverse effects of maternal depressive symptoms on child problem behavior trajectories become negligible after controlling for the father's involvement and other covariates including the child's age, sex and race.

Background: Efforts to elucidate risk factors for placental abruption are imperative due to the severity of complications it produces for both mother and fetus, and its contribution to preterm birth. Ethnicity-based differences in risk of placental abruption and preterm birth have been reported. We tested the hypotheses that race, after adjusting for other factors, is associated with the risk of placental abruption at specific gestational ages, and that there is a greater contribution of placental abruption to the increased risk of preterm birth in Black mothers, compared to White mothers.Methods: We conducted a population-based cohort study using the Missouri Department of Health's maternally-linked database of all births in Missouri (1989-1997) to assess racial effects on placental abruption and the contribution of placental abruption to preterm birth, at different gestational age categories (n = 664,303).Results: Among 108,806 births to Black mothers and 555,497 births to White mothers, 1.02% (95% CI 0.96-1.08) of Black births were complicated by placental abruption, compared to 0.71% (95% CI 0.69-0.73) of White births (aOR 1.32, 95% CI 1.22-1.43). The magnitude of risk of placental abruption for Black mothers, compared to White mothers, increased with younger gestational age categories. The risk of placental abruption resulting in term and extreme preterm births (< 28 weeks) was higher for Black mothers (aOR 1.15, 95% CI 1.02-1.29 and aOR 1.98, 95% CI 1.58-2.48, respectively). Compared to White women delivering in the same gestational age category, there were a significantly higher proportion of placental abruption in Black mothers who delivered at term, and a significantly lower proportion of placental abruption in Black mothers who delivered in all preterm categories (p < 0.05).Conclusion: Black women have an increased risk of placental abruption compared to White women, even when controlling for known coexisting risk factors. This risk increase is greatest at the earliest preterm gestational ages when outcomes are the poorest. The relative contribution of placental abruption to term births was greater in Black women, whereas the relative contribution of placental abruption to preterm birth was greater in White women. [ABSTRACT FROM AUTHOR]

Context. Child maltreatment remains a significant public health and social problem in the United States. Incidence data rely on substantiated reports of maltreatment known to official social service agencies.Objective. The objective of this study was to describe the epidemiologic features of child physical and sexual abuse, on the basis of maternal self-reports.Design, Setting, and Participants. Computer-assisted, anonymous, cross-sectional, telephone surveys (N = 1435) were conducted with mothers of children 0 to 17 years of age in North and South Carolina. Mothers were asked about potentially abusive behaviors used by either themselves or their husbands or partners in the context of other disciplinary practices. They were also asked about their knowledge of any sexual victimization their children might have experienced.Main Outcome Measures. The incidence of physical and sexual maltreatment determined through maternal reports.Results. Use of harsh physical discipline, equivalent to physical abuse, occurred with an incidence of 4.3%. Shaking of very young children as a means of discipline occurred among 2.6% of children <2 years of age. Mothers reported more frequent physical discipline of their children, including shaking, for themselves than for fathers or father figures. Nearly 11 of 1000 children were reported by their mothers as having been sexually victimized within the past year. The incidence of physical abuse determined with maternal self-reports was 40 times greater than that of official child physical abuse reports, and the sexual abuse incidence was 15 times greater. For every 1 child who sustains a serious injury as a result of shaking, an estimated 150 children may be shaken and go undetected. There was no statistically significant difference in the overall rates of physical or sexual maltreatment between the 2 states.Conclusions. Official statistics underestimate the burden of child maltreatment. Supplemental data obtained with alternative strategies can assist policymakers and planners in addressing needs and services within communities and states. These data support the need for continued interventions to prevent maltreatment. [ABSTRACT FROM AUTHOR]

Importance: The gut-first hypothesis of Parkinson disease (PD) has gained traction, yet potential inciting events triggering Parkinson pathology from gut-related factors remain unclear. While Helicobacter pylori infection is linked to mucosal damage (MD) and PD, it is unknown how upper gastrointestinal MD from any source increases PD risk., Objective: To evaluate any association between upper endoscopy findings of MD and subsequent clinical PD diagnosis., Design, Setting, and Participants: This was a retrospective cohort study of patients with no PD history undergoing upper endoscopy with biopsy between January 2000 and December 2005, with final follow-up assessments completed July 31, 2023. The study was conducted within the Mass General Brigham system, a multicenter network in the greater Boston, Massachusetts, area. Patients with MD were matched 1:3 to patients without MD based on age, sex, and date of initial endoscopy., Exposure: MD, defined as erosions, esophagitis, ulcers, or peptic injury, observed on upper endoscopy or pathology reports., Main Outcomes and Measures: The relative risk of PD given a history of MD, estimated using incident rate ratio (IRR) and multivariate Cox proportional hazard ratios (HRs)., Results: Of 9350 patients, participants had a mean (SD) age of 52.3 (20.3) years; 5177 (55.4%) were male; and 269 (2.9%) were Asian, 737 (7.9%) Black, and 6888 (73.7%) White. Most participants underwent endoscopy between the ages of 50 and 64 years (2842 [30.4%]). At baseline, patients with MD were more likely to have a history of H pylori infection, proton-pump inhibitor use, chronic nonsteroidal anti-inflammatory drug use, gastroesophageal reflux disease, smoking, constipation, and dysphagia. The mean (SD) follow-up time was 14.9 (6.9) years for the whole cohort, during which patients with MD were more likely to develop PD (IRR, 4.15; 95% CI, 2.89-5.97; P < .001) than those without MD, even after covariate adjustment (HR, 1.76; 95% CI 1.11-2.51; P = .01). Constipation, dysphagia, older age, and higher Charlson-Deyo Comorbidity Index were also associated with higher PD risk., Conclusions and Relevance: In this cohort study, a history of upper gastrointestinal MD was associated with elevated risk of developing a clinical PD diagnosis. Increased vigilance among patients with MD for future PD risk may be warranted.

Background: While dual-task walking requires the ability to integrate sensory information from multiple ongoing sources, it remains unknown whether dual-task walking is more affected than single-task walking by the multisensory integration ability., Research Question: How does the audiovisual temporal integration ability affect single-task and dual-task gaits in the aging population?, Methods: One hundred and thirty healthy middle-aged and older adults (age = 64.7 ± 6.4 years) completed an audiovisual simultaneity judgment (AVSJ) task and underwent single-task, motor dual-task, and cognitive dual-task gait assessments. In the AVSJ task, participants judged whether a flash and an auditory stimulus presented at different stimulus onset asynchronies were simultaneous. The accuracy and precision of the AVSJ performance were assessed using the point of subjective simultaneity (PSS) and the temporal binding window (δ), respectively. A lower absolute PSS and δ indicated better performance. Participants held a cup of water and performed serial-7 subtraction for motor and cognitive dual-task gait assessments, respectively. The spatiotemporal gait parameters and their variability were calculated. The influences of PSS and δ on the gait parameters of the three gaits were examined with multiple hierarchical regressions., Results: Only the cognitive dual-task gait was significantly affected by PSS and δ. Greater PSS predicted a longer single support time (β = 0.195, p = 0.024) and its variability (β = 0.224, p = 0.011). Greater δ predicted greater step time variability (β = 0.198, p = 0.022)., Significance: Declined perception of audiovisual simultaneity particularly degrades temporal control of cognitive dual-task walking, highlighting the importance of assessing and training this ability after midlife., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Partially reduced forms of titanium dioxide (sometimes called "black" titania) have attracted widespread interest as promising photocatalysts of oxidation due to their absorption in the visible region. The main approaches to produce it rely on postprocessing at high temperatures (up to 800 °C) and high pressures (up to 40 bar) or on highly reactive precursors ( e.g. , TiH 2 ), and yield powders with poorly controlled sizes, shapes, defect concentrations and distributions. We describe an approach for the one-step synthesis of TiO 2 colloidal nanocrystals at atmospheric pressure and temperatures as low as 280 °C. The temperature of the reaction allows the density of oxygen vacancies to be controlled by nearly two orders of magnitude independently of their size, shape, or colloidal stability. This synthetic pathway appears to produce vacancies that are homogeneously distributed in the nanocrystals, rather than being concentrated in an amorphous shell. As a result, the defects are protected from oxidation and result in stable optical properties in oxidizing environments.

Background: Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia., Objective: To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients., Design: Retrospective cohort study., Participants: National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System., Main Measures: Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy., Key Results: Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer)., Conclusion: Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objectives: Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication., Methods: Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity., Results: Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities., Conclusion: Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Self-harm (SH) increases significantly in early adolescence with great variability, and childhood maltreatment (CM) contributes to this increase. Understanding the developmental pathway from CM to SH could provide clues for SH prevention. This study used latent class analysis (LCA) to detect the phenotype of SH and explored the role of psychological resilience in the pathway from the CM to SH phenotype among 5724 early adolescents (52.5% male). Three interpretable phenotypes of SH were identified: low SH (57.8%), medium SH (29.0%), and high SH (13.2%). Furthermore, CM was positively associated with the SH phenotype, psychological resilience mediated the association between CM and the SH phenotype (all ps < 0.001), and a larger mediating effect was observed in the medium SH (22.41%). Our findings offer new perspectives that improving psychological resilience can be used as an efficient intervention to reduce the risk of SH among early adolescents who have experienced CM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This review summarizes the work on the use of plasmas to post-process nanostructures, in particular colloidal nanocrystals, as promising candidates for applications of heterogeneous catalysis. Using plasma to clean or modify the surface of nanostructures is a more precisely controlled method compared to other conventional methods, which is preferable when strict requirements for nanostructure morphology or chemical composition are necessary. The ability of plasma post-processing to create mesoporous materials with high surface areas and controlled microstructure, surfaces, and interfaces has transformational potential in catalysis and other applications that leverage surface/interface processes.

The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of a screening campaign and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. We initiated an HCV patient recall program to identify HCV participants who might not be treated after the HCV screening campaign. The program staff recalled HCV participants who were lost to follow-up via telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Among 185 participants infected with HCV, 109 (58.9%) obtained LTC. Compared with those who had LTC, those without LTC were older, had lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6%) persons had linkage to care. The proportion of LTC increased by 8.7%. In total, 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of the 82 patients with viremia, 78 (95.1%) received antiviral therapy, and 76 (97.4%) achieved a sustained virological response. After a community screening campaign, 59% of participants with anti-HCV-positive tests had LTC. The recall program increased this by 9%. However, 32% of HCV participants still could not be linked to care. Outreach care for non-LTC patients is a method worth trying in order to achieve the microelimination of HCV in rural communities.

The RNA-binding protein LIN28B represses the biogenesis of the tumor suppressor let-7. The LIN28B/let-7 axis regulates cell differentiation and is associated with various cancers. The RNA-binding protein Q (hnRNP Q) or SYNCRIP (Synaptotagmin Binding Cytoplasmic RNA Interacting Protein) has been implicated in mRNA splicing, mRNA transport, translation, and miRNAs biogenesis as well as metabolism in cancer. To determine whether hnRNP Q plays a role in the LIN28B/let-7 axis, we tested for interactions between hnRNP Q and LIN28B. We demonstrated that hnRNP Q interacts with LIN28B in an RNA-dependent manner. Knockdown of hnRNP Q caused reduced expression of a well-known let-7 target TRIM71, an E3 ubiquitin ligase that belongs to the RBCC/TRIM family, and also LIN28B, whose mRNA itself is down-regulated by let-7. In addition, hnRNP Q knockdown increased let-7 family miRNA levels and reduced the activity of luciferase reporters fused with the TRIM71 3'UTR or a synthetic 3'UTR carrying 8X let-7 complementary sites. Finally, depletion of hnRNP Q inhibited the proliferation of a hepatocellular carcinoma cell line, Huh7. This observation is consistent with the survival curve for liver cancer patients from the TCGA database, which indicates that high expression of hnRNP Q is a prognostic marker for a poor outcome in individuals afflicted with hepatocellular carcinoma. Together, our findings suggest that hnRNP Q interacts with LIN28B and modulates the LIN28B/let-7 axis in hepatocellular carcinoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This is an extremely rare case of complicated fetal esophageal atresia (EA) with tracheoesophageal fistula (TEF) and interrupted inferior vena cava (IVC) diagnosed by prenatal ultrsonography and successfully treated with surgical repair., Methods: A 35-year-old pregnant woman was referred to our center for prenatal ultrasound, and the fetus was found to have a series of abnormalities, such as an interrupted IVC associated with a dilated azygos vein, an upper neck pouch sign of the thorax, and polyhydramnios. With suspicion of EA with TEF and interrupted IVC, the infant was born at 39 weeks of gestation, and successfully underwent the surgical operation., Results: The baby was doing well after 21 months of follow-up., Conclusion: It is beneficial for the prenatal ultrasonic diagnosis of EA with TEF in optimizing labor care, postpartum treatment, and prompting neonatal management., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26-32 Y) and older children (12-14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Programmed death-1 (PD-1)/PD ligand-1 (PD-L1)-mediated immune escape contributes to cancer development and has been targeted as an anti-cancer strategy. Here, we show that inhibition of the RNA helicase DDX3 increased CD8 + T cell infiltration in syngeneic oral squamous cell carcinoma tumors. DDX3 knockdown compromised interferon-γ-induced PD-L1 expression and, in particular, reduced the level of cell-surface PD-L1. DDX3 promoted surface PD-L1 expression by recruiting the adaptor protein 2 (AP2) complex to the 3' UTR of PD-L1 mRNA. DDX3 depletion or 3' UTR truncation increased the binding of the coatomer protein complexes to PD-L1, leading to its intracellular accumulation. Therefore, this 3' UTR-dependent mechanism may counteract cellular negative effects on surface trafficking of PD-L1. Finally, pharmaceutic disruption of DDX3's interaction with AP2 reduced surface PD-L1 expression, supporting that the DDX3-AP2 pathway routes PD-L1 to the cell surface. Targeting DDX3 to modulate surface trafficking of immune checkpoint proteins may provide a potential strategy for cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Post-operative fluid restriction after transsphenoidal surgery (TSS) for pituitary tumors may effectively prevent delayed hyponatremia, the most common cause of readmission. However, implementation of individualized fluid restriction interventions after discharge is often complex and poses challenges for provider and patient. The purpose of this study was to understand the factors necessary for successful implementation of fluid restriction and discharge care protocols following TSS., Methods: Semi-structured interviews with fifteen patients and four caregivers on fluid discharge protocols were conducted following TSS. Patients and caregivers who had surgery before and after the implementation of updated discharge protocols were interviewed. Data were analyzed inductively using a procedure informed by rapid and thematic analysis., Results: Most patients and caregivers perceived fluid restriction protocols as acceptable and feasible when indicated. Facilitators to the protocols included clear communication about the purpose of and strategies for fluid restriction, access to the care team, and involvement of patients' caregivers in care discussions. Barriers included patient confusion about differences in the care plan between teams, physical discomfort of fluid restriction, increased burden of tracking fluids during recovery, and lack of clarity surrounding desmopressin prescriptions., Conclusion: Outpatient fluid restriction protocols are a feasible intervention following pituitary surgery but requires frequent patient communication and education. This evaluation highlights the importance of patient engagement and feedback to effectively develop and implement complex clinical interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The canine anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody is a potential therapeutic option for treating canine arthritis. The current treatments for arthritis in dogs have limitations due to side effects, emphasizing the need for safer and more effective therapies. The crystal structure of canine TNF-α (cTNF-α) was successfully determined at a resolution of 1.85 Å, and the protein was shown to assemble as a trimer, with high similarity to the functional quaternary structure of human TNF-α (hTNF-α). Adalimumab (Humira), a known TNF-α inhibitor, effectively targets and neutralizes TNF-α to reduce inflammation and has been used to manage autoimmune conditions such as rheumatoid arthritis. By comparing the structure of cTNF-α with the complex structure of hTNF-α and adalimumab-Fab, the epitope of adalimumab on cTNF-α was identified. The significant structural similarities of epitopes in cTNF-α and hTNF-α indicate the potential of using adalimumab to target cTNF-α. Therefore, a canine/human chimeric antibody, Humivet-R1, was created by grafting the variable domain of adalimumab onto a canine antibody framework derived from ranevetmab. Humivet-R1 exhibits potent neutralizing ability (IC 50  = 0.05 nM) and high binding affinity (EC 50  = 0.416 nM) to cTNF-α, comparable to that of adalimumab for both hTNF-α and cTNF-α. These results strongly suggest that Humivet-R1 has the potential to provide effective treatment for canine arthritis with reduced side effects. Here, we propose a structure-guided antibody design for the use of a chimeric antibody to treat canine inflammatory disease. Our successful development strategy can speed up therapeutic antibody discovery for animals and has the potential to revolutionize veterinary medicine., (© 2023 The Protein Society.)

Background: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear., Methods: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models., Results: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively., Conclusion: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial., (© The Author(s) 2023. Published by Oxford University Press.)

The ability to efficiently control charge and spin in the cuprate high-temperature superconductors is crucial for fundamental research and underpins technological development. Here, we explore the tunability of magnetism, superconductivity, and crystal structure in the stripe phase of the cuprate La[Formula: see text]Ba[Formula: see text]CuO[Formula: see text], with [Formula: see text] = 0.115 and 0.135, by employing temperature-dependent (down to 400 mK) muon-spin rotation and AC susceptibility, as well as X-ray scattering experiments under compressive uniaxial stress in the CuO[Formula: see text] plane. A sixfold increase of the three-dimensional (3D) superconducting critical temperature [Formula: see text] and a full recovery of the 3D phase coherence is observed in both samples with the application of extremely low uniaxial stress of [Formula: see text]0.1 GPa. This finding demonstrates the removal of the well-known 1/8-anomaly of cuprates by uniaxial stress. On the other hand, the spin-stripe order temperature as well as the magnetic fraction at 400 mK show only a modest decrease under stress. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. However, strain produces an inhomogeneous suppression of the spin-stripe order at elevated temperatures. Namely, a substantial decrease of the magnetic volume fraction and a full suppression of the low-temperature tetragonal structure is found under stress, which is a necessary condition for the development of the 3D superconducting phase with optimal [Formula: see text]. Our results evidence a remarkable cooperation between the long-range static spin-stripe order and the underlying crystalline order with the three-dimensional fully coherent superconductivity. Overall, these results suggest that the stripe- and the SC order may have a common physical mechanism., Competing Interests: Competing interests statement:The authors declare no competing interest.

Papillary renal cell carcinoma (PRCC) is a highly heterogeneous cancer, and PRCC patients with advanced/metastatic subgroup showed obviously shorter survival compared to other kinds of renal cell carcinomas. However, the molecular mechanism and prognostic predictors of PRCC remain unclear and are worth deep studying. The aim of this study is to identify novel molecular classification and construct a reliable prognostic model for PRCC. The expression data were retrieved from TCGA, GEO, GTEx and TARGET databases. CRISPR data was obtained from Depmap database. The key genes were selected by the intersection of CRISPR-Cas9 screening genes, differentially expressed genes, and genes with prognostic capacity in PRCC. The molecular classification was identified based on the key genes. Drug sensitivity, tumor microenvironment, somatic mutation, and survival were compared among the novel classification. A prognostic model utilizing multiple machine learning algorithms based on the key genes was developed and tested by independent external validation set. Our study identified three clusters (C1, C2 and C3) in PRCC based on 41 key genes. C2 had obviously higher expression of the key genes and lower survival than C1 and C3. Significant differences in drug sensitivity, tumor microenvironment, and mutation landscape have been observed among the three clusters. By utilizing 21 combinations of 9 machine learning algorithms, 9 out of 41 genes were chosen to construct a robust prognostic signature, which exhibited good prognostic ability. SERPINH1 was identified as a critical gene for its strong prognostic ability in PRCC by univariate and multiple Cox regression analyses. Quantitative real-time PCR and Western blot demonstrated that SERPINH1 mRNA and protein were highly expressed in PRCC cells compared with normal human renal cells. This study exhibited a new molecular classification and prognostic signature for PRCC, which may provide a potential biomarker and therapy target for PRCC patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Investigate how hypertension during pregnancy (HDP) and depression during pregnancy (DDP) independently and jointly affect infant birth outcomes., Methods: This population-based, retrospective cohort study included a sample of 68,052 women who participated in PRAMS 2016-2018 survey. Poisson regression was used for adjusted relative risks (aRRs)., Results: Compared to women without HDP and DDP, aRRs for PTB and LBW among women with both HDP and DDP are 2.04 (95% CI 1.73, 2.42) and 2.84 (95% CI 2.27, 3.56), respectively, albeit lower than the expected joint effect of risk., Conclusion: DDP may modify the association between HDP and PTB, LBW.