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Yao-Ching Huang,1 Wu-Chien Chien,2– 5,* Chi-Hsiang Chung,2– 4 Hsin-An Chang,6,7 Yu-Chen Kao,6,8 Fang-Jung Wan,6 Shi-Hao Huang,1 Ren-Jei Chung,1,* Richard S Wang,9 Bing-Long Wang,2,* Nian-Sheng Tzeng,7,8,* Chien-An Sun10,11 1Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 6Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 7Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 8Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan; 9Program of Data Analytic and Business Computing, Stern School of Business, New York University, USA; 10Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 11Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Nian-Sheng TzengDepartment of Psychiatry, School of Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-2-87923311 Ext 17484Fax +886-2-87927221Email pierrens@mail.ndmctsgh.edu.twBing-Long WangDepartment of Public Health, National Defense Medical Center, 116, Section 6, Minchuan E. Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-980-794951Email billwang1203@gmail.comBackground: Multiple sclerosis (MS) is a demyelinating disease that can damage neurons in the brain and spinal cord and is associated with several psychiatric disorders. However, few studies have evaluated the risk of psychiatric disorders in patients with MS by using a nationwide database. This study investigated the association between MS and the risk of psychiatric disorders.Methods: Using data from the Taiwan National Health Insurance Research Database from 2000 to 2015, we identified 1066 patients with MS. After adjustment for confounding factors, Fine and Gray’s competing risk model was used to compare the risk of psychiatric disorders during 15 years of follow-up.Results: Of the patients with MS, 531 (4622.86 per 105 person years) developed psychiatric disorders; by contrast, 891 of the 3198 controls (2485.31 per 105 person years) developed psychiatric disorders. Fine and Gray’s competing risk model revealed an adjusted hazard ratio (HR) of 5.044 (95% confidence interval = 4.448– 5.870, p < 0.001) after adjustment for all the covariates. MS was associated with depression, anxiety, bipolar disorder, sleep disorders, schizophrenia, schizophreniform disorder, and other psychotic disorders (adjusted HR: 12.464, 4.650, 6.987, 9.103, 2.552, 2.600, 2.441, and 2.574, respectively; all p < 0.001). Some disease-modifying drugs were associated with a lower risk of anxiety or depression.Conclusion: Patients with MS were determined to have a higher risk of developing a wide range of psychiatric disorders.Keywords: multiple sclerosis, psychiatric disorders, depression, anxiety

Meng Xu, Chang Liu, Jing Lin Mi, Ren Sheng Wang Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Radiation Oncology Clinical Medical Research Center of Guangxi, Nanning 530021, Guangxi, People’s Republic of ChinaCorrespondence: Ren Sheng WangDepartment of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Radiation Oncology Clinical Medical Research Center of Guangxi, No. 6 Shuangyong Road, Nanning 530021, Guangxi, People’s Republic of ChinaTel +86-771-5359339Fax +86-771-5350031Email 13807806008@163.comObjective: This study set out to institute an effective nomogram to predict the prognosis of nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI)-detected residual tumor at the end of intensity-modulated radiotherapy (IMRT).Background: This study retrospectively analyzed the prognostic factors of NPC using MRI-detected residual tumor at the end of IMRT, in order to individualize the treatment of patients with poor prognosis as early as possible.Methods: Overall, 162 NPC patients with local or regional residual tumor at the end of IMRT were retrospectively analyzed. Based on multivariate Cox regression analysis using the backward stepwise method, a nomogram was generated to predict the prognosis of these patients. Identification, calibration, clinical applicability and reproducibility were evaluated by C-index, time-dependent AUC, calibration curve and bootstrap verification. According to the best cut-off value of total score of prognoses calculated by X-tile software, all patients were separated into either low-risk or high-risk group.Results: The nomogram identified age, chemotherapy, N stage, lymph nodes necrosis are significant predictors of prognosis. The AUC of the prediction model is 0.754, and the consistency index is 0.724 (95% confidence interval is 0.659– 0.788). The model has good discrimination ability. Through bootstrapping test, the consistency index, corrected slope was 0.723, 0.861, respectively. The calibration slope of predicting 3-year and 5-year overall survival was 1.006 and 1.071, respectively. The calibration curve showed satisfactory calibration effect and good net benefit. The best cut-off value of total score of prognoses calculated by X-tile software was 149.1. Kaplan–Meier survival curve showed that OS and DMFS in the high-risk group were substantially reduced compared to those in the low-risk group.Conclusion: We constructed and validated a new nomogram to help clinicians understand the prognosis of NPC patients with residue at the end of IMRT. With an estimate of the individual risk, clinicians can start treatment decisions as early as possible for high-risk patients with poor prognosis.Keywords: nasopharyngeal carcinoma, residue, IMRT

Junyin Tan,* Li Jiang,* Xiaowei Cheng, Chunlin Wang, Jingshan Chen, Xiaoqing Huang, Peng Xie, Dongmei Xia, Rensheng Wang, Yong Zhang Department of Radiotherapy, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a critical role in the development, metastasis, and recurrence of tumors. This study aims to determine the correlation of single-nucleotide polymorphisms in the VEGF gene with the prognosis of nasopharyngeal carcinoma (NPC). The VEGF –460T/C gene polymorphisms in the genomic DNA of the blood samples of 338 patients with NPC were investigated through polymerase chain reaction and direct DNA sequencing. Results showed a significant association between the –460C-allele carriers and the aggressive forms of NPC as defined by stages N2–3 (odds ratio =1.820, 95% confidence interval [CI]: 1.118–2.962, P=0.015). Furthermore, the VEGF –460T/C polymorphism was significantly associated with 3-year overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (T/C + C/C vs T/T: 3-year OS 78.8% vs 95.1%, P=0.003; 3-year DMFS 80.2% vs 90.6%, P=0.036; 3-year PFS 73.9% vs 86.7%, P=0.042) but was not associated with the local recurrence-free survival (LRFS) of the patients. The multivariate analysis indicated that the VEGF –460C-allele carrier was an independent significant prognostic factor for OS (hazard ratio [HR] 4.096, 95% CI: 1.333–12.591, P=0.014). N classification was an independent significant prognostic factor for DMFS in patients with locoregionally advanced NPC (HR 3.674, 95% CI: 1.144–11.792, P=0.029). However, neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) was not superior to CCRT alone in terms of the 3-year OS, LRFS, DMFS, and PFS of patients with VEGF –460T/C polymorphism. In conclusion, the VEGF –460T/C gene polymorphism may negatively affect the clinical outcomes of patients with NPC and may be considered a potential prognostic factor for this disease. Keywords: vascular endothelial growth factor, gene polymorphism, nasopharyngeal carcinoma, clinical outcomes

BACKGROUND: Membranous nephropathy (MN) is a common cause of proteinuria and can be subdivided into idiopathic and secondary classifications. Most patients with MN present with associated systemic diseases that need to be identified before appropriately diagnosing idiopathic MN. However, the cause and clinical characteristics of MN in Chinese patients have not been investigated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with biopsy-proven MN at the Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. OUTCOME: The diagnosis of idiopathic and secondary MN was based on clinical, initial laboratory, and histological findings. RESULTS: 390 patients with MN were identified from 1985 to 2005. Of 390 patients with MN, 124 (31.8%) had idiopathic MN and 266 had secondary MN (68.2%). Of patients with idiopathic MN, 75 (60.5%) were men and 49 (39.5%) were women. Mean age was 43.9 +/- 13.2 years (range, 14 to 78 years). Common presentations of idiopathic MN were 60.5% with proteinuria (39.5% of whom presented with nephrotic syndrome), 29.8% with hypertension, 17.7% with hematuria, and 0.8% with decreased kidney function. In patients with secondary MN, causes were autoimmune diseases (73.3%), infections (17.7%), tumors (4.5%), and drugs or toxins (4.5%). Systemic lupus erythematosus was the most common autoimmune disease (predominately in younger women). Hepatitis B predominated in younger men. Greater levels of proteinuria were found in patients who presented with drugs or toxins compared with patients with other secondary MNs (P < 0.05). LIMITATIONS: Not all patients underwent all tests, particularly serum tumor markers, hepatitis C virus antibody, and hepatitis C virus RNA tests. CONCLUSION: Proteinuria was a common presentation in patients with idiopathic MN, which was predominately found in middle-aged to elderly men. Secondary MN was more common than idiopathic MN, and most secondary MN diagnoses were secondary to systemic lupus erythematosus and hepatitis B infection. Copyright © 2008 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a chronic autoimmune disease mediated by autoreactive T-cells. Several experimental therapies targeting T-cells are in clinical trials. To understand how these therapies affect T-cell responses in vivo, assays that directly measure human T-cell function are needed. In a blinded, multicenter, case-controlled study conducted by the Immune Tolerance Network, we tested responses in an immunoblot and T-cell proliferative assay to distinguish type 1 diabetic patients from healthy control subjects. Peripheral blood cells from 39 healthy control subjects selected for DR4 and 23 subjects with recently diagnosed type 1 diabetes were studied. Autoantibody responses were measured in serum samples. Positive responses in both assays were more common in peripheral blood mononuclear cells from new-onset type 1 diabetic patients compared with control subjects. The proliferative, immunoblot, and autoantibody assays had sensitivities of 58, 91, and 78% with specificities of 94, 83, and 85%, respectively. When cellular assays were combined with autoantibody measurements, the sensitivity of the measurements was 75% with 100% specificity. We conclude that cellular assays performed on peripheral blood have a high degree of accuracy in discriminating responses in subjects with type 1 diabetes from healthy control subjects. They may be useful for assessment of cellular autoimmune responses involved in type 1 diabetes. [ABSTRACT FROM AUTHOR]

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora., (© 2024. The Author(s).)

Objective: To investigate whether a new preoperative education and discharge planning protocol reduced unexpected discharge delays for patients undergoing reconstructive surgery for head and neck cancer., Methods: A quality improvement (QI) intervention was implemented in January 2021 with several components to address historically prolonged observed lengths of stay (LOS) with head and neck cancer patients. The intervention added a preoperative educational visit with a head and neck cancer advanced practice provider, a standardized preoperative speech and swallow assessment, a personalized patient care plan document, discussion of inpatient hospital stay expectations, and early discharge planning. The intervention group included patients who underwent the preoperative education protocol from February to December 2021. For comparison, an age and sex-matched control group was constructed from inpatients who had been admitted for similar procedures in the 2 years prior to the QI intervention (2019-2020) and received standard of care counseling., Results: Our study demonstrated a significant reduction in observed to expected LOS ratio after implementation of the intervention (1.24 ± 0.74 control, 0.95 ± 0.52 intervention; P = .012)., Discussion: We discuss a preoperative education QI intervention at our institution. Our findings demonstrate that our intervention was associated with decreased LOS for patients undergoing head and neck reconstructive surgeries., Implications for Practice: This QI study shows the benefit of a new standardized preoperative education and discharge planning protocol for patients undergoing head and neck reconstructive surgeries., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Incorporation of irreversible steps in pathway design enhances the overall thermodynamic favorability and often leads to better bioconversion yield given functional enzymes. Using this concept, here we constructed the first non-natural itaconate biosynthesis pathway driven by thioester hydrolysis. Itaconate is a commercially valuable platform chemical with wide applications in the synthetic polymer industry. Production of itaconate has long relied on the decarboxylation of TCA cycle intermediate cis-aconitate as the only biosynthetic route. Inspired by nature's design of itaconate detoxification, here we engineered a novel itaconate producing pathway orthogonal to native metabolism with no requirement of auxotrophic knock-out. The reversed degradation pathway initiates with pyruvate and acetyl-CoA condensation forming (S)-citramalyl-CoA, followed by its dehydration and isomerization into itaconyl-CoA then hydrolysis into itaconate. Phenylacetyl-CoA thioesterase (PaaI) from Escherichia coli was identified via screening to deliver the highest itaconate formation efficiency when coupled to the reversible activity of citramalate lyase and itaconyl-CoA hydratase. The preference of PaaI towards itaconyl-CoA hydrolysis over acetyl-CoA and (S)-citramalyl-CoA also minimized the inevitable precursor loss due to enzyme promiscuity. With acetate recycling, acetyl-CoA conservation, and condition optimization, we achieved a final itaconate titer of 1 g/L using the thioesterase driven pathway, which is a significant improvement compared to the original degradation pathway based on CoA transferase. This study illustrates the significance of thermodynamic favorability as a design principle in pathway engineering., 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.)

Motivation: Disease gene prioritization methods assign scores to genes or proteins according to their likely relevance for a given disease based on a provided set of seed genes. This scoring can be used to find new biologically relevant genes or proteins for many diseases. Although methods based on classical random walks have proven to yield competitive results, quantum walk methods have not been explored to this end., Results: We propose a new algorithm for disease gene prioritization based on continuous-time quantum walks using the adjacency matrix of a protein-protein interaction (PPI) network. We demonstrate the success of our proposed quantum walk method by comparing it to several well-known gene prioritization methods on three disease sets, across seven different PPI networks. In order to compare these methods, we use cross-validation and examine the mean reciprocal ranks of recall and average precision values. We further validate our method by performing an enrichment analysis of the predicted genes for coronary artery disease., Availability and Implementation: The data and code for the methods can be accessed at https://github.com/markgolds/qdgp., (© The Author(s) 2024. Published by Oxford University Press.)

The use of green methods to treat industrial waste and waste reuse has become a key environmental issue. In order to achieve this goal, this study treated waste phosphogypsum (PG) and produced modified PG biochar to adsorb and remove phosphorus from PG leachate, so that the PG pollution problem was controlled. In this study, PG was modified with sodium carbonate (Na 2 CO 3 ) to prepare a modified PG biochar that was used for the removal of phosphorus-containing wastewater. An X-ray diffraction (XRD) analysis of the modified PG revealed that the main component was calcium carbonate (CaCO 3 ), and a suitable amount of modified PG could load calcium oxide (CaO) onto the biochar and improve its physical properties. The experimental results showed that the modified PG biochar had a maximum phosphorus adsorption capacity of 132 mg/g. A further investigation of the mechanism of adsorption revealed the importance of electrostatic attraction and chemical precipitation, and it was found that the CaO in the modified PG biochar could effectively facilitate the conversion of phosphate to hydroxylapatite (Ca 5 (PO 4 ) 3 OH) in water. The phosphorus removal rate from leachate obtained from a landfill containing PG was 99.38% for a specific dose of the modified PG biochar. In this study, a PG pollution control technology was developed to realize the goal of replacing waste with waste., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To examine patient characteristics that impact serial observation adherence among vestibular schwannoma (VS) patients., Study Design: Retrospective chart review., Setting: Single tertiary care center., Methods: We selected for VS patients from 201 to 2020 who elected for serial observation as initial management. Patients under 18, with previous management, bilateral or intralabyrinthine VS, and neurofibromatosis type 2 were excluded. Demographics, tumor characteristics, and follow-up status were extracted. Single and multiple logistic regression was used to identify patient characteristics impacting follow-up., Results: We identified 507 VS patients who chose serial observation as initial management. Most were female (56.0%), white (73.0%), and married (72.8%). The mean age was 59.3 and most had private insurance (56.4%). Median Charlson Comorbidity Index was 2.00. Mean pure tone audiometry (PTA) average was 41.7 Hz. Average tumor size was 9.04 mm. Of 507 patients, 358 (70.6%) returned for at least one follow-up. On multiple logistic regression analysis, patients with private insurance (odds ratio [OR]: 0.39, confidence interval [CI]: 0.22-0.68; P = .001), racial minority background (OR: 0.54, CI: 0.35-0.83; P = .005), worse PTA averages (OR: 0.99, CI: 0.98-1.00; P = .044), and older age at diagnosis (OR: 0.97, CI: 0.95-1.00; P = .038) were less likely to follow-up., Conclusion: Private health insurance, racial minority background, worse PTA average, and older age were associated with decreased follow-up among adult VS patients electing serial observation. Patients with these characteristics may require additional support to ensure serial observation adherence., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: China has entered the era of digital health care after years of reforms in the health care system. The use of digital technologies in healthcare services is rapidly increasing, indicating the onset of a new period. The reform of health insurance has also entered a new phase., Objective: This study aims to investigate the evolution of health care insurance within the context of telemedicine and Internet Plus Healthcare (IPHC) during the digital health care era by using scientometric methods to analyze publication patterns, influential keywords, and research hot spots. It seeks to understand how health care insurance has adapted to the growing integration of IPHC and telemedicine in health care services and the implications for policy and practice., Methods: A total of 411 high-quality studies were curated from the China National Knowledge Infrastructure (CNKI) database in the Chinese language, scientometric analysis was conducted, and VOSviewer software was used to conduct a visualized analysis of keywords and hot spots in the literature., Results: The number of articles in this field has increased notably from 2000 to 2022 and has increased annually based on a curve of y=0.332exp (0.4002x) with R 2 =0.6788. In total, 62 institutions and 811 authors have published research articles in the Chinese language in this field. This study included 290 keywords and formulated a total of 5 hot-topic clusters of "telemedicine," "IPHC," "internet hospital," "health insurance payments," and "health insurance system.", Conclusions: Studies on the application of digital technologies in health care insurance has evolved from foundational studies to a broader scope. The emergence of internet hospitals has showcased the potential for integrating IPHC services into insurance payment systems. However, this development also highlights the necessity for enhanced interregional coordination mechanisms. The reform of health insurance payment is contingent upon ongoing advancements in digital technology and increased investment in electronic medical records and primary health care services. Future efforts should focus on integrating technology with administrative systems, advancing mobile health care solutions, and ensuring interoperability among various payment systems to improve efficiency and standardize health care services., (©Zhiyuan Hu, Xiaoping Qin, Kaiyan Chen, Yu-Ni Huang, Richard Szewei Wang, Tao-Hsin Tung, Yen-Ching Chuang, Bing-Long Wang. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 23.07.2024.)

The behavior of polyatomic molecules around their equilibrium positions can be regarded as that of quantum-coupled anharmonic oscillators. Solving the corresponding Schrödinger equations enables the interpretation or prediction of the experimental spectra of molecules. In this study, we developed a novel approach for solving the excited states of anharmonic vibrational systems. The normal coordinates of the molecules are transformed into new coordinates through a normalizing flow parameterized by a neural network. This facilitates the construction of a set of orthogonal many-body variational wavefunctions. This methodology has been validated on an exactly solvable 64-dimensional coupled harmonic oscillator, yielding numerical results with a relative error of 10-6. The neural canonical transformations are also applied to calculate the energy levels of two specific molecules, acetonitrile (CH3CN) and ethylene oxide (C2H4O). These molecules involve 12 and 15 vibrational modes, respectively. A key advantage of this approach is its flexibility concerning the potential energy surface, as it requires no specific form. Furthermore, this method can be readily implemented on large-scale distributed computing platforms, making it easy to extend to investigating complex vibrational structures., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background and Objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline., Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites., Results: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet., Conclusion: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: To determine if an explainable artificial intelligence (XAI) model enhances the accuracy and transparency of predicting embryo ploidy status based on embryonic characteristics and clinical data., Methods: This retrospective study utilized a dataset of 1908 blastocyst embryos. The dataset includes ploidy status, morphokinetic features, morphology grades, and 11 clinical variables. Six machine learning (ML) models including Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Support Vector Machine (SVM), AdaBoost (ADA), and Light Gradient-Boosting Machine (LGBM) were trained to predict ploidy status probabilities across three distinct datasets: high-grade embryos (HGE, n = 1107), low-grade embryos (LGE, n = 364), and all-grade embryos (AGE, n = 1471). The model's performance was interpreted using XAI, including SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) techniques., Results: The mean maternal age was 38.5 ± 3.85 years. The Random Forest (RF) model exhibited superior performance compared to the other five ML models, achieving an accuracy of 0.749 and an AUC of 0.808 for AGE. In the external test set, the RF model achieved an accuracy of 0.714 and an AUC of 0.750 (95% CI, 0.702-0.796). SHAP's feature impact analysis highlighted that maternal age, paternal age, time to blastocyst (tB), and day 5 morphology grade significantly impacted the predictive model. In addition, LIME offered specific case-ploidy prediction probabilities, revealing the model's assigned values for each variable within a finite range., Conclusion: The model highlights the potential of using XAI algorithms to enhance ploidy prediction, optimize embryo selection as patient-centric consultation, and provides reliability and transparent insights into the decision-making process., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD)., Methods: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n =15) or rituximab (Group RTX, n =18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes., Results: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients ( P <0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio ( P <0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy ( P <0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy ( P >0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections., Conclusion: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD., Competing Interests: Conflicts of Interest: Lou CY, None; Wang Y, None; Xing JY, None; Ma T, None; Tao L, None; Wang XT, None; Wang RS, None., (International Journal of Ophthalmology Press.)

The widespread dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) and its drug resistance transfer poses a global public health threat. While previous studies outlined CRKP's drug resistance mechanism, there is limited research on strategies inhibiting CRKP drug resistance spread. This study investigates the potential of Bifidobacterium longum ( B. longum ) FB1-1, a probiotic, in curbing the spread of drug resistance among CRKP by evaluating its cell-free supernatant (CFS) for antibacterial activity. Evaluating the inhibitory effect of FB1-1 CFS on CRKP drug resistance spread involved analyzing its impact on drug resistance and virulence gene expression; drug resistance plasmid transfer FB1-1 CFS exhibited an MIC range of 125 μL/mL against CRKP. After eight hours of co-culture, CFS achieved a 96% and 100% sterilization rate at two and four times the MIC, respectively. At sub-inhibitory concentrations (1/2× MIC), FB1-1 CFS reduced the expression of the bla&#95;KPC gene, which is pivotal for carbapenem resistance, by up to 62.13% across different CRKP strains. Additionally, it markedly suppressed the expression of the uge gene, a key virulence factor, by up to 91%, and the fim&#95;H gene, essential for bacterial adhesion, by up to 53.4%. Our study primarily focuses on determining the inhibitory effect of FB1-1 CFS on CRKP strains harboring the bla&#95;KPC gene, which is a critical resistance determinant in CRKP. Furthermore, FB1-1 CFS demonstrated the ability to inhibit the transfer of drug resistance plasmids among CRKP strains, thus limiting the horizontal spread of resistance genes. This study highlights FB1-1 CFS's inhibitory effect on CRKP drug resistance spread, particularly in strains carrying the bla&#95;KPC gene, thus offering a novel idea and theoretical foundation for developing antibacterial drugs targeting CRKP resistance.

Background: Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (PH) (classified as World Health Organization Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesised that cluster analysis would identify subphenotypes with differential responses to oral PAH therapy., Methods: Two k-means analyses were performed on a national cohort of US veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a haemodynamic model (H) limited to patients with right heart catheterisations (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects., Results: Three distinct clusters of Group 3 PH patients were identified. In the inclusive model (C1 I n=43, 21.9%; C2 I n=102, 52.0%; C3 I n=51, 26.0%), lung disease and spirometry drove cluster assignment. By contrast, in the haemodynamic model (C1 H n=44, 39.3%; C2 H n=43, 38.4%; C3 H n=25, 22.3%), right heart catheterisation data surpassed the importance of lung disease and spirometry. In the haemodynamic model, compared to C3 H , C1 H experienced the greatest hazard for respiratory failure or death (HR 6.1, 95% CI 3.2-11.8). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups., Conclusions: Cluster analysis identifies novel real-world subphenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodological approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies., Competing Interests: Conflict of interest: S.W. Johnson, R-S. Wang, M.R. Winter, K.R. Gillmeyer, R.H. Goldstein and R.S. Wiener have nothing to disclose; K. Zeder has received a Max Kade Fellowship from the Max Kade Foundation NY, and support from MSD, Ferrer and Janssen (outside the scope of the current work); E.S. Klings has received support from CSL Behring, Pfizer, Novartis, Novo Nordisk and United Therapeutics (all outside of the scope of the current work); B.A. Maron reports support from Actelion Pharmaceuticals, Deerfield Company and Tenax Therapeutics (all outside the scope of the current work)., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2024.)

Background and Purpose: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC)., Methods: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated., Results: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively., Conclusions: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group., (© 2024. The Author(s).)

Objective: To investigate the impact of adjuvant radiotherapy in isolated locally advanced oral cavity cancers (pT3N0M0) without adverse features., Methods: We selected all patients from the National Cancer Database (2004-2019) who underwent surgical treatment where the final pathology was T3N0M0 with negative margins. Demographics, details of treatment, and outcomes were abstracted. The impact of radiotherapy on survival was assessed with univariable, multivariable, and propensity score-matched analyses., Results: We identified 571 patients in our survival cohort. Most were male (348, 60.9%), and median age was 65. Less than one-third (176, 30.8%) received adjuvant radiotherapy. The median length of follow-up was 29 months. Overall, adjuvant radiotherapy was associated with improved survival (87.2% vs. 77.7%, at 2 years, p < 0.01). On multivariable analysis controlling for age and comorbidities, this survival difference persisted (HR: 0.62, 95% CI: 0.43-0.90, p = 0.01). In a propensity score-matched population of 278 patients matched on age and comorbidities, adjuvant radiotherapy was still associated with longer survival (87.4% vs. 78.5%, p = 0.014)., Conclusion: In our study, adjuvant radiotherapy was associated with improved survival in completely excised locally advanced oral cavity tumors (T3N0M0). However, a significant proportion of patients do not receive adjuvant radiotherapy. These findings highlight the need for continued efforts to promote guideline-recommended care., Level of Evidence: 3 Laryngoscope, 134:2236-2242, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Complications associated with the use of autologous and homologous costal cartilage for nasal tip stabilizing grafts in septorhinoplasty are not well understood. Objective: The authors review current literature to evaluate complications associated with autologous and irradiated homologous costal cartilage (IHCC) used for septal extension and columellar strut grafts in rhinoplasty. Method: A comprehensive literature search was conducted in PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Articles that used autologous or IHCC for either septal extension or columellar strut grafts in patients undergoing septorhinoplasty were included. The primary outcomes analyzed were postoperative complications. Results: A total of 14 studies representing 1358 patients were included. The pooled complication rate was 4.7%. IHCC grafts were associated with a higher incidence of complications ( n  = 21, 5.0% vs. n  = 44, 4.6%, p  = 0.01). Resorption was the most common complication in the IHCC group and occurred significantly more frequently than in the autologous costal cartilage (ACC) group ( n  = 10, 2.4% vs. n  = 5, 0.49%, p  = 0.002). Deviation/warping was the most common complication in the ACC group ( n  = 16, 1.7%). Conclusion: Autologous and irradiated homologous costal rhinoplasties remain safe procedures. The increased incidence of resorption associated with IHCC grafts should be considered during preoperative planning.

Objective: To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults. Methods: A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk. Results: The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles ( P trend <0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 ( RR =1.11, 95% CI 1.01-1.22, P =0.023), TyG 8.6-8.9 ( RR =1.16, 95%CI 1.06-1.27, P =0.023), and TyG≥9.0 ( RR =1.20, 95%CI 1.10-1.31, P =0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions: The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.

Background: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission., Aim: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance., Methods: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis., Results: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target., Conclusion: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ethnopharmacological Relevance: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood., Aim of the Study: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism., Materials and Methods: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg -1 ) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg -1 , i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice., Results: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD., Conclusions: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Genomic profiling is now available for risk stratification of cytologically indeterminate thyroid nodules (ITNs). Mutations in RAS genes ( HRAS , NRAS , KRAS ) are found in both benign and malignant thyroid nodules, although isolated RAS mutations are rarely associated with aggressive tumors. Because the long-term behavior of RAS -mutant ITNs is not well understood, most undergo immediate surgery. In this multicenter retrospective cohort study, we characterize tumor growth kinetics of RAS -mutant ITNs followed with active surveillance (AS) using serial ultrasound (US) scans and examine the histopathologic diagnoses of those surgically resected. Methods: US and histopathologic data were analyzed retrospectively from two cohorts: (1) RAS -mutant ITNs managed with AS at three institutions (2010-2023) and (2) RAS -mutant ITNs managed with immediate surgery at two institutions (2016-2020). AS cohort subjects had ≥3 months of follow-up and two or more US scans. Cumulative incidence of nodule growth was determined by the Kaplan-Meier method and growth by ≥72% change in tumor volume. Pathological diagnoses for the immediate surgery cohort were analyzed separately. Results: Sixty-two patients with 63 RAS -mutated ITNs under AS had a median diameter of 1.7 cm (interquartile range [IQR] 1.2-2.6) at time of diagnosis. During a median AS period of 23 months (IQR 9.5-53.5 months), growth was observed in 12 of 63 nodules (19.0%), with a cumulative incidence of 1.9% (1 year), 23.0% (3 years), and 28.0% (5 years). Most nodules (81.0%) demonstrated stability. Surgery was ultimately performed in 6 nodules, of which 1 (16.7%) was malignant. In the cohort of 209 RAS -mutant ITNs triaged to immediate surgery, 33% were malignant (23.9% American Thyroid Association [ATA] low-risk cancers, 7.2% ATA intermediate-risk, and 1.9% ATA high-risk. During a median follow-up of 6.9 (IQR 4.4-7.1) years, there were no disease-specific deaths in these patients. Conclusions: We describe the behavior of RAS -mutant ITNs under AS and find that most demonstrate stability over time. Of the resected RAS -mutant nodules, most were benign; of the cancers, most were ATA low-risk. Immediate surgical resection of all RAS -mutant ITNs appears to be a low-value practice. Further research is needed to help define cases most appropriate for AS or immediate surgery.

High drug development costs and the limited number of new annual drug approvals increase the need for innovative approaches for drug effect prediction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), led to a global pandemic with high morbidity and mortality. Although effective preventive measures exist, there are few effective treatments for hospitalized patients with SARS-CoV-2 infection. Drug repurposing and drug effect prediction are promising strategies that could shorten development time and reduce costs compared with de novo drug discovery. In this work, we present a machine learning framework to integrate a variety of target network features and physicochemical properties of compounds, and analyze their influence on the therapeutic effects for SARS-CoV-2 infection and on host cell cytotoxic effects. Random forest models trained on compounds with known experimental effects on SARS-CoV-2 infection and subsequent feature importance analysis based on Shapley values provided insights into the determinants of drug efficacy and cytotoxicity, which can be incorporated into novel drug discovery approaches. Given the complexity of molecular mechanisms of drug action and limited sample sizes, our models achieve a reasonable mean area under the receiver operating characteristic curve (ROC-AUC) of 0.73 on an unseen validation set. To our knowledge, this is the first work to incorporate a combination of network and physicochemical features of compounds into a machine learning model to predict drug effects on SARS-CoV-2 infection. Our systems pharmacology-based machine learning framework can be used to classify other existing drugs for SARS-CoV-2 infection and can easily be adapted to drug effect prediction for future viral outbreaks., (© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Taiwan has a substantial number of veterans, but knowledge regarding their emergency department (ED) visits during the coronavirus disease 2019 (COVID-19) pandemic remains limited. This study examined the characteristics of veterans' ED visits during Taiwan's COVID-19 epidemic., Methods: This was a cross-sectional study conducted at the ED of a large veteran medical center located in Taipei, Taiwan, from May 2018 to October 2021. We analyzed the numbers and features of visits in summer and autumn according to the first wave of the COVID-19 epidemic in Taiwan in 2021., Results: Medical institutions were positively associated with veteran status. Emergency department complaints of trauma (adjusted odds ratio [AOR] = 1.15, 95% CI: 1.06-1.25; summer P < .01) and chest pain/tightness (AOR = 1.65, 95% CI: 1.45-1.87; summer P < .01; AOR = 1.4, 95% CI: 1.26-1.55; P < .01) were associated with increased odds of being a veteran. Triage levels above 2 were positively associated with veteran status in the autumn model (AOR = 1.14, 95% CI: 1.07-1.22; P < .01). Patients hospitalized after ED visits were associated with reduced odds of veteran status (P < .01). Those who spent a long time in the ED were more likely to be veterans than those who spent a shorter time in the ED (P < .01). Veterans were less likely to visit the ED regardless of the time frame of the study period (P < .01), except during the COVID-19 outbreak in the autumn (2019-2020)., Conclusions: The distinctions in ED visits highlighted the individuality of veterans' medical needs. Our findings suggest that the veteran medical system can add to the focus on improving senior-friendly care, fall prevention, quality of life of institutionalized veterans, access for homeless veterans, and care for ambulatory care-sensitive conditions., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Life satisfaction (LS) is part of a positive psychological feeling that protects individuals from a physical decline in old age. A healthy lifestyle, including physical activity (PA) and a healthy diet, such as the intake of fruits and vegetables (F&V), can lead to a better experience of LS in older adults. However, the association between PA and F&V intake habits when occurring together in older adults is still unclear for LS. The study aimed to investigate the combined association of PA and F&V intake on LS among a cohort of older Taiwanese adults., Methods: Five waves of population-based data gathered by the Taiwan Longitudinal Survey on Aging between 1999 and 2015 were analyzed. The year 1999 was set as the baseline, and the number of respondents was 4,440. The independent variables included the frequency, duration, and intensity of PA and the frequency of F&V intake. LS was assessed by using the Life Satisfaction Index. We performed generalized estimating equations (GEE) analysis with adjustment for covariates of health behaviors and health indicators., Results: After adjusting for confounders, model 1 showed that moderate and high-PA levels significantly correlated with LS (odds ratio [OR] = 1.41, 95% CI = 1.12-1.79) and OR = 1.74, 95% CI = 1.50-2.02). Moreover, high-F&V intake significantly correlated with LS (OR = 2.07, 95% CI = 1.69-2.53). Regarding the combined association shown in model 2, compared with both the low PA and F&V intake group, there were significantly higher LS in the both-high-group (OR = 4.69, 95% CI = 3.49-6.31), only-high-F&V intake (OR = 2.87, 95% CI = 2.14-3.85), only-high-PA (OR = 2.48, 95% CI = 1.74-3.52)., Conclusions: Our findings show the significant combined association of PA and F&V intake on LS among older adults. In addition, older adults who engaged in higher frequency, duration, and intensity of daily PA combined more than seven times a week of F&V intake had significantly higher LS than those who only engaged in low PA or only intake less F&V. Adopting multiple healthy behaviors in daily life is a safe and effective approach to promote LS among older adults., (© 2024. The Author(s).)

Background: The pivotal role of Human Resource Management (HRM) in hospital administration has been acknowledged in research, yet the examination of HRM practices in the world's premier hospitals has been scant., Objective: This study explored how the world's leading hospitals attain operational efficiency by optimizing human resource allocation and melding development strategies into their HRM frameworks. A comparative analysis of the HRM frameworks in the top five global hospitals was undertaken to offer a reference model for other hospitals., Methods: This research offers a comparative exploration of the HRM frameworks utilized by the top five hospitals globally, underscoring both shared and distinct elements. Using a multi-case study methodology, the research scrutinized each hospital's HRM framework across six modules, drawing literature from publicly accessible sources, including websites, annual reports, and pertinent English-language scholarly literature from platforms such as Google Scholar, PubMed, Medline, and Web of Science., Results: The analyzed hospitals exhibited inconsistent HRM frameworks, yet all manifested potent organizational cultural attributes and maintained robust employee training and welfare policies. The design of the HR systems was strategically aligned with the hospitals' objectives, and the study established that maintaining a sustainable talent system is pivotal to achieving hospital excellence., Conclusion: The HRM frameworks of the five analyzed hospitals align with their developmental strategies and exhibit unique organizational cultural attributes. All five hospitals heavily prioritize aligning employee development with overall hospital growth and place a spotlight on fostering a healthy working environment and nurturing employees' sense of achievement. While compensation is a notable performance influencer, it is not rigorously tied to workload in these hospitals, with employees receiving mid-to-upper industry-range compensation. Performance assessment criteria focus on job quality and aligning employee actions with organizational values. Comprehensive welfare and protection are afforded to employees across all five hospitals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Qin, Huang, Chiu and Wang.)

Background: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) can accurately detect relative gene expression levels in biological samples. However, widely used reference genes exhibit unstable expression under certain conditions., Methods and Results: Here, we compared the expression stability of eight reference genes (RPLP0, RPS18, RPL13, EEF1A1, β-actin, GAPDH, HPRT1, and TUBB) commonly used in liproxstatin-1 (Lip-1)-treated K562 cells using RNA-sequencing and RT-qPCR. The expression of EEF1A1, ACTB, GAPDH, HPRT1, and TUBB was considerably lower in cells treated with 20 μM Lip-1 than in the control, and GAPDH also showed significant downregulation in the 10 μM Lip-1 group. Meanwhile, when we used geNorm, NormFinder, and BestKeeper to compare expression stability, we found that GAPDH and HPRT1 were the most unstable reference genes among all those tested. Stability analysis yielded very similar results when geNorm or BestKeeper was used but not when NormFinder was used. Specifically, geNorm and BestKeeper identified RPL13 and RPLP0 as the most stable genes under 20 μM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable under 10 μM Lip-1 treatment. TUBB and EEF1A1 were the most stable genes in both treatment groups according to the results obtained using NormFinder. An assumed most stable gene was incorporated into each software to validate the accuracy. The results suggest that NormFinder is not an appropriate algorithm for this study., Conclusions: Stable reference genes were recognized using geNorm and BestKeeper but not NormFinder. Overall, RPL13 and RPLP0 were the most stable reference genes under 20 μM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable genes under 10 μM Lip-1 treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Human resource management (HRM) in healthcare is an important component in relation to the quality and efficiency of healthcare delivery. However, a comprehensive overview is lacking to assess and track the current status and trends of HRM research in healthcare. This study aims to describe the current situation and global trends in HRM research in healthcare as well as to indicate the frontiers and future directions of research. The research methodology is based on bibliometric mapping using scientific visualization software (VOSviewer). The data were collected from the Web of Science(WoS) core citation database. After applying the search criteria, we retrieved 833 publications, which have steadily increased over the last 30 years. In addition, 93 countries and regions have published relevant research. The United States and Australia have made significant contributions in this area. Current research articles focus on topics clustered into performance, hospital/COVID-19, job satisfaction, human resource management, occupational/mental health, and quality of care. The most frequently co-occurring keywords are human resource management, job satisfaction, nurses, hospitals, health services, quality of care, COVID-19, and nursing. There is limited research on compensation management and employee relations management, so the current HRM research field still has not been able to present a complete and systematic roadmap. We propose that our colleagues should consider focusing on these research gaps in the future., (© 2023. The Author(s).)

Turbulence is a ubiquitous phenomenon in neutral and conductive fluids. According to classical theory, turbulence is a rotating flow containing vortices of different scales. Eddies play a fundamental role in the nonlinear cascade of kinetic energy at different scales in turbulent flow. In conductive fluids, the Alfvénic/kinetic Alfvénic wave (AW/KAW) is the new "cell" of magnetohydrodynamic (MHD) turbulence (frozen-in condition). Wave energy, which has equal kinetic and magnetic energy, is redistributed among multiple-scale Fourier modes and transferred from the large MHD scale to the small kinetic scale through the collision of counter-propagating Alfvénic wave packages propagating along the magnetic field line. Fluid-like eddy-dominant plasma flow turbulence has never been found in space since the launch of the first satellite in 1957. In this paper, we report the first observation of eddy-dominant turbulence within magnetic reconnection-generated fast flow in the Earth's tail plasma sheet by the Magnetospheric Multiscale Spacecraft (MMS). In eddy-dominant turbulent reconnection jet, ions dominate the flow field while electrons dominate current and magnetic fluctuations. Our findings shed new light on the nonlinear kinetic and magnetic energy cascade in MHD turbulence., (© 2023. The Author(s).)

Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity., (© 2023. Springer Nature Limited.)

As a sustainable management of fossil fuel resources and ecological environment protection, recycling used lubricating oil has received widespread attention. However, large amounts of waste lubricating-oil regeneration wastewater (WLORW) are inevitably produced in the recycling process, and challenges are faced by traditional biological treatment of WLORW. Thus, this study investigated the effectiveness of electrocoagulation (EC) as pretreatment and its removal mechanism. The electrolysis parameters (current density, initial pH, and inter-electrode distance) were considered, and maximal 60.06% of oil removal was achieved at a current density of 15 mA/cm 2 , initial pH of 7, and an inter-electrode distance of 2 cm. The dispersed oil of WLORW was relatively easily removed, and most of the oil removal was contributed by emulsified oil within 5-10 μm. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that effective removal of the biorefractory organic compounds could contribute to the improvement of biodegradability of WLORW. Thus, the 5-day biochemical oxygen demand/chemical oxygen demand ratio (BOD 5 /COD) was significantly enhanced by 4.31 times, which highly benefits future biological treatment. The routes of WLORW removal could be concluded as charge neutralization, adsorption bridging, sweep flocculation, and air flotation. The results demonstrate that EC has potential as an effective pretreatment technology for WLORW biological treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a novel delithiation process for epitaxial thin films of LiCoO 2 (001) cathodes using only physical methods, based on ion sputtering and annealing cycles. Preferential Li sputtering followed by annealing produces a surface layer with a Li molar fraction in the range 0.5 < x < 1, characterized by good crystalline quality. This delithiation procedure allows the unambiguous identification of the effects of Li extraction without chemical byproducts and experimental complications caused by electrolyte interaction with the LiCoO 2 surface. An analysis by X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) provides a detailed description of the delithiation process and the role of O and Co atoms in charge compensation. We observe the simultaneous formation of Co 4+ ions and of holes localized near O atoms upon Li removal, while the surface shows a (2 × 1) reconstruction. The delithiation method described here can be applied to other crystalline battery elements and provide information on their properties that is otherwise difficult to obtain.

Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24 mm Hg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP ⩾19 mm Hg ( N  = 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was <1.0 beginning at PAC ⩾3.0 ml/mm Hg and decreased progressively to ∼7 ml/mm Hg. A protective association between PAC ⩾3.0 ml/mm Hg and mortality was also observed in the validation cohort ( N  = 1,514; age, 60.2 yr [range = 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P  < 0.001) and 49% (95% confidence interval, 0.38-0.69; P  < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.

Purpose of Review: Disparities in prostate cancer care and outcomes have been well recognized for decades. The purpose of this review is to methodically highlight known racial disparities in the care of prostate cancer patients, and in doing so, recognize potential strategies for overcoming these disparities moving forward., Recent Findings: Over the past few years, there has been a growing recognition and push towards addressing disparities in cancer care. This has led to improvements in care delivery trends and a narrowing of racial outcome disparities, but as we highlight in the following review, there is more to be addressed before we can fully close the gap in prostate cancer care delivery. While disparities in prostate cancer care are well recognized in the literature, they are not insurmountable, and progress has been made in identifying areas for improvement and potential strategies for closing the care gap., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To examine the extent to which the urologist performing biopsy contributes to variation in prostate cancer detection during fusion-guided prostate biopsy., Methods: All men in the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry who underwent fusion biopsy at Michigan Medicine from August 2017 to March 2019 were included. The primary outcomes were clinically significant cancer detection rate (defined as Gleason Grade ≥2) in targeted cores and clinically significant cancer detection on targeted cores stratified by PI-RADS score. Bivariate and multivariable logistic regression analyses were performed., Results: A total of 1133 fusion biopsies performed by 5 providers were included. When adjusting for patient age, PSA, race, family history, prostate volume, clinical stage, and PI-RADS score, there was no significant difference in targeted clinically significant cancer detection rates across providers (range = 38.5%-46.9%, adjusted P-value = .575). Clinically significant cancer detection rates ranged from 11.1% to 16.7% in PI-RADS 3 (unadjusted P = .838), from 24.6% to 43.4% in PI-RADS 4 (adjusted P = .003), and from 69.4% to 78.8% in PI-RADS 5 (adjusted P = .766) lesions., Conclusion: There was a statistically significant difference in clinically significant prostate cancer detection in PI-RADS 4 lesions across providers. These findings suggest that even among experienced providers, variation at the urologist level may contribute to differences in clinically significant cancer detection rates within PI-RADS 4 lesions. However, the relative impact of biopsy technique, radiologist interpretation, and MR acquisition protocol requires further study., Competing Interests: DECLARATION OF COMPETING INTEREST Simpa S. Salami is supported in part by the Prostate Cancer Foundation, Department of Defense, the National Institutes of Health (the University of Michigan Prostate S.P.O.R.E., P50 CA186786-05; and the University of Michigan Comprehensive Cancer Center core grant, 2-P30-CA-046592–24), the Men of Michigan Prostate Cancer Research Fund, the A. Alfred Taubman Biomedical Research Institute, Robert Wood Johnson Foundation as part of the Harold Amos Medical Faculty Development Program (AMFDP), and the Urology Care Foundation Rising Stars in Urology Research Award Program and Astellas, Inc. He also is on a study advisory committee for Bayer Pharma and has a non-sponsored research agreement with GenomeDx. Matthew S. Davenport serves as the Treasurer of the Society of Advanced Body Imaging and receives royalties from Wolters Kluwer and uptodate.com. Arvin George has consulting agreements with Philips Medical (research) and Lina Medical (Consultant). For the remaining authors, there are no conflicts of interest., (Published by Elsevier Inc.)

Objectives: Crystalline silica, which is a causative agent of silicosis (an occupational disease), is manufactured in a variety of products (particles) with different particle characteristics, such as size and surface properties. In Japan, the products are currently uniformly controlled as crystalline silica, which is a substance subject to labeling and notification requirements. However, since the toxicity of silica particles reportedly varies depending on its characteristics, businesses are encouraged to conduct appropriate risk assessments for each product to prevent silicosis. Recently, silica particles have been reported to induce lysosomal membrane damage, leading to the activation of proinflammatory factors. An indirect method to evaluate lysosomal membrane damage known as the erythrocyte hemolysis assay, in which the erythrocyte membrane is assumed to be the lysosomal membrane, was performed. This study aimed to examine the possibility of constructing a screening system for proinflammatory potential prediction of silica particles based on their erythrocyte hemolytic activity., Methods: Hemolysis assays were performed on the silica particles with different sizes, crystallinity, and surface functional groups using the erythrocytes from a healthy volunteer. Additionally, the hemolytic activity of other element particles was compared with that of the silica particles, and 27 types of commercially available crystalline silica particle products underwent screening trials., Results: The hemolytic activity of silica particles was higher in crystalline than that in amorphous and increased with the decreasing size. The hemolytic reaction was particular to silica particles and rarely occurred in particles of other elements. Moreover, the hemolytic activity was significantly suppressed if the silica particles surface was modified with metal ions (Fe 3+ , Al 3+ ). The hemolytic activities of the crystalline silica products used industrially significantly differed., Conclusions: This study revealed that particle properties, such as size, crystallinity, and surface functional groups, affect the hemolytic activity of silica particles. Particularly, the surface functional groups (silanol groups) that are unique to silica particles were considered to be strongly involved in hemolytic activities. Since grading the commercially available crystalline silica particle products based on the hemolytic rate was possible, hemolytic activity was suggested to be an evaluation index for predicting the proinflammatory potential of silica particles.

COVID-19 is an infectious disease caused by SARS-CoV-2 leading to the ongoing global pandemic. Infected patients developed a range of respiratory symptoms, including respiratory failure, as well as other extrapulmonary complications. Multiple comorbidities, including hypertension, diabetes, cardiovascular diseases, and chronic kidney diseases, are associated with the severity and increased mortality of COVID-19. SARS-CoV-2 infection also causes a range of cardiovascular complications, including myocarditis, myocardial injury, heart failure, arrhythmias, acute coronary syndrome, and venous thromboembolism. Although a variety of methods have been developed and many clinical trials have been launched for drug repositioning for COVID-19, treatments that consider cardiovascular manifestations and cardiovascular disease comorbidities specifically are limited. In this review, we summarize recent advances in drug repositioning for COVID-19, including experimental drug repositioning, high-throughput drug screening, omics data-based, and network medicine-based computational drug repositioning, with particular attention on those drug treatments that consider cardiovascular manifestations of COVID-19. We discuss prospective opportunities and potential methods for repurposing drugs to treat cardiovascular complications of COVID-19., Competing Interests: Disclosures J.L. is scientific co-founder of Scipher Medicine, Inc., a network medicine-based therapeutics company. R.-S.W. has no conflicts of interest to declare.