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We compared the nano-structures of three samples of ZnO thin films grown on GaN withdifferent growth temperature conditions. Although disconnected spiral domain structures(of the order of 100 nm in width) were observed in the samples of high-temperature growth,their crystal qualities are generally better than the one grown at low temperature,either near the GaN interface or far away from the interface. In the sample ofhigh-temperature growth through the whole process, the domain structures extend fromthe interface with a smaller scale and almost vertical sharp boundaries. The samplegrown at the low temperature showed a generally continuous structure from theinterface. However, its crystal quality is quite poor. In the sample with initiallow-temperature growth and then high-temperature growth, the ZnO layer started with acontinuous structure, like the sample of low-temperature growth. However, it evolvedinto domain structures similar to the sample of high-temperature growth beyondabout 200 nm in thickness. The samples of high-temperature growth generally havehigher photon emission efficiencies. The sample grown at the high temperaturethrough the whole growth process has the highest emission quantum efficiency. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To define injury and repair in the context of critical illness. DESIGN: Review of the literature. RESULTS: The medical practice of critical care medicine has long been one of aggressive assistance and support: utilizing state of the art technology to support the functions of the human body until homeostasis is again achieved and the patient is functioning sufficiently to allow the support to discontinue. Injury is defined as the disruption of molecular, cellular, or organ functions resulting from an external or internal stimulus. Repair is defined as an adaptive process that occurs in response to injury and involves both local and systemic responses that serve to restore structure and regulation for the purpose of organ/tissue function. The study of injury in critical illness is now occurring 'upstream,' at the genetic and cellular levels, to understand how damaging effects of acute inflammation from injury can be prevented or modulated. CONCLUSION: To treat the patient with critical illness more effectively, it is important to understand both the cause of the insults and the repair processes triggered by the insults because both processes affect the eventual course of the critical illness. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic inflammatory disease and an estrogen-dependent disease, so dietary factors that can modulate estrogen activity may be clinically important. Dietary fiber, widely distributed in vegetables and fruits, is closely associated with a plant-based diet. Therefore, this study aims to analyze and explore the relationship between dietary fiber intake and the risk of endometriosis providing insights for future clinical significance and treatment approaches. This cross-sectional study obtained data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 for women aged 20-54 years. A total of 2840 subjects were finally included for analysis, 2599 (91.51%) in the non-endometriosis group and 241 (8.49%) in the endometriosis group. The study used dietary fibre intake as exposure variable and endometriosis risk as outcome variable. Through the use of multiple regression modelling, subgroup analyses, smoothed curve fitting, and threshold effect tests, we uncovered a significant link between exposure and outcome. In Model 2 (Multiple regression equation model after adjusting all confounding variables), after adjusting for confounders, dietary fiber intake was negatively associated with the likelihood of developing endometriosis(OR = 0.588, 95% CI = 0.360-0.959, p = 0.041). In subgroup analyses stratified by age, race, BMI, educational level, hypertension, diabetes,and hyperlipidemia, significant interactions were visualised from smoothed fitted curves. In the cross-sectional study, a connection was observed between a higher intake of dietary fiber and a decreased risk of endometriosis., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval The National Center for Health Statistics’ Ethics Committee has granted approval for this study, in accordance with the Declaration of Helsinki. The retrospective analysis used in this study ensured that no potential harm was caused to the participants. The study was conducted without revealing any personal information or compromising the privacy of the participants. Before attending, all participants were asked to sign a form stating their informed consent. Electronic downloads enable quick and convenient access to all necessary materials, which can be found at https://wwwn.cdc.gov/nchs/nhanes/default.aspx, (© 2024. The Author(s).)

Objective: To report the New England Trophoblastic Disease Center (NETDC) experience with atypical placental site nodules (APSN)., Methods: The NETDC registry was reviewed from 2005 to 2022 and clinical data abstracted. Expert pathologists in GTD reviewed available slides with concurrent immunohistochemical analysis. Targeted deep sequencing was performed for four cases., Results: Among 35 cases of APSN identified, 29 had clinical and demographic data available. Abnormal uterine bleeding (59.3%) was the most common presenting symptom. Most women (79.3%) had an antecedent live birth. Two cases were incidentally diagnosed after hysterectomy for other indications, and one case lost to follow-up. Among the remaining 26 cases, 11 (42.3%) opted for hysterectomy and 15 for re-sampling (57.7%), among whom 3 later underwent hysterectomy for persistent APSN. Subsequent obstetrical outcomes included 3 spontaneous abortions, 1 therapeutic abortion, 1 ectopic pregnancy, 2 cesarean sections, 1 cesarean hysterectomy, and 1 spontaneous vaginal delivery. Subsequent pathology was available for 26 cases: 4 epithelioid trophoblastic tumors (15.4%), 9 APSN (34.6%), 3 PSN (11.5%), and 10 without abnormalities (38.4%). Histopathologic characteristics of APSN included moderate to severe cytologic atypia, median Ki-67 proliferation index of 8%, and typical immunohistochemical profiles (diffuse or multifocal positivity for p63 and GATA-3 and absent or focal CD146). No histopathologic feature predicted ETT. Among 4 sequenced cases, no recurrent genomic features were identified., Conclusions: APSN is a rare form of gestational trophoblastic proliferation with uncertain malignant potential. While normal obstetric outcomes are possible, the persistence rate is high, and definitive management remains hysterectomy., Competing Interests: Declaration of competing interest The authors report no financial conflicts of interest related to this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: Systematic review and meta-analysis., Objective: This study aims to assess the effectiveness of lumbar segmental stabilization exercise (LSSE) in managing spondylolysis and spondylolisthesis., Summary of Background Data: Spondylolysis and spondylolisthesis are spinal disorders associated with lumbar segmental instability. LSSE has shown positive effects in treating these conditions; however, systematic reviews and meta-analyses are lacking., Materials and Methods: A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, including studies from the inception of the databases used up to January 2024, was conducted. Disability improvement and pain intensity change were the primary and secondary outcomes, respectively, standardized using Hedges g . Eligible articles underwent independent scrutiny by two authors, who also performed data extraction and quality assessment. Data pooling was accomplished using a random-effects model., Results: In total, five randomized controlled trials comprising 198 participants were included, revealing a trend effect toward disability improvement in the LSSE group (Hedges g =-0.598, 95% CI: -1.211 to 0.016, P =0.056, I2 =75.447%). When the LSSE was administered as a single treatment, disability improvement became significant (Hedge g =-1.325, 95% CI: -2.598 to -0.053, P =0.041, I2 =80.020%). No significant effect of LSSE on pain reduction was observed (Hedges g =-0.496, 95% CI: -1.082 to 0.090, P =0.097, I2 =73.935%)., Conclusions: In summary, our meta-analysis suggests that LSSE can potentially improve disability, especially when used as a single treatment. LSSE appears more beneficial in reducing disability than alleviating pain. Future research on different patient groups is needed to understand comprehensively LSSE's effects on other musculoskeletal disorders., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Autologous chimeric antigen receptor T-cell therapy presents promising treatment outcomes for various cancers. However, its potential is restrained by unique supply chain challenges, including dynamic patient health conditions and extended turnaround time. These challenges often lead to missed optimal treatment windows, impeding the effective delivery of life-saving treatments. This article presents SimPAC (simulation-based decision support for Patient-centric manufacturing of autologous cell therapies). SimPAC is designed to model and incorporate real-time patient health conditions into the supply chain decisions of autologous chimeric antigen receptor T-cell therapy. SimPAC integrates system dynamics and agent-based simulation techniques, facilitating the adaptation of manufacturing processes and production schedules based on real-time patient health conditions. SimPAC can model various patient disease progressions using parametric functions, nonparametric functions, or tabular data. Additionally, SimPAC offers easy configuration options to model various cell therapy supply chains. We provide two case studies to demonstrate the capabilities of SimPAC and highlight the benefits of patient-centric manufacturing, including improved survival rates and potential economic advantages. However, while the benefits are significant, our study also emphasizes the importance of balancing improved patient outcomes, economic viability and ethical considerations in the context of personalized medicine. SimPAC can be used to explore applications of this approach to diverse therapeutic contexts and supply chain configurations., 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 article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: This systematic review and meta-analysis aimed to evaluate the influence of core muscle training on throwing ball velocity among overhead throwing athletes., Design: A literature search was performed from inception to July 2023 for randomized controlled trials investigating the effects of core muscle training on overhead throwing ball velocity. The primary outcome was the change in standing throwing ball velocity. The secondary outcome focused on the enhancement of step/jump throwing ball velocity., Results: Ten randomized controlled trials were included, revealing a significant improvement in standing throwing ball velocity in the group undergoing core muscle training (Hedges' g = 0.701, 95% confidence interval = 0.339 to 1.063, P < 0.001). Longer treatment duration and a higher frequency of core muscle training sessions per week contributed to improved standing throwing ball velocity. However, core muscle training did not show significant benefits for step (Hedge's g = 0.463, 95% confidence interval = -0.058 to 0.985, P = 0.082) and jump throwing ball velocity (Hedges' g = 0.550, 95% confidence interval = -0.051 to 1.152, P = 0.073)., Conclusions: Core muscle training significantly enhanced standing ball throwing velocity. However, its effect on step/jump throwing ball velocity was less certain. Further research is needed to explore the impact of core muscle training (especially its long-term effects) on throwing ball velocity., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tzang et al.)

Terrestrial mud volcanoes represent surface features of channels for subsurface methane transport and, therefore, constitute an important source of methane emission from natural environments. How microbial processes regulate methane emissions in terrestrial mud volcanoes has yet to be fully addressed. This study demonstrated the geochemical characteristics and microbial communities of four mud volcano and seep sites in two geological settings of Sicily, Italy. At sites within the accretionary wedge that exhibited higher methane and sulfate concentrations, the communities were dominated by members capable of catalyzing methane and sulfate metabolisms and organic degradation. In particular, both anaerobic and aerobic methanotrophs were abundant and their abundance distribution coincided with the geochemical transition. In contrast, the sites near Mount Etna were characterized by high fluid salinity, CO 2 , and low methane and sulfate concentrations, with communities consisting of halophilic organic degraders and sulfur metabolizers, along with a minor presence of aerobic methanotrophs. Substantial variations in community composition and geochemistry across spatial and vertical redox gradients suggest that physicochemical contexts imposed by the geology, fluid path, and source characteristics play a vital role in shaping community composition and cycling of methane, sulfur and organic carbon in Sicily mud volcanoes., 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 Chen, Chiu, Tu, Italiano, Wang and Lin.)

Purpose: This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133 + ) ovarian cancer (OC) stem-like cells., Methods: CD133 + (CD133 positive) OVCAR4 and CD133 negative (CD133 - ) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133 + OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4)., Results: The performance of CD133 + OVCAR4 cells was much better than that of CD133 - OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133 - OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133 + OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133 + OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133 + OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs., Conclusion: The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133 + OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway., (© 2024. The Author(s).)

Primary endometrial squamous cell carcinoma (PESCC) is a rare malignant tumor. To investigate the clinical and pathological features of PESCC, two cases of PESCC in Fujian Maternal and Child Health Hospital were retrospectively studied and the literatures were reviewed. Both of the two cases were menopausal women aged 57-62 years, clinically presenting with "vaginal discharge". Case 1 was a non-keratinising squamous cell carcinoma with high-risk HPV infection. Tumor infiltrated in deep myometrium with multifocal intravascular thrombus and macro metastases to one pelvic lymph node (1/15) and abdominal aortic lymph node (1/1). Lung metastasis occurred 36 months after the surgery. After surgical resection and without postoperative supplemental therapy, the patient remained tumor-free for 110 months to date. Case 2 had a history of breast cancer for 5 years and long-term intake of aromatase inhibitor drugs without HPV infection. It was a keratinized squamous cell carcinoma. Tumor also infiltrated in deep myometrium with multifocal intravascular thrombus and one pelvic lymph node metastasis (1/18), However, no metastasis was seen elsewhere. To date, the patient survived for 16 months without tumor after surgery. Both of the two cases expressed squamous epithelial markers P40, P63, and CK5/6, but neither expressed PAX8 or PR. Case 1 had diffuse expression of P16, wild-type P53, and ER-negative. Case 2 had negative P16, mutant P53, and focal positive ER. PESCC is often associated with HPV infection and low estrogen levels. However, studies in the literatures have found that P16 expression is not always consistent with HPV infection, indicating that PESCC cannot be easily classified as HPV-associated or non-dependent like cervical cancer. There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC., 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 Zhang, Lin, Lin, Lin, Luo and Xu.)

Background: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance., Methods: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted., Results: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases., Conclusions: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen., (© 2024. The Author(s).)

Background: The pursuit of selective therapeutic delivery to target tissue types represents a key goal in the treatment of a range of adverse health issues, including diseases afflicting the heart. The development of new cardiac-specific ligands is a crucial step towards effectively targeting therapeutics to the heart., Methods: Utilizing an ex vivo and in vivo SELEX approaches, we enriched a library of 2'-fluoro modified aptamers for ventricular cardiomyocyte specificity. Lead candidates were identified from this library, and their binding and internalization into cardiomyocytes was evaluated in both ex vivo and in vivo mouse studies., Results: The ex vivo and in vivo SELEX processes generated an aptamer library with significant cardiac specificity over non-cardiac tissues such as liver and skeletal muscle. Our lead candidate aptamer from this library, CA1, demonstrates selective in vivo targeting and delivery of a fluorophore cargo to ventricular cardiomyocytes within the murine heart, while minimizing off-target localization to non-cardiac tissues, including the liver. By employing a novel RNase-based assay to evaluate aptamer interactions with cardiomyocytes, we discovered that CA1 predominantly internalizes into ventricular cardiomyocytes; conversely, another candidate CA41 primarily binds to the cardiomyocyte cell surface., Conclusions: These findings suggest that CA1 and CA41 have the potential to be promising candidates for targeted drug delivery and imaging applications in cardiac diseases., Competing Interests: CONFLICT OF INTEREST None

Background: The outer mitochondrial Rho GTPase 1, MIRO1, mediates mitochondrial motility within cells, but implications for vascular smooth muscle cell (VSMC) physiology and its roles invascular diseases, such as neointima formation following vascular injury are widely unknown., Methods: An in vivo model of selective Miro1 deletion in VSMCs was generated, and the animals were subjected to carotid artery ligation. The molecular mechanisms relevant to VSMC proliferation were then explored in explanted VSMCs by imaging mitochondrial positioning and cristae structure and assessing the effects on ATP production, metabolic function and interactions with components of the electron transport chain (ETC)., Results: MIRO1 was robustly expressed in VSMCs within human atherosclerotic plaques and promoted VSMC proliferation and neointima formation in mice by blocking cell-cycle progression at G1/S, mitochondrial positioning, and PDGF-induced ATP production and respiration; overexpression of a MIRO1 mutant lacking the EF hands that are required for mitochondrial mobility did not fully rescue these effects. At the ultrastructural level, Miro1 deletion distorted the mitochondrial cristae and reduced the formation of super complexes and the activity of ETC complex I., Conclusions: Mitochondrial motility is essential for VSMC proliferation and relies on MIRO1. The EF-hands of MIRO1 regulate the intracellular positioning of mitochondria. Additionally, the absence of MIRO1 leads to distorted mitochondrial cristae and reduced ATP generation. Our findings demonstrate that motility is linked to mitochondrial ATP production. We elucidated two unrecognized mechanisms through which MIRO1 influences cell proliferation by modulating mitochondria: first, by managing mitochondrial placement via Ca 2+ -dependent EF hands, and second, by affecting cristae structure and ATP synthesis., Competing Interests: The authors have declared that no conflict of interest exists.

NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT 1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT 1A receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT 1A receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders., (© 2024. The Author(s).)

Objective: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML)., Methods: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry., Results: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner ( r 24 h =0.7592, r 48 h =0.9456, and r 72 h =0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner ( r =0.9057 in 2.5 μmol/L group, r =0.9897 in 5 μmol/L group and r =0.9994 in 10 μmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner ( r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G 0 /G 1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G 0 /G 1 phase was increased and the cell synthesis was decreased., Conclusion: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.

Purpose: The implementation of the universal two-child policy contributes to adverse pregnancy outcomes, but how the policy change leads to adverse pregnancy outcomes is not well elaborated. In this study, we aimed to compare maternal characteristics and complications, accessed the change in the proportion of maternal characteristics and maternal complications, and evaluated the mediation of maternal characteristics on maternal complications., Methods: Demographic and clinical data of three-level sample facilities were extracted from China's National Maternity Near Miss Obstetrics Surveillance System from Jan 1, 2012 to May 31, 2021. The associations between the universal two-child policy and maternal risk factors, the universal two-child policy and maternal complications, and maternal risk factors and maternal complications were evaluated using multivariate logistic regression analyses, with odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis was used to estimate the potential mediation effects on the associations between the policy and maternal complications. Population-attributable fractions (PAF) were conducted to quantify the maternal complications burden attributable to the implementation of the universal two-child policy., Results: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facilities. After adjusting for covariables, there were significant associations between the universal two-child policy and maternal risk factors (P < 0.001), the universal two-child policy and an increased risk of maternal complications (P < 0.001), and maternal risk factors and maternal complications(P < 0.001). The effects of the universal two-child policy on maternal near miss and medical disease were significantly mediated by maternal risk factors with mediation proportions of 19.77% and 4.07% at the municipal-level sample facility, and mediation proportions for 2.72% at the county-level sample facility on medical disease. The universal two-child policy contributed 19.34%, 5.82%, 8.29%, and 46.19% in the incidence of the maternal near miss, antepartum or intrapartum complication, post-partum complication, and medical disease at municipal-level sample facility, respectively. The corresponding PAF% at county-level sample facility was 40.49% for maternal near miss, 32.39% for the antepartum or intrapartum complication, 61.44% for post-partum complication, and 77.72% for medical disease. For provincial-level sample facility, the incidence of maternal near miss, antepartum or intrapartum complications, and medical diseases decreased (P < 0.05) and no statistically significant difference occurred in the incidence of post-partum complications., Conclusions: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facility. Maternal risk factors may play a mediating role in the effect of policy change and maternal complications. Provincial hospitals have been able to improve the quality of perinatal health care and reduce adverse pregnancy outcomes by adjusting their obstetric service strategies in the context of the new birth policy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Methane-oxidizing bacteria (MOB) is a group of planktonic microorganisms that use methane as their primary source of cellular energy. For tropical lakes in monsoon Asia, there is currently a knowledge gap on MOB community diversity and the factors influencing their abundance. Herewith, we present a preliminary assessment of the MOB communities in three maar lakes in tropical monsoon Asia using Catalyzed Reporter Deposition, Fluorescence In-Situ Hybridization (CARD-FISH), 16S rRNA amplicon sequencing, and pmoA gene sequencing. Correlation analysis between MOB abundances and lakes' physicochemical parameters following seasonal monsoon events were performed to explain observed spatial and temporal patterns in MOB diversity. The CARD-FISH analyses detected the three MOB types (I, II, and NC10) which aligned with the results from 16S rRNA amplicons and pmoA gene sequencing. Among community members based on 16S rRNA genes, Proteobacterial Type I MOB (e.g., Methylococcaceae and Methylomonadaceae), Proteobacterial Type II (Methylocystaceae), Verrucomicrobial (Methylacidiphilaceae), Methylomirabilota/NC10 (Methylomirabilaceae), and archaeal ANME-1a were found to be the dominant methane-oxidizers in three maar lakes. Analysis of microbial diversity and distribution revealed that the community compositions in Lake Yambo vary with the seasons and are more distinct during the stratified period. Temperature, DO, and pH were significantly and inversely linked with type I MOB and Methylomirabilota during stratification. Only MOB type I was influenced by monsoon changes. This research sought to establish a baseline for the diversity and ecology of planktonic MOB in tropical monsoon Asia to better comprehend their contribution to the CH 4 cycle in tropical freshwater ecosystems., 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 Bicaldo, Padilla, Tu, Chen, Mendoza-Pascual, Vicera, de Leon, Poblete, Austria, Lopez, Kobayashi, Shiah, Papa, Okuda, Wang and Lin.)

Patellofemoral pain syndrome (PFPS) is one of the most common etiologies of knee pain and might be relieved with lumbopelvic manipulation (LPM). This meta-analysis aimed to investigate the effects of LPM on pain reduction in patients with PFPS. Electronic databases were searched from inception to December 2023 for randomized controlled trials (RCTs) investigating the effects of LPM on PFPS. The primary outcome was the change in visual analog or numeric rating scale scores assessing pain. Ten studies comprising 346 participants were included. Significant pain reduction was noted in the LPM group (Hedges' g = -0.706, 95% confidence interval [CI] = -1.197 to -0.214, p = 0.005, I2 = 79.624%) compared with the control group. Moreover, pain relief was more pronounced when LPM was combined with other physical therapies (Hedges' g = -0.701, 95% CI = -1.386 to -0.017, p = 0.045, I2 = 73.537%). No adverse events were reported during the LPM. The LPM appears to be a safe and effective adjuvant therapy for pain reduction in patients with PFPS. Clinicians should consider adding LPM to other physical therapies (e.g., quadriceps muscle strengthening) during the management of these patients.

Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping morphologic, immunohistochemical, and molecular features. While MAs occur in the cervix and are thought to arise from mesonephric remnants, MLAs occur in the endometrium and ovary and are believed to originate from transdifferentiation of Müllerian lesions. Both MAs and MLAs show a variety of architectural patterns, exhibit frequent expression of GATA3 by immunohistochemistry, and harbor KRAS mutations. In a recent article published in The Journal of Pathology, Kommoss and colleagues used DNA methylation profiling to extend these similarities and showed that MLAs and MAs cluster together based on their epigenetic signatures and are epigenetically distinct from other Müllerian adenocarcinomas. They also showed that MLAs and MAs harbor a high number of global copy number alterations. This study provides evidence that MLAs more closely resemble MAs than Müllerian carcinomas on an epigenetic level. As a result, the authors argue that MLA should be renamed 'mesonephric-type adenocarcinoma.' Further research is needed to establish the relationship between these two entities, their etiology, and pathogenesis. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses., (© 2024. The Author(s).)

Background: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters., Methods: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control., Results: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group., Conclusion: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management., (© 2024. The Author(s).)

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L -1 . Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L -1 . In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Background: Investigates the integration of an artificial intelligence tool, specifically ChatGPT, in nursing education, addressing its effectiveness in exam preparation and self-assessment., Objective: This study aims to evaluate the performance of ChatGPT, one of the most promising artificial intelligence-driven linguistic understanding tools in answering question banks for nursing licensing examination preparation. It further analyzes question characteristics that might impact the accuracy of ChatGPT-generated answers and examines its reliability through human expert reviews., Design: Cross-sectional survey comparing ChatGPT-generated answers and their explanations., Setting: 400 questions from Taiwan's 2022 Nursing Licensing Exam., Methods: The study analyzed 400 questions from five distinct subjects of Taiwan's 2022 Nursing Licensing Exam using the ChatGPT model which provided answers and in-depth explanations for each question. The impact of various question characteristics, such as type and cognitive level, on the accuracy of the ChatGPT-generated responses was assessed using logistic regression analysis. Additionally, human experts evaluated the explanations for each question, comparing them with the ChatGPT-generated answers to determine consistency., Results: ChatGPT exhibited overall accuracy at 80.75 % for Taiwan's National Nursing Exam, which passes the exam. The accuracy of ChatGPT-generated answers diverged significantly across test subjects, demonstrating a hierarchy ranging from General Medicine at 88.75 %, Medical-Surgical Nursing at 80.0 %, Psychology and Community Nursing at 70.0 %, Obstetrics and Gynecology Nursing at 67.5 %, down to Basic Nursing at 63.0 %. ChatGPT had a higher probability of eliciting incorrect responses for questions with certain characteristics, notably those with clinical vignettes [odds ratio 2.19, 95 % confidence interval 1.24-3.87, P = 0.007] and complex multiple-choice questions [odds ratio 2.37, 95 % confidence interval 1.00-5.60, P = 0.049]. Furthermore, 14.25 % of ChatGPT-generated answers were inconsistent with their explanations, leading to a reduction in the overall accuracy to 74 %., Conclusions: This study reveals the ChatGPT's capabilities and limitations in nursing exam preparation, underscoring its potential as an auxiliary educational tool. It highlights the model's varied performance across different question types and notable inconsistencies between its answers and explanations. The study contributes significantly to the understanding of artificial intelligence in learning environments, guiding the future development of more effective and reliable artificial intelligence-based educational technologies., Tweetable Abstract: New study reveals ChatGPT's potential and challenges in nursing education: Achieves 80.75 % accuracy in exam prep but faces hurdles with complex questions and logical consistency. #AIinNursing #AIinEducation #NursingExams #ChatGPT., Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Environmental temperature affects the composition, structure, and function of the gut microbial communities in host animals. To elucidate the role of gut microbiota in thermal adaptation, we designed a 2 species × 3 temperatures experiment, whereby we acclimated adult males of two agamid lizard species (warm-climate Leiolepis reevesii and cold-climate Phrynocephalus przewalskii ) to 20, 28, and 36°C for 2 weeks and then collected their fecal and small-intestinal samples to analyze and compare the microbiota using 16S rRNA gene amplicon sequencing technology. The fecal microbiota displayed more pronounced interspecific differences in microbial community than the small-intestinal microbiota in the two species occurring in thermally different regions. The response of fecal and small-intestinal microbiota to temperature increase or decrease differed between the two species, with more bacterial taxa affected by acclimation temperature in L. reevesii than in P. przewalskii. Both species, the warm-climate species in particular, could cope with temperature change by adjusting the relative abundance of functional categories associated with metabolism and environmental information processing. Functional genes associated with carbohydrate metabolism were enhanced in P. przewalskii , suggesting the contribution of the fecal microbiota to cold-climate adaptation in P. przewalskii . Taken together, our results validate the two hypotheses tested, of which one suggests that the gut microbiota should help lizards adapt to thermal environments in which they live, and the other suggests that microbial communities should be thermally more sensitive in warm-climate lizards than in cold-climate lizards., 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 Zhu, Chen, Du, Lin, Qu, Lin and Ji.)

Aims: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients., Methods: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens., Results: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally., Conclusion: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH., (© 2024 British Pharmacological Society.)

Break Up with Salt (BUWS) is a four-session community-based nutrition education program aimed at reducing key controllable hypertension risk factors. This pilot study utilized a pre-post survey design to assess short-term outcomes on food behaviors (including DASH diet eating patterns), physical activity, and overall well-being, in two groups of participants. The first "pilot" group (n = 25) completed a comprehensive, 16-item survey; the second "abbreviated" group (n = 27) completed a 5-item survey. The pilot group experienced improvements in whole grain ( p = 0.04), sweetened beverage consumption, watching/reducing sodium ( p = 0.04) and fat ( p = 0.05) consumption, and time spent sitting ( p = 0.04). The abbreviated group improved confidence in using food labels ( p = 0.02), following the DASH diet ( p < 0.01), preparing food without salt ( p = 0.03), selecting lower sodium items when eating out ( p = 0.04), and making a positive lifestyle change ( p = 0.01). The BUWS program provides information and teaches strategies to manage or prevent hypertension. By effectively improving diet and food behaviors, BUWS has the potential to reduce hypertension risk factors and improve the general health of participants.

Aim(s): To investigate the factorial structure, test-retest reliability, and internal consistency of the Older Volunteer Competency Scale and establish its psychometric properties., Design: Cross-sectional survey., Methods: A total of 1,000 older volunteers were recruited through random sampling and asked to complete the Older Volunteer Competency Scale. Subsequently, 100 participants were selected to participate in a second test to determine the scale's test-retest reliability. Factorial structure was assessed through exploratory factor analysis and confirmatory factor analysis, and internal consistency was assessed using Cronbach's α., Results: Favorable exploratory and confirmatory factor analysis results were obtained. In addition, the three dimensions of the Older Volunteer Competency Scale, namely service awareness, service skills, and interpersonal interaction, had high internal consistency and test-retest reliability., Conclusion: The Older Volunteer Competency Scale is an effective and reliable research instrument for evaluating competency and needs among older volunteers., Competing Interests: Declaration of competing interest The authors report no conflict of interests in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We investigated key signalling pathways' activity and mutational status of early-stage breast carcinomas with low and intermediate 21-gene recurrence score (RS) to identify molecular features that may predict recurrence., Methods: This is a retrospective case-control study of 18 patients with recurrent breast carcinoma with low and intermediate 21-gene RS (<25) and control group of 15 non-recurrent breast cancer patients. DNA and mRNA were extracted from tumour tissue. mRNA expression of genes involved in oestrogen receptor (ER), androgen receptor (AR), PI3K and MAPK signalling pathways was measured by real-time quantitative reverse transcription-qPCR (OncoSIGNal G4 test, InnoSIGN). Tumour mutational landscape was assessed by targeted DNA sequencing (Oncomine Precision Assay)., Results: There were no statistical differences between the groups' demographic and clinicopathological characteristics. PI3K pathway showed significantly higher activity in cases compared with controls (p=0.0014). Receiver operating characteristic curve analysis showed an area under the curve of 0.79 for PI3K pathway activity in the prediction of recurrent disease in low and intermediate 21-gene RS breast cancer. There was no difference in ER, AR and MAPK pathway activity. PIK3CA alterations were the most common driver mutations, but no difference was found between the groups (p=0.46) and no association with PI3K pathway activity (p=0.86). Higher Ki67 gene expression was associated with recurrences (p=0.042) CONCLUSION: Increased PI3K pathway activity, independent of PIK3CA mutations, may play a role in the recurrence of early-stage breast cancer with low and intermediate 21-gene RS. Pathway analysis can help to identify high-risk patients in this setting., Competing Interests: Competing interests: YW-R, DvS, SN and PAvdW are employees or contractors of InnoSIGN and own InnoSIGN shares and/or options. MS is scientific advisor and shareholder of C2i Genomics, Heidelberg Epignostix and Halo Dx, and a scientific advisor of Arima Genomics, and InnoSIGN, and received research funding from Lilly USA., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic neck pain (CNP) is a common musculoskeletal disorder. Pain neuroscience education (PNE) is a promising nonpharmacological intervention for CNP, however, its effectiveness remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness of PNE in treating CNP., Methods: Electronic databases from inception to February 2023 were searched for randomized controlled trials (RCTs) on the effects of PNE on CNP. The primary outcome was the change in pain intensity, and the secondary outcome was improvement in kinesiophobia, standardized using Hedges' g. Two authors independently scrutinized eligible articles, extracted data and assessed quality; a random-effects model was employed for data pooling., Results: In total, seven RCTs comprising 479 participants were included and demonstrated that PNE significantly reduced pain intensity (Hedges' g = -0.730, 95% CI = -1.340 to -0.119, p = 0.019, I 2  = 89.288%). Subgroup analysis revealed that the adult group experienced significant pain reduction after PNE, whereas the adolescent group did not. PNE also reduced kinesiophobia which was evaluated in four of seven RCTs (Hedges' g = -0.444, 95% CI = -0.735 to -0.154, p = 0.003, I 2  = 36.822%). The meta-regression analysis indicated that an increased intervention duration contributed to greater pain reduction. No adverse events were reported following PNE or the control treatment., Conclusions: PNE effectively reduced pain intensity and kinesiophobia in patients with CNP. A longer PNE time leads to greater pain reduction and is more effective in adults than in adolescents. Further studies are required to examine the long-term effects on CNP management., Significance: This is the first meta-analysis evaluating the effectiveness of treating chronic neck pain with pain neuroscience education. Pain neuroscience education is successful in reducing pain and decreasing kinesiophobia in the chronic neck pain population. Longer treatment time leads to greater pain reduction., (© 2023 European Pain Federation - EFIC ®.)

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.)

Background/purpose: The serpin peptidase inhibitor, clade E, member 2 (SERPINE2), is upregulated in breast cancer, prostate cancer, and urothelial carcinoma; however, limited information exists regarding its expression in oral cancer. Therefore, this study aimed to analyze the association between SERPINE2 expression and oral squamous cell carcinoma (OSCC) outcomes., Materials and Methods: SERPINE2 mRNA and protein expression in patients with head and neck squamous cell carcinoma and OSCC were investigated using online databases and tissue-array analysis. Its relationship with clinicopathological characteristics, OSCC prognosis and its biological function in OSCC cells were explored., Results: Analysis using online databases revealed higher SERPINE2 expression in tumor tissues and its role as a prognostic factor. High SERPINE2 protein levels were significantly correlated with adverse pathological parameters, including advanced clinical stage and tumor status ( P  < 0.001), lymph nodes ( P  = 0.014), and distant metastases ( P  = 0.013). High SERPINE2 expression was associated with worse overall survival ( P  < 0.001) and was identified as an independent prognostic factor for OSCC. In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines., Conclusion: This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background : Atopic dermatitis (AD) has the highest burden of any skin disease; however, the severity-associated factors remain unclear. Objective: To evaluate potential severity-associated factors of AD and to design and validate a severity prediction model to inform the management of AD patients. Methods: A cross-sectional study of 900 AD patients was conducted from December 2021 to October 2022 at our hospital. The primary outcome was disease severity, categorized as mild, moderate, or severe using the scoring atopic dermatitis index. Ordinal logistic regression and bootstrapped validation were used to derive and internally validate the model. Results: Increasing age, elevated eosinophil level, higher economic status, and urban residence were associated with severe AD. Breastfeeding, disinfectants and topical emollients use, and short duration of bathing were associated with mild AD. In the prediction model, predictors included age, eosinophil and economic status, residence, feeding, disinfectants and emollients use, and duration of bathing. Prediction models demonstrated good discrimination (bias-corrected concordance index [c-index] = 0.72) and good calibration. Conclusion: Risk factors for the severity of AD were identified that could aid the early prediction of AD progression. The predictive model included variables that are easily evaluated and could inform personalized prevention and therapy.

Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets ( p < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.

Lumbar radiculopathy causes lower back and lower extremity pain that may be managed with neural mobilization (NM) techniques. This meta-analysis aims to evaluate the effectiveness of NM in alleviating pain and reducing disability in patients with lumbar radiculopathy. We hypothesized that NM would reduce pain and improve disability in the lumbar radiculopathy population, leveraging the statistical power of multiple studies. Electronic databases from their inception up to October 2023 were searched for randomized controlled trials (RCTs) that explored the impact of NM on lumbar radiculopathy. Our primary outcome measure was the alteration in pain intensity, while the secondary one was the improvement of disability, standardized using Hedges' g . To combine the data, we employed a random-effects model. A total of 20 RCTs comprising 877 participants were included. NM yielded a significant reduction in pain intensity (Hedges' g = -1.097, 95% CI = -1.482 to -0.712, p < 0.001, I2 = 85.338%). Subgroup analyses indicated that NM effectively reduced pain, whether employed alone or in conjunction with other treatments. Furthermore, NM significantly alleviated disability, with a notable effect size (Hedges' g = -0.964, 95% CI = -1.475 to -0.453, p < 0.001, I2 = 88.550%), particularly in chronic cases. The findings provide valuable insights for clinicians seeking evidence-based interventions for this patient population. This study has limitations, including heterogeneity, potential publication bias, varied causal factors in lumbar radiculopathy, overall study quality, and the inability to explore the impact of neural pathology on NM treatment effectiveness, suggesting opportunities for future research improvements.

Background: To investigate the effectiveness of muscle energy technique (MET) for treatment of non-specific neck pain (NSNP)., Methods: A literature search was performed using electronic databases from their inception until October 2023 for randomized controlled trials (RCTs) that investigated the effects of MET on NSNP. A change in pain intensity and reduced disability were the primary and secondary outcomes, respectively, standardized using Hedges' g . A random effects model was used for data pooling., Results: This study included 26 RCTs comprising 1170 participants. The results showed that MET significantly reduced pain intensity (Hedges' g  = -0.967 95 % CI = -1.417 to -0.517, p  < 0.001). However, subgroup analysis revealed that this significant benefit was observed only when MET was combined with other treatments and not with MET monotherapy. MET also reduced disability (Hedges' g  = -0.545, 95 % CI = -1.015 to - 0.076, p  = 0.023). Meta-regression analysis showed that an increase in treatment duration/session per week contributed to greater pain reduction. No adverse events were reported following the MET., Conclusions: In conclusion, our meta-analysis suggests MET's potential effectiveness within a combined treatment for NSNP. However, the evidence's low certainty is likely influenced by bias and study variations. To strengthen these findings, future research should focus on higher-quality clinical trials, longer follow-up periods, and prediction interval presentations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ke-Vin Chang reports financial support was provided by 10.13039/501100004663Ministry of Science and Technology, Taiwan., (© 2023 The Authors.)

New colonies of Formosan subterranean termites are founded by monogamous pairs. During swarming season, alates (winged reproductives) leave their parental colony. After swarming, they drop to the ground, shed their wings, and male and female dealates find suitable nesting sites where they mate and become kings and queens of new colonies. The first generation of offspring is entirely dependent on the nutritional resources of the founder pair consisting of the fat and protein reserves of the dealates and their microbiota, which include the cellulose-digesting protozoa and diverse bacteria. Since termite kings and queens can live for decades, mate for life and colony success is linked to those initial resources, we hypothesized that gut microbiota of founders affect pair formation. To test this hypothesis, we collected pairs found in nest chambers and single male and female dealates from four swarm populations. The association of three factors (pairing status, sex of the dealates and population) with dealate weights, total protozoa, and protozoa Pseudotrichonympha grassii numbers in dealate hindguts was determined. In addition, Illumina 16S rRNA gene sequencing and the QIIME2 pipeline were used to determine the impact of those three factors on gut bacteria diversity of dealates. Here we report that pairing status was significantly affected by weight and total protozoa numbers, but not by P. grassii numbers and bacteria diversity. Weight and total protozoa numbers were higher in paired compared to single dealates. Males contained significantly higher P. grassii numbers and bacteria richness and marginally higher phylogenetic diversity despite having lower weights than females. In conclusion, this study showed that dealates with high body weight and protozoa numbers are more likely to pair and become colony founders, probably because of competitive advantage. The combined nutritional resources provided by body weight and protozoa symbionts of the parents are important for successful colony foundation and development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen 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.)

Objectives: We studied the prevalence and prognostic significance of mismatch repair deficient (MMRD) and p53 aberrant ovarian clear cell carcinoma (CCO) and their association with other prognostic and theranostic biomarkers (p16, HER2, PD-L1). We also aimed to identify morphologic features to serve as screening tools for immunohistochemical testing for these biomarkers., Methods: Tissue microarrays with 3-mm cores from 71 pure CCOs were immunostained with PMS2, MSH6, p53, p16, HER2, and PD-L1. Expression status was correlated with tumor recurrence/disease progression and survival. It was also correlated with morphologic features (tumor size, nuclear grade, tumor architecture, mitotic activity, presence of endometriosis, tumor budding, and tumor inflammation)., Results: p53 aberrant tumors were associated with shorter overall and recurrence-free survivals (P = .002 and P = .01, respectively). In multivariate analysis, p53 aberrant status and tumor stage were independently associated with recurrence/disease progression (hazard ratio [HR] = 3.31, P = .037 and HR = 1.465, P = .004, respectively). p53 aberrant status was associated with tumor budding (P = .037). MMRD, p16, HER2, and PD-L1 expression had no prognostic significance. HER2 and PD-L1 were expressed in 56% and 35% of tumors, respectively. MMRD was associated with tumor expression of PD-L1 (P > .05) but not with tumor inflammation., Conclusions: Aberrant p53 in CCO is infrequent but associated with poor prognosis independent of stage. Presence of tumor budding could be a screening tool for p53 testing. High prevalence of HER2 and PD-L1 expression indicates the eligibility of patients with CCO for ongoing clinical trials using these therapeutic targets., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Triple-negative breast cancers (TNBC) include diverse carcinomas with heterogeneous clinical behavior. DNA methylation is a useful tool in classifying a variety of cancers. In this study, we analyzed TNBC using DNA methylation profiling and compared the results to those of mutational analysis. DNA methylation profiling (Infinium MethylationEPIC array, Illumina) and 50-gene panel-targeted DNA sequencing were performed in 44 treatment-naïve TNBC. We identified 3 distinct DNA methylation clusters with specific clinicopathologic and molecular features. Cluster 1 (phosphoinositide 3-kinase/protein kinase B-enriched cluster; n = 9) patients were significantly older (mean age, 71 years; P = .008) with tumors that were more likely to exhibit apocrine differentiation (78%; P < .001), a lower grade (44% were grade 2), a lower proliferation index (median Ki-67, 15%; P = .002), and lower tumor-infiltrating lymphocyte fractions (median, 15%; P = .0142). Tumors carried recurrent PIK3CA and AKT1 mutations and a higher percentage of low HER-2 expression (89%; P = .033). Cluster 3 (chromosomal instability cluster; n = 28) patients were significantly younger (median age, 57 years). Tumors were of higher grade (grade 3, 93%), had a higher proliferation index (median Ki-67, 75%), and were with a high fraction of tumor-infiltrating lymphocytes (median, 30%). Ninety-one percent of the germline BRCA1/2 mutation carriers were in cluster 3, and these tumors showed the highest level of copy number alterations. Cluster 2 represented cases with intermediate clinicopathologic characteristics and no specific molecular profile (no specific molecular profile cluster; n = 7). There were no differences in relation to stage, recurrence, and survival. In conclusion, DNA methylation profiling is a promising tool to classify patients with TNBC into biologically relevant groups, which may result in better disease characterization and reveal potential targets for emerging therapies., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Tumor budding, largely considered a manifestation of epithelial-mesenchymal transition (EMT) is an established prognostic marker for several cancers. In a recent study, tumor budding was associated with poor clinical outcomes in early-stage ovarian clear cell carcinoma. Here, we evaluated the immune expression of 3 proteins shown to be associated with EMT (E-cadherin, β-catenin, and glypican-3) in 72 primary tumors of ovarian clear cell carcinoma with median follow-up of 39.47 mo. E-cadherin and β-catenin expression was further evaluated in tumor buds in 29 (40%) cases. In the tumor mass, diffuse membranous expression of E-cadherin and β-catenin was seen in 83% (60/72) and 81% (58/72) cases, respectively. Nuclear accumulation of E-cadherin was seen in 7 (10%) cases, while none of the cases showed nuclear β-catenin expression. Glypican-3 expression was diffuse in 33.3% (24/72), patchy in 29.2% (21/72), and absent in 37.5% (27/72) cases. Evaluation of tumor buds showed aberrant patterns of expression (complete loss/cytoplasmic accumulation/diminished, discontinuous incomplete membranous staining) of E-cadherin in 29/29 (100%) and of β-catenin in 26/29 (90%) cases. E-cadherin, β-catenin, and glypican-3 expression in the main tumor mass had no association with stage, lymph node status, recurrent/progressive disease, status at last follow-up, survival and histopathologic features ( P >0.05). Our finding of aberrant expression of both E-cadherin and β-catenin in tumor buds indicates involvement of Wnt signaling pathway/EMT in tumor budding and outlines its significance as a prognostic marker especially for early-stage ovarian clear cell carcinoma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Recent success of sequential administration of immunotherapy following radiotherapy (RT), often referred to as immunoRT, has sparked the urgent need for novel clinical trial designs to accommodate the unique features of immunoRT. For this purpose, we propose a Bayesian phase I/II design for immunotherapy administered after standard-dose RT to identify the optimal dose that is personalized for each patient according to his/her measurements of PD-L1 expression at baseline and post-RT. We model the immune response, toxicity, and efficacy as functions of dose and patient's baseline and post-RT PD-L1 expression profile. We quantify the desirability of the dose using a utility function and propose a two-stage dose-finding algorithm to find the personalized optimal dose. Simulation studies show that our proposed design has good operating characteristics, with a high probability of identifying the personalized optimal dose., (© 2023 Wiley-VCH GmbH.)

Objective: The objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China., Methods: The clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay., Results: Seventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment., Conclusion: Although preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians., 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 © 2023 Liu, Lin, Lin, Yang, Lin, Zhang, Huang, Liao, Zeng, Zeng, Cao, Zhu and Yang.)

Background: In patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), salvage chemotherapy regimens (e.g., rituximab, ifosfamide, carboplatin, and etoposide, R-ICE) yield poor outcomes. Carfilzomib, an irreversible proteasome inhibitor, can overcome acquired rituximab-chemotherapy resistance and, when combined with R-ICE, improves outcomes in patients with R/R DLBCL., Objective: This analysis aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model for carfilzomib in R/R DLBCL patients., Patients and Methods: In a single-center, open-label, prospective phase 1 study, patients received carfilzomib (10, 15, or 20 mg/m 2 ) on days 1, 2, 8, and 9, and standard doses of R-ICE on days 3-6 every 21 days (maximum of three cycles). Carfilzomib plasma concentrations up to 24 h postinfusion were measured by liquid chromatography coupled with tandem mass spectrometry. Proteasome activity (PD biomarker) in peripheral blood mononuclear cells was assessed on days 1-2 with sparse sampling. PK/PD models were developed using NONMEM v7.4.1 interfaced with Finch Studio v1.1.0 and PsN v4.7.0. Model selection was guided by objective function value, goodness-of-fit, and visual predictive checks. Stepwise covariate modeling was used for covariate selection., Results: Twenty-eight patients were enrolled in the PK/PD analysis, from whom 217 PK samples and 127 PD samples were included. Carfilzomib PK was best described by a two-compartment model with linear disposition (typical total clearance of 133 L/h). Proteasome activity was best characterized using a turnover model with irreversible inactivation. All parameters were estimated with good precision. No statistically significant covariates were identified., Conclusions: A validated population-based PK/PD model of carfilzomib was developed successfully. Further research is needed to identify sources of variability in response to treatment with carfilzomib in combination with R-ICE., Clinical Trial Registration: ClinicalTrials.gov identifier number NCT01959698., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study aimed to examine the relationship between self-perceived quality of transitional care and functional outcome among patients with stroke and fractures. The Care Transition Measure (CTM-15) was used to survey patient's self-perceived transitional care quality before discharge. General estimating equations were used to investigate the influences of transitional care quality on patient's functional outcomes at before, 1 week after, and 1 or 3 months after discharge. Among stroke patients, higher CTM-15 scores were positively associated with greater outcome in Instrumental Activities of Daily Living (IADL) following discharge. Higher scores for "reader-friendly written care plan," "consideration of patient's preferences," and "understanding of health management" had significantly positive effects on functional recovery in IADL among both patient groups following discharge. These findings suggest that heterogeneity in transitional care needs between medical and surgical patients shall not be overlooked. A one-size-fits-all strategy may be insufficient for ensuring patient care continuity following discharge., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Pulsed dye laser (PDL) is currently considered to be the first-line treatment for port-wine stains (PWSs) on the extremities despite its less than satisfactory therapeutic efficacy. Hemoporfin-mediated photodynamic therapy (HMME-PDT) is a vascular-targeted therapy that has rarely been used to treat PWSs on the extremities. Here, we evaluate the clinical efficacy and safety of HMME-PDT for the treatment of PWSs on the extremities., Methods: Clinical data and dermoscopic images of PWSs on the extremities were obtained from 65 patients who underwent HMME-PDT between February 2019 and December 2022. The clinical efficacy of HMME-PDT was analyzed by comparing the pre- and post-treatment images. The safety of HMME-PDT was evaluated through observation during the treatment period and post-treatment follow-up., Results: The efficacy rate of a single HMME-PDT session was 63.0% and that of two and three to six sessions was 86.7% and 91.3%, respectively. A positive correlation was found between therapeutic efficacy and the number of HMME-PDT sessions. The therapeutic efficacy of HMME-PDT was better on the proximal extremities than on other parts of the extremities (P = 0.038), and the efficacy of treating PWSs in each site was relatively improved with an increase of treatment time. The clinical efficacy of HMME-PDT differed across four PWS vascular patterns identified by dermoscopy (P = 0.019). However, there was no statistical difference in the therapeutic efficacy based on age, sex, type of PWS, and treatment history (P > 0.05), which may be partly attributed to the relatively small sample size or poor cooperation of infant patients. No obvious adverse reactions were observed during the follow-up period., Conclusions: HMME-PDT is a very safe and effective treatment for PWSs on the extremities. Multiple HMME-PDT treatments, lesions located in proximal limbs, and PWSs with type I and IV vascular patterns under dermoscopy were associated with higher efficacy of HMME-PDT. Dermoscopy may help predict the clinical efficacy of HMME-PDT., Trial Registration No: 2020KJT085., (© 2023. The Author(s).)