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Several life‐prolonging therapies for metastatic castration‐resistant prostate cancer (mCRPC) are available, including radium‐223 dichloride (223Ra), which was approved based on phase 3 data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real‐world evidence for 223Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223Ra was prescribed as part of routine practice by investigators. Patients with prior 223Ra treatment were excluded. The primary objective was to assess 223Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223Ra was first‐ or second‐line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5–6 223Ra cycles was 68.8%; this proportion was greater with first‐line use (84.3%) than second‐ (65.7%) or third‐/fourth‐line use (64.1%). More chemotherapy‐naïve patients (61.9%) completed the 6‐cycle 223Ra treatment than chemotherapy‐exposed patients (56.7%). Any‐grade treatment‐emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223Ra‐related adverse events. Median OS was 15.7 months (95% confidence interval 12.13–19.51); patients receiving 5–6 223Ra injections and earlier 223Ra use had longer OS than those receiving fewer injections and later 223Ra use. 223Ra provides a well‐tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases. [ABSTRACT FROM AUTHOR]

Biological particles, as a fraction of organic particles, potentially play a crucial role in ice nucleation processes. However, the contributions and relationships of biological components and organic matter (OM) to atmospheric ice nucleation remain largely unexplored. Here, total ice nucleating particles (INPs), heat‐resistant INPs, lysozyme‐resistant INPs, nanoscale INPs (<0.22 μm), and heat‐resistant nanoscale INPs in precipitation collected at the summit of Mt. Lu, China, were determined using droplet freezing assays coupled with corresponding pretreatments. Heat‐sensitive INPs and lysozyme‐sensitive INPs were considered as biological INPs and bacterial INPs, respectively. Microorganisms and OM molecules in precipitation were identified by high‐throughput sequencing technology and ultrahigh‐resolution mass spectrometry, respectively. Results revealed a predominant biological (heat‐sensitive) composition (78.8% and 93.2%) of total and nanoscale INPs at temperatures above −15°C. Specifically, bacterial (lysozyme‐sensitive) INPs accounted for 36.1% of the biological INPs at temperatures above −15°C. A notable correlation between sulfur‐containing organic compounds, mainly proteinaceous and lignin‐like substances, and INPs was uncovered, with a co‐occurrence network linking these compounds to Gram‐positive bacteria and Agaricomycetes. This study underscored the possible significance of sulfur‐containing organic compounds in the ice nucleation capacity of biological INPs, further shedding light on the ice nucleation mechanisms and potential sources of biological INPs. Plain Language Summary: Ice nucleating particles (INPs) are particles that facilitate the freezing of water at temperatures above the homogenous freezing point, impacting cloud formation and precipitation processes in the atmosphere. This study identified different types of INPs, microbes, and organic matter in precipitation sampled from Mt. Lu in southeastern China and investigated the connections among them. The findings suggested that a significant portion of INPs were of biological origin. Sulfur‐containing organic compounds likely played an important role in ice nucleation, which may originate from certain microbial taxa. This study helps us understand the role of microbes and organic molecules in ice formation, which has broader implications in areas such as preserving biological materials at low temperatures or facilitating artificial snow production. Key Points: Biological materials predominated among the ice nucleating particles (INPs) identified in precipitationSulfur‐containing organic compounds, associated with specific microbial taxa, likely acted as efficient INPs in precipitationThis study provides a preliminary understanding of the connections among INPs, organic matter, and microorganisms [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of osteoarthritis (OA) involves the progressive degradation of articular cartilage. Exosomes derived from mesenchymal stem cells (MSC-EXOs) have been shown to mitigate joint pathological injury by attenuating cartilage destruction. Optimization the yield and therapeutic efficacy of exosomes derived from MSCs is crucial for promoting their clinical translation. The preconditioning of MSCs enhances the therapeutic potential of engineered exosomes, offering promising prospects for application by enabling controlled and quantifiable external stimulation. This study aims to address these issues by employing pro-inflammatory preconditioning of MSCs to enhance exosome production and augment their therapeutic efficacy for OA. Methods: The exosomes were isolated from the supernatant of infrapatellar fat pad (IPFP)-MSCs preconditioned with a pro-inflammatory factor, TNF-α, and their production was subsequently quantified. The exosome secretion-related pathways in IPFP-MSCs were evaluated through high-throughput transcriptome sequencing analysis, q-PCR and western blot analysis before and after TNF-α preconditioning. Furthermore, exosomes derived from TNF-α preconditioned IPFP-MSCs (IPFP-MSC-EXOsTNF−α) were administered intra-articularly in an OA mouse model, and subsequent evaluations were conducted to assess joint pathology and gait alterations. The expression of proteins involved in the maintenance of cartilage homeostasis within the exosomes was determined through proteomic analysis. Results: The preconditioning with TNF-α significantly enhanced the exosome secretion of IPFP-MSCs compared to unpreconditioned MSCs. The potential mechanism involved the activation of the PI3K/AKT signaling pathway in IPFP-MSCs by TNF-α precondition, leading to an up-regulation of autophagy-related protein 16 like 1(ATG16L1) levels, which subsequently facilitated exosome secretion. The intra-articular administration of IPFP-MSC-EXOsTNF−α demonstrated superior efficacy in ameliorating pathological changes in the joints of OA mice. The preconditioning of TNF-α enhanced the up-regulation of low-density lipoprotein receptor-related protein 1 (LRP1) levels in IPFP-MSC-EXOsTNF−α, thereby exerting chondroprotective effects. Conclusion: TNF-α preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of IPFP-MSCs derived exosomes in the treatment of OA. [ABSTRACT FROM AUTHOR]

Poultry meat, an essential source of animal protein, requires stringent safety and quality measures to address public health concerns and growing international attention. This review examines both direct and indirect factors that compromise poultry meat quality in intensive farming systems. It highlights the integration of rapid and micro-testing with traditional methods to assess meat safety. The paper advocates for adopting probiotics, prebiotics, and plant extracts to improve poultry meat quality. [ABSTRACT FROM AUTHOR]

This study aims to provide an understanding of the preferences of student tourists regarding service attributes related to domestic accommodation. To clarify how lodging firms formulate policies for the student travel market, a "Relative to an Identified Distribution" (RIDIT) analysis in which responses are treated as ordinal data instead of equally spaced data is performed to examine the Likert-scale data obtained from 296 university students in Taiwan. In our RIDIT analytical results, respondents' preferences are sorted in descending importance. Of the examined attributes, "Cleanliness of rooms" is the attribute most prioritized by the students, followed by "Located in a safe neighborhood/feeling safe in the room" and "Close to scenic area for meeting the trip requirement". The attribute least prioritized by the students is "Interaction with other guests". This analysis provides conclusions that differ from those obtained through commonly used techniques including the arithmetic average and exploratory factor analysis. The preference rankings indicate that managers should focus on the most prioritized service attributes and implement the necessary measures to enhance their service quality and maximize customer satisfaction. [ABSTRACT FROM AUTHOR]

The association between influenza infection and thromboembolism (TE) events, including cardiovascular events, cerebrovascular events, pulmonary embolism, and deep vein thrombosis, is supported by compelling evidence. However, there is a disparity in the risk factors that impact the outcomes of severe influenza‐complicated TE in intensive care unit (ICU) patients. The objective of this study was to evaluate the outcomes of severe influenza‐complicated TE in ICU patients and identify any associated risk factors. Methods: A retrospective cohort study was conducted, recruiting consecutive patients with TE events admitted to the ICU between December 2015 through December 2018 at our institution in Taiwan. The study included a group of 108 patients with severe influenza and a control group of 192 patients with severe community‐acquired pneumonia. Associations between complicated TE, length of ICU stay, and 90‐day mortality were evaluated using logistic regression analysis, and risk factors were identified using univariate and multivariate generalized linear regression analyses. Results: TE event prevalence was significantly higher in ICU patients with severe influenza than in ICU patients with severe CAP (21.3% vs. 5.7%, respectively; p < 0.05). Patients with severe influenza who developed TE experienced a significant increase in the ratio of mechanical ventilation use, length of mechanical ventilation use, ICU stay, and 90‐day mortality when compared to patients without TE (all p < 0.05). The comparison of severe CAP patients with and without TE revealed no significant differences (p > 0.05). The development of thromboembolic events in patients with severe influenza or severe noninfluenza CAP is linked to influenza infection and hypertension (p < 0.05). Furthermore, complicated TE and the severity of the APACHE II score are risk factors for 90‐day mortality in ICU patients with severe influenza (p < 0.05). Conclusions: Patients with severe influenza and complicated TE are more likely to have an extended ICU stay and 90‐day mortality than patients with severe CAP. The risk is significantly higher for patients with a higher APACHE II score. The results of this study may aid in defining better strategies for early recognition and prevention of severe influenza‐complicated TE. [ABSTRACT FROM AUTHOR]

Selenium is a vital trace mineral that is crucial for maintaining regular biological processes in aquatic animals. In this study, a four-week dietary trial was carried out to assess the impact of bio-fermented selenium (Bio−Se) on the growth and immune response of Chinese mitten crabs, Eriocheir sinensis. The crabs were randomly allocated to five dietary treatment groups, each receiving a different dose of Bio−Se. The doses included 0, 0.3, 0.6, 1.5, and 3.0 mg/kg and were accurately measured in basal diet formulations. The results showed the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) in the 1.5 mg/kg Bio−Se group were the highest, and 3.0 mg/kg of Bio−Se has an inhibitory effect on the WGR, SGR, and SR. The activities of the immune enzymes, including glutathione peroxidase (GPX), superoxide dismutase (SOD), and acid phosphatase (ACP), of the hepatopancreas were significantly (p < 0.05) increased in the 1.5 mg/kg Bio−Se group, while they decreased (p < 0.05) in the 3.0 mg/kg feeding group compared to the 0 mg/kg feeding group. The concentration of maleic dialdehyde (MDA) exhibited the opposite pattern. Similarly, the mRNA expression levels of antimicrobial peptides (ALF-1, Crus-1, and LYS), ERK, and Relish genes were also observed to be the highest in the 1.5 mg/kg Bio−Se group compared with the other groups. Furthermore, the administration of 1.5 mg/kg of Bio−Se resulted in an increase in the thickness of the intestinal plica and mucosal layer, as well as in alterations in the intestinal microbial profile and bacterial diversity compared to the dose of 0 mg/kg of Bio−Se. Notably, the population of the beneficial bacterial phylum Fusobacteria was increased after crabs were fed the 1.5 mg/kg Bio−Se diet. In conclusion, the oral administration of 1.5 mg/kg of Bio−Se improved the growth efficiency, antioxidant capabilities, immunity, and intestinal health of E. sinensis. Through a broken-line analysis of the WGR against dietary Bio−Se levels, optimal dietary Bio−Se levels were determined to be 1.1 mg/kg. These findings contribute valuable insights to the understanding of crab cultivation and nutrition. [ABSTRACT FROM AUTHOR]

Overexpression of T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) on T cells has been observed in smokers. However, whether and how galectin‐9 (Gal‐9)/TIM‐3 signal between T‐regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke‐induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal‐9/TIM‐3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM‐3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM‐3 in CD4+ T cells was explored in a HAVCR2−/− mouse model and in mice that received recombinant anti‐TIM3. The crosstalk between Gal‐9 and Tim‐3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal‐9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal‐9. We observed a pro‐inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM‐3. The restrained phenotype of CD4+ T cells was perturbed when TIM‐3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal‐9. The interaction between Gal‐9 and TIM‐3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor‐related orphan receptor gamma t. The expression of Gal‐9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal‐9/Tim‐3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke‐induced airway/lung inflammation. [ABSTRACT FROM AUTHOR]

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer‐immunity cycle during treatment. In this study, an anti‐PD‐L1‐immobilized magnetic gold nanohut, AuNH‐2‐Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH‐2‐Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH‐2‐Ab simultaneously target and eliminate cancer cells and tumor‐associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH‐2‐Ab involving the detachment of the surface antibody for in situ PD‐L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate‐specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ‐confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. Methods: The PC‐3AR (PC‐3 cells re‐expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound‐healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro‐Western Array, co‐immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. Results: In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho‐AR Ser81 and yes‐associated protein 1 (YAP), decreased phospho‐YAP Ser217, and altered epithelial‐mesenchymal transition (EMT) proteins in PCa cells. Co‐IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen‐induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa‐miR‐5001‐5p but increased hsa‐miR‐203a and hsa‐miR‐210‐3p in PC‐3AR cells but not PC‐3 cells. Treatment with inhibitors targeting hsa‐miR‐203a/hsa‐miR‐210‐3p, or overexpression of hsa‐miR‐5001‐5p decreased YAP expression as well as suppressed the androgen‐induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has‐miR‐210‐3p in the presence of androgen. Conclusions: Our observations indicated that miRNAs 203a/210‐3p/5001‐5p regulate the androgen/AR/YAP‐induced PCa metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Although minimally invasive colorectal surgery has been proven to have a shorter hospital stay and fewer short-term complications than open surgery, the advantages of laparoscopic surgery for colorectal cancer patients undergoing hemodialysis have not been validated. This study compared the outcomes of open and laparoscopic approaches in these patients. Materials and methods: Between January 2007 and December 2020, we retrospectively analyzed the clinical data of 78 hemodialysis patients who underwent curative-intent, elective colorectal surgery. Patients were divided into two groups according to the surgical method: open and laparoscopic. Results: Postoperative morbidity (p = 0.480) and mortality (p = 0.598) rates and length of hospital stay (28.8 vs. 27.5 days, p = 0.830) were similar between the groups. However, laparoscopic surgery patients had a shorter return to clear liquid, full liquid, or soft food time than open surgery patients (p < 0.001, p = 0.007, and p = 0.002, respectively). Disease-free survival and long-term cancer-specific survival rates were also similar between the two groups (p = 0.353 and p = 0.201, respectively). Multivariate analysis revealed that intraoperative blood transfusion was a risk factor for severe complications and mortality (OR 6.055; p = 0.046), and the odds ratio (OR) of laparoscopic surgery was not significantly greater than that of open surgery (OR = 0.537, p = 0.337). Conclusion: Although laparoscopic surgery did not result in hemodialysis patients having a shorter postoperative hospital stay, our results suggest that the laparoscopic approach is as safe as open surgery for hemodialysis patients and may be beneficial for shortening the return time to food intake. [ABSTRACT FROM AUTHOR]

In recent years, the "dual carbon" issue has become a major focus of the international community. Changes in land use driven by anthropogenic activities have a profound impact on ecosystem structure and carbon cycling. This study quantitatively assesses the spatiotemporal changes in cropland occupation and supplementation in the Pearl River Delta from 2000 to 2020 using the InVEST model, analyzing the spatial clustering of carbon storage changes caused by variations in cropland area. The PLUS model was employed to simulate land-use patterns and the spatial distribution of carbon storage in four future development scenarios. The results indicate the following: (1) From 2000 to 2020, the net change rate of cropland area in the Pearl River Delta was −0.81%, with a decrease of 16.49 km2 in cropland area, primarily converted to built-up land and forest land. (2) Carbon storage in the Pearl River Delta exhibited a pattern of lower values in the center and higher values in the periphery. The terrestrial ecosystem carbon storage in the Pearl River Delta was 534.62 × 106 t in 2000, 518.60 × 106 t in 2010, and 512.57 × 106 t in 2020, showing an overall decreasing trend. The conversion of cropland and forest land was the main reason for the decline in total regional carbon storage. (3) The area of carbon sequestration lost due to cropland occupation was significantly greater than the area of carbon loss compensated by new cropland, indicating an imbalance in the quality of cropland occupation and supplementation as a crucial factor contributing to regional carbon loss. (4) Under the ecological priority scenario, the expansion of built-up land and the reduction in ecological land such as cropland and forest land were effectively controlled, resulting in the minimal loss of carbon storage. The soil organic carbon pool of cropland is the most active carbon pool in terrestrial ecosystems and has a significant impact on carbon storage. Clarifying the relationship between "cropland protection measures–land use changes–ecosystem carbon storage" will improve cropland protection policies, provide references for regional carbon sequestration enhancement, and support sustainable socio-economic development. [ABSTRACT FROM AUTHOR]

Background: Tau‐first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. Aim: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late‐onset AD (LOAD). Method: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three‐dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow‐up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed‐effects model. Results: The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short‐term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. Discussion: The biological properties of tau and the longitudinal cognitive‐imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short‐term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau. [ABSTRACT FROM AUTHOR]

Background: Chronic cough (CC), characterized as a cough lasting >8 weeks, is a common multi-factorial syndrome in the community, especially in older adults. Methods: Using a pre-existing algorithm to identify patients with CC within the 2011–2018 Medicare beneficiaries, we examined trends in gabapentinoid use through repeated cross-sectional analyses and identified distinct utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Individuals without CC but with any respiratory conditions related to cough served as a comparator group. Results: Among patients with CC, gabapentinoid use increased from 18.6% in 2011 to 24.1% in 2018 (p = 0.002), with a similar upward trend observed in the non-CC cohort but with overall lower usage (14.7% to 18.4%; p < 0.001). Patients with CC had significantly higher burdens of respiratory and non-respiratory comorbidities, as well as greater healthcare service and medication use compared to the non-CC cohort. The GBTM analyses identified three distinct gabapentinoid utilization trajectories for CC and non-CC patients: no use (77.3% vs. 84.5%), low use (13.9% vs. 10.3%), and high use (8.8% vs. 5.2%). Conclusions: Future studies are needed to evaluate the safety and effectiveness of gabapentinoid use in patients with refractory or unexplained CC in real-world settings. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is characterized by high mortality and morbidity rates. Vav guanine nucleotide exchange factors (VAVs), crucial for signal transduction between cell membrane receptors and intracellular mediators, have been implicated in carcinogenesis. However, their potential prognostic value in RCC remains unclear. The impact of 150 common VAV polymorphisms on RCC risk and survival was investigated in a cohort of 630 individuals. Publicly available gene expression datasets were utilized to analyze VAV gene expression in relation to patient outcomes. The VAV3 rs17019888 polymorphism was significantly associated with RCC risk and overall survival after adjusting for false discovery rates. Expression quantitative trait loci analysis revealed that the risk allele of rs17019888 is linked to reduced VAV3 expression. Analysis of 19 kidney cancer gene expression datasets revealed lower VAV3 expression in RCC tissues compared to normal tissues, with higher expression correlating with better prognosis. Gene set enrichment analysis demonstrated that VAV3 negatively regulates the ubiquitin–proteasome system, extracellular matrix and membrane receptors, inflammatory responses, matrix metalloproteinases, and cell cycle pathways. Furthermore, elevated VAV3 expression was associated with increased infiltration of B cells, macrophages, and neutrophils into the RCC tumor microenvironment. Our findings suggest that VAV3 gene variants influence RCC risk and survival, contributing to a favorable prognosis in RCC. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is an inflammatory follicular dermatological condition that typically affects the intertriginous and anogenital regions of the apocrine gland-bearing skin. The management of this chronic and recurring disease necessitates a combination of lifestyle changes, medication, and surgical approaches to achieve the best possible outcomes. While medical treatments are recommended for this multimodal disease, surgical therapy, which is the gold standard of treatment for HS, has proven to be the most effective treatment because it provides long-lasting local disease control, reduces the recurrence of lesions, and ensures complete healing of lesions. In the last decade, there has been exponential growth in research into various surgical techniques and reconstructive care, enabling patients to have more surgical options. There is a wide range of surgical management procedures available, such as incision and drainage, deroofing, excisional surgery, carbon dioxide laser therapy, and skin tissue-sparing excision with electrosurgical peeling. Among these surgical procedures, wide surgical excision is the best option since it can eradicate all the affected lesions. Meanwhile, the preferred approach to reconstruction at various anatomical locations remains debatable. Here, we review a variety of surgical treatments and reconstructive techniques for HS, particularly various flap techniques for the axillary, gluteal, and inframammary regions. [ABSTRACT FROM AUTHOR]

Background: Cancer burden from the elderly has been rising largely due to the aging population. However, research on the long‐term epidemiological trends in cancer of the elderly is lacking. Methods: Registry data of this population‐based cross‐sectional study were from the Surveillance, Epidemiology, and End Results (SEER) database. The study population aged 65 years or more, from geographically distinct regions. Joinpoint regression and JP Surv method were used to analyze cancer trends and survival. Results: Mortality rate during 1975–2020 decreased from 995.20 to 824.99 per 100,000 elderly persons, with an average annual decrease of 0.421% (95% CI, 0.378–0.464). While overall incidence increased with no significance. Prostate (29%) and breast (26%) cancer were the most common malignancies, respectively, in elderly males and females, and the mortality for both of the two (prostate 15%, breast 14%) ranked just behind lung and bronchus cancer, which had the highest mortality rates in males (29%) and females (23%). Many cancers showed adverse trends in the latest follow‐up periods (the last period calculated by the Joinpoint method). For intrahepatic cholangiocarcinoma, incidence (male Annual Percentage Change [APC] = 7.4*; female APC = 6.7*) and mortality (male APC = 3.0*; female APC = 3.3*) increased relatively fast, and its survival was also terrible (3‐year survival only 10%). Other cancers with recent increasing mortality included cancer of anus, anal canal and anorectum, retroperitoneum, pleura, peritoneum, etc. Most cancers had favorable trends of survival during the nearest follow‐up period. Conclusion: Against the background of overall improvement, many cancers showed adverse trends. Further research for the underlying mechanisms and targeted implements towards adverse trends is also urgent. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the long-term effects of repetitive mild traumatic brain injury (rmTBI) with varying inter-injury intervals by measuring diffusion tensor metrics, including mean diffusivity (MD), fractional anisotropy (FA), and diffusion magnitude (L) and pure anisotropy (q). Methods: Eighteen rats were randomly divided into three groups: short-interval rmTBI (n = 6), long-interval rmTBI (n = 6), and sham controls (n = 6). MD, FA, L, and q values were analyzed from longitudinal diffusion tensor imaging at days 50 and 90 after rmTBI. Immunohistochemical staining against neurons, astrocytes, microglia, and myelin was performed. Analysis of variance, Pearson correlation coefficient, and simple linear regression model were used. Results: At day 50 post-rmTBI, lower cortical FA and q values were shown in the short-interval group (p ≤ 0.038). In contrast, higher FA and q values were shown for the long-interval group (p ≤ 0.039) in the corpus callosum. In the ipsilesional external capsule and internal capsule, no significant changes were found in FA, while lower L and q values were shown in the short-interval group (p ≤ 0.028) at day 90. The q values in the external capsule and internal capsule were negatively correlated with the number of microglial cells and the total number of astroglial cells (p ≤ 0.035). Conclusion: Tensor scalar measurements, such as L and q values, are sensitive to exacerbated chronic injury induced by rmTBI with shorter inter-injury intervals and reflect long-term astrogliosis induced by the cumulative injury. Relevance statement: Tensor scalar measurements, including L and q values, are potential DTI metrics for detecting long-term and subtle injury following rmTBI; in particular, q values may be used for quantifying remote white matter (WM) changes following rmTBI. Key Points: The alteration of L and q values was demonstrated after chronic repetitive mild traumatic brain injury. Changing q values were observed in the impact site and remote WM. The lower q values in the remote WM were associated with astrogliosis. [ABSTRACT FROM AUTHOR]

Telomere resolvases are a family of DNA cleavage and rejoining enzymes that produce linear DNAs terminated by hairpin telomeres from replicated intermediates in bacteria that possess linear replicons. The telomere resolvase of Agrobacterium tumefaciens, TelA, has been examined at the structural and biochemical level. The N-terminal domain of TelA, while not required for telomere resolution, has been demonstrated to play an autoinhibitory role in telomere resolution, conferring divalent metal responsiveness on the reaction. The N-terminal domain also inhibits the competing reactions of hp telomere fusion and recombination between replicated telomere junctions. Due to the absence of the N-terminal domain from TelA/DNA co-crystal structures we produced an AlphaFold model of a TelA monomer. The AlphaFold model suggested the presence of two inhibitory interfaces; one between the N-terminal domain and the catalytic domain and a second interface between the C-terminal helix and the N-core domain of the protein. We produced mutant TelA's designed to weaken these putative interfaces to test the validity of the modeled interfaces. While our analysis did not bear out the details of the predicted interfaces the model was, nonetheless, extremely useful in guiding design of mutations that, when combined, demonstrated an additive activation of TelA exceeding 250-fold. For some of these hyperactive mutants stimulation of telomere resolution has also been accompanied by activation of competing reactions. However, we have also characterized hyperactive TelA mutants that retain enough autoinhibition to suppress the competing reactions. [ABSTRACT FROM AUTHOR]

Background: In Taiwan, residents with and without dementia mostly co-live in long-term care facilities. The behavioral and psychiatric symptoms of dementia residents often pose challenges for others living together. This study explored the symbiotic experiences of residents without dementia co-living with those with dementia in long-term care facilities in Taiwan to present their experiences of living together. Methods: This was a cross-sectional descriptive study with a phenomenological design. Semi-structured face-to-face interviews were conducted with 30 residents without dementia from three long-term care institutions in Taiwan. Colaizzi's data processing steps were used for analysis. Results: The analysis of interview transcripts revealed that the experiences of residents who lived with those with dementia were that of a "symbiosis." Three core themes were found: "the impact of co-living," "facing difficulties and coping," and "companionship and reciprocity." This study showed that residents without dementia may be affected by the behavioral and psychiatric symptoms of residents with dementia when co-living in long-term care facilities. However, there are also positive and mutually beneficial interactions between them. By helping people with dementia in their daily lives, residents without dementia feel happy and accomplished and their self-worth is enhanced. Furthermore, residents with dementia have more opportunities for social engagement and co-living interactions. Conclusion: These results can guide long-term care facilities without special care dementia units to support residents without dementia, reduce the interference of the behavioral and psychiatric symptoms of residents with dementia, and promote mutual benefits. However, these findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)‐positive early breast cancer (EBC). Methods: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2‐positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta‐regression analyses to investigate the effects of multiple covariates. Results: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68–2.05). Compared with nonconcurrent or non‐anthracycline‐containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04–2.12). The linear fixed‐effects meta‐regression analysis indicated that in trials including more patients with hormone receptor‐positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. Conclusions: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR‐negative, HER2‐positive tumors to enhance pCR rates, with caution advised for HR‐positive tumors due to potential cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background: Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO2 to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO2 capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications. Results: In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity. Conclusions: Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase‐9 and ‐3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor‐eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species‐mediated oxidative stress. Shear flow also regulated epithelial–mesenchymal transition (EMT) by increasing E‐cadherin and ZO‐1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device. [ABSTRACT FROM AUTHOR]

Crop wild relatives (CWR) provide a valuable resource for improving crops. They possess desirable traits that confer resilience to various environmental stresses. To fully utilize crop wild relatives in breeding and conservation programs, it is important to understand the genetic basis of their adaptation. Landscape genomics associates environments with genomic variation and allows for examining the genetic basis of adaptation. Our study examined the differences in allele frequency of 15,416 single nucleotide polymorphisms (SNPs) generated through genotyping by sequencing approach among 153 accessions of 15 wild eggplant relatives and two cultivated species from Africa, the principal hotspot of these wild relatives. We also explored the correlation between these variations and the bioclimatic and soil conditions at their collection sites, providing a comprehensive understanding of the genetic signals of environmental adaptation in African wild eggplant. Redundancy analysis (RDA) results showed that the environmental variation explained 6% while the geographical distances among the collection sites explained 15% of the genomic variation in the eggplant wild relative populations when controlling for population structure. Our findings indicate that even though environmental factors are not the main driver of selection in eggplant wild relatives, it is influential in shaping the genomic variation over time. The selected environmental variables and candidate SNPs effectively revealed grouping patterns according to the environmental characteristics of sampling sites. Using four genotype–environment association methods, we detected 396 candidate SNPs (2.5% of the initial SNPs) associated with eight environmental factors. Some of these SNPs signal genes involved in pathways that help adapt to environmental stresses such as drought, heat, cold, salinity, pests, and diseases. These candidate SNPs will be useful for marker‐assisted improvement and characterizing the germplasm of this crop for developing climate‐resilient eggplant varieties. The study provides a model for applying landscape genomics to other crops' wild relatives. [ABSTRACT FROM AUTHOR]

This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or sulfonic acid) ligands. Four different phenylated ligands, including sodium β-styrenesulfonate (SbSS), sodium benzenesulfonate (SBS), sodium p-toluenesulfonate (SPTS), and 4-dodecylbenzenesulfonic acid (DBSA), were employed to modify blue-emitting CsPbBr1.5Cl1.5 perovskite NCs, resulting in improved size uniformity and surface functionalization. Transmission electron microscopy and X-ray photoelectron spectroscopy confirmed the successful anchoring of sulfonate or sulfonic acid ligands on the surface of perovskite NCs. Moreover, the photoluminescence quantum yield increased from 32% of the original perovskite NCs to 63% of the SPTS-modified ones due to effective surface passivation. Time-resolved photoluminescence decay measurements revealed extended PL lifetimes for ligand-modified NCs, indicative of reduced nonradiative recombination. Thermal stability studies demonstrated that the SPTS-modified NCs retained nearly 80% of the initial PL intensity when heated at 60 °C for 10 min, surpassing the performance of the original NCs. These findings emphasize the optical and thermal stability enhancement of cesium-based perovskite NCs through surface passivation with suitable sulfonate ligands. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = −0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine associations of maternal folic acid supplementation (FAS) during pregnancy with childhood overweight or obesity (OWO) or adiposity. Methods: In a population‐based cohort of 1479 children, maternal FAS during pregnancy was assessed retrospectively by questionnaires. BMI and body fat percentages were measured at a mean age of 6.4 years. Pertinent factors were accounted for in data analyses. Results: Maternal FAS during pregnancy was negatively associated with OWO (adjusted odds ratio: 0.70; 95% CI: 0.50 to 0.99). There were inverse associations of maternal FAS during pregnancy with BMI z score (β: −0.22; 95% CI: −0.39 to −0.05), whole body fat percentage (β: −1.28; 95% CI: −2.27 to −0.30), trunk fat percentage (β: −1.41; 95% CI: −2.78 to −0.04), and limb fat percentage (β: −1.31; 95% CI: −2.32 to −0.30). Stratified analyses found inverse associations of FAS during pregnancy with OWO, BMI z score, and body fat percentages predominantly among children without breastfeeding and whose parents had a below‐tertiary educational level. Conclusions: This study provides novel evidence that maternal FAS during pregnancy was significantly associated with a decreased risk of childhood OWO and adiposity, particularly among children with no breastfeeding and lower parental educational level. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6–18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. Objective: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. Study Design: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. Results: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. Conclusion: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability. [ABSTRACT FROM AUTHOR]

Background: Gender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades. Methods: We conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test. Results: 665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals. Conclusion: The findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men. [ABSTRACT FROM AUTHOR]

Rationale: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. Objectives: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). Methods: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. Measurements and main results: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. Conclusions: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. Case presentation: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. Conclusions: M-B enema and suppository may be an effective treatment for chronic RP. [ABSTRACT FROM AUTHOR]

Background: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. Methods: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. Results: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). Conclusion: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention. [ABSTRACT FROM AUTHOR]

Many design guidelines have been proposed for piled embankments, most of which consider piles or columns as rigid inclusions. In this study, a small-scale physical model test was performed to investigate the load transfer mechanism of a geotextile-reinforced sand layer over a soft subsoil improved by semirigid columns. A multi-stage load was applied at the top of the sand layer until the columns started to yield. When the columns yielded, a reverse load transfer was observed. Vertical stresses were measured and analyzed in terms of efficacy and stress reduction ratio (SRR) with a comparison of existing design guidelines for assessing soil arching. Among the reviewed guidelines, the approach recommended by the Dutch guidelines provided the closest results to the experimental data, whereas the one adopted by the American guidelines predicted well the change in efficacy and SRR under different surcharge loads. However, the load transfer mechanism after the yielding of columns is beyond the scope of the existing design guidelines. In addition, it was found through regression analysis that the increment of vertical stresses on columns and surrounding soil followed an inclined line under partially undrained conditions during loading stages and a curve during consolidation. [ABSTRACT FROM AUTHOR]

This study explores the specific language learning strategies (LLS) employed by student-athletes in Higher Education institutions in Taiwan. Given these student-athletes' challenges in balancing academic and athletic commitments, understanding their adoption of LLS provides valuable pedagogical insights. This quantitative research gathered 150 responses, considering variables such as academic year, gender, duration of English study, and athletic specialization. Our findings indicate a moderate overall LLS usage, with a pronounced preference for metacognitive strategies. Strategies such as watching English shows and actively engaging in conversations were particularly favored. Conversely, kinesthetic and mnemonic approaches were less popular, such as acting out words or using rhymes. Delving deeper into the data, there were limited gender-based differences in LLS adoption. However, athletic specialization significantly influenced LLS preferences. Especially, martial arts or combat sports athletes had the highest LLS mean scores across all categories. These results highlight the distinct LLS preferences among Taiwanese student-athletes and suggest potential pedagogical adaptations to enhance their language learning experiences. [ABSTRACT FROM AUTHOR]

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot–Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2. Synopsis: This study unveils the first discovery of an INSC gene missense mutation causing axonal Charcot-Marie-Tooth disease (CMT) and examines the microtubule-stabilizing role of PAR3/INSC/LGN in the adult peripheral nervous system (PNS). Microtubule-stabilizing agents effectively reverse proprioception defects and necrosis in INSC mutation individuals. Identification of INSC as a potential pathogenic gene in adult-onset peripheral neuropathy. Demonstration of PAR3/INSC/LGN dysfunction leading to proprioceptive defects resembling gait abnormalities in patients with CMT. Requirement of PAR3/INSC/LGN for microtubule stabilization in the adult PNS. Reversal of both morphological and functional defects in a disease model through the use of microtubule-stabilizing agents, presenting a potential therapeutic strategy for peripheral neuropathy. This study unveils the first discovery of an INSC gene missense mutation causing axonal Charcot-Marie-Tooth disease (CMT) and examines the microtubule-stabilizing role of PAR3/INSC/LGN in the adult peripheral nervous system (PNS). Microtubule-stabilizing agents effectively reverse proprioception defects and necrosis in INSC mutation individuals. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; however, whether preoperative grip strength can predict functional outcomes in patients undergoing ARCR remains unknown. This study aimed to investigate the correlation between preoperative grip strength and postoperative shoulder function following ARCR. Methods: A total of 52 patients with full-thickness repairable RCTs were prospectively enrolled. Baseline parameters, namely patient characteristics and intraoperative findings, were included for analysis. Postoperative shoulder functional outcomes were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) questionnaire and Constant–Murley scores (CMSs). Patients were followed up and evaluated at three and six months after ARCR. The effects of baseline parameters on postoperative outcomes were measured using generalized estimating equations. Results: At three and six months postoperatively, all clinical outcomes evaluated exhibited significant improvement from baseline following ARCR. Within 6 months postoperatively, higher preoperative grip strength was significantly correlated with higher CMSs (β = 0.470, p = 0.022), whereas increased numbers of total suture anchors were significantly correlated with decreased CMSs (β = − 4.361, p = 0.03). Higher body mass index was significantly correlated with higher postoperative QDASH scores (β = 1.561, p = 0.03) during follow-up. Conclusions: Higher baseline grip strength predicts more favorable postoperative shoulder function following ARCR. A preoperative grip strength test in orthopedic clinics may serve as a predictor for postoperative shoulder functional recovery in patients undergoing ARCR. [ABSTRACT FROM AUTHOR]

Background: Despite being the gold standard for diagnosing osteoporosis, dual-energy X-ray absorptiometry (DXA) is an underutilized screening tool for osteoporosis. Objectives: This study proposed and validated a controllable feature layer of a convolutional neural network (CNN) model with a preprocessing image algorithm to classify osteoporosis and predict T -score on the proximal hip region via simple hip radiographs. Design: This was a single-center, retrospective study. Methods: An image dataset of 3460 unilateral hip images from 1730 patients (age ⩾50 years) was retrospectively collected with matched DXA assessment for T -score for the targeted proximal hip regions to train (2473 unilateral hip images from 1430 patients) and test (497 unilateral hip images from 300 patients) the proposed CNN model. All images were processed with a fully automated CNN model, X1AI-Osteo. Results: The proposed screening tool illustrated a better performance (sensitivity: 97.2%; specificity: 95.6%; positive predictive value: 95.7%; negative predictive value: 97.1%; area under the curve: 0.96) than the open-sourced CNN models in predicting osteoporosis. Moreover, when combining variables, including age, body mass index, and sex as features in the training metric, there was high consistency in the T -score on the targeted hip regions between the proposed CNN model and the DXA (r = 0.996, p < 0.001). Conclusion: The proposed CNN model may identify osteoporosis and predict T -scores on the targeted hip regions from simple hip radiographs with high accuracy, highlighting the future application for population-based opportunistic osteoporosis screening with low cost and high adaptability for a broader population at risk. Trial registration: TMU-JIRB N201909036. [ABSTRACT FROM AUTHOR]

This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2–4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese groups (BMI ≥ 27 kg/m2). A T-score ≤ − 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health. [ABSTRACT FROM AUTHOR]

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid‐cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow‐up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high‐level echo, well‐defined margins and moderate vascularity. [ABSTRACT FROM AUTHOR]

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10−16), Alzheimer's disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10−15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10−05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes. [ABSTRACT FROM AUTHOR]