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[This corrects the article DOI: 10.1371/journal.pone.0266608.].

We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nations population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.

INTRODUCTION: Community-based health interventions often demonstrate efficacy in clinical trial settings but fail to be implemented in the real-world. We sought to identify the key operational and contextual elements of the Los Angeles Barbershop Blood Pressure Study (LABBPS), an objectively successful community-based health intervention primed for real-world implementation. LABBPS was a cluster randomized control trial that paired the barbers of Black-owned barbershops with clinical pharmacists to manage uncontrolled hypertension in Black male patrons, demonstrating a substantial 21.6 mmHg reduction in systolic blood pressure. Despite this success, the LABBPS intervention has not expanded beyond the original clinical trial setting. The aim of this study was to determine the facilitating and limiting factors to expansion of the LABBPS intervention. METHODS: We undertook a qualitative assessment of semi-structured interviews with study participants performed after trial completion. Interviews included a total of 31 participants including 20 (6%) of the 319 LABBPS program participants (patrons), 10 (19%) barbers, and one (50%) clinical pharmacist. The semi-structured interviews were focused on perceptions of the medical system, study intervention, and influence of social factors on health. RESULTS: Several common themes emerged from thematic analysis of interview responses including: importance of care provided in a convenient and safe environment, individual responsibility for health and health-related behaviors, and engagement of trusted community members. In particular, patrons reported that receiving the intervention from their barber in a familiar environment positively influenced the formation of relationships with clinical pharmacists around shared efforts to improve medication adherence and healthy habits. All interviewee groups identified the trust diad, comprising the familiar environment and respected community member, as instrumental in increasing health-related behaviors to a degree not usually achieved by traditional healthcare providers. DISCUSSION: In conclusion, participants of an objectively successful community-based intervention trial consistently identified key features that could facilitate wider implementation and efficacy: social trust relationships, soliciting insights of trust bearers, and consistent engagement in a familiar community setting. These findings can help to inform the design and operations of future community-based studies and programs aiming to achieve a broad and sustainable impact.

Current models of early human subsistence economies suggest a focus on large mammal hunting. To evaluate this hypothesis, we examine human bone stable isotope chemistry of 24 individuals from the early Holocene sites of Wilamaya Patjxa (9.0-8.7 cal. ka) and Soro Mikaya Patjxa (8.0-6.5 cal. ka) located at 3800 meters above sea level on the Andean Altiplano, Peru. Contrary to expectation, Bayesian mixing models based on the isotope chemistry reveal that plants dominated the diet, comprising 70-95% of the average diet. Paleoethnobotanical data further show that tubers may have been the most prominent subsistence resource. These findings update our understanding of earliest forager economies and the pathway to agricultural economies in the Andean highlands. The findings furthermore suggest that the initial subsistence economies of early human populations adapting to new landscapes may have been more plant oriented than current models suggest.

BACKGROUND: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. METHODS: Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. RESULTS: Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04). CONCLUSION: We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.

Plate-based proteomic sample preparation offers a solution to the large sample throughput demands in the biotechnology field where hundreds or thousands of engineered microbes are constructed for testing is routine. Meanwhile, sample preparation methods that work efficiently on broader microbial groups are desirable for new applications of proteomics in other fields, such as microbial communities. Here, we detail a step-by-step protocol that consists of cell lysis in an alkaline chemical buffer (NaOH/SDS) followed by protein precipitation with high-ionic strength acetone in 96-well format. The protocol works for a broad range of microbes (e.g., Gram-negative bacteria, Gram-positive bacteria, non-filamentous fungi) and the resulting proteins are ready for tryptic digestion for bottom-up quantitative proteomic analysis without the need for desalting column cleanup. The yield of protein using this protocol increases linearly with respect to the amount of starting biomass from 0.5-2.0 OD*mL of cells. By using a bench-top automated liquid dispenser, a cost-effective and environmentally-friendly option to eliminating pipette tips and reducing reagent waste, the protocol takes approximately 30 minutes to extract protein from 96 samples. Tests on mock mixtures showed expected results that the biomass composition structure is in close agreement with the experimental design. Lastly, we applied the protocol for the composition analysis of a synthetic community of environmental isolates grown on two different media. This protocol has been developed to facilitate rapid, low-variance sample preparation of hundreds of samples and allow flexibility for future protocol development.

We have developed a cell-based outer vocal fold replacement (COVR) as a potential therapy to improve voice quality after vocal fold (VF) injury, radiation, or tumor resection. The COVR consists of multipotent human adipose-derived stem cells (hASC) embedded within a three-dimensional fibrin scaffold that resembles vocal fold epithelium and lamina propria layers. Previous work has shown improved wound healing in rabbit studies. In this pilot study in pigs, we sought to develop methods for large animal implantation and phonatory assessment. Feasibility, safety, and structural and functional outcomes of the COVR implant are described. Of eight pigs studied, six animals underwent COVR implantation with harvest between 2 weeks and 6 months. Recovery of laryngeal tissue structure was assessed by vibratory and histologic analyses. Recovery of voice function was assessed by investigating acoustic parameters that were derived specifically for pigs. Results showed improved lamina propria qualities relative to an injured control animal at 6 months. Acoustic parameters reflected voice worsening immediately after surgery as expected; acoustics displayed clear voice recovery in the animal followed for 6 months after COVR. These methods form the basis for a larger-scale long-term pre-clinical safety and efficacy study.

Social touch is an important form of interpersonal emotion regulation. In recent years, the emotion regulation effects of two types of touch have been studied extensively: handholding and stroking (specifically of skin with C-tactile afferents on the forearm, i.e. C-touch). While some studies compare their effectiveness, with mixed results, no study to date has examined which type of touch is subjectively preferred. Given the potential bidirectional communication provided by handholding, we hypothesized that to regulate intense emotions, participants would prefer handholding. In four pre-registered online studies (total N = 287), participants rated handholding and stroking, presented in short videos, as emotion regulation methods. Study 1 examined touch reception preference in hypothetical situations. Study 2 replicated Study 1 while also examining touch provision preferences. Study 3 examined touch reception preferences of participants with blood/injection phobia in hypothetical injection situations. Study 4 examined types of touch participants who have recently given birth recalled receiving during childbirth and their hypothetical preferences. In all studies, participants preferred handholding over stroking; participants who have recently given birth reported receiving handholding more than stroking. This was especially evident in Studies 1-3 in emotionally intense situations. These results demonstrate that handholding is preferred over stroking as a form of emotion regulation, especially in intense situations, and support the importance of two-way sensory communication for emotion regulation via touch. We discuss the results and possible additional mechanisms, including top-down processing and cultural priming.

Human exposure to low-to-moderate dose ionizing radiation (LMD-IR) is increasing via environmental, medical, occupational sources. Acute exposure to LMD-IR can cause subclinical damage to cells, resulting in altered gene expression and cellular function within the human brain. It has been difficult to identify diagnostic and predictive biomarkers of exposure using traditional research models due to factors including lack of 3D structure in monolayer cell cultures, limited ability of animal models to accurately predict human responses, and technical limitations of studying functional human brain tissue. To address this gap, we generated brain/cerebral organoids from human induced pluripotent stem cells to study the radiosensitivity of human brain cells, including neurons, astrocytes, and oligodendrocytes. While organoids have become popular models for studying brain physiology and pathology, there is little evidence to confirm that exposing brain organoids to LMD-IR will recapitulate previous in vitro and in vivo observations. We hypothesized that exposing brain organoids to proton radiation would (1) cause a time- and dose-dependent increase in DNA damage, (2) induce cell type-specific differences in radiosensitivity, and (3) increase expression of oxidative stress and DNA damage response genes. Organoids were exposed to 0.5 or 2 Gy of 250 MeV protons and samples were collected at 30 minute, 24 hour, and 48 hour timepoints. Using immunofluorescence and RNA sequencing, we found time- and dose-dependent increases in DNA damage in irradiated organoids; no changes in cell populations for neurons, oligodendrocytes, and astrocytes by 24 hours; decreased expression of genes related to oligodendrocyte lineage, astrocyte lineage, mitochondrial function, and cell cycle progression by 48 hours; increased expression of genes related to neuron lineage, oxidative stress, and DNA damage checkpoint regulation by 48 hours. Our findings demonstrate the possibility of using organoids to characterize cell-specific radiosensitivity and early radiation-induced gene expression changes within the human brain, providing new avenues for further study of the mechanisms underlying acute neural cell responses to IR exposure at low-to-moderate doses.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its genetic and geographical origins remain unclear, resulting in suspicions about its natural origin. In one of our previous studies, we reported the presence of a furin cleavage site RRAR in the junction region between S1 and S2 subunits of the spike protein, which was discovered as the first crucial clue for the origin tracing of SARS-CoV-2. In the present study, we conducted an integrative analysis of new genome data from bat Sarbecovirus strains reported after the COVID-19 outbreak. The primary results included the identification of BANAL-20-52, Rp22DB159, and S18CXBatR24 as three close relatives of SARS-CoV-2 and the successful detection of seven out of nine key genomic features (designated as RC0-7 and ORF8) observed in wild types of SARS-CoV-2 in the three close relatives from Laos, Vietnam, and Yunnan province of China, respectively. The most significant contribution of the present study lies in the detection of RC1 in wild genotype in a bat Sarbecovirus population BANAL-20-52 belonging to. Encoding a segment of the NSP3 protein, RC1 was discovered as the second crucial clue for the origin tracing of SARS-CoV-2. Although RC0, encoding the junction furin cleavage site, remains undetected outside of the SARS-CoV-2 genome, Feuang of Laos is the sole place where eight of the nine wild-type features (RC1-7 and ORF8) have been detected.

PurposeWe evaluated the IOP-lowering efficacy and safety of latanoprostene bunod (LBN) ophthalmic solution 0.024% (Vyzulta®), the first topical nitric oxide-donating prostaglandin analog (PGA), in clinical practice.Materials and methodsA retrospective medical chart review from July 2021 to July 2023 of patients with open-angle glaucoma receiving LBN with at least 1 year follow-up was conducted. All included patients received LBN 0.024% as a replacement for a PGA, with examinations at 1-, 3-, 6-and 12-months follow-up. Main outcome measures were IOP, retinal nerve fiber layer thickness, visual fields before/after LBN use and adverse effects. Subgroup analysis with glaucoma types and PGA use were performed for additional IOP reduction after LBN use.ResultsAmong 78 included patients, 47 patients (81 eyes), 60% with open-angle glaucoma (OAG) remained on LBN throughout 12-month follow-up. Baseline IOP was 18.2±4.2 mm Hg, and Prostaglandin analog (PGA)-IOP was 14.4 ± 3.0 mm Hg (21% mean IOP reduction). After switched to LBN, mean additional IOP reduction was 1.0 mm Hg at month 1, and the greatest reduction was 1.6 mm Hg (8.8% additional mean IOP reduction) at month 12 (PConclusionsAlthough high intolerable adverse effects including conjunctival hyperemia and eye irritation happened in the first month, remaining sixty percent of patients exhibited statistically significant additional IOP reductions in the replacement of other PGAs during 12 months of clinical use of LBN 0.024%.

Plants have developed precise defense mechanisms against cadmium (Cd) stress, with vacuolar compartmentalization of Cd2+ being a crucial process in Cd detoxification. The transport of Cd into vacuoles by these cation / H+ antiporters is powered by the pH gradient created by proton pumps. In this study, the full-length cDNA of a vacuolar H+-pyrophosphatase (V-PPase) gene from Boehmeria nivea (ramie), BnVP1, was isolated using the rapid amplification of cDNA ends (RACE) method. The open reading frame (ORF) of BnVP1 is 2292 bp, encoding a 763 amino acid V-PPase protein with 15 predicted transmembrane domains. Sequence alignment and phylogenetic analysis revealed that BnVP1 belongs to the Type I V-PPase family. Quantitative RT-PCR assays demonstrated that BnVP1 expression was significantly higher in ramie roots than in shoots. Cd treatments markedly induced BnVP1 expression in both roots and leaves of ramie seedlings, with a more pronounced effect in roots. Additionally, BnVP1 expression was significantly upregulated by the plant hormone methyl jasmonate (MeJA). Heterologous expression of BnVP1 in transgenic Arabidopsis significantly enhanced V-PPase activity in the roots. The growth performance, root elongation, and total chlorophyll content of transgenic plants with high tonoplast H+-PPase (V-PPase) activity were superior to those of wild-type plants. Overexpression of BnVP1 reduced membrane lipid peroxidation and ion leakage, and significantly increased Cd accumulation in the roots of transgenic Arabidopsis seedlings. This study provides new genetic resources for the phytoremediation of Cd-contaminated farmland.

The COVID-19 outbreak led to widespread school closures and the shift to remote teaching, potentially resulting in lasting negative impacts on teachers' psychological well-being due to increased workloads and a perceived lack of administrative support. Despite the significance of these challenges, few studies have delved into the long-term effects of perceived instructional leadership on teachers' psychological health. To bridge this research gap, we utilized longitudinal data from 927 primary and secondary school teachers surveyed in two phases: Time 1 in mid-November 2021 and Time 2 in early January 2022. Using hierarchical linear modeling (HLM), our findings revealed that perceptions of instructional leadership, especially the "perceived school neglect of teaching autonomy" at Time 1 were positively correlated with burnout levels at Time 2. Additionally, burnout at Time 2 was positively associated with psychological distress and acted as a mediator between the "perceived school neglect of teaching autonomy" and psychological distress. In light of these findings, we recommend that schools prioritize teachers' teaching autonomy and take proactive measures to mitigate burnout and psychological distress, aiming for the sustainable well-being of both teachers and students in the post-pandemic era.

ObjectivesThis study delves into the association between dietary niacin intake and Helicobacter pylori seropositivity, a topic gaining prominence in academic discourse. However, the precise role of Niacin in the development and progression of Helicobacter pylori seropositivity remains inadequately understood. Thus, this research aims to investigate the connections between H. pylori seropositivity and dietary niacin intake using a nationally representative sample of adults.MethodsA cross-sectional analysis encompassed 4,000 participants from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 1999 and 2000, all aged 20 years or older. The study employed the generalized additive model (GAM) and multivariate logistic regression to explore the potential relationship between niacin intake and Helicobacter pylori seropositivity. Subgroup analyses were performed based on gender, age, diabetes, hypertension, and hyperlipemia.ResultsAnalyzing cross-sectional data from NHANES 1999-2000 involving individuals aged 20 years and above revealed that out of 4,000 participants, 1,842 tested positive for H. pylori via serology. Multivariate analyses unveiled a significant inverse correlation between niacin intake and H. pylori seropositivity. Adjusted odds ratios (ORs) for dietary niacin intake in quartiles Q2 (13.31-19.26 mg/d), Q3 (19.27-27.42 mg/d), and Q4 (>27.42 mg/d) compared to Q1 (ConclusionThis study suggests a potential link between increased dietary niacin intake and reduced prevalence of Helicobacter pylori seropositivity. This correlation is bolstered by plausible mechanisms involving immunomodulatory function, mitochondrial dysfunction, and cellular oxidative stress.

The key to high-quality development in the textile and apparel industry lies in enhancing technological innovation and optimizing the efficiency of technological innovation. Based on data from 60 A-share listed companies in the textile and apparel sector in China from 2013 to 2022, this study employs a three-stage DEA model and the Malmquist index model to measure changes in technological innovation efficiency from static and dynamic perspectives. Additionally, it uses a Tobit model to analyze the impact and mechanisms of management and financial factors on technological innovation efficiency. The results indicate that: (1) Compared to the manufacturing industry and its sub-sectors, the overall technological innovation efficiency of listed textile and apparel companies was relatively low and showed a declining trend between 2013 and 2022; (2) Over the decade, the average total factor productivity of these listed companies increased by 1.7%, exhibiting a "W" shaped fluctuation, with technological progress, pure technical efficiency, and scale efficiency all showing weak improvement; (3) Management and financial factors significantly influence technological innovation efficiency. Specifically, employee quality, profitability, and operational capability are positively correlated with technological innovation efficiency and have long-term effectiveness, while firm age, management costs, equity concentration, development ability, and debt repayment capacity are negatively correlated with technological innovation efficiency; (4) Different types of enterprises show differences in the significance of management factors, while whether the same person holds both managerial positions significantly affects financial factors.

Diabetic peripheral neuropathy (DPN) is a common complication associated with diabetes, and can affect quality of life considerably. Dorsal root ganglion (DRG) plays an important role in the development of DPN. However, the relationship between DRG and the pathogenesis of DPN still lacks a thorough exploration. Besides, a more in-depth understanding of the cell type composition of DRG, and the roles of different cell types in mediating DPN are needed. Here we conducted single-cell RNA-seq (scRNA-seq) for DRG tissues isolated from healthy control and DPN rats. Our results demonstrated DRG includes eight cell-type populations (e.g., neurons, satellite glial cells (SGCs), Schwann cells (SCs), endothelial cells, fibroblasts). In the heterogeneity analyses of cells, six neuron sub-types, three SGC sub-types and three SC sub-types were identified, additionally, biological functions related to cell sub-types were further revealed. Cell communication analysis showed dynamic interactions between neurons, SGCs and SCs. We also found that the aberrantly expressed transcripts in sub-types of neurons, SGCs and SCs with DPN were associated with diabetic neuropathic pain, cell apoptosis, oxidative stress, etc. In conclusion, this study provides a systematic perspective of the cellular composition and interactions of DRG tissues, and suggests that neurons, SGCs and SCs play vital roles in the progression of DPN. Our data may provide a valuable resource for future studies regarding the pathophysiological effect of particular cell type in DPN.

More than 50% of caudates are threatened with extinction and are in need of ex-situ breeding programs to support conservation efforts and species recovery. Unfortunately, many salamander populations under human care can experience reproductive failure, primarily due to missing environmental cues necessary for breeding. Assisted reproductive technologies (ARTs) are a useful suite of techniques for overcoming or bypassing these missing environmental cues to promote breeding. Exogenous hormones are used to stimulate natural breeding behaviors or gamete expression for in-vitro fertilization or biobanking and are typically administered intramuscularly in caudates. While effective, intramuscular injection is risky to perform in smaller-bodied animals, resulting in health and welfare risks. This research investigated the spermiation response to hormone administration through a non-invasive oral bioencapsulation route using the tiger salamander (Ambystoma tigrinum) as a model species. Male salamanders were randomly rotated six weeks apart through four treatments (n = 11 males/treatment) in which animals received a resolving dose of gonadotropin-releasing hormone (GnRH) as follows: (1) Prime-Only (0.0 μg/g); (2) Low (0.25 μg/g); (3) Medium (1.0 μg/g); and (4) High (2.0 μg/g). All males were given a GnRH priming dose (0.25 μg/g) 24 hours prior to the resolving dose. Exogenous hormone was delivered inside of a cricket (Gryllodes sigillatus) that was presented as a food item by tweezers. Sperm samples were collected at 1, 3, 6, 9, 12, and 24 hours after the resolving dose and analyzed for quantity and quality. For all treatments, sperm concentration was produced in an episodic pattern over time. The Prime-Only treatment had a lower (p < 0.05) percent of sperm exhibiting normal morphology compared to treatments utilizing a resolving dose of GnRH. Overall, oral administration of GnRH is a feasible route of inducing spermiation in salamanders, yielding sperm of sufficient quantity and quality for in-vitro fertilization and biobanking efforts.

BackgroundNumerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations.MethodsAn electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4.ResultsA total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, PConclusionThis meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.

IntroductionLung cancer is the primary cause of cancer-related deaths worldwide, with high rates of morbidity and mortality. The most effective treatment for early stage (I-II) non-small cell lung cancer (NSCLC) is surgical resection. However, the extent of mediastinal lymph nodes removal required and the impact of their removal remains controversial. This systematic review and meta-analysis aimed to evaluate the postoperative complications in patients with stage I-II NSCLC who received mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS).Methods and analysisAccording to the predefined inclusion criteria, we will conduct a comprehensive search for randomized controlled trials (RCTs) and observational studies examining the postoperative complications of MLND compared to MLNS in patients with stage I-II NSCLC. The search will be performed across multiple databases including PubMed, Embase, the Cochrane Library, CNKI, WanFang, Sinomed, VIP, Duxiu, and Web of Science from inception to February 2024. Additionally, relevant literature references will be retrieved and hand searching of pertinent journals will be conducted. Screening, data extraction, and quality assessment will be performed by two independent reviewers. Review Manager 5.4 will be applied in analyzing and synthesizing. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence for the whole RCTs and used Newcastle-Ottawa scale to assess the methodologic quality of observational studies.Ethics and disseminationThis study did not include personal information. Ethical approval was not required for this study. This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal.ConclusionThis systematic review will contribute to compare the safety and survival benefits of these two surgical techniques for the treatment of early stage NSCLC, to further guide the selection of surgical approaches.Trial registrationThe protocol of the systematic review has been registered on Open Science Framework, with a registration number of DOI https://doi.org/10.17605/OSF.IO/N2Y5D.

BackgroundThis study aimed to compare the outcomes of double-armed two-suture longitudinal intussusception microsurgical vasoepididymostomy (LIVE) and single-armed two-suture LIVE techniques in patients with epididymal obstructive azoospermia (EOA). The main outcomes assessed were patency rates, patency time, semen quality and natural pregnancy rates.MethodsData from patients with EOA who underwent two-suture LIVE were obtained from databases including PubMed, EMBASE, and Web of Science. Weighted data were analyzed using a random-effects model, and weighted mean differences were reported.ResultsA total of 1574 patients with EOA from 24 studies were included. The overall patency rate was approximately 68% (95% confidence interval [CI]: 63-72%), with a patency time of approximately 4.63 months (95% CI: 4.15-5.12). The sperm concentration reached 26.90 million/ml and the sperm motility was 23.74%. The natural pregnancy rate was 38% (95% CI: 31-46%). The different definitions of patency do not seem to have any meaningful impact when comparing patency rates. There was no significant difference in patency rates, patency time, semen quality and natural pregnancy rates between the double-armed and single-armed LIVE techniques.ConclusionThe single-armed LIVE is a potential alternative surgical option when high quality double-needle sutures are not easily accessible.

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.

BackgroundWorldwide, an estimated 38.0 million people lived with the human immunodeficiency virus in 2019, and 3.4 million young people aged 15~24 years were living with HIV. Sub-Saharan Africa carries a significant HIV burden with West and Central Africa most affected with HIV. Among the young people living with HIV in West and Central Africa, an estimated 810,000 were aged 15~24 years. This study aimed to assess predictors that influence the uptake of HIV testing among youth aged 15~24 years in The Gambia.MethodsThe 2013 Gambia Demographic and Health Survey data for youth aged 15~24 years was used. The Andersen behavioral model of health service use guided this study. A cross-sectional study design was used on 6194 subjects, among which 4730 were female. The analysis employed Chi-squared tests and hierarchical logistic regression.ResultsLess than one-quarter of the youth 1404 (22.6%) had ever been tested for HIV. Young people aged 20~24 years (adjusted odds ratio (aOR): 1.98), who were females (aOR: 1.13), married youth (aOR: 3.89), with a primary (aOR: 1.23), secondary or higher education (aOR: 1.46), and who were from the Jola/Karoninka ethnic group (aOR: 1.81), had higher odds of having been tested for HIV. Those with adequate HIV knowledge and those who were sexually active and had aged at first sex ≥15 years (aOR: 3.99) and those

PurposeSarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes.MethodsWe systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results.ResultsTwenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015).ConclusionThe current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.

This paper analyzes the potential shortsightedness of enterprise managers through annual reports. Additionally, we use corporate financial statement data to measure enterprises over-financialization in terms of resource allocation. After testing with a causal inference model, we find that firms with managerial myopia significantly contribute to over-financialization. It remains robust even after the instrumental variable of whether the manager has experienced a famine is used. Furthermore, financial distress and financing constraints amplify the inclination of short-term-focused managers to amass greater financial assets.

This study utilizes data from A-share listed companies between 2011 and 2020 to empirically investigate the impact and mechanism of public welfare donations on the internal income gap of enterprises. The research findings indicate that public welfare donations significantly increase the per capita salary of management, while their impact on the per capita salary of ordinary employees is not significant, thus leading to an expansion of the internal income gap within enterprises. The results from mechanism testing reveal that the income tax benefits resulting from charitable donations and the rise in corporate operating income have contributed to an increase in excess rent shared by enterprises and employees. Due to a stronger bargaining power, management shares more excess rents, thereby widening the income gap within the enterprise. Heterogeneity analysis demonstrates that public welfare donations have a greater impact on the internal income gap of non-state-owned enterprises; however, limiting executive compensation and enhancing employees' bargaining power can mitigate this widening effect caused by public welfare donations on enterprise's internal income gap. The research value of this study is threefold. Firstly, there is a scarcity of studies on the impact of public welfare donations on the income gap within enterprises, and this study contributes to enriching the research in this area. Secondly, this paper examines the effect of tax incentives for public welfare donations on the internal income gap of enterprises, thereby deepening the research on the impact of tax reduction and fee reduction, as well as expanding our understanding of corporate income tax preferential policies. Thirdly, it offers insights into improving enterprise compensation systems and enhancing corporate governance. Senior executives can potentially allocate more excess rent through their strong bargaining power. If their compensation remains unrestricted, it may lead to a widening internal income gap and negatively affect company operational efficiency.

IntroductionVisceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer.MethodsWe identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models.ResultsIn total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer.ConclusionPatients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer.

Equitable and effective planning of urban park green spaces (UPGSs) is an important way to promote green and healthy urban development and improve citizens' quality of life. However, under the background of rapid urbanization, linear large cities, with their unique spatial forms and high-density population agglomerations, have brought special challenges for the planning and management of urban public green spaces. This study takes Lanzhou, a typical representative of high-density linear large cities in China, as a case study. Based on the improvement of the traditional Gaussian Two-Step Floating Catchment Area method (G2SFCA), combined with the Gini coefficient and the Lorentz curve, the social equity and spatial equity of UPGS supply-demand in the central urban area of Lanzhou were evaluated at the city and district scales. Meanwhile, the areas with shortage of UPGS supply-demand were accurately identified as the key areas for future optimization. The results show that: (1) There are significant differences in the equity of UPGS supply-demand in the linear large Lanzhou at the social and spatial levels, and most UPGS resources are enjoyed by a few people; (2) The spatial accessibility of UPGSs has an obvious "string of beads" distribution Characteristics, and the areas with high accessibility are mainly concentrated along rivers; (3) The equity of UPGS supply-demand exhibits a spatial gradient effect, which is characterized by a circle distribution. From the inside to the outside, it is as follows: good supply-dense population, good supply-sparse population, supply shortage-dense population, supply shortage-sparse population. Finally, based on the concept of "progressive micro-regeneration" and the Location Allocation model (LA), the optimal sites for new UPGSs were determined, maximizing the equity of UPGS supply-demand. This provides a practical reference for relevant management departments to optimize park layouts in the future.

Hardness is one of the basic parameters of water, and a high-level hardness of drinking water may be harmful to human health. Thus, it is very important to monitor drinking water hardness. In this work, a portable lateral flow distance-based paper sensor for the semi-quantitative detection of drinking water hardness is demonstrated. In the presence of Ca2+/Mg2+, the hydrogel can be formed via the chelation between sodium alginate and Ca2+/Mg2+, inducing a phase separation process. The viscosity change of the sodium alginate solution is directly related to the Ca2+/Mg2+ concentration and can be determined by the water lateral flow distance on test strips. The sensor successfully realizes the quantification of Ca2+ and Mg2+ in the range of 0-10 mmol L-1 and 4-20 mmol L-1, respectively. The recoveries are found varied from 95% to 108.9%. The water hardness is acceptable for drinking if the Cr values lies in the range of 0.259 to 0.419, and it is high with the Cr value above 0.595. Remarkably, the performance of the sensor is comparable with the commercial kit for real water samples, which avoids the subjective judgment. Overall, this method provides a portable approach for semi-quantitative detection of drinking water hardness with the merits of convenience and low cost, which shows great potential for the potential application.

Steganography, the use of algorithms to embed secret information in a carrier image, is widely used in the field of information transmission, but steganalysis tools built using traditional steganographic algorithms can easily identify them. Steganography without embedding (SWE) can effectively resist detection by steganography analysis tools by mapping noise onto secret information and generating secret images from secret noise. However, most SWE still have problems with the small capacity of steganographic data and the difficulty of extracting the data. Based on the above problems, this paper proposes image steganography without embedding carrier secret information. The objective of this approach is to enhance the capacity of secret information and the accuracy of secret information extraction for the purpose of improving the performance of security network communication. The proposed technique exploits the carrier characteristics to generate the carrier secret tensor, which improves the accuracy of information extraction while ensuring the accuracy of secret information extraction. Furthermore, the Wasserstein distance is employed as a constraint for the discriminator, and weight clipping is introduced to enhance the secret information capacity and extraction accuracy. Experimental results show that the proposed method can improve the data extraction accuracy by 10.03% at the capacity of 2304 bits, which verifies the effectiveness and universality of the method. The research presented here introduces a new intelligent information steganography secure communication model for secure communication in networks, which can improve the information capacity and extraction accuracy of image steganography without embedding.

Obstructive uropathy is a common kidney disease caused by elevated hydrostatic pressure (HP), but relevant molecular and cellular mechanisms have not yet been well understood. In this study, we ex vivo investigated the effects of elevated HP on human renal epithelial cells (HREpCs). Primary HREpCs were subjected to 100 cmH2O HP for 8 or 48 h. Then, the cells were cultured without HP stimulation for another 24 h or 72 h. Cell morphology showed almost no change after 8h HP treatment, but exhibited reversible elongation after 48h HP treatment. HP treatment for 8 h increased the expression of TGFB1 and VEGFA but decreased the expression of CSF2 and TGFB2. On the other hand, HP treatment for 48 h downregulated the expression of CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulated the expression of TGFB3. Interestingly, all changes induced by 48 h HP treatment were detected more severe compared to 8 h HP treatment. In conclusion, elongated ex vivo HP loading to renal epithelial cells induces reversible changes on cell morphology and disturbs the expression of several growth factors, which provides novel mechanistic insight on elevated HP-caused kidney injury such as obstructive uropathy.

ObjectiveSarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance.MethodsWe used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis.ResultsOur univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (β = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (β = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (βALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; βALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (β = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (β = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (β = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (βALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; βALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (β = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (β = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (β = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (β = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (β = 0.589; 95% CI: 0.372-0.806, P = 0.000).ConclusionsBidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.

Cognitive and social-emotional development in the first three years of life is associated with later skills. However, little is known about the paths of developmental delays in both cognitive and social-emotional skills before age 3 or to what extent these paths predict later developmental outcomes. The aim of this study is to examine the associations between the different paths of developmental delays in both cognitive and social-emotional skills of children before age 3 and the levels of development of the children when they are preschool age. Using a longitudinal data collected at three time points from 1245 children and their caregivers in rural China, we identified four different paths of developmental delays in cognitive and social-emotional before age 3 and examined how these paths are associated with different levels of developmental outcomes at preschool age. We used a non-parametric standardization approach and an ordinary least squares model to perform our analyses. Findings show that rates of developmental delays in either cognitive or social-emotional domain or both domains are high at all different time points, ranging from 20% to 55% for cognitive delays and 42% to 61% for social-emotional delays. Over half of children experienced deteriorating levels of either cognitive or social-emotional development before age 3. A large share of children was found to be persistently delayed in either domain. Only a small share of children raised their levels of development in either domain before age 3. In addition, we identified certain socioeconomic status of the family that are associated with never or deteriorating path of child developmental delays. More importantly, we revealed that different paths of developmental delays before age 3 have predictive power on different levels of developmental outcomes at preschool age. Our results suggest that actions are needed at the earliest times to improve child development when children are still infants or toddlers.

In this paper, the buckling behaviour of rectangular and skew plates with elastically restrained edges subjected to non-uniform mechanical edge loading is investigated. An analysis method is developed for calculating the critical buckling load of plates using the Ritz method under non-uniform mechanical edge loading, in which the shape function is expressed as Legendre polynomials. The in-plane stress distribution under non-uniform mechanical edge loading is defined by the pre-buckling analysis. Contributions of elastic boundary conditions are taken into accounted by giving different edge spring stiffnesses. The proposed method for buckling analysis of plates is validated by the comparison of exiting results in literature. Finally, the effects of the edge restrained stiffness, non-uniform edge loading, skew angle, aspect ratio and combined compression-shear load are discussed by parametric analysis.

BackgroundFrom 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS.MethodsThe data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution.ResultsA final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets.ConclusionsCompared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.

ObjectiveThis study aims to examine the validity of the MFS by analyzing the electronic medical records on fall risk in obstetrics and gynecology wards and determine the optimal cut-off score of the Morse Fall Scale.DesignA retrospective survey.MethodsThe research was conducted in an Obstetrics and Gynecology Hospital and a general hospital. The sample included 136 fall inpatients and 120 no-fall inpatients recruited from January 1st, 2020, to July 10th, 2022. The Morse Fall Scale was analyzed using the gold standard of patients who fell while hospitalized, assessing the area under the Receiver Operating Characteristic curve, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and Kappa.ResultsAt cut-off scores of 40, 45,50, and 55, the area under the Receiver Operating Characteristic curve was 0.772, 0.761, 0.749, and 0.763, respectively. The Youden index was 0.543, 0.521, 0.498, and 0.525, while Kappa values were 0.540, 0.518, 0.490, and 0.515. Sensitivity was 0.735, 0.713, 0.640, and 0.625; specificity was 0.808, 0.808, 0.858, and 0.900. The positive predictive values were 0.813, 0.808, 0.837, and 0.876, and the negative predictive values were 0.729, 0.713, 0.678, and 0.679. Accuracy were 0.770, 0.758, 0.742, and 0.754.ConclusionsThe Morse Fall Scale demonstrates good predictive performance for assessing fall risk in gynecology and obstetrics wards. The optimal cut-off score is 40.

Radiotherapy is a commonly used method in the treatment of bladder cancers (BC). Radiation-induced immunogenic cell death (ICD) is related to the immune response against cancers and their prognoses. Even though dendritic cells (DC) act as powerful antigen-presenting cells in the body, their precise role in this ICD process remains unclear. Accordingly, an in vitro study was undertaken to ascertain whether high-dose radiation-induced ICD of BC cells could regulate the immune response of DC. The results indicated that high-dose radiation treatments of BC cells significantly increased their levels of apoptosis, blocked their cell cycle in the G2/M phase, increased their expression of ICD-related proteins, and upregulated their secretion of CCL5 and CCL21 which control the directed migration of DC. It was also noted that expression of CD80, CD86, CCR5, and CCR7 on DC was upregulated in the medium containing the irradiated cells. In conclusion, the present findings illustrate that high-dose radiation can induce the occurrence of ICD within BC cells, concomitantly resulting in the activation of DC. Such findings could be of great significance in increasing the understanding how radiotherapy of BC may work to bring about reductions in cell activity and how these processes in turn lead to immunoregulation of the function of DC.

BackgroundMechanical ventilation (MV) is vital for critically ill ICU patients but carries significant mortality risks. This study aims to develop a predictive model to estimate hospital mortality among MV patients, utilizing comprehensive health data to assist ICU physicians with early-stage alerts.MethodsWe developed a Machine Learning (ML) framework to predict hospital mortality in ICU patients receiving MV. Using the MIMIC-III database, we identified 25,202 eligible patients through ICD-9 codes. We employed backward elimination and the Lasso method, selecting 32 features based on clinical insights and literature. Data preprocessing included eliminating columns with over 90% missing data and using mean imputation for the remaining missing values. To address class imbalance, we used the Synthetic Minority Over-sampling Technique (SMOTE). We evaluated several ML models, including CatBoost, XGBoost, Decision Tree, Random Forest, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Logistic Regression, using a 70/30 train-test split. The CatBoost model was chosen for its superior performance in terms of accuracy, precision, recall, F1-score, AUROC metrics, and calibration plots.ResultsThe study involved a cohort of 25,202 patients on MV. The CatBoost model attained an AUROC of 0.862, an increase from an initial AUROC of 0.821, which was the best reported in the literature. It also demonstrated an accuracy of 0.789, an F1-score of 0.747, and better calibration, outperforming other models. These improvements are due to systematic feature selection and the robust gradient boosting architecture of CatBoost.ConclusionThe preprocessing methodology significantly reduced the number of relevant features, simplifying computational processes, and identified critical features previously overlooked. Integrating these features and tuning the parameters, our model demonstrated strong generalization to unseen data. This highlights the potential of ML as a crucial tool in ICUs, enhancing resource allocation and providing more personalized interventions for MV patients.

ObjectiveThis study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs).MethodsTwenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group.Results(1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue.ConclusionsNesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype.

The Guangdong-Hong Kong-Macao Greater Bay Area has attracted attention for its extraordinary pace of economic development and is considered to be leading the way in China's transformation from a manufacturing to an innovation cluster. However, due to rapid economic expansion and rapid urbanization, the Great Bay Area still struggles with low energy efficiency and environmental degradation, which has slowed down the pace of development. Therefore, in order to alleviate energy pressure, promote the country's sustainable development and gain a competitive advantage in the global market, researching energy efficiency and improving energy utilization efficiency is crucial. In this study, macro-level energy efficiency indicators are constructed using energy consumption data from various cities in the Greater Bay Area for the period from 2000 to 2020, and the spatio-temporal evolution of energy efficiency is analysed. The results show that all cities in the Greater Bay Area experienced an increasing trend in energy efficiency from 2000 to 2019, with significant variation in growth rates and magnitudes between cities. Compared to the nine cities in Guangdong province, Hong Kong and Macao exhibited significantly superior energy efficiency, with Foshan recording the highest growth rate of 14%. In 2020, most cities experienced a decline in energy efficiency due to the COVID-19 pandemic, with Macao experiencing the greatest decrease at 57%. Hong Kong and Macao are both in the "low consumption and high efficiency" target region, while Guangzhou, Shenzhen and Zhuhai are consistently in the "both high" region. Changes in the industrial upgrading index correspond significantly with changes in energy efficiency trajectories, with the transition from primary to secondary and tertiary industries playing a more substantial role. There is no significant association found between the strength of environmental regulation and changes in energy efficiency. The study's findings indicate that the most effective way to achieve economic transformation in the majority of China's regions is to combine adequate environmental legislation with industrial structural adjustment.

PurposeThis study comprises an investigation of the role of meteorin-like (Metrnl) in an experimental model of diabetic kidney disease (DKD).MethodsTwenty-four db/db mice were randomly assigned to one of the following groups: DKD, DKD + Metrnl-/-, and DKD + Metrnl+/+. Plasma Metrnl concentrations were measured using ELISA. Kidney tissues were examined via western blotting, qRT-PCR, and immunohistochemistry to determine the expression levels of inflammatory factors. Electron microscopy was employed to observe stained kidney sections.ResultsCompared with the NC group, FBG, BW, and UACR were elevated in the DKD and Metrnl-/- groups, with severe renal pathological injury, decreased serum Metrnl concentration, decreased renal Metrnl expression, and increased expression levels of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA. In contrast, the Metrnl+/+ group showed decreased FBG and UACR, BUN, TC and TG, increased HDL-C and serum Metrnl concentration, increased renal Metrnl expression, and decreased expression of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA, compared to the DKD and Metrnl-/- groups. A Pearson bivariate correlation analysis revealed a negative correlation between UACR and Metrnl, and a positive correlation between UACR and TGF-β1.ConclusionUpregulation of renal Metrnl expression can improve renal injury by downregulating the expression of molecules in the TGF-β1/Smads signaling pathway in the renal tissues of type 2 diabetic mice; and by reducing the production of fibrotic molecules such as α-SMA.

PurposeThe abnormal growth factors-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells was known as a vital pathogenesis of proliferative vitreoretinopathy (PVR). This study aims to explore how survivin inhibition affects EMT induced by epidermal growth factor (EGF) in RPE cells.MethodsHuman primary RPE cells were identified in vitro. EMT in RPE cells was induced by EGF. Inhibition of survivin in RPE cells was accomplished through the use of a survivin inhibitor (YM155) and survivin siRNA. The viability, proliferation and migration of RPE cells was detected by methylthiazol tetrazolium assay, bromodeoxyuridine labeling assay, and wound healing assay, respectively. The EGF receptor /mitogen-activated protein kinase (EGFR/MAPK) proteins and EMT-related proteins were measured by western blot and immunofluorescence assay.ResultsEGF induced significant EMT in RPE cells, activated the phosphorylation of EGFR/MAPK signaling proteins, and caused changes to EMT-related proteins. YM155 suppressed RPE cells' viability, proliferation, and migration; induced the phosphorylation of EGFR, JNK, and P38MAPK; and down regulated EGFR and phosphorylated ERK. YM155 also increased expression of E-cadherin and ZO-1 proteins and reduced expression of N-cadherin, Vimentin, and α-SMA proteins. The EGF-induced increase of RPE cell proliferation and migration was constrained by survivin inhibition. Moreover, survivin inhibition in RPE cells suppressed the EGF-caused phosphorylation of EGFR/MAPK proteins and attenuated the EGF-induced reduction of E-cadherin and ZO-1 proteins and increase of N-cadherin, Vimentin, and α-SMA proteins.ConclusionsSurvivin inhibition attenuates EGF-induced EMT of RPE cells by affecting the EGFR/MAPK signaling pathway. Survivin might be a promising target for preventing PVR.

BackgroundThe role of postoperative radiotherapy (PORT) after complete tumor resection in patients with thymoma or thymic carcinoma remains controversial. We performed a meta-analysis to identify groups that would benefit from PORT.MethodsMultiple scientific databases were systematically searched for studies comparing overall survival (OS) and/or disease-free survival (DFS) between PORT and surgery alone in patients with completely resected thymomas or thymic carcinomas until April 10, 2024. A random-effects model was used for the statistical analysis.ResultsA total of 31 studies with 10543 patients were included (17 studies involving 4763 patients with thymoma, seven studies involving 1045 patients with thymic carcinoma, and seven studies involving 4735 patients with mixed histological types). Notably, PORT significantly prolonged OS (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.59-0.91) and DFS (HR = 0.62, 95% CI: 0.43-0.89). Similar results were also observed when the multivariate-adjusted HRs were used as the measure of effect (OS: HR = 0.60, 95% CI: 0.43-0.83; DFS: HR = 0.48, 95% CI: 0.29-0.79). In subgroup analyses, PORT was associated with a longer OS and DFS for thymoma (HR = 0.73, 95% CI: 0.56-0.96 and HR = 0.65, 95% CI: 0.46-0.93), thymic carcinoma (HR = 0.72, 95% CI: 0.49-1.07 and HR = 0.38, 95% CI: 0.19-0.77), and stage 3-4 disease (HR = 0.50, 95% CI: 0.34-0.74 and HR = 0.44, 95% CI: 0.27-0.70), but not for stage 2 disease (HR = 0.81, 95% CI: 0.55-1.19 and HR = 0.97, 95% CI: 0.51-1.83).ConclusionsPORT is likely to improve OS and DFS in patients with completely resected stage 3-4 thymoma or thymic carcinoma; however, the value of PORT for stage 2 disease requires further evaluation in large-scale studies.

In view of the lack of accurate models for discrete element simulation in the current research and development process of forage harvesting and crushing machinery, the contact parameters were calibrated based on Hertz-Mindlin (no slip) contact model by EDEM simulation software with alfalfa stalk at primary florescence as the research object. Based on the angle of repose, the restitution coefficient, static friction coefficient, rolling friction coefficient of alfalfa stalks were determined through the Placket-Burman test, steepest ascent test and Box-Behnken test. The simulation test of the repose angle was carried out with the determined contact parameters. The results showed that the relative error between the simulated repose angle and the physical test repose angle was 0.48%, which indicated that the calibrated contact parameters could truly reflect the physical characteristics of alfalfa stalks at the primary florescence. It provided a reliable model and parameter calibration method for the discrete element simulation in the research and development process of forage machinery, and also provided a reference for the research and optimization design of forage harvesting, crushing and processing machinery.

BackgroundThe tile-based approach has been widely used for slide-level predictions in whole slide image (WSI) analysis. However, the irregular shapes and variable dimensions of tumor regions pose challenges for the process. To address this issue, we proposed PathEX, a framework that integrates intersection over tile (IoT) and background over tile (BoT) algorithms to extract tile images around boundaries of annotated regions while excluding the blank tile images within these regions.MethodsWe developed PathEX, which incorporated IoT and BoT into tile extraction, for training a classification model in CAM (239 WSIs) and PAIP (40 WSIs) datasets. By adjusting the IoT and BoT parameters, we generated eight training sets and corresponding models for each dataset. The performance of PathEX was assessed on the testing set comprising 13,076 tile images from 48 WSIs of CAM dataset and 6,391 tile images from 10 WSIs of PAIP dataset.ResultsPathEX could extract tile images around boundaries of annotated region differently by adjusting the IoT parameter, while exclusion of blank tile images within annotated regions achieved by setting the BoT parameter. As adjusting IoT from 0.1 to 1.0, and 1-BoT from 0.0 to 0.5, we got 8 train sets. Experimentation revealed that set C demonstrates potential as the most optimal candidate. Nevertheless, a combination of IoT values ranging from 0.2 to 0.5 and 1-BoT values ranging from 0.2 to 0.5 also yielded favorable outcomes.ConclusionsIn this study, we proposed PathEX, a framework that integrates IoT and BoT algorithms for tile image extraction at the boundaries of annotated regions while excluding blank tiles within these regions. Researchers can conveniently set the thresholds for IoT and BoT to facilitate tile image extraction in their own studies. The insights gained from this research provide valuable guidance for tile image extraction in digital pathology applications.

Sex-determining mechanism is still ambiguous for sea cucumber Holothuria scabra which only manifests gonochorism in gonad. In this study, proteomic analysis was employed to delineate sex-related proteins and genes in gonads of H. scabra, subsequently validated through Quantitative real-time polymerase chain reaction (qRT-PCR). A total of 5,313 proteins were identified via proteome sequencing. Among these, 817 proteins exhibited expression in both the ovary and testis, with 445 proteins displaying up-regulation and 372 proteins showing down-regulation (ovary vs testis). Furthermore, 136 and 69 proteins were identified as ovary-specific and testis-specific Differentially Abundant Proteins (DAPs), respectively. And 9 DAP coding genes which play crucial role in ovary and testis were verified by qRT-PCR. Notably, 24 ovary-bias proteins enriched in ribosome pathway strongly indicated the crucial role of ribosome in ovary. This study serves to furnish novel evidence pertaining to sex differences in H. scabra.

PurposeButton battery nasal impactions pose serious risks due to complications and the need for prompt removal, yet research on interventions remains limited due to its rare occurrence. To delineate the clinical manifestations of nasal foreign bodies associated with button batteries and to explore treatment approaches focused on minimizing the reliance on general anesthesia and surgical interventions.MethodsThis study focuses on 176 cases of children who received treatment for nasal cavity button battery impactions. It encompasses various factors including age, gender, battery location, impaction duration, methods of extraction, and associated complications.ResultsThe incidence of nasal button battery cases among nasal foreign body instances was 1.16%, with a majority being males (60.23%) aged 1-5 years (98.29%). Utilizing a specially designed nasal foreign body hook and following established treatment protocols enabled the successful outpatient management of the majority of cases. Only 12 cases (6.82%) necessitated removal under general anesthesia due to management challenges in an outpatient setting. Furthermore, our findings indicated no linear correlation between the duration of battery retention and the risk of nasal septal perforation, which was observed in 31 cases (17.61%).ConclusionNasal foreign bodies caused by button batteries in children demand urgent attention due to their potentially grave outcomes. Our research is directed towards enhancing diagnostic and therapeutic strategies to bolster the success rates of outpatient removal, curtail the duration of foreign body retention, and diminish the reliance on general anesthesia.