Large-scale Studies Research Articles

Large-scale prospective serum metabolomic profiling reveals candidate predictive biomarkers for suspected preeclampsia patients

Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabolites in PE patients and identify potential predictive biomarkers for suspected PE patients (pregnant women who had already shown PE-related symptoms in the middle to late stages of pregnancy, but were not yet confirmatively diagnosed as PE.), a large-scale serum metabolomic analysis was conducted in this study with a prospective cohort of 328 suspected PE patients in the middle or late pregnancy stages, as well as a retrospective cohort of 30 healthy pregnant women and 30 PE patients. Using liquid chromatography mass spectrometry (LC − MS), serum metabolomic profiling revealed that the development of PE was closely associated with disturbed amino acid metabolism. Moreover, a panel of seven predictive biomarkers including 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, gamma-glutamyl-leucine, 2-hydroxyvaleric acid, LysoPC(16:1(9Z)/0:0), PC(DiMe(13,5)/MonoMe(13,5)), ADP-D-glycero-beta-D-manno-heptose and phenylalanyl-tryptophan were identified for PE development by performing multiple statistical analysis and LASSO regression analysis. The combination of these biomarkers showed promise in the prediction of PE development for suspected PE patients, with an AUC of 0.753 and 0.885 for the discovery and validation cohorts, respectively. These findings highlight the potential of large-scale prospective metabolomic studies combined with machine learning algorithms in identifying key biomarkers for predicting PE development, while retrospective metabolomics studies provide insights into the pathogenesis of PE.

Validation of the Food Safe Zone questionnaire for families of individuals with Prader-Willi syndrome

BackgroundPrader-Willi syndrome (PWS), a genetic neurodevelopmental disorder, is characterized by hyperphagia and significant behavioral problems. Hyperphagic individuals with PWS are chronically hungry yet rarely feel sated, and often engage in food-seeking behaviors. To avoid life-threatening obesity in their children, families implement food security strategies (e.g., locking food sources, constant supervision around food, alerting others). Although widely used, these strategies have yet to be systematically examined. We thus developed and analyzed the psychometric properties of a new measure of these diverse strategies, the Food Safe Zone, and evaluated them in relation to hyperphagic symptoms and demographic variables. In doing so, we also shine a light on the extraordinary efforts of families in managing their children’s hyperphagia.MethodsOur team developed 20 FSZ items that were revised for clarity and completeness in an iterative feedback process with stakeholders, including parents, PWS specialists, and individuals with PWS. The FSZ was pilot tested, descriptive findings were reviewed by additional stakeholders, and then administered to 624 parents in a large-scale study. Based on an open-ended question, “Is there anything else you do to ensure food safety?” two additional items were added and evaluated in a follow-up study.ResultsPrincipal component analyses revealed that 21 FSZ items loaded onto 5 factors that were readily interpretable, accounting for 67% of test variance: Alerting Others and Food Supervision in the Community; Locking or Restricting Food Sources; Checking for Food; At Home Supervision and Meals; and Avoiding Food Settings. Internal consistency and test-rest reliability were robust. Convergent validity analyses revealed that parents implemented FSZ strategies in response to the severity of their child’s hyperphagia, and not their child’s age, gender or PWS genetic subtype.ConclusionsThe psychometrically sound FSZ holds promise for future research, especially on the effects of food safety tactics on family members. In future clinical trials, the FSZ could also be used to help parents think critically about their food safety tactics in relation to their child’s hyperphagia, or as an exploratory endpoint; if hyperphagia is lessened, so too may food safety tactics, thereby enhancing familial quality of life.

Dural arteriovenous fistula research and management in China (DREAM-INI): initial characterization and patient cohort outcomes

BackgroundIntracranial dural arteriovenous fistulas (DAVFs) are rare lesions, making it challenging to fully understand and improve their management. Globally, only two major large-scale studies have focused on DAVFs. This report...

Uptake and hesitancy of the second booster dose of COVID-19 vaccine among the general population in China after the surge period of the COVID-19 pandemic: a large-scale national study

BackgroundAlthough the second booster dose of COVID-19 vaccines is available, vaccine hesitancy among the public may have peaked due to the surge in infections caused by the Omicron variant. To improve coverage of the second booster dose, it is crucial to investigate the prevalence of vaccine hesitancy among the general population during this period and explore the reasons for this phenomenon.MethodsA cross-sectional survey was conducted between January 5 to February 9, 2023. Variables including sociodemographics, mental health, COVID-19 infection status, COVID-19 vaccination status, and vaccine hesitancy were collected. Univariate and multivariate logistic regression analysis were performed to identify factors associated with the hesitancy of the second booster dose of COVID-19 vaccine among the general population.ResultsAmong the 10,623 participants, the uptake rate of the second booster dose was 4.3%. Among those who did not receive the second booster dose, 43.6% expressed vaccine hesitancy. The highest hesitancy rate was observed among participants who had not completed primary immunization (71.4%), followed by those with chronic diseases (48.6%) and those aged 60 and above (33.2%). The COVID-19 vaccine hesitancy was higher among females, participants with high incomes, those with a history of COVID-19 infection, those with depressive symptoms and post-traumatic stress disorder, and those with adverse events after COVID-19 vaccination. Conversely, lower hesitancy was observed among students, participants aged 60 and above, those from southern China, and those with higher level of perceived social support.ConclusionsCOVID-19 vaccine hesitancy remains prevalent among the general population in China after the surge period of the pandemic. Crucial steps, such as raising public awareness of the benefits and potential side effects of regular COVID-19 vaccination, ensuring timely monitoring and disclosure of pandemic information, and implementing targeted measures to improve social support and mental health, should be taken. These efforts will be instrumental in reducing vaccine hesitancy, advancing vaccination campaigns, and effectively preparing for the potential future outbreaks.

A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies.

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis.

Unveiling the metabolomic profile of growth hormone deficiency children using NMR spectroscopy

IntroductionThe diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery.ObjectiveTo characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1.MethodsNuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis.ResultsThe results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power.ConclusionsThis study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results.

The efficacy and safety of low-dose triple combination for hypertension treatment: a systematic review and meta-analysis of randomized controlled trials.

Recently, Low-dose triple single-pill combinations (LDTC) have become a promising option for managing hypertension. This review evaluates LDTC's effectiveness and safety versus standard care, monotherapy, and placebo for blood pressure (BP) control. A systematic review and meta-analysis of randomized controlled trials retrieved from PubMed, EMBASE, WOS, Scopus, and Cochrane from inception to September 2024. The analysis presented risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). PROSPERO ID: CRD42024595331. We identified five eligible trials with a total of 1,709 patients. LDTC had a higher rate of achieving BP < 140/90 at 4 to 6weeks (wk) (RR: 1.56; CI: 1.41, 1.72; p < 0.01) and at 8 to 12 wk (RR: 1.43; CI: 1.31, 1.57; P < 0.01). Additionally, LDTC significantly reduced the automated office systolic BP at 4 to 6 wk (MD: -8.80; CI: -10.16, -7.44; p < 0.01), 8 to 12 wk (MD: -8.30; CI: -11.18, -5.42; P < 0.01), and at 24 wk (MD: -6.94; CI: -10.56, -3.32; P < 0.01). However, LDTC indicated an increased rate of hypokalemia (RR: 2.25; CI: 1.50, 3.38; P < 0.01), with no difference between both groups in total adverse events (AEs) (P = 0.44), serious AEs (P = 0.79), treatment discontinuation due to AEs (P = 0.91), and the AEs of special interest (P = 0.54). LDTC therapy is effective and safe for hypertension management but poses potassium depletion. Further large-scale studies are essential to confirm its clinical benefits.

Health and well-being of staff in substance use services: The case of Scotland.

Background: Addressing high rates of drug and alcohol mortality requires a sustained commitment to supporting a resilient and skilled substance use workforce. Employee well-being in wider health and social care has been the subject of much empirical research, however there is a dearth of evidence specific to professionals working in substance use services.Methods: Data were derived from a cross-sectional survey of publicly-funded drug and alcohol services operating in Scotland during autumn 2021. Nested semi-log regression models estimated the associations between workplace characteristics and workforce composition, and the main outcome measure: non-Covid sickness absence. Qualitative data were analysed using thematic analysis.Results: 88 services, representing 43% of Scotland's drug and alcohol services, were included in the study. Factors significantly and positively associated with non-Covid sickness absence in multivariable analysis included average caseload per whole-time equivalent and number of whole-time equivalent clinical roles. Descriptive statistics show that vacancy rates and caseloads are comparatively higher in statutory services, and are also higher for clinical than non-clinical positions.Conclusion: This study revealed that and burnout leading to sickness absence are serious issues for frontline staff in drug and alcohol services, and these worsened during the Covid-19 pandemic. This research provides a foundation for validating the current findings via future large-scale longitudinal studies, and improving the well-being of people delivering health and social care services in substance use settings.

SPAGRM: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits

Sample relatedness is a major confounder in genome-wide association studies (GWAS), potentially leading to inflated type I error rates if not appropriately controlled. A common strategy is to incorporate a random effect related to genetic relatedness matrix (GRM) into regression models. However, this approach is challenging for large-scale GWAS of complex traits, such as longitudinal traits. Here we propose a scalable and accurate analysis framework, SPAGRM, which controls for sample relatedness via a precise approximation of the joint distribution of genotypes. SPAGRM can utilize GRM-free models and thus is applicable to various trait types and statistical methods, including linear mixed models and generalized estimation equations for longitudinal traits. A hybrid strategy incorporating saddlepoint approximation greatly increases the accuracy to analyze low-frequency and rare genetic variants, especially in unbalanced phenotypic distributions. We also introduce SPAGRM(CCT) to aggregate the results following different models via Cauchy combination test. Extensive simulations and real data analyses demonstrated that SPAGRM maintains well-controlled type I error rates and SPAGRM(CCT) can serve as a broadly effective method. Applying SPAGRM to 79 longitudinal traits extracted from UK Biobank primary care data, we identified 7,463 genetic loci, making a pioneering attempt to conduct GWAS for these traits as longitudinal traits.

Hemithyroidectomy Versus Total Thyroidectomy for Sporadic Medullary Thyroid Cancer: A Chinese Nationwide Large-Scale Cohort Study.

Medullary thyroid cancer (MTC) is a rare thyroid malignancy, with 70% to 80% of cases being sporadic (sMTC). Current guidelines recommend total thyroidectomy (TT) for all preoperatively suspicious sMTC, though there has been increasing support for reducing the surgical extent in recent years. However, relevant data are limited. This study aimed to comprehensively evaluate the safety of hemithyroidectomy (HT) in sMTC. This study included 797 patients with MTC who received curative-intent initial surgery at 19 participating referral centers. Genetic testing was performed to identify disease heredity. We evaluated the safety of HT in sMTC across 5 aspects: (1) prevalence of occult bilateral foci, (2) prevalence of contralateral lobe recurrence, (3) biochemical response, (4) structural recurrence-free survival (SRFS), and (5) overall survival (OS). Of the 797 patients, 648 were genetically confirmed as having sMTC. HT and TT were performed as the index surgery in 232 (35.8%) and 416 (64.2%) patients, respectively. In the TT group, bilateral foci were found in 34 (8.2%) patients, of whom only 10 (2.4%) had sonographically occult foci, and of these, only 3 (0.72%) had a maximal tumor size ≤2 cm. In the HT group, only 1.7% (4/232) had recurrence in the preserved lobe, with only 1 (0.43%) having a maximal tumor size ≤2 cm. After propensity score matching, 230 pairs of patients were included in further analysis. No significant differences were found in OS (log-rank: P=.484; Cox regression: P=.380), SRFS (log-rank: P=.914; Cox regression: P=.309), or biochemical response (chi-square: P=.744; logistic regression: P=.818) between the 2 groups. Subgroup analyses showed that HT conferred comparable structural and biochemical outcomes with TT in small (≤2 cm) sMTCs, even for patients with high-risk factors such as high preoperative calcitonin, multifocal disease, lymph node metastases, RETM918T mutation, and desmoplasia. For small unilateral sMTCs, HT may be considered an alternative treatment that does not compromise prognosis while avoiding additional complications associated with TT.

Enhancing patient care: pharmacotherapeutic monitoring in community pharmacies - a literature review

Background: The role of community pharmacies has been transitioning from traditional drug dispensing methods to include more patient-centred services such as pharmacotherapeutic monitoring. With the increasing complexity of medication regimens and the rising prevalence of chronic diseases, pharmacotherapeutic monitoring plays a crucial role in preventing medication-related problems. This study aims to review patient outcomes of community pharmacies’ involvement in pharmacotherapeutic monitoring services. It also highlights advances in the monitoring process, the challenges involved, and relevant solutions. Methods: A narrative review was conducted from 8 April 2024 to 9 May 2024, where data was extracted from multiple research studies indexed in PubMed, EBSCOHost, and Google Scholar databases. This review included only previous articles written in English and had information relevant to community pharmacy, patient care, innovations in pharmacotherapeutic monitoring, and challenges associated with the monitoring process in community pharmacies. Results: Implementation of pharmacotherapeutic monitoring in community pharmacies improves patient outcomes and satisfaction. It minimizes adverse events by ensuring optimal dosing and patient adherence, which in turn reduces medical expenses and duration of hospitalization. However, factors such as inefficient analytical resources, lack of skilled personnel, and huge financial costs complicate implementation of pharmacotherapeutic monitoring in community pharmacies. Conclusion: Community pharmacies’ participation in therapeutic drug monitoring is a promising development that prioritizes tailored patient care, eliminating the need for hospital visits. We recommend a multidisciplinary collaboration, robust electronic medical record systems, and large-scale research studies to provide sufficient evidence on the application of therapeutic drug monitoring in community pharmacies, to leverage this service. Also, policy and decision-makers should facilitate this practice by investing more in pharmacotherapeutic monitoring tools and training for community pharmacists.

Coexisting Obesity and Malnutrition and its Impact on Stroke and Brain structure: Insights from UK Biobank study.

The dual burden of malnutrition, characterized by the coexistence of malnutrition and obesity, represents a growing concern in global health.This study examines the association of combined effects of obesity and malnutrition with the risk of stroke and brain structure. Data from the UK Biobank, a large-scale population-based cohort study, were analyzed. Patients were stratified into nourished nonobese, malnourished nonobese, nourished obese, and malnourished obese. Malnutrition risk using objective scores, including the controlling nutritional status score (CONUT), nutritional risk index (NRI), and prognostic nutritional index (PNI). Obesity was defined as BMI ≥30. Cox proportional hazard models were used to assess the association between combined obesity and nutritional status and incident stroke. Kaplan-Meier curves for incident stroke were constructed. Linear regression models were used to evaluate the associations between combined obesity and nutritional status and brain structure. A total of 409,694 participants were included in the analysis. Among them, 37930 participants had imaging data. Kaplan-Meier curves illustrated a higher incidence of stroke in the malnourished obese group. Malnourished obese was found to increase the risk of stroke (HRCONUT 1.27, 95%CI [1.09 - 1.48]; HRNRI 2.61, 95%CI [2.03 - 3.36]; HRPNI 7.9, 95%CI [1.11 - 56.07]) , ischemic stroke (HRCONUT 1.29, 95%CI [1.08 - 1.54]; HRNRI 2.8, 95%CI [2.09 - 3.76]; HRPNI 8.43, 95%CI [1.19 - 59.83]) and hemorrhagic stroke (HRNRI 2.53, 95%CI [1.57 - 4.09]). Brain imaging analysis revealed associations between malnourished obese and certain structural parameters. Cerebral white matter hyperintensities may be associated with the occurrence of stroke. Malnourished obese is associated with the risk of stroke and brain structure parameters. Further research is needed to better understand the underlying mechanisms and develop targeted interventions for individuals with combined effects of obesity and malnutrition.

Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

BackgroundWith the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, the toxicity of these drugs is a growing concern. This study aimed to evaluate the adverse events (AEs) of IDH inhibitors based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsAE reports for IDH inhibitors (enasidenib, ivosidenib, and olutasidenib) were collected and analyzed from the time of launch through the first quarter of 2024. Only IDH inhibitors reported as the target drug and coded as the primary suspect (PS) were included in the analysis. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the Medical Dictionary for Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including the reporting odds ratio and the Bayesian confidence propagation neural network were performed in data mining to assess IDH inhibitor-relatedAEs. Differentiation syndrome was the AE of special interest.ResultsThe reports number of enasidenib, ivosidenib, and olutasidenib was 11 616 357, 10 067 250, and 2 563 464, respectively. A total of 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related signals involving 17 SOCs, and 7 olutasidenib-related signals involving 4 SOCs were obtained. The most signals reported were “blood and lymphatic system disorders,” “infections and infestations,” and “nervous system disorders” in enasidenib. For signals of ivosidenib, the most frequently reported were “gastrointestinal disorders,” “general disorders and administration site conditions,” and “injury, poisoning and procedural complications.” Ivosidenib was the only IDH inhibitor with signals in “cardiac disorders.” Differentiation syndrome events were reported in 89, 40, and 2 cases for enasidenib, ivosidenib, and olutasidenib, respectively. The median time to onset was 26–31 days for ivosidenib and enasidenib. AML was the most common indication in the differentiation syndrome reports.ConclusionsOur study identifies potential AE signals associated with IDH inhibitors and provides a broader understanding of the safety. The safety profiles highlight the need for long-term safety monitoring of IDH inhibitor recipients. Promptly monitoring and intervention in specific organ systems depending on the type of IDH inhibitor may improve the overall survival or enhance the quality of life. In the future, it will be necessary to validate our findings in prospective large-scale studies and to investigate the underlying mechanisms.

A Village-Scale Study Regarding Landscape Evolution and Ecological Effects in a Coastal Inner Harbor

The development of inner harbors has been accompanied by the destruction of natural landscapes, which in turn has led to numerous ecological problems. However, the temporal and spatial relationships between changes in the inner harbor landscape and ecological effects are not yet clear, and there are relatively few studies at smaller scales such as villages. In this study, we investigated Xieqian Harbor in Xiangshan County, along the eastern coast of China, and then analyzed the landscape change and evolutionary characteristics of the effects of carbon storage, soil conservation, and water yield at the village scale for the years 2000, 2010, and 2020. We then used the geographically and temporally weighted regression (GTWR) model to explore the spatiotemporal relationships between landscape variables and ecological effects. The results showed that the fragmentation and diversity of landscape patches increased from 2000 to 2020 due to reclamation and aquaculture, tourism development, and harbor construction, as reflected by the edge density (ED) and the Shannon diversity index (SHDI), which increased by 11.31% and 2.82%, respectively. This change resulted in a notable reduction of 572.6 thousand tons in carbon sequestration, 853 million tons in soil conservation, and 19 million cubic meters in water yield over the past 20 years. When temporal non-stationarity and spatial heterogeneity were combined, the relationship between landscape change and ecological effects became highly intricate, with varying responses across different time periods and locations. The area-weighted mean patch shape index (AWMSI) was a key factor affecting the three ecological effects. Our research confirmed that there was significant spatiotemporal heterogeneity in the effects of different landscape variables on ecological effects in inner harbors at the village scale. Compared with larger-scale studies, the results of village-scale studies revealed more precisely the impacts of localized landscape changes on ecological effects, providing support for the sustainable management of inner harbors and providing a new approach to integrating GTWR into landscape ecological time–space analysis research.

Surgical treatment of intramedullary spinal cord tumors: a systematic review

Intramedullary spinal cord tumors are a rare group of central nervous system tumors with special treatment approaches. The main problems are related to optimal time of surgery, invasiveness and recurrence of tumor. To review available literature data on the treatment of intramedullary spinal cord tumors, to summarize the main achievements and changes in treatment strategy over the past 5 years. We reviewed Russian- and English-language literature on the treatment of intramedullary spinal cord tumors over the past five years. The studies were selected in accordance with PRISMA recommendations. We analyzed literature data in the PubMed, eLibrary, Cochrane and Medline databases over the last 5 years. The studies were selected taking into account the relevance and quality of researches. Large-scale studies are rare due to rarity of intramedullary spinal cord tumors. The main changes in surgery for intramedullary spinal cord tumors in recent years have occurred due to changes in surgical tactics (emphasis on functional status rather total resection), improvement of equipment for adjustment of surgical approach (MRI, intraoperative monitoring, intraoperative ultrasound), more accurate and effective adjuvant therapy contributing to preoperative shrinkage of tumor and preservation of functionally important areas.

Funding Success of United States Federal Grant Applications Proposing to Study Therapeutic Applications of Psychedelics: A Survey Study

The author surveyed researchers about United States federal grant applications for therapeutic psychedelic research and their funding success. An anonymous survey was sent to corresponding authors of the 50 most-cited psychedelic research articles published after 2000 and also disseminated on Twitter. Ten researchers responded, reporting on 24 National Institutes of Health (NIH) grant applications for psilocybin, ibogaine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and other psychedelics, dating back to the early 1990s. Grant applications increased noticeably after 2006. Of the applications assessed, 16.7% were funded, below the NIH’s 23.4% average funding rate for R01-equivalent grants from 1998 to 2023. While no applications submitted before 2006–2010 were funded, the funding rate since then (19.05–22.2%) aligns with the NIH’s 20.6 ± 1.9% annual average for R01-equivalent grants from 2006 to 2023. Respondents generally perceived funding for psychedelic research as more difficult to obtain than for other areas, though recent improvements were noted. If the analyzed applications represent only a small subset of total submissions of applications proposing to study therapeutic applications of psychedelics, the findings may have limited generalizability and larger-scale validation studies would be required. However, this is difficult to determine since detailed data on unfunded NIH applications are not publicly available.

Higher education students' perceptions of ChatGPT: A global study of early reactions.

The paper presents the most comprehensive and large-scale global study to date on how higher education students perceived the use of ChatGPT in early 2024. With a sample of 23,218 students from 109 countries and territories, the study reveals that students primarily used ChatGPT for brainstorming, summarizing texts, and finding research articles, with a few using it for professional and creative writing. They found it useful for simplifying complex information and summarizing content, but less reliable for providing information and supporting classroom learning, though some considered its information clearer than that from peers and teachers. Moreover, students agreed on the need for AI regulations at all levels due to concerns about ChatGPT promoting cheating, plagiarism, and social isolation. However, they believed ChatGPT could potentially enhance their access to knowledge and improve their learning experience, study efficiency, and chances of achieving good grades. While ChatGPT was perceived as effective in potentially improving AI literacy, digital communication, and content creation skills, it was less useful for interpersonal communication, decision-making, numeracy, native language proficiency, and the development of critical thinking skills. Students also felt that ChatGPT would boost demand for AI-related skills and facilitate remote work without significantly impacting unemployment. Emotionally, students mostly felt positive using ChatGPT, with curiosity and calmness being the most common emotions. Further examinations reveal variations in students' perceptions across different socio-demographic and geographic factors, with key factors influencing students' use of ChatGPT also being identified. Higher education institutions' managers and teachers may benefit from these findings while formulating the curricula and instructions/regulations for ChatGPT use, as well as when designing the teaching methods and assessment tools. Moreover, policymakers may also consider the findings when formulating strategies for secondary and higher education system development, especially in light of changing labor market needs and related digital skills development.

First detection and molecular characterization of porcine epidemic diarrhea virus (PEDV) in India: evidence of a new variant in Karnataka

BackgroundPorcine epidemic diarrhea (PED) is a significant pig disease causing high mortality in suckling pigs and high morbidity across all age groups. It is highly prevalent in Southeast Asia, posing a threat of transboundary transmission to India. Although antibodies were detected as early as 2003 in Assam, there was no evidence of viral detection or molecular characterization until this study. This study reports the first clinical outbreak of PED in India, followed by the detection and genetic characterization of PED virus (PEDV) during 2022-23.MethodsThe outbreak was characterized, and fecal samples (n = 21) were collected from affected pigs. These samples were screened for PEDV using RT-PCR, targeting the N, S, and M genes. Serosurveillance was conducted in eight districts, and serum samples (n = 339) were tested for PEDV antibodies using ELISA. Partial N, S, and M gene sequencing, followed by phylogenetic analysis using MEGA v11.0.13, was performed to identify the prevailing genotype and variations in the coding region.ResultsThis study identified the first clinical outbreak of PEDV in India, with morbidity rates of 55-57.1% and symptoms including yellow watery diarrhea, vomiting, and abdominal pain. PEDV was confirmed in 17 of 21 fecal samples by amplifying the N, S, and M genes. Serosurveys showed seropositivity in Mandya (2.8%), Bengaluru Rural (6.6%), and Kolar (21.6%), districts indicating PEDV circulation in the state of Karnataka, India. The phylogenetic analysis of the S and M genes placed our study sequences within the Genotype 2a (G2a) clade, aligning with other known G2a strains. In contrast, the phylogenetic tree of the N gene clustered our sequences within the Genotype 1a (G1a) clade suggesting potential recombination. The Indian PEDV strains clustered with strains of China, with unique amino acid substitutions in the S gene, particularly in the receptor binding region.ConclusionThis study reports the first clinical outbreak of PED in India and identifies the circulating genotype of PEDV. The study emphasizes the need for large-scale surveillance studies to understand the disease’s status. Understanding PEDV’s genetic diversity and evolution is essential to develop area-specific vaccines to mitigate the disease impact on India’s pig population.

Immunogenicity and Safety of the Higher Valent Pneumococcal Conjugated Vaccine Compared to the 13-Valent Pneumococcal Conjugated Vaccine in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract Introduction The immunogenicity of PCV15 and PCV20 in older adults was approved based on comparative data with PCV13, though their relative immunogenicity and safety in this population remain undetermined. A systematic review and meta-analysis were conducted to provide insights, addressing the lack of large-scale efficacy studies. Methods A phrase 2 or 3 randomized controlled trials evaluating immunogenicity of a single dose of either PCV15 or PCV20 in older adults by the opsonophagocytic assay (OPA) geometric mean titer (GMT) response at 1-month postvaccination compared to PCV13 were included in analysis. Results In total, eight trials were eligible. PCV15 group demonstrated superior immunogenicity compared to PCV13 among older adults (GMTR: 1.11, 95% CI: 1.02–1.20). The PCV20 group demonstrated non-inferiority (exceeded 0.5 at one-month post-vaccination) in immunogenicity compared to PCV13 (GMTR: 0.84, 95% CI: 0.81–0.87). The incidence of local and systemic reactions was higher in the PCV15 group compared to the PCV13 group, with risk ratios (RR) of 1.23 (95% CI: 1.14, 1.32) and 1.15 (95% CI: 1.02, 1.29), respectively. PCV20 are well tolerated and exhibit a comparable rate of local and systemic reactions to PCV13 group. Conclusions These findings support the immunogenicity and safety of PCV15 and PCV20 for pneumococcal vaccination in older adults. Given its superior immune response, PCV15 may address the gaps left by PCV13. Despite higher antibody levels, the clinical effectiveness of these vaccines remains uncertain. Ongoing surveillances are essential to evaluate both vaccines impact on remaining vaccine-type pneumococcal disease.

Sex-specific associations between estimated glucose disposal rate and cognitive decline in middle-aged and older adults in China: a longitudinal cohort study

BackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.MethodsThis longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.ResultsHigher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000–0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002–0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.ConclusionHigher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.