Large-scale Studies Research Articles

Comparing Video Head Impulse Testing in Patients With Acute Vestibular Dysfunction

Objective: The video head impulse test (v-HIT) can evaluate the function of all semicircular canals (SCCs) in a short period. In this work, we sought to compare v-HIT results among 2 commercially available devices, the ICS impulse (Otometrics, Denmark) (ICS) and Eye See Cam (Interacoustics, Denmark) (ESC), among individuals with unilateral vestibular disorders. Design: Retrospective study (n = 15). Setting: St. Marianna University School of Medicine Hospital. Patients: Fifteen patients with acute unilateral vestibular disorders. Intervention: Two v-HIT devices were conducted across patients to compare the results of the 2 models. Main Outcome Measures: Gain values and pathological saccades for each SCC were compared across the 2 models. Monothermal caloric testing was performed to compare alongside v-HIT gain values. Results: There was no difference between the 2 models for the evaluation of the horizontal SCCs. There was a significant negative correlation (ESC: r = −0.52, ICS: r = −0.53) between caloric testing and the gain values of the 2 models. In the vertical SCCs, the gain values of ESC were significantly higher than the gain values of ICS. Detection of catch-up saccades in vertical SCCs was similar across the 2 models. Conclusion: For the horizontal SCCs, there was no difference in test results between the 2 models. However, in the vertical SCCs, gain values were variable across the 2 devices. Larger scale studies are needed to develop normative ranges for the vertical canals.

Sleep Pattern, Genetic Susceptibility, and Abdominal Aortic Aneurysm in UK Biobank Participants: Large-Scale Cohort Study

BackgroundAbdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality. ObjectivesThe authors aimed to explore the associations between sleep patterns and genetic susceptibility to AAA. MethodsWe included 344,855 UK Biobank study participants free of AAA at baseline. A sleep pattern was defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness, and an overall sleep score was constructed with a range from 0 to 5, where a high score denotes a healthy sleep pattern. Polygenic risk score based on 22 single nucleotide polymorphisms was categorized into tertiles and used to evaluate the genetic risk for AAA. Cox proportional hazards regression models were used to assess the association between sleep, genetic factors, and the incidence of AAA. ResultsDuring a median of 12.59 years of follow-up, 1,622 incident AAA cases were identified. The HR per 1-point increase in the sleep score was 0.91 (95% CI: 0.86-0.96) for AAA. Unhealthy sleep patterns, defined as a sleep score ranging from 0 to 3, were found to be associated with a higher risk of AAA for the intermediate (HR: 1.18, 95% CI: 1.06-1.31) and poor sleep patterns (HR: 1.40, 95% CI: 1.13-1.73), respectively, compared to the healthy pattern. Participants with poor sleep patterns and high genetic risks had a 2.5-fold higher risk of AAA than those with healthy sleep patterns and low genetic risk. ConclusionsIn this large prospective study, healthy sleep patterns were associated with a lower risk of AAA among participants with low, intermediate, or high genetic risk.

Genetic predisposition and antipsychotic treatment effect on metabolic syndrome in schizophrenia: a ten-year follow-up study using the Estonian Biobank

Schizophrenia (SCZ) patients exhibit 30% higher prevalence of metabolic syndrome (MetS) compared to the general population with its suboptimal management contributing to increased mortality. Large-scale studies providing real-world evidence of the underlying causes remain limited. To address this gap, we used real-world health data from the Estonian Biobank, spanning a median follow-up of ten years, to investigate the impact of genetic predisposition and antipsychotic treatment on the development of MetS in SCZ patients. Specifically, we set out to characterize antipsychotic treatment patterns, genetic predisposition of MetS traits, MetS prognosis, and body mass index (BMI) trajectories, comparing SCZ cases (n=677) to age- and sex-matched controls (n=2708). SCZ cases exhibited higher genetic predisposition to SCZ (OR=1.75, 95% CI 1.58-1.94), but lower polygenic burden for increased BMI (OR=0.88, 95% CI 0.88-0.96) and C-reactive protein (OR=0.88, 95% CI 0.81-0.97) compared to controls. While SCZ cases showed worse prognosis of MetS (HR 1.95, 95% CI 1.54-2.46), higher antipsychotic adherence within the first treatment year was associated with reduced long-term MetS incidence. Linear mixed modelling, incorporating multiple BMI timepoints, underscored the significant contribution of both, antipsychotic medication, and genetic predisposition to higher BMI, driving the substantially upward trajectory of BMI in SCZ cases. These findings contribute to refining clinical risk prediction and prevention strategies for MetS among SCZ patients and emphasize the significance of incorporating genetic information, long-term patient tracking, and employing diverse perspectives when analyzing real-world health data. EU Horizon 2020, Swedish Research Council, Estonian Research Council, Estonian Ministry of Education and Research, University of Tartu.

Evolution of publicly available large language models for complex decision-making in breast cancer care.

This study investigated the concordance of five different publicly available Large Language Models (LLM) with the recommendations of a multidisciplinary tumor board regarding treatment recommendations for complex breast cancer patient profiles. Five LLM, including three versions of ChatGPT (version 4 and 3.5, with data access until September 3021 and January 2022), Llama2, and Bard were prompted to produce treatment recommendations for 20 complex breast cancer patient profiles. LLM recommendations were compared to the recommendations of a multidisciplinary tumor board (gold standard), including surgical, endocrine and systemic treatment, radiotherapy, and genetic testing therapy options. GPT4 demonstrated the highest concordance (70.6%) for invasive breast cancer patient profiles, followed by GPT3.5 September 2021 (58.8%), GPT3.5 January 2022 (41.2%), Llama2 (35.3%) and Bard (23.5%). Including precancerous lesions of ductal carcinoma in situ, the identical ranking was reached with lower overall concordance for each LLM (GPT4 60.0%, GPT3.5 September 2021 50.0%, GPT3.5 January 2022 35.0%, Llama2 30.0%, Bard 20.0%). GPT4 achieved full concordance (100%) for radiotherapy. Lowest alignment was reached in recommending genetic testing, demonstrating a varying concordance (55.0% for GPT3.5 January 2022, Llama2 and Bard up to 85.0% for GPT4). This early feasibility study is the first to compare different LLM in breast cancer care with regard to changes in accuracy over time, i.e., with access to more data or through technological upgrades. Methodological advancement, i.e., the optimization of prompting techniques, and technological development, i.e., enabling data input control and secure data processing, are necessary in the preparation of large-scale and multicenter studies to provide evidence on their safe and reliable clinical application. At present, safe and evidenced use of LLM in clinical breast cancer care is not yet feasible.

Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study.

Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.

Comparing the incidence of Bladder Neck Stenosis post monopolar Transurethral Resection of the Prostate; small prostates versus larger prostates in the black African population

Monopolar Transurethral Resection of the Prostate (TURP) is the commonly done procedure for surgical removal of the prostate after open prostatectomy in our subregion. It is still a novel procedure in our subregion, as very few centers offer this procedure. It is generally believed that the size of the prostate may influence the development of complications of bladder neck stenosis. This is a dreaded complication, which requires further surgical procedure to correct in a resource-poor environment. We decided to compare the incidence of Bladder Neck Stenosis (BNS) in small vs larger prostates following monopolar TURP in our black African subregion. We prospectively studied 194 patients who underwent TURP in our facility from 2015 to 2022 that satisfied the inclusion criteria. Eighty-five participants (43.81%) had a small prostate (Transrectal Ultrasound, TRUS, weight <30 g), and 109 participants (56.19%) had a large prostate (TRUS weight >30 g). Overall, ten participants (5.15%) had postoperative BNS. Participants with smaller prostates had more incidence of bladder neck contracture than those with larger prostates, although this did not reach statistical significance, Fisher’s Exact test p=0.338. Multifactorial reasons and not prostate size alone may be responsible for BNS. There may be a need for larger-scale standardized studies on prostate size effect on BNS.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study

BackgroundObservational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.MethodsWe obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.ResultsIn the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10–5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).ConclusionsOur study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Wnt/β-catenin signaling is a therapeutic target in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/β-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF-wildtype ATC and a lack of effective treatment for BRAFV600EATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options. In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies. Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 (p < 0.05) and VWL-T60 (p < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T (p < 0.005) and THJ-21T (p < 0.001). We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC.

Falls, fracture and frailty risk in multiple sclerosis: a Mendelian Randomization study to identify shared genetics.

Patients with multiple sclerosis (MS) commonly present musculoskeletal disorders characterized by lower bone mineral density (BMD) and muscle weakness. However, the underlying etiology remains unclear. Our objective is to identify shared pleiotropic genetic effects and estimate the causal relationship between MS and musculoskeletal disorders. We conducted linkage disequilibrium score regression (LDSR), colocalization, and Mendelian randomization (MR) analyses using summary statistics from recent large-scale genome-wide association studies (GWAS), encompassing MS, falls, fractures, and frailty. Additional MR analyses explored the causal relationship with musculoskeletal risk factors, such as BMD, lean mass, grip strength, and vitamin D. We observed a moderate genetic correlation between MS and falls (RG = 0.10, P-value = 0.01) but not between MS with fracture or frailty in the LDSR analyses. MR revealed MS had no causal association with fracture and frailty but a moderate association with falls (OR: 1.004, FDR q-value = 0.018). We further performed colocalization analyses using nine SNPs that exhibited significant associations with both MS and falls in MR. Two SNPs (rs7731626 on ANKRD55 and rs701006 on OS9 gene) showed higher posterior probability of colocalization (PP.H4 = 0.927), suggesting potential pleiotropic effects between MS and falls. The nine genes are associated with central nervous system development and inflammation signaling pathways. We found potential pleiotropic genetic effects between MS and falls. However, our analysis did not reveal a causal relationship between MS and increased risks of falls, fractures, or frailty. This suggests that the musculoskeletal disorders frequently reported in MS patients in clinical studies are more likely attributed to secondary factors associated with disease progression and treatment, rather than being directly caused by MS itself.

The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism

Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder. During the last 15 years, advances in genomic technologies and the availability of increasingly large patient cohorts have greatly expanded our knowledge of the genetic architecture of ASD and its neurobiological mechanisms. Over two hundred risk regions and genes carrying rare de novo and transmitted high-impact variants have been identified. Additionally, common variants with small individual effect size are also important, and a number of loci are now being uncovered. At the same time, these new insights have highlighted ongoing challenges. In this perspective article, we summarize developments in ASD genetic research and address the enormous impact of large-scale genomic initiatives on ASD gene discovery.

The presence of a cribriform pattern is related to poor prognosis in lung adenocarcinoma after surgical resection: A meta-analysis.

Previous studies reported that the cribriform pattern (CP) was associated with poor prognosis in lung adenocarcinoma (ADC) patients; therefore, a meta-analysis was performed to thoroughly evaluate the prognostic impact of cribriform pattern in postoperative ADC patients. Eligible studies were retrieved from PubMed, Embase databases, and Web of Science until April 2023. Studies evaluating the effect of the cribriform pattern on the prognosis of postoperative ADC patients were included. Subsequently, subgroup analysis was conducted according to the proportion of the cribriform pattern, with disease-free survival (DFS) and/or overall survival (OS) as outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect estimates in the meta-analyses, which were performed with a random-effects model despite the heterogeneity. Nine studies published between 2015 and 2022 were included, with 4,289 ADC patients in total. The pooled results revealed a significantly poorer DFS (HR1.56, 95%CI 1.18-2.06, P = 0.11, I2 = 45%) and OS (HR2.11, 95%CI 1.63-2.72, P = 0.01, I2 = 56%) in patients with the cribriform pattern. Furthermore, the subgroup analysis showed that patients with a cribriform pattern (DFS: HR1.32, 95% CI 1.04-1.68 OS:HR2.30, 95% CI 1.55-3.39) and patients with a predominantly cribriform pattern (DFS:HR2.04, 95% CI 1.32--3.15 OS: HR1.92, 95% CI 1.41-2.61) were associated with poor prognosis. The presence of a cribriform pattern is related to poor prognosis in postoperative ADC patients, despite not being a main tumor component. However, the results should be confirmed by large-scale and prospective studies owing to the small sample and potential heterogeneity.

Professional beliefs of physicians and allied health professionals and their willingness to promote health in primary care: a cross-sectional survey

BackgroundPrimary care professionals could play a key role in health promotion implementation. A fundamental aspect that might affect the willingness of primary care professionals to strengthen health promotion, and about which we do not yet know much, are professional beliefs. Therefore, we conducted a quantitative survey to (1) compare professional beliefs and the willingness to work more in health promotion between five major primary care professions, and (2) investigate associations between professional beliefs and the willingness to work more in health promotion.MethodsA large-scale cross-sectional study based on a nation-wide web-based survey of primary care professionals in Switzerland was conducted from January to July 2022. The survey was addressed to pharmacists, physicians, medical practice assistants, nurses, and physiotherapists working in primary care in Switzerland. Differences between groups were tested using T-tests and Chi-square tests. Multivariable logistic regression analyses were used to evaluate the association between variables related to professional beliefs and the willingness to work more in health promotion.ResultsThe responses of 4’063 primary care professionals were used for analysis. Most primary care professionals revealed a salutogenetic attitude towards their primary care tasks. Members of all professions showed high awareness of their tasks in tackling increased risks of disease (80.2% of all participants). Especially allied health professionals wished to see a greater role of prevention in primary care (pharmacists: 72.4%, medical practice assistants: 63.9%, nurses: 75.6%, physiotherapists: 73.9% versus physicians: 46.9%). All professional groups showed a high willingness to work more in health promotion (88% of all participants). Salutogenetic beliefs of primary care professionals and their willingness to work more in health promotion are strongly associated. Participants agreeing that health promotion should play a greater role or that preventive consultations should be offered in primary care, are more willing to work more in health promotion compared to participants who disagree with these ideas.ConclusionsBoth affiliation to allied primary care professions and salutogenetic professional beliefs are associated with higher willingness to work more in health promotion. The high willingness provides evidence of a large, yet untapped potential. Promoting salutogenetic beliefs might further increase the willingness to engage in health promotion.

Sensitive periods of flexibility development at school age

The objective is to identify sensitive periods for the accentuated development of flexibility of schoolchildren. Methods: the scientific research was conducted on the basis of 60 schools in the city of Kirov, in Russia from September 14, 2022 to May 22, 2023. The pedagogical experiment involved 1,217 children (579 boys and 638 girls) from grades 1 to 11 of secondary school number 60 Kirov, Russia. Each lesson in the discipline "Physical education" lasted 40 minutes and took place 3 times a week. All students were engaged in the usual physical education program at school. All students took the tests at the beginning and at the end of the school year. The level of flexibility development was determined by the test "Leaning forward from a standing position on a gymnastic bench." Excel was used to process the results of the study, the Biostatistics-2022 program determined the reliability of the results of the T-Student study. Results: After the end of the study, the average indicators in each age group increased during the academic year. In the indicators of boys from the beginning to the end of the study, there was a significant and significant increase in flexibility indicators in the second grade (+15%), in the third grade (+17%) and in the fourth grade (+15%). In girls, a significant increase in the value is noted in the third grade (+16%), fifth grade (+14%) and sixth grade (+15%). In other age periods, there is not a significant increase in flexibility indicators (p&gt;0.05). Conclusion: As a result of this large-scale study, it can be argued that the targeted development of flexibility should be in boys aged 8 to 11 years, and in girls aged 9-10 years, 11-12 years and 12-13 years. Keywords: Physical exercises, Joint mobility, Muscle stretching, Physical education.

Impact of lactate/albumin ratio on prognostic outcomes in patients with concomitant heart failure and chronic kidney disease.

Previous studies have linked the lactate/albumin (L/A) ratio to poor outcomes in various conditions, but its connection to mortality in patients with both heart failure (HF) and chronic kidney disease (CKD) remains unclear. Using data from 1537 patients in MIMIC-IV, this study examined the relationship between L/A ratio and in-hospital and one-year mortality, employing Cox models, Kaplan-Meier (KM) analysis, and restricted cubic splines (RCS). The non-survivor group showed higher L/A ratios than survivors (1.04 ± 0.78 vs. 0.58 ± 0.29, p < 0.001), indicating a significant link between higher L/A ratios and mortality. Cox analysis identified the L/A ratio was significantly related to all-cause mortality both in-hospital (HR 2.033; 95% CI 1.576-2.624; p < 0.001) and one-year (HR 1.723; 95% CI 1.428-2.078; p < 0.001). The association between L/A ratio and mortality was non-linear and increasing. The KM survival curves demonstrated significantly poorer survival outcomes for the high L/A group compared to the low L/A group, a difference that was statistically validated by a significant log-rank test (log-rank p < 0.001). L/A ratio has a significant association with poor prognosis in patients with HF and CKD patients in a critical condition. This finding demonstrates that L/A ratio might be useful in identifying patients with HF and CKD at high risk of all-cause death. Further large-scale prospective studies are needed to verify these results and inform clinical decisions.

Effects of social distancing during COVID-19 on informal learning behaviours and work performance: the role of organisational remote working cultures

ABSTRACT We explored the impact of social distancing and the subsequent shift to remote work during the COVID-19 pandemic on informal learning behaviours and work performance. To accomplish this, we conducted a large-scale international study at the peak of the pandemic in 2021, utilising self-report questionnaires distributed via online social business networks, with a total of N = 1,236 participants. In our study, we developed a research model wherein social distancing served as the independent variable and remote working cultures as the moderating variable. This model was validated using confirmatory factor analysis and regression analysis techniques. Our investigation affirms that social distancing had adverse effects on informal learning within organisations. Additionally, it suggests that social distancing alone does not necessarily cultivate a remote working culture. However, our study reveals that a remote working culture can mitigate the repercussions of social distancing. Consequently, we observed positive effects on work performance through informal learning, even amidst the pandemic. A key outcome is that business leaders should promote a remote work culture and, based on this framework, establish hybrid work arrangements that effectively combine in-person and remote work.

Progression of swine fecal microbiota during early stages of life and its association with performance: a longitudinal study

BackgroundIt is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling.ResultsMicrobiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage.ConclusionThese findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Exploring Applications and Preparation Techniques for Cellulose Hydrogels: A Comprehensive Review

Cellulose hydrogels, formed either through physical or chemical cross-linking into a three-dimensional network from cellulose or its derivatives, are renowned for their exceptional water absorption capacities and biocompatibility. Rising demands for sustainable materials have spurred interest in cellulose hydrogels, attributed to their abundant supply, biodegradability, and non-toxic nature. These properties highlight their extensive potential across various sectors including biomedicine, the food industry, and environmental protection. Cellulose hydrogels are particularly advantageous in applications such as drug delivery, wound dressing, and water treatment. Recent large-scale studies have advanced our understanding of cellulose preparation and its applications. This review delves into the fundamental concepts, preparation techniques, and current applications of cellulose hydrogels in diverse fields. It also discusses the latest advances in nano-lignin-based hydrogels, providing a comprehensive overview of this promising material and offering insights and guidance for future research and development.

What about adolescents' mental health after the pandemics? An analyses of a grade II hospital.

Suicidal ideation and suicide are serious situations that affect children and adolescents. The restrictions imposed by the SARS-CoV-2 pandemic have had a significant negative impact, due to social isolation, prolonged screen exposure and reduced outdoor activities. This study aims to compare the access to the Pediatric Emergency Department due to suicidal ideation and suicide attempts before and during the pandemic. This descriptive and retrospective study analyzed clinical records of children/adolescents who attended a Level II Pediatric Emergency Department of a hospital due to suicidal ideation and/or suicide attempts, between March 2018 and March 2020 (pre-pandemic period) and April 2020 to March 2022 (pandemic period). Demographic (age and sex) and clinical (psychopharmacological therapy, discharge destination and follow-up psychiatric/psychological consultations) variables were collected. Statistical analysis was performed using Microsoft Excel 2022® and SPSS v20.0®, considering statistical significance at p<0.05. A total of 71 children/adolescents were admitted for suicidal ideation, with a median age of 15 years (minimum: 10 years, maximum: 17 years), 27 in pre-pandemic period and 44 in pandemic period (p<0.001). The majority were girls, with a significant increase in pandemic period (pre-pandemic: 55.6 %, pandemic: 79.6 %; p<0.05). The age group with the highest increase in admissions was 15 years. There was a significant increase in suicidal attempts among girls (p<0.05) as well as self-harm behaviors (p<0.01). There was also a significant increase in the number of psychology/child psychiatry follow-up consultations in pandemic period (p<0.05). Most patients were referred to another hospital in both periods (pre-pandemic: 55.6 %, pandemic: 68.2 %) at discharge. During the pandemic period, there was an increase in the number of suicidal ideation cases, particularly among females, as well as in suicide attempts cases, which appears to be correlated with the pandemic restrictions. Larger-scale studies are needed to draw more accurate conclusions.

A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis

ObjectiveThis meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models.MethodsA systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle’s RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias.ResultsThis meta-analysis included 24 studies involving 440 animals with methodological quality scores ranging from 4 to 6. The results demonstrated that curcumin treatment significantly improved Aspartate aminotransferase (AST) [standard mean difference (SMD) = -3.90, 95% confidence interval (CI) (−4.96, −2.83), p &amp;lt; 0.01, I2 = 85.9%], Alanine aminotransferase (ALT)[SMD = − 4.40, 95% CI (−5.40, −3.40), p &amp;lt; 0.01, I2 = 81.2%]. Sensitivity analysis of AST and ALT confirmed the stability and reliability of the results obtained. However, the funnel plot exhibited asymmetry. Subgroup analysis based on species and animal models revealed statistically significant differences among subgroups. Furthermore, curcumin therapy improved fibrosis degree, oxidative stress level, inflammation level, and liver synthesis function in animal models of liver fibrosis.ConclusionCurcumin intervention not only mitigates liver fibrosis but also enhances liver function, while concurrently modulating inflammatory responses and antioxidant capacity in animal models. This result provided a strong basis for further large-scale animal studies as well as clinical trials in humans in the future.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42024502671.