Mapping livestock density distribution in the Selenge River Basin of Mongolia using random forest.

Mapping dynamically distributed livestock in the vast steppe area based on statistical data collected by administrative units is very difficult as it is limited by the quality of statistical data and local geographical environment factors. While, spatial mapping of livestock gridded data is critical and necessary for animal husbandry management, which can be easily integrated and analyzed with other natural environment data. Facing this challenge, this study introduces a spatialization method using random forest (RF) in the Selenge River Basin, which is the main animal husbandry region in Mongolia. A spatialized model was constructed based on the RF to obtain high-resolution gridded distribution data of total livestock, sheep & goats, cattle, and horses. The contribution of factors influencing the spatial distribution of livestock was quantitatively analyzed. The predicted results showed that (1) it has high livestock densities in the southwestern regions and low in the northern regions of the Selenge River Basin; (2) the sheep & goats density was mainly concentrated in 0-125 sheep/km2, and the high-density area was mainly distributed in Khuvsgul, Arkhangai, Bulgan and part soums of Orkhon; (3) horses and cattle density were concentrated in 0-25 head/km2, mainly distributed in the southwest and central parts of the basin, with few high-density areas. This indicates that the RF simulation results effectively depict the characteristics of Selenge River Basin. Further study supported by Geodetector showed human activity was the main driver of livestock distribution in the basin. This study is expected to provide fundamental support for the precise regulation of animal husbandry in the Mongolian Plateau or other large steppe regions worldwide.

Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

The role of rhizosphere phages in soil health.

While the One Health framework has emphasized the importance of soil microbiomes for plant and human health, one of the most diverse and abundant groups-bacterial viruses, i.e. phages-has been mostly neglected. This perspective reviews the significance of phages for plant health in rhizosphere and explores their ecological and evolutionary impacts on soil ecosystems. We first summarize our current understanding of the diversity and ecological roles of phages in soil microbiomes in terms of nutrient cycling, top-down density regulation, and pathogen suppression. We then consider how phages drive bacterial evolution in soils by promoting horizontal gene transfer, encoding auxiliary metabolic genes that increase host bacterial fitness, and selecting for phage-resistant mutants with altered ecology due to trade-offs with pathogen competitiveness and virulence. Finally, we consider challenges and avenues for phage research in soil ecosystems and how to elucidate the significance of phages for microbial ecology and evolution and soil ecosystem functioning in the future. We conclude that similar to bacteria, phages likely play important roles in connecting different One Health compartments, affecting microbiome diversity and functions in soils. From the applied perspective, phages could offer novel approaches to modulate and optimize microbial and microbe-plant interactions to enhance soil health.

Phage selection drives resistance-virulence trade-offs in Ralstonia solanacearum plant-pathogenic bacterium irrespective of the growth temperature.

While temperature has been shown to affect the survival and growth of bacteria and their phage parasites, it is unclear if trade-offs between phage resistance and other bacterial traits depend on the temperature. Here, we experimentally compared the evolution of phage resistance-virulence trade-offs and underlying molecular mechanisms in phytopathogenic Ralstonia solanacearum bacterium at 25 °C and 35 °C temperature environments. We found that while phages reduced R. solanacearum densities relatively more at 25 °C, no difference in the final level of phage resistance was observed between temperature treatments. Instead, small colony variants (SCVs) with increased growth rate and mutations in the quorum-sensing (QS) signaling receptor gene, phcS, evolved in both temperature treatments. Interestingly, SCVs were also phage-resistant and reached higher frequencies in the presence of phages. Evolving phage resistance was costly, resulting in reduced carrying capacity, biofilm formation, and virulence in planta, possibly due to loss of QS-mediated expression of key virulence genes. We also observed mucoid phage-resistant colonies that showed loss of virulence and reduced twitching motility likely due to parallel mutations in prepilin peptidase gene, pilD. Moreover, phage-resistant SCVs from 35 °C-phage treatment had parallel mutations in type II secretion system (T2SS) genes (gspE and gspF). Adsorption assays confirmed the role of pilD as a phage receptor, while no loss of adsorption was found with phcS or T2SS mutants, indicative of other downstream phage resistance mechanisms. Additional transcriptomic analysis revealed upregulation of CBASS and type I restriction-modification phage defense systems in response to phage exposure, which coincided with reduced expression of motility and virulence-associated genes, including pilD and type II and III secretion systems. Together, these results suggest that while phage resistance-virulence trade-offs are not affected by the growth temperature, they could be mediated through both pre- and postinfection phage resistance mechanisms.

Bibliometrics analysis based on the Web of Science: Current trends and perspective of gastric organoid during 2010-2023.

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.

Chaihu Shugan Powder inhibits interstitial cells of cajal mitophagy through USP30 in the treatment of functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. MATERIALS AND METHODS: The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. RESULTS: Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3Ⅱ/LC3Ⅰ、PINK1、Parkin、PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. CONCLUSIONS: These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the up-regulation of via PINK1/Parkin pathway.

Effect of Chaihu-Shugan-San on functional dyspepsia and gut microbiota: A randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Shugan-San (CSS) is a classic traditional Chinese medicine (TCM) formula from the Ming Dynasty "Jingyue's Complete Works". In China, it is prevalent for the treatment of a wide range of ailments, with a particular emphasis on functional gastrointestinal disorders (FGIDs). Clinical evidence suggests that CSS has been found to be a highly effective therapeutic approach for the treatment of Functional Dyspepsia (FD), however, there is a limited amount of high-quality clinical evidence, particularly randomized, double-blind, placebo-controlled trials to support this claim. AIM OF THE STUDY: To evaluate the therapeutic efficacy of Chaihu-Shugan-San (CSS) for treating functional dyspepsia (FD) by comparing it to placebos, as well as to investigate the impact of CSS on the gut microbiota in individuals diagnosed with FD. MATERIALS AND METHODS: This was a randomized double-blind, placebo-controlled clinical trial implemented at Shuguang Hospital in Shanghai. Between May 2021 and December 2022, 94 participants satisfying the Rome IV diagnostic criteria for FD were enrolled. They were assigned randomly to either the CSS group or the placebo group, with an equal allocation ratio of 1:1. Patients in both groups received the intervention for four weeks. The primary outcome was the dyspepsia symptom scores evaluated by using single dyspepsia symptom scale (SDS) after four weeks of treatment. The secondary outcomes were the solid gastric empties rate measured by a barium strip method, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Functional dyspepsia Quality of life scale (FDDQL). In addition, after unblinding, 30 patients in the CSS group were randomly selected and divided into before and after treatment of the FD groups (FD1, FD2), and 30 healthy participants were selected as healthy control group (HC), and the gut microbiota was analyzed by 16S rRNA sequencing. RESULTS: After four weeks of treatment, the SDS score exhibited a significant improvement in the CSS group compared to the placebo group (t = 4.882; P ＜0.001). The difference in barium strip gastric emptying rate in the CSS group showed a significant ascent compared to the control group (P < 0.01). The HAMA, HAMD, and FDDQL scores in the CSS group showed a statistically significant increase compared to the control group (all P < 0.01). The results of 16S rRNA sequencing revealed that FD patients had less diverse and abundant microbiota than the healthy people. Additionally, the application of CSS resulted in the modulation of certain bacterial populations, leading to both up-regulation and down-regulation of their quantities. CONCLUSIONS: These findings suggested that CSS is more effective compared to a placebo in treating FD, relieves anxiety and depression, increases gastric emptying rate in FD patients, and that CSS also affects the bacterial community structure in FD patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2100045793. Registered 25 Mach 2021.

Association between plasma L-carnitine levels and mitochondrial DNA copy number.

Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = -0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.

"It's a feeling of complete disconnection": experiences of existential loneliness from youth to older adulthood.

BACKGROUND: Existential loneliness is a feeling which stems from a sense of fundamental separation from others and the world. Although commonly mentioned in the loneliness literature, there is relatively little empirical work on this construct, and existing work tends to focus on older and seriously ill individuals. The present study aimed to understand how people experience existential loneliness without specific constraints on precipitating factors like illness or age. METHODS: A qualitative online survey collected data from 225 adults aged 16 to 72 years old. Participants were asked to write about their experiences of existential loneliness and how these experiences compared to non-existential loneliness. Data were analysed using reflexive thematic analysis. RESULTS: Of 225 participants, 51% knew the meaning of "existential loneliness" upon accessing the survey and in total, 83% had experienced existential loneliness. 93% of these participants had also experienced loneliness that was not existential in nature. 175 participants provided qualitative data regarding their experiences of existential loneliness, from which four themes were identified: Existential loneliness is (1) A deeper form of loneliness, and (2) A feeling of deep disconnection, in which (3) Cognitive evaluations and negative emotions are central elements, and (4) Stress and mental health issues are perceived as relevant factors. CONCLUSIONS: Existential loneliness is a deeply rooted and impactful form of loneliness which involves feelings of profound separateness. This aspect of loneliness is deserving of further attention. Future research directions are suggested.

Engineering multifunctional rhizosphere probiotics using consortia of Bacillus amyloliquefaciens transposon insertion mutants.

While bacterial diversity is beneficial for the functioning of rhizosphere microbiomes, multi-species bioinoculants often fail to promote plant growth. One potential reason for this is that competition between different species of inoculated consortia members creates conflicts for their survival and functioning. To circumvent this, we used transposon insertion mutagenesis to increase the functional diversity within Bacillus amyloliquefaciens bacterial species and tested if we could improve plant growth promotion by assembling consortia of highly clonal but phenotypically dissimilar mutants. While most insertion mutations were harmful, some significantly improved B. amyloliquefaciens plant growth promotion traits relative to the wild-type strain. Eight phenotypically distinct mutants were selected to test if their functioning could be improved by applying them as multifunctional consortia. We found that B. amyloliquefaciens consortium richness correlated positively with plant root colonization and protection from Ralstonia solanacearum phytopathogenic bacterium. Crucially, 8-mutant consortium consisting of phenotypically dissimilar mutants performed better than randomly assembled 8-mutant consortia, suggesting that improvements were likely driven by consortia multifunctionality instead of consortia richness. Together, our results suggest that increasing intra-species phenotypic diversity could be an effective way to improve probiotic consortium functioning and plant growth promotion in agricultural systems.

Organo-Mediator Enabled Electrochemical Deuteration of Styrenes.

Despite widespread use of the deuterium isotope effect, selective deuterium labeling of chemical molecules remains a major challenge. Herein, a facile and general electrochemically driven, organic mediator enabled deuteration of styrenes with deuterium oxide (D2 O) as the economical deuterium source was reported. Importantly, this transformation could be suitable for various electron rich styrenes mediated by triphenylphosphine (TPP). The reaction proceeded under mild conditions without transition-metal catalysts, affording the desired products in good yields with excellent D-incorporation (D-inc, up to >99 %). Mechanistic investigations by means of isotope labeling experiments and cyclic voltammetry tests provided sufficient support for this transformation. Notably, this method proved to be a powerful tool for late-stage deuteration of biorelevant compounds.

RIN enhances plant disease resistance via root exudate-mediated assembly of disease-suppressive rhizosphere microbiota.

The RIPENING-INHIBITOR (RIN) transcriptional factor is a key regulator governing fruit ripening. While RIN also affects other physiological processes, its potential roles in triggering interactions with the rhizosphere microbiome and plant health are unknown. Here we show that RIN affects microbiome-mediated disease resistance via root exudation, leading to recruitment of microbiota that suppress the soil-borne, phytopathogenic Ralstonia solanacearum bacterium. Compared with the wild-type (WT) plant, RIN mutants had different root exudate profiles, which were associated with distinct changes in microbiome composition and diversity. Specifically, the relative abundances of antibiosis-associated genes and pathogen-suppressing Actinobacteria (Streptomyces) were clearly lower in the rhizosphere of rin mutants. The composition, diversity, and suppressiveness of rin plant microbiomes could be restored by the application of 3-hydroxyflavone and riboflavin, which were exuded in much lower concentrations by the rin mutant. Interestingly, RIN-mediated effects on root exudates, Actinobacteria, and disease suppression were evident from the seedling stage, indicating that RIN plays a dual role in the early assembly of disease-suppressive microbiota and late fruit development. Collectively, our work suggests that, while plant disease resistance is a complex trait driven by interactions between the plant, rhizosphere microbiome, and the pathogen, it can be indirectly manipulated using "prebiotic" compounds that promote the recruitment of disease-suppressive microbiota.

Gastrointestinal hospitalization during COVID-19 pandemic in the United States: Analysis of a nationwide inpatient sample.

BACKGROUND AND AIM: We aim to systematically investigate gastrointestinal (GI) hospitalizations in the United States during the early phase of the COVID-19 pandemic on a national level and the consequence that may inform practice and policies. METHODS: A retrospective cross-sectional analysis of adult hospitalizations with GI-related diagnoses or procedures in the United States in 2020 was used, with hospitalizations from 2016 to 2019 used for contextual information. RESULTS: Hospitalizations with principal and secondary GI diagnoses decreased by 13.3% and 8.2% from 2019 to 2020, respectively. Most GI diagnoses decreased in 2020, with a few exceptions including alcoholic liver disease (increased by 7.8% as a principal diagnosis) and acute liver failure (increased by 11.6% as a secondary diagnosis). The mortality rate of hospitalizations with GI disease increased in 2020 compared with 2019 (for principal diagnosis: adjusted odds ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001; for secondary diagnosis: adjusted odds ratio 1.10, 95% confidence interval 1.07-1.13, P < 0.001). Most GI procedures decreased except for a notable 8.3% increase in gastrostomy. The per-GI-hospitalization rate of procedures increased for hospitalizations with a principal GI diagnosis (56.4% vs 55.6%, P = 0.003) or unchanged for hospitalizations with secondary GI diagnoses (18.3% vs 18.2%, P = 0.512). CONCLUSION: The COVID-19 pandemic resulted in a decrease in the volume of GI hospitalizations and procedures in 2020, but there was an increase in the mortality rate and some specific diagnoses including alcoholic liver disease and acute liver failure. These findings will likely enlighten future research and healthcare resource allocation for GI diseases.

Dynamic prediction of displacement and deformation of any point on mining surface based on B-normal model.

The surface displacement and deformation of goaf caused by coal mining destroy the underground rock structure and surface ecological environment in the mining area and endanger the safety of human life and property. An accurate and efficient dynamic prediction system of mining subsidence is indispensable. Given the limited scope of the application of the probability integral model on the edge of the mobile basin, its poor prediction effect, and its low accuracy, a new mining subsidence prediction model based on the Boltzmann function is proposed. Combined with the transformed normal distribution time function, a B-normal prediction model that can predict the dynamic displacement and deformation of any point on the surface was constructed. The global optimal solution of the parameters of the dynamic prediction model was inversed by introducing particle swarm optimization shuffled frog leaping intelligent algorithm (PSO-SFLA), and then, the model was applied to the 8102 working face of the Guobei coal mine to dynamically predict the subsidence, inclination, curvature, horizontal displacement, and horizontal deformation of the goaf surface. The prediction results showed that on the strike and dip observation lines, the prediction accuracy of the dynamic subsidence and horizontal displacement of the surface could reach the centimeter level, the predicted root mean square error (RMSE) of dynamic tilt and horizontal deformation was less than 0.51 mm/m, and the predicted RMSE of dynamic curvature was within 0.020 mm/m2. The prediction results reflected the dynamic evolution law of surface displacement and deformation and verified the reliability of the B-normal dynamic prediction model, which can fully meet the needs of practical engineering applications.

Experiences of Loneliness Across the Lifespan: A Systematic Review and Thematic Synthesis of Qualitative Studies.

PURPOSE: Loneliness is a fundamentally subjective experience that is common at various life stages. Studies have qualitatively explored loneliness, but a comprehensive overview is lacking. This research therefore provides a fine-grained review of studies on loneliness experiences across the lifespan. METHODS: A systematic review and thematic synthesis were performed on studies that qualitatively investigated experiences of loneliness in people of any age from non-clinical populations. Sensitivity analysis assessed the impact of lower-quality studies and specific age groups on the findings. RESULTS: Twenty-nine studies of 1,321 participants aged between 7 and 103 were included. Fifteen descriptive themes and three overarching analytical themes were developed: (1) Loneliness is both psychological and contextual, (2) Loneliness centres on feelings of meaningful connection and painful disconnection, and (3) Loneliness can exist in a general, pervasive sense or can relate to specific other people or relationship types. Some features were particularly pertinent to children, younger adults, and older adults, respectively. CONCLUSIONS: Loneliness involves a primarily aversive psychological experience of perceived disconnection which is linked to physical, personal, and socio-political contexts and can be pervasive or relate to specific relationships or relationship types. An awareness of context, life stage, and personal experiences is essential to understand loneliness.

Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study.

BACKGROUND & AIMS: Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia; however, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive decline. METHODS: We conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use were determined according to review of medications during annual in-person study visits. Incident dementia was defined according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models. RESULTS: Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with changes in overall cognitive test scores over time (multivariable B, -0.002; standard error, 0.01; P = .85). Similarly, no associations were observed between H2RA use and all cognitive endpoints. CONCLUSIONS: In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

Associations of Telomere Length and Change With Cognitive Decline Were Modified by Sex and Race: The REGARDS Study.

INTRODUCTION: We examined the associations of baseline telomere length (TL) and TL change with cognitive function over time in older US adults, as well as differences by sex and race. METHODS: A total of 1820 cognitively healthy individuals (median baseline age: 63 years) were included. Telomere length was measured using qPCR-based method at baseline and among 614 participants in the follow-up examination 10 years later. Cognitive function was assessed by a four-test battery every 2 years. RESULTS: In multivariable-adjusted linear mixed models, longer baseline TL and smaller attrition/lengthening of TL over time were associated with better Animal Fluency Test score. Longer baseline TL was also linearly associated with better Letter Fluency Test score. The observed associations were consistently more pronounced in women than men and in Black compared to White participants. DISCUSSION: Telomere length may be a biomarker that predicts long-term verbal fluency and executive function, particularly in women and Black Americans.

Global increase of colorectal cancer in young adults over the last 30 years: an analysis of the Global Burden of Disease Study 2019.

OBJECTIVES: The US Preventive Services Task Force lowered the recommended starting age for colorectal cancer (CRC) screening in average-risk adults from 50 to 45 years. We aimed to estimate the global burden and trends of colorectal cancer in adults aged 20-49 years (early-onset CRC). METHODS: This is an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). The GBD 2019 estimation methods were used to describe the incidence, mortality, and disability-adjusted life years (DALYs) of early CRC from 1990 to 2019. Data from 204 countries and geographic areas were available. RESULTS: The global incidence rate of early-onset CRC increased from 4.2/100 000 to 6.7/100 000 from 1990 to 2019. Mortality and DALYs of early-onset CRC also increased. The CRC incidence rate increased faster in younger adults (1.6%) than in adults aged 50-74 years (0.6%) as measured by the annual percentage change. The increase in early-onset CRC incidence was consistently observed in all five socio-demographic index (SDI) regions and 190 out of 204 countries and territories. Middle and high-middle SDI regions had faster annual increases in early-onset CRC, which warrants further attention. CONCLUSIONS: The global incidence, mortality, and DALYs of early-onset CRC increased from 1990 to 2019. The increase in early-onset CRC incidence was prevalent worldwide. Several countries were found to have higher incidence rates than the United States or fast increase in early-onset CRC, which warrants further attention.

Uncovering the social determinants of brain injury rehabilitation.

Social determinants of health (SDH), such as social isolation and loneliness, are often more frequently experienced in brain injury survivors. The paper explores the personal experiences of loneliness among brain injury survivors during lockdown to negate health inequalities and improve rehabilitation for this population in the future. Twenty-four brain injury survivors participated in semi-structured interviews and questionnaires relating to loneliness, resilience and wellbeing. Three themes (the experience of loneliness, loneliness during the pandemic and loneliness after the pandemic) explored survivors' experiences of loneliness generally post-brain injury, but also chronicle how these feelings developed in lockdown and survivors' feelings regarding society returning to 'normal'. Future interventions should focus on reframing survivors' beliefs regarding societal expectations and minimise the pressure they experience to keep up with their peers physically and emotionally. Additionally, we recommend creating accessible peer support options for all brain injury survivors as an important step for alleviating loneliness.