Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial.

BACKGROUND: Diabetes leads to chronic kidney disease (CKD) and kidney failure, requiring dialysis or transplantation. Astragalus, a common herbal medicine and US pharmacopeia-registered food ingredient, is shown kidney protective by retrospective and preclinical data but with limited long-term prospective clinical evidence. This trial aimed to assess the effectiveness of astragalus on kidney function decline in macroalbuminuric diabetic CKD patients. METHODS: This randomized, assessor-blind, standard care-controlled, multi-center clinical trial randomly assigned 118 patients with estimated glomerular filtration rate (eGFR) of 30-90 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) of 300-5000 mg/g from 7 public outpatient clinics and the community in Hong Kong between July 2018 and April 2022 to add-on oral astragalus granules (15 gs of raw herbs daily equivalent) or to continue standard care alone as control for 48 weeks. Primary outcomes were the slope of change of eGFR (used for sample size calculation) and UACR of the intention-to-treat population. Secondary outcomes included endpoint blood pressures, biochemistry, biomarkers, concomitant drug change and adverse events. (ClinicalTrials.gov: NCT03535935) RESULTS: During the 48-week period, the estimated difference in the slope of eGFR decline was 4.6 ml/min/1.73m2 per year (95 %CI: 1.5 to 7.6, p = 0.003) slower with astragalus. For UACR, the estimated inter-group proportional difference in the slope of change was insignificant (1.14, 95 %CI: 0.85 to 1.52, p = 0.392). 117 adverse events from 31 astragalus-treated patients and 41 standard care-controlled patients were documented. The 48-week endpoint systolic blood pressure was 7.9 mmHg lower (95 %CI: -12.9 to -2.8, p = 0.003) in the astragalus-treated patients. 113 (96 %) and 107 (91 %) patients had post-randomization and endpoint primary outcome measures, respectively. CONCLUSION: In patients with type 2 diabetes, stage 2 to 3 CKD and macroalbuminuria, add-on astragalus for 48 weeks further stabilized kidney function on top of standard care.

Trees adjust nutrient acquisition strategies across tropical forest secondary succession.

Nutrient limitation may constrain the ability of recovering and mature tropical forests to serve as a carbon sink. However, it is unclear to what extent trees can utilize nutrient acquisition strategies - especially root phosphatase enzymes and mycorrhizal symbioses - to overcome low nutrient availability across secondary succession. Using a large-scale, full factorial nitrogen and phosphorus fertilization experiment of 76 plots along a secondary successional gradient in lowland wet tropical forests of Panama, we tested the extent to which root phosphatase enzyme activity and mycorrhizal colonization are flexible, and if investment shifts over succession, reflective of changing nutrient limitation. We also conducted a meta-analysis to test how tropical trees adjust these strategies in response to nutrient additions and across succession. We find that tropical trees are dynamic, adjusting investment in strategies - particularly root phosphatase - in response to changing nutrient conditions through succession. These changes reflect a shift from strong nitrogen to weak phosphorus limitation over succession. Our meta-analysis findings were consistent with our field study; we found more predictable responses of root phosphatase than mycorrhizal colonization to nutrient availability. Our findings suggest that nutrient acquisition strategies respond to nutrient availability and demand in tropical forests, likely critical for alleviating nutrient limitation.

Implications of Implementing the 2021 CKD-EPI Equation Without Race on Managing Patients With Kidney Disease in British Columbia, Canada.

Introduction: We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada. Methods: This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years. Results: A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94). Conclusion: CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD.

Motivation to participate in structured physical activity for autistic youth: A systematic scoping review.

LAY ABSTRACT: Autistic youth participate less in physical education classes and organised sport than their neurotypical peers. We conducted a review of existing studies to investigate what is known about what motivates (and does not motivate) autistic youth to take part in structured physical activities. We systematically searched electronic databases and found 18 publications that met the criteria to be included in this review. Data from these studies were extracted and mapped to the self-determination theory to identify factors that support (or undermine) motivation for autistic youth. We also discussed the findings with autistic individuals and other relevant stakeholders to discover how the review related to their experiences. Our results found competence (youth feeling competent in their athletic and social skills and abilities) to be the most reported psychological need impacting motivation for autistic youth. Intrinsic motivation (participating for enjoyment and satisfaction) was the most common facilitator of motivation. Autism-specific themes outside of the self-determination theory were mapped inductively, and we found that the sensory environment was a prominent theme reported to influence the motivation of autistic youth not covered by the self-determination theory. The findings of this review suggest that supporting the psychological needs of autistic youth can foster motivation to engage in physical activity, although how these needs are met can differ from their neurotypical peers. Future research should examine motivational factors that support engagement in structured physical activities through the lens of autistic youth and their experiences.

Improved assay development of pharmaceutical modalities using feedback-controlled liquid chromatography optimization.

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.

Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.

Venous congestion in septic shock quantified with point-of-care ultrasound: a pilot prospective multicentre cohort study.

PURPOSE: Venous congestion is a pathophysiologic state that can result in organ dysfunction, particularly acute kidney injury (AKI). We sought to evaluate the feasibility of performing a definitive observational study to determine the impact of venous congestion quantified using point-of-care ultrasound (POCUS) in patients with septic shock. METHODS: We conducted a prospective observational feasibility study at two intensive care units (ICUs). We recruited adult patients with septic shock within 12 hr of ICU admission. Using the validated Venous Excess Ultrasound Score (VEXUS), we quantified venous congestion on day 1 and day 3 of ICU admission. The primary feasibility outcome was successful completion rate of the two VEXUS scores. We performed a survival analysis to quantify the hazard of renal replacement therapy (RRT). RESULTS: We enrolled 75 patients from January 2022 to January 2023. The success rate of completion for VEXUS scans was 94.5% (95% confidence interval [CI], 89.5 to 97.6). Severe venous congestion was present in 19% (14/75) of patients on ICU admission day 1 and in 16% (10/61) of patients on day 3. Venous congestion on ICU admission may be associated with a higher risk of requiring RRT (unadjusted hazard ratio, 3.35; 95% CI, 0.94 to 11.88; P = 0.06). CONCLUSIONS: It is feasible to conduct a definitive observational study exploring the association between venous congestion quantified with POCUS and clinical outcomes in patients with septic shock. We hypothesize that venous congestion may be associated with an increased hazard of receiving RRT.

RéSUMé: OBJECTIF: La congestion veineuse est un état physiopathologique qui peut entraîner un dysfonctionnement des organes, en particulier une insuffisance rénale aiguë (IRA). Nous avons cherché à évaluer la faisabilité de la réalisation d'une étude observationnelle définitive pour déterminer l'impact de la congestion veineuse quantifiée à l'aide de l'échographie ciblée (POCUS) chez des patient·es en choc septique. MéTHODE: Nous avons réalisé une étude de faisabilité observationnelle prospective dans deux unités de soins intensifs (USI). Nous avons recruté des patient·es adultes souffrant d'un choc septique dans les 12 heures suivant leur admission aux soins intensifs. À l'aide du score VEXUS (score d'échographie de l'excès veineux) validé, nous avons quantifié la congestion veineuse au jour 1 et au jour 3 de leur admission aux soins intensifs. Le principal critère de faisabilité était le taux de réussite des deux scores VEXUS. Nous avons réalisé une analyse de survie pour quantifier le risque de thérapie de substitution rénale (TSR). RéSULTATS: Nous avons recruté 75 patient·es de janvier 2022 à janvier 2023. Le taux de réussite des scores VEXUS était de 94,5 % (intervalle de confiance [IC] à 95 %, 89,5 à 97,6). Une congestion veineuse sévère était présente chez 19 % (14/75) des patient·es au jour 1 d'admission aux soins intensifs et chez 16 % (10/61) des patient·es au jour 3. La congestion veineuse lors de l'admission aux soins intensifs peut être associée à un risque plus élevé de nécessiter une TSR (rapport de risque non ajusté, 3,35; IC 95 %, 0,94 à 11,88; P = 0,06). CONCLUSION: Il est possible de mener une étude observationnelle définitive explorant l'association entre la congestion veineuse quantifiée par POCUS et les devenirs cliniques chez les patient·es en choc septique. Nous émettons l'hypothèse que la congestion veineuse peut être associée à un risque accru de recevoir une thérapie de substitution rénale.

Cohort profile: The Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study.

BACKGROUND: The Children's Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study is a prospective cohort study of environmental influences on respiratory health in a rural, southeastern region of California (CA), which aims to longitudinally examine the contribution of a drying saline lake to adverse health impacts in children. OBJECTIVES: This cohort was established through a community-academic partnership with the goal of assessing the health effects of childhood exposures to wind-blown particulate matter (PM) and inform public health action. We hypothesize that local PM sources are related to poorer children's respiratory health. POPULATION: Elementary school children in Imperial Valley, CA. DESIGN: Prospective cohort study. METHODS: Between 2017 and 2019, we collected baseline information on 731 children, then follow-up assessments yearly or twice-yearly since 2019. Data have been collected on children's respiratory health, demographics, household characteristics, physical activity and lifestyle, via questionnaires completed by parents or primary caregivers. In-person measurements, conducted since 2019, repeatedly assessed lung function, height, weight and blood pressure. Exposure to air pollutants has been assessed by multiple methods and individually assigned to participants using residential and school addresses. Health data will be linked to ambient and local sources of PM, during and preceding the study period to understand how spatiotemporal trends in these environmental exposures may relate to respiratory health. PRELIMINARY RESULTS: Analyses of respiratory symptoms indicate a high prevalence of allergies, bronchitic symptoms and wheezing. Asthma diagnosis was reported in 24% of children at enrolment, which exceeds both CA state and US national prevalence estimates for children. CONCLUSIONS: The Children's AIRE cohort, while focused on the health impacts of the drying Salton Sea and air quality in Imperial Valley, is poised to elucidate the growing threat of drying saline lakes and wind-blown dust sources to respiratory health worldwide, as sources of wind-blown dust emerge in our changing climate.

Exploring the Molecular Tapestry: Organ-Specific Peptide and Protein Ultrafiltrates and Their Role in Therapeutics.

This study aims to characterize the proteome composition of organ-derived protein extracts from rabbits. Protein isolation was performed using soft homogenization and size exclusion via ultrafiltration. The proteome analysis of the ultrafiltrates was conducted using gel electrophoresis, and the mass spectrometry data were subjected to gene ontology analysis. Proteomic profiling revealed comprehensive protein profiles associated with RNA regulation, fatty acid binding, inflammatory response, oxidative stress, and metabolism. Additionally, our results demonstrate the presence of abundant small proteins, as observed in the mass spectrometry datasets. Small proteins and peptides are crucial in transcription modulation and various biological processes. The protein networks identified in the ultrafiltrates have the potential to enhance and complement biological therapeutic interventions. Data are available via ProteomeXchange with identifier PXD050039.

Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Oral Nutritional Supplement Prescription and Patient-Reported Symptom Burden Among Patients With Late-Stage Non-Dialysis Chronic Kidney Disease.

Background: Malnutrition and protein-energy wasting (PEW) are nutritional complications of advanced chronic kidney disease (CKD) that contribute to morbidity, mortality, and decreased quality of life. No previous studies have assessed the effect of oral nutritional supplements (ONSs) on patient-reported symptom burden among patients with non-dialysis CKD (CKD-ND) who have or are at risk of malnutrition/PEW. Objective: The objective of this study was (1) to quantify the associations between baseline nutritional parameters and patient-reported symptom scores for wellbeing, tiredness, nausea, and appetite and (2) to compare the change in symptom scores among patients prescribed ONS with patients who did not receive ONS in a propensity-score-matched analysis. Design: This study conducted observational cohort analysis using provincial registry data. Setting: This study was done in multidisciplinary CKD clinics in British Columbia. Patients: Adult patients >18 years of age with CKD-ND entering multidisciplinary CKD clinics between January 1, 2010-July 31, 2019 who had at least 2 Edmonton Symptom Assessment System Revised: Renal (ESASr:Renal) assessments. Measurements: The measurements include nutrition-related parameters such as body mass index (BMI), serum albumin, serum phosphate, serum bicarbonate, neutrophil-to-lymphocyte ratio (NLR), and ESASr:Renal scores (overall and subscores for wellbeing, tiredness, nausea, and appetite). Methods: Multivariable linear regression was applied to assess associations between nutritional parameters and ESASr:Renal scores. Propensity-score matching using the greedy method was used to match patients prescribed ONS with those not prescribed ONS using multiple demographic, comorbidity, health care utilization, and temporal factors. Linear regression was used to assess the association between first ONS prescription and change in ESASr:Renal overall score and subscores for wellbeing, tiredness, nausea, and appetite. Results: Of total, 2076 patients were included. Higher baseline serum albumin was associated with lower overall ESASr:Renal score (-0.20, 95% confidence interval [CI] = -0.40 to -0.01 per 1 g/L increase in albumin), lower subscores for tiredness (-0.04, 95% CI = -0.07 to -0.01), nausea (-0.03, 95% CI = -0.04 to -0.01), and appetite (-0.03, 95% CI = -0.06 to -0.01). Higher BMI was associated with higher overall ESASr:Renal score (0.32, 95% CI = 0.16 to 0.48 per 1 kg/m2 increase in BMI), higher symptom subscores for wellbeing (0.02, 95% CI = 0.00 to 0.04) and tiredness (0.05, 95% CI = 0.02 to 0.07). Higher baseline NLR was associated with higher overall score (0.21, 95% CI = 0.03 to 0.39 per 1 unit increase in NLR), higher symptom subscores for wellbeing (0.03, 95% CI = 0.01 to 0.05) and nausea (0.03, 95% CI = 0.02 to 0.05). In the propensity-score-matched analysis, there were no statistically significant associations between ONS prescription and change in overall ESASr:Renal (beta coefficient for change in ESASr:Renal = 0.17, 95% CI = -2.64 to 2.99) or for subscores for appetite, tiredness, nausea, and wellbeing. Limitations: Possible residual confounding. The ESASr:Renal assessments were obtained routinely only in patients with G5 CKD-ND and/or experiencing significant CKD-related symptoms. Conclusions: This exploratory observational analysis of patients with advanced non-dialysis CKD demonstrated BMI, serum albumin, and NLR were modestly associated with patient-reported symptoms, but we did not observe an association between ONS use and change in ESASr:Renal scores.

Contexte: La malnutrition et la dénutrition protéino-énergétique (DPÉ) sont des complications nutritionnelles de l'insuffisance rénale chronique (IRC) de stade avancé qui contribuent à la morbidité, à la mortalité et à la diminution de la qualité de vie associées à la maladie. Aucune étude n'a évalué l'effet des suppléments nutritionnels administrés par voie orale (SNO) sur le fardeau des symptômes autodéclarés par les patients non dialysés atteints d'IRC (IRC-ND) et souffrant de malnutrition/DPÉ ou risquant d'en souffrir. Objectifs: (1) Quantifier les associations entre les paramètres nutritionnels initiaux et les scores des symptômes autodéclarés en lien avec le bien-être, la fatigue, les nausées et l'appétit. (2) Comparer, dans une analyse des scores de propension appariés, la variation des scores associés aux symptômes des patients ayant reçu une ordonnance de SNO par rapport aux patients n'en ayant pas reçu. Conception: Analyse de cohorte observationnelle à partir des données du registre provincial. Cadre: Cliniques multidisciplinaires d'IRC en Colombie-Britannique. Sujets: Des patients adultes atteints d'IRC-ND admis entre le 1er janvier 2010 et le 31 juillet 2019 dans des cliniques multidisciplinaires d'IRC avec au moins deux évaluations selon l'Échelle d'évaluation Edmonton pour l'insuffisance rénale (ESASr:renal­Edmonton Symptom Assessment System Revised: Renal). Mesures: Les paramètres liés à la nutrition: indice de masse corporelle (IMC), albumine sérique, phosphate sérique, bicarbonate sérique, rapport neutrophiles/lymphocytes (RNL), ainsi que les scores ESASr:renal (scores globaux et scores secondaires pour le bien-être, la fatigue, les nausées et l'appétit). Méthodologie: La régression linéaire multivariable a servi à évaluer les associations entre les paramètres nutritionnels et les scores ESASr:renal. Une correspondance des scores de propension par la méthode Greedy a été utilisée pour apparier des patients ayant reçu ordonnance de SNO avec des patients n'en ayant pas reçu selon plusieurs facteurs démographiques, les comorbidités, l'utilisation des soins de santé et des facteurs temporels. La régression linéaire a servi à évaluer l'association entre la première ordonnance de SNO et la variation des scores globaux et des scores secondaires de l'ESASr:renal pour le bien-être, la fatigue, les nausées et l'appétit. Résultats: Au total, 2 076 patients ont été inclus à l'étude. Un taux d'albumine sérique plus élevé à l'inclusion était associé à un score ESASr:rénal global plus faible (-0,20 [IC 95 %: -0,40 à -0,01 pour 1 g/L d'augmentation de l'albumine]) et à des scores secondaires plus faibles pour la fatigue (-0,04 [IC 95 %: -0,07 à -0,01]), les nausées (-0,03 [IC 95 %: -0,04 à 0,01]) et l'appétit (0,03 [IC 95 %: -0,06 à -0,01]). Un IMC plus élevé était associé à un score ESASr:renal global plus élevé (0,32 [IC 95 %: 0,16 à 0,48 par augmentation de 1 kg/m2 de l'IMC]), des scores secondaires de symptômes plus élevés pour le bien-être (0,02 [IC 95 %: 0,00 à 0,04]) et la fatigue (0,05 [IC 95 %: 0,02 à 0,07]). Un RNL initial plus élevé était associé à un score ESASr:renal global plus élevé (0,21 [IC 95 %: 0,03 à 0,39 par unité d'augmentation du RNL]), des scores secondaires de symptômes plus élevés pour le bien-être (0,03 [IC 95 %: 0,01 à 0,05]) et les nausées (0,03 [IC 95 %: 0,02 à 0,05]). Dans l'analyse des scores de propension appariés, aucune association statistiquement significative n'a été observée entre une ordonnance de SNO et une variation significative dans les scores globaux de l'ESASr:renal (coefficient bêta de variation de l'ESASr:rénal: 0,17 [IC 95 %: -2,64 ­ à 2,99]) ou les scores secondaires pour l'appétit, la fatigue, les nausées et le bien-être. Limites: Possibilité de facteurs de confusion résiduels. Les évaluations ESASr:renal ont été effectuées de routine uniquement pour les patients atteints d'IRC-ND G5 et/ou présentant des symptômes importants liés à l'IRC. Conclusion: Cette analyse observationnelle exploratoire portant sur des patients atteints d'IRC avancée non dialysés a démontré que l'IMC, l'albumine sérique et le RNL étaient associés de façon modeste aux symptômes autodéclarés. Toutefois, aucune association n'a été observée entre une ordonnance de SNO et une variation des scores ESASr:renal.

Toward a coordinated understanding of hydro-biogeochemical root functions in tropical forests for application in vegetation models.

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest-climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics that represent important functional processes in tropical forests. We focus on: (1) fine-root strategies for soil resource exploration, (2) coupling and trade-offs in fine-root water vs nutrient acquisition, and (3) aboveground-belowground linkages in plant resource acquisition and use. We suggest avenues for representing these extremely diverse plant communities in computationally manageable and ecologically meaningful groups in models for linked aboveground-belowground hydro-nutrient functions. Tropical forests are undergoing warming, shifting rainfall regimes, and exacerbation of soil nutrient scarcity caused by elevated atmospheric CO2. The accurate model representation of tropical forest functions is crucial for understanding the interactions of this biome with the climate.

Las características de las raíces de los bosques tropicales y las estrategias de adquisición de recursos están subrepresentadas en modelos de vegetación, lo que dificulta la predicción del efecto de cambio de clima para estos ecosistemas ricos en carbono. Los bosques tropicales a menudo tienen combinaciones únicas a nivel mundial de alta biodiversidad taxonómica y funcional, estacionalidad de precipitación, y suelos infértiles, dando lugar a patrones distintos en los rasgos y funciones de las raíces en comparación con los ecosistemas de latitudes más altas. Integramos los avances recientes en nuestra comprensión de la función subterránea de los bosques tropicales en modelos de vegetación, centrándonos en la adquisición de agua y nutrientes. Ofrecemos comparaciones de avances recientes en la comprensión empírica y de modelos de las características de las raíces que representan procesos funcionales importantes en los bosques tropicales. Nos centramos en: (1) estrategias de raíces finas para adquisición de recursos del suelo, (2) acoplamiento y compensaciones entre adquisición del agua y de nutrientes, y (3) vínculos entre funciones sobre tierra y debajo del superficie en bosques tropicales. Sugerimos vías para representar estas comunidades de plantas extremadamente diversas en grupos computacionalmente manejables y ecológicamente significativos en modelos. Los bosques tropicales se están calentando, tienen cambios en los regímenes de lluvias, y tienen una exacerbación de la escasez de nutrientes del suelo causada por el elevado CO2 atmosférico. La representación precisa de las funciones de los bosques tropicales en modelos es crucial para comprender las interacciones de este bioma con el clima.

Differential associations of mask mandates on COVID-19 infection and mortality by community social vulnerability.

BACKGROUND: The COVID-19 pandemic in the United States has disproportionately impacted communities deemed vulnerable to disease outbreaks. Our objectives were to test (1) whether infection and mortality decreased in counties in the most vulnerable (highest) tercile of the Social Vulnerability Index (SVI), and (2) whether disparities between terciles of SVI were reduced, as the length of mask mandates increased. METHODS: Using the New York Times COVID-19 and the Centers for Disease Control and Prevention SVI and mask mandate datasets, we conducted negative binomial regression analyses of county-level COVID-19 cases and deaths from 1/2020-11/2021 on interactions of SVI and mask mandate durations. RESULTS: Mask mandates were associated with decreases in mid-SVI cases (IRR: 0.79) and deaths (IRR: 0.90) and high-SVI cases (IRR: 0.89) and deaths (IRR: 0.88). Mandates were associated with the mitigation of infection disparities (Change in IRR: 0.92) and mortality disparities (Change in IRR: 0.85) between low and mid-SVI counties and mortality disparities between low and high-SVI counties (Change in IRR: 0.84). DISCUSSION: Mask mandates were associated with reductions in COVID-19 infection and mortality and mitigation of disparities for mid and high-vulnerability communities. CONCLUSIONS: Ongoing COVID-19 response efforts may benefit from longer-standing infection control policies, particularly in the most vulnerable communities.

Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas.

BACKGROUND: Colorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aimed to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients. METHODS: A case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analysed with the correlation/trend test based on the additive model. SNP variants with association testing -log10 p value ≥5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation. RESULTS: Glycolysis was uncovered as the top hallmark gene set. Transcripts from two of the five genes profiled, hematopoietic substrate 1 associated protein X 1 (HAX1) and hyaluronan-mediatedmotility receptor (HMMR), were significantly upregulated in the metastasis-positive tumours. In contrast to disease-risk variants, HAX1 appeared to act synergistically with HMMR in significantly impacting metastasis-free survival. Examining the subtype datasets with FUMA and Ingenuity Pathway Analysis (IPA) identified distinct pathways demonstrating sexual dimorphism in CRC metastasis. CONCLUSIONS: Combining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of patients with stage I-III CRC.

Exosomes; a Potential Source of Biomarkers, Therapy, and Cure for Type-1 Diabetes.

The scourge of type-1 diabetes (T1D) is the morbidity and mortality it and its complications cause at a younger age. This propels the constant search for better diagnostic, treatment, and management strategies, with the ultimate quest being a cure for T1D. Recently, the therapeutic potential of exosomes has generated a lot of interest. Among the characteristics of exosomes of particular interest are (a) their regenerative capacity, which depends on their "origin", and (b) their "content", which determines the cell communication and crosstalk they influence. Other functional capacities, including paracrine and endocrine homeostatic regulation, pathogenic response ability resulting in insulin secretory defects or ß-cell death under normal metabolic conditions, immunomodulation, and promotion of regeneration, have also garnered significant interest. Exosome "specificity" makes them suitable as biomarkers or predictors, and their "mobility" and "content" lend credence to drug delivery and therapeutic suitability. This review aims to highlight the functional capacities of exosomes and their established as well as novel contributions at various pathways in the onset and progression of T1D. The pathogenesis of T1D involves a complex crosstalk between insulin-secreting pancreatic ß-cells and immune cells, which is partially mediated by exosomes. We also examine the potential implications for type 2 diabetes (T2D), as the link in T2D has guided T1D exploration. The collective landscape presented is expected to help identify how a deeper understanding of exosomes (and their cargo) can provide a framework for actionable solutions to prevent, halt, or change the very course of T1D and its complications.

Automated Reference Kidney Histomorphometry using a Panoptic Segmentation Neural Network Correlates to Patient Demographics and Creatinine.

Reference histomorphometric data of healthy human kidneys are lacking due to laborious quantitation requirements. We leveraged deep learning to investigate the relationship of histomorphometry with patient age, sex, and serum creatinine in a multinational set of reference kidney tissue sections. A panoptic segmentation neural network was developed and used to segment viable and sclerotic glomeruli, cortical and medullary interstitia, tubules, and arteries/arterioles in digitized images of 79 periodic acid-Schiff (PAS)-stained human nephrectomy sections showing minimal pathologic changes. Simple morphometrics (e.g., area, radius, density) were measured from the segmented classes. Regression analysis was used to determine the relationship of histomorphometric parameters with age, sex, and serum creatinine. The model achieved high segmentation performance for all test compartments. We found that the size and density of nephrons, arteries/arterioles, and the baseline level of interstitium vary significantly among healthy humans, with potentially large differences between subjects from different geographic locations. Nephron size in any region of the kidney was significantly dependent on patient creatinine. Slight differences in renal vasculature and interstitium were observed between sexes. Finally, glomerulosclerosis percentage increased and cortical density of arteries/arterioles decreased as a function of age. We show that precise measurements of kidney histomorphometric parameters can be automated. Even in reference kidney tissue sections with minimal pathologic changes, several histomorphometric parameters demonstrated significant correlation to patient demographics and serum creatinine. These robust tools support the feasibility of deep learning to increase efficiency and rigor in histomorphometric analysis and pave the way for future large-scale studies.