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We employed least-cost and circuit theory modeling to model the connectivity among previously defined Jaguar Conservation Units (JCUs) at the southern limit of the jaguarís range in Argentina, Bolivia, Brazil and Paraguay, in order to assess the effects of deforestation and land use change between 2000 and 2014. Due to uncertainty about possible limitations to jaguar dispersal, we examined connectivity where linkages were not cost-limited and limited to 1000 km cost-weighted distance. When linkage length was not cost-limited, total linkage area decreased by 9%, and mean least-cost distance and mean effective resistance increased by 6 and 31%, respectively, from 2000 to 2014. Limiting linkages to 1000 km cost-weighted distance indicated that the southern- and eastern-most JCUs were isolated as early as 2000 and that the number of linkages between the other JCUs decreased between 2000 and 2014, causing the linkage area to decrease by 27% while the least-cost distance of the remaining linkages increased by a mean of 4% and effective resistance increased on average by 44%. By limiting linkages to a plausible cost-weighted distance, we demonstrated that JCUs in the Atlantic Forest, Argentine Chaco and the Argentine/Bolivian Yungas have been isolated since at least 2000, and that there has been a loss of connectivity through eastern Bolivia, increased resistance in the remaining linkages and a constriction of all but one linkage to a minimum width of

Current research on dietary supplements (primarily survey-based prevalence studies and clinical trials of safety and efficacy) is inadequate for understanding how consumers use supplements in the real world. Analyzing interview data from formative research with dietary supplement users (N=60), we observed skepticism in the way our informants interpret scientific information about supplements, trust in referrals from those they feel are like them, and experimentation with products in order to tailor them to their bodies and needs. We stress the need for qualitative research focusing on patterns of supplement use in context (rather than as isolated supplements in fixed doses), the network effect of supplement use, and the way information about supplements is translated and transmitted. Furthermore, we urge clinicians to pay careful attention not only to whether patients are taking dietary supplements, but also how supplements are being used alone and in combination with other supplements, pharmaceuticals, and over-the-counter (OTC) medications. [ABSTRACT FROM AUTHOR]

Recent research shows that more women than ever before are in management positions. While there has been substantial literature addressing gender differences in male and female management styles and the barriers women encounter as they enter careers in human services management, little is known about the strategies, skills, and resources women have found to be useful tools in moving into and up the managerial ladder. The authors explore women's perceptions of organizational, personal, and professional development factors which influence their careers in management and the strategies they utilize in resolving these issues. Recommendations are made as to how more women can be encouraged to enter leadership roles in the ever changing, turbulent human services environment. [ABSTRACT FROM AUTHOR]

Introduction: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed., Methods: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS)., Results: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001)., Conclusion: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Importance: Although there is a known association between urinary incontinence (UI) and fall risk, it is unclear if having both UI and fecal incontinence, or dual incontinence (DI), increases this risk., Objective: The objective of our study was to elucidate a relationship between DI and falls., Study Design: This was a retrospective cohort study at a tertiary academic health system of female patients 65 years and older presenting for a new patient visit to a urogynecology health care professional for UI from 2019 to 2021. Demographic data and responses to intake questionnaires on fall and markers of frailty were extracted. Multivariable logistic regression was performed to identify factors associated with fall adjusting for covariates identified upon univariate comparison., Results: A total of 2,814 women were included in the analysis; 2,661 patients reported UI alone, and 153 reported DI. A greater proportion of women with DI reported a fall in the past year compared with those with UI alone (22.9% vs 12.2%, P < 0.001). Univariable comparison showed that these 2 groups differed regarding age, body mass index, and estimated median household income. On multivariable logistic regression, DI was significantly associated with falls (adjusted odds ratio 2.56; 95% confidence interval, 1.02-5.46). Other factors independently associated with falls in older women with UI include (adjusted odds ratio, 95% confidence interval): lower income groups (2.35, 1.50-3.67 for $20,000-$40,000, compared with $100,000 and higher-income group), difficulty with activities of daily living (1.60, 1.25-2.13), and unintentional weight loss (1.68, 1.05-2.68)., Conclusion: Patients with DI have a 2-fold higher risk of fall compared with patients with UI alone., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Although selenium deficiency correlates with colorectal cancer (CRC) risk, the roles of the selenium-rich antioxidant selenoprotein P (SELENOP) in CRC remain unclear. In this study, we defined SELENOP's contributions to sporadic CRC. In human single-cell cRNA-Seq (scRNA-Seq) data sets, we discovered that SELENOP expression rose as normal colon stem cells transformed into adenomas that progressed into carcinomas. We next examined the effects of Selenop KO in a mouse adenoma model that involved conditional, intestinal epithelium-specific deletion of the tumor suppressor adenomatous polyposis coli (Apc) and found that Selenop KO decreased colon tumor incidence and size. We mechanistically interrogated SELENOP-driven phenotypes in tumor organoids as well as in CRC and noncancer cell lines. Selenop-KO tumor organoids demonstrated defects in organoid formation and decreases in WNT target gene expression, which could be reversed by SELENOP restoration. Moreover, SELENOP increased canonical WNT signaling activity in noncancer and CRC cell lines. In defining the mechanism of action of SELENOP, we mapped protein-protein interactions between SELENOP and the WNT coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). Last, we confirmed that SELENOP-LRP5/6 interactions contributed to the effects of SELENOP on WNT activity. Overall, our results position SELENOP as a modulator of the WNT signaling pathway in sporadic CRC.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

H3K4me1 methyltransferases MLL3 (KMT2C) and MLL4 (KMT2D) are critical for enhancer activation, cell differentiation and development. However, roles of MLL3/4 enzymatic activities and MLL3/4-mediated enhancer H3K4me1 in these processes remain unclear. Here we report that constitutive elimination of both MLL3 and MLL4 enzymatic activities prevents initiation of gastrulation and leads to early embryonic lethality in mice. However, selective elimination of MLL3/4 enzymatic activities in embryonic, but not extraembryonic, lineages leaves gastrulation largely intact. Consistent with this, embryonic stem cells (ESCs) lacking MLL3/4 enzymatic activities can differentiate toward the three embryonic germ layers but show aberrant differentiation to extraembryonic endoderm (ExEn) and trophectoderm. The failure in ExEn differentiation can be attributed to markedly reduced enhancer-binding of the lineage-determining transcription factor GATA6. Furthermore, we show that MLL3/4-catalyzed H3K4me1 is largely dispensable for enhancer activation during ESC differentiation. Together, our findings suggest a lineage-selective, but enhancer activation-independent, role of MLL3/4 methyltransferase activities in early embryonic development and ESC differentiation., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer. Equimolar mixtures, with slightly closer chain packing, exhibit a similar but weaker response. The latter also tend to incorporate more solvent during this electrochemical phase transition, at levels similar to those of pure DMPS. Reflectivity measurements reveal greater solvation of lipid layers for DMPS > 30 mol %, matching the greater propensity for DMPS-rich bilayers to incorporate water. Taken together, the data indicate that the range of 10-35 mol % DMPS provides optimum bilayer properties (in flexibility and function as a barrier), which may explain why the DMPS content of cell membranes tends to be found within this range.

Approximately 60-70 million people suffer from traumatic brain injury (TBI) each year. Animal models continue to be paramount in understanding mechanisms of cellular dysfunction and testing new treatments for TBI. Enhancing the translational potential of novel interventions therefore necessitates testing pre-clinical intervention strategies with clinically relevant cognitive assays. This study used a unilateral parietal lobe controlled cortical impact (CCI) model of TBI and tested rats on a touchscreen-based Paired Associates Learning (PAL) task, which is part of the Cambridge Neuropsychological Test Automated Battery. In humans, the PAL task has been used to assess cognitive deficits in the ability to form stimulus-location associations in a multitude of disease states, including TBI. Although the use of PAL in animal models could be important for understanding the clinical severity of cognitive impairment post-injury and throughout intervention, to date, the extent to which a rat model of TBI produces deficits in PAL task performance has not yet been reported. This study details the behavioral consequences of the CCI injury model with a Trial-by-Trial analysis of PAL performance that enables behavioral strategy use to be inferred. Following behavior, the extent of the injury was quantified with histology and staining for the presence of glial fibrillary acid protein and ionized calcium-binding adapter molecule 1. Rats that received unilateral CCI were impaired on the PAL task and showed more aberrant response-driven behavior. The magnitude of PAL impairment was also correlated with Iba1 staining in the thalamus. These observations suggest that PAL could be useful for pre-clinical assessments of novel interventions for treating TBI., Competing Interests: Conflict of interest Authors report no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Synovial sarcoma is a rare soft tissue sarcoma which frequently involves the upper or lower extremities. Soft tissue sarcomas including synovial sarcoma have a propensity to metastasize to the lungs, and there are very few reports of metastatic lesions in other locations.Here, we report a case of a 49-year-old patient who underwent neoadjuvant chemoradiation for an upper extremity synovial sarcoma and presented approximately 4 years later with abdominal pain and hemoperitoneum and was ultimately found to have metastatic synovial sarcoma involving the greater curvature of the stomach and surrounding peri-gastric soft tissue. We describe the multidisciplinary management of this complex patient presentation and propose that expanded surveillance imaging beyond that of the local tumor resection bed and the chest may be beneficial especially in tumors with high-risk features., (© 2023. The Author(s).)

Fruit and Vegetable Prescription (FVRx) programs rely on diverse community and clinic partnerships to improve food security and fruit and vegetable consumption among medically underserved patient populations. Despite the growth in these programs, little is known about the feasibility or effectiveness of the unique partnerships developed to implement FVRx programs conducted in both community and free safety-net clinic settings. A 6-month nonrandomized controlled trial of an FVRx program was pilot tested with 54 Supplemental Nutrition Assistance Program (SNAP)-eligible adults with diet-related chronic conditions. The intervention combined monthly produce prescriptions for local produce at a farmers market, SNAP-Ed direct nutrition education, and health screenings for low-income adults. Process and outcome evaluations were conducted with respective samples using administrative program data (recruitment, retention, and prescription redemption) and self-administered pre- and postintervention surveys with validated measures on dietary intake, nutrition knowledge and behavior, and food purchasing practices. Descriptive statistical analyses were conducted. The FVRx program retained 77.3% of participants who spent nearly 90% of their prescription dollars. After the intervention, the FVRx group reported significantly increased total intake of fruits and vegetables, knowledge of fresh fruit and vegetable preparation, purchase of fresh fruits and vegetables from a farmers market, and significantly altered food purchasing practices compared with the control group. Community-based nutrition education organizations enhance the feasibility and effectiveness of community and clinic-based FVRx programs for improving low-income adults' ability to enhance food and nutrition-related behaviors.

Objective: To examine Fruit and Vegetable Prescription (FVRx) Program participants' and nonparticipants' experiences and perceptions of farm direct (FD) settings., Design: Multiple-case study of adults with low income from 3 study groups: (1) FVRx intervention (produce prescription, nutrition education [NE], financial literacy education, health screening), (2) NE only, and (3) control (standard health care). Participant interviews with each group at baseline and 6 months., Setting: Supplemental Nutrition Assistance Program-Education (SNAP-Ed) eligible adults from 3 Georgia counties., Participants: A total of 46 adults with ≥ 1 diet-related condition., Phenomena of Interest: Fruit and Vegetable Prescription Program participant and nonparticipant experiences and perceptions of FD settings., Analysis: Constant comparative methods and thematic analysis of qualitative interview data across groups., Findings: Two main themes emerged: (1) baseline FD setting experiences and perceptions and (2) divergent experiences and perceptions with FD settings postintervention. Participants across each group employed price-conscious food purchasing practices because of limited food budgets, limiting local food access. Combining produce prescription, NE, and farmers' market access enhanced FVRx participant associations with FD settings to reinforce motivation for accessing and purchasing fruits and vegetables beyond program participation., Conclusions and Implications: Fruit and Vegetable Prescription Programs reduce multiple barriers to participating in FD settings compared with NE or standard health care alone., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

The Pantanal wetland harbours the second largest population of jaguars in the world. Alongside climate and land-use changes, the recent mega-fires in the Pantanal may pose a threat to the jaguars' long-term survival. To put these growing threats into perspective, we addressed the reach and intensity of fires that have affected jaguar conservation in the Pantanal ecoregion over the last 16 years. The 2020 fires were the most severe in the annual series, burned 31% of the Pantanal and affected 45% of the estimated jaguar population (87% of these in Brazil); 79% of the home range areas, and 54% of the protected areas within home ranges. Fires consumed core habitats and injured several jaguars, the Pantanal's apex predator. Displacement, hunger, dehydration, territorial defence, and lower fecundity are among the impacts that may affect the abundance of the species. These impacts are likely to affect other less mobile species and, therefore, the ecological stability of the region. A solution to prevent the recurrence of mega-fires lies in combating the anthropogenic causes that intensify drought conditions, such as implementing actions to protect springs, increasing the number and area of protected areas, regulating fire use, and allocating fire brigades before dry seasons., (© 2022. The Author(s).)

The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of "NASH-associated macrophages" can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH., (© 2022. The Author(s).)

Fate-determining transcription factors (TFs) can promote lineage-restricted transcriptional programs from common progenitor states. The inner cell mass (ICM) of mouse blastocysts co-expresses the TFs NANOG and GATA6, which drive the bifurcation of the ICM into either the epiblast (Epi) or the primitive endoderm (PrE), respectively. Here, we induce GATA6 in embryonic stem cells-that also express NANOG-to characterize how a state of co-expression of opposing TFs resolves into divergent lineages. Surprisingly, we find that GATA6 and NANOG co-bind at the vast majority of Epi and PrE enhancers, a phenomenon we also observe in blastocysts. The co-bound state is followed by eviction and repression of Epi TFs, and quick remodeling of chromatin and enhancer-promoter contacts thus establishing the PrE lineage while repressing the Epi fate. We propose that co-binding of GATA6 and NANOG at shared enhancers maintains ICM plasticity and promotes the rapid establishment of Epi- and PrE-specific transcriptional programs., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a 'ground truth' epigenomic landscape at this critical stage of neurogenesis., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The true prevalence of COVID-19 is difficult to estimate due to the absence of random population-based testing. To estimate current and past COVID-19 infection prevalence in a large urban area, we conducted a population-based survey in St. Louis County, Missouri., Methods: The population-based survey of active infection (PCR) and seroprevalence (IgG antibodies) of adults (≥18 years) was conducted through random-digit dialing and targeted sampling of St. Louis County residents with oversampling of Black residents. Infection prevalence of residents was estimated using design-based and raking weighting., Results: Between August 17 and October 24, 2020, 1245 residents completed a survey and underwent PCR testing; 1073 residents completed a survey and underwent PCR and IgG testing or self-reported results. Weighted prevalence estimates of residents with active infection were 1.9% (95% CI, 0.4%-3.3%) and 5.6% were ever infected (95% CI, 3.3%-8.0%). Overall infection hospitalization and fatality ratios were 4.9% and 1.4%, respectively., Conclusions: Through October 2020, the percentage of residents that had ever been infected was relatively low. A markedly higher percentage of Black and other minorities compared to White residents were infected with COVID-19. The St. Louis region remained highly vulnerable to widespread infection in late 2020., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

It is well established that degradation of perforant path fibers is associated with age-related cognitive dysfunction and CA3 hyperactivity. Whether this fiber loss triggers a cascade of other functional changes within the hippocampus circuit has not been causatively established, however. Thus, the current study evaluated the effect of perforant path fiber loss on neuronal activity in CA3 and layer II of the lateral entorhinal cortex (LEC) in relation to mnemonic similarity task performance. Expression of the immediate early gene Arc was quantified in rats that received a unilateral right hemisphere transection of the perforant path or sham surgery that cut the cortex but left the fibers intact. Behavior-related expression of Arc mRNA was measured to test the hypothesis that fiber loss leads to elevated activation of CA3 and LEC neurons, as previously observed in aged rats that were impaired on the mnemonic similarity task. Transection of perforant path fibers, which has previously been shown to lead to a decline in mnemonic similarity task performance, did not alter Arc expression. Arc expression in CA3, however, was correlated with task performance on the more difficult discrimination trials across both surgical groups. These observations further support a link between CA3 activity and mnemonic similarity task performance but suggest the reduced input from the entorhinal cortex to the hippocampus, as observed in old age, does not causatively elevate CA3 activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cooper, Thompson, Turner, Watson, Lubke, Logan, Maurer and Burke.)

Objectives: The coronavirus disease of 2019 (COVID-19) pandemic declared by the World Health Organization on March 11, 2020 impacted healthcare services with provider and patient cancellations, delays, and patient avoidance or delay of emergency department or urgent care. Limited data exist on the population proportion affected by delayed healthcare, which is important for future healthcare planning efforts. Our objective was to evaluate the impact of the COVID-19 pandemic on healthcare service cancellations or delays and delays/avoidance of emergency/urgent care overall and by population characteristics., Study Design: This was a cross-sectional study., Methods: Our sample (n = 2314) was assembled through a phone survey from 8/12/2020-10/27/2020 among non-institutionalized St. Louis County, Missouri, USA residents ≥18 years. We asked about provider and patient-initiated cancellations or delays of appointments and pandemic-associated delays/avoidance of emergency/urgent care overall and by participant characteristics. We calculated weighted prevalence estimates by select resident characteristics., Results: Healthcare services cancellations or delays affected ∼54% (95% CI 50.6%-57.1%) of residents with dental (31.1%, 95% CI 28.1%-34.0%) and primary care (22.1%, 95% CI 19.5%-24.6%) being most common. The highest prevalences were among those who were White, ≥65 years old, female, in fair/poor health, who had health insurance, and who had ≥1 medical condition. Delayed or avoided emergency/urgent care impacted ∼23% (95% CI 19.9%-25.4%) of residents with a higher prevalence in females than males., Conclusions: Healthcare use disruptions impacted a substantial proportion of residents. Future healthcare planning efforts should consider these data to minimize potential morbidity and mortality from delayed care., (© 2022 The Author(s).)

Objective: To understand the design and implementation models of US produce prescription programs., Methods: In a mixed-methods study, program providers completed an online survey and an individual phone interview regarding their 2019 programming., Results: Twenty-three programs completed surveys; 20 completed interviews. Program locations included the mid-Atlantic (26%), Northeast (9%), Midwest (30%), Southwest (17%), and Western regions (17%). Although program models varied, programs generally included a health care visit, usually at a safety-net clinic, and nutrition education, typically counseling, advice, or classes. Prescriptions tended to be farmers market vouchers worth a median of $15 a week (interquartile range, $7.81-$20.00). Transportation was a problem for nearly half of the programs., Conclusions and Implications: Current produce prescription program characteristics and operations can serve as a blueprint for new and existing programs. Future research should determine program best practices and the opportunity cost between program standardization and local flexibilities., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract., Methods: Transgenic Gpr64 mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire of intestinal Gpr64 mCherry -positive tuft cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64 mCherry was crossed into the general tuft cell reporter Trpm5 GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNA-seq analysis., Results: Expression of the Gpr64 mCherry reporter was identified in multiple organs and specifically in olfactory microvillous cells, enteric nerves, and importantly in respiratory and GI tuft cells. In the small intestine, cell ablation targeting Gpr64-expressing epithelial cells eliminated tuft cells. Transcriptional analysis of small intestinal Gpr64 mCherry -positive tuft cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5 GFP :Gpr64 mCherry mice revealed sequential expression of initially Trpm5 GFP and subsequently also Gpr64 mCherry in maturing intestinal tuft cells. RNA-seq analysis of small intestinal tuft cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft cells., Conclusions: GPR64 is expressed in chemosensory epithelial cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft cells., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: AOAC Method 2015.06 is a Final Action Official MethodSM for the determination of 12 elements (Na, Mg, P, K, Ca, Cr, Mn, Fe, Cu, Zn, Se, and Mo) in infant formula and adult nutritional products, based on inductively coupled plasma (ICP)-MS. Currently, its scope does not include certain kinds of formulations used in India. The method would likely be used more in Indian laboratories if its performance were characterized on Indian matrixes., Objective: In this study we describe a typical single-laboratory validation (SLV) exercise designed to characterize the precision and accuracy of AOAC Method 2015.06 for common Indian nutritional matrixes so that the scope of the method can be extended to include them., Method: Six matrixes specific to the Indian market were carried through an SLV and the Standard Method Performance Requirements (SMPRs®) previously published for this method were used to evaluate the results., Results: The method demonstrated typical repeatability (<5% RSD), and intermediate precision (5-8% RSD) on the Indian matrixes, with very few exceptions. Accuracy was demonstrated by overspike recoveries in the range of 90-110% over 3 days for the Indian matrixes, as well as excellent agreement with previously published results for three additional matrixes tested. Some of the new Indian matrixes required alternate sample preparation procedures versus the usual reconstitution prescribed by the SMPRs., Conclusions: The SLV results showed that AOAC Method 2015.06 can be extended to include these Indian matrices., Highlights: The two special sample preparation procedures can now be considered validated., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Large terrestrial carnivores have undergone some of the largest population declines and range reductions of any species, which is of concern as they can have large effects on ecosystem dynamics and function. 1-4 The jaguar (Panthera onca) is the apex predator throughout the majority of the Neotropics; however, its distribution has been reduced by >50% and it survives in increasingly isolated populations. 5 Consequently, the range-wide management of the jaguar depends upon maintaining core populations connected through multi-national, transboundary cooperation, which requires understanding the movement ecology and space use of jaguars throughout their range. 6-8 Using GPS telemetry data for 111 jaguars from 13 ecoregions within the four biomes that constitute the majority of jaguar habitat, we examined the landscape-level environmental and anthropogenic factors related to jaguar home range size and movement parameters. Home range size decreased with increasing net productivity and forest cover and increased with increasing road density. Speed decreased with increasing forest cover with no sexual differences, while males had more directional movements, but tortuosity in movements was not related to any landscape factors. We demonstrated a synergistic relationship between landscape-scale environmental and anthropogenic factors and jaguars' spatial needs, which has applications to the conservation strategy for the species throughout the Neotropics. Using large-scale collaboration, we overcame limitations from small sample sizes typical in large carnivore research to provide a mechanism to evaluate habitat quality for jaguars and an inferential modeling framework adaptable to the conservation of other large terrestrial carnivores., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With the broader introduction of genomic medicine in research and clinical care, an increasing number of persons are offered genetic testing. Many factors, including genetic literacy, may impact the utilization of genetic results by patients and their families. We developed a rapid, self-administered measure of genetic literacy, called Genetic Literacy Fast Test (GeneLiFT). We next evaluated the association of GeneLiFT scores with the comprehension of limitations of genomic medicine in participants undergoing genetic testing in the NIH-sponsored eMERGE III study at Columbia University Irving Medical Center, New York. All participants underwent genetic screening for variants in 74 actionable genes associated with adult-onset disorders. A diverse cohort of 724 participants completed the survey (60% women, 45% less than 40 years old, and 53% self-reported White non-Hispanic ancestry). The GeneLiFT was validated using known group differences based on education, health literacy, and numeracy, and with questions assessing genetic knowledge. GeneLiFT identified multiple standard genetics terms, that is, jargon, not recognized by more than 50% of participants (including actionability and pathogenicity). Low genetic literacy, identified in 210 participants (29%), was significantly associated with poor understanding of the limitations of genetic testing (p-values < 10 -9 ). This association was independent of education, health literacy, and numeracy levels, highlighting the importance of directly measuring genetic literacy. Low genetic literacy was also associated with low satisfaction with the informed consent process. GeneLiFT is a practical tool for rapid assessment of genetic literacy in large studies or clinical care. GeneLiFT will allow future research to efficiently assess the role of genetic literacy on the clinical impact of genetic testing., (© 2020 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Objective: The purpose of this paper is to describe a participant-driven, online text message-based social support network that emerged from an eLearning nutrition education and supplemental produce intervention., Methods: Adults (n = 20) who utilized a safety-net clinic for their healthcare participated in a 12-week smartphone-based nutrition education eLearning program using loaned smartphones. Participants also received a box of fresh produce weekly. Participants received weekly text message reminders to collect their produce, and from this researcher-initiated reminder text, a supportive, participant-led, all-group text message thread commenced. Researchers collected all 471 text messages in this all-group thread and included them in the qualitative content analysis of pre and post intervention focus groups., Results: The original design of the eLearning nutrition education program was to asynchronously engage learners with nutrition education resources. However, participants themselves initiated a robust group text message support system through which they shared encouragement, recipes, grocery shopping tips, and images of food they prepared with the produce box amongst themselves for the duration of the 12-week intervention., Conclusion: The novel nature by which these participants voluntarily engaged in this peer-to-peer nutrition education-focused text message conversation exemplifies participants becoming agents in their own learning experience and will be used to enhance future eLearning nutrition education experiences developed by our team., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: The goal of this study was to investigate the importance of central hormone-sensitive lipase (HSL) expression in the regulation of food intake and body weight in mice to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite., Methods: Using pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis under basal conditions during acute stress and high-fat diet feeding., Results: We found that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers in the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout, or brain-specific deletion of HSL prevents a decrease in food intake normally seen in response to acute stress and is associated with the increased expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP). Increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity., Conclusions: Our results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and sensing of a high-fat diet., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with multiple congenital anomalies caused by hemizygous variants in OTUD5 , encoding a K48/K63 linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of select chromatin regulators (e.g., ARID1A/B, histone deacetylase 2, and HCF1), mutations of which underlie diseases that exhibit phenotypic overlap with OTUD5 patients. Loss of OTUD5 during differentiation leads to less accessible chromatin at neuroectodermal enhancers and aberrant gene expression. Our study describes a previously unidentified disorder we name LINKED (LINKage-specific deubiquitylation deficiency-induced Embryonic Defects) syndrome and reveals linkage-specific ubiquitin cleavage from chromatin remodelers as an essential signaling mode that coordinates chromatin remodeling during embryogenesis., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Biology research is becoming increasingly dependent on large-scale, "big data," networked research initiatives. At the same time, there has been a corresponding effort to expand undergraduate participation in research to benefit student learning and persistence in science. This essay examines the confluence of this trend through eight years of a collaboration within a successful biology research network that explicitly incorporates undergraduates into large-scale scientific research. We draw upon interviews with faculty in this network to consider the interplay of scientific and pedagogical objectives at the heart of this undergraduate-focused network research project. We identify ways that this network has expanded and diversified access to scientific knowledge production for faculty and students and examine a goal conflict that emerged around the dual objectives of mentoring emerging scientists while producing high-quality scientific data for the larger biology community. Based on lessons learned within this network, we provide three recommendations that can support institutions and faculty engaging in networked research projects with undergraduates: (1) establish rigorous protocols to ensure data and database quality, (2) protect personnel time to coordinate network and scientific processes, and (3) select appropriate partners and establish explicit expectations for specific collaborations.

Background & Purpose: Pandemics such as COVID-19 can lead to severe shortages in healthcare resources, requiring the development of evidence-based Crisis Standard of Care (CSC) protocols. A protocol that limits the resuscitation of out-of-hospital cardiac arrests (OHCA) to events that are more likely to result in a positive outcome can lower hospital burdens and reduce emergency medical services resources and infection risk, although it would come at the cost of lives lost that could otherwise be saved. Our primary objective was to evaluate candidate OHCA CSC protocols involving known predictors of survival and identify the protocol that results in the smallest resource burden, as measured by the number of hospitalizations required per favorable OHCA outcome achieved. Our secondary objective was to describe the effects of the CSC protocols in terms of health outcomes and other measures of resource burden., Methods: We conducted a retrospective cohort study of adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) database. Non-traumatic OHCA events from 2018 were included (n = 79,533). Candidate CSC protocols involving combinations of known predictors of good survival for OHCA were applied to the existing dataset to measure the resulting numbers of resuscitation attempts, transportations to hospital, hospital admissions, and favorable neurological outcomes. These outcomes were also assessed under Standard Care, defined as no CSC protocol applied to the data., Results: The CSC protocol with the smallest number of hospitalizations per survivor with a favorable neurological outcome was that an OHCA resuscitation should only be attempted if the arrest was witnessed by emergency medical services or the first monitored rhythm was shockable (number of hospitalizations: 2.26 [95% CI: 2.21-2.31] vs. 3.46 [95% CI: 3.39-3.53] under Standard Care). This rule resulted in significant reductions in resource utilization (46.1% of hospitalizations and 29.2% of resuscitation attempts compared to Standard Care) while still preserving 70.5% of the favorable neurological outcomes under Standard Care. For every favorable neurological outcome lost under this CSC protocol, 6.3 hospital beds were made free that could be used to treat other patients., Conclusion: In a pandemic scenario, pre-hospital CSC protocols that might not otherwise be considered have the potential to greatly improve overall survival, and this study provides an evidence-based approach towards selecting such a protocol. As this study was performed using data generated before the COVID-19 pandemic, future studies incorporating pandemic-era data will further help develop evidence-based CSC protocols., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data., (© 2020 The Authors. Ecology © 2020 The Ecological Society of America.)

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6&#95;Fezf2 and L2-3&#95;Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.

The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system cell types spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >457,000 individuals. Developing a novel strategy for integrating scRNA-seq data with GWAS data, we identified 26, exclusively neuronal, cell types from the hypothalamus, subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (p<1.6×10 -4 ). Using genes harboring coding mutations associated with obesity, we replicated midbrain cell types from the anterior pretectal nucleus and periaqueductal gray (p<1.2×10 -4 ). Together, our results suggest that brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies., Competing Interests: PT, JT, TP No competing interests declared, (© 2020, Timshel et al.)

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum., (© 2020 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)