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Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis. Across solid tumor types, F1CDx demonstrated a high analytical concordance with both PCR (n = 264) and IHC (n = 279) with an overall percent agreement (OPA) of 97.7% and 97.8%, respectively. As part of a retrospective bridging clinical study from KEYNOTE-158 Cohort K and KEYNOTE-164, patients with MSI-H tumors as determined by F1CDx demonstrated an objective response rate (ORR) of 43.0% to pembrolizumab. In real-world cancer patients from a deidentified clinicogenomic database, F1CDx was at least equivalent in assessing clinical outcome following immunotherapy compared with MMR IHC. Demonstrated analytical and clinical performance of F1CDx led to the pan-tumor FDA approval in 2022 of F1CDx to identify MSI-H solid tumor patients for treatment with pembrolizumab. F1CDx is an accurate, reliable, and FDA-approved method for the identification of MSI-H tumors for treatment with pembrolizumab. [ABSTRACT FROM AUTHOR]

The neocortex varies in size and complexity among mammals due to the tremendous variability in the number and diversity of neuronal subtypes across species. The increased cellular diversity is paralleled by the expansion of the pool of neocortical progenitors and the emergence of indirect neurogenesis during brain evolution. The molecular pathways that control these biological processes and are disrupted in neurological disorders remain largely unknown. Here we show that the transcription factors BRN1 and BRN2 have an evolutionary conserved function in neocortical progenitors to control their proliferative capacity and the switch from direct to indirect neurogenesis. Functional studies in mice and ferrets show that BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate progenitor behavior. Analysis of transcriptomics data from genetically modified macaques provides evidence that these molecular pathways are conserved in non-human primates. Our findings thus demonstrate that BRN1/2 are central regulators of gene expression programs in neocortical progenitors critical to determine brain size during evolution. How the diversity and number of neuronal subtypes across species drives neocortical size and complexity remains incompletely understood. Here authors demonstrate BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate evolutionarily conserved neocortical progenitor behavior across species and determine brain size. [ABSTRACT FROM AUTHOR]

Purpose of Review: This paper aims to investigate the crucial role of palliative care in the management of chronic liver disease (CLD) and cirrhosis. Faced with a global surge in liver-related morbidity and mortality, our goal is to understand the impact of early engagement with palliative care specialists on symptom management, quality of life, and the overall trajectory of advanced liver disease. Recent Findings: While strides have been made in preventing and treating specific etiologies of CLD, such as viral infections, the escalating rates of alcohol use and obesity present new challenges for physicians. Despite advancements, liver transplantation unfortunately remains an elusive solution for many due to various constraints. Our review underscores the underutilization of palliative care in this context, emphasizing its potential to mitigate symptoms and enhance the overall well-being of patients and their caregivers. Summary: Implementing palliative care early during CLD proves instrumental in reducing symptoms, hospitalizations, and resource utilization. This not only improves the quality of life for patients but also signifies a paradigm shift in approaching the uncertainties surrounding advanced liver disease. Urging further research and global initiatives, our findings advocate for a comprehensive integration of palliative care in the holistic management of patients with advanced liver disease. [ABSTRACT FROM AUTHOR]

Artificial neural networks, deep-learning methods and the backpropagation algorithm1 form the foundation of modern machine learning and artificial intelligence. These methods are almost always used in two phases, one in which the weights of the network are updated and one in which the weights are held constant while the network is used or evaluated. This contrasts with natural learning and many applications, which require continual learning. It has been unclear whether or not deep learning methods work in continual learning settings. Here we show that they do not—that standard deep-learning methods gradually lose plasticity in continual-learning settings until they learn no better than a shallow network. We show such loss of plasticity using the classic ImageNet dataset and reinforcement-learning problems across a wide range of variations in the network and the learning algorithm. Plasticity is maintained indefinitely only by algorithms that continually inject diversity into the network, such as our continual backpropagation algorithm, a variation of backpropagation in which a small fraction of less-used units are continually and randomly reinitialized. Our results indicate that methods based on gradient descent are not enough—that sustained deep learning requires a random, non-gradient component to maintain variability and plasticity.The pervasive problem of artificial neural networks losing plasticity in continual-learning settings is demonstrated and a simple solution called the continual backpropagation algorithm is described to prevent this issue. [ABSTRACT FROM AUTHOR]

The retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a high DHA content is important for vision, surprisingly little is known about the mechanisms of DHA enrichment in the retina. Furthermore, the biological processes controlled by DHA in the eye remain poorly defined as well. Here, we combined genetic manipulations with lipidomic analysis in mice to demonstrate that acyl-CoA synthetase 6 (Acsl6) serves as a regulator of the unique composition of retinal membranes. Inactivation of Acsl6 reduced the levels of DHA-containing phospholipids, led to progressive loss of light-sensitive rod photoreceptor neurons, attenuated the light responses of these cells, and evoked distinct transcriptional response in the retina involving the Srebf1/2 (sterol regulatory element binding transcription factors 1/2) pathway. This study identifies one of the major enzymes responsible for DHA enrichment in the retinal membranes and introduces a model allowing an evaluation of rod functioning and pathology caused by impaired DHA incorporation/retention in the retina. Acyl-CoA synthetase 6 (Acsl6)-facilitated enrichment of docosahexaenoic acid (DHA) in the retina is essential for rod photoreceptor function, viability and control of basal activity of the Srebf1/2 pathway. [ABSTRACT FROM AUTHOR]

Agricultural environments are becoming increasingly contaminated with plastic pollution. Plastics in the environment can also provide a unique habitat for microbial biofilm, termed the 'plastisphere', which can also support the persistence of human pathogens such as Salmonella. Human enteric Salmonella enterica serovar Typhimurium can enter agricultural environments via flooding or from irrigation with contaminated water. Using soil mesocosms we quantified the ability of S. Typhimurium to persist on microplastic beads in two agriculturally relevant soils, under ambient and repeat flood scenarios. S. Typhimurium persisted in the plastisphere for 35 days in both podzol and loamy soils; while during multiple flood events was able to survive in the plastisphere for up to 21 days. S. Typhimurium could dissociate from the plastisphere during flooding events and migrate through soil in leachate, and importantly could colonise new plastic particles in the soil, suggesting that plastic pollution in agricultural soils can aid S. Typhimurium persistence and facilitate further dissemination within the environment. The potential for increased survival of enteric human pathogens in agricultural and food production environments due to plastic contamination poses a significant public health risk, particularly in potato or root vegetable systems where there is the potential for direct contact with crops. [ABSTRACT FROM AUTHOR]

Little is known of the macrobenthos supported within stingray feeding pits. Compared to adjacent unpitted areas during low tide, macrobenthic abundance and biodiversity within the stingray pits might be expected to be (i) greater, the water-retaining pits functioning like rock pools; (ii) no different, since macrofaunal recolonisation can occur very rapidly; or (iii) less, consequent on the substratum changes that typify depressions in soft sediments. In both (i) and (iii) differences in composition of the supported assemblages would be expected, though not in (ii). To differentiate between these alternative hypotheses, faunal characteristics within intertidal stingray pits were compared to those in the adjacent background sandflat in Moreton Bay, Queensland, where the prey of the rays are the decapod crustaceans Trypaea and Mictyris that otherwise structure the benthic system. Results generally (though not totally) support hypothesis (ii), it being consistently found that feeding pits supported less macrobenthic abundance than the surrounding sandflat but subequal taxon density, evenness and patchiness of their faunas, and their taxonomic compositions were very similar. Such feeding pits undoubtedly structure many intertidal sandflats and increase both their topographical complexity and their habitat diversity, but this is not reflected in increased macrobenthic biodiversity. [ABSTRACT FROM AUTHOR]

We introduce an hp-version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and hp-version a priori error analysis of the proposed method, by deriving suitable hp-approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented. [ABSTRACT FROM AUTHOR]

Clonal hematopoiesis, the expansion of blood stem cells with oncogenic mutations, is associated with an increased risk of hematological cancers and non-hematological conditions like cardiovascular disease. This study used Mendelian randomization to investigate modifiable risk factors for clonal hematopoiesis. The researchers found no significant relationship between clonal hematopoiesis and genetically predicted lifetime smoking, dietary intake, or levels of fatty acids and lipoproteins or inflammatory factors. However, there was an association between clonal hematopoiesis and genetically predicted levels of vitamins B6 and B12, as well as basal metabolic rate. The study provides insight into the etiology of clonal hematopoiesis and suggests that these modifiable traits may not be major risk factors for its development. [Extracted from the article]

Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima. The development related myb-like 1 (drmy1) mutant generates noise in auxin signaling that disrupts robustness in sepal initiation. Here, we find that increased expression of CUP-SHAPED COTYLEDON1 (CUC1), a boundary specification transcription factor, in drmy1 underlies this loss of robustness. CUC1 surrounds and amplifies stochastic auxin noise in drmy1 to form variably positioned auxin maxima and sepal primordia. Removing CUC1 from drmy1 provides time for noisy auxin signaling to resolve into four precisely positioned auxin maxima, restoring robust sepal initiation. However, removing CUC1 decreases the intensity of auxin maxima and slows down sepal initiation. Thus, CUC1 increases morphogenesis speed but impairs robustness against auxin noise. Further, using a computational model, we find that the observed phenotype can be explained by the effect of CUC1 in repolarizing PIN FORMED1 (PIN1), a polar auxin transporter. Lastly, our model predicts that reducing global growth rate improves developmental robustness, which we validate experimentally. Thus, our study illustrates a tradeoff between speed and robustness during development. Morphogenesis speed may be antagonistic to its robustness. In an Arabidopsis flower, the transcription factor CUC1 increases the speed of sepal initiation but can disrupt its robustness against stochastic auxin noise. Removing CUC1 reduces morphogenesis speed but improves robustness. [ABSTRACT FROM AUTHOR]

Background: Obesity and its related medical conditions are well-established contributors to the development of chronic kidney disease (CKD). Metabolic and bariatric surgery (MBS), including procedures such as sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is a potential intervention for these individuals. However, the heightened risk of postoperative complications casts doubts on the suitability of MBS in this population. Our aim is to evaluate the long-term safety, anthropometric and renal outcomes of MBS in patients with CKD. Methods: A retrospective review of patients who underwent primary laparoscopic MBS with a BMI ≥ 35 kg/m2 and a preoperative diagnosis of stage 2 to 5 CKD. Criteria for CKD diagnosis and staging were based on estimated glomerular filtration rate measurements in accordance with established guidelines. Anthropometric and renal outcomes were measured at 3-, 6-, 12-, 24- and 60-months postoperatively. Results: A total of 302 patients (177 SG, 125 RYGB) were included. RYGB was preferred for patients with stage 3 CKD, while SG was more common in stages 4 and 5. At 5-year follow-up, percentage of total weight loss was higher in the RYGB cohort compared to SG (25.1% vs. 18.6%, p = 0.036). Despite SG patients having more advanced CKD, the incidence of late complications was significantly higher following RYGB, with 11 incidents (8.8%), compared to the SG cohort with only 4 cases (2.3%) (p = 0.014). In those with preoperative CKD stage 3, 76 patients (43.2%) improved to stage 2, with another 9 patients (5.1%) improving further to stage 1. Of all patients, 63 (20.8%) eventually received a successful renal transplant. Conclusions: MBS is an effective strategy for sustained weight loss in patients with CKD with acceptable complications rates. RYGB leads to a higher percentage of overall weight loss, albeit with an elevated likelihood of late surgical complications. Future studies are needed to determine the safety of MBS in this demographic. [ABSTRACT FROM AUTHOR]

Lower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). This study quantifies the effect of LBNP on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP). Twenty-four subjects (12 male, 12 female) were subjected to graded LBNP in 0° supine and 15° head-down tilt (HDT) postures from 0 mmHg to –50 mmHg in 10 mmHg increments. IOP decreased significantly with LBNP pressure in 0° supine (by 0.7 ± 0.09 mmHg per 10 mmHg LBNP pressure, p < 0.001) and in 15° HDT (by 1.0 ± 0.095 mmHg per 10 mmHg of LBNP pressure, p < 0.001). MAPeye significantly decreased by 0.9 ± 0.4 mmHg per 10 mmHg of LBNP pressure in 0° supine (p = 0.016) but did not significantly change with LBNP in 15° HDT (p = 0.895). OPP did not significantly change with LBNP in 0° supine (p = 0.539) but it significantly increased in 15° HDT at 1.0 ± 0.3 mmHg per 10 mmHg of LBNP pressure (p = 0.010). Sex did not have a significant effect on OPP, MAPeye, or IOP in any condition. In 15° HDT, the reduction in IOP during increasing negative pressure, combined with the relatively constant MAPeye, led to the increase in OPP. Furthermore, results suggest that LBNP, while effective in reducing IOP, is not effective in reducing OPP across all postures investigated. [ABSTRACT FROM AUTHOR]

This article discusses the importance of medication optimization in improving the recovery of patients in intensive care units (ICUs). It highlights the need for close monitoring and tailored care, including medication, during the critical illness and beyond the ICU. The article emphasizes the common problem of inappropriate continuation of medication after ICU discharge, particularly psychotropic medicines, and the negative consequences it can have on patient outcomes and healthcare utilization. The authors suggest implementing evidence-based bundled care, improving medication reconciliation and review processes, enhancing communication and education, and engaging patients and families in shared decision-making to optimize medication regimens and improve patient recovery. [Extracted from the article]

The increasing atmospheric concentrations of greenhouse gases will place humans in climates that are unprecedented in the evolution of the species. I use the ecological definition of the human niche in climate space, and combine this with a new constellation of methods from extreme value statistics to study human occupation near the boundaries of that niche. I find that the temperature distribution has a thin tail whereas the tail of precipitation is thick. This thick tail reflects that humans are used to a wide range of rainfall regimes, so future precipitation changes, although leading to unprecedented rainfall, are less likely to pose a major challenge. An increase in temperature, on the other hand, will put hundreds of millions of people in heat that is not just unprecedented and but also hard to imagine from extrapolating current temperatures. These findings are qualitatively similar but an order of magnitude smaller than previous studies. [ABSTRACT FROM AUTHOR]

We assess the impact of changes in oil prices on building permit applications in the top oil-producing counties, using monthly data between 2004 and 2021. In the long-run, a positive shock in oil prices increases the number of home permit applications in Lea and McKenzie Counties. Long-run point estimates also reveal that a 10 percent increase in oil prices reduces building plans by 2 and 3.4 percent in Kern and Oklahoma Counties, respectively. In Midland and McKenzie Counties, only long-run changes in oil prices impact home investment decisions while short-run changes have no impact. The inverse relationship between oil prices and permit applications hints that investors may dampen construction plans in lieu of higher costs of raw materials during periods of higher energy prices. Threshold Autoregressive model findings demonstrate that changes in permit applications occur during periods of high oil prices. Our findings imply that the expansionary monetary or fiscal policies that would be required to revive the housing market would need to be regime and region specific. Thus, coordination between regional lending units and investors is important and can boost recoveries from economic downturns. [ABSTRACT FROM AUTHOR]

Background: Many individuals with systemic sclerosis (SSc) are at heightened risk for COVID-19 related morbidity and isolation due to interstitial lung disease, frailty, and immunosuppressant use. Minimal research has explored loneliness predictors in individuals with chronic illnesses during COVID-19. This study evaluated moderators of loneliness trajectories in individuals with SSc during COVID-19. Methods: Longitudinal data were analyzed across 30 timepoints from April 2020 to May 2022 from 775 adults in the Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 Cohort. Hierarchical linear modeling evaluated cross-level moderators of loneliness trajectories, including marital status, baseline number of household members, number of virtual or telephone one-on-one or virtual group conversations, number of hours spent enjoying in-person household conversations or activities, and satisfaction with quality of in-person household conversations (all in the past week). Level-1 moderation analyses assessed effects of conversation, activity, and satisfaction means and slopes over time. Results: Baseline values were not statistically significant moderators of loneliness trajectories. Higher mean (averaged over time) virtual or telephone one-on-one and in-person household conversations, in-person household activity, and in-person household conversation satisfaction were associated with lower loneliness trajectories (ps <.05). The relationship between in-person household conversation satisfaction and loneliness trajectory was statistically significantly but minimally attenuated over time (p <.001). Conclusions: For people with SSc, higher mean conversation, activity, and satisfaction variables were associated with lower levels of loneliness during the pandemic, but changes in these social variables were generally not predictive of changes in loneliness. [ABSTRACT FROM AUTHOR]

We note that the atmosphere has distinct tropical and extratropical regimes. The tropical regime is significantly dependent on the greenhouse effect and is characterized by temperatures that are largely horizontally homogenized. The extratropical regime is dominated by large scale unstable convective eddies that transport heat between the tropics and the poles (leaving the poles warmer than they otherwise would be) and serve to determine the temperature difference between the tropics and the poles. Changes in tropical temperature and in the tropics-to-pole temperature difference both contribute to changes in global mean temperature. It turns out that changes in global mean temperature associated with major climate change (i.e., the last glacial maximum and the warm period of the Eocene about 50 million years ago) were associated primarily with changes in the tropics-to-pole temperature differences. By contrast, changes in global mean temperature over the past 150 years or so are almost entirely associated with changes in tropical temperature. Thus, there is no intrinsic amplification associated with a change in the tropics-to-pole temperature difference. However, model simulations of climate behave differently from both observations and from each other. In particular, they all show more significant contributions for the tropics-to-pole temperature difference – sometimes much more significant. They also show excessive tropical warming. [ABSTRACT FROM AUTHOR]

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography. [ABSTRACT FROM AUTHOR]

Background: Human epidermal growth factor-2 (HER2) overexpression is an oncogenic driver in many solid tumors, including urothelial bladder cancer (UBC). In addition, activating mutations in the ERBB2 gene have been shown to play an oncogenic role similar to ERBB2 amplification. Objective: To describe and compare the frequency and nature of genomic alterations (GA) of ERBB2-altered (mutations, amplification) and ERBB2 wild-type UBC. Patients and Methods: Using a hybrid capture-based comprehensive profiling assay, 9518 UBC cases were grouped by ERBB2 alteration and evaluated for all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genome-wide loss of heterozygosity (gLOH), and genomic mutational signature. PD-L1 expression was measured by immunohistochemistry (Dako 22C3). Categorical statistical comparisons were performed using Fisher's exact tests. Results: A total of 602 (6.3%) UBC cases featured ERBB2 extracellular domain short variant (SV) GA (ECDmut+), 253 (2.7%) cases featured ERBB2 kinase domain SV GA (KDmut+), 866 (9.1%) cases had ERBB2 amplification (amp+), and 7797 (81.9%) cases were ERBB2 wild-type (wt). European genetic ancestry of ECDmut+ was higher than ERBB2wt. Numerous significant associations were observed when comparing GA by group. Notably among these, CDKN2A/MTAP loss were more frequent in ERBB2wt versus ECDmut+ and amp+. ERBB3 GA were more frequent in ECDmut+ and KDmut+ than ERBB2wt. TERT GA were more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. TOP2A amplification was significantly more common in ECDmut+ and amp+ versus ERBB2wt, and TP53 SV GA were significantly higher in ERBB2 amp+ versus ERBB2wt. Mean TMB levels were significantly higher in ECDmut+, KDmut+, and amp+ than in ERBB2wt. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBEC) signature was more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. No significant differences were observed in PD-L1 status between groups, while gLOH-high status was more common in amp+ versus ERBB2wt. MSI-high status was more frequent in KDmut+ versus ERBB2wt, and in ERBB2wt than in amp+. Conclusions: We noted important differences in co-occurring GA in ERBB2-altered (ECDmut+, KDmut+, amp+) versus ERBB2wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the ERBB2-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for ERBB2-altered UBC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic fluid collections (PFCs) may recur after resolution with endoscopic transmural drainage (ETD) and standard stent removal (SSR). Herein, we compared the efficacy and safety of leaving long-term indwelling plastic stents (LTIS) vs. standard stent removal after PFC resolution with ETD. Methods: We performed a systematic review of MEDLINE, EMBASE, CINAHL, Scopus, and Cochrane databases from inception to September 2022. Full-text articles comparing long-term (> 6 months) outcomes of LTIS and SSR were eligible, as well as single-arm studies with ≥ 10 patients with LTIS. Two independent reviewers selected studies, extracted data, and assessed the risk of bias using the Newcastle–Ottawa Scale. Measured outcomes included the following: (A) PFC recurrence; (B) interventions for PFC recurrence; (C) technical success; and (D) adverse events (AEs). Meta-analysis was carried out using random-effects models. Results: We included 16 studies, encompassing 1285 patients. Compared to SSR after PFC resolution with ETD, LTIS was associated with significantly lower risk of PFC recurrence (3% vs. 23%; OR 0.22 [95%CI 0.09–0.52]; I2 = 45%) and need for interventions (2% vs. 14%; OR 0.35 [95%CI 0.16–0.78]; I2 = 0%). The superiority of LTIS on reducing PFC recurrence was found with walled-off necrosis, with or without disconnected pancreatic duct, and with placement of ≥ 2 LTIS. When using LTIS, the pooled proportion of AEs was 8% (95%CI 4–11%) and technical success was 93% (95%CI 86–99%). Conclusions: Our results show that LTIS after PFC resolution with ETD is feasible, safe, and superior to SSR in reducing the risk of PFC recurrence and need for interventions. [ABSTRACT FROM AUTHOR]

Transcription factors belonging to the family of ethylene response factors (ERFs) in plants function in disease resistance to pathogens. One of the tobacco ERF genes, NtERF5, inhibits the accumulation of tobacco mosaic virus (genus Tobamovirus) when overexpressed in tobacco carrying the resistance gene N. Here, we report that NtERF5 can function as a transcriptional activator through binding of the GCC-box in planta. We then determined whether overexpression of NtERF5 in tobacco lacking the N gene (nn tobacco) inhibited infection by potato virus X (PVX: genus Potexvirus). Transient overexpression of NtERF5 inhibited the accumulation of PVX without affecting virus spread and increased the transcript levels of NtPRB-1b and NtPR6, which are jasmonic acid/ethylene-signaling marker genes encoding pathogenesis-related (PR) proteins. Stable overexpression of NtERF5 in nn tobacco also resulted in decreased PVX accumulation and the induction of the expression of NtPRB-1b and NtPR6. Our results revealed that overexpression of NtERF5 limited successful infection and accumulation of PVX, suggesting the role of NtERF5 as a positive regulator of basal defense against virus infection. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) grown in high-density monolayers (sheets) are promising vehicles for numerous bioengineering applications. When MSC sheets are maintained in prolonged cultures, they undergo rapid senescence, limiting their downstream efficacy. Although rapamycin is a potential agent that can inhibit senescence in cell cultures, no study has investigated rapamycin's effect on MSCs grown in high-density culture and its effect on downstream target gene expression. In this study, placental-derived MSCs (PMSCs) were seeded at high density to generate PMSC sheets in 24 hours and were then treated with rapamycin or vehicle for up to 7 days. Autophagy activity, cell senescence and apoptosis, cell size and granularity, and senescence-associated cytokines (IL-6 and IL-8) were analyzed. Differential response in gene expression were assessed via microarray analysis. Rapamycin significantly increased PMSC sheet autophagy activity, inhibited cellular senescence, decreased cell size and granularity at all timepoints. Rapamycin also significantly decreased the number of cells in late apoptosis at day 7 of sheet culture, as well as caspase 3/7 activity at all timepoints. Notably, while rapamycin decreased IL-6 secretion, increased IL-8 levels were observed at all timepoints. Microarray analysis further confirmed the upregulation of IL-8 transcription, as well as provided a list of 396 genes with 2-fold differential expression, where transforming growth factor-β (TGF-β) signaling were identified as important upregulated pathways. Rapamycin both decreased senescence and has an immunomodulatory action of PMSCs grown in sheet culture, which will likely improve the chemotaxis of pro-healing cells to sites of tissue repair in future bioengineering applications. Graphical bstract: [ABSTRACT FROM AUTHOR]

Objective: To identify the association between multidisciplinary clinic (MDC) management and disparities in treatment for patients with pancreatic cancer. Background: Socioeconomic status (SES) predicts treatment and survival for pancreatic cancer. Multidisciplinary clinics (MDCs) may improve surgical management for these patients. Methods: This is a retrospective cohort study (2010–2018) of all pancreatic cancer patients within a large, regional hospital system with a high-volume pancreatic cancer MDC. The primary outcome was receipt of treatment (surgery, chemotherapy, radiation, clinical trial participation, and palliative care); the secondary outcomes were overall survival and MDC management. Multiple logistic regressions were used for binary outcomes. Survival was analyzed using Kaplan–Meier survival analysis, Cox proportional hazards, and inverse probability of treatment weighting (IPTW). Results: Of the 4141 patients studied, 1420 (34.3%) were managed by the MDC. MDC management was more likely for patients who were younger age, married, and privately insured, while less likely for low SES patients (all p < 0.05). MDC patients were more likely to receive all treatments, including neoadjuvant chemotherapy (OR 3.33, 95% CI 2.82–3.93), surgery (OR 1.39, 95% CI 1.15–1.68), palliative care (OR 1.21, 95% CI 1.05–1.38), and clinical trial participation (OR 3.76, 95% CI 2.86–4.93). Low SES patients were less likely to undergo surgery outside of the MDC (OR 0.47, 95% CI 0.31–0.73) but there was no difference within the MDC (OR 1.10, 95% CI 0.68–1.77). Across multiple survival analyses, low SES predicted inferior survival outside of the MDC, but there was no association among MDC patients. Conclusion: Multidisciplinary team-based care increases rates of treatment and eliminates socioeconomic disparities for pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Nobel laureates cluster together. 696 of the 727 winners of the Nobel Prize in physics, chemistry, medicine, and economics belong to one single academic family tree. 668 trace their ancestry to Emmanuel Stupanus, 228 to Lord Rayleigh (physics, 1904). Craig Mello (medicine, 2006) counts 51 Nobelists among his ancestors. Chemistry laureates have the most Nobel ancestors and descendants, economics laureates the fewest. Chemistry is the central discipline. Its Nobelists have trained and are trained by Nobelists in other fields. Nobelists in physics (medicine) have trained (by) others. Economics stands apart. Openness to other disciplines is the same in recent and earlier times. The familial concentration of Nobelists is lower now than it used to be. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to discuss a generalization of the bubble transform to differential forms. The bubble transform was discussed in Falk and Winther (Found Comput Math 16(1):297–328, 2016) for scalar valued functions, or zero-forms, and represents a new tool for the understanding of finite element spaces of arbitrary polynomial degree. The present paper contains a similar study for differential forms. From a simplicial mesh T of the domain Ω , we build a map which decomposes piecewise smooth k-forms into a sum of local bubbles supported on appropriate macroelements. The key properties of the decomposition are that it commutes with the exterior derivative and preserves the piecewise polynomial structure of the standard finite element spaces of k-forms. Furthermore, the transform is bounded in L 2 and also on the appropriate subspace consisting of k-forms with exterior derivatives in L 2 . [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic performance and reliability of 18 CT signs to diagnose cecal volvulus, a surgical emergency, versus a group of non-volvulus mimickers. Materials and methods: Four radiologists retrospectively and independently assessed 18 CT signs in 191 patients with cecal volvulus (n = 63) or a non-volvulus control group ((n = 128), including cecal bascule (n = 19), mobile cecum (n = 95), and colonic pseudo-obstruction (n = 14)) at a single institution from 2013 to 2021. Fleiss' kappa coefficient was used to assess inter-reader agreement. For diagnostic performance metrics, we assessed sensitivity, specificity, and positive and negative predictive values. For predictive performance, all 18 signs were included in bivariate and stepwise lasso multivariate logistic regression models to diagnose cecal volvulus. Performance was assessed by ROC curves. Results: 191 patients (mean age: 63 years +/− 15.5 [SD]; 135 women) were included in the study. Nine of the 18 CT signs of cecal volvulus demonstrated good or better (> 0.6) inter-reader agreement. Individual CT signs with sensitivity, specificity, positive and negative predictive values all above 70% for diagnosing cecal volvulus were transition point, bird beak, and X-marks-the-spot. A lasso regression model determined four CT features: transition point, bird beak, coffee bean, and whirl had excellent prediction (AUC =.979) for cecal volvulus if all present. Conclusion: CT signs for cecal volvulus that have high sensitivity and specificity include: transition point, bird beak, and X-marks-the-spot and were reliable in distinguishing non-volvulus mimickers. If the following four features were present: transition point, bird beak, coffee bean, and whirl, there was excellent prediction (AUC =.979) for cecal volvulus. [ABSTRACT FROM AUTHOR]

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan–Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06–3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86–3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials. [ABSTRACT FROM AUTHOR]

Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.A stripped-envelope supernova, SN 2022jli, shows 12.4-day periodic undulations during the declining light curve, and narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts. [ABSTRACT FROM AUTHOR]

Dof (DNA binding with one finger) proteins are plant-specific transcription factors involved in gene regulation during abiotic and biotic stresses. Our previous studies suggested that tobacco Dof proteins, including BBF3, can upregulate the expression of the virus resistance N gene as well as resistance-related genes. In this study, we generated and characterized transgenic tobacco lines carrying the N gene that overexpressed BBF3 cDNA constitutively. In the absence of virus challenge, the BBF3 overexpression caused no developmental defects and no changes in the N transcript level, although the transcript levels of some defense-related genes were affected compared with levels in non-transgenic plants. TMV infection induced a hypersensitive reaction (HR) with larger necrotic lesions in transgenic lines than in non-transgenic plants, but there was no change in total virus accumulation per lesion in a standardized area. Activation of the N gene expression in non-transgenic plants during synchronously-induced HR was followed by downregulation of BBF3 gene expression. Constitutive overexpression of the BBF3 transgene resulted in higher accumulation of the N gene as well as HR marker genes (Hin1 and Hsr203j) and lower accumulation of salicylic acid- and jasmonic acid-signaling marker genes (PR1-a and PR-1b). In particular, the expression of PR-1b was remarkably suppressed in the BBF3-overexpressing transgenic lines. Dof-binding motifs were confirmed in the upstream regions of all target genes examined. Our results suggest that BBF3 has a role in modulating the expression of genes associated with virus elicitor recognition and defense responses resulting in larger areas of HR-associated cell death. [ABSTRACT FROM AUTHOR]

Previous research on the physical and mental health of firefighters indicates higher risk of coronary disease, stroke, cancer, hearing loss, and decreased mobility, as well as suicide risk, depression, anxiety, and substance use than in the general population. In spite of this, there is minimal research available on evidence-based interventions to reduce the impact of high-stress and high-trauma work on the mental health and well-being of firefighters. In collaboration with the Salt Lake City Fire Department, we conducted a feasibility study to understand how psychological resilience training influences the mental and social health of firefighters. A pre-intervention survey (n = 186) provided baseline data on firefighters' mental health and wellbeing. Domains measured were depression, anxiety, stress, post-traumatic stress disorder, substance use, suicide risk, willingness to attend couple's therapy, and quality of life. Three hundred firefighters then received three 90-minute training sessions on MindShield™, a newly-developed trauma-informed, mindfulness-based intervention. Analysis of measurement instrument completion rates suggests firefighters were amenable to the process, though concerns about data privacy may have inhibited response on certain instruments. Qualitative data derived from four post-intervention focus groups (n = 33) informed recommendations for future intervention delivery: shorter training sessions, leaving the training with a tangible reminder of the MindShield™ tools, embedding firefighters more into the training presentation, and clarifying data access and privacy protocols. Both the intervention and measurement tools used were generally well-received, indicating MindShield™ is a feasible intervention to mitigate the impact of high-stress, high-trauma work on firefighters. [ABSTRACT FROM AUTHOR]

Patients with single ventricle defects undergoing the Fontan procedure eventually face Fontan failure. Long-term cavopulmonary assist devices using rotary pump technologies are currently being developed as a subpulmonary power source to prevent and treat Fontan failure. Low hydraulic resistance is a critical safety requirement in the event of pump failure (0 RPM) as a modest 2 mmHg cavopulmonary pressure drop can compromise patient hemodynamics. The goal of this study is therefore to assess the passive performance of a viscous impeller pump (VIP) we are developing for Fontan patients, and validate flow simulations against in-vitro data. Two different blade heights (1.09 mm vs 1.62 mm) and a blank housing model were tested using a mock circulatory loop (MCL) with cardiac output ranging from 3 to 11 L/min. Three-dimensional flow simulations were performed and compared against MCL data. In-silico and MCL results demonstrated a pressure drop of < 2 mmHg at a cardiac output of 7 L/min for both blade heights. There was good agreement between simulation and MCL results for pressure loss (mean difference − 0.23 mmHg 95% CI [0.24–0.71]). Compared to the blank housing model, low wall shear stress area and oscillatory shear index on the pump surface were low, and mean washout times were within 2 s. This study demonstrated the low resistance characteristic of current VIP designs in the failed condition that results in clinically acceptable minimal pressure loss without increased washout time as compared to a blank housing model under normal cardiac output in Fontan patients. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy (SLNB) is an important staging and prognostic tool for cutaneous melanoma (CM). However, there exists a knowledge gap regarding whether sociodemographic characteristics are associated with receipt of SLNB for T1b CMs, for which there are no definitive recommendations for SLNB per current National Comprehensive Cancer Network guidelines. We performed a retrospective analysis of the 2012–2018 National Cancer Database, identifying patients with American Joint Committee on Cancer staging manual 8th edition stage T1b CM, and used multivariable logistic regression to analyze associations between sociodemographic characteristics and receipt of SLNB. Among 40,458 patients with T1b CM, 23,813 (58.9%) received SLNB. Median age was 62 years, and most patients were male (57%) and non-Hispanic White (95%). In multivariable analyses, patients of Hispanic (aOR 0.67, 95%CI 0.48–0.94) and other (aOR 0.78, 95%CI 0.63–0.97) race/ethnicity, and patients aged > 75 (aOR 0.33, 95%CI 0.29–0.38), were less likely to receive SLNB. Conversely, patients in the highest of seven socioeconomic status levels (aOR 1.37, 95%CI 1.13–1.65) and those treated at higher-volume facilities (aOR 1.29, 95%CI 1.14–1.46) were more likely to receive SLNB. Understanding the underlying drivers of these associations may yield important insights for the management of patients with melanoma. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoking is suggested as a risk factor for colorectal cancer (CRC), but the complex relationship and the potential pathway are not fully understood. Methods: We performed two-sample Mendelian randomisation (MR) analyses with genetic instruments for smoking behaviours and related DNA methylation in blood and summary-level GWAS data of colorectal cancer to disentangle the relationship. Colocalization analyses and prospective gene-environment interaction analyses were also conducted as replication. Results: Convincing evidence was identified for the pathogenic effect of smoking initiation on CRC risk and suggestive evidence was observed for the protective effect of smoking cessation in the univariable MR analyses. Multivariable MR analysis revealed that these associations were independent of other smoking phenotypes and alcohol drinking. Genetically predicted methylation at CpG site cg17823346 [ZMIZ1] were identified to decrease CRC risk; while genetically predicted methylation at cg02149899 would increase CRC risk. Colocalization and gene-environment interaction analyses added further evidence to the relationship between epigenetic modification at cg17823346 [ZMIZ1] as well as cg02149899 and CRC risk. Discussion: Our study confirms the significant association between tobacco smoking, DNA methylation and CRC risk and yields a novel insight into the pathogenic effect of tobacco smoking on CRC risk. [ABSTRACT FROM AUTHOR]

This paper investigates whether shocks in oil prices affect the level of crime in Kern County, California's top oil producing county. Monthly data from 2003 to 2018 is employed using a nonlinear autoregressive distributed lag model to test the asymmetric effects of these changes. Results for Kern County indicate that in the long-run, a negative shock in oil prices increases criminal activity while short-run oil price changes have no effect on criminal activity. Results from neighboring counties indicate that positive shocks to oil prices increase criminal activity in wealthy regions. Findings from generalized impulse response functions indicate that criminal activity in Los Angeles, Kings and San Bernardino Counties respond to shocks from Kern County's crime rates. They also indicate that criminal activity in Inyo and Los Angeles Counties influence Kern County's crime rate. [ABSTRACT FROM AUTHOR]

The current study was designed based on the life balance areas of positive orientation and depression. General mattering and life satisfaction are important positive psychological factors for individuals. The purpose of the study was to investigate both theoretical and empirical gaps in our knowledge of whether general mattering and life satisfaction, which are positive psychology elements, predict aggression among college students. Turkish college students (n = 1467) participated in the study. The results revealed life satisfaction and general mattering had direct effects on positive orientation and indirect effects on depression and aggression. Positive orientation and depression were significant mediators between positive psychology factors and aggression. In this sense, the current study serves the science-practitioner model with the implications for research and practice. [ABSTRACT FROM AUTHOR]

In this work, we present a perspective on the role machine intelligence can play in supporting human abilities. In particular, we consider research in rehabilitation technologies such as prosthetic devices, as this domain requires tight coupling between human and machine. Taking an agent-based view of such devices, we propose that human–machine collaborations have a capacity to perform tasks which is a result of the combined agency of the human and the machine. We introduce communicative capital as a resource developed by a human and a machine working together in ongoing interactions. Development of this resource enables the partnership to eventually perform tasks at a capacity greater than either individual could achieve alone. We then examine the benefits and challenges of increasing the agency of prostheses by surveying literature which demonstrates that building communicative resources enables more complex, task-directed interactions. The viewpoint developed in this article extends current thinking on how best to support the functional use of increasingly complex prostheses, and establishes insight toward creating more fruitful interactions between humans and supportive, assistive, and augmentative technologies. [ABSTRACT FROM AUTHOR]

The first positive Neumann eigenvalue of the Laplacian is shown to be maximal for a spherical cap among simply connected domains covering up to 94 % of the 2-sphere. The previous best result, by Bandle, was 50 % . [ABSTRACT FROM AUTHOR]

Objectives: We used a novel combined analysis to evaluate various factors associated with failure to surgical resection in non-metastatic gastric cancer. Methods: We identified factors associated with the receipt of surgery in publicly available clinical trial data for gastric cancer and in the National Cancer Database (NCDB) for patients with stages I–III gastric adenocarcinoma. Next, we evaluated variable importance in predicting the receipt of surgery in the NCDB. Results: In published clinical trial data, 10% of patients in surgery-first arms did not undergo surgery, mostly due to disease progression and 15% of patients in neoadjuvant therapy arms failed to reach surgery. Effects related to neoadjuvant administration explained the increased attrition (5%). In the NCDB, 61.7% of patients underwent definitive surgery. In a subset of NCDB patients resembling those enrolled in clinical trials (younger, healthier, and privately insured patients treated at high-volume and academic centers) the rate of surgery was 79.2%. Decreased likelihood of surgery was associated with advanced age (OR 0.97, p < 0.01), Charlson–Deyo score of 2+ (OR 0.90, p < 0.01), T4 tumors (OR 0.39, p < 0.01), N+ disease (OR 0.84, p < 0.01), low socioeconomic status (OR 0.86, p = 0.01), uninsured or on Medicaid (OR 0.58 and 0.69, respectively, p < 0.01), low facility volume (OR 0.64, p < 0.01), and non-academic cancer programs (OR 0.79, p < 0.01). Conclusion: Review of clinical trials shows attrition due to unavoidable tumor and treatment factors (~ 15%). The NCDB indicates non-medical patient and provider characteristics (i.e., age, insurance status, facility volume) associated with attrition. This combined analysis highlights specific opportunities for improving potentially curative surgery rates. [ABSTRACT FROM AUTHOR]

Abstract Post‐translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O‐GlcNAcylation and the expression of O‐GlcNAc transferase (OGT), the enzyme adding the O‐GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical‐induced colitis. Paneth cell‐specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical‐induced colitis. On the other hand, the augmentation of O‐GlcNAc signaling by inhibiting O‐GlcNAcase, the enzyme removing O‐GlcNAcylation, alleviated chemical‐induced colitis. Our data reveal that protein O‐GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.

This report describes proteolytic fragmentation and clearance of bovine lactoferrin (bLF) upon intravaginal administration in premenopausal women. Tablet formulations (MTbLF) containing 300 mg of bLF progressed through three phases: Pre-Dissolution, Dissolution, and Washout, over a 30-h time course. Tablets dissolved slowly, replenishing intact 80 kDa bLF in vaginal fluid (VF) as proteolysis occurred. bLF was initially cleaved approximately in half between its N- and C-lobes, then degraded into sub-fragments and small peptides. The extent of proteolysis was less than 10–20% across multiple subjects. Concentrations of both intact 80 kDa bLF and smaller fragments decreased in VF with a similar time course suggesting washout not proteolysis was the main clearance mechanism. Concentrations of intact and/or nicked 80 kDa bLF peaked between 4 and 8 h after administration and remained above 5 mg/mL for approximately 24 h. Experiments with protease inhibitors in ex vivo VF digests suggested an aspartyl protease was at least partially responsible for bLF cleavage. However, digestion with commercial pepsin or in vivo in the human stomach, demonstrated distinctly different patterns of fragments compared to vaginal proteolysis. Furthermore, the 3.1 kDa antimicrobial peptide lactoferricin B was not detected in VF. This suggests pepsin-like aspartyl proteases are not responsible for vaginal proteolysis of bLF. [ABSTRACT FROM AUTHOR]

Despite the widespread adoption of motion-triggered camera traps, studies using camera traps to characterize wildlife communities in residential areas in North America are limited. To fill this data gap, we placed camera traps over three seasons in 22 residential neighborhoods within Dutchess County, NY. To account for imperfect detection, we applied individual-level and community-level Bayesian site-occupancy models to these data. Overall, we captured 64,639 independent detections over 17,820 camera trap days. We detected between 17 and 22 mammal and non-passerine bird species in each of the seasons of data collection, while our community models estimated between 24 and 33 mammal and non-passerine bird species in each season. Small, cryptic species were not reliably captured by camera traps, limiting our ability to model their occupancy. We identified five species: raccoons (Procyon lotor), eastern gray squirrels (Sciurus carolinensis), red foxes (Vulpes vulpes), Virginia opossums (Didelphis virginiana), and white-tailed deer (Odocoileus virginianus) found in all neighborhoods. The most common covariate included in our final occupancy models was the percent of area within each neighborhood that was an impervious surface, which positively affected occupancy for some species, and negatively affected occupancy for others. Forest cover, the second most common variable in our final models, negatively affected occupancy for all species. Our estimates characterize a baseline for quantifying species richness and composition in residential areas of Dutchess County, NY and surrounding regions, and offer a comparison to similar studies in natural areas. Overall, the results improve understanding of how residential landscapes affect individual species and communities. [ABSTRACT FROM AUTHOR]

Depression and antidepressant medications increase risk for type 2 diabetes. Cambodian-Americans have exceedingly high rates of both depression and diabetes. This paper reports outcomes of a diabetes prevention trial for Cambodian-Americans with depression. Primary outcomes were HbA1c, insulin resistance and depressive symptoms. Participants were aged 35–75, Khmer speaking, at risk for diabetes, and met study criteria for likely depression by either (a) antidepressant medication and/or (b) prolonged elevated depressive symptoms. Participants were randomized to one of three community health worker (CHW) interventions: (1) lifestyle intervention called Eat, Walk, Sleep (EWS), (2) EWS plus medication therapy management sessions with a pharmacist/CHW team to resolve drug therapy problems (EWS + MTM), or, (3) social services (SS; control). Assessments were at baseline, post-treatment (12 months), and follow-up (15 months). The n = 188 participants were 78% female, average age of 55 years, half had a household income < $20,000, and modal educational attainment was 7.0 years. Compared to the other arms, EWS + MTM showed a significant decrease in HbA1c and a trend for reduced inflammation and stress hormones. Depressive symptoms improved for EWS and EWS + MTM relative to SS. There was no change in insulin resistance. Cardiometabolic and mental health can be improved in tandem among immigrant and refugee groups. [ABSTRACT FROM AUTHOR]

Purpose of Review: Basilar artery occlusion (BAO) is one of the most devastating forms of ischemic stroke with historically high mortality and disability rates. Here, we evaluate the current interventions available to clinicians and present the most recent evidence from randomized clinical trials in support of endovascular thrombectomy as the treatment of choice for BAO. Recent Findings: Two recent randomized clinical trials (ATTENTION and BAOCHE) have provided convincing evidence of the superiority of endovascular thrombectomy over medical management for patients with BAO. Although questions regarding the generalizability of these trial results and optimal treatment protocols remain, enhancements to neuroendovascular devices and techniques now provide hope for clinicians and patients battling BAO. Summary: Diagnostic evaluation of BAO requires computerized tomography, magnetic resonance, or digital subtraction angiographic imaging, with the latter considered the gold standard, and enabling intervention to proceed rapidly following imaging acquisition. Intravenous thrombolysis should be performed in eligible patients within 4.5 h of symptom onset. Mechanical endovascular thrombectomy should be performed in eligible patients within 6 h of symptom onset, or up to 24 h in patients with evidence of salvageable tissue, especially in the brainstem. [ABSTRACT FROM AUTHOR]