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Objectives: To identify domains of persisting problems at 4 months after discharge in patients previously hospitalized due to COVID-19, with a focus on a subgroup of patients reporting symptoms to an extent indicative of rehabilitation needs., Design: Ambidirectional observational cohort study., Patients: All patients with a laboratory-confirmed COVID-19 diagnosis admitted to hospital in a Swedish healthcare region during the period 1 March to 31 May 2020. After exclusion, 94% of all survivors (n = 433) participated in the study. Forty-three percent (n = 185) of these reported persisting problems indicating rehabilitation needs and formed a subgroup., Methods: Explorative factor analysis based on results from comprehensive telephone interviews covering persisting symptoms, including assessment of impact on daily life., Results: Seven domains were identified, comprising problems related to vision, cognition, mental fatigue, swallowing, voice, sensorimotor dysfunction, and feeling anxious/depressed. The patients in the subgroup reported a median of 8 symptoms/limitations affecting everyday life, and two-thirds reported symptoms/limitations in 3 or more domains., Conclusion: Seven problem domains corresponding to specific modalities of rehabilitative interventions were identified. A majority of patients reported problems from several domains, indicating the need for multiprofessional teams in post-COVID-19 rehabilitation. Screening of patients previously hospitalized due to COVID-19 should cover all 7 domains of persisting problems.

The β chain rearrangement in T cells is a two-step process where first D β and J β bind, and only then V β is joined to the complex. We here show that the frequency of human and mouse V β J β combinations deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional (F) rearrangements, but also slightly in non-functional (NF) rearrangements. Preferred V β J β combinations in F clones are shared between donors and samples, suggesting a common structural mechanism for these biases in addition to any host-specific antigen-induced peripheral selection. The sharing holds even in clones with J β 1 that share the same D β 1 gene. V β J β usage is correlated with the Molecular Weight and Isoelectric Point in F clones. The pairing is also observed in the Double Positive cells in mice thymocytes, suggesting that the selection leading to such a pairing occurs before thymic selection. These results suggest an additional structural checkpoint in the beta chain development prior to thymic selection during the T cell receptor expression. Understanding this structural selection is important for the distinction between normal and aberrant T cell development, and crucial for the design of engineered TCRs., 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. t:, (Copyright © 2022 Levi and Louzoun.)

Introduction: Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation and result in increased hospital length of stay (LOS) and healthcare costs. Low-volume bowel preparation (LV-BP; sodium sulfate, potassium sulfate, and magnesium sulfate ) has been shown to improve outpatient bowel preparation quality compared with standard high-volume bowel preparations (HV-BP; polyethylene glycol ). However, its efficacy in hospitalized patients has not been well-studied. We assessed the impact of LV-BP on time to colonoscopy, hospital LOS, and bowel preparation quality among inpatients., Methods: We performed a propensity score-matched analysis of adult inpatients undergoing colonoscopy who received either LV-BP or HV-BP before colonoscopy at a quaternary academic medical center. Multivariate regression models with feature selection were developed to assess the association between LV-BP and study outcomes., Results: Among 1,807 inpatients included in this study, 293 and 1,514 patients received LV-BP and HV-BP, respectively. Among the propensity score-matched population, LV-BP was associated with a shorter time to colonoscopy (β: -0.43 [95% confidence interval: -0.56 to -0.30]) while having similar odds of adequate preparation (odds ratio: 1.02 [95% confidence interval: 0.71-1.46]; P = 0.92). LV-BP was also significantly associated with decreased hospital LOS among older patients (age ≥ 75 years), patients with chronic kidney disease, and patients who were hospitalized with gastrointestinal bleeding., Discussion: LV-BP is associated with decreased time to colonoscopy in hospitalized patients. Older inpatients, inpatients with chronic kidney disease, and inpatients with gastrointestinal bleeding may particularly benefit from LV-BP. Prospective studies are needed to further establish the role of LV-BP for inpatient colonoscopies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

A binary state on a graph means an assignment of binary values to its vertices. A time-dependent sequence of binary states is referred to as binary dynamics. We describe a method for the classification of binary dynamics of digraphs, using particular choices of closed neighbourhoods. Our motivation and application comes from neuroscience, where a directed graph is an abstraction of neurons and their connections, and where the simplification of large amounts of data is key to any computation. We present a topological/graph theoretic method for extracting information out of binary dynamics on a graph, based on a selection of a relatively small number of vertices and their neighbourhoods. We consider existing and introduce new real-valued functions on closed neighbourhoods, comparing them by their ability to accurately classify different binary dynamics. We describe a classification algorithm that uses two parameters and sets up a machine learning pipeline. We demonstrate the effectiveness of the method on simulated activity on a digital reconstruction of cortical tissue of a rat, and on a nonbiological random graph with similar density., (© 2022 Massachusetts Institute of Technology.)

Objective: To report vision-related symptoms and neuro-visual clinical signs in patients approximately 4 months after discharge from hospitalization after COVID-19 infection. To report on coexisting functional and activity limitations., Design: The study is part of an ambidirectional population-based cohort study., Setting: An outpatient setting in a hospital environment., Participants: Patients from a population-based cohort study including all patients with laboratory-confirmed COVID-19 admitted to hospital during a 3-month period in a health care region in Sweden. Among patients who, based on a standardized telephone interview, were identified as having persisting rehabilitation needs 4 months after discharge (n=185), several (n=57) reported vision-related symptoms. All 57 patients were invited to a neuro-visual examination. Six patients declined, 6 were unavailable, and 3 did not fulfil the inclusion criteria. Thus, 42 patients were included in the analysis (N=42)., Interventions: Not applicable., Main Outcome Measures: Vision-related symptoms, neuro-visual function, and coexisting impairments affecting activities of daily life and participation., Results: A total of 31% of patients with rehabilitation needs after COVID-19 reported vision-related symptoms. Reading-related issues (73.8%), blurry vision (69.0%), and light sensitivity (66.7%) were the most common symptoms. Patients with reading-related issues showed a higher level of eye strain ( P <.001). Neuro-visual deficits were found in 83.3% of the patients, mainly concerning eye teaming (23.1%-66.7%) and eye movement (28.6%-30.8%) functions. Patients with vision-related symptoms reported fatigue and 18 other coexisting symptoms to a greater extent ( P ≤.0001 to .049)., Conclusions: Neuro-visual symptoms and signs should be considered when assessing rehabilitation needs after COVID-19. The association between vision-related issues and coexisting symptoms with an effect on body function and activity and/or participation underlines the need for multiprofessional rehabilitation assessment and intervention., (© 2022 The Authors.)

Women with low household income and from racial/ethnic minority groups are at elevated risk of food insecurity. Food insecurity during pregnancy is associated with overall less healthy diets, lower intake of the pregnancy-supportive nutrients iron and folate, and significant variations in diet across the course of a month. The goal of this study was to explore the impact of an ongoing $40/month supplement for fruits and vegetables (F&Vs) provided to pregnant people enrolled in the Special Supplemental Nutrition Program for Women and Children (WIC). Our primary outcome was food insecurity using the USDA 6-item survey, and our secondary outcome was dietary intake of F&Vs based on the 10-item Dietary Screener Questionnaire. Participants in intervention and comparison counties completed surveys at enrollment and approximately three months later (n = 609). Mean ± SD food insecurity at baseline was 3.67 ± 2.79 and 3.47 ± 2.73 in the intervention and comparison groups, respectively, and the adjusted between-group change from baseline to follow-up in food insecurity was 0.05 [95% CI: −0.35, 0.44] (p > 0.05). F&V intake (in cup equivalents) was 2.56 ± 0.95 and 2.51 ± 0.89 at baseline in the two groups, and the adjusted mean between-group difference in changes from baseline was −0.06 [−0.23, 0.11] (p > 0.05). Recruitment and data collection for this study coincided with the most intensive of America’s COVID relief efforts. Our results may indicate that small increases in highly targeted food resources make less of a difference in the context of larger, more general resources being provided to individuals and households in need.

Research on mental health pays increasing attention to the influence of social institutions on subjective well-being over the life course. Yet little research has considered how belief in the promise of legal institutions may have beneficial effects for well-being. Through structural equation models of longitudinal data, our findings suggest that belief in the neutrality and fairness of legal institutions has salutary effects for mental health net of social and economic status and across individuals from a wide range of ethnic groups. By combining research in the sociology of mental health, cultural sociology, social psychology, and the sociology of law, we extend the emerging literature on the institutional determinants of mental health by including attention to law as one of the central organizing institutions of social life.

Freshwaters are a very valuable resource in arid areas, such as Mediterranean countries. Freshwater systems are vulnerable ecological habitats, significantly disturbed globally and especially in arid areas. The Sea of Galilee is the largest surface freshwater body in the Middle East. It is an isolated habitat supporting unique fish populations, including endemic species and populations on the edge of their distribution range. Using the Sea of Galilee for water supply, fishing and recreation has been placing pressure on these fish populations. Therefore, efficient monitoring and effective actions can make a difference in the conservation of these unique fish populations. To set a baseline and develop molecular tools to do so, in this study, DNA barcoding was used to establish a database of molecular species identification based on sequences of Cytochrome C Oxidase subunit I gene. DNA barcodes for 22 species were obtained and deposited in Barcode of Life Database. Among these, 12 barcodes for 10 species were new to the database and different from those already there. Barcode sequences were queried against the database and similar barcodes from the same and closely related species were obtained. Disagreements between morphological and molecular species identification were identified for five species, which were further studied by phylogenetic and genetic distances analyses. These analyses suggested the Sea of Galilee contained hybrid fish of some species and other species for which the species definition should be reconsidered. Notably, the cyprinid fish defined as Garra rufa, should be considered as Garra jordanica. Taken together, along with data supporting reconsideration of species definition, this study sets the basis for further using molecular tools for monitoring fish populations, understanding their ecology, and effectively managing their conservation in this unique and important habitat and in the region., Competing Interests: The authors have declared that no competing interests exist.

Background: Survival among critically ill COVID-19 patients varies between countries and time periods. Mortality rates up to 60% have been reported in intensive care units (ICUs). Standard-of-care has evolved throughout the pandemic. The purpose of the study was to explore management and mortality of COVID-19 ICU-patients during the first pandemic wave and assess their post-ICU health status., Methods: We conducted an exploratory observational ambidirectional population-based study of ICU-patients with COVID-19 in a Swedish county during 1 March-30 June 2020. Primary outcome was 60-day mortality with secondary outcomes including treatments, complications, self-reported general health and dyspnoea post-discharge. Patients were consecutively divided into equal tertiles with cut-offs on April 4 and April 20, 2020, to analyse time trends., Results: One hundred patients, median age was 63 years, were included, and 60-day mortality rate was 22%. Ninety-one percent had moderate/severe ARDS and 88% required mechanical ventilation. In the first tertile of patients 60-day mortality was 33%, declining to 15% and 18% in the following two. This reduction paralleled increased use of thromboprophylaxis, less steep rise of treated ICU-patients per day and expanded ICU resources. Four months post-discharge, 63% of survivors reported self-assessed decline in general health retrospectively compared to prior COVID-19., Conclusions: In this cohort, the initial 60-day mortality quickly declined, despite continuous admittance of critically ill patients. This was parallel to adaptation to increased workload and more intense thromboembolic prophylaxis. A majority of survivors reported declined general health four months after discharge. Further studies on long-term health status of ICU-survivors are indicated., (© 2022 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Trimethylamine N-oxide (TMAO) is a diet derived compound directly introduced through foodstuff, or endogenously synthesized from its precursors, primarily choline, L-carnitine, and ergothioneine. New evidence outlines high TMAO plasma concentrations in patients with overt cardiovascular disease, but its direct role in pathological development is still controversial. The purpose of the study was to evaluate the role of TMAO in affecting key intracellular factors involved in endothelial dysfunction development, such as reactive oxygen species, mitochondrial health, calcium balance, and nitric oxide release using bovine aortic endothelial cells (BAE-1). Cell viability and oxidative stress indicators were monitored after acute and prolonged TMAO treatment. The role of TMAO in interfering with the physiological purinergic vasodilatory mechanism after ATP stimulation was defined through measurements of the rise of intracellular calcium, nitric oxide release, and eNOS phosphorylation at Ser1179 (eNOS Ser1179 ). TMAO was not cytotoxic for BAE-1 and it did not induce the rise of reactive oxygen species and impairment of mitochondrial membrane potential, either in the basal condition or in the presence of a stressor. In contrast, TMAO modified the purinergic response affecting intracellular ATP-induced calcium increase, nitric oxide release, and eNOS Ser1179 . Results obtained suggest a possible implication of TMAO in impairing the endothelial-dependent vasodilatory mechanism.

Cyclic adenosine 3',5'-monophosphate (cAMP)-elevating agents, such as β 2 -adrenergic receptor (β 2 -AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limited by unwanted side effects because of unrestricted cAMP elevation in the airways and in distant organs. Here, we identified the A-kinase anchoring protein phosphoinositide 3-kinase γ (PI3Kγ) as a critical regulator of a discrete cAMP signaling microdomain activated by β 2 -ARs in airway structural and inflammatory cells. Displacement of the PI3Kγ-anchored pool of protein kinase A (PKA) by an inhaled, cell-permeable, PI3Kγ mimetic peptide (PI3Kγ MP) inhibited a pool of subcortical PDE4B and PDE4D and safely increased cAMP in the lungs, leading to airway smooth muscle relaxation and reduced neutrophil infiltration in a murine model of asthma. In human bronchial epithelial cells, PI3Kγ MP induced unexpected cAMP and PKA elevations restricted to the vicinity of the cystic fibrosis transmembrane conductance regulator (CFTR), the ion channel controlling mucus hydration that is mutated in cystic fibrosis (CF). PI3Kγ MP promoted the phosphorylation of wild-type CFTR on serine-737, triggering channel gating, and rescued the function of F508del-CFTR, the most prevalent CF mutant, by enhancing the effects of existing CFTR modulators. These results unveil PI3Kγ as the regulator of a β 2 -AR/cAMP microdomain central to smooth muscle contraction, immune cell activation, and epithelial fluid secretion in the airways, suggesting the use of a PI3Kγ MP for compartment-restricted, therapeutic cAMP elevation in chronic obstructive respiratory diseases.

The COVID-19 pandemic resulted in widespread school closures, reducing access to school meals for millions of students previously participating in the US Department of Agriculture (USDA) National School Lunch Program (NSLP). School-prepared meals are, on average, more nutritious than home-prepared meals. In the absence of recent data measuring changes in children's diets during the pandemic, this article aims to provide conservative, back-of-the-envelope estimates of the nutritional impacts of the pandemic for school-aged children in the United States. We used administrative data from the USDA on the number of NSLP lunches served in 2019 and 2020 and nationally representative data from the USDA School Nutrition and Meal Cost Study on the quality of school-prepared and home-prepared lunches. We estimate changes in lunchtime calories and nutrients consumed by NSLP participants from March to November 2020, compared to the same months in 2019. We estimate that an NSLP participant receiving no school meals would increase their caloric consumption by 640 calories per week and reduce their consumption of nutrients such as calcium and vitamin D. Because 27 to 78 million fewer lunches were served per week in March-November 2020 compared to the previous year, nationally, students may have consumed 3 to 10 billion additional calories per week. As students return to school, it is vital to increase school meal participation and update nutrition policies to address potentially widening nutrition disparities.

Food insecurity is associated with increased risk of chronic disease and poor dietary intake. The United States charitable food system, a complex network of food banks, pantries and congregate meal sites, provides food for millions of low-income households each year. Food banks and pantries play a critical role in supporting food security and are an important contributor to dietary intake for its clients. In recent years, there has been an increased focus on sourcing and supplying more nutritious foods within the charitable food system. Despite this, there is a lack of alignment in how the charitable food system defines and tracks the nutritional quality of food.In 2019, Healthy Eating Research convened a panel of nutrition, charitable food system and food policy experts to create a set of evidence-based nutrition standards. Standards were developed based on a review of the literature and existing nutrition ranking systems, while also considering the operational needs and capacity of the charitable food system. The panel provided recommendations for eleven distinct food categories: fruits and vegetables, grains, protein, dairy, non-dairy alternatives, beverages, mixed dishes, processed and packaged snacks, desserts, condiments and cooking staples, and other miscellaneous items. Products are ranked into three tiers, choose often (green), choose sometimes (yellow) or choose rarely (red), based on designated saturated fat, sodium, and added sugar thresholds. This paper outlines the expert panel's approach and summarizes the barriers and opportunities for implementing these standards across the charitable food system., (© 2022. The Author(s).)

Food banks and pantries provide food to millions of food-insecure households each year. However, there has been limited research to understand the extent to which they improve food security. This is a secondary, prespecified analysis of a randomized controlled trial (ClinicalTrials.gov ID: NCT02569060). We examined whether an enhanced food bank intervention impacted the food security status of adults with diabetes. Using a crossover design, participants ( n  = 568) were randomly assigned to receive the intervention (usual pantry services plus twice-monthly diabetes-specific food boxes, diabetes self-management education, health care referrals, and glucose monitoring) or 6 mo of usual services. Results demonstrate a statistically significant improvement in food insecurity among participants following the intervention phase compared with the control phase (mean: 0.49-point decrease; 95% CI: 0.21, 0.77; P  = 0.0006). This finding adds to evidence that the charitable food system plays an important role in mitigating short-term food insecurity for adults with diabetes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To identify risk factors in first pregnancy for perinatal mortality in the subsequent pregnancy., Methods: A retrospective population-based nested case-control study was conducted, including all women with two first singleton consecutive deliveries. Women with perinatal mortality in their first pregnancy were excluded, and cases with perinatal mortality in the second pregnancy were compared with controls who delivered a live birth. Characteristics and complications of the first pregnancy were compared between the groups using multivariable logistic models., Results: A total of 43 043 women were included in the study, 385 (0.9%) were cases. Cases, as compared with controls (live births), were younger (22.62 ± 4.0 vs 23.22 ± 4.0 years), with shorter inter-pregnancy interval (1.38 ± 1.55 vs 1.56 ± 1.53 years), and were more likely to have the following complications in their first pregnancy: severe pre-eclampsia (3.4% vs 1.7%), small for gestational age (12.5% vs 8.0%), preterm delivery (17.7% vs 7.8%), and congenital or chromosomal malformations (9.6% vs 5.9%). In multivariable analysis the risk for perinatal mortality was greater with each additional complication (adjused odds ratio [aOR] 1.64, 95% confidence interval [CI] 1.30-2.07, P < 0.001; aOR 2.55, 95% CI 1.61-4.04, P < 0.001; aOR 7.88, 95% CI 3.81-16.29, P < 0.001 for one, two, and three or more complications, compared with no complications, respectively)., Conclusion: Complications in first pregnancy ending with live birth are associated with increased risk for perinatal mortality in a subsequent pregnancy., (© 2021 International Federation of Gynecology and Obstetrics.)

In motor-related brain regions, movement intention has been successfully decoded from in-vivo spike train by isolating a lower-dimension manifold that the high-dimensional spiking activity is constrained to. The mechanism enforcing this constraint remains unclear, although it has been hypothesized to be implemented by the connectivity of the sampled neurons. We test this idea and explore the interactions between local synaptic connectivity and its ability to encode information in a lower dimensional manifold through simulations of a detailed microcircuit model with realistic sources of noise. We confirm that even in isolation such a model can encode the identity of different stimuli in a lower-dimensional space. We then demonstrate that the reliability of the encoding depends on the connectivity between the sampled neurons by specifically sampling populations whose connectivity maximizes certain topological metrics. Finally, we developed an alternative method for determining stimulus identity from the activity of neurons by combining their spike trains with their recurrent connectivity. We found that this method performs better for sampled groups of neurons that perform worse under the classical approach, predicting the possibility of two separate encoding strategies in a single microcircuit., Competing Interests: The authors have declared that no competing interests exist.

Compared to traditional paper surveys, online surveys offer a convenient, efficient, and socially distant way to conduct human subjects research. The popularity of online research has grown in recent decades. However, without proper precautions, false respondents pose a serious risk to data integrity. In this paper, we describe our research team's own encounter with survey fraud, steps taken to preserve the integrity of our study, and implications for future public health research.

Cancer patients are at an increased risk of cardiovascular events. Both old-generation cytostatics/cytotoxics and new-generation "targeted" drugs can in fact damage cardiomyocytes, endothelial cells of veins and arteries, specialized cells of the conduction system, pericardium, and valves. A new discipline, cardio-oncology, has therefore developed with the aim of protecting cancer patients from cardiovascular events, while also providing them with the best possible oncologic treatment. Anthracyclines have long been known to elicit cardiotoxicity that, depending on treatment- or patient-related factors, may progress with a variable velocity toward cardiomyopathy and systolic heart failure. However, early compromise of diastolic function may precede systolic dysfunction, and a progression of early diastolic dysfunction to diastolic rather than systolic heart failure has been documented in long-term cancer survivors. This chapter first describes general notions about hypertension in the cancer patient and then moves on reviewing the pathophysiology and clinical trajectories of diastolic dysfunction, and the molecular mechanisms of anthracycline-induced diastolic dysfunction. Diastolic dysfunction can in fact be caused and/or aggravated by hypertension. Pharmacologic foundations and therapeutic opportunities to prevent or treat diastolic dysfunction before it progresses toward heart failure are also reviewed, with a special emphasis on the mechanisms of action of drugs that raised hopes to treat diastolic dysfunction in the general population (sacubitril/valsartan, guanylyl cyclase activators, phosphodiesterase inhibitors, ranolazine, inhibitors of type-2 sodium-glucose-inked transporter). Cardio-oncologists will be confronted with the risk:benefit ratio of using these drugs in the cancer patient., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To develop a text analytics methodology to analyze in a refined manner the drivers of primary care physicians' (PCPs') electronic health record (EHR) inbox work., Study Design: This study used 1 year (2018) of EHR inbox messages obtained from the Epic system for 184 PCPs from 18 practices., Methods: An advanced text analytics latent Dirichlet allocation model was trained on physicians' inbox message texts to identify the different work themes managed by physicians and their relative share of workload across physicians and clinics., Results: The text analytics model identified 30 different work themes rolled up into 2 categories of medical and administrative tasks. We found that 50.8% (range across physicians, 34.5%-61.9%) of the messages were concerned with medical issues and 34.1% (range, 23.0%-48.9%) focused on administrative matters. More specifically, 13.6% (range, 7.1%-22.6%) of the messages involved ambiguous diagnosis issues, 13.2% (range, 6.9%-18.8%) involved condition management issues, 6.7% (range, 1.9%-13.4%) involved identified symptoms issues, 9.5% (range, 5.2%-28.9%) involved paperwork issues, and 17.6% (range, 9.3%-27.1%) involved scheduling issues. Additionally, there was significant variability among physicians and practices., Conclusions: This study demonstrated that advanced text analytics provide a reliable data-driven methodology to understand the individual physician's EHR inbox management work with a significantly greater level of detail than previous approaches. This methodology can inform decision makers on appropriate workflow redesign to eliminate unnecessary workload on PCPs and to improve cost and quality of care, as well as staff work satisfaction.

Background: This report describes and objectivizes reported problems among a cohort of previously hospitalized COVID-19 patients by clinical examination and determination of the required level of rehabilitation sevices., Methods: This report forms part of the Linköping COVID-19 Study (LinCoS) that included 745 individuals from one of 21 Swedish healthcare regions, Region Östergötland (RÖ), admitted to hospital for COVID-19 during March 1st-May 31st, 2020. In this descriptive ambidirectional cohort study, all 185 individuals who had reported concerning persisting symptoms were invited to a multi-professional clinical assessment of somatic, functional, affective, neuropsychological status and rehabilitation needs. Rehabilitation needs were assessed using three sub-scales of the Rehabilitation Complexity Scale-Extended., Findings: Among the 158 (85·4%) cases consenting and included in the analysis, we found a broad array of symptoms and signs attributable to COVID-19 involving respiratory, visual, auditory, motor, sensory and cognitive functions that could be confirmed clinically at five months post-discharge. This translated into 16% [95% CI 13-20] of survivors (70/433) of the total regional cohort of hospitalised patients requiring further rehabilitative interventions at follow-up. Weakness in extremities was reported in 28·5% [21·6, 36·2] (45/158). On examination, clinically overt muscle weakness could be corroborated in 15 individuals (10·5%) [6·1, 16·4]. 48% [40, 56] (76/158) reported cognitive symptoms, while the physician noted overt cognitive impairments in only 3% [1·1, 7·5]. In neuropsychological testing, 37% [28-46] (45/122) performed 1.5 SD below the norm, indicating neurocognitive deficits. Fifty-five individuals (34·8%) [27·4, 42·8] reported new or aggravated pain. In three fourths of them, it exerted a 'moderate' or worse detrimental effect on their ability to work., Interpretation: Our study underscores the importance of providing extensive examination of cases with persisting problems after COVID-19, especially since symptoms such as fatigue and breathlessness are highly nonspecific, but may represent significant underlying functional impairments. Robust neurocognitive testing should be performed, as cognitive problems may easily be overlooked during routine medical consultation. In the Swedish context, most rehabilitative interventions could be provided in a primary care setting. A substantial minority of patients should be triaged to specialized rehabilitation services., Competing Interests: The authors declare no conflicts of interest., (© 2021 Published by Elsevier Ltd.)

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients., Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients., Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332 , Candidatus Saccharimonas , and Haemophilus were all underrepresented in the hospitalized population., Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19., (© 2021 The Authors.)

In June 2019, California expanded Supplemental Nutrition Assistance Program (SNAP) eligibility to Supplemental Security Income (SSI) beneficiaries for the first time. This research assesses the experience and impact of new SNAP enrollment among older adult SSI recipients, a population characterized by social and economic precarity. We conducted semi-structured, in-depth interviews with 20 SNAP participants to explore their experiences with new SNAP benefits. Following initial coding, member-check groups allowed for participants to provide feedback on preliminary data analysis. Findings demonstrate that SNAP enrollment improved participants' access to nutritious foods of their choice, contributed to overall budgets, eased mental distress resulting from poverty, and reduced labor spent accessing food. For some participants, SNAP benefit amounts were too low to make any noticeable impact. For many participants, SNAP receipt was associated with stigma, which some considered to be a social "cost" of poverty. Increased benefit may be derived from pairing SNAP with other public benefits. Together, the impacts of and barriers to effective use of SNAP benefits gleaned from this study deepen our understanding of individual- and neighborhood-level factors driving health inequities among low-income, disabled people experiencing food insecurity and SNAP recipients.

Abstract: Anti-tumor necrosis factor alpha (anti-TNFα) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD) and carry risks for adverse events. We aimed to assess the relationship between anti-TNFα trough concentrations and adverse events rate among pediatric patients with IBD. The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of trough concentration (TC) were reviewed retrospectively for the presence of adverse events. The study cohort included 135 eligible patients (59 [43.7%] girls, mean age at diagnosis 12.9 [±3] years, 111 [82.2%] Crohn disease) who had 1589 measurements of TCs (1037 [63%] infliximab). During a median follow-up period of 1.7 years (IQR 1.1-2.7), we recorded 156 adverse events in 50 patients (37%). Higher TCs were not associated with higher rate of anti-TNFα-related adverse events whereas these events (excluding increase in liver transaminases) were associated with younger age., Competing Interests: D.S.S. received for last 3 years consultation and lecturing fees from AbbVie and research support from Takeda. A.A. received for last 3 years consultation and lecturing fees from Abbvie and Takeda and research grants from Abbvie and Janssen. The remaining authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

We previously demonstrated that the selective retinoic acid receptor (RAR) β 2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. We hypothesized that by decreasing oxidative stress and consequent fibrogenesis, AC261066 could attenuate the development of contractile dysfunction in post-ischemic heart failure (HF). We tested this hypothesis in vivo using an established murine model of myocardial infarction (MI), obtained by permanent occlusion of the left anterior descending coronary artery. Treating mice with AC261066 in drinking water significantly attenuated the post-MI deterioration of echocardiographic indices of cardiac function, diminished remodeling, and reduced oxidative stress, as evidenced by a decrease in malondialdehyde level and p38 mitogen-activated protein kinase expression in cardiomyocytes. The effects of AC261066 were also associated with a decrease in interstitial fibrosis, as shown by a marked reduction in collagen deposition and α -smooth muscle actin expression. In cardiac murine fibroblasts subjected to hypoxia, AC261066 reversed hypoxia-induced decreases in superoxide dismutase 2 and angiopoietin-like 4 transcriptional levels as well as the increase in NADPH oxidase 2 mRNA, demonstrating that the post-MI cardioprotective effects of AC261066 are associated with an action at the fibroblast level. Thus, AC261066 alleviates post-MI cardiac dysfunction by modulating a set of genes involved in the oxidant/antioxidant balance. These AC261066 responsive genes diminish interstitial fibrogenesis and remodeling. Since MI is a recognized major cause of HF, our data identify RAR β 2 as a potential pharmacological target in the treatment of HF. SIGNIFICANCE STATEMENT: A previous report showed that the selective retinoic acid receptor (RAR) β 2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. This study shows that AC261066 attenuates the development of contractile dysfunction and maladaptive remodeling in post-ischemic heart failure (HF) by modulating a set of genes involved in oxidant/antioxidant balance. Since myocardial infarction is a recognized major cause of HF, these data identify RAR β 2 as a potential pharmacological target in the treatment of HF., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Objectives: To report findings on brain MRI and neurocognitive function, as well as persisting fatigue at long-term follow-up after COVID-19 hospitalisation in patients identified as high risk for affection of the central nervous system., Design: Ambidirectional observational cohort study., Setting: All 734 patients from a regional population in Sweden with a laboratory-confirmed COVID-19 diagnosis admitted to hospital during the period 1 March to 31 May 2020., Participants: A subgroup (n=185) with persisting symptoms still interfering with daily life at a telephone follow-up 4 months after discharge were invited for a medical and neuropsychological evaluation. Thirty-five of those who were assessed with a neurocognitive test battery at the clinical visit, and presented a clinical picture concerning for COVID-19-related brain pathology, were further investigated by brain MRI., Main Outcome Measures: Findings on brain MRI, neurocognitive test results and reported fatigue., Results: Twenty-five patients (71%) had abnormalities on MRI; multiple white matter lesions were the most common finding. Sixteen patients (46%) demonstrated impaired neurocognitive function, of which 10 (29%) had severe impairment. Twenty-six patients (74%) reported clinically significant fatigue. Patients with abnormalities on MRI had a lower Visuospatial Index (p=0.031) compared with the group with normal MRI findings., Conclusions: In this group of patients selected to undergo MRI after a clinical evaluation, a majority of patients had abnormal MRI and/or neurocognitive test results. Abnormal findings were not restricted to patients with severe disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective. Extraction of temporal features of neuronal activity from electrophysiological data can be used for accurate classification of neural networks in healthy and pathologically perturbed conditions. In this study, we provide an extensive approach for the classification of human in vitro neural networks with and without an underlying pathology, from electrophysiological recordings obtained using a microelectrode array (MEA) platform. Approach. We developed a Dirichlet mixture (DM) Point Process statistical model able to extract temporal features related to neurons. We then applied a machine learning algorithm to discriminate between healthy control and pathologically perturbed in vitro neural networks. Main Results. We found a high degree of separability between the classes using DM point process features (p-value <0.001 for all the features, paired t-test), which reaches 93.10 of accuracy (92.37 of ROC AUC) with the Random Forest classifier. In particular, results show a higher latency in firing for pathologically perturbed neurons (43 ± 16 ms versus 67 ± 31 ms,μIGfeature distribution). Significance. Our approach has been successful in extracting temporal features related to the neurons' behaviour, as well as distinguishing healthy from pathologically perturbed networks, including classification of responses to a transient induced perturbation., (© 2021 IOP Publishing Ltd.)

Coherent wake emission may be generated only by sufficiently high-contrast driving laser pulses. When the laser contrast is too low, the formed long-scale-length plasma cannot support its generation. In this Letter, we show how, by gently spoiling a pristine laser contrast in an engineered way, coherent wake emission becomes inhibited in the center of the irradiated substrate only, thus forming an annular-shaped source of coherent extreme ultraviolet (XUV) pulses. We present an analytical model that describes the phenomenon and validation of its predictions in the experiment and the simulation. We also show how the ion-acoustic velocity dependency on the laser intensity may be obtained from the emission patterns and offer examples for future applications.

Spinal cord injury (SCI) challenges many aspects of life. Common secondary health conditions are sensorimotor impairments, autonomic dysfunction affecting bowel, bladder, sexual and cardiovascular function, pressure ulcers, pulmonary dysfunction, pain and psychological distress. Primary rehabilitation and lifelong follow-up from a specialized interdisciplinary rehabilitation team is needed to attain and maintain maximum functioning and participation in all aspects of life, and to reduce the risk of complications in the acute and chronic phases after SCI. Most of the almost 300 people who sustain a SCI in Sweden each year can today be expected to live long lives. However, the growing population of people aging with long-term SCI and the increasing number of older adults sustaining an SCI are major challenges for the health care system.  Important research areas are improved neurological diagnostics, regenerative research and long-term consequences of aging with SCI.

In the last several decades, the U.S. Health care industry has undergone a massive consolidation process that has resulted in the formation of large delivery networks. However, the integration of these networks into a unified operational system faces several challenges. Strategic problems, such as ensuring access, allocating resources and capacity efficiently, and defining case-mix in a multi-site network, require the correct modeling of network costs, network trade-offs, and operational constraints. Unfortunately, traditional practices related to cost accounting, specifically the allocation of overhead and labor cost to activities as a way to account for the consumption of resources, are not suitable for addressing these challenges; they confound resource allocation and network building capacity decisions. We develop a general methodological optimization-driven framework based on linear programming that allows us to better understand network costs and provide strategic solutions to the aforementioned problems. We work in collaboration with a network of hospitals to demonstrate our framework applicability and important insights derived from it., (© 2021. The Author(s).)

Recent advances in T cell repertoire (TCR) sequencing allow for the characterization of repertoire properties, as well as the frequency and sharing of specific TCR. However, there is no efficient measure for the local density of a given TCR. TCRs are often described either through their Complementary Determining region 3 (CDR3) sequences, or theirV/J usage, or their clone size. We here show that the local repertoire density can be estimated using a combined representation of these components through distance conserving autoencoders and Kernel Density Estimates (KDE). We present ELATE-an Encoder-based LocAl Tcr dEnsity and show that the resulting density of a sample can be used as a novel measure to study repertoire properties. The cross-density between two samples can be used as a similarity matrix to fully characterize samples from the same host. Finally, the same projection in combination with machine learning algorithms can be used to predict TCR-peptide binding through the local density of known TCRs binding a specific target., Competing Interests: The authors have declared that no competing interests exist.

Background: COVID-19 has accelerated interest in and need for online delivery of healthcare. We examined the reach, engagement and effectiveness of online delivery of lifestyle change programs (LCP) modelled after the Diabetes Prevention Program (DPP) in a multistate, real-world setting., Methods: Longitudinal, non-randomized study comparing online and in-person LCP in a large multistate sample delivered over 1 year. Sample included at-risk adults (n = 26,743) referred to online (n = 9) and in-person (n = 11) CDC-recognized LCP from a multi-state registry (California, Florida and Colorado) between 2015 and 2018. The main outcome was effectiveness (proportion achieving > 5% weight loss) at one-year. Our secondary outcomes included reach (proportion enrolled among referred) and engagement (proportion ≥ 9 sessions by week 26). We used logistic regression modelling to assess the association between participant- and setting -level characteristics with meaningful weight loss., Results: Online LCP effectiveness was lower, with 23% of online participants achieving > 5% weight loss, compared with 35% of in-person participants (p < 0.001). More adults referred to online programs enrolled (56% vs 51%, p < 0.001), but fewer engaged at 6-months (attendance at ≥9 sessions 46% vs 66%, p < 0.001) compared to in-person participants., Conclusions: Compared to adults referred to in-person LCP, those referred to online LCP were more likely to enroll and less likely to engage. Online participants achieved modest meaningful weight loss. Online delivery of LCP is an attractive strategy to deliver and scale DPP, particularly with social distancing measures currently in place. However, it is unclear how to optimize delivery models for maximal impact given trade-offs in reach and effectiveness.

BACKGROUNDThe COVID-19 vaccines currently in use require 2 doses to achieve optimal protection. Currently, there is no indication as to whether individuals who have been exposed to SARS-CoV-2 should be vaccinated, or whether they should receive 1 or 2 vaccine doses.METHODSWe tested the antibody response developed after administration of the Pfizer/BioNTech vaccine in 124 health care professionals, of whom 57 had a previous history of SARS-CoV-2 exposure with or without symptoms.RESULTSPostvaccine antibodies in SARS-CoV-2-exposed individuals increased exponentially within 5 to 18 days after the first dose compared to naive subjects (P < 0.0001). In a multivariate linear regression (LR) model we showed that the antibody response depended on the IgG prevaccine titer and on the exposure to SARS-CoV-2. In symptomatic SARS-CoV-2-exposed individuals, IgG reached a plateau after the second dose, and those who voluntarily refrained from receiving the second dose (n = 7) retained their antibody response. Gastrointestinal symptoms, muscle pain, and fever markedly positively correlated with increased IgG responses. By contrast, all asymptomatic/paucisymptomatic and unexposed individuals showed an important increase after the second dose.CONCLUSIONOne vaccine dose is sufficient in symptomatic SARS-CoV-2-exposed subjects to reach a high titer of antibodies, suggesting no need for a second dose, particularly in light of current vaccine shortage.TRIAL REGISTRATIONClinicalTrials.gov NCT04387929.FUNDINGDolce & Gabbana and the Italian Ministry of Health (Ricerca corrente).

Delays in seeking emergency care stemming from patient reluctance may explain the rise in cases of out-of-hospital cardiac arrest and associated poor health outcomes during the COVID-19 pandemic. In this study we used emergency medical services (EMS) call data from the Boston, Massachusetts, area to describe the association between patients' reluctance to call EMS for cardiac-related care and both excess out-of-hospital cardiac arrest incidence and related outcomes during the pandemic. During the initial COVID-19 wave, cardiac-related EMS calls decreased (-27.2 percent), calls with hospital transportation refusal increased (+32.5 percent), and out-of-hospital cardiac arrest incidence increased (+35.5 percent) compared with historical baselines. After the initial wave, although cardiac-related calls remained lower (-17.2 percent), out-of-hospital cardiac arrest incidence remained elevated (+24.8 percent) despite fewer COVID-19 infections and relaxed public health advisories. Throughout Boston's fourteen neighborhoods, out-of-hospital cardiac arrest incidence was significantly associated with decreased cardiac-related calls, but not with COVID-19 infection rates. These findings suggest that patients were reluctant to obtain emergency care. Efforts are needed to ensure that patients seek timely care both during and after the pandemic to reduce potentially avoidable excess cardiovascular disease deaths.

Objective: To describe data completeness, targeting and reliability of the Swedish version of the Spinal Cord Independence Measure Self-Report (s-SCIM-SR)., Design: Translation and reliability study., Subjects: Programme participants (n = 48) and peer mentors (n = 42) with spinal cord injury enrolled in the INTERnational Project for the Evaluation of "activE Rehabilitation" (inter-PEER)., Methods: The translation process was based on guidelines/recommendations, and involved expert competence, including consumers. The s-SCIM-SR was distributed online, once for programme participants and twice for peer mentors., Results: Sixty-nine individuals (77%) obtained a total score. Most missing data were found in the items Respiration and Using the toilet. Cronbach's alpha for the full scale was 0.89, for Self-care 0.92, for Respiration and sphincter management 0.37 and for Mobility 0.86. The intraclass correlation coefficient was excellent for all subscales and the full scale. Measures of variability showed high sensitivity to changes and Bland Altman analyses revealed no systematic changes between evaluation points., Conclusion: These results support the data completeness, targeting and reliability of the Swedish version of the SCIM-SR. However, some problems were found in the subscale Respiration and sphincter management. The s-SCIM-SR can be considered psychometrically sound and suitable to assess physical independence among persons with spinal cord injury in Swedish community settings.

Objective: Determination of types and frequencies of complications related to ITDD therapy, and assessment of possible risk factors for such complications., Methods: Retrospective study (1999-2014) including all ITDD-implantations at one regional center in Sweden. Descriptors comprised: sex; age; medical condition; body weight index; preoperative ASA-grade; presence of indwelling urinary catheters, feeding tubes, and/or daily urinary or anal incontinence; primary or re-implantation; type of pump and catheter; drug delivered; weekday of surgery; surgical procedure time; surgeon; experience of surgeon; surgical theater; and type of antibiotic prophylaxis. All deaths during the study period were assessed as regards possible relation to ITDD. Data were analyzed with SPSS 25, using Chi 2 test for correlations between descriptors and complications., Results: 231 ITDD pump implantations/re-implantations occurred in 159 patients. Seventy-eight (34%) instances of complications were found: 33 catheter-associated; 6 pump-associated; and 29 infection-associated, where 16 were surgical site infections. A higher infection rate occurred in pump re-implantations, as compared to primary implantations (p = 0.002), and in patients with traumatic spinal cord injury (TSCI) as compared to other diagnoses (p = 0.02). Cloxacillin as antibiotic prophylaxis correlated with a higher infection risk (p = 0.005) relative to other antibiotic prophylaxis. Prolonged surgical procedure time in re-implantations correlated positively with increased catheter-associated complications (p = 0.006)., Conclusion: Complications in ITDD therapy were common, comprising catheter-, infection-, and pump-associated mishaps. A comprehensive system of care needs to be present for managing complications. Future studies may show less complications due to improved protocols and equipment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In California, Supplemental Security Income beneficiaries were ineligible to receive Supplemental Nutrition Assistance Program (SNAP) benefits until a June 2019 policy change. The objective of this study was to determine whether SNAP eligibility was associated with changes in food insecurity and health among older adults and adults with disabilities., Methods: We administered a survey to SSI recipients (N = 213) before (May-August 2019) and after (September 2019-January 2020) the policy change. We examined changes in food insecurity (primary outcome), health status, stress, medication adherence, and dietary intake from baseline to follow-up. Multivariable analyses adjusted for age, sex/gender, race/ethnicity, and education., Results: Of 213 participants at baseline, 56.8% were male, 43.7% were Black/African American, 88.7% had an annual income of less than $15,000, and 89.7% were currently housed. Of 157 participants at follow-up, 114 (72.6%) were newly enrolled in SNAP. At follow-up, compared with baseline, participants were less likely to report food insecurity (83.1% vs 67.5%, P < .001), required less additional money for food ($73.33 vs $47.72 weekly, P < .001), were more likely to report excellent/very good health (26.8% vs 27.6%, P < .001), and were less likely to report cost-related medication nonadherence (24.1% vs 17.7%, P < .001) or use free food programs (82.6% vs 74.5%, P < .001). We found no changes in dietary intake., Conclusion: SNAP uptake rates were high after the policy change. Policies that support older adults and adults with disabilities to enroll in or maintain SNAP benefits may improve health outcomes.

Objectives: To assess the prevalence of residual trans-lesion connectivity in persons with chronic clinically complete spinal cord injury (discompleteness) by neurophysiological methods., Participants: A total of 23 adults with chronic sensorimotor complete spinal cord injury, identified through regional registries the regional spinal cord registry of Östergötland, Sweden., Methods: Diagnosis of clinically complete spinal cord injury was verified by standardized neurological examination. Then, a neurophysiological examination was performed, comprising electroneurography, electromyography, sympathetic skin response and evoked potentials (sensory, laser and motor). Based on this assessment, a composite outcome measure, indicating either strong, possible or no evidence of discomplete spinal cord injury, was formed., Results: Strong neurophysiological evidence of discomplete spinal cord injury was found in 17% (4/23) of participants. If also accepting "possible evidence", the discomplete group comprised 39% (9/23). The remaining 61% showed no neurophysiological evidence of discompleteness. However, if also counting reports of subjective sensation elicited during neurophysiological testing in the absence of objective findings, 52% (12/23) showed indication of discomplete spinal cord injury., Conclusion: Evidence of discomplete spinal cord injury can be demonstrated using standard neurophysiological techniques in a substantial subset of individuals with clinically complete spinal cord injury. This study adds to the evidence base indicating the potential of various modes of cross-lesional sensorimotor functional restoration in some cases of chronic clinically complete spinal cord injury.

Background: Persistence of antibodies to SARS-CoV-2 viral infection may depend on several factors and may be related to the severity of disease or to the different symptoms., Methods: We evaluated the antibody response to SARS-CoV-2 in personnel from 9 healthcare facilities and an international medical school and its association with individuals' characteristics and COVID-19 symptoms in an observational cohort study. We enrolled 4735 subjects (corresponding to 80% of all personnel) for three time points over a period of 8-10 months. For each participant, we determined the rate of antibody increase or decrease over time in relation to 93 features analyzed in univariate and multivariate analyses through a machine learning approach., Results: Here we show in individuals positive for IgG (≥12 AU/mL) at the beginning of the study an increase [ p   =   0 . 0002 ] in antibody response in paucisymptomatic or symptomatic subjects, particularly with loss of taste or smell (anosmia/dysgeusia: OR 2.75, 95% CI 1.753 - 4.301), in a multivariate logistic regression analysis in the first three months. The antibody response persists for at least 8-10 months., Conclusions: SARS-CoV-2 infection induces a long lasting antibody response that increases in the first months, particularly in individuals with anosmia/dysgeusia. This may be linked to the lingering of SARS-CoV-2 in the olfactory bulb., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2021.)

Vipera walser is the most recently recognized European viper. This rare species is endemic to a small area in the Piedmont Alps of Italy, but its closest relatives are found among the Caucasian viper species. In order to provide a starting point for a phylogenetic and biogeographic investigation based on osteology, and including fossils remains, we analyzed four specimens of V. walser and compared them with specimens of the four other Italian viper species. Based on these specimens, we improved the diagnosis of V. walser and provided a first evaluation of intraspecific variability and ontogenetic variation. The skull of V. walser is subject to significant variation, most likely related to ontogeny in some cases (i.e., development of the parietal crest, development of the basioccipital process, shape of the posterior margin of the parabasisphenoid, shape of the quadrate). Based on the studied material, it is possible to distinguish V. walser from the other Italian vipers by the shape of the occipital crest of the supraoccipital, which is posteriorly directed, whereas it is laterally directed in the other species. The osteological diagnosibility provides further support for the validity of V. walser as a distinct species from Vipera berus., (© 2020 Wiley Periodicals LLC.)

Objective: Gastrointestinal (GI) bleeding commonly requires intensive care unit (ICU) in cases of potentialhaemodynamiccompromise or likely urgent intervention. However, manypatientsadmitted to the ICU stop bleeding and do not require further intervention, including blood transfusion. The present work proposes an artificial intelligence (AI) solution for the prediction of rebleeding in patients with GI bleeding admitted to ICU., Methods: A machine learning algorithm was trained and tested using two publicly available ICU databases, the Medical Information Mart for Intensive Care V.1.4 database and eICU Collaborative Research Database using freedom from transfusion as a proxy for patients who potentially did not require ICU-level care. Multiple initial observation time frames were explored using readily available data including labs, demographics and clinical parameters for a total of 20 covariates., Results: The optimal model used a 5-hour observation period to achieve an area under the curve of the receiving operating curve (ROC-AUC) of greater than 0.80. The model was robust when tested against both ICU databases with a similar ROC-AUC for all., Conclusions: The potential disruptive impact of AI in healthcare innovation is acknowledge, but awareness of AI-related risk on healthcare applications and current limitations should be considered before implementation and deployment. The proposed algorithm is not meant to replace but to inform clinical decision making. Prospective clinical trial validation as a triage tool is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Inform coronavirus disease 2019 (COVID-19) infection prevention measures by identifying and assessing risk and possible vectors of infection in nursing homes (NHs) using a machine-learning approach., Design: This retrospective cohort study used a gradient boosting algorithm to evaluate risk of COVID-19 infection (ie, presence of at least 1 confirmed COVID-19 resident) in NHs., Setting and Participants: The model was trained on outcomes from 1146 NHs in Massachusetts, Georgia, and New Jersey, reporting COVID-19 case data on April 20, 2020. Risk indices generated from the model using data from May 4 were prospectively validated against outcomes reported on May 11 from 1021 NHs in California., Methods: Model features, pertaining to facility and community characteristics, were obtained from a self-constructed dataset based on multiple public and private sources. The model was assessed via out-of-sample area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in the training (via 10-fold cross-validation) and validation datasets., Results: The mean AUC, sensitivity, and specificity of the model over 10-fold cross-validation were 0.729 [95% confidence interval (CI) 0.690‒0.767], 0.670 (95% CI 0.477‒0.862), and 0.611 (95% CI 0.412‒0.809), respectively. Prospective out-of-sample validation yielded similar performance measures (AUC 0.721; sensitivity 0.622; specificity 0.713). The strongest predictors of COVID-19 infection were identified as the NH's county's infection rate and the number of separate units in the NH; other predictors included the county's population density, historical Centers of Medicare and Medicaid Services cited health deficiencies, and the NH's resident density (in persons per 1000 square feet). In addition, the NH's historical percentage of non-Hispanic white residents was identified as a protective factor., Conclusions and Implications: A machine-learning model can help quantify and predict NH infection risk. The identified risk factors support the early identification and management of presymptomatic and asymptomatic individuals (eg, staff) entering the NH from the surrounding community and the development of financially sustainable staff testing initiatives in preventing COVID-19 infection., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

In 2019, the National School Lunch Program and School Breakfast Program served approximately 15 million breakfasts and 30 million lunches daily at low or no cost to students.Access to these meals has been disrupted as a result of long-term school closures related to the COVID-19 pandemic, potentially decreasing both student nutrient intake and household food security. By the week of March 23, 2020, all states had mandated statewide school closures as a result of the pandemic, and the number of weekly missed breakfasts and lunches served at school reached a peak of approximately 169.6 million; this weekly estimate remained steady through the final week of April.We highlight strategies that states and school districts are using to replace these missed meals, including a case study from Maryland and the US Department of Agriculture waivers that, in many cases, have introduced flexibility to allow for innovation. Also, we explore lessons learned from the pandemic with the goal of informing and strengthening future school nutrition policies for out-of-school time, such as over the summer.

Despite research on the causes of populism and on the narratives of populist leaders, there is little empirical work on the relationship between populist attitudes and behavior, notably including criminal behavior. Our overarching concern is the recurrent social volatility of metaphorical populist themes that are central to impactful political messaging. Drawing on a national United States survey conducted around the 2016 election, we use multilevel models to show that the politically charged exclusionary boundaries of "America First" populism are behaviorally connected to increased odds of having been arrested. We argue that the rapid redrawing of social boundaries that make up populist attitudes is closely connected with the effects of economic and political frustrations during times of rapid social change. In the process, we develop a behavioral analysis of the social volatility of the recurrent populist movement in America., Competing Interests: The authors declare no competing interest.

Squalene (SQ) is a natural triterpene widely distributed in nature. It is a metabolic intermediate of the sterol biosynthetic pathway and represents a possible target in different metabolic and oxidative stress-related disorders. Growing interest has been focused on SQ's antioxidant properties, derived from its chemical structure. Strong evidence provided by ex vivo models underline its scavenging activity towards free radicals, whereas only a few studies have highlighted its effect in cellular models of oxidative stress. Given the role of unbalanced free radicals in both the onset and progression of several cardiovascular diseases, an in depth evaluation of SQ's contribution to antioxidant defense mechanisms could represent a strategic approach in dealing with these pathological conditions. At present experimental results overall show a double-edged sword role of squalene in cardiovascular diseases and its function has to be better elucidated in order to establish intervention lines focused on its features. This review aims to summarize current knowledge about endogenous and exogenous sources of SQ and to point out the controversial role of SQ in cardiovascular physiology.

Video Photoplethysmography (vPPG) allows for estimation of blood volume pulse (BVP) from the skin by means of a video camera recording at high frequency rate. The estimation procedure presents several drawbacks in its application to real world conditions, such as light changes or movements that often generate artifacts in the extracted BVP waveform. In addition, the process requires a skin segmentation algorithm to distinguish skin pixels from the background. To date, even the most refined skin segmentation algorithms still need a manual definition that could lead to incorrect pixel classification, and consequently to a decrease in the signal-to-noise ratio (SNR). We here propose a fully autonomic procedure able to extract BVP from video recordings of the skin in real world conditions.The experimental protocol is designed to record the signals of interest and to evaluate changes in the Autonomic Nervous System modulation of the heart during a baseline condition and a controlled breathing phase. Video recordings are gathered from 4 young healthy subjects (age: 21±1 years). vPPG signals are processed in order to extract the BVP waveform, and a peak detection algorithm detects pulse wave peaks that are then used to compute specific measures of heart rate variability (HRV).The procedure is successfully validated by comparing the extracted HRV measures against those extracted using a finger photoplethysmograph (fPPG) using three different skin segmentation algorithms from BVP signals.

Objective: Spinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI., Methods: We used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation)., Results: Somatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants., Conclusions: Our results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI., Significance: Identifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

As a leading effort to improve the welfare of smallholder farmers, several governments have led major reforms in improving market access for these farmers through online agricultural platforms. Leveraging collaboration with the state government of Karnataka, India, this paper provides an empirical assessment on the impact of such a reform-implementation of the Unified Market Platform (UMP)-on market prices and farmers' profitability. UMP was created in 2014 to unify all trades in the agricultural wholesale markets of the state to be carried out within a single platform. By November 2019, 62.8 million metric tons of commodities valued at $21.7 billion (USD) have been traded on UMP. Employing a difference-in-differences method, we demonstrate that the impact of UMP on modal prices varies substantially across commodities. In particular, the implementation of UMP has yielded an average 5.1%, 3.6%, and 3.5% increase in the modal prices of paddy, groundnut, and maize. Furthermore, UMP has generated a greater benefit for farmers who produce higher-quality commodities. Given low profit margins of smallholder farmers (2 to 9%), the range of profit improvement is significant (36 to 159%). In contrast, UMP has no statistically significant impact on the modal prices of cotton, green gram, or tur. Using detailed market data from UMP, we analyze how features related to logistical challenges, bidding efficiency, in-market concentration, and the price discovery process differ between commodities with and without a significant price increase due to UMP. These analyses lead to several policy insights regarding the design of similar agri-platforms in developing countries., Competing Interests: Competing interest statement: M.R. is the Managing Director & CEO of Rashtriya e Market Services Private Limited.

Background: Infectious disease outbreaks form major setbacks to aquaculture production and to further development of this important sector. Cyprinid herpes virus-3 (CyHV-3) is a dsDNA virus widely hampering production of common carp (Cyprinus carpio), one of the most farmed fish species worldwide. Genetically disease resistant strains are highly sought after as a sustainable solution to this problem. To study the genetic basis and cellular pathways underlying disease resistance, RNA-Seq was used to characterize transcriptional responses of susceptible and resistant fish at day 4 after CyHV-3 infection., Results: In susceptible fish, over four times more differentially expressed genes were up-regulated between day 0 and 4 compared to resistant fish. Susceptible and resistant fish responded distinctively to infection as only 55 (9%) of the up-regulated genes were shared by these two fish types. Susceptible fish elicited a typical anti-viral response, involving interferon and interferon responsive genes, earlier than resistant fish did. Furthermore, chemokine profiles indicated that the two fish types elicited different cellular immunity responses. A comparative phylogenetic approach assisted in chemokine copies annotation pointing to different orthologous copies common to bony-fishes and even carp-specific paralogs that were differentially regulated and contributed to the different response of these two fish types. Susceptible fish up-regulated more ccl19 chemokines, which attract T-cells and macrophages, the anti-viral role of which is established, whereas resistant fish up-regulated more cxcl8/il8 chemokines, which attract neutrophils, the antiviral role of which is unfamiliar., Conclusions: Taken together, by pointing out transcriptional differences between susceptible and resistant fish in response to CyHV-3 infection, this study unraveled possible genes and pathways that take part in disease resistance mechanisms in fish and thus, enhances our understanding of fish immunogenetics and supports the development of sustainable and safe aquaculture.