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Radiomics features (RFs) serve as quantitative metrics to characterize shape, density/intensity, and texture patterns in radiological images. Despite their promise, RFs exhibit reproducibility challenges across acquisition settings, thus limiting implementation into clinical practice. In this investigation, we evaluate the effects of different CT scanners and CT acquisition protocols (KV, mA, field-of-view, and reconstruction kernel settings) on RFs extracted from lumbar vertebrae of a cadaveric trunk. Employing univariate and multivariate Generalized Linear Models (GLM), we evaluated the impact of each acquisition parameter on RFs. Our findings indicate that variations in mA had negligible effects on RFs, while alterations in kV resulted in exponential changes in several RFs, notably First Order (94.4%), GLCM (87.5%), and NGTDM (100%). Moreover, we demonstrated that a tailored GLM model was superior to the ComBat algorithm in harmonizing CT images. GLM achieved R2 > 0.90 in 21 RFs (19.6%), contrasting ComBat's mean R2 above 0.90 in only 1 RF (0.9%). This pioneering study unveils the effects of CT acquisition parameters on bone RFs in cadaveric specimens, highlighting significant variations across parameters and scanner datasets. The proposed GLM model presents a robust solution for mitigating these differences, potentially advancing harmonization efforts in Radiomics-based studies across diverse CT protocols and vendors., (© 2024. The Author(s).)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a cell model now widely used to investigate pathophysiological features of cardiac tissue. Given the invaluable contribution hiPSC-CM could make for studies on cardio-metabolic disorders by defining a postnatal metabolic phenotype, our work herein focused on monitoring the insulin response in CM derived from the hiPSC line UKBi015-B. Western blot analysis on total cell lysates obtained from hiPSC-CM showed increased phosphorylation of both AKT and AS160 following insulin treatment, but failed to highlight any changes in the expression dynamics of the glucose transporter GLUT4. By contrast, the Western blot analysis of membrane fractions, rather than total lysates, revealed insulin-induced plasma membrane translocation of GLUT4, which is known to also occur in postnatal CM. Thus, these findings suggest that hiPSC-derived CMs exhibit an insulin response reminiscent to that of adult CMs regarding intracellular signaling and GLUT4 translocation to the plasma membrane, representing a suitable cellular model in the cardio-metabolic research field. Moreover, our studies also demonstrate the relevance of analyzing membrane fractions rather than total lysates in order to monitor GLUT4 dynamics in response to metabolic regulators in hiPSC-CMs.

Background/Objectives: Inflammatory bowel diseases (IBDs) are chronic disorders that require close monitoring with imaging techniques such as magnetic resonance enterography (MRE). Standardization of radiological reports is crucial for the optimal management of IBD. We surveyed Italian radiologists regarding their experiences with MRE examinations and reporting for IBD. Methods: All members of the Italian Society of Medical and Interventional Radiology (SIRM) were invited to complete an anonymous questionnaire in April 2023. Comparison tests between variables were assessed using the χ 2 test or Fisher exact test according to the least frequency group. Significance level was set for p -value < 0.05. Results: A total of 253 radiologists responded to the survey. Around 70% of the respondents declared personal clinical experience with IBD. Great agreement with the items included and described for both disease activity (i.e., intestinal wall thickness, presence of mucosal ulcers, presence of edema, mucous enhancement) and complications was reported. One-third of the respondents regularly used a structured MRE report. Centers with a high number of IBD patients per year (>1000) mostly used 3 T scanners or both 1.5 T and 3 T scanners ( p < 0.001). The incorporation of scores of disease activity was associated with university and high-volume hospitals ( p < 0.001). Conclusions: This survey highlighted the current routine practice and experience of MRE reports of IBD patients among Italian radiologists. We found deficiencies in the use of radiological scores in MRE reports and attendance at IBD multidisciplinary meetings.

Radiomics features (RFs) studies have showed limitations in the reproducibility of RFs in different acquisition settings. To date, reproducibility studies using CT images mainly rely on phantoms, due to the harness of patient exposure to X-rays. The provided CadAIver dataset has the aims of evaluating how CT scanner parameters effect radiomics features on cadaveric donor. The dataset comprises 112 unique CT acquisitions of a cadaveric truck acquired on 3 different CT scanners varying KV, mA, field-of-view, and reconstruction kernel settings. Technical validation of the CadAIver dataset comprises a comprehensive univariate and multivariate GLM approach to assess stability of each RFs extracted from lumbar vertebrae. The complete dataset is publicly available to be applied for future research in the RFs field, and could foster the creation of a collaborative open CT image database to increase the sample size, the range of available scanners, and the available body districts., (© 2024. The Author(s).)

Significance: Near-infrared laser illumination is a non-invasive alternative/complement to classical stimulation methods in neuroscience but the mechanisms underlying its action on neuronal dynamics remain unclear. Most studies deal with high-frequency pulsed protocols and stationary characterizations disregarding the dynamic modulatory effect of sustained and activity-dependent stimulation. The understanding of such modulation and its widespread dissemination can help to develop specific interventions for research applications and treatments for neural disorders., Aim: We quantified the effect of continuous-wave near-infrared (CW-NIR) laser illumination on single neuron dynamics using sustained stimulation and an open-source activity-dependent protocol to identify the biophysical mechanisms underlying this modulation and its time course., Approach: We characterized the effect by simultaneously performing long intracellular recordings of membrane potential while delivering sustained and closed-loop CW-NIR laser stimulation. We used waveform metrics and conductance-based models to assess the role of specific biophysical candidates on the modulation., Results: We show that CW-NIR sustained illumination asymmetrically accelerates action potential dynamics and the spiking rate on single neurons, while closed-loop stimulation unveils its action at different phases of the neuron dynamics. Our model study points out the action of CW-NIR on specific ionic-channels and the key role of temperature on channel properties to explain the modulatory effect., Conclusions: Both sustained and activity-dependent CW-NIR stimulation effectively modulate neuronal dynamics by a combination of biophysical mechanisms. Our open-source protocols can help to disseminate this non-invasive optical stimulation in novel research and clinical applications., (© 2024 The Authors.)

Background: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD)., Methods: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores., Results: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037)., Conclusions: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans., Competing Interests: Declaration of competing interest The following authors disclose conflicts of interest: Federica Furfaro received consulting fees from Amgen, AbbVie and lecture fees from Janssen and Pfizer; Mariangela Allocca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, AbbVie and Pfizer; Gionata Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion; Silvio Danese served as a speaker, consultant, and advisory board member for Schering-Plow, Abbott (AbbVie) Laboratories, Merck, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson; Alessandro Armuzzi has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, and Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Tigenix; and research grants from MSD, Pfizer, Takeda and Biogen; Maria Rescigno reports payment or honoraria for speaking engagements from Fondazione Internazionale Menarini; Riccardo Levi has received funds from Esaote. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. All remaining authors declare no financial or non-financial competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Infectious diseases challenge health and welfare of humans and animals. Unlike for humans, breeding of genetically resistant animals is a sustainable solution, also providing unique research opportunities. Chances to survive a disease are improved by disease resistance, but depend also on chances to get infected and infect others. Considerable knowledge exists on chances of susceptible and resistant animals to survive a disease, yet, almost none on their infectivity and if and how resistance and infectivity correlate. Common carp (Cyprinus carpio) is widely produced in aquaculture, suffering significantly from a disease caused by cyprinid herpes virus type 3 (CyHV-3). Here, the infectivity of disease-resistant and susceptible fish types was tested by playing roles of shedders (infecting) and cohabitants (infected) in all four type-role combinations. Resistant shedders restricted spleen viral load and survived more than susceptible ones. However, mortality of susceptible cohabitants infected by resistant shedders was lower than that of resistant cohabitants infected by susceptible shedders. Virus levels in water were lower in tanks with resistant shedders leading to lower spleen viral loads in cohabitants. Thus, we empirically demonstrated that disease resistant fish survive better and infect less, with implications to epidemiology in general and to the benefit of aquaculture production., (© 2024. The Author(s).)

Spectral splitting of high harmonic radiation is observed when a gas target is irradiated with a high-energy laser pulse, having an extreme amount of frequency chirp. The phenomenon, which may be observed only by using a multi-TW laser system, originates from the temporal evolution of the phase-matching conditions. We illustrate how these conditions are mapped to the spectral domain, and present experimental evidence which is validated by our model.

During more than 3 years since its emergence, SARS-CoV-2 has shown great ability to mutate rapidly into diverse variants, some of which turned out to be very infectious and have spread throughout the world causing waves of infections. At this point, many countries have already experienced up to six waves of infections. Extensive academic work has focused on the development of models to predict the pandemic trajectory based on epidemiological data, but none has focused on predicting variant-specific spread. Moreover, important scientific literature analyzes the genetic evolution of SARS-CoV-2 variants and how it might functionally affect their infectivity. However, genetic attributes have not yet been incorporated into existing epidemiological modeling that aims to capture infection trajectory. Thus, this study leverages variant-specific genetic characteristics together with epidemiological information to systematically predict the future spread trajectory of newly detected variants. The study describes the analysis of 9.0 million SARS-CoV-2 genetic sequences in 30 countries and identifies temporal characteristic patterns of SARS-CoV-2 variants that caused significant infection waves. Using this descriptive analysis, a machine-learning-enabled risk assessment model has been developed to predict, as early as 1 week after their first detection, which variants are likely to constitute the new wave of infections in the following 3 months. The model's out-of-sample area under the curve (AUC) is 86.3% for predictions after 1 week and 90.8% for predictions after 2 weeks. The methodology described in this paper could contribute more broadly to the development of improved predictive models for variants of other infectious viruses., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Israel's region forms a continental bridge; hence, the freshwater fish fauna in Israel consists of unique populations of species that originated from Africa, Asia, or Europe and are often endemic or at the edge of their distribution range. Worldwide, fish biodiversity suffers significantly from pressures and disturbances of freshwater habitats, especially in arid regions, such as in parts of Israel. Biodiversity conservation requires efficient tools for monitoring changes in populations. DNA barcoding, by complementing and enhancing species identification, provides such monitoring tools. In this study, over 200 specimens representing over 28 species were DNA barcoded and together with previously available records, a DNA barcoding database for freshwater fish of Israel was established. Of the 71 distinct barcodes generated, 37% were new, attesting to the uniqueness of fish populations in Israel. For most species, morphological and molecular species identifications agreed. However, discrepancies were found for five genera. Based on DNA barcoding, we propose Acanthobrama telavivensis as a junior synonym for Acanthobrama lissneri . In Garra spp., we propose splitting Garra nana into two species and assigning Garra rufa in the region to Garra jordanica , or possibly to two species. Israeli Pseudophoxinus kervillei is not the same species as in Syria and Lebanon. However, Pseudophoxinus syriacus might not be endangered since it is genetically very similar to Pseudophoxinus drusensis . In Israel, instead of five reported Oxynoemacheilus species, combining DNA barcoding with morphology suggests only three. Genetic and geographic separation suggested that Aphanius mento is likely a species complex. The study provides a thorough barcoding database, suggests significant species reconsiderations in the region, and highlights the Sea of Galilee and the Beit She'an valley streams as biodiversity "hotspots." This study will therefore promote further studying of the fish species in the region and their ecology, as well as the monitoring and conservation of freshwater fish biodiversity in Israel and the region., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: The HLA region is the hallmark of balancing selection, argued to be driven by the pressure to present a wide variety of viral epitopes. As such selection on the peptide-binding positions has been proposed to drive HLA population genetics. MHC molecules also directly binds to the T-Cell Receptor and killer cell immunoglobulin-like receptors (KIR)., Methods: We here combine the HLA allele frequencies in over six-million Hematopoietic Stem Cells (HSC) donors with a novel machine-learning-based method to predict allele frequency., Results: We show for the first time that allele frequency can be predicted from their sequences. This prediction yields a natural measure for selection. The strongest selection is affecting KIR binding regions, followed by the peptide-binding cleft. The selection from the direct interaction with the KIR and TCR is centered on positively charged residues (mainly Arginine), and some positions in the peptide-binding cleft are not associated with the allele frequency, especially Tyrosine residues., Discussion: These results suggest that the balancing selection for peptide presentation is combined with a positive selection for KIR and TCR binding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Levi, Levi and Louzoun.)

Allopolyploids often experience subgenome dominance, with one subgenome showing higher levels of gene expression and greater gene retention. Here, we address the functionality of both subgenomes of allotetraploid common carp (Cyprinus carpio) by analysing a functional network of interferon-stimulated genes (ISGs) crucial in anti-viral immune defence. As an indicator of subgenome dominance we investigated retainment of a core set of ohnologous ISGs. To facilitate our functional genomic analysis a high quality genome was assembled (WagV4.0). Transcriptome data from an in vitro experiment mimicking a viral infection was used to infer ISG expression. Transcriptome analysis confirmed induction of 88 ISG ohnologs on both subgenomes. In both control and infected states, average expression of ISG ohnologs was comparable between the two subgenomes. Also, the highest expressing and most inducible gene copies of an ohnolog pair could be derived from either subgenome. We found no strong evidence of subgenome dominance for common carp., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Tomato (Solanum lycopersicum) is a prominent fruit with rich genetic resources for crop improvement. By using a phenotype-guided screen of over 7900 tomato accessions from around the world, we identified new associations for complex traits such as fruit weight and total soluble solids (Brix). Here, we present the phenotypic data from several years of trials. To illustrate the power of this dataset we use two case studies. First, evaluation of color revealed allelic variation in phytoene synthase 1 that resulted in differently colored or even bicolored fruit. Secondly, in view of the negative relationship between fruit weight and Brix, we pre-selected a subset of the collection that includes high and low Brix values in each category of fruit size. Genome-wide association analysis allowed us to detect novel loci associated with total soluble solid content and fruit weight. In addition, we developed eight F2 biparental intraspecific populations. Furthermore, by taking a phenotype-guided approach we were able to isolate individuals with high Brix values that were not compromised in terms of yield. In addition, the demonstration of novel results despite the high number of previous genome-wide association studies of these traits in tomato suggests that adoption of a phenotype-guided pre-selection of germplasm may represent a useful strategy for finding target genes for breeding., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41-79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46-69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence ( C c ) and variance in compartment's size ( C MD ) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences ( P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and C c were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and C MD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and C MD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in C c were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to C c , the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and C MD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: H chain rearrangement in B cells is a two-step process where first D H binds J H , and only then V H is joined to the complex. As such, there is no direct rearrangement between V H and J H ., Results: Nevertheless, we here show that the V H JH combinations frequency in humans deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional rearrangements, and much less in out-of-frame rearrangements. The bias cannot be explained by preferred binding for D H genes or a preferred reading frame. Preferred V H J H combinations are shared between donors., Discussion: These results suggest a common structural mechanism for these biases. Through development, thepreferred V H J H combinations evolve during peripheral selection to become stronger, but less shared. We propose that peripheral Heavy chain V H J H usage is initially shaped by a structural selection before the naive B cellstate, followed by pathogen-induced selection for host specific V H - J H pairs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Levi, Dvorkin and Louzoun.)

Food insecurity increases the risk of developing diabetes and its complications. In this article, we describe the complex relationship that exists between food insecurity and diabetes and describe potential mechanisms that may underlie this association. We then describe how two different types of interventions, food-is-medicine and federal nutrition assistance programs, may help address both food insecurity and health. Finally, we outline the research, policy, and practice opportunities that exist to address food insecurity and reduce diabetes-related health disparities., (© 2023 by the American Diabetes Association.)

Essential amino acids (AAs) play a key role in stimulating intestinal adaptation after massive small gut resection. The nutritional effect of dietary amino acids during intestinal regrowth has received considerable attention in recent years. This review explores the significance of dietary amino acids in the nutritional management of infants and children with intestinal failure and short bowel syndrome (SBS) as reported in the medical literature over the last three decades. A literature search was conducted using electronic databases. Breast milk emerged as the first-line enteral regimen recommended for infants with SBS. Hydrolyzed formulas (HFs) or amino acid formulas (AAFs) are recommended when breast milk is not available or if the infant cannot tolerate whole protein milk. The superiority of AAFs over HFs has never been demonstrated. Although glutamine (GLN) is the main fuel for enterocytes, GLN supplementation in infants with SBS showed no difference in the child's dependence upon parenteral nutrition (PN). Circulating citrulline is considered a major determinant of survival and nutritional prognosis of SBS patients. Early enteral nutrition and dietary supplementation of AAs following bowel resection in children are essential for the development of intestinal adaptation, thereby eliminating the need for PN.

Background: The International Spinal Cord Injury (SCI) Activities and Participation Basic Data Set (APBDS) was created to facilitate comparisons of levels of function and disability in SCI individuals worldwide., Aim: Evaluating the reliability and validity of the APBDS's Hebrew translation was our goal., Design: Observational, cross-sectional study., Setting: University and Outpatient Rehabilitation Department of a Medical Center., Population: Individuals with spinal cord injury (SCI)., Methods: The APBDS's Hebrew version was administered to fifty individuals with SCI. Reliability was evaluated through Cronbach Alpha Test and a test-retest method. Validity was determined by testing for convergence with the World Health Organization Disability Assessment Scale (WHODAS) 2.0 and the Medical Outcomes Short Form Health Survey (SF-12)., Results: The Hebrew APBDS had a high test-retest reliability (ICC=0.792) and an adequate Cronbach alpha test (α=0.792). Significant convergent validity was partial with both the WHODAS 2.0 (strong in the self-care objective (r=-0.648) and subjective (r=-0.666), moderate in the total objective (r=-0.640) and subjective (r=-0.570) domains of the APBDS) and the SF-12 (moderate between the total objective domain and the Physical composite score (r=0.378), poor with the Mental composite score (r=0.310))., Conclusions: Although the Hebrew APBDS's moderate reliability and validity warrants further research, it opens new vistas regarding assessment of SCI individuals' satisfaction, activity, and participation., Clinical Rehabilitation Impact: We feel that this data set may be used in the long-term follow-up of SCI individuals in the Sheba SCI rehabilitation registry.

Background: Few studies have reported the long-term health effects of COVID-19. The regional population-based Linköping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission., Methods: This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records., Findings: Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months., Interpretation: This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection., Funding: The study was funded by Region Östergötland., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Author(s).)

Comparisons among the different vaccines against SARS-CoV-2 are important to understand which type of vaccine provides more protection. This study aimed to evaluate the real-life efficacy through symptomatic infection and the humoral response of six different vaccines against SARS-CoV-2-BNT162b2, mRNA-1273, ChAdOx1-S, CoronaVac, Ad26.COV2, and Ad5-nCoV. This multicentric observational longitudinal study involved hospitals from Mexico and Brazil in which volunteers who received complete vaccination schemes were followed for 210 days after the last dose. SARS-CoV-2 Spike 1-2 IgG levels were taken before receiving the first vaccine, 21 days after each dose, and the last sample at six months (+/-1 month) after the last dose. A total of 1132 individuals exposed to five COVID-19 waves were included. All vaccines induced humoral responses, and mRNA vaccines had the highest antibody levels during follow-up. At six months, there was a decline in the SARS-CoV-2 Spike 1-2 IgG antibody titers of 69.5% and 36.4% in subjects with negative and positive history of infection respectively. Infection before vaccination and after complete vaccination scheme correlated with higher antibody titers. The predictors of infection were vaccination with CoronaVac compared to BNT162b2 and ChAdOx1-S. In the presence of comorbidities such as diabetes, rheumatoid arthritis, or dyslipidemia, CoronaVac lowered the risk of infection.

Endothelial function is essential in the maintenance of systemic homeostasis, whose modulation strictly depends on the proper activity of tissue-specific angiocrine factors on the physiopathological mechanisms acting at both single and multi-organ levels. Several angiocrine factors take part in the vascular function itself by modulating vascular tone, inflammatory response, and thrombotic state. Recent evidence has outlined a strong relationship between endothelial factors and gut microbiota-derived molecules. In particular, the direct involvement of trimethylamine N-oxide (TMAO) in the development of endothelial dysfunction and its derived pathological outcomes, such as atherosclerosis, has come to light. Indeed, the role of TMAO in the modulation of factors strictly related to the development of endothelial dysfunction, such as nitric oxide, adhesion molecules (ICAM-1, VCAM-1, and selectins), and IL-6, has been widely accepted. The aim of this review is to present the latest studies that describe a direct role of TMAO in the modulation of angiocrine factors primarily involved in the development of vascular pathologies.

Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16-39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January-May 2021, compared with the years 2019-2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes., (© 2022. The Author(s).)

Introduction: Addressing nutrition disparities and preventing obesity require multi-level interventions, including policies that address the nutrition environment and other social determinants of health. The Nutrition and Obesity Policy Research Evaluation Network (NOPREN) was established in 2009 to conduct transdisciplinary research and accelerate the translation and implementation of science-based policy interventions. This study examined NOPREN's collaborative practices and identified opportunities to improve network impact., Methods: Using a mixed-methods approach, we combined quantitative survey data (n = 106) and in-depth, qualitative interviews (n = 18) to evaluate the experiences of NOPREN members and understand the extent to which NOPREN was achieving its goals., Results: Using the Consolidated Framework for Collaborative Research (CFCR), quantitative and qualitative results were organized into 11 themes. We find that NOPREN's structure and standardized processes facilitate connections to individuals and resources, foster relationships, and support effective cross-sector collaborations. Areas of improvement include capacity building and a more intentional approach towards recruitment of a diverse membership., Conclusion: A collaborative research network can build synergy across sectors and accelerate knowledge transfer. These findings will be used to inform the network's strategic priorities to maximize impact. Findings may also inform similar collaborative efforts for addressing complex public health problems., (© 2023. The Author(s).)

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings., Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine., Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models., Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038)., Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

The immune memory repertoire encodes the history of present and past infections and immunological attributes of the individual. As such, multiple methods were proposed to use T-cell receptor (TCR) repertoires to detect disease history. We here show that the counting method outperforms two leading algorithms. We then show that the counting can be further improved using a novel attention model to weigh the different TCRs. The attention model is based on the projection of TCRs using a Variational AutoEncoder (VAE). Both counting and attention algorithms predict better than current leading algorithms whether the host had CMV and its HLA alleles. As an intermediate solution between the complex attention model and the very simple counting model, we propose a new Graph Convolutional Network approach that obtains the accuracy of the attention model and the simplicity of the counting model. The code for the models used in the paper is provided at: https://github.com/louzounlab/CountingIsAlmostAllYouNeed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akerman, Isakov, Levi, Psevkin and Louzoun.)

The Cohen Diabetic rat is a model of type 2 diabetes mellitus that consists of the susceptible (CDs/y) and resistant (CDr/y) strains. Diabetes develops in CDs/y provided diabetogenic diet (DD) but not when fed regular diet (RD) nor in CDr/y given either diet. We recently identified in CDs/y a deletion in Sdf2l1 , a gene that has been attributed a role in the unfolded protein response (UPR) and in the prevention of endoplasmic reticulum (ER) stress. We hypothesized that this deletion prevents expression of SDF2L1 and contributes to the pathophysiology of diabetes in CDs/y by impairing UPR, enhancing ER stress, and preventing CDs/y from secreting sufficient insulin upon demand. We studied SDF2L1 expression in CDs/y and CDr/y. We evaluated UPR by examining expression of key proteins involved in both strains fed either RD or DD. We assessed the ability of all groups of animals to secrete insulin during an oral glucose tolerance test (OGTT) over 4 weeks, and after overnight feeding (postprandial) over 4 months. We found that SDF2L1 was expressed in CDr/y but not in CDs/y. The pattern of expression of proteins involved in UPR, namely the PERK (EIF2α, ATF4 and CHOP) and IRE1 (XBP-1) pathways, was different in CDs/y DD from all other groups, with consistently lower levels of expression at 4 weeks after initiation of DD and coinciding with the development of diabetes. In CDs/y RD, insulin secretion was mildly impaired, whereas in CDs/y DD, the ability to secrete insulin decreased over time, leading to the development of the diabetic phenotype. We conclude that in CDs/y DD, UPR participating proteins were dysregulated and under-expressed at the time point when the diabetic phenotype became overt. In parallel, insulin secretion in CDs/y DD became markedly impaired. Our findings suggest that under conditions of metabolic load with DD and increased demand for insulin secretion, the lack of SDF2L1 expression in CDs/y is associated with UPR dysregulation and ER stress which, combined with oxidative stress previously attributed to the concurrent Ndufa4 mutation, are highly likely to contribute to the pathophysiology of diabetes in this model.

Background: Fecal calprotectin (FC) is a marker of mucosal inflammation in inflammatory bowel disease (IBD). We aimed to assess the effect of anti-tumor necrosis factor alpha (TNFα) therapy on FC levels in children with IBD., Methods: The medical records of pediatric patients treated with anti-TNFα agents (2015-2020) were reviewed retrospectively. 63 patients had FC levels measured prior to anti TNFα induction with sequential measurements during follow-up. The main outcome measures were time to FC response according to cutoffs of 250, 150, 100 and 50 µgr/gr., Results: Mean age was 13.6 ± 3 years [females 28 (44.4%), Crohn's 55 (87%)]. Outcomes of < 250, < 150, < 100 and < 50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%), respectively. The median time for achieving these cutoffs was 4.8 (1.8-15.6), 7.9 (2.6-16.4), 10.0 (3.5-20.5) and 18.5 (7.0-64.7) months, respectively. Shorter time from diagnosis to treatment was associated with achievement of FC < 50 µgr/gr (p = 0.03). There was no association between age, disease type, anti-TNFα type, inflammatory markers, disease activity indices at baseline and induction anti-TNFα trough concentration and FC response., Conclusions: FC response was achieved by the majority of patients treated with anti-TNFα within a short period of time. FC normalization in responders required almost one year., Impact: Fecal calprotectin response was achieved by the majority of pediatric patients within a relatively short period of time after anti-TNFα induction and maintenance therapy. Fecal calprotectin normalization required an average period of approximately one year in responders. The faster response of fecal calprotectin is associated with shorter time from diagnosis to anti-TNFα treatment. Inflammatory bowel disease treating physicians should be aware of the relatively prolonged time to fecal calprotectin normalization and to allow enough time for anti-TNFα therapy to express its full potential prior to significant interventions., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

While many have advocated for widespread closure of Chinese wet and wholesale markets due to numerous zoonotic disease outbreaks (e.g., SARS) and food safety risks, this is impractical due to their central role in China's food system. This first-of-its-kind work offers a data science enabled approach to identify market-level risks. Using a massive, self-constructed dataset of food safety tests, market-level adulteration risk scores are created through machine learning techniques. Analysis shows that provinces with more high-risk markets also have more human cases of zoonotic flu, and specific markets associated with zoonotic disease have higher risk scores. Furthermore, it is shown that high-risk markets have management deficiencies (e.g., illegal wild animal sales), potentially indicating that increased and integrated regulation targeting high-risk markets could mitigate these risks., (© 2022. The Author(s).)

The advent of vaccines against SARS-CoV-2 has drastically reduced the level of hospitalization with severe COVID-19 disease in infected individuals. However, the diffusion of variants of concern still challenge the protection conferred by vaccines raised against the wild-type form of the virus. Here, we have characterized the antibody response to the BNT162b2 (Comirnaty) mRNA vaccine in patients infected with the Omicron variant. We analyzed a population of 4354 vaccinated healthcare workers (HCW) from 7 different hospitals in Italy and monitored infection with SARS-CoV-2 Omicron. We correlated infection with the antibody response after vaccination. We found that a lower level of IgG, younger age, and the presence of allergies correlate with increased infection during the Omicron wave, and that infections correlate with wild-type spike protein antibody titers below 350 BAU/mL. These results support the necessity of a fourth booster dose, particularly for individuals with lower levels of antibodies.

Background: Understanding association between factors related to clinical work environment and well-being can inform strategies to improve physicians' work experience., Objective: To model and quantify what drivers of work composition, team structure, and dynamics are associated with well-being., Design: Utilizing social network modeling, this cohort study of physicians in an academic health center examined inbasket messaging data from 2018 to 2019 to identify work composition, team structure, and dynamics features. Indicators from a survey in 2019 were used as dependent variables to identify factors predictive of well-being., Participants: EHR data available for 188 physicians and their care teams from 18 primary care practices; survey data available for 163/188 physicians., Main Measures: Area under the receiver operating characteristic curve (AUC) of logistic regression models to predict well-being dependent variables was assessed out-of-sample., Key Results: The mean AUC of the model for the dependent variables of emotional exhaustion, vigor, and professional fulfillment was, respectively, 0.665 (SD 0.085), 0.700 (SD 0.082), and 0.669 (SD 0.082). Predictors associated with decreased well-being included physician centrality within support team (OR 3.90, 95% CI 1.28-11.97, P=0.01) and share of messages related to scheduling (OR 1.10, 95% CI 1.03-1.17, P=0.003). Predictors associated with increased well-being included higher number of medical assistants within close support team (OR 0.91, 95% CI 0.83-0.99, P=0.05), nurse-centered message writing practices (OR 0.89, 95% CI 0.83-0.95, P=0.001), and share of messages related to ambiguous diagnosis (OR 0.92, 95% CI 0.87-0.98, P=0.01)., Conclusions: Through integration of EHR data with social network modeling, the analysis highlights new characteristics of care team structure and dynamics that are associated with physician well-being. This quantitative methodology can be utilized to assess in a refined data-driven way the impact of organizational changes to improve well-being through optimizing team dynamics and work composition., (© 2022. The Author(s).)

Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI., Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed., Results: We recruited 1867 individuals [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with previous SARS-CoV-2 infection, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naïve SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had the highest number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001)., Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response only correlates with AEs in patients previously exposed to SARS-CoV-2., Registration Number: ClinicalTrials.gov, identifier NCT05228912., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Romero-Ibarguengoitia, González-Cantú, Pozzi, Levi, Mollura, Sarti, Sanz-Sánchez, Rivera-Salinas, Hernández-Ruíz, Armendariz-Vázquez, Del Rio-Parra, Barco-Flores, González-Facio, Azzolini, Barbieri, de Azevedo Dias, Henriques Guimarães Júnior, Bastos-Borges, Acciardi, Paez-Bo, Teixeira and Rescigno.)

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.

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.

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.

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.)

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.

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.

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.)