Search

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).)

Purpose: To evaluate the efficacy of US-guided vacuum-assisted biopsy (US-VAB) in radiologic-pathologic (rad-path) discordance in women with suspicious breast lesions., Methods: Two thousand three hundred and sixty patients with 2385 BI-RADS category 4 and 5 lesions underwent percutaneous US-guided CNB. Thirty-six lesions were classified as discordant benign and underwent second-line US-VAB. A 14-gauge needle was utilized for CNB and 10-gauge for US-VAB. Final pathology was the reference standard for women who underwent surgery, imaging follow-up in other cases. Rates of malignancy for US-VAB and subsequent surgery were evaluated. Lesions with upgrade and no upgrade to second-line VAB were compared in terms of patient's age, lesion type and characteristics, size and BI-RADS category. Positive predictive value (PPV), negative predictive value (NPV) for BI-RADS categories and diagnostic performance for second-line US-VAB were calculated. p value < 0.05 was considered statistically significant (t-test, Mann-Whitney, χ 2 )., Results: US-VAB identified 10 B2, 9 B3 and 17 B5 lesions with upgrade to malignancy of 47.2% (17/36). There were 8 invasive no special type, 7 ductal in situ, 1 invasive lobular carcinoma and 1 angiosarcoma, and their distribution among BI-RADS categories was: 2/2 in BI-RADS 5 (100%), 12/18 in BI-RADS 4C (67%) and 3/16 in BI-RADS 4B lesions (19%) (p = 0.006). Of the remaining 19 lesions, 6 underwent surgery and 2 were upgraded to ductal carcinoma in situ; 13 underwent radiological follow-up and one resulted malignant. False-negative rate for US-VAB was 15.8% (3/19) with final upgrade to malignancy of 55% (20/36). The univariate analysis revealed mass shape (p = 0.008) and BI-RADS categories (p = 0.006) to be associated with upgrade to malignancy. Sensitivity, specificity, PPV, NPV and accuracy for US-VAB were 85, 100, 100, 84 and 92%, respectively., Conclusions: US-VAB identified almost 50% of cancers missed by CNB, avoiding surgical biopsies and validating as an effective mini-invasive approach in rad-path discordance., (© 2024. Italian Society of Medical Radiology.)

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.

Objective: To quantify the distribution of cauda equina nerve roots in supine and upright positions using manual measurements and radiomics features both in normal subjects and in lumbar spinal canal stenosis (LSCS) patients., Methods: We retrospectively recruited patients who underwent weight-bearing MRI in supine and upright positions for back pain. 3D T2-weighted isotropic acquisition (3D-HYCE) sequences were used to develop a 3D convolutional neural network for identification and segmentation of lumbar vertebrae. Para-axial reformatted images perpendicular to the spinal canal and parallel to each vertebral endplate were automatically extracted. From each level, we computed the maximum antero-posterior (AP) and latero-lateral (LL) dispersion of nerve roots; further, radiomics features were extracted to quantify standardized metrics of nerve root distribution., Results: We included 16 patients with LSCS and 20 normal subjects. In normal subjects, nerve root AP dispersion significantly increased from supine to upright position (p < 0.001, L2-L5 levels), and radiomics features showed an increase in non-uniformity. In LSCS subjects, in the upright position AP dispersion of nerve roots and entropy-related features increased caudally to the stenosis level (p < 0.001) and decreased cranially (p < 0.001). Moreover, entropy-related radiomics features negatively correlated with pre-operative Pain Numerical Rating Scale. Comparison between normal subjects and LSCS patients showed a difference in AP dispersion and increase of variance cranially to the stenosis level (p < 0.001) in the upright position., Conclusions: Nerve root distribution inside the dural sac changed between supine and upright positions, and radiomics features were able to quantify the differences between normal and LSCS subjects., Clinical Relevance Statement: The distribution of cauda equina nerve roots and the redundant nerve root sign significantly varies between supine and upright positions in normal subjects and spinal canal stenosis patients, respectively. Radiomics features quantify nerve root dispersion and correlates with pain severity., Key Points: • Weight-bearing MRI depicts spatial distribution of the cauda equina in both supine and upright positions in normal subjects and spinal stenosis patients. • Radiomics features can quantify the effects of spinal stenosis on the dispersion of the cauda equina in the dural sac. • In the orthostatic position, dispersion of nerve roots is different in lumbar spinal stenosis patients compared to that in normal subjects; entropy-related features negatively correlated with pre-operative Pain Numerical Rating Scale., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

This article explores affectivity, temporality, and their interrelation in patients who contracted COVID-19 during the first wave of the pandemic in Sweden and with symptoms indicative of post-COVID-19 Condition (PCC) that remained one year after the infection. It offers a qualitative phenomenological philosophy analysis, showing how being ill with acute COVID-19 and with symptoms indicative of PCC can entail a radically altered self-world relation. We identify two examples of pre-intentional (existential) feelings: that of listlessness and that of not being able to sense what is real and not real, both of which, in different ways, imply a changed self-world relation. We offer an analysis of intentional feelings: how the fear of not "returning" to one's previous self and the hope of such a return weave together the present and the absent, as well as the past and the future, in ways that make the future appear as constricted, disquieting, or lost. We argue that a phenomenological differentiation among experiences of living with symptoms indicative of PCC-through attention to the way intentional affectivity and pre-intentional affectivity help shape the embodied self's attunement to the world-is apt to yield a better understanding of the variations within these experiences and contribute to clinical practice., (© 2024. The Author(s).)

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.)

Introduction: Postmarketing drug safety surveillance research has focused on the product-patient interaction as the primary source of variability in clinical outcomes. However, the inherent complexity of pharmaceutical manufacturing and distribution, especially of biologic drugs, also underscores the importance of risks related to variability in manufacturing and supply chain conditions that could potentially impact clinical outcomes. We propose a data-driven signal detection method called HMMScan to monitor for manufacturing lot-dependent changes in adverse event (AE) rates, and herein apply it to a biologic drug., Methods: The HMMScan method chooses the best-fitting candidate from a family of probabilistic Hidden Markov Models to detect temporal correlations in per lot AE rates that could signal clinically relevant variability in manufacturing and supply chain conditions. Additionally, HMMScan indicates the particular lots most likely to be related to risky states of the manufacturing or supply chain condition. The HMMScan method was validated on extensive simulated data and applied to three actual lot sequences of a major biologic drug by combining lot metadata from the manufacturer with AE reports from the US FDA Adverse Event Reporting System (FAERS)., Results: Extensive method validation on simulated data indicated that HMMScan is able to correctly detect the presence or absence of variable manufacturing and supply chain conditions for contiguous sequences of 100 lots or more when changes in these conditions have a meaningful impact on AE rates. Applying the HMMScan method to FAERS data, two of the three actual lot sequences examined exhibited evidence of potential manufacturing or supply chain-related variability., Conclusions: HMMScan could be utilized by both manufacturers and regulators to automate lot variability monitoring and inform targeted root-cause analysis. Broad application of HMMScan would rely on a well-developed data input pipeline. The proposed method is implemented in an open-source GitHub repository., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.)

Early bed assignments of elective surgical patients can be a useful planning tool for hospital staff; they provide certainty in patient placement and allow nursing staff to prepare for patients' arrivals to the unit. However, given the variability in the surgical schedule, they can also result in timing mismatches-beds remain empty while their assigned patients are still in surgery, while other ready-to-move patients are waiting for their beds to become available. In this study, we used data from four surgical units in a large academic medical center to build a discrete-event simulation with which we show how a Just-In-Time (JIT) bed assignment, in which ready-to-move patients are assigned to ready-beds, would decrease bed idle time and increase access to general care beds for all surgical patients. Additionally, our simulation demonstrates the potential synergistic effects of combining the JIT assignment policy with a strategy that co-locates short-stay surgical patients out of inpatient beds, increasing the bed supply. The simulation results motivated hospital leadership to implement both strategies across these four surgical inpatient units in early 2017. In the several months post-implementation, the average patient wait time decreased 25.0% overall, driven by decreases of 32.9% for ED-to-floor transfers (from 3.66 to 2.45 hours on average) and 37.4% for PACU-to-floor transfers (from 2.36 to 1.48 hours), the two major sources of admissions to the surgical floors, without adding additional capacity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners., Materials and Methods: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions., Results: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years)., Conclusion: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis., (© 2023. Italian Society of Medical Radiology.)

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.)

This observational cohort study explored objective neurocognitive deficits in COVID-19 patients five months after discharge, and any associations with demographic factors and disease severity indicators. Medical notes of all COVID-19 patients admitted to hospital in Region Östergötland, Sweden, March-May 2020, were reviewed. After applying exclusion criteria, 433 patients were screened by telephone. Of these, 185 patients reported persistent and concerning post-COVID-19 problems, including but not restricted to cognitive functions, and were invited to a clinical evaluation. The Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and Colour-Word Interference Test (CWIT) were used to assess immediate memory, visuo-spatial function, language, attention, delayed memory, and executive function. A total of 133 patients had valid test performances. Mean RBANS Global Cognition Score was 83.4, with 37% scoring below cut-off (1.5 SD). Deficits in Attention and Memory indices were most common, each affecting approximately 30% of the patients. After adjustment for sex, language, level of education and premorbid function, neurocognitive performance was positively associated with length of hospital stay, but not with the disease severity indicators WHO CPS and CRP. Findings support that comprehensive neuropsychological assessment should be performed when patients report post-COVID-19 symptoms that affect daily life.

In an observational study, we analyzed 1293 healthcare workers previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 34.1% developed postacute sequelae of SARS-CoV-2 infection (also known as long COVID). Using a multivariate logistic regression model, we demonstrate that the likelihood of developing long COVID in infected individuals rises with the increasing of duration of infection and that 3 doses of the BNT162b2 vaccine are protective, even during the Omicron wave., Competing Interests: Potential conflicts of interest. M. R. reports payment or honoraria for speaking engagements from Fondazione Internazionale Menarini. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.)

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.)

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.)

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.)

Background: We investigated the personal philosophies of eight persons with a tetraplegic condition (four male, four female), all living in Sweden with a chronic spinal cord injury (SCI) and all reporting a good life. Our purpose was to discover if there is a philosophical mindset that may play a role in living a good life with a traumatic SCI., Methods: Two rounds of in-depth qualitative interviews were performed by the same interviewer, a philosophical practitioner by training (de Miranda). The second round systematically covered the following elements: bodily sense, sense of self, sense of belonging, sense of the possible, sense of purpose and philosophical sense. This six-step method developed by de Miranda is called SMILE&#95;PH, an acronym for Sense-Making Interviews Looking at Elements of Philosophical Health., Results: All the interviewees, as a consequence of their trauma, reported having gone through a reinvention of themselves which implied questioning the meaning and purpose of their life in particular and life in general. A philosophical rather than realistic sense of the possible was abstracted toward teleological growth. All interviewees developed a sense of purpose based on self-interested altruism and solidarity with disabled peers., Conclusions: To reinvent a good life with SCI, in addition to physical training and willpower, one needs to consider philosophical questions about the self and life, what Kant called the cosmic interests of reason: What may I hope? What must I do? What can I know? Our results indicate that we should, in the future, explore what the philosophical health approach may bring to rehabilitation processes in the months or years that follow the trauma., (© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

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.)

The US Department of Agriculture's Economic Research Service leads the federal government in data development and research on food security in US households. Nutrition security is an emerging concept that, although closely related, is distinct from food security. No standard conceptualization or measure of nutrition security currently exists. We review the existing research on nutrition security and how it is informed by the more robust literature on food security and diet quality. Based on this review, we propose a conceptual framework for understanding nutrition security and its relationship to food security. We identify two constructs (healthy diets and nutritional status) and multiple subconstructs that form the basis of nutrition security. The proposed framework and corresponding constructs are intended to provide ( a ) understanding of how nutrition security arises and how it differs from food security, ( b ) background on why assessment and monitoring of nutrition security is important, and ( c ) guidance for a research agenda that will further clarify the meaning of nutrition security and its measurement.

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.

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).)

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.

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).)

The COVID-19 crisis has forced education systems around the world to switch hurriedly from learning in class to learning via online technology. One of the common platforms worldwide for teaching online was zoom. Working under uncertain conditions and facing rapid changes are characteristics of the twenty-first century. Coping adaptively with these challenges requires teachers to apply twenty-first century skills such as creativity and metacognition in their teaching. The purpose of the present study was to examine whether teachers integrate metacognition and creativity in their online lessons more than in classroom instruction. To examine the research question, we analyzed 50 lesson reports (25 for each learning environment) using a mixed-method design model. We used a performance assessment that was based on a creativity metacognitive teaching reports index. Teachers reported greater use of the 'debugging' metacognitive component in online lessons than in classroom lessons. Also, an online environment could provide a suitable platform for promoting students' learning process and encourage teachers to be more creative in terms of diversifying their teaching methods and developing student's creativity. However, the originality component of creativity was less pronounced in online lesson reports. These results can contribute to the field of blended learning and to the literature dealing with the adaptation of teaching to learning environments in the twenty-first century in general and during pandemics in particular., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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.

Proper nutrition is critical for maternal and neonatal health. In January 2017, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Francisco, California, began providing an additional $40 per month in fruit and vegetable (F&V) benefits to pregnant clients with the goal of improving food security and nutrition-related outcomes. We evaluated whether pregnant women on WIC who received this additional F&V benefit exhibited better perinatal and birth outcomes compared with those who received standard WIC benefits. We used 2010-2019 birth certificate data from the National Center for Health Statistics. The intervention group consisted of WIC participants living in San Francisco (SF) County (intervention county) and whose first trimester started after January 2017. We used a quasi-experimental synthetic control method to compare trends between the intervention and control groups (a weighted sample of other California counties that did not distribute additional F&V benefits). Outcomes included low birth weight, preterm birth, small-for-gestational-age, gestational diabetes, and gestational weight gain. No significant differences in maternal and neonatal outcomes among WIC recipients in SF and synthetic control group were observed after the F&V benefits were distributed. Prior studies have shown that additional F&V benefits have positive effects on maternal and infant outcomes, indicating that F&V vouchers are a promising strategy for supporting equitable health outcomes. Our null results suggest that more rigorous research is needed to determine their optimal dose and duration, especially in high-cost-of-living areas, and to examine more upstream and structural interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

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).)

Purpose: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs)., Methods: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs., Results: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215-2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023-1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493-0.971). Noteworthy, no significant differences in LGLZE (p = 0.94), GLN (p = 0.40) and NGDTM contrast (p = 0.54) were found between fractured subjects with BMD T score < - 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis., Conclusions: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

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.)