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BACKGROUND: Patients hospitalized with COVID-19 can clinically deteriorate after a period of initial stability, making optimal timing of discharge a clinical and operational challenge. OBJECTIVE: To determine risks for post-discharge readmission and death among patients hospitalized with COVID-19. DESIGN: Multicenter retrospective observational cohort study, 2020-2021, with 30-day follow-up. PARTICIPANTS: Adults admitted for care of COVID-19 respiratory disease between March 2, 2020, and February 11, 2021, to one of 180 US hospitals affiliated with the HCA Healthcare system. MAIN MEASURES: Readmission to or death at an HCA hospital within 30 days of discharge was assessed. The area under the receiver operating characteristic curve (AUC) was calculated using an internal validation set (33% of the HCA cohort), and external validation was performed using similar data from six academic centers associated with a hospital medicine research network (HOMERuN). KEY RESULTS: The final HCA cohort included 62,195 patients (mean age 61.9 years, 51.9% male), of whom 4704 (7.6%) were readmitted or died within 30 days of discharge. Independent risk factors for death or readmission included fever within 72 h of discharge; tachypnea, tachycardia, or lack of improvement in oxygen requirement in the last 24 h; lymphopenia or thrombocytopenia at the time of discharge; being ≤ 7 days since first positive test for SARS-CoV-2; HOSPITAL readmission risk score ≥ 5; and several comorbidities. Inpatient treatment with remdesivir or anticoagulation were associated with lower odds. The models AUC for the internal validation set was 0.73 (95% CI 0.71-0.74) and 0.66 (95% CI 0.64 to 0.67) for the external validation set. CONCLUSIONS: This large retrospective study identified several factors associated with post-discharge readmission or death in models which performed with good discrimination. Patients 7 or fewer days since test positivity and who demonstrate potentially reversible risk factors may benefit from delaying discharge until those risk factors resolve.

In a retrospective metatranscriptomics study, we identified tick-borne encephalitis virus (TBEV) to be the causative agent for a fatal non-suppurative meningoencephalitis in a three-week-old Dalmatian puppy in Switzerland. Further investigations showed that the two other littermates with similar signs and pathological lesions were also positive for TBEV. By using an unbiased approach of combining high-throughput sequencing (HTS) and bioinformatics we were able to solve the etiology and discover an unusual case of TBEV in three young puppies. Based on our findings, we suggest that a vector-independent transmission of TBEV occurred and that most likely an intrauterine infection led to the severe and fulminant disease of the entire litter. We were able to demonstrate the presence of TBEV RNA by in situ hybridization (ISH) in the brain of all three puppies. Furthermore, we were able to detect TBEV by RT-qPCR in total RNA extracted from formalin-fixed and paraffin embedded (FFPE) blocks containing multiple peripheral organs. Overall, our findings shed light on alternative vector-independent transmission routes of TBEV infections in dogs and encourage veterinary practitioners to consider TBEV as an important differential diagnosis in neurological cases in dogs.

Abstract Background Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6–5.0% of cases, but the underlying mechanisms remain largely unknown. Methods To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70–80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). Results ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. Conclusions ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.

Introduction Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART.Methods and analysis B-Free is a multistage, randomised, multicentre, open-label, non-inferiority trial, embedded within the Swiss HIV Cohort Study and conducted in collaboration with cohorts of PWH in the Netherlands and France. Cohort participants with a history of ART change due to virologic failure and who maintain HIV virologic suppression with an ART regimen consisting of a pharmacological booster and at least two drugs from classes other than nucleoside reverse transcriptase inhibitors are included. Patients with major drug resistance mutations against DTG or DOR and individuals with chronic hepatitis B virus infection are not eligible for the study. Individuals are randomised 1:1 to either receiving co-formulated DTG/3TC and DOR once daily or continuing their boosted ART regimen. The primary outcome is the proportion of individuals lacking virologic control (HIV-RNA ≥50 cp/mL) at 48 weeks, according to the Food and Drug Administration snapshot algorithm. Changes in DDI burden (assessed using a DDI score), treatment satisfaction (assessed using the HIV Treatment Satisfaction Questionnaire), quality of life and mental health represent key secondary outcomes. Additional secondary outcomes include the proportion of individuals developing new resistance-associated mutations and changes in quality of life and mental health. In a qualitative substudy, we will conduct semistructured interviews with a subset of participants to assess their expectations and experiences towards HIV treatment and clinical research in general. Enrolling 210 individuals will provide 80% power to demonstrate non-inferiority, defined as less than 8% absolute increase in loss of viral suppression in individuals randomised to DOR/DTG/3TC (one-sided type I error rate of 0.025).Ethics and dissemination The study was approved by the competent ethics committees (reference number BASEC 2023–01060) and the regulatory authority Swissmedic (reference number 701655) in Switzerland before the enrolment of the first participant. Approval by the European Medicines Agency and local ethical committees in the Netherlands and France will be obtained prior to including participants in these countries. Participant’s written informed consent is obtained by the investigators before enrolment. The results of all major B-Free study outcomes will be submitted to peer-reviewed journals that enable Open Access publication.Trial registration number Swiss National Clinical Trials Portal (SNCTP000005686, registered on 06 November 2023) and Clinicaltrials.gov (NCT06037564, registered on 07 September 2023).

Background Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics. Methods and Results We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra‐axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester. Conclusions Structural covariance networks offer a sensitive, data‐driven approach to explore whole‐brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

In recent years, mathematical models of decision making, such as the diffusion model, have been endorsed in individual differences research. These models can disentangle different components of the decision process, like processing speed, speed-accuracy trade-offs, and duration of non-decisional processes. The diffusion model estimates individual parameters of cognitive process components, thus allowing the study of individual differences. These parameters are often assumed to show trait-like properties, that is, within-person stability across tasks and time. However, the assumption of temporal stability has so far been insufficiently investigated. With this work, we explore stability and change in diffusion model parameters by following over 270 participants across a time period of two years. We analysed four different aspects of stability and change: rank-order stability, mean-level change, individual differences in change, and profile stability. Diffusion model parameters showed strong rank-order stability and mean-level changes in processing speed and speed-accuracy trade-offs that could be attributed to practice effects. At the same time, people differed little in these patterns across time. In addition, profiles of individual diffusion model parameters proved to be stable over time. We discuss implications of these findings for the use of the diffusion model in individual differences research.

Abstract Structural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22–38 weeks gestational age range.

Abstract The stronger people hold self-enhancing (that is, egoistic or hedonic) values, the less they tend agree with pro-environmental efforts. An exploratory (N = 901) and a confirmatory study (N = 404) examined the effectiveness of pro-environmental messages matched to individuals' values. Findings indicate that strong endorsement of self-transcendent (that is, altruistic or biospheric) values is associated with unspecific endorsement of pro-environmental messages, while individuals endorsing self-enhancement values respond positively only to value-matched appeals.

Abstract This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented. Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24–36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66–100% visibility of relevant craniofacial and head structures in the SVR output, and 20–100% and 60–90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20–36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing. Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy. Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.

[This corrects the article DOI: 10.1158/2767-9764.CRC-21-0060.][This corrects the article DOI: 10.1158/2767-9764.CRC-21-0060.].

7SK non-coding RNA (7SK) negatively regulates RNA polymerase II (RNA Pol II) elongation by inhibiting positive transcription elongation factor b (P-TEFb), and its ribonucleoprotein complex (RNP) is hijacked by HIV-1 for viral transcription and replication. Methylphosphate capping enzyme (MePCE) and La-related protein 7 (Larp7) constitutively associate with 7SK to form a core RNP, while P-TEFb and other proteins dynamically assemble to form different complexes. Here, we present the cryo-EM structures of 7SK core RNP formed with two 7SK conformations, circular and linear, and uncover a common RNA-dependent MePCE-Larp7 complex. Together with NMR, biochemical, and cellular data, these structures reveal the mechanism of MePCE catalytic inactivation in the core RNP, unexpected interactions between Larp7 and RNA that facilitate a role as an RNP chaperone, and that MePCE-7SK-Larp7 core RNP serves as a scaffold for switching between different 7SK conformations essential for RNP assembly and regulation of P-TEFb sequestration and release.

The EU and other states have made legislative efforts to clarify data mining in copyrightable works, but the situation remains obscure and confusing, especially in a globalised field where international legislation can contribute to opacity. The present paper aims at asserting a common position of three communities representing biodiversity sciences and data specialists on this issue and to propose common and best practice guidelines so that they become universally accepted rules.As scientific data users, we take the standpoint that scientific data are not copyrightable and, furthermore, they can be accessed, shared and reused freely. Thus, once legal access has been gained to copyrighted publications, the data within those scholarly publications can be considered to be open data that is freely extractable. This set of recommendations has been reached specifically for scientific use and societal benefits.

Abstract Background Little is known about knee mechanics and muscle control after augmented ACL repair. Our aim was to compare knee biomechanics and leg muscle activity during walking between the legs of patients 2 years after InternalBraceTM-augmented anterior cruciate ligament repair (ACL-IB) and between patients after ACL-IB and ACL reconstruction (ACL-R), and controls. Methods Twenty-nine ACL-IB, 27 sex- and age-matched ACL-R (hamstring tendon autograft) and 29 matched controls completed an instrumented gait analysis. Knee joint angles, moments, power, and leg muscle activity were compared between the involved and uninvolved leg in ACL-IB (paired t-tests), and between the involved legs in ACL patients and the non-dominant leg in controls (analysis of variance and posthoc Bonferroni tests) using statistical parametric mapping (SPM, P uninvolved) and maximum knee flexion moment during stance (-0.07Nm/kg, CI [-0.13;-0.00]; involved ACL-R). Compared to controls, ACL-IB (SPM: 0–3%GC, P = 0.015; 98–100%, P = 0.016; DP: -6.3 mm, CI [-11.7;-0.8]) and ACL-R (DP: -6.0 mm, CI [-11.4;-0.2]) had lower (maximum) anterior tibia position around heel strike. ACL-R also had lower maximum knee extension moment (DP: -0.13Nm/kg, CI [-0.23;-0.02]) and internal knee rotation moment (SPM: 34–41%GC, P

Background This study aimed to quantify the mechanoresponse of 10 blood marker candidates for joint metabolism to a walking stress test in patients with knee osteoarthritis and to determine the association among marker kinetics and with accumulated load and patient reported outcomes. Methods 24 patients with knee osteoarthritis completed questionnaires, and a 30-minute walking stress test with six blood serum samples and gait analysis. Concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases (MMP)-1, -3, and -9, epitope resulting from cleavage of type II collagen by collagenases (C2C), type II procollagen (CPII), interleukin (IL)-6, proteoglycan (PRG)-4, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and resistin were determined by enzyme-linked immunosorbent assays, Joint load (moments and compartmental forces) was estimated using musculoskeletal modeling using gait analysis data. Results COMP and MMP-3 showed an immediate increase after the walking stress followed by a decrease. MMP-9 and resistin showed a delayed decrease below pre-stress levels. ∆COMP correlated with ∆MMP-3 for most time points. ∆MMP-9 correlated with ∆resistin for most time points. The load-induced increase in blood marker levels correlated among blood markers and time points. C2C and resistin correlated positively and C2C/CPII and MMP2 correlated negatively with load during gait. Immediate relative ∆CPII and ∆MMP1 and delayed relative ∆COMP, ∆IL6, ∆C2C, ∆CPII, ∆MMP1 and ∆MMP3 correlated with the load accumulated during the walking stress. Baseline C2C levels correlated with Knee Osteoarthritis Outcome Score (KOOS) subscales and load-induced changes in MMP-3 with KOOS and Short Form 36 quality of life subscores (P Conclusions The distinct and differentiated physiological response to the walking stress depends on accumulated load and appears relevant for patient reported osteoarthritis outcome and quality of life and warrants further investigation in the context of disease progression. ClinicalTrials.gov registration: NCT02622204