Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of chondroitin sulfate proteoglycan sulfation allows delayed sympathetic reinnervation after cardiac ischemia–reperfusion

Sympathetic nerve loss in the heart predicts the risk of ventricular arrhythmias after myocardial infarction (MI) in patients. Sympathetic denervation after cardiac ischemia–reperfusion is sustained by matrix components chondroitin sulfate proteoglycans (CSPGs) in the cardiac scar. We showed that 4,6‐sulfation of CSPGs was critical for preventing nerve growth into the scar. Promoting early reinnervation with therapeutics reduces arrhythmias during the first 2 weeks after MI, but the longer‐term consequences of restoring innervation are unknown. Therefore, we asked if the beneficial effects of early reinnervation were sustained. We compared cardiac function and arrhythmia susceptibility 40 days after MI in mice treated on Days 3–10 with vehicle or with intracellular sigma peptide to restore innervation. Surprisingly, both groups had normal innervation density in the cardiac scar 40 days after MI, indicating delayed reinnervation of the infarct in vehicle‐treated mice. That coincided with similar cardiac function and arrhythmia susceptibility in the two groups. We investigated the mechanism allowing delayed reinnervation of the cardiac scar. We found that CSPG 4,6‐sulfation, which is elevated early after ischemia–reperfusion, was reduced to control levels allowing reinnervation of the infarct. Thus, remodeling of extracellular matrix weeks after injury leads to remodeling of sympathetic neurons in the heart.
Immunosuppressants exert differential effects on pan‐coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir

Abstract Background Immunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs. Objective This study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan‐coronavirus infection in cell and human airway organoids (hAOs) culture models. Methods Different coronaviruses (including wild type, delta and omicron variants of SARS‐CoV‐2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested. Results Dexamethasone and 5‐aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6‐thioguanine (6‐TG), tofacitinib and filgotinib treatment dose‐dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS‐CoV‐2 was 0.62 μM and the half maximum cytotoxic concentration (CC50) was above 30 μM, which resulted in a selective index (SI) of about 50. The anti‐coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6‐TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity. Conclusions Different immunosuppressants have distinct effects on coronavirus replication, with 6‐TG, MPA, tofacitinib and filgotinib possessing pan‐coronavirus antiviral activity. The combinations of MPA, 6‐TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.
Patients with positive patch test to formaldehyde can be safely vaccinated with formaldehyde‐containing vaccines

Prophylactic vaccination against influenza and other epidemic viruses is recommended for citizens above 65 years. Several vaccines may contain traces of formaldehyde and are contra‐indicated in patients hypersensitive (in the broadest possible meaning) to formaldehyde. Thorough knowledge on the various subtypes of hypersensitivity is sparse among non‐dermatologists and non‐allergists, and therefore many patients are prevented from vaccination based on a positive patch test to formaldehyde. The purpose of this retrospective study was to investigate whether patients with positive patch test to formaldehyde subsequently receiving a formaldehyde‐containing vaccine and developed a severe adverse reaction.
GraphscoreDTA: optimized graph neural network for protein–ligand binding affinity prediction

Abstract Motivation Computational approaches for identifying the protein–ligand binding affinity can greatly facilitate drug discovery and development. At present, many deep learning-based models are proposed to predict the protein–ligand binding affinity and achieve significant performance improvement. However, protein–ligand binding affinity prediction still has fundamental challenges. One challenge is that the mutual information between proteins and ligands is hard to capture. Another challenge is how to find and highlight the important atoms of the ligands and residues of the proteins. Results To solve these limitations, we develop a novel graph neural network strategy with the Vina distance optimization terms (GraphscoreDTA) for predicting protein–ligand binding affinity, which takes the combination of graph neural network, bitransport information mechanism and physics-based distance terms into account for the first time. Unlike other methods, GraphscoreDTA can not only effectively capture the protein–ligand pairs’ mutual information but also highlight the important atoms of the ligands and residues of the proteins. The results show that GraphscoreDTA significantly outperforms existing methods on multiple test sets. Furthermore, the tests of drug–target selectivity on the cyclin-dependent kinase and the homologous protein families demonstrate that GraphscoreDTA is a reliable tool for protein–ligand binding affinity prediction. Availability and implementation The resource codes are available at https://github.com/CSUBioGroup/GraphscoreDTA.
A prediction model to refine the timing of an early second‐look laparoscopic exploration in patients with colon cancer at high risk of early peritoneal metastasis recurrence

In patients at high risk of peritoneal metastasis (PM) recurrence following surgical treatment of colon cancer (CC), second‐look laparoscopic exploration (SLLE) is mandatory; however, the best timing is unknown. We created a tool to refine the timing of early SLLE in patients at high risk of PM recurrence.
Plasma Heating and Confinement in GOL-3 Multi Mirror Trap

Recent results of the experiments at GOL-3 facility are presented. In present configuration of the device, plasma with a density of 1014[divided by]1016 cm-3 is confined in a 12-meter-long solenoid, which comprises 55 corrugation cells with mirror ratio Bmax/Bmin=4.8/3.2 T. The plasma in the solenoid is heated up to 2-4 keV temperature by a high power relativistic electron beam (˜1 MeV, ˜30 kA, ˜8 μs, ˜120 kJ) injected through one of the ends. Mechanism of experimentally observed fast ion heating, issues of plasma stability and confinement are discussed.
Ethnographic understandings of sexual and reproductive health and HIV care for adolescents in Blantyre, Malawi

Abstract Sexual and reproductive health (SRH) care and support are provided to adolescents living with HIV, with the aim to build safer sex negotiation skills, sexual readiness and reproductive preparedness while reducing unintended pregnancies and sexually transmitted infections. We consider how different settings might either constrain or facilitate access to resources and support. Ethnographic research was conducted in Malawi in teen club clinic sessions at an enhanced antiretroviral clinic from November 2018 to June 2019. Twenty-one individual and five group interviews were conducted with young people, caregivers, and healthcare workers, and were digitally recorded, transcribed, and translated into English for thematic analysis. Drawing on socio-ecological and resilience theories, we considered the different ways in which homes, schools, teen club clinics, and community settings all functioned as interactional, relational, and transformational spaces to allow young people to talk about and receive information on sexuality and health. Young people perceived that comprehensive SRH support enhanced their knowledge, sexual readiness, and reproductive preparedness. However, their desire to reproduce at an early age complicated their adoption of safer sex negotiation skills and SRH care. Engaging and talking about SRH and related issues varied according to physical and social space, suggesting the value of multiple locations for support and resources for young people with HIV.
Individualized targeting is warranted in subcallosal cingulate gyrus deep brain stimulation for treatment‐resistant depression: A tractography analysis

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment‐resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity‐based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography‐based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra‐ and inter‐subject variance using test–retest dataset. Two tractography‐based targets were identified. Tractography‐based target‐1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography‐based target‐2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography‐based target to anatomy‐based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± SD of targets between intra‐ and inter‐subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG‐DBS target planning procedure.
Micro-computed tomography evaluation of the effects of orthodontic force on immature maxillary first molars and alveolar bone mineral density of Sprague–Dawley rats

Objective To investigate changes in the immature teeth of Sprague–Dawley rats during orthodontic treatment and to explore the changes in the peri-radicular alveolar bone through micro-computed tomography (CT). Methods Twenty-five 26-day-old male Sprague–Dawley rats were included. The maxillary left first molar was moved mesially under a continuous force of 30 cN, and the right first molar served as the control. After orthodontic treatment for 7, 14, 21, 28, and 42 days, the root length, tooth volume, and alveolar bone mineral density (BMD) around the mesial root were measured through micro-CT. Results The immature teeth continued to elongate after application of orthodontic force. The root length on the force side was significantly smaller than that on the control side, whereas the differences in the volume change between both sides were not statistically significant. Alveolar bone in the coronal part of the compression and tension sides showed no difference in BMD between the experimental and control groups. The BMD of the experimental group decreased from day 14 to day 42 in the apical part of the compression side and increased from day 7 to day 42 in the apical part of the tension side. The BMD of the experimental group decreased in the root apex part on day 7. Conclusions The root length and volume of immature teeth showed continued development under orthodontic forces. Alveolar bone resorption was observed on the compression side, and bone formation was observed on the tension side.
Bet‐hedging via dispersal aids the evolution of plastic responses to unreliable cues

Adaptive plasticity is expected to evolve when informative cues predict environmental variation. However, plastic responses can be maladaptive even when those cues are informative, if prediction mistakes are shared across members of a generation. These fitness costs can constrain the evolution of plasticity when initial plastic mutants use of cues of only moderate reliability. Here, we model the barriers to the evolution of plasticity produced by these constraints and show that dispersal across a metapopulation can overcome them. Constraints are also lessened, though not eliminated, when plastic responses are free to evolve gradually and in concert with increased reliability. Each of these factors be viewed as a form of bet‐hedging: by lessening correlations in the fates of relatives, dispersal acts as diversifying bet‐hedging, while producing submaximal responses to a cue can be understood as a conservative bet‐hedging strategy. While poor information may constrain the evolution of plasticity, the opportunity for bet‐hedging may predict when that constraint can be overcome.
Temporal intra‐host variability of mpox virus genomes in multiple body tissues

Whole‐genome sequencing (WGS) has been widely used for the genomic characterization and the phylogenesis of mpox virus (MPXV) 2022 multi‐country outbreak. To date, no evidence has been reported on intra‐host evolution within samples collected over time from a single patient with long‐term infection. Fifty‐one samples were collected from five patients at different time points post‐symptom onset. All samples were confirmed as MPXV DNA positive, amplified by a multiplexed PCR amplicon, and sequenced by WGS. Complete MPXV genomes were assembled by reference mapping and then aligned to perform phylogenetic and hierarchical clustering analysis. Large intra‐host variability was observed among the MPXV genomes sequenced from samples of two immunocompromised with advanced HIV‐1 infection patients with prolonged MPXV shedding. Overall, 20 nucleotide mutations were identified in the 32 genomes from HIV patients, differently distributed in samples collected from different tissues and at different time points. No sequence compartmentalization nor variation was observed in the three patients with rapid viral clearance. MPXV exhibits adaptation to changing environments within the infected host and consequently demonstrates tissue compartmentalization. Further studies are needed to elucidate the role of this adaptation in forming a pool of genetic variability and contributing to viral persistence and its clinical implications.
Vertically molybdenum disulfide nanosheets on carbon cloth using CVD by controlling growth atmosphere for electrocatalysis

Molybdenum disulfide (MoS2) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS2 during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS2 nanosheets were fabricated on carbon cloth (CC) using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS2 exhibits excellent HER activity due to the combination of optimized microstructures and coupling with CC. Our findings provide new insights to design advanced MoS2-based electrocatalysts for HER.
LOGICAL CONSEQUENCE AS TRUTH-PRESERVATION

It is often suggested that truth-preservation is insufcient for logical consequence, and that consequence needs to satisfy a further condition of relevance. Premises and conclusion in a valid consequence must be relevant to one another, and truth-preservation is too coarsegrained a notion to guarantee that. Thus logical consequence is the intersection of truth-preservation and relevance. This situation has the absurd consequence that one might concede that the conclusion of an argument was true (since the argument had true premises and was truth-preserving); yet should refuse to infer the conclusion from the premises, in the absence of demonstration of the relevance of the premises to the conclusion. The error lies in giving insufcient attention to the notion of truthpreservation. Relevance is no separable ingredient in the analysis of logical consequence, but a necessary condition of it. If an argument really is truth-preserving, then that in itself is enough to show that the premises are (logically) relevant to the conclusion.
Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma

Objective: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). Background: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. Methods: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan–Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. Results: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70–0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. Conclusions: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.
Reassessing the survival benefit of deceased donor liver transplantation: retrospective cohort study

Introduction: Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing’s ‘Share-15’ policy states that candidates with MELD-Na scores of 15 or greater have priority to receive local organ offers compared to candidates with lower MELD-Na scores. Since the inception of this policy, major changes in the primary etiologies of end-stage liver disease have occurred and previous assumptions need to be recalibrated. Methods: The authors retrospectively analyzed the Scientific Registry of Transplant Recipients database between 2012 and 2021 to determine life years saved by DDLT at each interval of MELD-Na score and the time-to-equal risk and time-to-equal survival versus remaining on the waitlist. The authors stratified our analysis by MELD exception points, primary disease etiology, and MELD score. Results: On aggregate, compared to remaining on the waitlist, a significant 1-year survival advantage of DDLT at MELD-Na scores as low as 12 was found. The median life years saved at this score after a liver transplant was estimated to be greater than 9 years. While the total life years saved were comparable across all MELD-Na scores, the time-to-equal risk and time-to-equal survival decreased exponentially as MELD-Na scores increased. Conclusion: Herein, the authors challenge the perception as to the timing of DDLT and when that benefit occurs. The national liver allocation policy is transitioning to a continuous distribution framework and these data will be instrumental to defining the attributes of the continuos allocation score.
Compact frequency-quadrupled pulsed 1030nm fiber laser

A compact 1030nm fiber laser for ultraviolet generation at 257.5nm is presented. The laser employs a short length of highly-doped, large core (20μm), coiled polarization-maintaining ytterbium-doped double-clad fiber pumped by a wavelength-stabilized 975nm diode. It is passively Q-switched via a Cr4+:YAG saturable absorber and generates 2.4W at 1030nm in a 110μJ pulse train. Lithium triborate (LBO) and beta-barium borate (BBO) are used to achieve 325mW average power at the fourth harmonic. The laser's small form factor, narrow linewidth and modest power consumption are suitable for use in a man-portable ultraviolet Raman explosives detection system.
Nasal spray of an IgM‐like ACE2 fusion protein HH‐120 accelerates SARS‐CoV‐2 clearance: A single‐center propensity score‐matched cohort study

HH‐120, a recently developed IgM‐like ACE2 fusion protein with broad‐spectrum neutralizing activity against all ACE2‐utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH‐120 nasal spray in SARS‐CoV‐2‐infected subjects. Eligible symptomatic or asymptomatic SARS‐CoV‐2‐infected participants were enrolled in a single‐arm trial to receive the HH‐120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real‐world data of SARS‐CoV‐2‐infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH‐120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH‐120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment‐emergent adverse events and treatment‐related adverse events of HH‐120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH‐120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS‐CoV‐2‐infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH‐120 nasal spray in large‐scale randomized controlled clinical trials.