Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6–7 Months of age: A Phase 1/2 Randomized Trial

Abstract Background Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post–ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post–dose 2. Conclusions ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.
Clinical utilization of multiple antibodies of Mycobacterium tuberculosis for serodiagnosis evaluation of tuberculosis: a retrospective observational cohort study

Abstract Objectives We aimed to investigate clinical uncertainties by characterizing the accuracy and utility of commercially available antibodies of Mycobacterium tuberculosis in the diagnostic assessment of suspected tuberculosis in high-burden countries. Methods We conducted a retrospective, descriptive, cohort study among participants aged ≥ 18 years with suspected tuberculosis in Nanning, Guangxi, and China. Participants were tested for M. tuberculosis infection using commercially available antibodies against Mycobacterum tuberculosis. Specificity, sensitivity, negative and positive predictive values, and negative and positive likelihood ratios of the tests were determined. Sputum specimens and bronchoalveolar lavage fluid were sent for mycobacterial culture, Xpert MTB/RIF assay, and cell-free M. tuberculosis DNA or RNA assay. Blood samples were used for IGRAs, T-cell counts (CD3 + CD4+ and CD3 + CD8+), and antibodies to tuberculosis test. Results Of the 1857 participants enrolled in this study, 1772 were included in the analyses, among which, 1311 were diagnosed with active tuberculosis. The specificity of antibody against 16kD for active tuberculosis was 92.7% (95% confidence interval [CI]: 89.3–95.4) with a positive likelihood ratio for active tuberculosis cases of 3.1 (95% CI: 2.1–4.7), which was higher than that of antibody to Rv1636 (90.5% [95% CI: 86.6–93.5]), antibody to 38kD (89.5% [95% CI: 85.5–92.7]), antibody against CFP-10 (82.6% [95% CI: 77.9–86.7]), and antibody against LAM (79.3% [95% CI: 74.3–83.7]). Sensitivity ranged from 15.8% (95% CI: 13.9–17.9) for antibody against Rv1636 to 32.9% (95% CI: 30.4–35.6) for antibody to LAM. Conclusions Commercially available antibodies against to Mycobacterium tuberculosis do not have sufficient sensitivity for the diagnostic evaluation of active tuberculosis. However, antibody against Rv1636 and 16kD may have sufficiently high specificities, high positive likelihood ratios, and correspondingly high positive predictive values to facilitate the rule-in of active tuberculosis. HIGHLIGHTS Existing M. tuberculosis antigens do achieve a limited sensitivity and negative predictive value to rule out a diagnosis of tuberculosis. M. tuberculosis antigens may help to rule in a diagnosis of active or latent tuberculosis in clinical setting among the high burden tuberculosis countries. This study is the largest retrospective, descriptive, cohort study to evaluate the clinical utilization of existing M. tuberculosis antigens integrating M. tuberculosis immunogens in patients with suspected active tuberculosis in high-burden country. KEY MESSAGES Existing antibodies against M. tuberculosis antigens exhibit limited sensitivity for ruling out TB. Multiple TB antibodies against M. tuberculosis antigens may aid in identifying cases of active or latent tuberculosis. The biggest cohort for investigating clinical applications of TB antibodies.
Noncanonical autophagy is a new strategy to inhibit HSV-1 through STING1 activation

ABSTRACT STING1 (stimulator of interferon response cGAMP interactor 1) plays an essential role in immune responses for virus inhibition via inducing the production of type I interferon, inflammatory factors and macroautophagy/autophagy. In this study, we found that STING1 activation could induce not only canonical autophagy but also non-canonical autophagy (NCA) which is independent of the ULK1 or BECN1 complexes to form MAP1LC3/LC3-positive structures. Whether STING1-induced NCA has similar characters and physiological functions to canonical autophagy is totally unknown. Different from canonical autophagy, NCA could increase single-membrane structures and failed to degrade long-lived proteins, and could be strongly suppressed by interrupting vacuolar-type H+-translocating ATPase (V-ATPase) activity. Importantly, STING1-induced NCA could effectively inhibit DNA virus HSV-1 in cell model. Moreover, STING1 [1–340], a STING1 mutant lacking immunity and inflammatory response due to deletion of the tail end of STING1, could degrade virus through NCA alone, suggesting that the antiviral effect of activated STING1 could be separately mediated by inherent immunity, canonical autophagy, and NCA. In addition, the translocation and dimerization of STING1 do not rely on its immunity function and autophagy pathway. Similar to canonical autophagy, LC3-positive structures of NCA induced by STING1 could finally fuse with lysosomes, and the degradation of HSV-1 could be reverted by inhibition of lysosome function, suggesting that the elimination of DNA virus via NCA still requires the lysosome pathway. Collectively, we proved that besides its classical immunity function and canonical autophagy pathway, STING1-induced NCA is also an efficient antiviral pathway for the host cell. Abbreviations: ATG: autophagy related; Baf: bafilomycin A1; CASM: conjugation of LC3 to a single membrane; CGAS: cyclic GMP-AMP synthase; cGAMP: cyclic GMP-AMP; CQ: chloroquine; CTD: C-terminal domain; CTT: C-terminal tail; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; HSV-1: herpes simplex virus 1; IRF3: interferon regulatory factor 3; IFNs: interferons; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; RB1CC1/FIP200: RB1 inducible coiled-coil 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TGOLN2/TGN46: trans-golgi network protein 2; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H+-translocating ATPase; VSV: vesicular stomatitis virus
Proteomic analysis of zebrafish folliculogenesis identifies YB-1 (Ybx1/ybx1) as a potential gatekeeping molecule controlling early ovarian folliculogenesis

Abstract As in mammals, ovarian folliculogenesis in teleosts also consists of two phases: the primary growth (PG) and secondary growth (SG) phases, which are analogous to the preantral and antral phases respectively in mammals. In this study, we performed a proteomic analysis on zebrafish follicles undergoing the PG–SG transition aiming to identify factors involved in the event. Numerous proteins showed significant changes, and the most prominent one was Y-box binding protein 1 (YB-1; Ybx1/ybx1), a transcription factor and mRNA-binding protein. YB-1 belongs to the Y-box binding protein family, which also includes the gonad-specific YB-2. Interestingly, phylogenetic analysis showed no YB-2 homolog in zebrafish. Although ybx1 mRNA was expressed in various tissues, its protein Ybx1 was primarily produced in the gonads, similar to YB-2 in other species. In the ovary, Ybx1 protein started to appear in early follicles newly emerged from the germ cell cysts, reached the highest level in late PG oocytes, but decreased precipitously when the follicles entered the SG phase. In PG follicles, Ybx1 might function as a key component of the messenger ribonucleoprotein particles (mRNPs) in association with other RNA-binding proteins. Similar to mammalian YB-1, zebrafish Ybx1 also contains functional signals that determine its intracellular localization. In conclusion, Ybx1 may play dual roles of YB-1 and YB-2 in zebrafish. In the ovary, Ybx1 binds mRNAs to stabilize them while preventing their translation. At PG–SG transition, Ybx1 is removed to release the masked mRNAs for translation into functional proteins, leading to follicle activation. Graphical Abstract
High-flow nasal cannula versus noninvasive ventilation after extubation in hypercapnic patients with COPD: A retrospective analysis

To the Editor : Invasive ventilation is a necessary form of respiratory support in the intensive care unit. Noninvasive ventilation (NIV) is frequently used as a sequential respiratory support following extubation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) to prevent the recurrence of respiratory failure, avoid reintubation, and improve the prognosis. [1] However, some patients may have a poor tolerance to NIV, and possibly leading to the development of face pressure ulcers and dys-expectoration. A high-flow nasal cannula (HFNC) delivers a heated and humidified air/oxygen mixture at high flow through a nasal cannula. In recent years, HFNC has been widely used in respiratory support in children and adults and accepted as a sequential therapy in patients after extubation. Studies have shown that HFNC is not inferior to NIV in hypoxemic respiratory failure, especially in some specific conditions. [2,3] These conditions include patients at high risk of respiratory failure after extubation, post-extubation application for acute respiratory failure, and prevention of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Nevertheless, several confounding mediators such as hypercapnia or dys-expectoration, were not taken into
Narrative strategies to re-signify sexual violence among gender and sexuality diverse Central American migrants in Tijuana

Abstract This study discusses how gender and sexuality diverse Central American migrants, currently staying at shelters in Tijuana, reconstruct experiences of sexual violence in their lives, both during childhood and throughout their migratory journey. It analyses the narrative strategies used to re-signify these experiences in the present, to construct possible futures as sexual subjects. In-depth autobiographical interviews were conducted with nine Central American migrants of diverse genders and sexualities and were analysed using an approach inspired by dramaturgical analysis. We identified the most significant events, characters and settings related to experiences of sexual violence. Three main strategies of resignification were identified: the reaffirmation of pleasure, desire, or consent; the decision to emigrate; and entry into loving-affective relationships. The focus on the analysis of sexual violence before and during the migration event represents a contribution to the ongoing debate on sexuality, gender, and migration. Strategies of resignification allow participants to imagine possible narratives future as subjects who wish to express their gender identity and sexuality freely.
Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(μ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(μ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.
Characterizing the Force-Motion Tradeoff in Body-Powered Transmission Design

Upper-limb prosthesis users continue to reject devices despite continued research efforts. Today, the passive topology of body-powered prehensors, which physically transmits grasp force and position data between user and device, results in improved performance over myoelectric alternatives. However, the loads and postures on the user’s body also result in discomfort, fatigue, and worsened grasp force control. Despite the long history and everyday adoption of body-powered prehensors in society, the measurement of how specific body loads and postures affect grasp performance and user experience has yet to be systematically studied. In this work, we present a body-powered prosthesis emulator to independently change required input forces and motions to study the positive and negative effects provided by the inherent haptic feedback. Using a simulated grasping task, we collect functional and qualitative data from 15 participants using a shoulder harness interface. Outcomes show that lowering required input motions and forces independently reduces negative outcomes, with diminishing returns below 1:1 output mappings. Given the tradeoff between force and motion in traditional body-powered transmissions, a transmission ratio of 1:1 balances both requirements. The purpose of this study is to inform future prehensor designs that leverage the transparency of body-power to deliver high functionality while mitigating user discomfort.
Influence of electrode gap on breakdown voltages of a multi-gap pseudospark discharge device under nanosecond pulses

Pseudospark-sourced electron beams of high energy can be produced in multi-gap pseudospark devices under high breakdown voltages. The breakdown voltages and the gap separation of the discharge device have been studied. Collisional ionization in the gaps has been semi-quantitatively analyzed. Based on the results, the influence of the electrode gap on the breakdown voltages has been verified. Collisional ionization during device discharge begins initially in the first gap near the cathode. The electrons produced in the first gap move towards the second gap and contribute to the collisional ionization in the second gap. The process proceeds to successive gaps with collisional ionization occurring in all gaps. For wider gap separations, the number of collisional ionizations in the gap is large, and hence, more electrons move through the intermediate electrodes into the posterior gaps. This creates a cascading of collisional ionizations, leading to a decrease in breakdown voltage. The influence of the coeffic.
Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes

ABSTRACT In eukaryotic genomes, hundreds to thousands of potential start sites of DNA replication named origins are dispersed across each of the linear chromosomes. During S-phase, only a subset of origins is selected in a stochastic manner to assemble bidirectional replication forks and initiate DNA synthesis. Despite substantial progress in our understanding of this complex process, a comprehensive ‘identity code’ that defines origins based on specific nucleotide sequences, DNA structural features, the local chromatin environment, or 3D genome architecture is still missing. In this article, we review the genetic and epigenetic features of replication origins in yeast and metazoan chromosomes and highlight recent insights into how this flexibility in origin usage contributes to nuclear organization, cell growth, differentiation, and genome stability.
Neuropsychiatric symptoms and imbalance of atrophy in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left–right and dorso‐ventral axes. Little is known about how these structural imbalances impact clinical symptomatology. The goal of this study was to assess the frequency of frontotemporal asymmetry (right‐ or left‐lateralization) and dorsality (ventral or dorsal predominance of atrophy) and to investigate their clinical correlates. Neuropsychiatric symptoms and structural images were analyzed for 250 patients with behavioral variant frontotemporal dementia. Frontotemporal atrophy was most often symmetric while left‐lateralized (9%) and right‐lateralized (17%) atrophy were present in a minority of patients. Atrophy was more often ventral (32%) than dorsal (3%) predominant. Patients with right‐lateralized atrophy were characterized by higher severity of abnormal eating behavior and hallucinations compared to those with left‐lateralized atrophy. Subsequent analyses clarified that eating behavior was associated with right atrophy to a greater extent than a lack of left atrophy, and hallucinations were driven mainly by right atrophy. Dorsality analyses showed that anxiety, euphoria, and disinhibition correlated with ventral‐predominant atrophy. Agitation, irritability, and depression showed greater severity with a lack of regional atrophy, including in dorsal regions. Aberrant motor behavior and apathy were not explained by asymmetry or dorsality. This study provides additional insight into how anatomical heterogeneity influences the clinical presentation of patients with behavioral variant frontotemporal dementia. Behavioral symptoms can be associated not only with the presence or absence of focal atrophy, but also with right/left or dorsal/ventral imbalance of gray matter volume.
Prophylactic therapy for prevention of surgical site infection after extraction of third molar: An overview of reviews

Background To compare the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars with different degree of impaction. Material and Methods Systematic reviews and meta-analyses evaluating the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars were included. An electronic search was performed in PubMed, EMBASE, and the Cochrane Database of Systematic reviews. AMSTAR 2 tool was used to evaluate the confidence in results from the included reviews. Descriptive analyses were performed. Results Six reviews were included. A significant benefit of different antibiotics to the prevention of site infection after extraction of third molars was reported. Amoxicillin/amoxicillin clavulanic acid could significantly reduce the rate of surgical site infection versus placebo. Chlorhexidine gel could significantly reduce the frequency of alveolar osteitis versus placebo. Conclusions Based on the limited evidence, there is a significant benefit of prophylactic therapy while the comparative effect of different types of prophylactic regimes are controversial. Key words:Third molar extraction, antibiotics, chlorhexidine, overview.
How safe are heartburn medications and who should use them?

ABSTRACT Introduction Heartburn is a frequent symptom occurring in daily clinical practice and is mainly associated with gastroesophageal reflux disease (GERD). However, it can be stimulated by various factors and diseases other than GERD can present with heartburn. Therefore, physicians must be very careful in distinguishing GERD from non-GERD conditions in their patients, particularly when heartburn is refractory to anti-reflux medications. Areas covered The aim of this narrative review was to analyze the medical literature regarding the prevalence of heartburn and the various clinical disorders which can be present with this symptom. The type of medications usually adopted for treating heartburn and their grade of safety have been reviewed using an extensive computerized (Medline/PubMed) search with particular focus on the last 20 years. Expert opinion Many drugs can be used for relieving heartburn in patients with GERD, although PPIs are the pharmacological agents with the greatest efficacy. However, it must be highlighted that many non-GERD conditions may present clinically with this symptom whose intensity does not differ between GERD and functional esophageal disorders, which represent about 50% of all patients with suspected GERD. It is very important to identify these functional conditions because their treatment differs completely from that of GERD.
Tacrolimus population pharmacokinetics in adult heart transplant patients

Tacrolimus is an immunosuppressant largely used in heart transplantation. However, the calculation of its exposure based on the area under the curve (AUC) requires the use of a population pharmacokinetic (PK) model. The aims of this work were (i) to develop a population PK model for tacrolimus in heart transplant patients, (ii) to derive a maximum a posteriori Bayesian estimator (MAP‐BE) based on a limited sampling strategy (LSS) and (iii) to estimate probabilities of target attainment (PTAs) for AUC and trough concentration (C0).
Family perspectives of ex situ heart perfusion

Pediatric patients awaiting a heart transplant have high waitlist mortality. Several strategies have been utilized to decrease waiting times, but a mortality risk still exists. New medical technologies may improve waiting times and associated mortality. Ex situ heart perfusion (ESHP) is one such technology, which can decrease the impact of cold ischemia on the donor heart and allow for a longer out‐of‐body time. Adoption of such technology in pediatric heart transplantation will require support from end users, including patient and families. The aim of this qualitative study was to report the perspectives of families with experience related to pediatric HTx toward ESHP.