Miracle-dz/UniFAR-FTUs huggingface dataset:
CD4:CD8 Ratio and CD8 Cell Count and Their Prognostic Relevance for Coronary Heart Disease Events and Stroke in Antiretroviral Treated Individuals: The Swiss HIV Cohort Study

Supplemental Digital Content is Available in the Text. Introduction: HIV infection leads to a persistent expansion of terminally CD8 T cells and CD8 T suppressor cells, a marker of chronic immune activation leading to a low CD4:CD8 ratio that may persist in the presence of potent antiretroviral therapy and regained CD4 helper cells. It remains unclear whether a low CD4:CD8 ratio is associated with cardiovascular diseases. Methods: We conducted an observational cohort study to investigate the association of immune depression and activation as characterized by the proxy of the CD4:CD8 ratio on the hazard of coronary heart disease (CHD) and stroke among treated individuals living with HIV, while accounting for viral load and known risk factors for cardiovascular diseases and exposure to abacavir or protease inhibitors. We used Cox proportional hazard models with time-dependent cumulative and lagged exposures to account for time-evolving risk factors and avoid reverse causality. Results: CD4, CD8, and CD4:CD8 immunological markers were not associated with an increased hazard for CHD. CD8 cell count lagged at 12 months above 1000 cells per μL increased the hazard of stroke, after adjusting for sociodemographics, cardiovascular risk factors, and exposure to specific types of antiretroviral drugs. Conclusions: This analysis of treated HIV-positive individuals within a large cohort with long-term follow-up does not provide evidence for a prognostic role of immune dysregulation regarding CHD. However, increased CD8 cell count may be a moderate risk factor for stroke. Early detection and treatment of HIV-positive individuals are crucial for an optimal immune restoration and a limited CD8 cells expansion.
SARS‐CoV‐2 Omicron and its current known unknowns: A narrative review

The emergence of the SARS‐CoV‐2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1. 1.529. 1 (BA.1), BA.1 + R346K (BA.1.1), and B.1. 1.529. 2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub‐variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor‐binding domain, there is reduced detection by conventional RT‐PCR and rapid antigen tests. Moreover, the two‐dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub‐variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub‐variants. Such research is necessary to improve the management and prevention of Omicron infection.
Masking Vibrations and Contact Force Affect the Discrimination of Slip Motion Speed in Touch

Multiple cues contribute to the discrimination of slip motion speed by touch. In our previous article, we demonstrated that masking vibrations at various frequencies impaired the discrimination of speed. In this article, we extended the previous results to evaluate this phenomenon on a smooth glass surface, and for different values of contact force and duration of the masking stimulus. Speed discrimination was significantly impaired by masking vibrations at high but not at low contact force. Furthermore, a short pulse of masking vibrations at motion onset produced a similar effect as the long masking stimulus, delivered throughout slip motion duration. This last result suggests that mechanical events at motion onset provide important cues to the discrimination of speed.
A notion of weak convergence in metric spaces

We discuss some basic properties of polar convergence in metric spaces. This notion has been introduced in (17) as an appropriate mode of con- vergence which allows to extend to Banach spaces the analysis of the defect of compactness, relative to gauge groups, already established in Hilbert spaces. Polar convergence is closely connected with the notion of �-convergence al- ready known from several years (see (12)). Possible existence of a topology which induces polar convergence is also investigated. Some applications of polar convergence follow.
Mirror neurons and empathy-related regions in psychopathy: Systematic review, meta-analysis, and a working model

ABSTRACT Mirror neurons have been associated with empathy. People with psychopathic traits present low levels of empathy. To analyze this, a systematic review of fMRI studies of people with psychopathic traits during an emotional facial expression processing task was performed. The regions of interest were structures associated with the mirror neuron system: ventromedial prefrontal cortex (vmPFC), inferior parietal lobe (IPL), inferior frontal gyrus and superior temporal sulcus. The analysis was also extended to structures related to affective empathy (insula, amygdala and anterior cingulate cortex) and to two more emotional processing areas (orbitofrontal cortex and fusiform gyrus). Hypoactivation was more frequently observed in regions of the mirror neuron system from people with high psychopathic traits, as well as in the emotional processing structures, and those associated with affective empathy, except for the insula, where it presented higher activity. Differences were observed for all types of emotions. The results suggest that the mirror neuron system is altered in psychopathy and their relationship with affective empathy deficits is discussed.
Disseminated Gonococcal Infections in Manitoba, Canada: 2013 to 2020

Disseminated gonococcal infections have increased in Manitoba, Canada, since 2013. Genotyping revealed that disseminated gonococcal infection is associated with Neisseria gonorrhoeae strains that are phylogenetically diverse but share the porB-2206 allele. Background Gonorrhea, when left untreated, can enter the blood and cause disseminated gonococcal infections (DGIs). Disseminated gonococcal infections, which can include dermatitis, tenosynovitis, migratory polyarthralgia, and arthritis, have been increasing in Manitoba (MB), Canada, since 2013. Endocarditis, a rare DGI, was identified in 3 MB patients in 2018 and 2019. Methods Antimicrobial resistance, molecular types, and resistance-associated mutations were determined for MB DGI isolates (n = 103) identified from 2013 to 2020 using phenotypic and genotypic methods. Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) of residual nucleic acid amplification testing samples (n = 13) from 2019 and 2020 were also determined. Results The increase in DGI in MB in 2019 and 2020 was due to the NG-MAST 11508 molecular type with porB-2206, a persistent PorB protein structure type “A” allele. These isolates had low-level resistance to erythromycin and tetracycline. Conclusions Molecular surveillance of gonorrhea and, in particular, gonococcal strains resulting in DGI is imperative to monitor clonal transmission within populations. These data can be used to alert public health of emerging issues and support public health interventions.
Formative objective structured clinical examination with immediate feedback improves surgical clerks’ self-confidence and clinical competence

Abstract Objective Clerkship is crucial for fourth-year medical students before entering the clinical environment. However, lack of confidence impairs clerks’ performance during the clinical rotation. We assess the impact of formative Objective Structured Clinical Examination (OSCE) with immediate feedback on surgical clerks’ self-confidence and clinical competence. Methods This is a prospective randomized controlled study. Thirty-eight fourth-year medical students starting their surgical clerkship were randomly divided into the control group (n = 19) and the OSCE group (n = 19), where an extra 6-station formative OSCE was given prior to the surgical rotation with immediate feedback on the participant’s performance. Self-confidence assessment (SCA) was collected from each participant before, right after the formative OSCE and one month later. Clinical competence was assessed using a mini-clinical evaluation exercise (mini-CEX) with a case of acute abdominal pain and direct observation of procedural skills (DOPS) with incision and suture one month later. Results The SCAs were significantly improved in the OSCE group right after the training, and a month later, compared to the control group. The mini-CEX score was significantly higher in the OSCE group compared to the control group, but not the DOPS score of incision and suture. Conclusion The formative OSCE with immediate feedback could significantly enhance surgical clerks’ self-confidence and their clinical competence when taking the history, performing the physical examination, and in clinical reasoning; however, the formative OSCE did not improve their dexterity in performing the procedural skills.
Dysregulated stem cell niches and altered lymphocyte recirculation cause B and T cell lymphopenia in WHIM syndrome

Gain-of-function (GOF) mutations in CXCR4 cause WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, characterized by infections, leukocyte retention in bone marrow (BM), and blood leukopenias. B lymphopenia is evident at early progenitor stages, yet why do CXCR4 GOF mutations that cause B (and T) lymphopenia remain obscure? Using a CXCR4 R334X GOF mouse model of WHIM syndrome, we showed that lymphopoiesis is reduced because of a dysregulated mesenchymal stem cell (MSC) transcriptome characterized by a switch from an adipogenic to an osteolineage-prone program with limited lymphopoietic activity. We identify lymphotoxin beta receptor (LTβR) as a critical pathway promoting interleukin-7 (IL-7) down-regulation in MSCs. Blocking LTβR or CXCR4 signaling restored IL-7 production and B cell development in WHIM mice. LTβR blocking also increased production of IL-7 and B cell activating factor (BAFF) in secondary lymphoid organs (SLOs), increasing B and T cell numbers in the periphery. These studies revealed that LTβR signaling in BM MSCs and SLO stromal cells limits the lymphocyte compartment size. Description Increased LTÃ¯Â¢R signaling in mesenchymal stem cells reduces IL-7 production and causes lymphopenia in WHIM syndrome. Subpar sustenance for lymphocytes WHIM syndrome, a human inborn error of immunity featuring reduced numbers of circulating lymphocytes, is caused by gain-of-function mutations in CXCR4. Zehentmeier et al. investigated stromal cell abnormalities contributing to lymphopenia by analyzing gene expression by bone marrow mesenchymal stem cells (MSCs) in a mouse model of the R334X WHIM-inducing mutation. Bone marrow MSCs in the mutant mice exhibited reduced expression of the gene for IL-7, a cytokine critical for early B cell differentiation, because of excess signaling through the lymphotoxin beta receptor (LTβR). Reduced expression of the gene for IL-7 in bone marrow and impaired lymphocyte access to survival niches in secondary lymphoid organs contributed to the lymphopenia. These findings demonstrate that CXCR4 and LTβR are viable targets for therapies to ameliorate the immunodeficiency of WHIM syndrome.
Investigate the stemness of adult adipose‐derived stromal cells based on single‐cell RNA‐sequencing

The cellular heterogeneity and genetic features of stemness of adipose‐derived stromal cells (ADSCs) remain unclear. Using single‐cell RNA sequencing (scRNA‐seq), we investigated the genomic features of the stemness gene in ADSCs with genetic variability. We cultured the ADSCs isolated from the fat waste of a healthy adult volunteers undergoing cosmetic plastic surgery to the third generation, used the BD Rhapsody platform to perform scRNA‐seq, then used Monocle2 to analyze the growth and development trajectory of ADSCs, Cellular Trajectory Reconstruction Analysis Using Gene Counts and Expression (CytoTRACE) to evaluate the stemness gene characteristics in ADSCs clusters, and Beam to analyze the expression change characteristics of the main stemness related genes of ADSCs. According to the scRNA‐seq data of 5325 ADSCs, they could be classified into nine cell clusters. According to CytoTRACE analysis, Cluster 3 of ADSCs had the highest stemness, whereas Cluster 8 had the lowest stemness. Pseudotime analysis revealed that Cluster 3 of ADSCs was primarily dispersed in the middle part of the growth and development trajectory, whereas Cluster 8 was primarily distributed at the end. We summarized the stemness of Cluster 3 in ADSCs with high expression of TPM1 and CCND1 genes in the metaphase of growth and development is the strongest, whereas the stemness of Cluster 8 with high expression of FICD, CREBRF, SDF2L1, HERPUD1, and HYOU1 genes in the telophase of growth and development is the weakest, providing a theoretical basis for screening and improving the therapeutic effect of ADSCs in cell transplantation research.
Seasonal adjustment of leaf embolism resistance and its importance for hydraulic safety in deciduous trees

Abstract Embolism resistance is often viewed as seasonally stable. Here we examined the seasonality in the leaf xylem vulnerability curve (VC) and turgor loss point (ΨTLP) of nine deciduous species that originated from Mediterranean, temperate, tropical, or sub‐tropical habitats and were growing on the Volcani campus, Israel. All four Mediterranean/temperate species exhibited a shift of their VC to lower xylem pressures (Ψx) along the dry season, in addition to two of the five tropical/sub‐tropical species. In three of the species that exhibited VC seasonality, it was critical for avoiding embolism in the leaf. In total, seven out of the nine species avoided embolism. The seasonal VC adjustment was over two times higher as compared with the seasonal adjustment of ΨTLP, resulting in improved hydraulic safety as the season progressed. The results suggest that seasonality in the leaf xylem vulnerability is common in species that originate from Mediterranean or temperate habitats that have large seasonal environmental changes. This seasonality is advantageous because it enables a gradual seasonal reduction in the Ψx without increasing the danger of embolism. The results also highlight that measuring the minimal Ψx and the VC at different times can lead to erroneous estimations of the hydraulic safety margins. Changing the current hydraulic dogma into a seasonal dynamic in the vulnerability of the xylem itself should enable physiologists to understand plants' responses to their environment better.
Computational imaging using a mode-mixing cavity at microwave frequencies

We present a 3D computational imaging system based on a mode-mixing cavity at microwave frequencies. The core component of this system is an electrically large rectangular cavity with one corner re-shaped to catalyze mode mixing, often called a Sinai Billiard. The front side of the cavity is perforated with a grid of periodic apertures that sample the cavity modes and project them into the imaging scene. The radiated fields are scattered by the scene and are measured by low gain probe antennas. The complex radiation patterns generated by the cavity thus encode the scene information onto a set of frequency modes. Assuming the first Born approximation for scattering dynamics, the received signal is processed using computational methods to reconstruct a 3D image of the scene with resolution determined by the diffraction limit. The proposed mode-mixing cavity is simple to fabricate, exhibits low losses, and can generate highly diverse measurement modes. The imaging system demonstrated in this letter can find application in security screening and medical diagnostic imaging.
Implicit Differential Equations From the Singularity Theory Viewpoint

Geometrically this equation determines a line field, that is a line is assigned to each point in the plane, with the specified slope, and a solution is a smooth curve with the property that at each of its points it is tangent to the given line. Of course the generally isolated points in the plane where the functions a and b both vanish are special, and are referred to as singular points of the ordinary differential equation (ODE). An implicit differential equation, on the other hand, will generally determine several lines through a given point (x, y) in the plane, and hence several solution curves there. It can roughly be thought of as the superposition of a number of ODE’s and singularities can arise in three ways. There are those points where two or more of the lines coincide, those where one of the constituent ODE’s has a singularity, and points where both occur.
Enrichment of hepatic glycogen and plasma glucose from H₂18O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice

Deuterated water (2H2O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2H can distort metabolic information and mediate toxicity. 18O‐water (H218O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well‐defined mechanisms, but to date it has not been evaluated in any animal model. Mice were given H218O during overnight feeding and 18O‐enrichments of liver glycogen, triglyceride glycerol (TG), and blood glucose were quantified by 13C NMR and mass spectrometry (MS). Enrichment of oxygens 5 and 6 relative to body water informed indirect pathway contributions from the Krebs cycle and triose phosphate sources. Compared with mice fed normal chow (NC), mice whose NC was supplemented with a fructose/glucose mix (i.e., a high sugar [HS] diet) had significantly higher indirect pathway contributions from triose phosphate sources, consistent with fructose glycogenesis. Blood glucose and liver TG 18O‐enrichments were quantified by MS. Blood glucose 18O‐enrichment was significantly higher for HS versus NC mice and was consistent with gluconeogenic fructose metabolism. TG 18O‐enrichment was extensive for both NC and HS mice, indicating a high turnover of liver triglyceride, independent of diet. Thus H218O informs hepatic carbohydrate biosynthesis in similar detail to 2H2O but without KIE‐associated risks.
Perioperative management of myeloproliferative neoplasms: A pan‐Canadian physician survey and international expert opinion

To the Editor: Myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are stem cell-derived hematologic malignancies characterized by variable rates of fibrotic and leukemic transformation with concurrent risk of both thrombotic and hemorrhagic complications. While surgery is recognized as a significant situational risk factor for thrombosis in the general population, 1 this risk has been predicated to be further increased in patients with MPN. In the surgical setting, the prothrombotic effect of elevated hematocrit (Hct), hyperviscosity, increased cell turnover, and stasis may be amplified, conceivably compounding morbidity and mortality due to cardiovascular events. 2 In addition, concurrently acquired von Willebrand disease and platelet dysfunction may increase the risk of hemorrhagic complications. 3 One of the most com-prehensive studies on this subject to date corroborated this, disclosing high rates of both perioperative thrombosis (7%) and hemorrhage (10.5%) in patients with PV/ET, despite most (74%) having optimally controlled peripheral blood counts prior to procedure and receiving anticoagulation prophylaxis post-surgery. 4 Importantly, while some experts advise maintaining Hct <45% (PV), normalizing blood counts for at least 3 + months prior to elective surgery, standard (5 – 7 day) interruption of low-dose aspirin, and systematic perioperative anticoagulation prophylaxis, 5,6 there is limited evidence-based data substantiating these approaches, and consequently, no authoritative consensus regarding optimal perioperative management in this population.
Production of diverse brGDGTs by Acidobacterium Solibacter usitatus in response to temperature, pH, and O2 provides a culturing perspective on brGDGT proxies and biosynthesis

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial membrane lipids that are frequently employed as paleoenvironmental proxies because of the strong empirical correlations between their relative abundances and environmental temperature and pH. Despite the ubiquity of brGDGTs in modern and paleoenvironments, the source organisms of these enigmatic compounds have remained elusive, requiring paleoenvironmental applications to rely solely on observed environmental correlations. Previous laboratory and environmental studies have suggested that the globally abundant bacterial phylum of the Acidobacteria may be an important brGDGT producer in nature. Here, we report on experiments with a cultured Acidobacterium, Solibacter usitatus, that makes a large portion of its cellular membrane (24 ± 9% across all experiments) out of a structurally diverse set of tetraethers including the common brGDGTs Ia, IIa, IIIa, Ib, and IIb. Solibacter usitatus was grown across a range of conditions including temperatures from 15 to 30°C, pH from 5.0 to 6.5, and O2 from 1% to 21%, and demonstrated pronounced shifts in the degree of brGDGT methylation across these growth conditions. The temperature response in culture was in close agreement with trends observed in published environmental datasets, supporting a physiological basis for the empirical relationship between brGDGT methylation number and temperature. However, brGDGT methylation at lower temperatures (15 and 20°C) was modulated by culture pH with higher pH systematically increasing the degree of methylation. In contrast, pH had little effect on brGDGT cyclization, supporting the hypothesis that changes in bacterial community composition may underlie the link between cyclization number and pH observed in environmental samples. Oxygen concentration likewise affected brGDGT methylation highlighting the potential for this environmental parameter to impact paleotemperature reconstruction. Low O2 culture conditions further resulted in the production of uncommon brGDGT isomers that could be indicators of O2 limitation. Finally, the production of brGTGTs (trialkyl tetraethers) in addition to the previously discovered iso‐C15‐based mono‐ and diethers in S. usitatus suggests a potential biosynthetic pathway for brGDGTs that uses homologs of the archaeal tetraether synthase (Tes) enzyme for tetraether synthesis from diethers.