Miracle-dz/UniFAR-FTUs huggingface dataset:
Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently down-regulated the cell surface expression of the antigen-presenting molecule, CD1d, to suppress the function of iNKT cells. E protein is a small membrane protein and a viroporin that plays important roles in virion packaging and envelopment during viral morphogenesis. We showed that the transmembrane domain of E protein was responsible for suppressing CD1d expression by specifically reducing the level of mature, post-ER forms of CD1d, suggesting that it suppressed the trafficking of CD1d proteins and led to their degradation. Point mutations demonstrated that the putative ion channel function was required for suppression of CD1d expression and inhibition of the ion channel function using small chemicals rescued the CD1d expression. Importantly, we discovered that among seven human coronaviruses, only E proteins from highly pathogenic coronaviruses including SARS-CoV-2, SARS-CoV and MERS suppressed CD1d expression, whereas the E proteins of human common cold coronaviruses, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1, did not. These results suggested that E protein-mediated evasion of NKT cell function was likely an important pathogenesis factor, enhancing the virulence of these highly pathogenic coronaviruses. Remarkably, activation of iNKT cells with their glycolipid ligands, both prophylactically and therapeutically, overcame the putative viral immune evasion, significantly mitigated viral pathogenesis and improved host survival in mice. Our results suggested a novel NKT cell-based anti-SARS-CoV-2 therapeutic approach.
Diagnostic performance of microUltrasound at MRI‐guided confirmatory biopsy in patients under active surveillance for low‐risk prostate cancer

Active surveillance (AS) represents a standard of care of low‐risk prostate cancer (PCa). However, the identification and monitoring of AS candidates remains challenging. Microultrasound (microUS) is a novel high‐resolution imaging modality for transrectal ultrasonography (TRUS). We explored the impact of microUS TRUS and targeted biopsies in mpMRI‐guided confirmatory biopsies.
The Humeral Head Push–Pull Plate Technique: An Alternative Way to Stabilize the Humeral Head in Varus Angulated Proximal Humeral Fractures in the Elderly

Supplemental Digital Content is Available in the Text. Summary: Despite the introduction of different surgical techniques and implants, osteoporotic varus displaced fractures of the proximal humerus treated with an angular stable plate have still a high risk of recurrence and/or screw penetration leading to revision surgery. Here, we describe a technique where we use an alternative approach to stabilize the humeral head by the use of apical subchondral bone anchors tightened to an angular stable plate. This technique eliminated the need for screws in the upper part of the humeral head, allowing the upper angular stable screws to be redirected to the inferomedial part of the humeral head. We named this technique the humeral head push–pull plate technique or H2P3 in its abbreviated form. The technique is presented in combination with a case series.
A genome sequence for Biomphalaria pfeifferi, the major vector snail for the human-infecting parasite Schistosoma mansoni

Background Biomphalaria pfeifferi is the world’s most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi. Methodology/Principal findings Based largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago. Conclusions/Significance The genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.
Are more courses of immunochemotherapy beneficial for the short‐term outcome of locally advanced esophageal squamous cell carcinoma?

Immune checkpoint inhibitor (ICI) monotherapy and neoadjuvant immunochemotherapy have shown promising results in esophageal carcinoma. However, it is still unclear whether more courses of immunochemotherapy are therapeutically better. We aimed to investigate the safety and efficacy of three courses of neoadjuvant treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Nouvelles approches du «théorème» de Fermat

© Société mathématique de France, 1988, tous droits réservés. L’accès aux archives de la collection « Astérisque » (http://smf4.emath.fr/ Publications/Asterisque/) implique l’accord avec les conditions générales d’utilisation (http://www.numdam.org/conditions). Toute utilisation commerciale ou impression systématique est constitutive d’une infraction pénale. Toute copie ou impression de ce fichier doit contenir la présente mention de copyright.
Experimental Verification of the Importance of The Nonlinear Curvature in the Response of a Cantilever Beam

An experimental and theoretical investigation into the first- and second-mode responses of a parametrically excited slender cantilever beam is presented. Inclusion of quadratic damping in the analytical model significantly improves the agreement between the experimental and theoretical results. In addition, the experimental results verify that the often ignored nonlinear curvature terms play a dominant role in the response of the first mode and that the nonlinear inertia terms play a dominant role in the response of the second mode.
The Safe Landing warm up technique modification programme: An effective anterior cruciate ligament injury mitigation strategy to improve cutting and jump-movement quality in soccer players

ABSTRACT The objective of the study was to evaluate the effectiveness of the Safe Landing (SL), a 6-week technique-modification (TM) programme, on cutting and jump-landing movement quality in football players. In a non-randomized design, 32 male semi-professional football players from two Spanish clubs participated in the study: one served as the control group (CG, n = 11), while the other performed the SL (n = 15). Performance and movement quality of drop vertical jump and 70º change of direction (COD70) were evaluated through 2D video footage pre- and post-intervention. In such tasks, the Landing Error Scoring System for first (LESS1) and second (LESS2) landings, and the Cutting Movement Assessment Score (CMAS) were used for assessing movement quality. Pre-to-post changes and baseline-adjusted ANCOVA were used. Medium-to-large differences between groups at post-test were shown in CMAS, LESS1 and LESS2 (p < 0.082, ղ2 = 0.137–0.272), with small-to-large improvements in SL (p < 0.046, ES=0.546–1.307), and CG remaining unchanged (p > 0.05) pre-to-post. In COD70 performance, large differences were found between groups (p < 0.047, ղ2 = 0.160–0.253), with SL maintaining performance (p > 0.05, ES=0.039–0.420), while CG moderately decreasing performance (p = 0.024, ES=0.753) pre-to-post. The SL is a feasible and effective TM program to improve movement quality and thus potential injury risk in cutting and landing, while not negatively affecting performance.
The Effect of Mechanical Thrombectomy on the Incidence of Poststroke Cognitive Impairment: A Systematic Review of Inhomogeneous Literature

Introduction: The aim of this study was to evaluate the effect of mechanical thrombectomy (MT) on the incidence of poststroke cognitive impairment (PSCI) in anterior circulation stroke. Methods: Literature research was performed on PubMed/OVID/Cochrane CENTRAL for studies published in 2015–2022. A review of the references of the included papers was performed for further eligible articles. Clinical characteristics, NIHSS, dementia tests, and outcomes were recorded. The exclusion criteria were nonhuman and non-English. Studies qualities were assessed with MINORS/RoB2 and GRADE. A meta-analysis was performed using the standardized mean difference (Cohen’s d) to measure effect size. Results: Four studies were included in the systematic review after screening 749 articles. No significant differences were found for age and gender (years: 66.70 ± 11.14 vs. 67.59 ± 10.11, p = 0.37; male 53.8% vs. 56.4%, p = 0.57). MT patients had a more severe stroke than that of the control group (NIHSS: 14.70 ± 4.31 vs. 11.17 ± 4.12; p < 0.0001). The control group consisted of medical therapy-alone patients in all studies. I2 was 76.95%, and Q was 43.4%. MT patients have better performance in overall cognition (d = 0.33 [0.074–0.58]) and in several cognitive domains than in the control group (TMT-A, d = 0.37 [0.04–0.70]; TMT-B, d = 0.35 [0.12–0.58]; digit span test [backward], d = 0.61 [0.18–1.06]; colored progressive matrices, d = 0.48 [0.05–0.91]; Stroop test [word reading], d = 0.60 [0.17–1.03]; color naming, d = 0.51 [0.08–0.94]; Rey-Osterrieth Complex Figure [immediate recall], d = 0.79 [0.35–1.23]; Rey Auditory Verbal Learning Test [immediate recall], d = 0.79 [0.36–1.23]; delayed recall, d = 0.46 [0.035–0.89]; and MOCA, d = 0.46 [−0.04 to 0.96]). Medical therapy patients had a higher score in coping strategy than MT patients (COPE-28 acceptance, d = −1.00 [−1.53 to −0.48]). Conclusions: The incidence of PSCI is lower in MT patients than in the control group.
Aerodynamic Performance of Cambered Heaving Airfoils

c = airfoil mean chord cd = instantaneous drag coefficient cl = instantaneous lift coefficient cl = time average lift coefficient cP = instantaneous input power coefficient cP = time average input power coefficient ct = instantaneous thrust coefficient (ct cd) ct = time average thrust coefficient f = heaving frequency ha = heaving amplitude k = reduced frequency, fc=U1 Re = Reynolds number, U1c= St = Strouhal number, 2fha=U1 t = time U1 = freestream velocity = propulsive efficiency, ct= cP = fluid kinematic viscosity = fluid density
Pharmacological approaches to treat intestinal pain

ABSTRACT Introduction Pain is one of the most substantial factors responsible for lowering quality of life in patients with intestinal diseases. Its multifactorial pathogenesis makes intestinal pain difficult to manage with currently available medications, especially considering the risk of serious adverse effects and exacerbation of underlying disease. Areas covered The most commonly administered drugs in intestinal pain are medications forming the so-called analgesic ladder, which act directly on pain sensation: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids in full range of activity strength. However, there are also many groups of supportive medications, which target intestinal pain indirectly and therefore, differs in applicability depending on underlying conditions and their pathophysiology, e.g. antispasmodics, antidepressants, probiotics, and biological anti-inflammatory drugs. In this review, we concentrated on possible analgesic options in patients suffering from irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), and colorectal cancer (CRC). Moreover, we examined future perspectives in treating abdominal pain with medications targeting transient receptor potential channels, the endocannabinoid system and other promising options, including new formulations of already known drugs and new peripherally restricted opioids. Expert opinion There is constant need for improvement of intestinal analgesia and novel pharmacological approaches, from which interaction with TRP receptors is a particularly promising direction.
Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial

Objective Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. Methods RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). Results Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. Conclusions Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. Trial registration number NCT01697267; ClinicalTrials.gov identifier
Epistemic Uncertainty in the Calculation of Margins

Epistemic uncertainty, characterizing lack-of-knowledge, is often prevalent in engineering applications. However, the methods we have for analyzing and propagating epistemic uncertainty are not as nearly widely used or well-understood as methods to propagate aleatory uncertainty (e.g. inherent variability characterized by probability distributions). In this paper, we examine three methods used in propagating epistemic uncertainties: interval analysis, Dempster-Shafer evidence theory, and second-order probability. We demonstrate examples of their use on a problem in structural dynamics, specifically in the assessment of margins. In terms of new approaches, we examine the use of surrogate methods in epistemic analysis, both surrogate-based optimization in interval analysis and use of polynomial chaos expansions to provide upper and lower bounding approximations. Although there are pitfalls associated with surrogates, they can be powerful and efficient in the quantification of epistemic uncertainty.
Rickettsia conorii Subspecies israelensis in Captive Baboons

Hamadryas baboons (Papio hamadryas) may transmit zoonotic vector-borne pathogens to visitors and workers frequenting zoological parks. We molecularly screened 33 baboons for vector-borne pathogens. Three (9.1%) of 33 animals tested positive for Rickettsia conorii subspecies israelensis. Clinicians should be aware of potential health risks from spatial overlapping between baboons and humans.
Telehealth-Guided Virtual Reality for Recovery of Upper Extremity Function Following Stroke

This rater-blinded, randomized control trial (RCT) investigated the effectiveness of a Glove Rehabilitation Application for Stroke Patients (GRASP) virtual reality home exercise program (HEP) for upper extremity (UE) motor recovery following stroke. The GRASP system facilitates the use of the affected UE in simulated instrumental activities of daily living (IADLs). Participants were asked to use the system at home in asynchronous telehealth sessions 4 times per week over 8 weeks. A non-blinded occupational therapist (OT) provided synchronous telehealth visits biweekly. Analysis comparing pre- and post-assessment results for the Fugl-Meyer UE assessment (FMUE) shows a clinically important and statistically significant between-group difference for participants completing the GRASP HEP protocol compared with usual and customary care controls. Statistically significant and clinically important differences were also found in Motor Activity Log (MAL) scores. This evidence provides support for the effectiveness of home-based, IADL-focused, virtual reality therapy with telehealth support.
A Class of Random Convex Polytopes

0. Summary. In Section 1 it is shown that n interior points of the (k 1)dimensional simplex Sk define a partition of Sk into (kl-i) convex polytopes R(n) which are in one-one correspondence with the partitions of n into a sum of k nonnegative integers. If the n points are uniformly and independently distributed over Sk9 then R(n) becomes a random polytope. Basic properties of the random R(n) are given in Section 2. Section 3 presents an algorithm which can be used to compute the distribution of any extremal vertex of R(n).
Numerical simulation of high-current vacuum arcs with an external axial magnetic field

Numerical simulations are presented for physical behavior and heat flux to the anode of high-current diffuse of arcs as found in vacuum interrupters. The magnetohydrodynamic approach is applied. Of importance is the consideration of energy balance. Heat flux densities to the anode are predicted in the right order of magnitude and essential physical details of the high-current vacuum arc are disclosed. Only at low or no axial magnetic field superimposed externally and low-arc currents, the anode-directed flow of plasma of diffuse arcs reveals supersonic conditions. Otherwise, subsonic conditions exist. In supersonic diffuse arcs, the anode-directed plasma flow is decelerated and highest pressures appear in front of the anode. At subsonic conditions the highest pressure prevails in the cathode region and the pressure gradient drives the flow to the anode. The transition from diffuse to diffuse columnar arc seems to occur when the evaporation rate of metal vapor from the contact surfaces approaches the emission rate of plasma from the body of cathode spots. Diffuse columnar arcs have moderate pressure variations from cathode to anode. With rising plasma density, the energy loss from the emission of electromagnetic radiation increases and can no longer be neglected.
EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort

Abstract The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.
The process of Transformative Learning in Dialog Café with Health Professionals and Citizens/Patients

Introduction: Dialogue Café, which is an inclusive process that provides a platform for the exchange of ideas or perspectives on certain issues, is a suitable approach to facilitating mutual understanding between health professionals and citizens/patients. However, little is known about the effects of the Dialogue Café on participants in the context of health communication. Previous studies suggest that transformative learning occurs after dialogue. Objectives: This study aimed to clarify the process of the transformative learning process among participants of the Dialog Café and to evaluate whether their transformative learning would lead to an understanding of others’ perspectives. Methods: We conducted a psychometric analysis of a web-based questionnaire consisting of 72 items for participants of Dialog Café held from 2011 to 2013 in Tokyo and studied the relationships between various concepts using structural equation modeling (SEM). To evaluate the validity and reliability of concept measurement, we conducted an exploratory factor analysis and a confirmatory factor analysis. Results: The questionnaire response rate was 39.5% (141/357), of which 80 (56.7%) respondents were health professionals and 61 (43.3%) respondents were citizens/patients. The SEM analysis revealed that transformative learning occurred in both groups. The process of transformative learning consisted of 2 types; one process leading directly to “perspective transformation” and the other leading to “perspective transformation” via “critical self-reflection” and “disorienting dilemmas. ” “Perspective transformation” was related to “understanding others” in both groups. Among health professionals, “perspective transformation” was related to “transformation of awareness toward patients/users. ” Conclusion: Dialog Café can facilitate the process of transformative learning among participants, and transformative learning may lead to mutual understanding between health professionals and citizens/patients.
Effect of the combination of diuretics, renin–angiotensin–aldosterone system inhibitors, and non‐steroidal anti‐inflammatory drugs or metamizole (triple whammy) on hospitalisation due to acute kidney injury: A nested case–control study

Concomitant use of diuretics, renin–angiotensin–aldosterone system (RAAS) inhibitors, and non‐steroidal anti‐inflammatory drugs (NSAIDs) or metamizole, known as ‘triple whammy’ (TW), has been associated with an increased risk of acute kidney injury (AKI). Nevertheless, there is still uncertainty on its impact in hospitalisation and mortality. The aim of the study was to analyse the association between exposure to TW and the risk of hospitalisation for AKI, all‐cause mortality and the need for renal replacement therapy (RRT).