Miracle-dz/UniFAR-FTUs huggingface dataset:
Human T-bet governs the generation of a distinct subset of CD11chighCD21low B cells

High-level expression of the transcription factor T-bet characterizes a phenotypically distinct murine B cell population known as “age-associated B cells” (ABCs). T-bet–deficient mice have reduced ABCs and impaired humoral immunity. We describe a patient with inherited T-bet deficiency and largely normal humoral immunity including intact somatic hypermutation, affinity maturation and memory B cell formation in vivo, and B cell differentiation into Ig-producing plasmablasts in vitro. Nevertheless, the patient exhibited skewed class switching to IgG1, IgG4, and IgE, along with reduced IgG2, both in vivo and in vitro. Moreover, T-bet was required for the in vivo and in vitro development of a distinct subset of human B cells characterized by reduced expression of CD21 and the concomitantly high expression of CD19, CD20, CD11c, FCRL5, and T-bet, a phenotype that shares many features with murine ABCs. Mechanistically, human T-bet governed CD21loCD11chi B cell differentiation by controlling the chromatin accessibility of lineage-defining genes in these cells: FAS, IL21R, SEC61B, DUSP4, DAPP1, SOX5, CD79B, and CXCR4. Thus, human T-bet is largely redundant for long-lived protective humoral immunity but is essential for the development of a distinct subset of human CD11chiCD21lo B cells. Description Germline mutation of TBX21 reveals a requirement for T-bet in the generation of a distinct subset of CD11chiCD21lo human B cells. T-bet teaches the ABCs Humans and mice have atypical B cell subsets associated with chronic infection or autoimmunity. In mice, this subset has been called “age-associated B cells” (ABCs) in mice and may depend on B cell expression of the T-bet transcription factor. Yang et al. analyzed B cells from a rare patient with inherited T-bet deficiency to define which human B cell subsets depend on T-bet. Most human antibody responses and B cell subsets persisted in this patient, but a distinct subset of B cells with high CD11c and low CD21 expression failed to differentiate. This study provides fresh insights into the transcriptional regulation of a subset of atypical B cells in humans and suggests targeted approaches to selectively inhibiting the contribution of T-bet–dependent to human immune dysfunction.
Microbiome profile of soil and rhizosphere plants growing in traditional oil mining land in Wonocolo, Bojonegoro, Indonesia

Abstract Traditional oil mining poses negative effects on the environment through pollution with crude oil. One of the traditional mining sites in Wonocolo, Bojonegoro, Indonesia was reported to contaminate the surrounding area with a high level of crude oil. Therefore, this study aims to examine the microbiome profiles of contaminated soil and the rhizosphere of naturalized plants growing at the sites. It was conducted in Wonocolo, Bojonegoro to obtain an insight into the possible remediation efforts of using indigenous hydrocarbon-degrading bacteria and naturalized plants as in situ remediation agents. The results showed that the soil located close to the oil well-contained a high level of crude oil at 24.8%, and exhibited a distinct microbiome profile compared to those located further which had lower crude oil contamination of 14.15, 10.89, and 4.9%. Soil with the highest level of crude oil contamination had a comparatively higher relative abundance of assA, an anaerobic alkene-degrading gene. Meanwhile, the rhizosphere of the two naturalized plants, Muntingia calabura, and Pennisetum purpureum, exhibited indifferent microbiome profiles compared to the soil. They were found to contain less abundant hydrocarbon-degrading genes, such as C230, PAH-RHD-GP, nahAc, assA, and alkB suggesting that these naturalized plants might not be a suitable tool for in-situ remediation. NOVELTY STATEMENT This study provides information on the microbiome profile of soil and rhizosphere crude oil contaminated sites. The rhizosphere of growing plants in the crude-oil contaminated site exhibited a similar microbiome profile as in soil, with a lower relative abundance of hydrocarbon-degrading genes. Commonly, most inhabitant plants of the contaminated site have great potential as a phytoremediator agent, however, two largely abundant species were found to possess low potential.
Longitudinal Associations among Machiavellianism, Popularity Goals, and Adolescents’ Cyberbullying Involvement: The Role of Gender

Abstract Drawing on the social-ecological perspective, this longitudinal study investigated the potential moderating effect of gender in the relationships among Machiavellianism, popularity goals, and cyberbullying involvement (i.e. victimization, perpetration) among adolescents from China, Cyprus, India, and the United States. There were 2,452 adolescents (M age = 14.85; SD = .53; 13–16 years old; 49.1% girls) from China, Cyprus, India, and the United States included in this study. They completed surveys on Machiavellianism, popularity goals, and cyberbullying victimization and perpetration during the fall of 2014 (Time 1). One year later, during the fall of 2015, adolescents completed surveys on cyberbullying victimization and perpetration. Findings revealed that Machiavellianism and popularity goals were both associated positively with Time 2 cyberbullying victimization and perpetration for all adolescents. The associations between Machiavellianism and Time 2 cyberbullying perpetration and between popularity goals and Time 2 cyberbullying perpetration were stronger for Chinese and Indian boys than girls. Opposite patterns were found for popularity goals and Time 2 cyberbullying perpetration for adolescents from the United States. Gender did not moderate any of the associations for Cypriot adolescents or for Time 2 cyberbullying victimization. The social-ecological perspective provides a useful understanding of how various contexts influence bullying.
Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study

Objective The lifetime recurrence rate (RR) of axial spondyloarthritis (axSpA) among first-degree relatives (FDR) and the effect of proband’s gender, HLA-B27 and radiographic status is unclear. Our 35-year-follow-up family study has enabled these issues to be addressed. Methods In 1985, 363 ankylosing spondylitis (AS) probands (members of the Swiss AS Patient Society) and 806 FDR recruited into the study, completed questionnaires regarding axSpA manifestations, underwent a physical examination and most also underwent pelvic radiography and HLA-B27 typing. At follow-up in 2018–2019, of the former participants whose current addresses could be retrieved, 162 had died and 485 (125 patients with AS plus 360 FDR) completed a postal questionnaire. Results At follow-up, 48 of 177 HLA-B27(+) FDR had developed axSpA, an RR of 27.1% (95% CI 20.6% to 33.7%). 27/148 (18.2%) children of AS probands (modified New York (mNY) criteria) were affected versus 2/50 (4.0%) children of non-radiographic axSpA probands (p=0.0138, OR=5.36; 95% CI 1.23 to 23.40). Children of female probands were more often affected (12/22; 54.5%) than of male probands (15/78; 19.2%) (p=0.0003; OR=4.89; 95% CI 1.96 to 12.23). This increased risk applies equally to sons and daughters. Conclusion The lifetime RR of axSpA for HLA-B27(+) FDR is substantial (27.1%), and disease severity (as defined by radiographic sacroiliitis by the mNY criteria) is an additional risk factor. Affected mothers pass on the disease significantly more often to their offspring than do affected fathers. These findings may lead to better assessment of lifetime risk for axSpA in the offspring. Moreover, investigation of this gender effect may uncover additional putative disease susceptibility factors.
Feasibility, Safety, and Preliminary Efficacy of Very Low-Volume Interval Training in Advanced Cancer Patients

ABSTRACT Purpose High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (CRF) and health-related outcomes in various chronic diseases, including cancer. However, data on feasibility and efficacy of HIIT in advanced cancer patients are still sparse, presumably because of safety concerns, like suspected immunosuppression after vigorous exercise. This randomized, sham-intervention controlled study aimed to investigate feasibility, safety, and preliminary efficacy of very low-volume HIIT (LOW-HIIT) in advanced cancer patients. Methods Twenty-seven patients (55.4 ± 13.2 yr) with different advanced cancers (Union for International Cancer Control [UICC] III/IV) were randomly allocated to LOW-HIIT (n = 13), consisting of 5 × 1 min cycle ergometer intervals (14 min per session total duration) at 80% to 95% HRpeak (two sessions per week for 12 wk), or a sham intervention (n = 14) performing light physical mobilization exercises (SHAM). Primary outcomes were attrition and attendance rates, with values of ≤25% and ≥80%, respectively, considered acceptable. Secondary outcomes were safety, protocol fidelity, physiological (including CRF measures) and patient-reported outcomes (including fatigue and quality of life). Results One of 13 patients (8%) receiving LOW-HIIT dropped out. Mean attendance rate was ~93%. The prescribed minimum exercise intensity was consistently reached by all patients. Low-volume HIIT was well tolerated and not associated with any serious adverse event nor with increased infection susceptibility. There were no biochemical signs of acute immunosuppression after LOW-HIIT. Contrarily, differentiation and degranulation of natural killer cells was acutely increased postexercise. Low-volume HIIT improved CRF measures including peak oxygen uptake, self-reported fatigue, physical, and social functioning. No significant changes occurred in the SHAM group. Conclusions Low-volume HIIT can be regarded as feasible and safe in advanced cancer patients. Our preliminary data indicate favorable acute effects on NK-cells and beneficial chronic adaptations in CRF, fatigue, and aspects of quality of life.
Machining Center Efficiency Optimization Using Artificial Intelligence

This paper presents machining parameters optimization based on usage of artificial intelligence. To increase efficiency and productivity of machine tool, optimal cutting parameters have to be obtained. In order to find optimal cutting parameters, genetic algorithm (GA) was used as optimal solution finder. GA is optimization algorithm based on artificial intelligence. Optimization has to yield minimum machining time and minimum production cost, while considering technological and material constrains.
Immune Mice Against Reinfection with Herpes the Vaginal Mucosae and Sensory Ganglia of T Lymphocytes Are Required for Protection of

Intravaginal inoculation of mice with an attenuated strain of herpes simplex virus type 2 (HSV-2) resulted in vigorous HSV-speciﬁc immune responses that protected against subsequent challenge with fully virulent HSV-2 strains. Even in the presence of high titers of HSV-speciﬁc Ab, T cell-dependent mechanisms were required for protection of the vaginal mucosae of HSV-immune mice and could be detected by 24 h after intravaginal reinoculation. Depletion of speciﬁc T cell subsets from HSV-immune mice before HSV-2 reinoculation demonstrated that CD4 1 T cells were primarily responsible for this protection. Similarly, optimal protection of the sensory ganglia against reinfection with HSV-2 was dependent on the presence of T cells. Infectious HSV-2 was not detected in the sensory ganglia or spinal cord of HSV-immune mice depleted of only CD4 1 or CD8 1 T cells, suggesting that the T cell-mediated protection could be provided by either subset. Similarly, neutralization of IFN- g during challenge of HSV-immune mice resulted in diminished protection of the vaginal mucosa, but not of the sensory ganglia. These results suggest that the ability to induce vigorous HSV-speciﬁc T cell responses is an important consideration in the design of vaccines to protect both the vaginal mucosa and sensory ganglia against HSV-2. The Journal of Immunology, 1998, 160: 6093–6100.
The Diversifying Experience-Creativity Model: Taking a Broader Conceptual View of the Multiculturalism-Creativity Link.

We examine the multiculturalism – creativity link from the perspective of diversifying experiences research. Multicultural experiences can be construed as diversifying experiences - highly unusual and unexpected events or situations (e.g., unusual educational experiences, early life adversity) that push individuals outside the frameworks of their ordinary every-day lives, forcing them to embrace new and uncommon ideas. Our review identifies a range of diversifying experiences (e.g., multicultural exposure, unexpected adversity, violations of expectations) that have been found to influence creativity. We introduce the Diversifying Experience to Creativity Model (DECM), where we argue for a curvilinear relationship between diversifying experiences and creativity, whereby creativity improves as a result of moderate (but not low or high) levels of diversifying experiences. We also propose adaptive personal resources as the key moderator, and threat and challenge appraisals as the key mediators of the diversifying experience – creativity relation. When adaptive resources are high, moderate diversifying experiences are appraised primarily as a challenge, facilitating creativity, whereas when adaptive resources are low, moderate diversifying experiences are appraised primarily as a threat, derailing creativity. This broad and parsimonious theoretical framework can help clarify and expand research on when and why various diversifying experiences (including multicultural experiences) facilitate creativity.
Combinatorial theory of q,t-Schröder polynomials, parking functions and trees

COMBINATORIAL THEORY OF Q,T-SCHRODER POLYNOMIALS, PARKING FUNCTIONS AND TREES Chunwei Song James Haglund We study various aspects of lattice path combinatorics. A new object, which has Dyck paths as its subset and is named Permutation paths, is considered and relative theories are developed. We prove a class of tree enumeration theorems and connect them to parking functions. The limit case of (q, t)-Schroder Theorem is investigated. In the end, we derive a formula for the number of m-Schroder paths and study its q and (q, t)-analogues.
Edinburgh Research Explorer Kalirin and CHD7

Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria.
Some Remarks On The Convergence Of Picard Iteration To A Fixed Point For A Continuous Mapping

Some examples are given to illustarte that the characterization in [8] for the convergence of Picard iteration to a fixed point for a continuous mapping, is false. Throughout this paper, let T be a mapping from a nonempty subset D of a metric space X into X and let F(T) be a fixed point set of T. A mapping T : D ! X is called nonexpansive if for each x,y 2 D, d(T(x),T(y)) d(x,y). T is said to be quasi-nonexpansive if for each x 2 D and for every p 2 F(T), d(T(x),p) d(x,p). T is conditionally quasi-nonexpansive if it is quasi-nonexpansive whenever F(T) 6= ;. Since convergence theorems of iterations to a fixed point for nonexpansive mapping are discussed in [1-2], many results on the convergence of some iterations to fixed points for nonexpansive, quasi-nonexpansive and generalized types of quasi-nonexpansive mappings in metric and Banach spaces have appeared (for example, [3-8]). Following Ghosh and Debnath [4], if D is a convex subset of a normed space X and T : D ! D, Ishikawa introduced the following iteration
Institutional Knowledge at Singapore Management University Institutional Knowledge at Singapore Management University Smartwatch-based early gesture detection & trajectory tracking Smartwatch-based early gesture detection & trajectory tracking for interactive gesture-driven applications for interact

The paper explores the possibility of using wrist-worn devices (specifically, a smartwatch) to accurately track the hand movement and gestures for a new class of immersive, interactive gesture-driven applications. These interactive applications need two special features: (a) the ability to identify gestures from a continuous stream of sensor data early–i.e., even before the gesture is complete, and (b) the ability to precisely track the hand’s trajectory, even though the underlying inertial sensor data is noisy. We develop a new approach that tackles these requirements by first building a HMM-based gesture recognition framework that does not need an explicit segmentation step, and then using a per-gesture trajectory tracking solution that tracks the hand movement only during these predefined gestures. Using an elaborate setup that allows us to realistically study the table-tennis related hand movements of users, we show that our approach works: (a) it can achieve 95% stroke recognition accuracy. Within 50% of gesture, it can achieve a recall value of 92% for 10 novice users and 93% for 15 experienced users from a continuous sensor stream; (b) it can track hand movement during such strokeplay with a median accuracy of 6.2 cm.
Identifying routine predictors of to line in Type 2 diabetes: a retrospective cohort analysis in a large primary care database

-2-Abstract Aims: Non-adherence to medication is a major problem for patients with diabetes leading to poor response to therapy. Many factors associated with poor adherence have been identified, but their combined predictive ability has not been assessed. We investigated whether combinations of routinely available clinical features can predict which patients are likely to be non-adherent. Materials and methods: 67882 patients with prescription records for their first and second oral glucose lowering therapies were identified from electronic healthcare records (Clinical Practice Research Datalink (CPRD)). Non-adherence was defined as a medical possession ratio (MPR) ≤80%. Potential predictors were examined including age at diagnosis, sex, BMI, duration of diabetes, HbA1c, Charlson Index and other recent prescriptions. Results: Routine clinical features were poor at predicting non-adherence to the first diabetes therapy (c-statistic=0.601 for all in combined model). Non-adherence to the second drug was better predicted for all combined factors (c=0.715) but this improvement was predominantly a result of including adherence to the first drug (c=0.695 for this alone). Patients with MPR≤80% on their first drug were 3.6 (95% CI 3.3,3.8) times more likely to be non-adherent on their second drug (32% v 9%). Conclusions: Although certain clinical features are associated with poor adherence, their performance for predicting who is likely to be non-adherent, even when combined, is weak. The strongest predictor of adherence to second-line therapy is adherence to the first therapy. Examining previous prescription records could offer a practical way for clinicians to identify potentially non-adherent patients and is an area warranting further research.
Different mismatch concepts for MRI-guided thrombolysis in unknown onset stroke Running Head : Perfusion-diffusion mismatch in the WAKE-UP trial

Objective : To explore the prevalence of the perfusion-weighted imaging (PWI) - diffusion-weighted imaging (DWI) mismatch and response to intravenous thrombolysis in the WAKE-UP trial. Methods : We performed a prespecified post-hoc analysis of ischemic stroke patients screened for DWI - fluid-attenuated inversion recovery (FLAIR) mismatch in WAKE-UP who underwent PWI. We defined PWI-DWI mismatch as ischemic core volume <70 ml, mismatch volume >10 ml and mismatch ratio >1.2. Primary efficacy endpoint was a modified Rankin Scale score of 0-1 at 90 days, adjusted for age and symptom severity. Results : Of 1,362 magnetic resonance imaging (MRI) screened patients, 431 underwent PWI. Of these, 57 (13%) had a double mismatch, 151 (35%) only a DWI-FLAIR mismatch and 54 (13%) only a PWI-DWI mismatch. DWI-FLAIR mismatch was more prevalent than PWI-DWI mismatch (48%; 95% CI 43%-53% vs 26%; 95% CI 22%-30%, p<0.0001). Screening for either one of the mismatch profiles resulted in a yield of 61% (95% CI 56%-65%). Prevalence of PWI-DWI copyright. mismatch was similar in patients with (27%) or without (24%) DWI-FLAIR mismatch (p= 0.52). In an exploratory analysis in the small subgroup of 208 randomized patients with PWI, PWI-DWI mismatch status did not modify the treatment response (p for interaction= 0.73). Interpretation : Evaluating both the DWI-FLAIR and PWI-DWI mismatch pattern in patients with unknown time of stroke onset will result in the highest yield of thrombolysis treatment. The treatment benefit of alteplase in patients with a DWI-FLAIR mismatch seems not merely driven by the presence of a PWI-DWI mismatch, although this analysis was underpowered.
blocking NMDA in the cortex.

We have shown that a number of anticonvulsant drugs can reduce glutamate release at synapses in the rat entorhinal cortex (EC) in vitro . We have also shown that presynaptic NMDA receptors (NMDAr) tonically facilitate glutamate release at these synapses. In the present study we determined whether, phenytoin, gabapentin and felbamate may reduce glutamate release by blocking the presynaptic NMDAr. Whole cell patch clamp recordings of spontaneous excitatory postsynaptic currents (sEPSCs) were used as a monitor of presynaptic glutamate release. Postsynaptic NMDAr were blocked with internal dialysis with an NMDAr channel blocker. The antagonist, 2-AP5, reduced the frequency of sEPSCs by blocking the presynaptic facilitatory NMDAr, but did not occlude a reduction in sEPSC frequency by gabapentin or phenytoin. Felbamate also reduced sEPSC frequency, but this effect was occluded by prior application of 2-AP5. Thus, whilst all three drugs can reduce glutamate release, only the action of felbamate seems to be due to interaction with presynaptic NMDAr.