Miracle-dz/UniFAR-FTUs huggingface dataset:
Real Differences and Overlooked Similarities

Jack Paine (JP) and Alrik Thiem, Michael Baumgartner, and Damien Bol (TBB) provide diametrically opposed answers to the hotly debated question as to whether set-theory-based methods constitute a family of methods sui generis or whether not only set methods can be subsumed under the existing statistical framework, but also, if so, should be abandoned. I find TBB’s argument convincing that due to their different mathematical foundations, these two families of methods cannot be directly translated, let alone unified into one. Notwithstanding this, it seems clear to me that work must continue on identifying conceptual similarities and differences, and to elaborate on each method’s respective strengths and weaknesses. Because I mostly agree with TBB, I only briefly comment on some of their claims and then dedicate the rest of the text to JP.
Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

OBJECTIVE Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US. METHODS We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service. RESULTS UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, 95% CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3-11.0 and OR 17.3, 95% CI 1.8-162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti-signal recognition particle autoantibodies. CONCLUSION This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies.
Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism*

Selenium is an essential dietary element with antioxidant roles in immune regulation, but there is little understanding of how this element acts at the molecular level in host defense and inflammatory disease. Selenium is incorporated into the amino acid selenocysteine (Sec), which in turn is inserted into selenoproteins in a manner dependent on Sec tRNA[Ser]Sec. To investigate the molecular mechanism that links selenium to T cell immunity, we generated mice with selenoprotein-less T cells by cell type-specific ablation of the Sec tRNA[Ser]Sec gene (trsp). Herein, we show that these mutant mice exhibit decreased pools of mature T cells and a defect in T cell-dependent antibody responses. We also demonstrate that selenoprotein deficiency leads to oxidant hyperproduction in T cells and thereby suppresses T cell proliferation in response to T cell receptor stimulation. These findings offer novel insights into immune function of selenium and physiological antioxidants.
Characterization of Yersinia pestis Interactions with Human Neutrophils In vitro

Yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. The bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. Neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and Y. pestis have been demonstrated in vivo. In contrast to macrophages, neutrophils have been considered non-permissive to Y. pestis intracellular survival. Several studies have shown killing of the vast majority of Y. pestis ingested by human neutrophils. However, survival of 10–15% of Y. pestis after phagocytosis by neutrophils is consistently observed. Furthermore, these surviving bacteria eventually replicate within and escape from the neutrophils. We set out to further characterize the interactions between Y. pestis and human neutrophils by (1) determining the effects of known Y. pestis virulence factors on bacterial survival after uptake by neutrophils, (2) examining the mechanisms employed by the neutrophil to kill the majority of intracellular Y. pestis, (3) determining the activation phenotype of Y. pestis-infected neutrophils, and (4) characterizing the Y. pestis-containing phagosome in neutrophils. We infected human neutrophils in vitro with Y. pestis and assayed bacterial survival and uptake. Deletion of the caf1 gene responsible for F1 capsule production resulted in significantly increased uptake of Y. pestis. Surprisingly, while the two-component regulator PhoPQ system is important for survival of Y. pestis within neutrophils, pre-induction of this system prior to infection did not increase bacterial survival. We used an IPTG-inducible mCherry construct to distinguish viable from non-viable intracellular bacteria and determined the association of the Y. pestis-containing phagosome with neutrophil NADPH-oxidase and markers of primary, secondary and tertiary granules. Additionally, we show that inhibition of reactive oxygen species (ROS) production or Src family kinases increased survival of intracellular bacteria indicating that both ROS and granule-phagosome fusion contribute to neutrophil killing of Y. pestis. The data presented here further our understanding of the Y. pestis neutrophil interactions and suggest the existence of still unknown virulence factors involved in Y. pestis survival within neutrophils.
Learning Robust Locality Preserving Projection via p-Order Minimization

Locality preserving projection (LPP) is an effective dimensionality reduction method based on manifold learning, which is defined over the graph weighted squared L2-norm distances in the projected subspace. Since squared L2-norm distance is prone to outliers, it is desirable to develop a robust LPP method. In this paper, motivated by existing studies that improve the robustness of statistical learning models via L1-norm or not-squared L2-norm formulations, we propose a robust LPP (rLPP) formulation to minimize the p-th order of the L2-norm distances, which can better tolerate large outlying data samples because it suppress the introduced biased more than the L1-norm or not squared L2-norm minimizations. However, solving the formulated objective is very challenging because it not only non-smooth but also non-convex. As an important theoretical contribution of this work, we systematically derive an efficient iterative algorithm to solve the general p-th order L2-norm minimization problem, which, to the best of our knowledge, is solved for the first time in literature. Extensive empirical evaluations on the proposed rLPP method have been performed, in which our new method outperforms the related state-of-the-art methods in a variety of experimental settings and demonstrate its effectiveness in seeking better subspaces on both noiseless and noisy data.
RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex‐specific effects

Genome‐wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under‐represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex‐differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex‐differences exist in the transcriptomic signature of ASD. The present study quantified genome‐wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same‐sex, proximal‐aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD‐related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n = 12 sibling pairs), as compared with the set of male samples (n = 24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation‐based gene‐set analyses and weighted gene co‐expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. Autism Res 2017, 10: 439–455. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On-Speech Masking and Multitalker Localization

Binaural hearing helps normal-hearing listeners localize sound sources and understand speech in noise. However, it is not fully understood how far this is the case for bilateral cochlear implant (CI) users. To determine the potential benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs) were measured in seven Japanese bilateral CI recipients using Helen test sentences (translated into Japanese) in a two-talker speech interferer presented from the front (co-located with the target speech), ipsilateral to the first-implanted ear (at +90° or −90°), and spatially symmetric at ±90°. Spatial release from masking was calculated as the difference between co-located and spatially separated SCTs. Localization was assessed in the horizontal plane by presenting either male or female speech or both simultaneously. All measurements were performed bilaterally and unilaterally (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial release from masking were improved with bilateral CIs, demonstrating mean bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially symmetric speech mixture. Localization performance varied strongly between subjects but was clearly improved with bilateral over unilateral CIs with the mean localization error reduced by 27°. Surprisingly, adding a second talker had only a negligible effect on localization.
The Role of Brain Structure and Function in the Association Between Inflammation and Depressive Symptoms: A Systematic Review

Objective Major depressive disorder and related symptoms have been shown to be associated with inflammation, and this association is likely to be mediated through changes in brain structure and function. This article provides a systematic review of studies that have used brain imaging techniques to identify neural mechanisms linking inflammation and depressive symptoms. Methods A systematic search of online databases identified 26 studies that fulfilled the inclusion and exclusion criteria. Results In general, increased peripheral inflammation was associated with differences in function in several subcortical regions, as well as medial and ventral prefrontal regions—both at rest (7 studies) and during exposure to emotional stimuli (14 studies). Also, increased activation in some of these regions was associated with depression (18 studies). Too few studies have measured neuroinflammation markers (three) or brain structure (three), so generalizations about these mechanisms cannot yet be made. Conclusions This review supports the view that peripheral inflammation is an etiological process that may influence depression via effects on brain function. Several methodological inconsistencies in the extant literature need to be addressed, most notably a lack of formal mediational testing in longitudinal designs and inconsistencies across imaging methods and inflammation induction and measurement techniques. Further work is also required to establish the mechanisms by which basal inflammation levels influence brain function and depressive symptoms in both healthy and clinical samples.
Correlation analysis between frequencies of circulating antigen‐specific IgG‐bearing memory B cells and serum titers of antigen‐specific IgG

Recent studies in mice have indicated that the long‐lasting specific antibody responses seen after vaccination are probably due to the existence of long‐lived plasma cells. Therefore, because the maintenance of humoral immunity does not necessarily reflect continuous restimulation of long‐lived memory B cells, the question arises as to what degree antibody immunity, as determined by measuring serum immunoglobulin titers against a particular antigen, and memory B cell immunity, as determined by counting circulating memory B cells with specificity for that same antigen, correlate. Here, using a new assay combining two‐step immunomagnetic enrichment with multiparameter flow cytometry to detect, enumerate and characterize antigen‐specific memory B cells, we show for tetanus toxin C‐fragment in blood of normal tetanus toxoid vaccinized donors, and for wasp venom phospholipase A1B in blood of wasp venom‐allergic donors undergoing an immune therapy with wasp venom, that there is no statistically significant linear correlation between the frequencies of circulating antigen‐specific IgG‐bearing memory B cells and the serum titers of antigen‐specific IgG. This lack of a statistically significant linear correlation is in accordance with the idea that B memory cells and plasma cells represent independently controlled forms of immunological memory.
Association of posttraumatic stress disorder and depression with all-cause and cardiovascular disease mortality and hospitalization among Hurricane Katrina survivors with end-stage renal disease.

OBJECTIVES We determined the association of psychiatric symptoms in the year after Hurricane Katrina with subsequent hospitalization and mortality in end-stage renal disease (ESRD) patients. METHODS A prospective cohort of ESRD patients (n = 391) treated at 9 hemodialysis centers in the New Orleans, Louisiana, area in the weeks before Hurricane Katrina were assessed for posttraumatic stress disorder (PTSD) and depression symptoms via telephone interview 9 to 15 months later. Two combined outcomes through August 2009 (maximum 3.5-year follow-up) were analyzed: (1) all-cause and (2) cardiovascular-related hospitalization and mortality. RESULTS Twenty-four percent of participants screened positive for PTSD and 46% for depression; 158 participants died (79 cardiovascular deaths), and 280 participants were hospitalized (167 for cardiovascular-related causes). Positive depression screening was associated with 33% higher risk of all-cause (hazard ratio [HR] = 1.33; 95% confidence interval [CI] = 1.06, 1.66) and cardiovascular-related hospitalization and mortality (HR = 1.33; 95% CI = 1.01, 1.76). PTSD was not significantly associated with either outcome. CONCLUSIONS Depression in the year after Hurricane Katrina was associated with increased risk of hospitalization and mortality in ESRD patients, underscoring the long-term consequences of natural disasters for vulnerable populations.
Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

ABSTRACT We studied the expression of a subset of chemokines, including RANTES/CCL5, MIP-1α/CCL3, IP-10/CXCL10, and MCP-1/CCL2, in Toll-like receptor (TLR)-competent and -deficient mice after infection with Leishmania major. Chemokine expression at the site of infection (the footpad), in the draining lymph nodes and in the spleens of infected animals was determined by using two different methods of analysis. The results indicate that L. major infection causes overall upregulation of RANTES/CCL5, MIP-1α/CCL3, IP-10/CXCL10, and MCP-1/CCL2 in the footpads and lymph nodes, while expression of these chemokines is constitutive in the spleens of TLR4-competent mice (C57BL/10ScSn) and TLR4-deficient mice (C57BL10/ScN). Different patterns of expression were detected depending on the time postinfection, but there was little variation in the expression of these four chemokines in the presence or absence of TLR4.
Study of chitosan microparticles with bone marrow mesenchymal stem cells for bone tissue regeneration

Experiments were aimed at testing the hybrid microparticles (MPs) “Chitosan and Chitosan with Calcium Phosphate” as suitable constructs for “bone marrow mesenchymal cells” (BMSCs) attachment, proliferation in vitro and to evaluate the use of “ hybrid microparticles with bone marrow mesenchymal cells constructs”, aiding bone tissue regeneration/healing in a rat femur critical size defect model. The particle were prepared with emulsification process, BMSCs harvested from rats were femurs. Cells attachment was evaluated using manual cell counting with hemocytometer. Size and surface structure of particles was assessed with Scanning electron microscope images. In vivo studies included a partial thickness 5 mm length segmental defect model of femur in 8 rats. Control group had the defect treated with metal plate only and the experiment group received transplant containing both MP and BMSC’s. A semi qualitative analysis of bone regeneration performed using X-rays, showed significant bone regeneration in experiment group at end of 4 weeks as compared to 8 weeks in previous studies.
Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction

Objectives Although guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular ejection fraction (LVEF) <50%, severe left ventricular dysfunction (LVEF <35%) is thought to confer high surgical risk. We sought to determine if a survival benefit exists with AVR compared with medical management in this high-risk, relatively rare population. Methods A large institutional echocardiography database was queried to identify patients with severe AR and LVEF <35%. Manual chart review was performed. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for comorbidities and age was then calculated using the weighted average of the individual survival curves. Results Initially, 2 54 614 echocardiograms were considered, representing 1 45 785 unique patients, of which 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. Absolute mortality was 27.8% in the AVR group and 91.2% in the medical management group. After multivariate adjustment, end-stage renal disease (HR=17.633, p=0.0335) and peripheral arterial disease (HR=6.050, p=0.0180) were associated with higher mortality. AVR was associated with lower mortality (HR=0.143, p=0.0490). Mean follow-up time of the study cohort was 6.58 years, and mean survival for patients undergoing AVR was 6.31 years. Conclusions Even after adjustment for clinical characteristics and patient age, AVR is associated with higher survival for patients with low LVEF and severe AR. Although treatment selection bias cannot be completely eliminated by this analysis, these results provide some evidence that surgery may be associated with prolonged survival in this high-risk patient group.
A support method for the contextual interpretation of biomechanical data

In the clinical field, biomechanical data provided by advanced technical devices are still underexploited. Data analysis usually consists of extracting attributes or computing synthetic values from temporal data and exploiting them by means of a monovariable statistical method. This article proposes a method to support clinicians, especially those in orthopedics, in the contextual interpretation of biomechanical data. We propose to characterize temporal biomechanical data by means of fuzzy space-time windows and to induce fuzzy decision trees to map the biomechanical and clinical data related to patients. Then, we present a method for objectively explaining a given clinical characteristic of a particular patient; this method is derived using the fuzzy rule base generated from the trees and a satisfiability measure. We have applied our method to real data in order to provide an objective explanation of the subjective self-evaluation of the functional status of patients with a shoulder prosthesis, and evaluate it by means of the stratified tenfold cross validation method. The mean explanation rate-which corresponds to the mean proportion of the patients belonging to test sets whose functional state is explained by the proposed method-exceeds 80% for more than half of the decision trees, and exceeds 70% for 94% of the trees. By supporting clinicians during the biomechanical data interpretation process, our method helps them take the objective biomechanical measurements in the medical practice into account, particularly in orthopedics. It can also make subjective evaluations more objective by mapping subjective and objective data
Leadership Training in Graduate Medical Education: A Systematic Review.

Background Leadership is a critical component of physician competence, yet the best approaches for developing leadership skills for physicians in training remain undefined. Objective We systematically reviewed the literature on existing leadership curricula in graduate medical education (GME) to inform leadership program development. Methods Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched MEDLINE, ERIC, EMBASE, and MedEdPORTAL through October 2015 using search terms to capture GME leadership curricula. Abstracts were reviewed for relevance, and included studies were retrieved for full-text analysis. Article quality was assessed using the Best Evidence in Medical Education (BEME) index. Results A total of 3413 articles met the search criteria, and 52 were included in the analysis. Article quality was low, with 21% (11 of 52) having a BEME score of 4 or 5. Primary care specialties were the most represented (58%, 30 of 52). The majority of programs were open to all residents (81%, 42 of 52). Projects and use of mentors or coaches were components of 46% and 48% of curricula, respectively. Only 40% (21 of 52) were longitudinal throughout training. The most frequent pedagogic methods were lectures, small group activities, and cases. Common topics included teamwork, leadership models, and change management. Evaluation focused on learner satisfaction and self-assessed knowledge. Longitudinal programs were more likely to be successful. Conclusions GME leadership curricula are heterogeneous and limited in effectiveness. Small group teaching, project-based learning, mentoring, and coaching were more frequently used in higher-quality studies.