Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-related lymphomas in adults served in the public health network

Abstract Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma. We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma. The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%). Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used. In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors. We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.
Derived Polymorphic Amplified Cleaved Sequence (dPACS): A Novel PCR-RFLP Procedure for Detecting Known Single Nucleotide and Deletion–Insertion Polymorphisms

Most methods developed for detecting known single nucleotide polymorphisms (SNP) and deletion–insertion polymorphisms (DIP) are dependent on sequence conservation around the SNP/DIP and are therefore not suitable for application to heterogeneous organisms. Here we describe a novel, versatile and simple PCR-RFLP procedure baptised ‘derived Polymorphic Amplified Cleaved Sequence’ (dPACS) for genotyping individual samples. The notable advantage of the method is that it employs a pair of primers that cover the entire fragment to be amplified except for one or few diagnostic bases around the SNP/DIP being investigated. As such, it provides greater opportunities to introduce mismatches in one or both of the 35–55 bp primers for creating a restriction site that unambiguously differentiates wild from mutant sequences following PCR-RFLP and horizontal MetaPhorTM gel electrophoresis. Selection of effective restriction enzymes and primers is aided by the newly developed dPACS 1.0 software. The highly transferable dPACS procedure is exemplified here with the positive detection (in up to 24 grass and broadleaf species tested) of wild type proline106 of 5-enolpyruvylshikimate-3-phosphate synthase and its serine, threonine and alanine variants that confer resistance to glyphosate, and serine264 and isoleucine2041 which are key target-site determinants for weed sensitivities to some photosystem II and acetyl-CoA carboxylase inhibiting herbicides, respectively.
Genomic Prediction of Additive and Non-additive Effects Using Genetic Markers and Pedigrees

The genetic merit of individuals can be estimated using models with dense markers and pedigree information. Early genomic models accounted only for additive effects. However, the prediction of non-additive effects is important for different forest breeding systems where the whole genotypic value can be captured through clonal propagation. In this study, we evaluated the integration of marker data with pedigree information, in models that included or ignored non-additive effects. We tested the models Reproducing Kernel Hilbert Spaces (RKHS) and BayesA, with additive and additive-dominance frameworks. Model performance was assessed for the traits tree height, diameter at breast height and rust resistance, measured in 923 pine individuals from a structured population of 71 full-sib families. We have also simulated a population with similar genetic properties and evaluated the performance of models for six simulated traits with distinct genetic architectures. Different cross validation strategies were evaluated, and highest accuracies were achieved using within family cross validation. The inclusion of pedigree information in genomic prediction models did not yield higher accuracies. The different RKHS models resulted in similar predictions accuracies, and RKHS and BayesA generated substantially better predictions than pedigree-only models. The additive-BayesA resulted in higher accuracies than RKHS for rust incidence and in simulated additive-oligogenic traits. For DBH, HT and additive-dominance polygenic traits, the RKHS- based models showed slightly higher accuracies than BayesA. Our results indicate that BayesA performs the best for traits with few genes with major effects, while RKHS based models can best predict genotypic effects for clonal selection of complex traits.
Factors, mechanisms and implications of chromatin condensation and chromosomal structural maintenance through the cell cycle

A series of well‐orchestrated events help in the chromatin condensation and the formation of chromosomes. Apart from the formation of chromosomes, maintenance of their structure is important, especially for the cell division. The structural maintenance of chromosome (SMC) proteins, the non‐SMC proteins and the SMC complexes are critical for the maintenance of chromosome structure. While condensins have roles for the DNA compaction, organization, and segregation, the cohesin functions in a cyclic manner through the cell cycle, as a “cohesin cycle. ” Specific mechanisms maintain the architecture of the centromere, the kinetochore and the telomeres which are in tandem with the cell cycle checkpoints. The presence of chromosomal territories and compactness differences through the length of the chromosomes might have implications on selective susceptibility of specific chromosomes for induced genotoxicity.
Noise Exposure and Background Noise Tolerance in Listeners With Normal Audiograms.

Purpose Tolerance for background noise when listening to speech has been found to vary greatly between individuals, despite clinically similar audiograms. Recent work suggests that listeners at risk for noise-induced hearing loss (NIHL) self-report greater annoyance of background sounds compared with listeners at lower risk for NIHL. To date, the relationship between noise exposure levels and background noise tolerance has not been studied using objective noise exposure level measurements and quantitative (i.e., not questionnaire-based) background noise tolerance measures. Method Acceptable Noise Level (ANL; Nabelek, Tucker, & Letowski, 1991 ) scores and week-long noise dosimetry measurements were obtained for 56 normal-hearing college students, 22 of whom were routinely exposed to levels of noise that exceed recommended exposure limits (higher risk). The remaining 34 participants did not exceed recommended exposure limits (lower risk). Results The lower risk group's average daily noise dose was 26%, whereas the higher risk group accrued an average daily noise dose of 461%. The lower risk group was found to be more tolerant of background noise than the higher risk group, with mean ANL scores of 3.1 dB and 5.4 dB signal-to-noise ratio, respectively. A small but statistically significant relationship between ANL and noise dose was found, indicating that higher levels of noise exposure were associated with lower background noise tolerance. Conclusions Results suggest that young adults at higher risk for NIHL based on objective noise exposure data have a slightly lower tolerance for background noise when listening to speech. These findings open avenues for future work on background noise tolerance in more diverse noise-exposed populations.
Hydrogen Induced Etching Features of Wrinkled Graphene Domains

Wrinkles are observed commonly in CVD (chemical vapor deposition)-grown graphene on Cu and hydrogen etching is of significant interest to understand the growth details, as well as a practical tool for fabricating functional graphene nanostructures. Here, we demonstrate a special hydrogen etching phenomenon of wrinkled graphene domains. We investigated the wrinkling of graphene domains under fast cooling conditions and the results indicated that wrinkles in the monolayer area formed more easily compared to the multilayer area (≥two layers), and the boundary of the multilayer area tended to be a high density wrinkle zone in those graphene domains, with a small portion of multilayer area in the center. Due to the site-selective adsorption of atomic hydrogen on wrinkled regions, the boundary of the multilayer area became a new initial point for the etching process, aside from the domain edge and random defect sites, as reported before, leading to the separation of the monolayer and multilayer area over time. A schematic model was drawn to illustrate how the etching of wrinkled graphene was generated and propagated. This work may provide valuable guidance for the design and growth of nanostructures based on wrinkled graphene.
Mechanisms of Innate and Acquired Resistance to Anti-EGFR Therapy: A Review of Current Knowledge with a Focus on Rechallenge Therapies

Innate and acquired resistance to anti-EGFR therapy (EGFRi) is a major limitation in the treatment of metastatic colorectal cancer (mCRC). Although RAS genes are the most commonly mutated innate and acquired oncogenes in cancer, there are a number of other mechanisms that limit the effectiveness of EGFRi. Patients with innate resistance have been found to contain BRAFV600E mutations, and possibly MET, MEK, PIK3CA, PTEN, and HER2 alterations. Meanwhile, BRAFV600E mutations may also be involved in acquired resistance to EGFRi, in addition to EGFR ectodomain mutations, MET alterations, and possibly HER2 amplification. In addition, paracrine effects and cell-fate mechanisms of resistance are being increasingly described as contributing to acquired resistance. Utilization of circulating tumor DNA has been paramount in monitoring the dynamic nature of acquired resistance and has helped to guide treatment decisions, particularly in the EGFRi rechallenge setting. Herein, we provide an in-depth review of EGFRi-resistance mechanisms and describe the current therapeutic landscape in the hopes of identifying effective rechallenge strategies.
A NICE game of Minecraft: philosophical flaws underpinning UK depression guideline nosology

Categorising mental disorders for purposes of diagnosis, research and practice has historically been justified on philosophical terms as a pragmatic activity; categories which have been subject to wide-ranging philosophical critique have been defended on the grounds that they serve as heuristic devices providing loose representations of shared experiences, not labels for real structures. In acknowledgement of this, there has been increasing recognition that subclassifying multiple discrete forms of persistent depression moves too far away from the notion of a heuristic and that attempts to create more precise categories become less clinically useful. Hence the most recent Diagnostic and Statistical Manual of Mental Disorders (V.5) and International Classification of Diseases (V.11) both group persistent forms of depression together. However, the UK National Institute for Health and Care Excellence has delineated certain subclassifications of persistent depression in its new guideline, which grossly distorts the phenomenology of depression. This approach commits a fundamental philosophical error in conflating absence of knowledge with knowledge of absence. In this sense, the new guideline appears to be engaging in an activity akin to the digital game Minecraft, in which the craft of building structures from units of construction is largely divorced from the laws of physics. The risk of ignoring these philosophical errors and making false claims about scientific plausibility is that the guideline recommendations inevitably represent a highly distorted phenomenology of depression and will be of very little value to patients or practitioners looking for guidance on best possible treatment options.
Temporary Workers’ Skipping of Meals and Eating Alone in South Korea: The Korean National Health and Nutrition Examination Survey for 2013–2016

Available evidence suggests that social disadvantages are inextricably linked to unhealthy eating behaviors. Given that temporary workers face insecure employment and uncertainty in their work’s terms and conditions, issues relevant to maintaining healthy eating behavior are likely to be affected. This study investigated the association between temporary employments and, specifically, the status and frequency of meal skipping and of eating alone among temporary and permanent Korean workers. We used data from the 2013–2016 Korean National Health and Nutrition Examination Survey. A total of 5912 working people were included as the study population. We classified them as temporary workers (n = 3036) and permanent workers (n = 2876). Eating behaviors included meal skipping and eating alone. The rate and frequency of meal skipping and eating alone were higher in temporary workers. After adjustment for potential confounders, the likelihoods for temporary workers’ skipping lunch was twice as high (OR = 1.95, 95% CI 1.45–2.63) as for permanent workers. In particular, temporary workers had four-fold-increased odds (OR = 4.12, 95% CI 2.29–7.41) of eating alone three times per day relative to permanent workers. We found that temporary workers were more likely to skip meals and eat alone than were permanent workers.
Education Research: Flipped classroom in neurology

How to most effectively deliver a large amount of information in an engaging environment that encourages critical thinking is a question that has long plagued educators. With ever-increasing demands on both resident and faculty time, from shrinking duty hours to increased patient complexity, combined with the exponential growth of medical knowledge and unequal access to the spectrum of neurologic subspecialties around the country, this question has become especially pertinent to neurology residency training. A team of educators from the American Academy of Neurology's A.B. Baker Section on Neurological Education sought to review the current evidence regarding the implementation of the flipped classroom format. This educational model has only recently been applied to health care education along the training continuum, and a small collection of articles has, so far, used disparate methods of curricular implementation and assessment. While the feedback from learners is generally positive, a number of obstacles to implementation exist, most notably learner time commitments. These are presented with discussion of potential solutions along with suggestions for future studies.
The Relationship Between Neuropathic Pain and Spinal Alignment: Independent Risk Factors for Low Quality of Life in Middle-Aged and Elderly People.

MINI: In multivariate logistic regression analysis in 1,128 elderly people, NeP(+) (odds ratio (OR): 3.01), positive spinal inclination (OR: 1.14), and high VAS for LBP (OR: 1.04) were identified as risk factors for low physical QOL, and NeP(+) (OR: 5.32) was the only significant risk factor for low mental QOL. STUDY DESIGN Prospective research in middle-aged and elderly people OBJECTIVE. : To investigate low back pain (LBP) and neuropathic pain (NeP); spinal alignment and range of motion (ROM); spinal degenerative changes in plain radiography; osteoporosis; muscle strength; and physical ability as possible risk factors for poor QOL. SUMMARY OF BACKGROUND DATA The aging of society has led to an increase in elderly people with chronic pain, including LBP and NeP. However, there has been no analysis of NeP and spinal sagittal alignment as potential risk factors for decreased QOL in the healthy general population. METHODS The subjects were 1,128 people (male 473, female 655, average age: 64.3 years) who attended an annual health checkup in Yakumo study. The prevalence of LBP and sciatica were investigated using a visual analogue scale (VAS), and NeP was defined as ≥13 points on the painDETECT questionnaire. Sagittal spinal alignment with spinal ROM was also measured. Body mass index, muscle strength, physical ability, osteoporosis, and lumbar degenerative changes were measured, and SF-36 was used for QOL analysis. RESULTS NeP was present in 113 people (10%). The NeP(+) subjects had significantly more severe pain, lower gait speed, higher osteoporosis rate, lumbar kyphosis, and larger spinal inclination (p < 0.01) compared to NeP(-) subjects. On SF-36, physical and mental QOL were significantly lower for NeP(+) subjects (p < 0.0001). In multivariate logistic regression analysis adjusted for age and gender, NeP(+) (odds ratio (OR): 3.01), positive spinal inclination (OR: 1.14), and high VAS for LBP (OR: 1.04) were identified as risk factors for low physical QOL, and NeP(+) (OR: 5.32) was the only significant risk factor for low mental QOL. CONCLUSIONS These results suggest that interventions for NeP and other identified risk factors may contribute to improvement of low physical and mental QOL in middle-aged and elderly people. LEVEL OF EVIDENCE 2.
Neural Mechanisms for Accepting and Rejecting Artificial Social Partners in the Uncanny Valley

Artificial agents are becoming prevalent across human life domains. However, the neural mechanisms underlying human responses to these new, artificial social partners remain unclear. The uncanny valley (UV) hypothesis predicts that humans prefer anthropomorphic agents but reject them if they become too humanlike—the so-called UV reaction. Using fMRI, we investigated neural activity when subjects evaluated artificial agents and made decisions about them. Across two experimental tasks, the ventromedial prefrontal cortex (VMPFC) encoded an explicit representation of subjects' UV reactions. Specifically, VMPFC signaled the subjective likability of artificial agents as a nonlinear function of humanlikeness, with selective low likability for highly humanlike agents. In exploratory across-subject analyses, these effects explained individual differences in psychophysical evaluations and preference choices. Functionally connected areas encoded critical inputs for these signals: the temporoparietal junction encoded a linear humanlikeness continuum, whereas nonlinear representations of humanlikeness in dorsomedial prefrontal cortex (DMPFC) and fusiform gyrus emphasized a human–nonhuman distinction. Following principles of multisensory integration, multiplicative combination of these signals reconstructed VMPFC's valuation function. During decision making, separate signals in VMPFC and DMPFC encoded subjects' decision variable for choices involving humans or artificial agents, respectively. A distinct amygdala signal predicted rejection of artificial agents. Our data suggest that human reactions toward artificial agents are governed by a neural mechanism that generates a selective, nonlinear valuation in response to a specific feature combination (humanlikeness in nonhuman agents). Thus, a basic principle known from sensory coding—neural feature selectivity from linear–nonlinear transformation—may also underlie human responses to artificial social partners. SIGNIFICANCE STATEMENT Would you trust a robot to make decisions for you? Autonomous artificial agents are increasingly entering our lives, but how the human brain responds to these new artificial social partners remains unclear. The uncanny valley (UV) hypothesis—an influential psychological framework—captures the observation that human responses to artificial agents are nonlinear: we like increasingly anthropomorphic artificial agents, but feel uncomfortable if they become too humanlike. Here we investigated neural activity when humans evaluated artificial agents and made personal decisions about them. Our findings suggest a novel neurobiological conceptualization of human responses toward artificial agents: the UV reaction—a selective dislike of highly humanlike agents—is based on nonlinear value-coding in ventromedial prefrontal cortex, a key component of the brain's reward system.
Improving an Unstructured CFD Solver for Aeroacoustics Applications

This paper reports on the development of a computational methodology for the simulation of aeroacoustics problems. An acoustic analogy is adopted and a in-house threedimensional unstructured flow solver is coupled to the Actran/LA commercial finite element solver that uses a variational formulation of the Lighthill analogy. Numerical investigations are performed in order to assess the appropriate level of accuracy required for the computational fluid dynamics part of this methodology.
Interactions between structural remodeling and volumetric growth in right ventricle in response to pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV). The associated RV free wall (RVFW) adaptation could consist of myocardial hypertrophy, augmented intrinsic contractility, collagen fibrosis, and structural remodeling in an attempt to cope with pressure overload. If RVFW adaptation cannot maintain the RV stroke volume, RV dilation will prevail as an exit mechanism which usually decompensates the RV function leading to RV failure. Our knowledge of the factors determining the transition from the upper limit of RVFW adaptation to RV decompensation and the role of fiber remodeling events in this transition remains very limited. Computational heart models that connect the growth and remodeling (G\&R) events at the fiber and tissue levels with alterations in the organ-level function are essential to predict the temporal order and the compensatory level of the underlying mechanisms. In this work, building upon our recent rodent heart models (RHM) of PAH, we integrated mathematical models that describe time-evolution volumetric growth of the RV and structural remodeling of the RVFW. Results suggest that augmentation of the intrinsic contractility of myofibers accompanied by an increase in passive stiffness of RVFW is among the first remodeling events through which the RV strives to maintain the cardiac output. Interestingly, we found that the observed reorientation of the myofibers towards the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the contractile pattern of RVFW and advanced along with RV dilation at later stages of PAH development.
Heart Failure Differentially Modulates Natural (Sinoatrial Node) and Ectopic (Pulmonary Veins) Pacemakers: Mechanism and Therapeutic Implication for Atrial Fibrillation

Heart failure (HF) frequently coexists with atrial fibrillation (AF) and dysfunction of the sinoatrial node (SAN), the natural pacemaker. HF is associated with chronic adrenergic stimulation, neurohormonal activation, abnormal intracellular calcium handling, elevated cardiac filling pressure and atrial stretch, and fibrosis. Pulmonary veins (PVs), which are the points of onset of ectopic electrical activity, are the most crucial AF triggers. A crosstalk between the SAN and PVs determines PV arrhythmogenesis. HF has different effects on SAN and PV electrophysiological characteristics, which critically modulate the development of AF and sick sinus syndrome. This review provides updates to improve our current understanding of the effects of HF in the electrical activity of the SAN and PVs as well as therapeutic implications for AF.