Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic active Epstein–Barr virus infection: a bi-faceted disease with inflammatory and neoplastic elements

Abstract Chronic active Epstein–Barr virus infection (CAEBV) is one of the Epstein–Barr virus (EBV)-positive T- or NK-cell lymphoproliferative diseases. It is characterized by clonal proliferation of EBV-infected T or NK cells and their infiltration into systemic organs, leading to their failure. Inflammatory symptoms, fever, lymphadenopathy and liver dysfunction are main clinical findings of CAEBV. EBV itself contributes to the survival of the host cells via induction of CD40 and CD137 expression and constitutive activation of NF-κB. Accumulation of gene mutations in the infected cells may lead to the development of highly malignant lymphoma or leukemia. Furthermore, constitutive activation of STAT3 is detected in the infected cells, which not only promotes cell survival but also enhances production of inflammatory cytokines. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only effective treatment strategy for eradication of EBV-infected T or NK cells. However, active disease at the time of allo-HSCT (defined as presence of fever, liver dysfunction, progressive skin lesions, vasculitis or uveitis) is a negative prognostic factor. Establishment of chemotherapy regimens for effective resolution of disease activity in patients with CAEBV is a key imperative. Based on the recently unraveled molecular mechanisms CAEBV development, pathways mediated by NF-κB or JAK/STAT are potential novel therapeutic targets.
Stress-induced dislocations in silicon integrated circuits

Many of the processes used in the fabrication of silicon integrated circuits lead to the development of stress in the silicon substrate. Given enough stress, the substrate will yield by generating dislocations. We examine the formation of stress-induced dislocations in integrated circuit structures. Examples are presented from bipolar and MOS-based integrated circuit structures that were created during developmental studies. The underlying causes of oxidation-induced stress and the effect on such stress of varying oxidation conditions are discussed. The knowledge thus gained is used to explain dislocation generation during the formation of a shallow-trench isolation structure. The importance of ion-implantation processes in nucleating dislocations is illustrated using structures formed by a deep-trench isolation process and a process used to form a trench capacitor in a DRAM cell. The effect of device layout geometry on dislocation generation is also examined. We show how TEM observations can be used to provide more information than solely identifying those process conditions under which dislocations are generated. By combining TEM observations with stress analysis, we show how the sources of stress responsible for dislocation movement can be identified.
Learning More from Finger Tapping in Parkinson's Disease: Up and Down from Dyskinesia to Bradykinesia

The finger tapping test evaluates bradykinesia, focusing on decrement in rate, amplitude, or both with repetitive action. Vertical positioning of the hands during this task may also be clinically relevant. We developed a “TAP score,” measuring the vertical level above the lap where the patient performs the finger tapping ranging from 1 (task performed with the hand close to the lap) to 4 (above the head). In this pilot study, we retrospectively applied the TAP score in addition to usual motor scales during acute levodopa challenge in 123 PD patients (of whom 88 presented l‐dopa‐induced dyskinesia [LID]). TAP ON was higher than TAP OFF. Patients with LID presented higher TAP ON. TAP ON was related to LID severity, whereas TAP OFF was inversely related to the OFF motor symptoms. The TAP score may be a measure of proximal movement amplitude representing an easy method to evaluate defective or excessive motor output in patients with advanced disease.
10-Hydroxycamptothecin induces apoptosis in human fibroblasts by regulating miRNA-23b-3p expression

10-Hydroxycamptothecin (HCPT) effectively controls epidural fibrosis, but the exact underlying mechanisms remain ambiguous. Abnormal microRNA (miR)-23b-3p expression has been detected in various types of fibrotic tissues that are present in different diseases. The aim of the present study was to elucidate the mechanisms through which HCPT induces fibroblast apoptosis. Reverse transcription-quantitative polymerase chain reactions were performed on six traumatic scar samples and matched normal skin samples; traumatic scar formation was revealed to be significantly inversely associated with miR-23b-3p expression. In addition, the miR-23b-3p expression level in human fibroblasts was examined following HCPT treatment. The effects of HCPT and miR-23b-3p on fibroblast apoptosis were assessed using terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling, flow cytometry and western blot analysis. The results demonstrated that HCPT treatment notably increased miR-23b-3p expression levels and accelerated fibroblast apoptosis. Therefore, upregulation of miR-23b-3p expression was demonstrated to promote fibroblast apoptosis, consistently with the effects of HCPT. The results of the present study indicated that HCPT may induce fibroblast apoptosis by regulating miR-23b-3p expression.
Short-Term Mediterranean Diet Improves Endurance Exercise Performance: A Randomized-Sequence Crossover Trial

Abstract Objective: Healthful dietary patterns have constituents that are known to improve exercise performance, such as antioxidants, nitrates, and alkalizing effects. However, ergogenic effects of such diets have not been evaluated. We hypothesized that a short-term Mediterranean diet results in better exercise performance, as compared to a typical Western diet. Methods: Eleven recreationally active women (n = 7) and men (n = 4) (body mass index, 24.6 ± 3.2 kg/m2; age 28 ± 3 years) were studied in a randomized-sequence crossover study, in which they underwent exercise performance testing on one occasion after 4 days of a Mediterranean diet and on another occasion after 4 days of a Western diet. A 9- to 16-day washout period separated the two trials. Endurance exercise performance was evaluated with a 5-km treadmill time trial. Anaerobic exercise performance tests included a Wingate cycle test, a vertical jump test, and hand grip dynamometry. Results: Five-kilometer run time was 6% ± 3% shorter (faster) in the Mediterranean diet trial than in the Western diet trial (27.09 ± 3.55 vs 28.59 ± 3.21 minutes; p = 0.030) despite similar heart rates (160 ± 5 vs 160 ± 4 beats/min; p = 0.941) and ratings of perceived exertion (14.6 ± 0.5 vs 15.0 ± 0.5; p = 0.356). No differences between the diet conditions were observed for anaerobic exercise tests, including peak and mean power from the Wingate test (both p ≥ 0.05), the vertical jump test (p = 0.19), and the hand grip strength test (p = 0.69). Conclusions: Our findings extend existing evidence of the health benefits of the Mediterranean diet by showing that this diet is also effective for improving endurance exercise performance in as little as 4 days. Further studies are warranted to determine whether a longer-term Mediterranean diet provides greater benefits and whether it might also be beneficial for anaerobic exercise performance and muscle strength and power.
Serum Albumin Trend Is a Predictor of Mortality in ICU Patients With Sepsis

Introduction: Patients admitted to the hospital with sepsis are 8 times more likely to die than patients with other diagnoses. There is no diagnostic test that clearly identifies the presence of the dysregulated host response that is central to sepsis. Researchers have identified serum albumin as a possible predictor of mortality in a number of critically ill patient populations. However, these studies primarily focus on the levels on admission, neglecting the clinically significant decrease that occurs subsequently. The purpose of this study was to examine the relationship between the trend of serum albumin over time and mortality in adults admitted to the intensive care unit (ICU) with sepsis. Methods: This retrospective, correlational study used existing medical record data. All patients admitted to the ICU at a Midwestern regional medical center with a primary sepsis diagnosis were included in the initial sample. Logistic regression analysis was used to assess the ability of serum albumin to predict mortality. Results: Serum albumin trend, admission serum albumin level, and lowest serum albumin level were significant unique predictors of mortality. The probability of survival decreases by 70.6% when there is a strong negative trend in serum albumin level, by 63.4% when admission serum albumin is ≤2.45 g/dl, and by 76.4% when the lowest serum albumin is ≤1.45 g/dl. Conclusion: Clinicians are encouraged to measure serum albumin levels in patients with sepsis. Low serum albumin levels and a strong negative trend in serial measurements should instigate aggressive monitoring and treatment in this population.
Reasons for low uptake of a psychological intervention offered to cancer survivors with elevated depressive symptoms

In line with screening guidelines, cancer survivors were consecutively screened on depressive symptoms (as part of standard care), with those reporting elevated levels of symptoms offered psychological care as part of a trial. Because of the low uptake, no conclusions could be drawn about the interventions' efficacy. Given the trial set‐up (following screening guidelines and strict methodological quality criteria), we believe that this observational study reporting the flow of participation, reasons for and characteristics associated with nonparticipation, adds to the debate about the feasibility and efficiency of screening guidelines.
Differential susceptibility effects of maternal sensitivity in childhood on small for gestational age adults’ wealth

Abstract Being born small for gestational age (SGA) is considered a developmental vulnerability. Alternatively, SGA may be viewed as a marker for individual susceptibility to environmental experiences. The aim was to test if individuals born SGA are more susceptible to both negative and positive environmental experiences assessed by sensitive parenting in childhood compared with those born appropriate for gestational age (AGA). The target outcome was wealth in young adulthood. A total of 438 participants (SGA, n = 109; AGA, n = 329) were studied as part of the prospective Bavarian Longitudinal Study of neonatal at-risk children. Maternal sensitivity was observed during a standardized mother-child interaction task, and IQ was assessed with the Kaufman Assessment Battery for Children at age 6 years. At age 26, participants’ wealth was assessed with a comprehensive composite score. Individuals born SGA were found to be more susceptible to the effects of sensitive parenting after controlling for gestational age and IQ at age 6 years. When maternal sensitivity was lower than average, SGA adults did worse than AGA adults, but when exposed to above-average maternal sensitivity in childhood, they obtained significantly higher wealth than their AGA peers by 26 years of age.
Adult Hippocampal Neurogenesis in Different Taxonomic Groups: Possible Functional Similarities and Striking Controversies

Adult neurogenesis occurs in many species, from fish to mammals, with an apparent reduction in the number of both neurogenic zones and new neurons inserted into established circuits with increasing brain complexity. Although the absolute number of new neurons is high in some species, the ratio of these cells to those already existing in the circuit is low. Continuous replacement/addition plays a role in spatial navigation (migration) and other cognitive processes in birds and rodents, but none of the literature relates adult neurogenesis to spatial navigation and memory in primates and humans. Some models developed by computational neuroscience attribute a high weight to hippocampal adult neurogenesis in learning and memory processes, with greater relevance to pattern separation. In contrast to theories involving neurogenesis in cognitive processes, absence/rarity of neurogenesis in the hippocampus of primates and adult humans was recently suggested and is under intense debate. Although the learning process is supported by plasticity, the retention of memories requires a certain degree of consolidated circuitry structures, otherwise the consolidation process would be hampered. Here, we compare and discuss hippocampal adult neurogenesis in different species and the inherent paradoxical aspects.
Regarding “patient‐reported versus physiologic swallowing outcomes in patients with head and neck cancer after chemoradiation”

The recent article by Kirsh et al. highlights the limitations of using patient-reported quality-of-life (QoL) outcomes to measure the toxicity of cancer treatments. The authors do not mention an important contribution by the study that deserves more discussion. The study by Kirsh et al. is a meticulous evaluation of the relationship between patient-reported and physiologic swallowing measures after chemoradiation therapy for head and neck cancer. The main finding is that, “Assessment of swallowing physiology showed that function worsened after chemoradiation therapy, but this did not correlate with patient-reported quality-of-life measures. ” Dr. Ringash from the Princess Margaret Hospital has written several editorials noting this finding in head and neck cancer trials. The main reason that QoL scores often do not reflect objective physiologic deficits is a psychological phenomenon called the adaptation principle. We have written a short review of this subject. The reason to expand on the Kirsh et al. study in this letter is that failure to understand the limitations of patientreported QoL evaluation compromises the ability to make conclusions about treatment efficacy. An example of this issue in head and neck cancer includes the high-profile publications concluding that transoral surgery is the “optimal” treatment for oropharynx cancer because patientreported QoL scores return to near baseline a year or more after treatment. This conclusion ignores the near-universal finding of favorable long-term QoL scores following most treatment programs. As Kirsh et al. demonstrate, patientreported QoL often does not reflect important physiologic problems. Appreciating how this study contributes to the expanding body of knowledge on the limitations of QoL evaluation will improve clinical trial design and the accuracy of conclusions about treatment efficacy.
Sources of Dietary Salt in North and South India Estimated from 24 Hour Dietary Recall

Recent data on salt intake levels in India show consumption is around 11 g per day, higher than the World Health Organization’s (WHO) recommended intake of 5 g per day. However, high-quality data on sources of salt in diets to inform a salt reduction strategy are mostly absent. A cross-sectional survey of 1283 participants was undertaken in rural, urban, and slum areas in North (n = 526) and South (n = 757) India using an age-, area-, and sex-stratified sampling strategy. Data from two 24-h dietary recall surveys were transcribed into a purpose-built nutrient database. Weighted salt intake was estimated from the average of the two recall surveys, and major contributors to salt intake were identified. Added salt contributed the most to total salt intake, with proportions of 87.7% in South India and 83.5% in North India (p < 0.001). The main food sources of salt in the south were from meat, poultry, and eggs (6.3%), followed by dairy and dairy products (2.6%), and fish and seafood (1.6%). In the north, the main sources were dairy and dairy products (6.4%), followed by bread and bakery products (3.3%), and fruits and vegetables (2.1%). Salt intake in India is high, and this research confirms it comes mainly from added salt. Urgent action is needed to implement a program to achieve the WHO salt reduction target of a 30% reduction by 2025. The data here suggest the focus needs to be on changing consumer behavior combined with low sodium, salt substitution.
Electromyogram-Related Neuromuscular Electrical Stimulation for Restoring Wrist and Hand Movement in Poststroke Hemiplegia: A Systematic Review and Meta-Analysis

Background. Clinical trials have demonstrated some benefits of electromyogram-triggered/controlled neuromuscular electrical stimulation (EMG-NMES) on motor recovery of upper limb (UL) function in patients with stroke. However, EMG-NMES use in clinical practice is limited due to a lack of evidence supporting its effectiveness. Objective. To perform a systematic review and meta-analysis to determine the effects of EMG-NMES on stroke UL recovery based on each of the International Classification of Functioning, Disability, and Health (ICF) domains. Methods. Database searches identified clinical trials comparing the effect of EMG-NMES versus no treatment or another treatment on stroke upper extremity motor recovery. A meta-analysis was done for outcomes at each ICF domain (Body Structure and Function, Activity and Participation) at posttest (short-term) and follow-up periods. Subgroup analyses were conducted based on stroke chronicity (acute/subacute, chronic phases). Sensitivity analysis was done by removing studies rated as poor or fair quality (PEDro score <6). Results. Twenty-six studies (782 patients) met the inclusion criteria. Fifty percent of them were considered to be of high quality. The meta-analysis showed that EMG-NMES has a robust short-term effect on improving UL motor impairment in the Body Structure and Function domain. No evidence was found in favor of EMG-NMES for the Activity and Participation domain. EMG-NMES had a stronger effect for each ICF domain in chronic (≥3 months) compared to acute/subacute phases. Conclusion. EMG-NMES is effective in the short term in improving UL impairment in individuals with chronic stroke.
Depression and risk of cognitive dysfunctions in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is not only a motor disorder: More than 50% of patients have cognitive dysfunctions over the course of the disease. At the same time, mood disorders may also occur in ALS patients following diagnosis due to the fatal prognosis; however, little data are available on any depression beforehand. Starting from these considerations, the aim of our study was to investigate the occurrence of depression in Italian ALS patients prior to diagnosis, evaluating its prevalence in the subjects who have developed cognitive dysfunctions and in those who did not.
Longitudinal Pathways From Shyness in Early Childhood to Personality in Adolescence: Do Peers Matter?

Temperamental shyness in childhood is theorized to be an important contributor for adolescent personality. However, empirical evidence for such pathways is scarce. Using longitudinal data (N = 939 children, 51% boys) across 17 years, the aim of this study was to examine how shyness development throughout childhood predicted personality traits in adolescence, and the role of peers in these associations. Results from piecewise latent growth curve modeling showed early shyness levels to predict lower emotional stability and openness in adolescence, whereas early shyness levels and growth across childhood predicted lower extraversion. Peer problems in early adolescence accounted for these associations. This study is the first to demonstrate the role of childhood shyness and peer relations for adolescents' personality development.
Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study

OBJECTIVE To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6–23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0–4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β −7.0 g/day, 95% CI −12.4 to −1.7 per additional LP allele), nonalcoholic beverages (β −18.0 g/day, 95% CI −34.4 to −1.6), and wine (β −4.8 g/day, 95% CI −9.1 to −0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93–1.05). CONCLUSIONS rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.
An artificial neural network model for clinical score prediction in Alzheimer disease using structural neuroimaging measures

Background The development of diagnostic and prognostic tools for Alzheimer disease is complicated by substantial clinical heterogeneity in prodromal stages. Many neuroimaging studies have focused on case–control classification and predicting conversion from mild cognitive impairment to Alzheimer disease, but predicting scores from clinical assessments (such as the Alzheimer’s Disease Assessment Scale or the Mini Mental State Examination) using MRI data has received less attention. Predicting clinical scores can be crucial in providing a nuanced prognosis and inferring symptomatic severity. Methods We predicted clinical scores at the individual level using a novel anatomically partitioned artificial neural network (APANN) model. The model combined input from 2 structural MRI measures relevant to the neurodegenerative patterns observed in Alzheimer disease: hippocampal segmentations and cortical thickness. We evaluated the performance of the APANN model with 10 rounds of 10-fold cross-validation in 3 experiments, using cohorts from the Alzheimer’s Disease Neuroimaging Initiative (ADNI): ADNI1, ADNI2 and ADNI1 + 2. Results Pearson correlation and root mean square error between the actual and predicted scores on the Alzheimer’s Disease Assessment Scale (ADNI1: r = 0.60; ADNI2: r = 0.68; ADNI1 + 2: r = 0.63) and Mini Mental State Examination (ADNI1: r = 0.52; ADNI2: r = 0.55; ADNI1 + 2: r = 0.55) showed that APANN can accurately infer clinical severity from MRI data. Limitations To rigorously validate the model, we focused primarily on large cross-sectional baseline data sets with only proof-of-concept longitudinal results. Conclusion The APANN provides a highly robust and scalable framework for predicting clinical severity at the individual level using high-dimensional, multimodal neuroimaging data.