Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender Difference in the Relationships between Inflammatory Markers, Serum Uric Acid and Framingham Risk Score

The purpose of the present study was to explore the role of gender in the relation of high-sensitivity C-reactive protein (hsCRP), white blood cell (WBC) count, and serum uric acid (UA) to the risk of future cardiovascular disease (CVD) events. In total, 404 workers were recruited to obtain the measurements of serum markers for CVD risk. Demographic data, nutrition, exercise, smoking, and alcohol consumption were assessed through a questionnaire. The Framingham Risk Score (FRS) was adopted to estimate the risk of future CVD events. Multiple linear regression models were used to determine CVD risk markers in relation to the FRS by gender. The hsCRP was not significantly correlated with the FRS for all workers after adjusting for covariates, including demographic data and health-related lifestyle. WBC count was positively correlated with FRS for all workers, but WBC count did not show an interaction with gender with respect to the FRS. Serum UA showed an interaction with gender on the FRS, and UA positively correlated with the FRS in males though not in females. With respect to CVD prevention, the WBC count can be used to monitor the risk for all workers. Due to a gender difference shown in the relationship between serum UA and the FRS, serum UA can be a monitor of the risk of future CVD events in male workers only.
Integration of signals from different cortical areas in higher order thalamic neurons

Significance Higher order thalamic neurons receive input from layer 5 cells of different cortical regions. We address the issue of a possible convergence of information from these different cortical areas onto individual thalamic relay cells. We leverage advances in genetic labeling and serial electron microscopy to address this question. Using dual labeling to distinguish inputs from sensory and motor cortical areas, we provide evidence of integration of different cortical signals on single thalamic relay cells in the posterior medial nucleus. This provides insight into the complex functioning of thalamus. Higher order thalamic neurons receive driving inputs from cortical layer 5 and project back to the cortex, reflecting a transthalamic route for corticocortical communication. To determine whether or not individual neurons integrate signals from different cortical populations, we combined electron microscopy “connectomics” in mice with genetic labeling to disambiguate layer 5 synapses from somatosensory and motor cortices to the higher order thalamic posterior medial nucleus. A significant convergence of these inputs was found on 19 of 33 reconstructed thalamic cells, and as a population, the layer 5 synapses were larger and located more proximally on dendrites than were unlabeled synapses. Thus, many or most of these thalamic neurons do not simply relay afferent information but instead integrate signals as disparate in this case as those emanating from sensory and motor cortices. These findings add further depth and complexity to the role of the higher order thalamus in overall cortical functioning.
Psychometric validation of the French version of the Suicidal Ideation Attributes Scale (SIDAS-FR)

Abstract The purpose of this study was to validate in French the Suicidal Ideation Attributes Scale (SIDAS) using an online community survey that was completed by 2304 French-speaking Quebec participants (adolescents and adults). The SIDAS-FR demonstrated high internal consistency (α = .83), a unifactorial structure, and strong convergent validity with relevant constructs. Cutoff scores of ≥13 for moderate severity and ≥20 for high severity of suicidal ideations were optimal. The excellent psychometric properties of the French-Canadian version of the SIDAS support its use as an effective tool for online screening of suicidal ideations, for both adolescents and adults.
Does oxidatively damaged DNA drive amyloid-β generation in Alzheimer’s disease? A hypothesis

Abstract In Alzheimer’s disease (AD), amyloid-β (Aβ) generation and upstream β-secretase 1 (BACE1) expression appear to be driven by oxidative stress via c-Jun N-terminal kinase (JNK), p38, and Interferon-Induced, Double-Stranded RNA-Activated Protein Kinase (PKR). In addition, inflammatory molecules, including lipopolysaccharide (LPS), induce genes central to Aβ genesis, such as BACE1, via nuclear factor-κB (NFκB). However, additional triggers of Aβ generation remain poorly understood and might represent novel opportunities for therapeutic intervention. Based on mechanistic studies and elevated ectopic oxidatively damaged DNA (oxoDNA) levels in preclinical AD, mild cognitive impairment, and AD patients, we hypothesize oxoDNA contributes to β-amyloidosis starting from the earliest stages of AD through multiple pathways. OxoDNA induces mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), thereby sensitizing the brain to oxidative stress-induced JNK activation and BACE1 transcription. It also induces myeloid differentiation primary response 88 (MyD88) and activates protein kinase CK2, thereby increasing NFκB activation and BACE1 induction. OxoDNA increases oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2) ectopic localization, likely augmenting JNK-mediated BACE1 induction. OxoDNA likely also promotes β-amyloidosis via absent in melanoma 2 (AIM2) induction. Falsifiable predictions of this hypothesis include that deoxyribonuclease treatment should decrease Aβ and possibly slow cognitive decline in AD patients. While formal testing of this hypothesis remains to be performed, a case report has found deoxyribonuclease I treatment improved a severely demented AD patient’s Mini-Mental Status Exam score from 3 to 18 at 2 months. There is preliminary preclinical and clinical evidence suggesting that ectopic oxidatively damaged DNA may act as an inflammatory damage-associated molecular pattern contributing to Aβ generation in AD, and deoxyribonuclease I should be formally evaluated to test whether it can decrease Aβ levels and slow cognitive decline in AD patients.
Epidemiology of Injuries in National Collegiate Athletic Association Women's Softball: 2014-2015 Through 2018-2019.

CONTEXT Women's softball athletes account for approximately 9% of all female athletes competing within the National Collegiate Athletic Association (NCAA). BACKGROUND Routine surveillance of NCAA women's softball injuries is important for identifying the emerging injury patterns in this sport. METHODS Exposure and injury data collected during competitive seasons in the NCAA Injury Surveillance Program during 2014-2015 through 2018-2019 (5 years) academic years were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics; injury rate ratios (IRRs) were used to examine differential injury rates. RESULTS The overall injury rate was 3.92 per 1000 athlete exposures. Practice and preseason injury rates increased during 2015/16 through 2018/19. Most injuries were shoulder (15.2%), hand/wrist (11.8%), knee (11.2%), and head/face injuries (11.2%) and were classified as contusions (14.2%), sprains (14.1%), and inflammatory conditions (14.1%). Concussion (6.8%) was the most commonly reported injury, and concussion incidence fluctuated during 2014-2015 through 2018-2019. SUMMARY Results indicate an increasing trend in practice and preseason injury incidence. Findings also suggest that workload accumulation in the shoulder and the mechanisms of concussion warrant further attention in this population.
Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms

Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients with neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffin-embedded (FFPE), and fresh frozen (FF) samples. CTC CNV profiling demonstrated recurrent chromosomal alterations in previously reported NEN copy number hotspots, including the prognostically relevant loss of chromosome 18. Unsupervised hierarchical clustering revealed CTCs with distinct clonal lineages as well as significant intra- and inter-patient genomic heterogeneity, including subclonal alterations not detectable by bulk analysis and previously unreported in NEN. Notably, we also demonstrated the presence of genomically distinct CTCs according to the enrichment strategy utilized (EpCAM-dependent vs size-based). This work has significant implications for the identification of therapeutic targets, tracking of evolutionary change, and the implementation of CTC-biomarkers in cancer.
A novel vehicle-mounted sticky trap; an effective sampling tool for savannah tsetse flies Glossina morsitans morsitans Westwood and Glossina morsitans centralis Machado

Background Black screen fly round (BFR) is a mobile sampling method for Glossina morsitans. This technique relies on the ability of operator(s) to capture flies landing on the screen with hand nets. In this study, we aimed to evaluate a vehicle-mounted sticky panel trap (VST) that is independent of the operator’s ability to capture flies against BFR, for effective and rapid sampling of G. m. morsitans Westwood and G. m. centralis Machado. We also determined the influence of the VST colour (all-blue, all-black or 1:1 blue-black), orientation and presence of odour attractants on tsetse catch. Methodology/Principal findings Using randomised block design experiments conducted in Zambia, we compared and modelled the number of tsetse flies caught in the treatment arms using negative binomial regression. There were no significant differences in the catch indices of the three colour designs and for in-line or transversely oriented panels for both subspecies (P > 0.05). When baited with butanone and 1-octen-3-ol, VST caught 1.38 (1.11–1.72; P < 0.01) times more G. m. centralis flies than the un-baited trap. Attractants did not significantly increase the VST catch index for G. m. morsitans (P > 0.05). Overall, the VST caught 2.42 (1.91–3.10; P < 0.001) and 2.60 (1.50–3.21; P < 0.001) times more G. m. centralis and G. m. morsitans respectively, than the BFR. The VST and BFR took 10 and 35 min respectively to cover a 1 km transect. Conclusion/Significance The VST is several times more effective for sampling G. m. morsitans and G. m. centralis than the BFR and we recommend its use as an alternative sampling tool.
Epidemiology of Injuries in National Collegiate Athletic Association Men's Soccer: 2014-2015 Through 2018-2019.

CONTEXT The National Collegiate Athletic Association has sponsored men's soccer programs since 1959, and the popularity of the sport has grown over time. BACKGROUND Routine examinations of athlete injuries are important for identifying emerging temporal patterns. METHODS Exposure and injury data collected in the National Collegiate Athletic Association Injury Surveillance Program from 2014-2015 through 2018-2019 were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics, and injury rate ratios were used to examine differential injury rates. RESULTS The overall injury rate was 8.51 per 1000 athlete exposures. Lateral ligament complex tears (ankle sprains) (9.2%), hamstring tears (7.0%), and concussions (5.2%) were the most commonly reported injuries. Rates of lateral ligament complex tears remained stable from 2014-2015 through 2018-2019, whereas hamstring tear rates decreased and concussion rates increased. SUMMARY The findings of this study were in line with the existing epidemiological evidence, although notable temporal patterns were observed. Incidence trajectories of commonly observed injuries warrant particular attention in the future.
A Novel Intronic Splice—Site Mutation of the CYP11A1 Gene Linked to Adrenal Insufficiency with 46,XY Disorder of Sex Development

A novel CYP11A1: c.1236 + 5G > A was identified, expanding the mutation spectrum of the congenital adrenal insufficiency with 46,XY sex reversal. In a now 17-year-old girl delivered full-term (G2P2, parents unrelated), adrenal failure was diagnosed in the first year of life based on clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. At the time, hormonal tests revealed primary adrenocortical insufficiency and steroid profiles showed lack of products of steroidogenesis, and since then the patient has been treated with substitution doses of hydrocortisone and fludrocortisone. At the age of 14, considering the absence of puberty symptoms, extended diagnostic tests revealed elevated LH levels (26.5 mIU/mL) with pre-puberty FSH levels (4.9 mIU/mL), low estradiol (28 pmol/L), testosterone (<2.5 ng/mL), and extremely high levels of ACTH (4961 pg/mL). A cytogenetic study revealed a 46 XY karyotype. A molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene. Compound heterozygosity for the CYP11A1 gene with a known pathogenic variant in one allele and a novel splice site mutation in the second allele is most probably responsible for congenital adrenal insufficiency with 46,XY sex reversal. We discuss the necessity of cytogenetic test in the case of early onset of adrenal failure in the absence of steroidogenesis metabolites in the steroid profile.
Exergaming to improve balance and decrease the risk of falling in adults with knee osteoarthritis: a mixed-methods feasibility study

ABSTRACT Background Exergaming (exercise and gaming) is useful in improving balance in various health conditions, yet there is limited research regarding its application in individuals with knee osteoarthritis (OA). Objectives The primary aim of this study was to investigate the feasibility and acceptability of exergaming using Nintendo Wii Fit™ to improve balance and reduce the risk of falls in individuals with knee OA. Methods A mixed-methods explanatory sequential study design was utilized in this study. Participants with knee OA and history of falling participated in a single-group pre-post experimental study design: eight weeks of usual care followed by eight weeks of an exergaming program. This was followed by semi-structured focus groups to determine the acceptability of the study. Results The pre-defined feasibility criteria such as recruitment, retention rate (83%), and compliance (78%) were successfully met. The participants found the frequency and duration of the assessment and intervention sessions acceptable. Participants reported enjoying the exergaming, finding it motivating and interactive despite some barriers with technology. No adverse events were reported. There were encouraging results in the clinical outcome measures such as knee muscle strength, balance, fear of falling, and performance of physical function. Conclusion The study found that it is feasible and acceptable to use Nintendo Wii Fit™ as an exergaming tool to improve balance and decrease the risk of falling in adults with knee OA. Findings from this feasibility study are encouraging and support the need to conduct a fully powered randomized controlled trial study.
Removal of endosulfan residues from vegetables by household processing

,potato) and summer vegetables (brinjal, tomato, okra) grown under controlled supervised field trials. Highest ER was found at raw stage in brinjal (2.43 mg/kg) followed by okra (1.83 mg/kg) and spinach (1.25 mg/kg) and lowest in potato (0.177 mg/kg). ER in vegetables was found to be reduced as follows: washing, 15-30; peeling, 60-67; and cooking, 13-35%. High levels of ERs exceeding maximum residue limits (MRLs) were observed in brinjal and tomato samples at raw stage. However , vegetable
Anti–platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and COVID-19 vaccine Janssen (Ad26.COV2.S), and associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies activating platelets through FcγRIIa receptors have also been identified in COVID-19 patients. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in-silico prediction tools and 3D-modelling. The SARS-CoV-2 spike protein and PF4 share at least one similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 VITT patients cross-reacted with SARS-CoV-2 spike protein. Sera from 222 PCR-confirmed COVID-19 patients from five European centers were tested by PF4/heparin ELISA and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in 19 of 222 (8.6%) COVID-19 patient sera. However, only four showed weak to moderate platelet activation in the presence of PF4, and none of these patients developed thrombotic complications. Among 10 of 222 (4.5%) COVID-19 patients with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in COVID-19 patients of the present study were not associated with thrombotic complications.
Italian Version of the Relationship Profile Test (RPT-I): Temporal Stability, Construct Validity, and Cross-Cultural Comparison

Abstract This study presents the adaptation to the Italian context of the Relationship Profile Test (RPT; Bornstein & Languirand), a self-report measure of Destructive Overdependence (DO), Dysfunctional Detachment (DD), and Healthy Dependency (HD). The RPT was administered to a community sample of 661 nonclinical Italian adults together with the Attachment Style Questionnaire, the Relational-Interdependent Self-Construal Scale, the Rosenberg Self-Esteem Scale, the Self-Compassion Scale, the Positive Affect-Negative Affect Scale, and the Toronto Alexithymia Scale. A randomly selected subset of participants (n = 67) completed the RPT again approximately 5 months after the first administration. The factor structure of the RPT obtained in the main sample was compared with that obtained in a sample of 603 adult participants from the US and was found to be similar. Internal consistency for DO, DD, and HD scores in the Italian sample fell between the acceptable to good range, and test-retest reliability coefficients were all above . 70. The three scales yielded the expected pattern of correlations with theoretically related constructs, documenting good criterion validity. Findings are discussed in light of the literature on the RPT as a measure of interpersonal dependency and detachment. Suggestions for future research are offered.
Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC specific T-cell bispecific antibody.

Antibody-based immunotherapy is a promising strategy for targeting chemo-resistant leukemic cells. However, classical antibody-based approaches are restricted to targeting lineage-specific cell-surface antigens. By targeting intracellular antigens, a large number of other leukemia-associated targets would become accessible. In this study, we evaluated a novel T-cell bispecific (TCB) antibody, generated using CrossMab and knob-into-holes technology, containing a bivalent T-cell receptor-like binding domain that recognizes the RMFPNAPYL peptide derived from the intracellular tumor antigen Wilms' tumor 1 (WT1) in the context of human leukocyte antigen (HLA) A*02. Binding to CD3ε recruits T cells irrespective of their T-cell receptor specificity. WT1-TCB elicited antibody-mediated T-cell cytotoxicity against AML cell lines in a WT1- and HLA-restricted manner. Specific lysis of primary AML cells was mediated in ex vivo long-term co-cultures utilizing allogenic (mean specific lysis: 67±6% after 13-14 days; ±SEM; n=18) or autologous, patient-derived T cells (mean specific lysis: 54±12% after 11-14 days; ±SEM; n=8). WT1-TCB-treated T cells exhibited higher cytotoxicity against primary AML cells than an HLA-A*02 RMF-specific T-cell clone. Combining WT1-TCB with the immunomodulatory drug lenalidomide further enhanced antibody-mediated T-cell cytotoxicity against primary AML cells (mean specific lysis on day 3-4: 45.4±9.0% vs 70.8±8.3%; p=0.015; ±SEM; n=9-10). In vivo, WT1-TCB-treated humanized mice bearing SKM-1 tumors showed a significant and dose-dependent reduction in tumor growth. In summary, we show that WT1-TCB facilitates potent in vitro, ex vivo and in vivo killing of AML cell lines and primary AML cells; these results led to the initiation of a phase I trial in patients with r/r AML (NCT04580121).
Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

Abstract Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.
Epidemiology of Injuries in National Collegiate Athletic Association Women's Soccer: 2014-2015 Through 2018-2019.

CONTEXT The National Collegiate Athletic Association held the first women's soccer championship in 1982; sponsorship and participation have greatly increased since. BACKGROUND Routine examinations of athlete injuries are important for identifying emerging temporal patterns. METHODS Exposure and injury data collected in the National Collegiate Athletic Association Injury Surveillance Program during the 2014-2015 through 2018-2019 seasons were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics, and injury rate ratios were used to examine differential injury rates. RESULTS The overall injury rate was 8.33 per 1000 athlete-exposures. Lateral ligament complex tears (ankle sprains) (8.6%), concussions (8.3%), and quadriceps tears (5.0%) were the most commonly reported injuries. Rates of lateral ligament complex tears followed an increasing trajectory during the study period, whereas quadriceps tear rates fluctuated during the early years, and concussion rates decreased then increased. SUMMARY The findings of this study were mostly consistent with existing evidence; notable temporal patterns were observed with regard to lateral ligament complex tears and concussions.