Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between prior use of anti-diabetic medication and breast cancer stage at diagnosis

ABSTRACT Background Knowledge regarding antidiabetic medication (ADM) use prior to breast cancer (BC) diagnosis remains limited. The objectives were to (1) evaluate if the prior use of ADM was associated with BC stage at diagnosis and (2) identify and compare patient characteristics among BC patients using different ADMs. Research design and methods Newly diagnosed female BC patients exposed to any medication during one year prior to cancer diagnosis were identified in 2008–2013 Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Stage at diagnosis, categorized as early and advanced, was the primary outcome. Chi-square tests were used to compare characteristics and logistic regression models were applied to examine the effect while controlling for patient’s characteristics. Results A total of 1,719 female BC patients used ADM while 6,084 patients were non-ADM users. Although a higher proportion of ADM users (20.36%) were diagnosed with advanced stage compared to the non-ADM users (14.46%), the difference was not statistically significant after adjusting for the patients’ characteristics. Besides, insulin users were more likely to be diagnosed with advanced stage (adjusted odds ratio 1.69; 95% CI 1.15, 2.48) compared to metformin users. Conclusions The association between ADM use and BC diagnostic characteristics varied based on different treatments.
Gir and Guzerat cow milk production and composition according to lactation stage, somatic cell count, physiological state and body condition

This work was realized to evaluate lactation stage, physiological state, somatic cell count (SCC) and body condition score (BCS) on production and composition of cow's milk from Gir and Guzerat breeds were studied. Ninety-eight cows were analyzed and classified according to their physiological state, lactation stage, SCC and BCS. Milk production was weighed monthly to obtain production data. Composed samples were collected in vials containing preservatives and sent to the laboratory for analysis. Data were used for statistic descriptive analysis and analysis of variance. Higher milk production in the first 60 days of lactation was observed. Fat, protein and total solids concentration increased according to the increase of days in milk; while lactose concentration decreased. Higher levels of fat, protein and total solids in milk of non-pregnant cows were observed; while pregnant cows had higher daily production and higher lactose content in their milk. Higher lactose levels in milk were observed in animals with lower SCC. The BCS had no effect on milk composition or on somatic cell count. Zebu cow milk production and composition are influenced by lactation stage, physiological state and SCC.
Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee

Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.
Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes.

BACKGROUND Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor α that has already been approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown. METHODS In this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration-time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile. RESULTS A total of 84 participants underwent randomization - 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose-adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies. CONCLUSIONS Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545.).
The potential effects of clinical antidiabetic agents on SARS‐CoV‐2

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is currently posing significant threats to public health worldwide. It is notable that a substantial proportion of patients with sever COVID‐19 have coexisting diabetic conditions, indicating the progression and outcome of COVID‐19 may relate to diabetes. However, it is still unclear whether diabetic treatment principles can be used for the treatment of COVID‐19.
HD-tDCS as a neurorehabilitation technique for a case of post-anoxic leukoencephalopathy

ABSTRACT Post-anoxic leukoencephalopathy is a rare event that causes global demyelination secondary to anoxic injury. Given the nature and extent of the damage, cognitive and functional deficits are typically chronic even after standard therapies. Here, we describe a novel treatment approach that used high definition transcranial direct-current stimulation (HD-tDCS) with a 62-year-old male who was 5 years post-anoxic leukoencephalopathy secondary to an accidental drug overdose. HD-tDCS was administered over the left lateral prefrontal cortex across 29 daily sessions at 2 mA (20 min/session) in order to address dysexecutive behaviors. Results demonstrated improved delayed memory and trends for improved visuospatial and semantic fluency performance as well as improved insight and daily functioning, all of which returned to baseline by the end of a 10 week no-contact follow up period. Resting state fMRI connectivity results mirrored these changes by showing increased dorsal attention and cingulo-opercular but reduced ventral attention network connectivity after session 29, all of which returned to baseline at follow-up. These findings suggest HD-tDCS may benefit functioning even following serious and pervasive anoxic injury. Findings also suggest the need for continued HD-tDCS for maintenance purposes, though future work is needed to identify optimal dose-response information.
The Protective Roles of Butein on Indomethacin Induced Gastric Ulcer in Mice.

Objective Butein is a potential agent first isolated from Rhus verniciflua that has medicinal value in East Asia and has been used in the treatment of gastritis, gastric cancer, and atherosclerosis since ancient times. The aim of our study is to show, for the first time, the anti-ulcerative effect of butein in indomethacin induced gastric ulcer in mice. Materials and Methods A total of 42 mice were fasted 24 hours for the ulcer experiment, and 10, 20, and 40 mg/kg doses of butein were evaluated for their antiulcer activity. Famotidine 40 mg/kg was used as a positive control group. For ulcer induction, 25 mg/kg dose of indomethacin was administered to the mice and after 6 hours all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels of stomachs were evaluated by Real Time PCR, and Superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were determined by ELISA. Results Butein administration exerted 50.8%, 65.9%, and 87.1% antiulcer effects at 10, 20, and 40 mg/kg, respectively. Butein administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Furthermore, butein administration increased stomach PGE2 levels and decreased COX-1 and COX-2 mRNA levels. Conclusion Butein has been shown to have a healing effect on ulcers in macroscopic examinations in our study. We observed that butein has antioxidant and anti-cytokine properties in gastric tissue. Butein could be an important alternative in the treatment of indomethacin-induced ulcers. Whether butein is a partial agonist of the COX enzyme should be investigated in future studies.
Resting‐State Functional Connectivity Predicts STN DBS Clinical Response

Deep brain stimulation of the subthalamic nucleus is a widely used adjunctive therapy for motor symptoms of Parkinson's disease, but with variable motor response. Predicting motor response remains difficult, and novel approaches may improve surgical outcomes as well as the understanding of pathophysiological mechanisms. The objective of this study was to determine whether preoperative resting‐state functional connectivity MRI predicts motor response from deep brain stimulation of the subthalamic nucleus.
Impact of severe obesity on exercise performance in heart failure with preserved ejection fraction

Obesity plays an important role in functional impairment in HFpEF. The mechanisms underlying decreased functional capacity in obese HFpEF are not clear. We assessed the cardiac and peripheral determinants of exercise performance in HFpEF patients with class 2 obesity in the upright position, representative of posture when performing functional activities.
Home-Based Pediatric Teleneuropsychology: A validation study.

OBJECTIVE To evaluate home-based teleneuropsychology in a pediatric cohort to determine if assessment via in-person and home-based videoconference yield similar results. The second objective was to determine the level of satisfaction with videoconference-based assessment among participants and caregivers. METHOD Fifty-eight participants, aged 6-20 years, were recruited through specialty programs for pediatric demyelinating disorders. Each participant was administered the same brief neuropsychological battery of common measures twice, once during an in-person session and once during a remote home-based videoconference session. Order of sessions was counterbalanced and time between assessments ranged from 1 to 50 days. It was hypothesized that results obtained through in-person vs. remote videoconference sessions would not be significantly different and that most participants and caregivers would rate the experience with teleneuropsychology as satisfactory. RESULTS Mann-Whitney U tests showed no significant differences in results obtained in the in-person first vs. remote videoconference first sessions or the change in performance across sessions. Satisfaction ratings by participants and caregivers were largely favorable for the use of the videoconference testing format. CONCLUSIONS The current study is the first to validate home-based teleneuropsychology and is the first to validate teleneuropsychological assessment in a pediatric sample. Future studies should replicate these findings as well as expand on sample size, diversity of populations evaluated, and the assessment tools administered. Careful consideration of ethical and practical factors should be given before providing pediatric teleneuropsychology services.
Maternal regulation of inflammatory cues is required for induction of preterm birth

Infection-driven inflammation in pregnancy is a major cause of spontaneous preterm birth (PTB). Both systemic infection and bacterial ascension through the vagina/cervix to the amniotic cavity are strongly associated with PTB. However, the contribution of maternal or fetal inflammatory responses in the context of systemic or localized models of infection-driven PTB is not well defined. Here, using intraperitoneal or intraamniotic LPS challenge, we examined the necessity and sufficiency of maternal and fetal Toll-like receptor (TLR) 4 signaling in induction of inflammatory vigor and PTB. Both systemic and local LPS challenge promoted induction of inflammatory pathways in uteroplacental tissues and induced PTB. Restriction of TLR4 expression to the maternal compartment was sufficient for induction of LPS-driven PTB in either systemic or intraamniotic challenge models. In contrast, restriction of TLR4 expression to the fetal compartment failed to induce LPS-driven PTB. Vav1-Cre–mediated genetic deletion of TLR4 suggested a critical role for maternal immune cells in inflammation-driven PTB. Further, passive transfer of WT in vitro–derived macrophages and dendritic cells to TLR4-null gravid females was sufficient to induce an inflammatory response and drive PTB. Cumulatively, these findings highlight the critical role for maternal regulation of inflammatory cues in induction of inflammation-driven parturition.
Fetal brain biometry in isolated mega cisterna magna: MRI and US study

Abstract Objective To characterize the biometric parameters in ultrasound and brain MRI of fetuses with isolated mega cisterna magna (MCM). Methods Cross-sectional historical cohort study conducted at a single tertiary medical center between 2011 and 2018. All fetuses underwent US and brain MRI scans. Matching analysis was performed according to gender and gestational age. Results The study included a total of 103 fetuses; 44 fetuses with isolated MCM in the study group, and a control group of 59 fetuses with normal CNS. The study group had larger biparietal diameter (BPD) (86 vs. 79.8 mm, p = .001) and head circumference (HC) (318 vs. 292 mm, p < .001) on ultrasound. On MRI, study group had larger occipitofrontal diameter (OFD) (99 vs. 92 mm, p < .001) and BPD (77 vs. 72 mm, p < .001). Male fetuses’ prevalence was higher in the study group (77.3% vs. 47.5%). After matching 20 fetuses from each group, the study group had larger HC (310.1 versus 300.7 mm, p = .029) and OFD (113.4 versus 108.3 mm, p = .009) on ultrasound, and larger OFD (97.4 versus 94.6, p = .013) on brain MRI. Conclusions Isolated MCM may be related to other large fetal CNS biometric measurements in both ultrasound and MRI and might be influenced by fetal gender.
Effects of Heparin on Mouse Pregnancy and Human Trophoblast Cell Lines

Severe preeclampsia (sPE) is a life threatening pregnancy disorder originating from the placenta. The exchange surface in the placenta is formed by a layer of syncytiotrophoblast (SCT) cells, which are formed and rejuvenated via terminal differentiation of the underlying proliferative villous cytotrophoblast (VCT) cells. The balance of VCT proliferation and differentiation is thought to be abnormal in sPE. Heparin, classically an anticoagulant drug, decreases recurrence in women at risk of sPE by 50% via unknown mechanisms. We studied the effects of heparin on proliferation and differentiation on trophoblast cells using human cell lines and mice. Heparin caused upregulated expression of PCNA, a proliferation marker, in choriocarcinoma BeWo cells as a model of VCT cells. Heparin in mice caused upregulated expression of suspected trophoblast progenitor markers (Eomes, Sca1), without altering syncytial differentiation. Hence we suspect that heparin improves pregnancy outcome by promoting VCT cell proliferation.
[Psychosocial risks, occupational stress and burnout syndrome in university workers from a Bioanalysis School].

OBJECTIVE To evaluate psychosocial risks, occupational stress and burnout syndrome in university workers from a Venezuelan bioanalysis school. MATERIALS AND METHODS Descriptive, cross-sectional study performed with a sample of 75 workers. The analysis of psychosocial risks, occupational stress and burnout syndrome was done using the CoPsoQ-istas21 methodology. RESULTS The main psychosocial risks were work rhythm (80.8%) and insecure working conditions (54.9%). The most unfavorable health situations included double presence (52.7%); the intermediate situations were related to role conflict (38.9%); and the most favorable situations were associated with recognition (98.6%) and vertical confidence (94.3%). Both occupational stress (3%) and burnout syndrome (5%) were observed in the most unfavorable situations. There were direct relationships between seniority and wage scale (r=0.361; p<0.001); between occupational stress and burnout syndrome (r=0.512; p<0.01); and between work satisfaction and self-perceived health status (r=0.485; p<0.01). CONCLUSIONS The description of positions and functions performed by workers should be analyzed and reinforced; moreover, staff performance indicators should be built and better mechanisms for work planning and systems of information should be established to help improve the School's managerial model.
Comparative Efficacy and Safety of Conservative Care for Pregnancy-Related Low Back Pain: A Systematic Review and Network Meta-analysis.

OBJECTIVE More than half of pregnant women experience pregnancy-related low back pain (LBP). Pregnancy-related LBP greatly affects activities of daily life, and, although many interventions have been proposed, the optimal treatment for pregnancy-related LBP remains unclear. The purpose of this study was to compare conservative care strategies on their efficacy and safety for women with pregnancy-related LBP through systematic review with pairwise meta-analysis and network meta-analysis. METHODS MEDLINE, Embase, the Cochrane Library, AMED, CINAHL, PEDro, PsycINFO, and ClinicalTrials.gov were searched from inception to November 2019. Randomized controlled trials and observational controlled studies were included without restriction to language, sample size, or duration of follow-up. Two independent investigators extracted the data and assessed the risk of bias. The quality of evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS Twenty-three studies were included in the qualitative synthesis (18 randomized controlled trials were included in the network meta-analysis). For women with LBP during pregnancy, progressive muscle relaxation therapy (mean difference = -3.96; 95% CI = -7.19 to -0.74; moderate-quality evidence) and Kinesio Taping (mean difference = -3.71; 95% CI = -6.55 to -0.87; low-quality evidence) reduced pain intensity (Visual Analog Scale, range = 0-10) compared with placebo. Moderate-quality evidence suggested that transcutaneous electrical nerve stimulation improved physical function (mean difference = -6.33; 95% CI = -10.61 to -2.05; Roland Morris Disability Questionnaire, range = 0-24) compared with placebo. CONCLUSIONS For patients with LBP during pregnancy, progressive muscle relaxation therapy and Kinesio Taping may help to decrease pain, and transcutaneous electrical nerve stimulation may improve physical function. IMPACT This review helps fill the gap in evidence regarding optimal treatment for pregnancy-related LBP.
Modelling Potential Geographical Access of the Population to Public Hospitals and Quality Health Care in Romania

The geographical accessibility to hospitals relies on the configuration of the hospital network, spatial impedance and population distribution. This paper explores the potential geographic accessibility of the population to public hospitals in Romania by using the Distance Application Program Interface (API) Matrix service from Google Maps and open data sources. Based on real-time traffic navigation data, we examined the potential accessibility of hospitals through a weighted model that took into account the hospital competency level and travel time while using personal car transportation mode. Two scenarios were generated that depend on hospitals’ level of competency (I–V). When considering all categories of hospitals, access is relatively good with over 80% of the population reaching hospitals in less than 30 min. This is much lower in the case of hospitals that provide complex care, with 34% of the population travelling between 90 to 120 min to the nearest hospital classed in the first or second category of competence. The index of spatial accessibility (ISA), calculated as a function of real travel time and level of competency of the hospitals, shows spatial patterns of services access that highlight regional disparities or critical areas. The high concentration of infrastructure and specialised medical personnel in particular regions and large cities limits the access of a large part of the population to quality health services with travel time and distances exceeding optimal European level values. The results can help decision-makers to optimise the location of health services and improve health care delivery.