Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet dysfunction during trauma involves diverse signaling pathways and an inhibitory activity in patient-derived plasma

BACKGROUND Trauma-induced coagulopathy occurs in about 25% of injured patients and accounts for about 10% of deaths worldwide. Upon injury, hemostatic function may decline due to vascular dysfunction, clotting factor deficiencies, hyperfibrinolysis, and/or platelet dysfunction. We investigated agonist-induced calcium signaling in platelets obtained over time from trauma patients. METHODS Platelets from trauma patients and healthy donors were monitored via intracellular calcium mobilization and flow cytometry markers (&agr;2b&bgr;3 activation, P-selectin display, and phosphatidylserine exposure) following stimulation with a panel of agonists (adenosine 5′-diphosphate sodium salt, U46619, convulxin, PAR-1/4 activating peptides, iloprost) used in isolation or in pairwise tests. Furthermore, healthy donor platelets were tested in heterologous plasma isolated from healthy subjects and trauma patients. RESULTS When exposed to agonists over the first 24 hours postinjury, trauma patient platelets mobilized less calcium in comparison to healthy platelets. Partial recovery of platelet activity was observed in about a third of patients after 120 hours, although not fully obtaining healthy baseline function. Flow cytometry markers of trauma platelets were similar to healthy platelets prior to stimulation, but were depressed in trauma platelets stimulated with adenosine 5′-diphosphate sodium salt or convulxin. Also, washed healthy platelets showed a significant reduction in calcium mobilization when reconstituted in plasma from trauma patients, relative to healthy plasma, at all plasma doses tested. CONCLUSION Platelet dysfunction in trauma patients included poor response to multiple agonists relevant to hemostatic function. Furthermore, the inhibitor effect of patient plasma on healthy platelets suggests that soluble plasma species may downregulate endogenous or transfused platelets during trauma.
Long-term safety and tolerability of cariprazine as adjunctive therapy in major depressive disorder

Lack of treatment response is a critical problem in major depressive disorder (MDD). Cariprazine is a D3-preferring dopamine D3/D2 receptor partial agonist and 5-HT1A partial agonist. This phase 3, multicenter, open-label, long-term (26-week), flexible-dose (1.5–4.5 mg/day) study assessed the long-term safety and tolerability of cariprazine used adjunctively with antidepressant therapy in adult patients with MDD who had either completed a lead-in study (n=311) or had been newly recruited (n=131). A higher percentage of continuing patients (66.2%) than new patients (35.9%) completed the study. The most common reason for discontinuation was adverse events (AEs; 13.9%); 79% of patients experienced a treatment-emergent AE [most common: akathisia (15.9%,) headache (11.6%)]. Serious AEs occurred in 2% of patients; two deaths occurred (one traffic accident, one completed suicide, both considered unrelated to treatment). The mean changes in clinical laboratory, cardiovascular, and ophthalmologic parameters were generally not clinically relevant. The mean (SD) changes from the open-label baseline in Montgomery–Åsberg Depression Rating Scale total score and Clinical Global Impression-Severity score at week 26 were −7.3 (9.5) and −1.0 (1.2), respectively. By week 26, 53.3% of patients were in remission (Montgomery–Åsberg Depression Rating Scale total score⩽10). The results suggest that cariprazine was generally safe and well tolerated as adjunctive therapy to treat MDD.
The Role of Real Time Elastography in the Diagnosis of a Patient with Liver Cirrhosis and Carcinoma of the Uncinate Process of the Pancreas - Case Study

ABSTRACT: Hepatic cirrhosis represents the most advanced stage of any chronic liver disease characterized by progressive fibrosis. We report the case of a patient with carcinoma of the uncinate process of the pancreas and an occult form of liver cirrhosis. We concluded, based on the bioclinical profile, that the jaundice syndrome had an underlying mixed mechanism, obstructive and hepatic. Although, the clinical suspicion of pancreatic cancer was backed up by ultrasound, computed tomography and magnetic resonance imaging, we did not obtain, through these imaging investigations, any indicative features of liver cirrhosis. In order to further evaluate the presence of liver cirrhosis, we assessed liver stiffness using two non-invasive methods: Transient Elastography and Real Time Tissue Elastography (RTE). We observed highly suggestive features of liver cirrhosis only through RTE, although its diagnostic accuracy still needs large validation studies. Intraoperative assessment confirmed the diagnosis of liver cirrhosis, changing also the type of surgical approach and patient prognosis.
Estimating fat-free mass in elite youth male soccer players: cross-validation of different field methods and development of prediction equation

ABSTRACT This study determined the most effective field method for quantifying fat-free mass (FFM) in elite youth male soccer players compared to dual X-ray absorptiometry (DXA) values and to develop prediction equations for FFM based on anthropometric variables. Forty-one male elite-standard youth soccer players, ages 16.2–18.0 years, undertook FFM assessments including bioelectrical impedance analysis, and different skinfold-based prediction equations. DXA provided a criterion measure of FFM. Correlation coefficients, bias, limits of agreement, and differences were used as validity measures, and regression analyses to develop soccer-specific prediction equations. Slaughter et al (1988), Durnin and Wormersley (1974), and Sarria et al (1998) equations showed the lowest biases, and no significant, standardized, and substantial differences against DXA. The new youth soccer-specific anthropometric equation explained 91% of the DXA-derived FFM variance using three circumferences, eight skinfolds, and one bone breadth. All field methods compared in this study may not be adequate for estimating FFM in elite youth male soccer players, except the equations of Slaughter et al (1988), Durnin and Wormersley (1974), and Sarria et al (1998). We recommend the use of the new soccer-specific equation proposed in this study as a valid alternative to DXA to quantify FFM among elite youth male players.
Pre-season Fitness Level and Injury Rate in Professional Soccer – A Prospective Study

Abstract The aim of the present study was to assess prospectively the effect of pre-season fitness on injury rate during the competitive season among professional soccer players. Thirty-one players participated in the study during two consecutive competitive seasons (2015–16 and 2016–17; a squad of 22 players in each season). During the 6-week pre-season training period (8 training sessions and a friendly match every week, 14–18 training hours/week) there was a significant improvement in VO2 max, a significant increase in ideal and total sprint time and no change in vertical jump, flexibility and repeated sprint-test performance decrement. During the two consecutive seasons, 28 injuries were recorded. Ten injuries were classified as mild (missing 3–7 days of practice/match), 8 as moderate (missing 8–28 days) and 10 as severe (missing >28 days). The rate of match injuries was higher (9.4 per 1000 match hours) compared to practice injuries (4.7 per 1000 training hours). Most injuries were overuse injuries (72%) of the lower limbs (71%). Most of match injuries occurred during the last 15 min of each half. There were no differences in fitness characteristics in the beginning of pre-season training between injured and non-injured players. However, improvements in VO2 max during the pre-season training period were significantly lower among injured players (0.9±5.5%) compared to non-injured players (10.4±6.5%, p<0.05). Our results emphasize the importance of pre-season training in professional soccer players not only for improvement in fitness but also for injury prevention during the following competitive season.
Efavirenz Pharmacokinetics during Pregnancy and Infant Washout

Background Limited data exist on efavirenz pharmacokinetics in HIV-positive pregnant women and neonatal washout. Methods HIV-infected pregnant women receiving 600 mg efavirenz once daily had intensive steady-state 24-h pharmacokinetics profiles during the second trimester (2T), third trimester (3T) and 6–12 weeks postpartum (PP). Maternal and umbilical cord blood samples were drawn at delivery and neonatal washout pharmacokinetics were determined. Therapeutic targets were the estimated 10th percentile efavirenz area under the concentration–time curve (AUC) in non-pregnant historical controls (40.0 μg•h/ml) and a trough concentration (C24 h) of 1 μg/ml. Data were prospectively collected within two trials: IMPAACT P1026s (United States) and PANNA (Europe). Results Among 42 women studied, 15, 42 and 40 had efavirenz pharmacokinetic data available in 2T, 3T and PP, respectively. Median (range) 3T age 33 (20.7–43.5) years, weight 74 (50–132) kg and gestational age 33.4 (28.4–37.9 weeks). Efavirenz AUC during the 3T (60 μg•h/ml) was similar to that reported in non-pregnant adults (58 μg•h/ml). Exposure in the 2T was lower, but within the 0.80–1.25 range. C24 concentrations during pregnancy were lower compared to historical controls on 600 mg efavirenz, however, they were similar to the C24 concentrations after equally potent dose of 400 mg efavirenz. Cord blood/maternal plasma concentration ratio (range) was 0.67 (0.36–0.95). Among 23 infants with washout data available, median (interquartile range) elimination half-life was 65.6 h (40.6–129). HIV RNA viral loads at delivery were <400 and <50 copies/ml for 96.7% and 86.7% of women, respectively. In 3T and PP, respectively, 8/41 (19%) and 6/40 (15%) had AUC below target; 7/41 (17%) and 3/39 (8%) had C24 below target. Conclusions Efavirenz exposure was similar during pregnancy compared with PP, C24 was in line with C24 after 400 mg equipotent efavirenz dosing. Efavirenz readily crossed the placenta and infant elimination half-life was over twice that of maternal participants. Clincaltrials.gov identifiers: NCT00825929 and NCT00042289.
Stitching of sensor-navigated 3D ultrasound datasets for the determination of large thyroid volumes - a phantom study.

AIMS Thyroid volume has to be measured in goiters prior to radioiodine treatment to calculate the needed amount of radioactivity. Modern clinical equipment for ultrasonography shows the trend to smaller probes, so that larger goiters do not fit any longer into the probe's field of view. This study evaluated the feasibility and accuracy of stitching procedures applied to thyroid volumetric analysis performed using three-dimensional ultrasound (3D-US). MATERIAL AND METHODS Ad hoc thyroid phantoms of different shapes (regular, nodular, thickened isthmus) and volumes (ranging between 50 and 400 mL) were developed. In 15 such phantoms the left and right lobes were separately scanned, and the 3D-US datasets were then assembled (stitched) using predefined landmarks and dedicated software. Volumetric analysis was then assessed via a conventional ellipsoid model (em) and manual tracing (mt). The correlation of measured and reference volumes was determined using Pearson's correlation coefficients and Bland and Altman limits of agreement. RESULTS The results showed a high level of agreement (with correlation coefficients ranging from 0.974 to 0.999) for all shapes and volumes tested, including the largest volume of 400 mL. The mt method, although more time consuming, proved superior to the em. CONCLUSIONS Stitching-mediated thyroid volumetric analysis is accurate, and its clinical performance should be investigated in future studies.
Neonatal Intubation Practice and Outcomes: An International Registry Study

In this study, we report results of a novel international airway registry of endotracheal intubation in the NICU and DR settings. BACKGROUND AND OBJECTIVES: Neonatal tracheal intubation is a critical but potentially dangerous procedure. We sought to characterize intubation practice and outcomes in the NICU and delivery room (DR) settings and to identify potentially modifiable factors to improve neonatal intubation safety. METHODS: We developed the National Emergency Airway Registry for Neonates and collected standardized data for patients, providers, practices, and outcomes of neonatal intubation. Safety outcomes included adverse tracheal intubation–associated events (TIAEs) and severe oxygen desaturation (≥20% decline in oxygen saturation). We examined the relationship between intubation characteristics and adverse events with univariable tests and multivariable logistic regression. RESULTS: We captured 2009 NICU intubations and 598 DR intubations from 10 centers. Pediatric residents attempted 15% of NICU and 2% of DR intubations. In the NICU, the first attempt success rate was 49%, adverse TIAE rate was 18%, and severe desaturation rate was 48%. In the DR, 46% of intubations were successful on the first attempt, with 17% TIAE rate and 31% severe desaturation rate. Site-specific TIAE rates ranged from 9% to 50% (P < .001), and severe desaturation rates ranged from 29% to 69% (P = .001). Practices independently associated with reduced TIAEs in the NICU included video laryngoscope (adjusted odds ratio 0.46, 95% confidence interval 0.28–0.73) and paralytic premedication (adjusted odds ratio 0.38, 95% confidence interval 0.25–0.57). CONCLUSIONS: We implemented a novel multisite neonatal intubation registry and identified potentially modifiable factors associated with adverse events. Our results will inform future interventional studies to improve neonatal intubation safety.
Asymptomatic carriage of Streptococcus pneumoniae detected by qPCR on the palm of hands of populations in rural Senegal

Aside from malaria, infectious diseases are an important cause of death in sub-Saharan Africa and continue to pose major public health problems in African countries, notably pneumonia. Streptococcus pneumoniae remains the most common bacterial cause of pneumonia in all age groups. The skin is one of the main infection sites followed by the oropharynx. The skin carriage of certain pathogenic bacteria such as S. pneumoniae is often ignored or under-diagnosed. Finally, the mode of transmission of these infections remains uncertain. Here, we hypothesized that skin could play a role in the transmission of these infections. We collected 649 cotton swabs from a healthy population in Dielmo and Ndiop, rural Senegal. The sampling was carried out on the palm of the hands. After DNA extraction and actin control, qPCR targeting eight different bacteria was performed on 614 skin samples. We detected Streptococcus pneumoniae in 33.06% (203/614), Staphylococcus aureus in 18.08% (111/614) and Streptococcus pyogenes in 1.95% (12/614) of samples. A skin S. pneumoniae carriage was detected in more than a third of a rural population in rural Africa, highlighting the need to develop hand disinfection programs in order to reduce the burden of infections.
Symbiotic unicellular cyanobacteria fix nitrogen in the Arctic Ocean

Significance Biological dinitrogen (N2) fixation (BNF) is an important source of nitrogen in marine systems. Until recently, it was believed to be primarily limited to subtropical open oceans. Marine BNF is mainly attributed to cyanobacteria. However, recently an unusual N2-fixing unicellular cyanobacteria (UCYN-A)/haptophyte symbiosis was reported with a broader temperature range than other N2-fixing cyanobacteria. We report that the UCYN-A symbiosis is present and fixing N2 in the Western Arctic and Bering Seas, further north than any previously reported N2-fixing marine cyanobacteria. Nanoscale secondary ion mass spectrometry enabled us to directly show that the symbiosis was fixing N2. These results show that N2-fixing cyanobacteria are not constrained to subtropical waters and challenge commonly held ideas about global marine N2 fixation. Biological dinitrogen (N2) fixation is an important source of nitrogen (N) in low-latitude open oceans. The unusual N2-fixing unicellular cyanobacteria (UCYN-A)/haptophyte symbiosis has been found in an increasing number of unexpected environments, including northern waters of the Danish Straight and Bering and Chukchi Seas. We used nanoscale secondary ion mass spectrometry (nanoSIMS) to measure 15N2 uptake into UCYN-A/haptophyte symbiosis and found that UCYN-A strains identical to low-latitude strains are fixing N2 in the Bering and Chukchi Seas, at rates comparable to subtropical waters. These results show definitively that cyanobacterial N2 fixation is not constrained to subtropical waters, challenging paradigms and models of global N2 fixation. The Arctic is particularly sensitive to climate change, and N2 fixation may increase in Arctic waters under future climate scenarios.
Pivotal prognostic and diagnostic role of the long non-coding RNA colon cancer-associated transcript 1 expression in human cancer

Long non-coding RNAs (lncRNAs) have been classically defined as regulatory RNA members >200 nucleotides in length, without detectable open-reading frames to encode proteins. Previous studies have demonstrated that lncRNAs serve critical roles in multiple cancer types. Colon cancer-associated transcript 1 (CCAT1), a novel cancer-associated lncRNA, is significantly overexpressed in a number of malignancies. Functionally, as an oncogenic lncRNA, CCAT1 is involved in proliferation, migration, cell cycle progression, apoptosis, chemoresistance and other biological processes of cancer cells through complex regulation mechanisms in the cytoplasm or nucleus. In clinical applications, CCAT1 is additionally positively associated with histological differentiation, tumour node metastasis stage, vascular invasion, overall survival and recurrence-free survival, which demonstrates its important role as a diagnostic and prognostic marker in cancer. The present review summarises the current research progress of the oncogenic potential and clinical uses of CCAT1 in various human cancer types.
Recent Stressful Life Events (SLE) and Adolescent Mental Health: Initial Validation of the LEIA, a New Checklist for SLE Assessment According to Their Severity, Interpersonal, and Dependent Nature

The main aim of the present study was to develop and validate a checklist for adolescents, the Life Events Inventory for Adolescents (LEIA), for screening stressful life events (SLEs) of different nature (major–minor, dependent–independent, and personal–interpersonal). The LEIA was administered together with another SLE checklist (Escala de Acontecimientos Vitales [Life Events Scale], EAV), and with measures of life satisfaction and externalizing and internalizing symptoms. The results showed that the kappa and the percentage agreement reliability indices were adequate. Regarding validity evidences, the correlations found between the LEIA and the EAV ranged from . 65 to . 69, and between the LEIA and the psychopathological symptoms ranged from . 26 to . 38. Specifically, major dependent noninterpersonal SLEs were the best predictors of externalizing psychopathology; while major independent noninterpersonal SLEs were the best predictors of internalizing symptoms and low life satisfaction. To conclude, the LEIA could be considered an adequate checklist to screen for SLEs in adolescents.
Perioperative antithrombotic therapy does not increase the incidence of early postoperative thromboembolic complications and bleeding in kidney transplantation – a retrospective study

Perioperative antithrombotic therapy could play a role in preventing thromboembolic complications (TEC) after kidney transplantation (KTx), but little is known on postoperative bleeding risks. This retrospective analysis comprises 2000 single‐organ KTx recipients transplanted between 2011 and 2016 in the two largest transplant centers of the Netherlands. TEC and bleeding events were scored ≤7 days post‐KTx. Primary analyses were for associations of antithrombotic therapy with incidence of TEC and bleeding. Secondary analyses were for associations of other potential risk factors. Mean age was 55 ± 14 years, 59% was male and 60% received a living donor kidney. Twenty‐one patients (1.1%) had a TEC. Multiple donor arteries [OR 2.79 (1.15–6.79)] and obesity [OR 2.85 (1.19–6.82)] were identified as potential risk factors for TEC. Bleeding occurred in 88 patients (4.4%) and incidence varied significantly between different antithrombotic therapies (P = 0.006). Cardiovascular disease [OR 2.01 (1.18–3.42)], pre‐emptive KTx [OR 2.23 (1.28–3.89)], postoperative heparin infusion [OR 1.69 (1.00–2.85)], and vitamin K antagonists [OR 6.60 (2.95–14.77)] were associated with an increased bleeding risk. Intraoperative heparin and antiplatelet therapy were not associated with increased bleeding risk. These regimens appear to be safe for the possible prevention of TEC without increasing the risk for bleeding after KTx.
Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks

Significance Interlocked feedback loops promote robustness and stability in a system and are a feature of circadian clocks in both animal and plants. The mammalian circadian clock is known to consist of two transcriptional feedback loops, relying on the transcriptional activity of the master complex CLOCK:BMAL1 and the feedback regulation by its target genes. Our research extends this knowledge by proposing a feedback loop in peripheral circadian oscillators and highlights the underlying mechanisms mediated by the unappreciated CLOCK:BMAL1 transrepression activity of the circadian nuclear receptor HNF4A. Further, our data suggest that the hepatic roles of HNF4A are circadian. Either expression level or transcriptional activity of various nuclear receptors (NRs) have been demonstrated to be under circadian control. With a few exceptions, little is known about the roles of NRs as direct regulators of the circadian circuitry. Here we show that the nuclear receptor HNF4A strongly transrepresses the transcriptional activity of the CLOCK:BMAL1 heterodimer. We define a central role for HNF4A in maintaining cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Not only transcript level but also genome-wide chromosome binding of HNF4A is rhythmically regulated in the mouse liver. ChIP-seq analyses revealed cooccupancy of HNF4A and CLOCK:BMAL1 at a wide array of metabolic genes involved in lipid, glucose, and amino acid homeostasis. Taken together, we establish that HNF4A defines a feedback loop in tissue-specific mammalian oscillators and demonstrate its recruitment in the circadian regulation of metabolic pathways.