Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum Copeptin Levels Predict the Return of Spontaneous Circulation and the Short-Term Prognosis of Patients with Out-of-Hospital Cardiac Arrest: A Randomized Control Study

Abstract Introduction: Early and accurate prediction of survival to hospital discharge following resuscitation after cardiac arrest (CA) is a major challenge. Biomarkers can be used for early and accurate prediction of survival and prognosis following resuscitation after CA, but none of those identified so far are sufficient by themselves. Hypothesis/Problem: The goal of this study was to investigate the predictive power of the serum copeptin level for determining the return of spontaneous circulation (ROSC) and prognosis of patients with non-traumatic out-of-hospital cardiac arrest (OHCA) who underwent cardiopulmonary resuscitation (CPR). Methods: A total of 76 consecutive consenting adult patients who were diagnosed as non-traumatic OHCA and 63 age- and sex-matched healthy controls were enrolled. The patients were divided into two groups based on whether or not they had ROSC. The ROSC group was divided into two sub-groups according to whether death occurred within 24 hours or after 24 hours following ROSC. Serum copeptin, high-sensitivity cardiac troponin (hs-cTnI), creatine kinase-muscle/brain (CK-MB), glucose, and blood gas values were compared between the groups. Results: Serum copeptin levels were significantly higher in the patient group than control group (P <.001). Receiving operator characteristic analysis revealed a cut-off copeptin level of 27.29pmol/L, with 98.7% sensitivity and 100.0% specificity, for distinguishing patients from controls. Serum copeptin levels were significantly lower in the ROSC group than non-ROSC group (P = .018). Additionally, the mean serum hs-cTnI level was significantly higher in the ROSC group than non-ROSC group (P = .032). However, there were no significant differences in the mean serum glucose level and CK-MB levels or arterial blood gas levels between the ROSC and non-ROSC groups (all P >.05). Ten (38.5%) of the patients died within the first 24 hours after ROSC, whereas 16 (61.5%) survived longer than 24 hours. Serum copeptin levels were significantly lower in patients who survived longer than 24 hours compared with those who died within the first 24 hours. Moreover, the mean CPR duration was significantly lower in patients surviving more than 24 hours compared with less than 24 hours. Conclusion: The serum copeptin level may serve as a guide in diagnostic decision making to predict ROSC in patients undergoing CPR and determining the short-term prognosis of patients with ROSC.
Comparison of Neonatal Outcomes With the Use Cefotaxime Versus Ceftazidime in a Neonatal Intensive Care Unit.

OBJECTIVES There is a national drug shortage of cefotaxime, and ceftazidime is recommended as an alternative to cefotaxime for neonates. This study evaluated culture-positive late-onset sepsis (LOS), multidrug resistant organisms (MDROs), and other neonatal outcomes with the use of ceftazidime compared with cefotaxime in neonates. METHODS This was a single-center, retrospective cohort study of neonatal subjects who received at least 24 hours of ceftazidime or cefotaxime between April 1, 2015, and August 1, 2017. Subjects were excluded if they received the alternate antibiotic for more than 24 hours. RESULTS A total of 101 subjects were included (ceftazidime, n = 58; cefotaxime, n = 43). Median gestational ages were significantly different between groups (28.1 [IQR, 25.0-36.6] weeks versus 32.3 [IQR, 26.9-37.4] in the ceftazidime and cefotaxime groups, respectively, p < 0.05). Results showed a non-statistically significant increased incidence of culture-positive LOS (17.2% versus 2.3%, respectively, adjusted OR 6.51 [95% CI, 0.78-55.23], p = 0.09) and MDRO infections (5.2% versus 0%, respectively, p = 0.26) with the use of ceftazidime compared with cefotaxime. There was a statistically significant increased risk of stage II to III necrotizing enterocolitis (NEC) with the use of ceftazidime (22.4% versus 2.3%, respectively, adjusted OR 9.68 [95% CI, 1.18-79.45], p = 0.04). CONCLUSIONS This study found a statistically significant increase in stage II to III NEC with the use of ceftazidime compared with cefotaxime. There was a higher rate of culture-positive LOS and MDRO infections with ceftazidime, but this was not significant. Further research is warranted to assess the implications ceftazidime use in neonates.
Activity of Cefiderocol and Comparators against Isolates from Cancer Patients

Cefiderocol inhibited 97.5% of 478 Gram-negative isolates from cancer patients at ≤4 mg/liter. It had potent activity against extended-spectrum β-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species isolates. Amikacin, ceftazidime-avibactam, and meropenem had appreciable activity against non-CRE Enterobacteriaceae. ABSTRACT Cefiderocol inhibited 97.5% of 478 Gram-negative isolates from cancer patients at ≤4 mg/liter. It had potent activity against extended-spectrum β-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species isolates. Amikacin, ceftazidime-avibactam, and meropenem had appreciable activity against non-CRE Enterobacteriaceae. No comparators were active against multidrug-resistant P. aeruginosa isolates. Only trimethoprim-sulfamethoxazole had appreciable activity against S. maltophilia isolates. Overall, cefiderocol was associated with the lowest level of resistance.
Tyrosine phosphorylation of the AMPA receptor subunit GluA2 gates homeostatic synaptic plasticity

Significance Throughout an organism’s life span, neural circuits mediate sensory and cognitive processing via synaptic plasticity, which involves synapse-specific Hebbian plasticity and network-level homeostatic plasticity. Synaptic strengthening and weakening are finely tuned by changes in postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) -type glutamate receptors (AMPARs). We have elucidated a biochemical regulation of AMPARs that is specific to homeostatic synaptic plasticity while sparing Hebbian plasticity mechanisms. Specifically, phosphorylation of the AMPAR subunit, GluA2, at tyrosine-876 is required for homeostatic synaptic strengthening by dictating GluA2 binding to glutamate receptor interacting protein 1 (GRIP1), a scaffolding protein crucial for synaptic upscaling. This finding elucidates a mechanism through which neurons can maintain a range of synaptic signaling while not compromising their responsiveness to subsequent synaptic activity. Hebbian plasticity, comprised of long-term potentiation (LTP) and depression (LTD), allows neurons to encode and respond to specific stimuli; while homeostatic synaptic scaling is a counterbalancing mechanism that enables the maintenance of stable neural circuits. Both types of synaptic plasticity involve the control of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) abundance, which is modulated by AMPAR phosphorylation. To address the necessity of GluA2 phospho-Y876 in synaptic plasticity, we generated phospho-deficient GluA2 Y876F knock-in mice. We show that, while GluA2 phospho-Y876 is not necessary for Hebbian plasticity, it is essential for both in vivo and in vitro homeostatic upscaling. Bidirectional changes in GluA2 phospho-Y876 were observed during homeostatic scaling, with a decrease during downscaling and an increase during upscaling. GluA2 phospho-Y876 is necessary for synaptic accumulation of glutamate receptor interacting protein 1 (GRIP1), a crucial scaffold protein that delivers AMPARs to synapses, during upscaling. Furthermore, increased phosphorylation at GluA2 Y876 increases GluA2 binding to GRIP1. These results demonstrate that AMPAR trafficking during homeostatic upscaling can be gated by a single phosphorylation site on the GluA2 subunit.
Detection and dynamics of anti‐platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia

Abstract Background Antiplatelet antibodies are detected in multiple diseases including primary immune thrombocytopenia (ITP). Dynamics of how these antibodies change over time in ITP is unknown in dogs. Hypothesis/Objectives Antiplatelet antibodies (APA) will be detected in thrombocytopenic dogs with multiple etiologies and dynamics of APA in dogs with ITP can be used to evaluate response to treatment and relapse. Determine APA at the time of diagnosis in thrombocytopenic dogs and serially in primary ITP dogs. Animals Seventy‐nine thrombocytopenic dogs and 28 primary ITP dogs. Methods Direct flow cytometry was performed in thrombocytopenic dogs at initial evaluation and serially in suspected primary ITP dogs. In primary ITP dogs, a 2‐tailed Fisher's exact test was performed comparing survival to discharge between dogs with and without melena and to relate response to treatment and relapse to changes in APA and platelet count (repeated measures analysis, Spearman correlation). Results Twenty percent (16/79) of thrombocytopenic non‐ITP dogs with infectious, neoplastic, or other diseases and all primary ITP dogs were positive for APA. Melena at initial evaluation was associated with decreased survival to discharge (odds ratio 0.06; P = .01). Persistence of APA was not associated with response to treatment, but recurrence of antibodies was associated with relapse (odds ratio 205.0; P < .01). There was no difference in percentage of APA or platelet count at initial diagnosis between dogs that did or did not respond to treatment. Conclusions and Clinical Importance Serial monitoring of APA in dogs with primary ITP appeared beneficial for determining relapse of disease.
Endometriosis-associated pain scores and biomarkers in users of the etonogestrel-releasing subdermal implant or the 52-mg levonorgestrel-releasing intrauterine system for up to 24 months

Abstract Objectives: The aims of the study were to correlate endometriosis-associated pain, evaluated by visual analogue scale (VAS) scores, with serum levels of etonogestrel (ENG), levonorgestrel (LNG), CA-125 and soluble CD23 in users of the ENG implant or the 52-mg LNG-releasing intrauterine system (52 mg LNG-IUS) for up to 2 years after device placement. Methods: A randomised trial was conducted at the University of Campinas Medical School, Brazil. All participants (n = 103) had had endometriosis-associated chronic pelvic pain or dysmenorrhoea, or both, for more than 6 months. Participants were randomly assigned to use an ENG implant (experimental treatment) or a 52-mg LNG-IUS (active comparator). Follow-up was conducted 6 monthly for up to 24 months after device placement. Dysmenorrhoea and chronic pelvic pain were evaluated using a VAS and the scores were correlated with serum levels of ENG, LNG, CA-125 and soluble CD23. Results: Both progestin-only contraceptives significantly reduced VAS scores for dysmenorrhoea and chronic pelvic pain and reduced serum levels of soluble CD23 (p < 0.001). Serum levels of CA-125 decreased only in the ENG implant group after 24 months’ use of the device (p < 0.001). No correlation was found between pain scores and ENG or LNG serum levels over time (p > 0.005). Conclusion: Both contraceptives improved dysmenorrhoea and chronic pelvic pain scores in women with endometriosis-associated pain and they reduced serum levels of soluble CD23; however, serum levels of CA-125 were reduced only in ENG implant users over the 24-month study period.
Changes in serum hepcidin according to thyrometabolic status in patients with Graves’ disease

Introduction Hepcidin is an acute-phase protein and a key regulator of iron homeostasis. Anaemia frequently occurs in patients with thyroid dysfunction, and hepcidin may be a potential link. Objectives Prospective assessment of hepcidin serum concentration and other parameters related to Fe homeostasis in hyperthyroid patients in the course of GD at diagnosis and during remission. Patients and Methods Out of the 70 patients recruited, 42 (32 women, 10 men), aged 42.5 ± 15.1 years, met the inclusion criteria. Clinical and biochemical assessment, including hepcidin measurement by ELISA, was performed at baseline (T0) and after restoration of euthyroidism (T1). Results Hepcidin concentration at T0 in the 24 patients who completed the study was significantly higher than the value during euthyroidism (28.7 (8.1–39.4) ng/mL vs 7.9 (4.3–12.9) ng/mL, P < 0.001). Hepcidin level was most significantly correlated with ferritin (rho = 0.723) in women at T0. In both men (377 (171–411) vs 165 (84–237) ng/mL, P = 0.001) and women (84 (23–104) vs 35 (16–64) ng/mL, P = 0.001), a significant decrease in ferritin level was demonstrated following therapy. A significant (P < 0.001) increase in mean corpuscular volume (MCV) (83.5 (82.5–87.1) vs 89.5 (88.8–90.0) fL) and mean concentration of haemoglobin (MCH) (29.0 (28.0–29.4) vs 30.4 (29.5–31.1) pg) was observed. Conclusions Hepcidin and ferritin decrease significantly during the transition from a hyperthyroid state to euthyroidism in patients with GD. The observed changes occur in parallel to iron homeostasis fluctuations. During the transition from the hyperthyroid state to euthyroidism, the improvement of haematological status is reflected mainly by the increase in MCV and MCH.
Cleaning products and asthma risk: a potentially important public health concern

[See related article at [www.cmaj. ca/lookup/doi/10.1503/cmaj.190819][2]][2] KEY POINTS Prevalence of pediatric asthma in Canada is 13% and has increased over time. [1][2] Asthma often begins early in childhood, and lifelong complications, including airway remodelling, can begin as early as the
Microglia in the developing retina couple phagocytosis with the progression of apoptosis via P2RY12 signaling

Background Microglia colonize the developing vertebrate central nervous system coincident with detection of developmental apoptosis. Our understanding of apoptosis in intact tissue in relation to microglial clearance of dying cells is largely based on fixed samples, which is limiting given that microglia are highly motile and mobile phagocytes. Here, we used a system of microglial depletion and in vivo real-time imaging in zebrafish to directly address microglial phagocytosis of apoptotic cells during normal retinal development, the relative timing of phagocytosis in relation to apoptotic progression, and the contribution of P2RY12 signaling to this process. Results Depletion of microglia resulted in accumulation of numerous apoptotic cells in the retina. Real-time imaging revealed precise timing of microglial engulfment with the progression of apoptosis, and dynamic movement and displacement of engulfed apoptotic cells. Inhibition of P2RY12 signaling delayed microglial clearance of apoptotic cells. Conclusions Microglial engulfment of dying cells is coincident with apoptotic progression and requires P2RY12 signaling, indicating that microglial P2RY12 signaling is shared between development and injury response. Our work provides important in vivo insight into the dynamics of apoptotic cell clearance in the developing vertebrate retina and provides a basis to understand microglial phagocytic behavior in health and disease. Bullet Points Levels and location of developmental apoptosis in the zebrafish retina are elusive due to rapid and efficient clearance by microglia Microglial clearance of apoptotic cells is timed with the progression of apoptosis of the engulfed cell so that many cells are cleared in relatively early apoptotic stages P2RY12 signaling is involved in microglial sensing and clearance of cells undergoing normal developmental apoptosis, indicating shared signals in microglial responses to cell death in both healthy and injured tissue Grant Sponsors NIH NIGMS Grant No. P20 GM103408
Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

Endemic Burkitt lymphoma (eBL) is an aggressive childhood B‐cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein–Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology‐based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0–15 years enrolled in northern Uganda and typed by accurate high‐resolution HLA sequencing methods. HLA results were analyzed at one‐ or two‐field resolution. Odds ratios and 95% confidence intervals (aOR, 95% CI) for eBL risk associated with common HLA alleles versus alleles that were rare (<1%) or differed by <2% between the cases and controls as the reference category, were estimated using multiple logistic regression adjusting for age, sex, microgeography, region, malaria positivity and treatment history, and genetic variants associated with eBL. Compared to the controls, eBL cases had a lower frequency of HLA‐A*02 (aOR = 0·59, 95% CI 0·38–0·91), HLA‐B*41 (aOR = 0·36, 95% CI 0·13–1·00), and HLA‐B*58 alleles (aOR = 0·59, 95% CI 0·36–0·97). eBL cases had a lower frequency of HLA‐DPB1 homozygosity (aOR = 0·57, 95% CI 0·40–0·82) but a higher frequency of HLA‐DQA1 homozygosity (aOR = 2·19, 95% CI 1·42–3·37). Our results suggest that variation in HLA may be associated with eBL risk.
Weight Status, Adherence to the Mediterranean Diet, Physical Activity Level, and Sleep Behavior of Italian Junior High School Adolescents

Inadequate diet, physical activity, and sleep-related behaviors are potential risk factors for overweight and obese, therefore we investigated the relations between body mass index (BMI) and behavioral factors in a sample of Italian adolescents. Four hundred nine Italian secondary school students (46% females, 12.5 ± 0.6 y.o.) were enrolled in this cross-sectional study. Anthropometric measures, adherence to the Mediterranean Diet (KIDMED), physical activity level (PAQ-C), sleep duration, daytime sleepiness (PDSS), sleep quality, and school achievement data were collected through an online questionnaire. The percentage of overweight adolescents was slightly lower (14%) compared to the regional and the national figures. Approximately 88% of the sample reported a medium/high adherence to the Mediterranean Diet and 77% a moderate/vigorous physical activity level. The average sleep duration was in line with the international sleep recommendation for adolescents and 82% had a medium/high sleep quality. No differences were found between genders except for BMI (lower in females). Unexpectedly, no differences were found among the BMI groups (normal weight vs. overweight vs. obese) for lifestyle variables; in contrast, Mediterranean Diet adherence was associated with sleep habits. Further investigation is required to better explore the associations among behavioral variables involved in adolescents’ healthy development.
Effect of Copper on the Mitochondrial Carnitine/Acylcarnitine Carrier Via Interaction with Cys136 and Cys155. Possible Implications in Pathophysiology

The effect of copper on the mitochondrial carnitine/acylcarnitine carrier (CAC) was studied. Transport function was assayed as [3H]carnitine/carnitine antiport in proteoliposomes reconstituted with the native protein extracted from rat liver mitochondria or with the recombinant CAC over-expressed in E. coli. Cu2+ (as well as Cu+) strongly inhibited the native transporter. The inhibition was reversed by GSH (reduced glutathione) or by DTE (dithioerythritol). Dose-response analysis of the inhibition of the native protein was performed from which an IC50 of 1.6 µM for Cu2+ was derived. The mechanism of inhibition was studied by using the recombinant WT or Cys site-directed mutants of CAC. From the dose-response curve of the effect of Cu2+ on the recombinant protein, an IC50 of 0.28 µM was derived. Inhibition kinetics revealed a non-competitive type of inhibition by Cu2+. However, a substrate protection experiment indicated that the interaction of Cu2+ with the protein occurred in the vicinity of the substrate-binding site. Dose-response analysis on Cys mutants led to much higher IC50 values for the mutants C136S or C155S. The highest value was obtained for the C136/155S double mutant, indicating the involvement of both Cys residues in the interaction with Cu2+. Computational analysis performed on the WT CAC and on Cys mutants showed a pattern of the binding energy mostly overlapping the binding affinity derived from the dose-response analysis. All the data concur with bridging of Cu2+ with the two Cys residues, which blocks the conformational changes required for transport cycle.
Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3β pathway in C2C12 myoblasts

Abstract Purpose: Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation. Materials and methods: Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured. Results: Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3β play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3β were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3β, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3β signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation. Conclusions: Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3βpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.