Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole Blood Administration: Comparison of In Vitro Platelet Function of Pressure Bag, Pressure Bag With Fluid Warming Device, and Rapid Infuser Methods

Background: Use of low-titer group O whole blood for emergent transfusion of patients with unknown blood type became AABB approved in January 2018. Since that time, there is increasing use of whole blood in massive transfusion protocols. Whole blood stored at refrigerator temperature (2–4 °C) contains functional platelets that some research proposes may provide better clot dynamics than standard platelets, which are stored at room temperature (20–24 °C). Conventional teaching does not promote infusion of platelet products with pressure or warming, due to concerns of activation and subsequent inactivity of the infused platelets. Although a few reports found no significant changes in platelet function with warming or pressure during infusion of conventional room-temperature-stored platelets, there is limited data to support use of warming or pressure for infusion of whole blood products containing cold-stored platelets. Methods: This study design is to evaluate and compare three commonly used methods of administering blood products in a massive transfusion setting for their potential effects on platelets contained within whole blood units (pressure bag alone, pressure bag with fluid warming line, and rapid infuser). Results: Platelet function of 10 units tested pre- and post-infusion by thromboelastography (TEG) and platelet aggregation studies found no significant difference in platelet activity pre- and post-infusion with any of the three methods evaluated. Conclusions: This study supports the use of rapid infuser or pressure bag devices (with or without warming) as acceptable for infusion of whole blood products. Infusion of whole blood with warming is preferable to prevent potential transfusion-associated hypothermia.
Prevalence of COVID-19 Antibodies in Healthcare Workers at the Peak of the Pandemic in Mumbai, India: A Preliminary Study

Healthcare worker (HCW) infections due to COVID-19 are of serious consequence. Testing for antibodies against COVID-19 in HCWs has been previously recommended. We conducted a serosurvey in HCWs at a private hospital in Mumbai which is treating COVID patients. A total of 244 HCWs were tested. The prevalence of infection in asymptomatic HCWs was 4.3% and in previously symptomatic untested HCWs was 70%. We recommend that HCWs with a previous history of COVID symptoms who were not tested/tested negative by reverse transcription–polymerase chain reaction should be tested for antibodies at least 2 weeks after onset of symptoms.
Alteration of the Renin–Angiotensin–Aldosterone System in Shock: Role of the Dipeptidyl Peptidase 3

We read with interest the article published by Bellomo and colleagues, which explored some of the alterations of the renin–angiotensin–aldosterone system (RAAS) during catecholamine-resistant vasodilatory shock, mostly of septic origin, using data from the ATHOS-3 (Phase 3 Angiotensin II for the Treatment of High-Ouptut Shock) trial (1). In this work, the authors demonstrated that there was increased renin concentration in most patients, which was associated with a high angiotensin I/angiotensin II ratio and a bad prognosis (2). As the latter ratio is inversely associated with ACE (angiotensinconverting enzyme) activity, the authors suggest that RAAS perturbations might be related to a decrease in ACE activity in the context of sepsis-associated endotheliopathy. We would like to propose another, coexisting rather than competing, hypothesis of the RAAS perturbation observed during septic shock. As highlighted by Bellomo and colleagues (1), insufficient activation of the AT1R (angiotensin II type 1 receptor) can be caused by AT1R blockade or decreased angiotensin II generation by ACE. On the basis of recent discoveries, we propose enhanced degradation of angiotensin II as a third possibility related to an excess release of DPP3 (dipeptidyl peptidase 3) in the plasma of patients with septic shock (3). DPP3 is a zinc-dependent metalloprotease that cleaves the N-terminal extremity of various bioactive peptides, including angiotensins, enkephalins, and endorphins (4). Interestingly, although DPP3 hydrolyzes angiotensin II into angiotensin IV, it has no direct effect on angiotensin I, thus leading to an increased angiotensin I/angiotensin II ratio, consistent with Bellomo and colleagues’ findings (5, 6). Under these conditions, as pointed out by the authors, decreased AT1R stimulation then triggers the production of renin. Although the plasmatic concentration of DPP3 is low in healthy subjects, an increase in plasmatic DPP3 concentration and activity has been observed in patients with sepsis. In addition, DPP3 activity is higher in septic shock than in severe sepsis and higher in decedents than in survivors of septic shock (3). In a rat model of septic shock with septic cardiomyopathy induced by cecal ligation and puncture, circulating DPP3 activity is also increased (7). Furthermore, in this preclinical model, inhibition of DPP3 activity with procizumab (a-DPP3 monoclonal antibody) quickly restored cardiac function as
The prevalence of loyalty program use and its association with higher risk gambling in Australia

Abstract Background and aims Loyalty programs are implemented widely by gambling operators to provide customers with additional prizes and benefits for consistent patronage. The aim of this paper was to examine whether loyalty programs were more commonly reported by higher risk gamblers in large population studies conducted in Australia. Method This paper examines the prevalence of loyalty program use and the association with problem gambling in Australia using data from seven out of 13 public gambling prevalence surveys conducted over the last decade. Results Evidence drawn from six of these seven studies showed consistent positive association between loyalty card use and higher risk gambling in venue-based gamblers. At least 40% of problem gamblers reported loyalty card use compared with only around 10% of gamblers in general. Discussion These observations suggest that there is a need to conduct more focused investigations on the utilisation of loyalty programs by higher risk gamblers. Conclusions It will be important to examine whether loyalty programs encourage or extend gambling sessions, but also how they can be used to facilitate responsible gambling initiatives and inform further behavioural research.
Age- and Sex-Related Morphometric Changes and Asymmetry in the Orbito-Zygomatic Region.

The aims of this study were to obtain cephalometric data of orbito-zygomatic skeleton using CT axial images and to determine the presence of sexual dimorphism, normal range of facial asymmetry, and the age-related changes.This study used data from 315 CT scan series of skeletally normal subjects (159 males and 156 females) between the ages of 18 to 90. Two different levels of axial sections were used. In total, 11 measurements were performed and 5 of them were bilateral.The mean values and standard deviations were calculated. Gender and age related changes and asymmetry degree were investigated.Mean values of measurements except left medial orbital wall length, right and left medial orbital wall protrusion, right and left lateral orbital wall angle were significantly larger in males for all age groups. Majority of the measurements was formed by the individuals with larger right side. Similar tendencies were observed for craniofacial asymmetry in both sexes and in different age groups. There were no significant craniofacial asymmetries between age and gender groups in terms of the cephalometric measurements. Mid-interorbital distance had a negative correlation (r = -0.11 and P = 0.043) and interzygomatic buttress distance had a positive correlation (r = 0.15 and P = 0.005) with age.Morphological properties such as sexual dimorphism, symmetry, age related changes are important parameters especially for plastic surgery discipline. The authors hope the data can be helpful in diagnosis and surgical treatment of craniofacial diseases, estimating the prognosis and preparation of the facial prosthesis.
Patterns and determinants of modern contraceptive discontinuation among women of reproductive age: Analysis of Kenya Demographic Health Surveys, 2003–2014

Objectives This study aimed to examine patterns and determinants of modern contraceptive discontinuation among women in Kenya. Methods Secondary analysis was conducted using national representative Kenya Demographic and Health Surveys of 2003, 2008/9, and 2014. These household cross-sectional surveys targeted women of reproductive age from 15 to 49 years who had experienced an episode of modern contraceptive use within five years preceding the surveys from 2003 (n = 2686), 2008/9 (n = 2992), and 2014 (5919). The contraceptive discontinuation rate was defined as the number of episodes discontinued divided by the total number of episodes. Weighted descriptive statistics, multivariable logistic regression analysis, and Cox proportional hazards analysis were used to examine the determinants of contraceptive discontinuation. Results The 12-month contraceptive discontinuation rate for all methods declined from 37.5% in 2003 and 36.7% in 2008/9 to 30.5% in 2014. Consistently across the three surveys, intrauterine devices had the lowest 12-month discontinuation rate (6.4% in 2014) followed by implants (8.0%, in 2014). In 2014, higher rates were seen for pills (44.9%) and male condoms (42.9%). The determinants of contraceptive discontinuation among women of reproductive age in the 2003 survey included users of short-term contraception methods, specifically for those who used male condoms (hazard ratio [HR] = 3.30, 95% confidence interval [CI] = 2.13–5.11) and pills (HR = 2.68; 95CI = 1.79–4.00); and younger women aged 15–19 year (HR = 2.07; 95% CI = 1.49–2.87) and 20–24 years (HR = 1.94; 95% CI = 1.61–2.35). The trends in the most common reasons for discontinuation from 2003 to 2014 revealed an increase among those reporting side effects (p = 0.0002) and those wanting a more effective method (p<0.0001). A decrease was noted among those indicating method failure (p<0.0001) and husband disapproval (p<0.0001). Conclusions Family planning programs should focus on improving service quality to strengthen the continuation of contraceptive use among those in need. Women should be informed about potential side effects and reassured on health concerns, including being provided options for method switching. The health system should avail a wider range of contraceptive methods and ensure a constant supply of commodities for women to choose from. Short-term contraceptive method users and younger women may need greater support for continued use.
Effect of dietary supplementation with Allium mongolicum Regel extracts on growth performance, carcass characteristics, and the fat color and flavor-related branched-chain fatty acids concentration in ram lambs

Objective This study aimed to investigate the effect of dietary supplementation with Allium mongolicum Regel extracts on the growth performance, carcass characteristics, fat color, and concentrations of three branched-chain fatty acids related to flavor in ram lambs. Methods Sixty 3-month-old, male, small-tailed Han sheep were selected and randomly allocated into four groups in a randomized block design. Four feeding treatments were used: i) a basal diet without supplementation as the control group (CK); ii) the basal diet supplemented with 10 g/lamb/d Allium mongolicum Regel powder as the AMR group; iii) the basal diet supplemented with 3.4 g/lamb/d Allium mongolicum Regel water extract as the AWE group; and iv) the basal diet supplemented with 2.8 g/lamb/d Allium mongolicum Regel ethanol extract as the AFE group. Results The results demonstrated that the dry matter intake was lower for the AFE group than that in other groups (p = 0.001). The feed conversion ratio was greater for the AFE than that in other groups (p = 0.039). Dietary supplementation with Allium mongolicum Regel powder and its extracts decreased the concentrations of 4-methyloctanoic acid (MOA) (p<0.001), 4-ethyloctanoic acid (EOA) (p<0.001), and 4-methylnonanoic acid (MNA) (p = 0.044) in perirenal adipose tissue compared to those observed in the CK lambs. Dietary supplementation with Allium mongolicum Regel powder and its extracts decreased the concentrations of MOA (p<0.001) and EOA (p<0.001) in dorsal subcutaneous adipose tissue compared to those in the CK lambs. The concentrations of MOA (p<0.001) and EOA (p = 0.002) in omental adipose tissue were significantly affected by treatment, although there was a tendency for lower MNA (p = 0.062) in AMR, AWE, and AFE lambs than that in CK lambs. Conclusion This study demonstrated that Allium mongolicum Regel and its extracts could significantly promote feed efficiency, although dry matter intake decreased and could decrease the MOA and EOA concentrations related to characteristic flavor and odor of body fat in lambs, except for tail adipose tissue.
Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common Mesenchymal Neoplasm of the gastrointestinal tract. The tumorigenesis of GISTs has been associated with the gain-of-function mutation and abnormal activation of the stem cell factor receptor (c-KIT) and platelet-derived growth factor receptor alpha (PDGFRα) kinases. Hence, inhibitors that target c-KIT and PDGFRα could be a therapeutic option for the treatment of GISTs. The available approved c-KIT/PDGFRα inhibitors possessed low efficacy with off-target effects, which necessitated the development of potent inhibitors. We performed computational studies of 48 pyrazolopyridine derivatives that showed inhibitory activity against c-KIT and PDGFRα to study the structural properties important for inhibition of both the kinases. The derivative of phenylurea, which has high activities for both c-KIT (pIC50 = 8.6) and PDGFRα (pIC50 = 8.1), was used as the representative compound for the dataset. Molecular docking and molecular dynamics simulation (100 ns) of compound 14 was performed. Compound 14 showed the formation of hydrogen bonding with Cys673, Glu640, and Asp810 in c-KIT, and Cys677, Glu644, and Asp836 in PDGFRα. The results also suggested that Thr670/T674 substitution in c-KIT/PDGFRα induced conformational changes at the binding site of the receptors. Three-dimensional quantitative structure–activity relationship (3D-QSAR) models were developed based on the inhibitors. Contour map analysis showed that electropositive and bulky substituents at the para-position and the meta-position of the benzyl ring of compound 14 was favorable and may increase the inhibitory activity against both c-KIT and PDGFRα. Analysis of the results suggested that having bulky and hydrophobic substituents that extend into the hydrophobic pocket of the binding site increases the activity for both c-KIT and PDGFRα. Based on the contour map analysis, 50 compounds were designed, and the activities were predicted. An evaluation of binding free energy showed that eight of the designed compounds have potential binding affinity with c-KIT/PDGFRα. Absorption, distribution, metabolism, excretion and toxicity (ADMET) and synthetic feasibility tests showed that the designed compounds have reasonable pharmaceutical properties and synthetic feasibility. Further experimental study of the designed compounds is recommended. The structural information from this study could provide useful insight into the future development of c-KIT and PDGFRα inhibitors.
Glucagon-Like Peptide-1 Regulates the Proopiomelanocortin Neurons of the Arcuate Nucleus both Directly and Indirectly via Presynaptic Action

Glucagon-like peptide-1 (GLP-1) exerts its anorexigenic effect at least partly via the proopiomelanocortin (POMC) neurons of the arcuate (ARC) nucleus. These neurons are known to express GLP-1 receptor (GLP-1R). The aim of the study was to determine whether in addition to its direct effect, GLP-1 also modulates how neuronal inputs can regulate the POMC neurons by acting on presynaptic terminals, ultrastructural and electrophysiological studies were performed on tissues of adult male mice. GLP-1R-immunoreactivity was associated with the cell membrane of POMC neurons and with axon terminals forming synapses on these cells. The GLP-1 analog exendin 4 (Ex4) markedly increased the firing rate of all examined POMC neurons and depolarized these cells. These effects of Ex4 were prevented by intracellular administration of the G-protein blocker guanosine 5′-[β-thio]diphosphate trilithium salt (GDP-β-S). Ex4 also influenced the miniature postsynaptic currents (mPSCs) and evoked PSCs of POMC neurons. Ex4 increased the frequency of miniature excitatory PSCs (EPSCs) and the amplitude of the evoked EPSCs in half of the POMC neurons. Ex4 increased the frequency of miniature inhibitory PSCs (IPSCs) and the amplitudes of the evoked IPSCs in one-third of neurons. These effects of Ex4 were not influenced by intracellular GDP-β-S, indicating that GLP-1 signaling directly stimulates a population of axon terminals innervating the POMC neurons. The different Ex4 responsiveness of their mPSCs indicates the heterogeneity of the POMC neurons of the ARC. In summary, our data demonstrate that in addition to its direct excitatory effect on the POMC neurons, GLP-1 signaling also facilitates the presynaptic input of these cells by acting on presynaptically localized GLP-1R.
Cannabis use‐related working memory deficit mediated by lower left hippocampal volume

The association between cannabis exposure and working memory impairment and its neural substrates remain unclear. In this cross‐sectional observational study, we investigated this by examining the relationship between frequency of exposure to cannabis, working memory performance and regional brain volumes and tested whether lower volumes of cortical and subcortical structures mediate the association between cannabis exposure and working memory deficit using the Human Connectome Project data from 234 individuals with self‐reported cannabis exposure and 174 individuals unexposed to cannabis. We tested the relationship between self‐reported frequency of cannabis exposure and list‐sorting working memory task performance (total number of correct responses), between T1 weighted MRI‐derived regional grey‐matter volumes and working memory task performance as well as between frequency of cannabis exposure and brain volumes after controlling for potential confounders. Finally, mediation analysis was carried out to test whether deficit in working memory performance associated with cannabis use was mediated by its association with lower grey‐matter volume. Participants who reported higher frequency of cannabis use tended to have lower number of correct responses in the list‐sorting working memory task and lower bilateral hippocampal volumes. Association between severity of cannabis exposure as indexed by frequency of cannabis use and impairment in working memory was mediated by lower left hippocampal volume in cannabis users. We report evidence in support of the left hippocampus volume‐mediated working memory impairment associated with recreational cannabis exposure. Future studies employing prospective longitudinal design are necessary to examine the cause–effect relationships of cannabis exposure on working memory and brain volumes.
The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER–Golgi membrane contact sites

Wakana et al. describe a new role for SCAP, a key regulatory protein in cholesterol metabolism, in promoting Golgi PI4P turnover and the biogenesis of the TGN-derived transport carriers CARTS via interaction with the cholesterol/PI4P exchange machinery at ER–Golgi membrane contact sites.
Efficacy and safety of apixaban in patients with active malignancy and acute deep venous thrombosis

Objectives Low-molecular weight heparin (LMWH) has been approved for treatment of deep venous thrombosis and venous thromboembolism which are associated with cancer. The efficacy and safety of apixaban in management of acute deep venous thrombosis associated with active malignancy is still an unresolved issue. The aim of our study is to evaluate the efficacy and safety of apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous LMWH. Methods Of 138 randomized patients, 100 patients with active malignancy presenting with acute deep venous thrombosis and still treated with chemotherapy were assigned to either oral apixaban therapy or subcutaneous low-molecular weight heparin (enoxaparin) through randomized clinical study in 1:1 ratio. All patients were followed up to six months. The primary end point was major bleeding, while secondary end points were recurrent deep venous thrombosis or venous thromboembolism, minor or non-fatal bleeding and mortality related to massive pulmonary embolism. Results Both groups were matched regarding their baseline demographic, clinical and laboratory characteristics. We had 84 patients with metastatic cancer (stage 4). The most prevalent type of malignancy was cancer colon (42% of cases). There was no significant difference between both groups regarding the incidence of primary and secondary end points. There were no reported mortality cases related to massive pulmonary embolism in both groups. Conclusion In this limited study, there was no difference in the major bleeding, recurrent deep venous thrombosis or minor bleeding in patients with active malignancy when treated with either apixaban or LMWH. Trial registration: ClinicalTrials.gov (NCT04462003). Registered 7 July 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04462003
NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY Central Nervous System Cancers, Version 3.2020

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described. J Natl Compr Canc Netw 2020;18(11):1537–1570 doi: 10.6004/jnccn.2020. 0052 NCCN CATEGORIES OF EVIDENCE AND CONSENSUS Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category2A:Basedupon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. All recommendations are category 2A unless otherwise noted. Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.