bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors predicting poor anticoagulant control on warfarin in a Thai population with non-valvular atrial fibrillation (NVAF): the ACAChE score
Authors: Lertsanguansinchai Piyoros , Huntrakul Anurut , Rungpradubvong Voravut , Chokesuwattanaskul Ronpichai , Prechawat Somchai 
Published: June 2021

Abstract
Background
In many low- to middle-income countries in Asia, patients with NVAF usually received warfarin for thromboembolic prevention due to cost-effectiveness. The SAMe-TT2R2 score has been proposed to predict TTR in NVAF patients. However, the SAMe-TT2R2 score has not been much validated in Asian population. Interestingly, it may overestimate patients who had TTR < 65% due to regarding being Asians as a risk factor.

Objectives
To determine the factors predicting poor anticoagulant control on warfarin, create new scoring system, and compare with the SAMe-TT2R2 score in a Thai population with NVAF.

Methods
This is a retrospective study in a tertiary care hospital. We enrolled NVAF patients who received warfarin from January 2014 to December 2018. TTR was calculated based on Rosendaal method. Multiple logistic regression and AUC-ROC curve were used for analysis.

Results
A total of 864 patients were enrolled with mean age of 73.6 ± 11.58 years. The mean TTR was 48.1 ± 25.2%. Using multivariate regression analysis, the predictive factors for TTR < 65% were antiplatelet use (OR 4.49, p ≤ 0.001), LVEF < 40% (OR 1.92, p = 0.037), chronic kidney disease (GFR < 50 ml/min/1.73 m2) (OR 1.68, p = 0.013), history of CHF (OR 1.7, p = 0.047), and age ≥ 75 years (OR 1.4, p = 0.037). Based on the regression coefficients, we developed the new scoring system called ACAChE score [A, antiplatelet use (4 points); C, chronic kidney disease, GFR < 50 ml/min/1.73 m2 (2 points); A, age ≥ 75 years (1 point); Ch, history of CHF (2 points); E, LVEF < 40% (2 points)]. ROC curve showed discrimination performance of the ACAChE score and SAMe-TT2R2 score for prediction of TTR < 65% with the C-statistic of 0.62 (95%CI 0.57–0.65) and 0.54 (95%CI 0.50–0.58), respectively.

Conclusion
In Thai NVAF patients, the ACAChE score (antiplatelet use, chronic kidney disease (GFR < 50 ml/min/1.73 m2), age ≥ 75 years, history of congestive heart failure, and LVEF < 40%) has better prediction for TTR < 65% than SAMe-TT2R2 score. Thus, it expected to guide the selection of oral anticoagulation in Asian patients with NVAF.
Diagnostic accuracy of Leucine-rich α-2 glycoprotein (LRG) as a urinary biomarker in pediatric appendicitis: a prospective observational pilot study from Eastern India
Authors: Mahalik Santosh Kumar , Bandyopadhyay Debapriya , Tripathy Bikasha Bihary , Pati Akash Bihari , Mohanty Manoj Kumar 
Published: June 2021

Abstract
Background
Recently, several serum and urinary biomarkers have been investigated for diagnosis of acute appendicitis. Urinary biomarkers seem to be advantageous in children as it is non-invasive, painless, and easy to perform. Leucine-rich α-2-glycoprotein (LRG) is regarded as a reliable urinary biomarker for the diagnosis of pediatric appendicitis. A prospective observational pilot study was conducted in children presenting with abdominal pain. Assessment of pediatric appendicitis score (PAS), routine blood tests, and measurements of urinary LRG was done. The present study aimed to evaluate the diagnostic accuracy of urine LRG in appendicitis in Indian children and to assess the concentration of urine LRG at which it will guide the management.

Results
LRG had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.586 (95% CI 0.407–0.766). There was no specific cut-off identified using Youden’s index. ROC analysis of the PAS score resulted in an AUC of 0.821 (95% CI 0.691–0.952). Using Youden’s index, the cut-off for PAS scoring was identified as 6.5 with the sensitivity of 80%, the specificity of 76.2%, positive predictive value 76.19%, negative predictive value as 80%, and diagnostic accuracy of 78%.

Conclusions
LRG could not show better diagnostic performance compared to routine blood tests and PAS scores. There was no specific cut-off value at which it will differentiate mesenteric adenitis and acute appendicitis and guide their management. With 78% diagnostic accuracy, PAS score (> 6) is still a better tool for the diagnosis of acute appendicitis.

Trial registration
Clinical Trials Registry Government of India, CTRI/2018/01/011182, Registered on: 08 Jan 2018.
Definition, Prevalence, and Risk Factors of Low Sex Hormone-Binding Globulin in US Adults
Authors: Wang Yutang 
Published: June 2021

AbstractContextLower sex hormone-binding globulin (SHBG) is associated with many diseases including cardiovascular disease, cancer, polycystic ovarian syndrome, arthritis, and liver disease. However, the definition of low SHBG and its prevalence in US adults are unknown.ObjectiveTo define low SHBG and to determine its prevalence and risk factors in US adults.Design, Setting, and ParticipantsThis cohort study included adults ≥20 years from the US National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 who had fasting serum SHBG.ExposuresNHANES coverage during 2013-2016.Main Outcomes MeasuresDefinition, prevalence, and risk factors of low SHBG.ResultsThis study included 4093 adults (weighted sample size of 204 789 616) with a mean (SD) age of 47.5 (17.0) years. In a “healthy” reference sub-cohort of 1477 adults, low SHBG was defined as SHBG &lt; 12.3 nmol/L in men &lt; 50 years, &lt;23.5 nmol/L in men ≥ 50 years, &lt;14.5 nmol/L in women &lt; 30 years, and &lt;21.9 nmol/L in women ≥ 30 years. The estimated US national prevalence of low SHBG was 3.3% in men, 2.7% in women, and 3.0% overall. Risk factors for this condition in both men and women included higher body mass index, diabetes, ethnicity (being other than Hispanic, non-Hispanic black, or non-Hispanic white), chronic obstructive pulmonary disease, coronary heart disease, and smoking.ConclusionsThis study established the criteria for low SHBG among US adults. The estimated US national prevalence of low SHBG was 3.3% in men and 2.7% in women.
Endocrine Dysfunction in Patients With Myotonic Dystrophy
Authors: Winters Stephen J 
Published: June 2021

Abstract
Myotonic dystrophy is a dominantly inherited multisystem disorder that results from increased CTG repeats in the 3′ region of the myotonic dystrophy protein kinase gene (DMPK). The mutant DMPK mRNA remains in the nucleus and sequesters RNA-binding proteins, including regulators of mRNA splicing. Myotonic dystrophy is characterized by a highly variable phenotype that includes muscle weakness and myotonia, and the disorder may affect the function of many endocrine glands. DMPK mRNA is expressed in muscle, testis, liver, pituitary, thyroid, and bone; the mutated form leads to disruption of meiosis and an increase in fetal insulin receptor-A relative to adult insulin receptor-B, resulting in adult primary testicular failure and insulin resistance predisposing to diabetes, respectively. Patients with myotonic dystrophy are also at increased risk for hyperlipidemia, nonalcoholic fatty liver disease, erectile dysfunction, benign and malignant thyroid nodules, bone fractures, miscarriage, preterm delivery, and failed labor during delivery. Circulating parathyroid hormone and adrenocorticotropic hormone levels may be elevated, but the mechanisms for these associations are unclear. This review summarizes what is known about endocrine dysfunction in individuals with myotonic dystrophy.
Mild Idiopathic Infantile Hypercalcemia—Part 1: Biochemical and Genetic Findings
Authors: Lenherr-Taube Nina , Young Edwin J , Furman Michelle , Elia Yesmino , Assor Esther , Chitayat David , Uster Tami , Kirwin Susan , Robbins Katherine , Vinette Kathleen M B , Daneman Alan , Marshall Christian R , Collins Carol , Thummel Kenneth , Sochett Etienne , Levine Michael A 
Published: June 2021

Abstract

Context
Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms.

Objective
This work aims to characterize the genetic associations and biochemical profile of mild IIH.

Methods
This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands.

Results
The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria.

Conclusion
The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.
Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells
Authors: Keen Kim L , Petersen Andrew J , Figueroa Alexander G , Fordyce Benjamin I , Shin Jaeweon , Yadav Rachita , Erdin Serkan , Pearce Robert A , Talkowski Michael E , Bhattacharyya Anita , Terasawa Ei 
Published: June 2021

AbstractGonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons. Second, addition of kisspeptin to FGF8 further increased the efficiency rates of GnRH neurogeneration. Third, we generated a fluorescent marker mCherry labeled human embryonic GnRH cell line (mCh-hESC) using a CRISPR-Cas9 targeting approach. Fourth, we examined physiological characteristics of GnRH (mCh-hESC) neurons: similar to GnRH neurons in vivo, they released the GnRH peptide in a pulsatile manner at ~60 min intervals; GnRH release increased in response to high potassium, kisspeptin, estradiol, and neurokinin B challenges; and injection of depolarizing current induced action potentials. Finally, we characterized developmental changes in transcriptomes of GnRH neurons using hESC, hiPSC, and mCh-hESC. The developmental pattern of transcriptomes was remarkably similar among the 3 cell lines. Collectively, human stem cell–derived GnRH neurons will be an important tool for establishing disease models to understand diseases, such as idiopathic hypothalamic hypogonadism, and testing contraceptive drugs.
A functional genetic screen identifies aurora kinase b as an essential regulator of Sox9-positive mouse embryonic lung progenitor cells
Authors: Ah-Cann Casey , Wimmer Verena C. , Weeden Clare E. , Marceaux Claire , Law Charity W. , Galvis Laura , Filby Caitlin E. , Liu Joy , Breslin Kelsey , Willson Tracy , Ritchie Matthew E. , Blewitt Marnie E. , Asselin-Labat Marie-Liesse 
Published: June 2021

ABSTRACT
Development of a branching tree in the embryonic lung is crucial for the formation of a fully mature functional lung at birth. Sox9+ cells present at the tip of the primary embryonic lung endoderm are multipotent cells responsible for branch formation and elongation. We performed a genetic screen in murine primary cells and identified aurora kinase b (Aurkb) as an essential regulator of Sox9+ cells ex vivo. In vivo conditional knockout studies confirmed that Aurkb was required for lung development but was not necessary for postnatal growth and the repair of the adult lung after injury. Deletion of Aurkb in embryonic Sox9+ cells led to the formation of a stunted lung that retained the expression of Sox2 in the proximal airways, as well as Sox9 in the distal tips. Although we found no change in cell polarity, we showed that loss of Aurkb or chemical inhibition of Aurkb caused Sox9+ cells to arrest at G2/M, likely responsible for the lack of branch bifurcation. This work demonstrates the power of genetic screens in identifying novel regulators of Sox9+ progenitor cells and lung branching morphogenesis.
Ca2+ release via InsP3Rs enhances RyR recruitment during Ca2+ transients by increasing dyadic [Ca2+] in cardiomyocytes
Authors: Demydenko Kateryna , Sipido Karin R. , Roderick H. Llewelyn 
Published: June 2021

ABSTRACT
Excitation–contraction coupling (ECC) relies on temporally synchronized sarcoplasmic reticulum (SR) Ca2+ release via ryanodine receptors (RyRs) at dyadic membrane compartments. Neurohormones, such as endothelin-1 (ET-1), that act via Gαq-associated G protein-coupled receptors (GPCRs) modulate Ca2+ dynamics during ECC and induce SR Ca2+ release events involving Ca2+ release via inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs). How the relatively modest Ca2+ release via InsP3Rs elicits this action is not resolved. Here, we investigated whether the actions of InsP3Rs on Ca2+ handling during ECC were mediated by a direct influence on dyadic Ca2+ levels and whether this mechanism contributes to the effects of ET-1. Using a dyad-targeted genetically encoded Ca2+ reporter, we found that InsP3R activation augmented dyadic Ca2+ fluxes during Ca2+ transients and increased Ca2+ sparks. RyRs were required for these effects. These data provide the first direct demonstration of GPCR and InsP3 effects on dyadic Ca2+, and support the notion that Ca2+ release via InsP3Rs influences Ca2+ transients during ECC by facilitating the activation and recruitment of proximal RyRs. We propose that this mechanism contributes to neurohormonal modulation of cardiac function.
This article has an associated First Person interview with the first author of the paper.
Associative learning of non-sugar nectar components: amino acids modify nectar preference in a hawkmoth
Authors: Broadhead Geoffrey T. , Raguso Robert A. 
Published: June 2021

ABSTRACT
The nearly ubiquitous presence of amino acids in the nectar of flowering plants has led to significant interest in the relevance of these compounds to pollinator behavior and physiology. A number of flower-visiting animals exhibit behavioral preferences for nectar solutions containing amino acids, but these preferences vary by species and are often context or condition dependent. Furthermore, the relative strength of these preferences and potential influence on the foraging behavior of flower-visiting animals remains unclear. Here, we used innate preference tests and associative learning paradigms to examine the nectar preferences of the flower-visiting hawkmoth Manduca sexta, in relation to both sugar and amino acid content. Manduca sexta exhibited a strong preference for higher sucrose concentrations, while the effect of amino acids on innate feeding preference was only marginally significant. However, with experience, moths were able to learn nectar composition and flower color associations and to forage preferentially (against innate color preference) for nectar with a realistic amino acid composition. Foraging moths responding to learned color cues of nectar amino acid content exhibited a behavioral preference comparable to that observed in response to a 5% difference in nectar sucrose concentration. These results demonstrate that experienced foragers may assess nectar amino acid content in addition to nectar sugar content and caloric value during nectar-foraging bouts.
Single motherhood, social independence and non-communicable disease (NCD) outcomes among young females (15-24 years old) in South Africa
Authors: De Wet-Billings Nicole 
Published: June 2021

Background: Non-communicable diseases (NCDs) acquired during youth follow into and affect adulthood. The association between young mother’s social independence and NCD status is of policy interest due to its effect on economic and social development. This study aimed to determine the causal relationship between social independence and NCD outcomes among young, single mothers in South Africa. Methods: Data from the South African National Income Dynamics Survey (NIDS) in 2008 and 2017 was used to determine if single mothers developed hypertension, diabetes or asthma by various indicators of social independence, including highest level of education and employment status. The sample was initially made-up of unmarried females (15-24 years old) without any children in 2008. Both fertility and social independence was followed-up to 2017. Results: In total, 66 young females developed an NCD by 2017 and 87% (n=57) of these women had a child in the interim period. Employment of young females increased from 4.78% in 2008 to 37.79% in 2017, but completion of secondary or tertiary education declined from 67.94% in 2008 to 56.01% in 2017. In addition, half (50.88%) of the young females were partially independent by 2017, with only 11.03% being fully independent at this time. Finally, logistic regression results showed that the likelihood of developing an NCD increased if young females with children were not socially independent. Conclusions: The relationship between social independence and NCDs suggest that policies and programmes in South Africa need to incorporate socioeconomic status as a determinant of disease and in particular, need to address socioeconomic indicators as additive measures and not autonomous indicators.
SARS-CoV-2 and the role of fomite transmission: a systematic review
Authors: Onakpoya Igho J. , Heneghan Carl J. , Spencer Elizabeth A. , Brassey Jon , Plüddemann Annette , Evans David H. , Conly John M. , Jefferson Tom 
Published: June 2021

Background:SARS-CoV-2 RNA has been detected in fomites which suggests the virus could be transmitted via inanimate objects. However, there is uncertainty about the mechanistic pathway for such transmissions. Our objective was to identify, appraise and summarise the evidence from primary studies and systematic reviews assessing the role of fomites in transmission. Methods:This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis.Results:We found 64 studies: 63 primary studies and one systematic review (n=35). The settings for primary studies were predominantly in hospitals (69.8%) including general wards, ICU and SARS-CoV-2 isolation wards. There were variations in the study designs including timing of sample collection, hygiene procedures, ventilation settings and cycle threshold. The overall quality of reporting was low to moderate. The frequency of positive SARS-CoV-2 tests across 51 studies (using RT-PCR) ranged from 0.5% to 75%. Cycle threshold values ranged from 20.8 to 44.1. Viral concentrations were reported in 17 studies; however, discrepancies in the methods for estimation prevented comparison. Eleven studies (17.5%) attempted viral culture, but none found a cytopathic effect. Results of the systematic review showed that healthcare settings were most frequently tested (25/35, 71.4%), but laboratories reported the highest frequency of contaminated surfaces (20.5%, 17/83). Conclusions:The majority of studies report identification of SARS-CoV-2 RNA on inanimate surfaces; however, there is a lack of evidence demonstrating the recovery of viable virus. Lack of positive viral cultures suggests that the risk of transmission of SARS-CoV-2 through fomites is low. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.
Case Report: Heparin-induced thrombocytopenia during COVID-19 outbreak: the importance of scoring system in differentiating with sepsis-induced coagulopathy
Authors: Wardhani Louisa Fadjri Kusuma , Dewi Ivana Purnama , Suwanto Denny , Ardiana Meity 
Published: June 2021

Background: COVID-19 disease is accompanied by derangement of coagulation with a risk of fatal thromboembolic formation. COVID-19 patients are among those indicative for heparin treatment. Increased heparin administration among COVID-19 patients increased heparin induced-thrombocytopenia's risk with/without thrombocytopenia. Case presentation: We present a 71-year-old male patient who came to the emergency department (ED) with a COVID-19 clinical manifestation that PCR nasopharyngeal swab confirmed. He was assessed to have acute respiratory distress syndrome (ARDS), as shown by rapid progression of hypoxemic respiratory failure and bilateral pulmonary infiltrate. He was then treated with moxifloxacin, remdesivir, dexamethasone, heparin pump, and multivitamins. During admission, his respiratory symptoms got worse, so he transferred to the ICU for NIV support. On the ninth day of admission, he had gross hematuria followed by a rapid fall of platelet count. We used two different scoring systems (4Ts and HEP scoring system) to confirm the diagnosis of heparin-induced thrombocytopenia (HIT). Following the discontinuation of heparin injection, the thrombocyte continued to rise, and hematuria disappeared. Conclusion: Heparin-induced thrombocytopenia is associated with an increased risk of severe disease and mortality among COVID-19 patients. The differential diagnosis of HIT could be difficult among COVID-19 patients as thrombocytopenia can also be caused by infection progression. We use two scoring systems, 4Ts and HEP scoring, that can help us to manage the patient. With good management, we can avoid patient morbidity and mortality.