bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of in‐hospital hypokalemia using machine learning and first hospitalization day records in patients with traumatic brain injury
Authors: Zhou Zhengyu , Huang Chiungwei , Fu Pengfei , Huang Hong , Zhang Qi , Wu Xuehai , Yu Qiong , Sun Yirui 
Published: October 2022

AbstractAimsHypokalemia is a common complication following traumatic brain injury, which may complicate treatment and lead to unfavorable outcomes. Identifying patients at risk of hypokalemia on the first day of admission helps to implement prophylactic treatment, reduce complications, and improve prognosis.MethodsThis multicenter retrospective study was performed between January 2017 and December 2020 using the electronic medical records of patients admitted due to traumatic brain injury. A propensity score matching approach was adopted with a ratio of 1:1 to overcome overfitting and data imbalance during subgroup analyses. Five machine learning algorithms were applied to generate a best‐performed prediction model for in‐hospital hypokalemia. The internal fivefold cross‐validation and external validation were performed to demonstrate the interpretability and generalizability.ResultsA total of 4445 TBI patients were recruited for analysis and model generation. Hypokalemia occurred in 46.55% of recruited patients and the incidences of mild, moderate, and severe hypokalemia were 32.06%, 12.69%, and 1.80%, respectively. Hypokalemia was associated with increased mortality, while severe hypokalemia cast greater impacts. The logistic regression algorithm had the best performance in predicting decreased serum potassium and moderate‐to‐severe hypokalemia, with an AUC of 0.73 ± 0.011 and 0.74 ± 0.019, respectively. The prediction model was further verified using two external datasets, including our previous published data and the open‐assessed Medical Information Mart for Intensive Care database. Linearized calibration curves showed no statistical difference (p > 0.05) with perfect predictions.ConclusionsThe occurrence of hypokalemia following traumatic brain injury can be predicted by first hospitalization day records and machine learning algorithms. The logistic regression algorithm showed an optimal predicting performance verified by both internal and external validation.
Impact of induction therapy on cytomegalovirus infection and post‐transplant outcomes in pediatric heart transplant recipients receiving routine antiviral prophylaxis
Authors: Zang Suhua , Zhang Xin , Niu Jianli , Das Bibhuti B. 
Published: October 2022

AbstractObjectivesInduction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti‐thymocyte globulin (ATG) versus basiliximab as induction therapy on post‐transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis.ResultsOf the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow‐up was 3.0 (IQR, 1.7–4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p = .418), CMV viremia (22% vs. 19.6%, p = .769), and CMV‐positive tissue biopsy (30% vs. 22%, p = .486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p = .022) and CAV (4% vs. 23.9%, p = .006) with no difference in mortality (8% vs. 15.2%, p = .343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR, .31; 95% CI, .09–.94; p = .039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI, .54–7.89; p = .292), CAV (HR, .30; 95% CI, .04–2.58; p = .275), and mortality (HR, .39; 95% CI, .09–1.82; p = .233) compared to basiliximab induction.Discussion and conclusionsIn conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy.
The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence
Authors: Arnold Jonathon C. , McCartney Danielle , Suraev Anastasia , McGregor Iain S. 
Published: October 2022

AbstractGlobal interest in the non‐intoxicating cannabis constituent, cannabidiol (CBD), is increasing with claims of therapeutic effects across a diversity of health conditions. At present, there is sufficient clinical trial evidence to support the use of high oral doses of CBD (e.g., 10–50 mg/kg) in treating intractable childhood epilepsies. However, a question remains as to whether “low‐dose” CBD products confer any therapeutic benefits. This is an important question to answer, as low‐dose CBD products are widely available in many countries, often as nutraceutical formulations. The present review therefore evaluated the efficacy and safety of low oral doses of CBD. The review includes interventional studies that measured the clinical efficacy in any health condition and/or safety and tolerability of oral CBD dosed at less than or equal to 400 mg per day in adult populations (i.e., ≥18 years of age). Studies were excluded if the product administered had a Δ9‐tetrahydrocannabinol content greater than 2.0%. Therapeutic benefits of CBD became more clearly evident at doses greater than or equal to 300 mg. Increased dosing from 60 to 400 mg/day did not appear to be associated with an increased frequency of adverse effects. At doses of 300–400 mg, there is evidence of efficacy with respect to reduced anxiety, as well as anti‐addiction effects in drug‐dependent individuals. More marginal and less consistent therapeutic effects on insomnia, neurological disorders, and chronic pain were also apparent. Larger more robust clinical trials are needed to confirm the therapeutic potential of lower (i.e., <300 mg/day) oral doses of CBD.
Quantification of changes in human islet G protein‐coupled receptor mRNA expression in obesity
Authors: Lyu Zekun , Zhao Min , Atanes Patricio , Persaud Shanta Jean 
Published: October 2022

AbstractBackgroundG protein‐coupled receptors (GPCRs) play crucial roles in regulating islet function, with Gαs‐ and Gαq‐coupled receptors being linked to the stimulation of insulin secretion. We have quantified the mRNA expression of 384 non‐olfactory GPCRs in islets isolated from lean and obese organ donors to determine alterations in islet GPCR mRNA expression in obesity.MethodsRT‐qPCR was used to quantify GPCR mRNAs relative to five reference genes (ACTB, GAPDH, PPIA, TBP, and TFRC) in human islets isolated from lean (BMI = 22.6 ± 0.5) and obese (BMI = 32.0 ± 0.8) donors.ResultsOverall, 197 and 256 GPCR mRNAs were detected above trace level in islets from lean and obese donors, respectively, with 191 GPCR mRNAs being common to the lean and obese groups. 40.9% (n = 157) and 27.1% (n = 104) of the mRNAs were expressed at trace level whilst 7.8% and 6.3% were absent in islets from lean and obese donors, respectively. Hundred and seventeen GPCR mRNAs were upregulated at least twofold in islets from obese donors, and there was >twofold downregulation of 21 GPCR mRNAs. Of particular interest, several receptors signalling via Gαs or Gαq showed significant mRNA upregulation in islets from obese donors (fold increase: PTH2R: 54.0 ± 14.6; MC2R: 34.3 ± 11.5; RXFP1: 8.5 ± 2.1; HTR2B: 6.0 ± 2.0; GPR110: 3.9 ± 1.2; PROKR2: 3.9 ± 0.7).ConclusionsUnder conditions of obesity, human islets showed significant alterations in mRNAs encoding numerous GPCRs. The increased expression of Gαs‐ and Gαq‐coupled receptors that have not previously been investigated in β‐cells opens up possibilities of novel therapeutic candidates that may lead to the potentiation of insulin secretion and/or β‐cell mass to regulate glucose homeostasis.
Generic lamotrigine extended‐release tablets are bioequivalent to innovator drug in fully replicated crossover bioequivalence study
Authors: Fang Lanyan , Li Zhichuan , Kinjo Minori , Lomonaco Sara , Zheng Nan , Jiang Wenlei , Zhao Liang 
Published: October 2022

AbstractObjectiveLamotrigine is a commonly prescribed antiepileptic drug. U.S. Food and Drug Administration (FDA)–funded clinical studies have demonstrated bioequivalence (BE) for generic lamotrigine immediate‐release (IR) products in epilepsy patients with generic substitution. To address the potential concerns about the risk of generic‐brand substitution of lamotrigine extended‐release (ER) products, considering the complexity of controlled release systems and pharmacokinetic variations associated with possible within‐subject variability (WSV), this prospective study assessed (1) BE of generic and brand lamotrigine ER products in a fully replicated BE study design in healthy subjects and (2) whether such fully replicated study design and WSV data can better support the approval of generic lamotrigine ER products.MethodsThis open‐label, single‐dose, two‐treatment, four‐period, two‐sequence, fully replicated crossover BE study compared generic lamotrigine ER tablet to brand Lamictal XR (200 mg) in 30 healthy subjects under fed conditions. Pharmacokinetics (PK) profiles were generated based on intensive blood sampling up to 144 h.ResultsThe two products showed comparable peak plasma concentration (Cmax), area under the concentration‐time curve (AUC) from time zero to the last measurable time point (AUC0‐t) and AUC extrapolated to infinity (AUC0‐inf), whereas median time to Cmax(Tmax) values differed, that is, 10 h for generic and 22 h for brand products, respectively. WSVs for PK metrics were small (~8% of Cmaxand ~6% of AUC) and similar between these two products. PK simulation predicted equivalent PK measurements of both products at steady state and after brand‐to‐generic switch, except the first day upon switching. No serious adverse events were reported.SignificanceThe generic lamotrigine ER tablet product demonstrates BE to the brand product in a fully replicated BE study design with healthy subjects, supporting the adequacy of the two‐way crossover study design to demonstrate BE and generic‐brand substitution of lamotrigine ER products.
Comparison of behavioural tendencies between “dangerous dogs” and other domestic dog breeds – Evolutionary context and practical implications
Authors: Hammond Alexa , Rowland Thomas , Mills Daniel S. , Pilot Małgorzata 
Published: October 2022

AbstractAggressive behaviour by dogs is a considerable social problem, but the ability to predict which individuals may have increased aggressive tendencies is very limited, restricting the development of efficient preventive measures. There is a common perception that certain breeds are more likely to exhibit aggressive behaviour, which has contributed to the introduction of breed‐specific legislation. The rationale for such legislation explicitly assumes high heritability of this trait while also implying relatively little variation within breeds; these assumptions are largely untested. We compared behavioural tendencies between 8 breeds that are subject to legislation in at least one country and 17 breeds that are not subject to legislation using two validated psychometric tools: the Dog Impulsivity Assessment Scale (DIAS), which scores elements of impulsivity, including a tendency for aggressive behaviour, and Positive and Negative Activation Scale (PANAS), which scores sensitivity to positive and negative stimuli (which may trigger aggressive responses). We found that the two groups of breeds do not differ significantly in the specific DIAS factor relating to aggressive behaviour, “Aggression Threshold and Response to Novelty”, or any other DIAS and PANAS factors. We found large variations in all behavioural tendencies measured by both psychometric scales within both groups and within each breed studied. Taken together, our findings indicate that breed alone is not a reliable predictor of individual behavioural tendencies, including those related to aggression, and therefore breed‐specific legislation is unlikely to be an effective instrument for reducing risk.
Metabarcoding reveals high diversity of benthic foraminifera linked to water masses circulation at coastal Svalbard
Authors: Nguyen Ngoc‐Loi , Pawłowska Joanna , Angeles Inès Barrenechea , Zajaczkowski Marek , Pawłowski Jan 
Published: October 2022

AbstractArctic marine biodiversity is undergoing rapid changes due to global warming and modifications of oceanic water masses circulation. These changes have been demonstrated in the case of mega‐ and macrofauna, but much less is known about their impact on the biodiversity of smaller size organisms, such as foraminifera that represent a main component of meiofauna in the Arctic. Several studies analyzed the distribution and diversity of Arctic foraminifera. However, all these studies are based exclusively on the morphological identification of specimens sorted from sediment samples. Here, we present the first assessment of Arctic foraminifera diversity based on metabarcoding of sediment DNA samples collected in fjords and open sea areas in the Svalbard Archipelago. We obtained a total of 5,968,786 reads that represented 1384 amplicon sequence variants (ASVs). More than half of the ASVs (51.7%) could not be assigned to any group in the reference database suggesting a high genetic novelty of Svalbard foraminifera. The sieved and unsieved samples resolved comparable communities, sharing 1023 ASVs, comprising over 97% of reads. Our analyses show that the foraminiferal assemblage differs between the localities, with communities distinctly separated between fjord and open sea stations. Each locality was characterized by a specific assemblage, with only a small overlap in the case of open sea areas. Our study demonstrates a clear pattern of the influence of water masses on the structure of foraminiferal communities. The stations situated on the western coast of Svalbard that are strongly influenced by warm and salty Atlantic water (AW) are characterized by much higher diversity than stations in the northern and eastern part, where the impact of AW is less pronounced. This high diversity and specificity of Svalbard foraminifera associated with water mass distribution indicate that the foraminiferal metabarcoding data can be very useful for inferring present and past environmental conditions in the Arctic.
Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock‐inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors
Authors: Kostaki Evangelia Georgia , Limnaios Stefanos , Adamis Georgios , Xylomenos Georgios , Chini Maria , Mangafas Nikos , Lazanas Marios , Patrinos Stavros , Metallidis Simeon , Tsachouridou Olga , Papastamopoulos Vasileios , Chatzidimitriou Dimitrios , Antoniadou Anastasia , Papadopoulos Antonios , Protopapas Konstantinos , Tsiara Chrysa , Psichogiou Mina , Basoulis Dimitrios , Pilalas Dimitrios , Paraskeva Dimitra , Chrysos Georgios , Paparizos Vasileios , Kourkounti Sofia , Sambatakou Helen , Bolanos Vasileios , Sipsas Nikolaos V. , Lada Malvina , Barbounakis Emmanouil , Kantzilaki Evrikleia , Panagopoulos Periklis , Petrakis Vasilis , Drimis Stelios , Katsarolis Ioannis , Lagiou Pagona , Hatzakis Angelos , Magiorkinis Gkikas , Skoura Lemonia , Paraskevis Dimitrios 
Published: October 2022

AbstractObjectivesHIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis.MethodsOur nationwide sample included HIV‐1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999–2015. Our analysis was based on the molecularly inferred HIV‐1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B.ResultsAnalysis of the determinants of LP was conducted using either CD4 counts or AIDS‐defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age‐dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks.ConclusionsWe demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.
Granulocyte–macrophage colony‐stimulating factor–stimulated human macrophages demonstrate enhanced functions contributing to T‐cell activation
Authors: Farzam‐kia Negar , Lemaître Florent , Carmena Moratalla Ana , Carpentier Solorio Yves , Da Cal Sandra , Jamann Hélène , Klement Wendy , Antel Jack , Duquette Pierre , Girard Jean Marc , Prat Alexandre , Larochelle Catherine , Arbour Nathalie 
Published: October 2022

AbstractGranulocyte–macrophage colony‐stimulating factor (GM‐CSF) has been implicated in numerous chronic inflammatory diseases, including multiple sclerosis (MS). GM‐CSF impacts multiple properties and functions of myeloid cells via species‐specific mechanisms. Therefore, we assessed the effect of GM‐CSF on different human myeloid cell populations found in MS lesions: monocyte‐derived macrophages (MDMs) and microglia. We previously reported a greater number of interleukin (IL)‐15+ myeloid cells in the brain of patients with MS than in controls. Therefore, we investigated whether GM‐CSF exerts its deleterious effects in MS by increasing IL‐15 expression on myeloid cells. We found that GM‐CSF increased the proportion of IL‐15+ cells and/or IL‐15 levels on nonpolarized, M1‐polarized and M2‐polarized MDMs from healthy donors and patients with MS. GM‐CSF also increased IL‐15 levels on human adult microglia. When cocultured with GM‐CSF–stimulated MDMs, activated autologous CD8+ T lymphocytes secreted and expressed significantly higher levels of effector molecules (e.g. interferon‐γ and GM‐CSF) compared with cocultures with unstimulated MDMs. However, neutralizing IL‐15 did not attenuate enhanced effector molecule expression on CD8+ T lymphocytes triggered by GM‐CSF–stimulated MDMs. We showed that GM‐CSF stimulation of MDMs increased their expression of CD80 and ICAM‐1 and their secretion of IL‐6, IL‐27 and tumor necrosis factor. These molecules could participate in boosting the effector properties of CD8+ T lymphocytes independently of IL‐15. By contrast, GM‐CSF did not alter CD80, IL‐27, tumor necrosis factor and chemokine (C–X–C motif) ligand 10 expression/secretion by human microglia. Therefore, our results underline the distinct impact of GM‐CSF on human myeloid cells abundantly present in MS lesions.
Accounting for Non‐ignorable Sampling and Non‐response in Statistical Matching
Authors: Marella Daniela , Pfeffermann Danny 
Published: October 2022

SummaryData for statistical analysis is often available from different samples, with each sample containing measurements on only some of the variables of interest. Statistical matching attempts to generate a fused database containing matched measurements on all the target variables. In this article, we consider the use of statistical matching when the samples are drawn by informative sampling designs and are subject to not missing at random non‐response. The problem with ignoring the sampling process and non‐response is that the distribution of the data observed for the responding units can be very different from the distribution holding for the population data, which may distort the inference process and result in a matched database that misrepresents the joint distribution in the population. Our proposed methodology employs the empirical likelihood approach and is shown to perform well in a simulation experiment and when applied to real sample data.
Women are underrepresented in cardiac resynchronization therapy trials
Authors: Ahmad Javaria , Ahmad Hassaan A. , Surapaneni Phani , Penagaluri Ashritha , Desai Sapna , Dominic Paari 
Published: October 2022

AbstractIntroductionCurrent guidelines for cardiac resynchronization therapy (CRT) device implant are the same across both sexes however women have been traditionally underrepresented in randomized controlled trials (RCTs). We aimed to identify if the number of women included in CRT trials is representative of the real‐world burden of heart failure (HF) in women.MethodsRCTs evaluating the benefit of CRT in HF patients referenced in the 2012 EHRA/HRS expert consensus statement on CRT in HF were included. Studies were evaluated for gender representation, baseline variables, and gender‐based analysis of outcomes.ResultsA total of 10 CRT trials including 8107 patients were studied. Of the total patient population in these RCTs, only 23% were women. Analysis of outcomes based on sex was reported only in 5 out of 10 trials. Of these five trials reporting sex‐based outcomes, multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT‐CRT) and resynchronization–defibrillation for ambulatory heart failure trial (RAFT) showed a greater benefit in women compared to men. Both MADIT and RAFT trials had a lower ejection fraction (EF) cut‐off in the inclusion criteria (EF ≤ 30%) compared to the studies that did not find gender‐based differences in the outcome (inclusion criteria: EF ≤ 35% or 40%). Additionally, women had less ischemic cardiomyopathy and more left bundle branch block (LBBB) compared to men in these two trials.ConclusionWomen are underrepresented in CRT trials; however, they have been shown to derive a greater benefit from CRT compared to men. Appropriate measures should be taken in future studies to enhance the participation of women in clinical trials for more generalizable evidence.
Changes in MCP‐1, HGF, and IGF‐1 expression in endometrial stromal cells, PBMCs, and PFMCs of endometriotic women following 1,25(OH)2D3 treatment
Authors: Heidari Sahel , Kolahdouz‐Mohammadi Roya , Khodaverdi Sepideh , Mohammadi Tahereh , Delbandi Ali‐Akbar 
Published: October 2022

Abstract1,25(OH)2D3 has anti‐inflammatory and growth inhibitory effects. Our study explored the effect of 1,25(OH)2D3 treatment on the expression of monocyte chemotactic protein‐1 (MCP‐1), hepatocyte growth factor (HGF), and insulin‐like growth factor‐1 (IGF‐1) by peripheral blood mononuclear cells (PBMCs), peritoneal fluid mononuclear cells (PFMCs), endometrial stromal cells (ESCs), and its effect on the proliferation of PBMCs and PFMCs of patients with endometriosis compared with controls. PBMCs, PFMCs, and ESCs were obtained from 10 endometriosis patients and 10 non‐endometriotic individuals. After treating cells with 0.1 μM of 1,25(OH)2D3 for 6, 24, and 48 h, the gene and protein expression of mentioned factors were evaluated by real‐time PCR and ELISA methods, respectively. 1,25(OH)2D3 treatment significantly reduced the protein expression of MCP‐1, HGF, and IGF‐1 in PBMCs and PFMCs of endometriotic patients at 48 h (p < 0.05–<0.01). Also, this treatment significantly reduced MCP‐1, HGF, and IGF‐1 gene and/or protein expression in EESCs and EuESCs at 24 and 48 h (p < 0.05–<0.01). 1,25(OH)2D3 treatment also reduced the proliferation of PBMCs and PFMCs of endometriotic patients compared with controls (p < 0.01). 1,25(OH)2D3 can be considered as a potentially effective agent in the prevention and treatment of endometriosis along with other therapies.