bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254
Authors: Spinner Christoph D , Felizarta Franco , Rizzardini Giuliano , Philibert Patrick , Mitha Essack , Domingo Pere , Stephan Christoph J , DeGrosky Michelle , Bainbridge Veronica , Zhan Joyce , Dumitrescu Teodora Pene , Jeffrey Jerry L , Xu Jianfeng , Halliday Fiona , Gan Jianjun , Johnson Mark , Gartland Martin , Joshi Samit R , Lataillade Max 
Published: January 2022

Abstract

Background
GSK3640254 (GSK’254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy.

Methods
This phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK’254 monotherapy administered with food (moderate-fat meal) in HIV-1–positive, treatment-naive adults. In part 1, participants received GSK’254 10 or 200 mg for 10 days. In part 2, participants received GSK’254 40, 80, or 140 mg for 7 days, modified from 10 days by a protocol amendment to decrease potential for resistance-associated mutations (RAMs). The primary endpoint was maximum change from baseline in HIV-1 RNA.

Results
Maximum changes in HIV-1 RNA of −0.4, −1.2, −1.0, −1.5, and −2.0 log10 occurred with GSK’254 10, 40, 80, 140, and 200 mg, respectively. Regardless of dosing duration, doses ≥40 mg resulted in ≥1-log10 declines in HIV-1 RNA. Plasma PK was generally dose proportional to 140 mg but non-proportional between 140 and 200 mg. Four participants in the 200-mg group developed RAMs on day 11 in part 1, 1 with phenotypic resistance. No RAMs occurred in part 2. Adverse events (AEs) were reported by 22 (65%) participants; headache was the most common (n = 4). Two non–drug-related serious AEs occurred. All AEs were of mild-to-moderate intensity, except for 2 grade 3 non–drug-related AEs in 1 participant.

Conclusions
This monotherapy study established a dose–antiviral response relationship for GSK’254. No safety or tolerability concerns were noted. These results supported dose selection for the ongoing phase IIb study (ClinicalTrials.gov: NCT04493216).

Clinical Trials Registration
NCT03784079.
Angiogenic Biomarkers for Risk Stratification in Women with Preeclampsia
Authors: Docheva Nikolina , Arenas Gabriel , Nieman Kristin M , Lopes-Perdigao Joana , Yeo Kiang-Teck J , Rana Sarosh 
Published: January 2022

Abstract

Background
Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity worldwide. Diagnosis of the condition is currently limited to utilization of nonspecific signs and symptoms. However, identification of potential pathogenic biomarkers may support earlier diagnosis and ultimately improved prognosis.

Content
The current models of preeclampsia suggest that the disease has components of abnormal placentation, a degree of angiogenic imbalance and endothelial dysfunction. Angiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin increase while placental growth factor concentrations decrease in the circulation weeks before the onset of the disease. Multiple studies have looked at the capacity of angiogenic factors for the prediction of preeclampsia and adverse pregnancy outcomes.

Summary
The goal of this review is to focus on the role of angiogenic factors in the pathogenesis of preeclampsia and use of angiogenic biomarkers for risk stratification, diagnosis, and prognosis of the disease.
Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction
Authors: Wang Xinyi , Ju Jianqing , Chen Zhuo , Lin Qian , Zhang Zihao , Li Qiuyi , Zhang Jie , Xu Hao , Chen Keji 
Published: January 2022

Abstract

Aims
Treatment of heart failure with preserved ejection fraction (HFpEF) is urgently needed; however, effective treatments are lacking. Current evidence showed a possible association between the use of calcium channel blockers (CCBs) and improved outcomes in HFpEF patients. We aimed to investigate the impact of CCBs on mortality in patients with HFpEF.

Methods and results
This was a post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular and noncardiovascular mortality. We analysed hazard ratios (HRs) in patients taking CCBs compared with those not taking CCBs using Cox proportional hazard models. We considered 3440 HFpEF patients. The mean follow-up period was 3.4 ± 1.7 years, and 530 patients died during the study period. All-cause mortality rates in patients taking and not taking CCB were 37.3 and 50.8 events per 1000 person-years, respectively. The adjusted HR for all-cause mortality was significantly lower in those taking CCBs than those not taking CCBs [HR: 0.72, 95% confidence interval (CI): 0.59–0.88, P = 0.001]. The risk of cardiovascular and noncardiovascular mortality was also significantly lower in patients taking CCBs than in those not taking CCBs (HR: 0.75, 95% CI: 0.59–0.96, P = 0.023 and HR: 0.68, 95% CI: 0.49–0.93, P = 0.018, respectively).

Conclusion
The use of CCBs was associated with reduced risks of mortality in patients with HFpEF.
Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals
Authors: Koh Yu Han , Lew Leslie Z W , Franke Kyle B , Elliott Adrian D , Lau Dennis H , Thiyagarajah Anand , Linz Dominik , Arstall Margaret , Tully Phillip J , Baune Bernhard T , Munawar Dian A , Mahajan Rajiv 
Published: January 2022

Abstract

Aims
To systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment.

Methods and results
PubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25–1.53, I2 = 90.3%; follow-up 3.8–25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66–3.74, I2 = 0.0%; follow-up 0.25–3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11–1.73, I2 = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58–2.64, I2 = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke.

Conclusion
Atrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke. PROSPERO CRD42018109185.
Prevalence of Malnutrition, Its Risk Factors, and the Use of Nutrition Support in Patients with Inflammatory Bowel Disease
Authors: Liu Jing , Ge Xiaolong , Ouyang Chunhui , Wang Dongxu , Zhang Xiaoqi , Liang Jie , Zhu Weiming , Cao Qian 
Published: January 2022

Abstract

Background
Malnutrition is prevalent among patients with inflammatory bowel disease (IBD). Nutritional profiles among Asian patients with IBD have seldom been investigated. We assessed the prevalence of and risk factors for malnutrition, use of nutrition support, and sociopsychological status associated with malnutrition among patients with IBD in China.

Methods
Patients with ulcerative colitis and Crohn’s disease (CD) recruited from 43 tertiary referral hospitals were screened for malnutrition and nutrient deficiencies in this cross-sectional study. The use of nutrition support was recorded. The sociopsychological status was assessed by subjective questionnaires. Factors associated with malnutrition were analyzed, and multivariate regression was used to determine independent predictors for malnutrition.

Results
We recruited 1013 patients with a median age of 35.0 years, 58.5% of them had CD, and 61.4% of all patients were male. Overall, 49.5% (n = 501) of patients were diagnosed with malnutrition, including 57.0% of patients with CD, 38.8% of patients with ulcerative colitis, and 44.1% of patients with quiescent or mildly active disease. Nutrient deficiencies were prevalent despite the absence of malnutrition. Malnutrition was associated with adverse sociopsychological status, including decreased social support, higher perceived stress, and impaired quality of life. Moderate to severe disease activity and extensive disease were 2 independent risk factors for malnutrition. In total, 41.6% of patients received nutrition support, and patients with risk factors were more likely to receive nutrition support.

Conclusions
Malnutrition was highly prevalent and associated with adverse consequences in Chinese patients with IBD. Malnutrition screening and early initiation of nutrition support are essential components in IBD care.
Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn’s Disease: A Pilot Study
Authors: Chen Yu-Jun , Chen Bai-Li , Liang Mei-Juan , Chen Shu-Ling , Li Xue-Hua , Qiu Yun , Pang Lan-Lan , Xia Qing-Qing , He Yao , Zeng Zhi-Rong , Chen Min-Hu , Mao Ren , Xie Xiao-Yan 
Published: January 2022

Abstract

Background
Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn’s disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy.

Methods
Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14.

Results
Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P &lt; .001, P &lt; .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3 ± 8.7 kPa vs 15.3 ± 4.7 kPa; P = .022) and bowel wall thickness (8.5 ± 2.3 mm vs 6.9 ± 1.5 mm; P = .027) in the nonresponse group were significantly higher than in the response group.

Conclusions
This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.
The impact of pertussis vaccine programme changes on pertussis disease burden in Manitoba, 1992–2017—an age-period-cohort analysis
Authors: Wilkinson Krista , Righolt Christiaan H , Elliott Lawrence J , Fanella Sergio , Mahmud Salaheddin M 
Published: January 2022

Abstract

Background
Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992–2017).

Methods
We identified all laboratory-confirmed cases of pertussis from Manitoba’s Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence.

Results
During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995.

Conclusions
The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981–95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period.
Growth of Unbounded Subsets in Nilpotent Groups, Random Mapping Statistics and Geometry of Group Laws
Authors: Greenfeld Be’eri , Lavner Hagai 
Published: January 2022

AbstractFor a group $G$ let $\gamma ^{\max }_G(n)$ denote the maximum number of length-$n$ words over an arbitrary $n$-letter subset of $G$. If $G$ is finitely generated and residually finite, then either $\gamma ^{\max }_G(n)$ is exponentially bounded, if and only if $G$ is virtually abelian, or $\gamma ^{\max }_G(n)\geq ~\left (e^{-\frac {1}{4}}+o(1)\right )n^n$; the latter bound cannot be improved, namely, it is attained for the Heisenberg group. For higher-step free nilpotent groups we have $(1-o(1))n^n\leq \gamma ^{\max }_G(n)\lneq n^n$. As a key ingredient in the proof, we calculate the number of pair histograms of functions $f\colon [n]\rightarrow [n]$ and the probability that a random function $f\colon [n]\rightarrow [n]$ can be uniquely determined by its pair histogram. We analyze group laws of the Heisenberg group by means of closed paths attached to words in the free group and their projected oriented polygons.
Numbers and narratives: how qualitative methods can strengthen the science of paediatric antimicrobial stewardship
Authors: Woods-Hill Charlotte Z. , Xie Anping , Lin John , Wolfe Heather A. , Plattner Alex S. , Malone Sara , Chiotos Kathleen , Szymczak Julia E. 
Published: January 2022

AbstractAntimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance of such methods and as a starting point for further work. We describe key differences between qualitative and quantitative methods, and the potential benefits of qualitative approaches. We present examples of qualitative research in five discrete topic areas of high relevance for paediatric stewardship work: provider attitudes; provider prescribing behaviours; stewardship in low-resource settings; parents’ perspectives on stewardship; and stewardship work focusing on select high-risk patients. Finally, we explore the opportunities for multidisciplinary academic collaboration, incorporation of innovative scientific disciplines and young investigator growth through the use of qualitative research in paediatric stewardship. Qualitative approaches can bring rich insights and critically needed new information to antimicrobial and diagnostic stewardship efforts in children. Such methods are an important tool in the armamentarium against worsening antimicrobial resistance, and a major opportunity for investigators interested in moving the needle forward for stewardship in paediatric patients.
Synthetic Cannabinoid Receptor Agonists in Postmortem Casework in Scotland
Authors: Seywright Alice , Irvine Alexander F. D , McKeown Denise A , Wylie Fiona M , Torrance Hazel J 
Published: January 2022

Abstract
Synthetic cannabinoid receptor agonists (SCRAs) have been a concern to forensic toxicologists since their emergence as drugs of abuse in the mid-late 2000s. The extent of their use in Scotland appears to be low especially when compared to other drug groups such as opioids and benzodiazepines. There is a concern, however, that the use is widespread in prison populations in particular. In this work, samples of blood and urine collected during routine postmortem examination between April 2017 and March 2019 were subjected to analysis of SCRA compounds. Circumstantial and demographic information was collected on positive cases to build up a body of evidence for where SCRAs may be most likely to contribute to the cause of death. Thirteen out of 133 cases (10%) tested were positive for one or more compound in one or more matrix. Overall, the detection of 5F-MDMB-PINACA or its O-desmethyl acid metabolite was most common, followed by the metabolite shared by AB-FUBINACA and MMB-FUBINACA. SCRA-positive cases were predominantly males (92%), and the age range of all decedents was 21–49 years old (median 36 years). The majority of cases were certified as drug-related deaths (DRDs, 38%), natural/medical (31%) or suicide (23%), and two of the DRDs mentioned SCRAs specifically in the cause of death. The concentrations of SCRAs detected did not seem to be as important to the determination of the cause of death as their mere presence, but quantitative results were reported (where possible) in order to build up a body of evidence for SCRA concentrations in different case types.
Treatment of a rare recurrent pulmonary arteriovenous malformation after multiple embolization by robotic-assisted thoracoscopic surgery
Authors: Li Tong , Hao Peng , Lv Xiaojing , Tian Hui 
Published: January 2022

Abstract
Pulmonary arteriovenous malformations (PAVMs) are a rare pulmonary arteriovenous direct traffic vascular malformation, which directly connect the pulmonary artery to the pulmonary vein without pulmonary capillary bed. Currently, surgical resection and percutaneous transcatheter embolization are the main mode of treatment. Embolization is gradually becoming the preferred treatment for people with PAVMs, because it is less invasive and easy to repeat. We describe a case of PAVMs with hemoptysis that relapsed again after three times of embolization and then only presented new symptoms of transient ischemic attack. Finally, the patient was treated by Da Vinci robotic-assisted thoracoscopic surgery, and there were no obvious post-operative complications and recurrence. It is the first report of multiple recurrent complex PAVMs and we present our experience with the treatment of recurrent PAVMs.
How the spectral energy distribution and galaxy morphology constrain each other, with application to morphological selection using galaxy colours
Authors: Uzeirbegovic Emir , Martin Garreth , Kaviraj Sugata 
Published: January 2022

ABSTRACT
We introduce an empirical methodology to study how the spectral energy distribution (SED) and galaxy morphology constrain each other and implement this on ∼8000 galaxies from the HST CANDELS survey in the GOODS-South field. We show that the SED does constrain morphology and present a method that quantifies the strength of the link between these two quantities. Two galaxies with very similar SEDs are around three times more likely to also be morphologically similar, with SED constraining morphology most strongly for relatively massive red ellipticals. We apply our methodology to explore likely upper bounds on the efficacy of morphological selection using colour. We show that, under reasonable assumptions, colour selection is relatively ineffective at separating homogeneous morphologies. Even with the use of up to six colours for morphological selection, the average purity in the resultant morphological classes is only around 60 per cent. While the results can be improved by using the whole SED, the gains are not significant, with purity values remaining around 70 per cent or below.
Velocity gradients: magnetic field tomography towards the supernova remnant W44
Authors: Liu Mingrui , Hu Yue , Lazarian A 
Published: January 2022

ABSTRACT
As a novel approach for tracing interstellar magnetic fields, the velocity gradient technique (VGT) has been proven to be effective for probing magnetic fields in the diffuse interstellar medium (ISM). In this work, we verify the VGT in a broader context by applying the technique to a molecular cloud interacting with the supernova remnant (SNR) W44. We probe the magnetic fields with the VGT using CO, $\rm HCO^+$ and H i emission lines and make a comparison with the Planck 353-GHZ dust polarization. We show that the VGT gives an accurate measurement that coheres with the Planck polarization especially in intense molecular gas emission regions. We further study the foreground’s contribution on the polarization that results in misalignment between the VGT and the Planck measurements in low-intensity molecular gas areas. We advance the VGT to achieve magnetic field tomography by decomposing the SNR W44 into various velocity components. We show that W44’s velocity component at v ∼ 45 km s−1 exhibits the largest coverage and gives best agreement with Planck polarization in terms of magnetic field orientation.
Optical properties of Peaked Spectrum radio sources
Authors: Nascimento R S , Rodríguez-Ardila A , Dahmer-Hahn L , Fonseca-Faria M A , Riffel R , Marinello M , Beuchert T , Callingham J R 
Published: January 2022

ABSTRACT
In this work, we study the optical properties of compact radio sources selected from the literature in order to determine the impact of the radio-jet in their circumnuclear environment. Our sample includes 58 Compact Steep Spectrum (CSS) and GigaHertz Peaked Spectrum (GPS) and 14 Megahertz-Peaked spectrum (MPS) radio sources located at z ≤ 1. The radio luminosity (LR) of the sample varies between Log LR ∼ 23.2 and 27.7 W Hz−1. We obtained optical spectra for all sources from SDSS-DR12 and performed a stellar population synthesis using the starlight code. We derived stellar masses (M⋆), ages 〈t⋆〉, star formation rates (SFR), metallicities 〈Z⋆〉 and internal reddening AV for all young AGNs of our sample. A visual inspection of the SDSS images was made to assign a morphological class for each source. Our results indicate that the sample is dominated by intermediate to old stellar populations and there is no strong correlation between optical and radio properties of these sources. Also, we found that young AGNs can be hosted by elliptical, spiral and interacting galaxies, confirming recent findings. When comparing the optical properties of CSS/GPS and MPS sources, we do not find any significant difference. Finally, the Mid-Infrared WISE colours analysis suggests that the compact radio sources defined as powerful AGNs are, in general, gas-rich systems.