bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of on-treatment cancer safety events with daprodustat versus conventional erythropoiesis-stimulating agents—post hoc analyses of the ASCEND-ND and ASCEND-D trials
Authors: Singh Ajay K , McCausland Finnian R , Claggett Brian L , Wanner Christoph , Wiecek Andrzej , Atkins Michael B , Carroll Kevin , Perkovic Vlado , McMurray John J V , Wittes Janet , Snapinn Steven , Blackorby Allison , Meadowcroft Amy , Barker Tara , DiMino Tara , Mallett Stephen , Cobitz Alexander R , Solomon Scott D 
Published: December 2022

ABSTRACT

Background
The prespecified on-treatment analysis of ASCEND-ND (NCT02876835) raised concerns about a higher relative risk of cancer-related adverse events (AEs) with daprodustat vs darbepoetin in patients with anaemia of CKD. This concern was not observed in dialysis patients in ASCEND-D (NCT02879305).

Methods
ASCEND-ND randomized 3872 patients to daprodustat or darbepoetin. ASCEND-D randomized 2964 patients to daprodustat or conventional erythropoiesis-stimulating agents (ESAs). In both studies ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). The prespecified on-treatment approach examined relative risks for cancer AEs up to the last dose date + 1 day. In these analyses, owing to different dosing intervals between arms, Cox models were used to estimate the daprodustat effect by various follow-up periods (censoring at last dose date, last dose date + dosing intervals, or end of study).

Results
In ASCEND-ND, the safety of daprodustat vs darbepoetin on cancer-related AEs depended on the duration of follow-up after last dose date: hazard ratio (HR) 1.04 [95% confidence interval (CI) 0.77, 1.40] at end of study [HR 1.12 (95% CI 0.81, 1.56) for last dose date + dosing interval; HR 1.50 (95% CI 1.04, 2.15) for last dose date + 1 day]. In ASCEND-D, no excess risk of cancer-related AEs was observed with any model examined.

Conclusions
Prespecified on-treatment analyses for cancer-related AEs appeared to result in biased risk estimates in ASCEND-ND by preferentially under-counting events from patients assigned to darbepoetin. Analyses accounting for longer darbepoetin dosing intervals, or extending follow-up, resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D, where ESA comparator dosing intervals are closer to daprodustat.

Trial registration
The ASCEND-ND trial is registered with ClinicalTrials.gov (NCT02876835); the ASCEND-D trial is registered with ClinicalTrials.gov (NCT02879305).
Effects of the genetic variants of alcohol-metabolizing enzymes on lipid levels in Asian populations: a systematic review and meta-analysis
Authors: Luo Zhi , Cheng Jun , Wang Yanggan 
Published: December 2022

AbstractContextEmerging evidence indicates that variants of alcohol-metabolizing enzymes may influence lipid metabolism.ObjectiveThis study aimed to investigate whether the rs671 and rs1229984 variants affect lipid levels in East Asian individuals.Data SourcesPubMed, Foreign Medical Journal Service, Embase, Cochrane Library, Scopus, MEDLINE, Web of Science, Web of Knowledge, Wanfang, and Chinese Biomedical Literature databases were searched until December 31, 2021.Data ExtractionMeta-analyses of studies that examined the effects of alcohol-metabolizing enzyme variants on lipid levels, as well as the interaction with alcohol intake, were selected. Data extraction was conducted independently by two investigators and confirmed by the third.Data AnalysisIn total, 86 studies (179 640 individuals) were analyzed. The A allele of rs671 (a functional variant in the ALDH2 gene) was linked to higher levels of low-density lipoprotein cholesterol (LDL-C) and lower levels of triglycerides and high-density lipoprotein cholesterol. In contrast, the A allele of the rs1229984 (a functional variant in the ADH2 gene) was associated only with lower levels of LDL-C. The effects of rs671 and rs1229984 on lipid levels were much stronger in Japanese than in Chinese individuals and in males than in females. Regression analysis indicated that the effects of rs671 on lipid levels were independent of alcohol intake in an integrated East Asian population (ie, Japanese, Chinese, and Korean individuals). Intriguingly, alcohol intake had a statistical influence on lipid levels when the sample analyzed was restricted to Japanese individuals or to males.ConclusionsThe rs671 and rs1229984 variants of alcohol-metabolizing enzymes have significant effects on lipid levels and may serve as genetic markers for lipid dyslipidemia in East Asian populations. Circulating lipid levels in Japanese individuals and in males were modulated by the interaction between rs671 and alcohol intake.
Is Symbolic Religious Establishment Permitted Within the European Convention? A Legal, Political, and Pragmatic Perspective
Authors: Pierik Roland 
Published: December 2022

Abstract
This article discusses the role of the European Court of Human Rights in regulating the symbolic establishment of religion by the Convention States in their public sphere. The analysis starts from the rather controversial Lautsi decisions and distinguishes three perspectives on such cases. The legal perspective focuses on the way the Court would usually answer a legal question underlying a controversial subject as an interpretation of the Convention and Protocols understood as the living instrument it is today. The political perspective focuses on the preferred solution of the democratic majority in the relevant the Convention State, which is sometimes diametrically opposed to the Court’s assessment. The pragmatic perspective explains how the Court deals with such clashes. In controversial cases, the Court sometimes is critical of the state for violating Convention rights, but remains, as a supranational court, critically dependent on the sufficient support of these states. This implies that the Court is sometimes forced to act pragmatically. To maintain the overall stability of the Convention system of human rights protection, the Court is sometimes required to make legally suboptimal decisions in specific controversial cases.
TheSymbiodiniumProteome Response to Thermal and Nutrient Stresses
Authors: Oakley Clinton A , Newson Grace I , Peng Lifeng , Davy Simon K 
Published: December 2022

AbstractCoral bleaching is primarily caused by high sea surface temperatures, and nutrient enrichment of reefs is associated with lower resilience to thermal stress and ecological degradation. Excess inorganic nitrogen relative to phosphate has been proposed to sensitize corals to thermal bleaching. We assessed the physiological and proteomic responses of cultures of the dinoflagellate coral symbiont Symbiodinium microadriaticum to elevated temperature under low-nutrient, high-nutrient and phosphate-limited conditions. Elevated temperature induced reductions of many chloroplast proteins, particularly the light-harvesting complexes, and simultaneously increased the abundance of many chaperone proteins. Proteomes were similar when the N:P ratio was near the Redfield ratio, regardless of absolute N and P concentrations, but were strongly affected by phosphate limitation. Very high N:P inhibited Symbiodinium cell division while increasing the abundance of chloroplast proteins. The proteome response to phosphate limitation was greater than that to elevated temperature, as measured by the number of differentially abundant proteins. Increased physiological sensitivity to high temperatures under high nutrients or imbalanced N:P ratios was not apparent; however, oxidative stress response proteins were enriched among proteins responding to thermal stress under imbalanced N:P ratios. These data provide a detailed catalog of the effects of high temperatures and nutrients on a coral symbiont proteome.
Carbohydrate vitrification in aerosolized saliva is associated with the humidity-dependent infectious potential of airborne coronavirus
Authors: Nieto-Caballero Marina , Davis Ryan D , Fuques Eddie , Gomez Odessa M , Huynh Erik , Handorean Alina , Ushijima Shuichi , Tolbert Margaret , Hernandez Mark 
Published: December 2022

Abstract
An accepted murine analogue for the environmental behavior of human SARS coronaviruses was aerosolized in microdroplets of its culture media and saliva to observe the decay of its airborne infectious potential under relative humidity (RH) conditions relevant to conditioned indoor air. Contained in a dark, 10 m3 chamber maintained at 22°C, murine hepatitis virus (MHV) was entrained in artificial saliva particles that were aerosolized in size distributions that mimic SARS-CoV-2 virus expelled from infected humans’ respiration. As judged by quantitative PCR, more than 95% of the airborne MHV aerosolized was recovered from microdroplets with mean aerodynamic diameters between 0.56 and 5.6 μm. As judged by its half-life, calculated from the median tissue culture infectious dose (TCID50), saliva was protective of airborne murine coronavirus through a RH range recommended for conditioned indoor air (60% &lt; RH &lt; 40%; average half-life = 60 minutes). However, its average half-life doubled to 120 minutes when RH was maintained at 25%. Saliva microaerosol was dominated by carbohydrates, which presented hallmarks of vitrification without efflorescence at low RH. These results suggest that dehydrating carbohydrates can affect the infectious potential coronaviruses exhibit while airborne, significantly extending their persistence under the drier humidity conditions encountered indoors.
Preoperative Exercise Has a Modest Effect on Postoperative Pain, Function, Quality of Life, and Complications: A Systematic Review and Meta-Analysis
Authors: Hayashi Kazuhiro , Janowski Adam , Lesnak Joseph B , Sluka Kathleen A 
Published: December 2022

Abstract

Objective
Preoperative exercise (prehabilitation) is commonly used as a method to reduce pain and improve function postoperatively. The purpose of this systematic review was to determine therapeutic benefits of preoperative exercise on postoperative pain, function, quality of life (QOL), and risk of complications across various types of surgeries.

Methods
Three electronic databases were used to perform a literature search. Full articles with randomized designs comparing a preoperative exercise program vs no formal program were included. The primary outcome was postoperative pain. QOL, function, and postoperative complications were analyzed as secondary outcomes. The primary meta-analysis was performed in those with joint replacement surgery because there were only 5 with other surgical types.

Results
A total of 28 articles were included, of which 23 were from individuals with total joint replacement surgery. Preoperative exercise resulted in lower pain ≤2 months and 3 to 5 months after joint replacement surgery with a moderate standardized mean difference (95% CI at &lt;2 months = −0.34 [−0.59 to −0.09]; at 3 to 5 months = −0.41 [−0.70 to −0.11]) compared with nonexercised controls. However, ≥6 months after joint replacement surgery, preoperative exercise groups showed no significant differences in postoperative pain (standardized mean difference = −0.17 [−0.35 to 0.01]) compared with nonexercised controls. QOL and subjective and objective function were improved ≤2 months after joint replacement surgery but were not different ≥6 months post-surgery. Reduction in risk of postoperative complications was favored with preoperative exercise.

Conclusion
Preoperative exercise has a modest effect on postoperative pain, function, and quality of life within the first 6 months after surgery and reduces the risk of developing postoperative complications in individuals undergoing joint replacement surgery. The effect of preoperative exercise on other surgery types is inconclusive.

Impact
This systematic review supports using preoperative exercise to improve pain and function outcomes for those with joint replacement surgery.
Overcoming separation between counterparts due to unknown proper motions in catalogue cross-matching
Authors: Wilson Tom J 
Published: December 2022

Abstract
To perform precise and accurate photometric catalogue cross-matches – assigning counterparts between two separate data sets – we need to describe all possible sources of uncertainty in object position. With ever-increasing time baselines between observations, like 2MASS in 2001 and the next generation of surveys, such as the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST), Euclid, and the Nancy Grace Romantelescope, it is crucial that we can robustly describe and model the effects of stellar motions on source positions in photometric catalogues. While Gaia has revolutionized astronomy with its high-precision astrometry, it will only provide motions for ≈10 per cent of LSST sources; additionally, LSST itself will not be able to provide high-quality motion information for sources below its single-visit depth, and other surveys may measure no motions at all. This leaves large numbers of objects with potentially significant positional drifts that may incorrectly lead matching algorithms to deem two detections too far separated on the sky to be counterparts. To overcome this, in this paper, we describe a model for the statistical distribution of on-sky motions of sources of given sky coordinates and brightness, allowing for the cross-match process to take into account this extra potential separation between Galactic sources. We further detail how to fold these probabilistic proper motions into Bayesian cross-matching frameworks, such as those of Wilson & Naylor. This will vastly improve the recovery of, for example, very red objects across optical-infrared matches, and decrease the false match rate of photometric catalogue counterpart assignment.
Why is Syria a War but Not Afghanistan? Nationality-based Aid and Protection in Turkey’s Syria Refugee Response
Authors: Almasri Shaddin 
Published: December 2022

Abstract
This article argues that, following the most recent influx of Syrians, refugee reception and aid policies in Turkey has shifted to be differentiated depending on the nationality of refugee groups. This research relies on a case study methodology and assesses changes in reception and aid access policies undertaken in Turkey post the Syrian influx and European Union (EU)–Turkey deal. In doing so it critically analyses differentiated access by refugee nationality, specifically Syrians and Afghans. This begins with an analysis of differences between refugee groups in how protection status is issued, followed by an investigation of differentiated access to programmes and assistance, and the role that EU-led negotiations and aid programmes play in re-enforcing Syrian-focused inclusion. Through a methodology that combines a review of law, policy and relevant literature and semi-structured interviews with key informants, this article makes two conclusions: first, that policies in Turkey unfolded to differentiate and distinguish Syrian refugees, against other refugee groups, as part of the response to the influx. Secondly, as objects of migration diplomacy between the EU and Turkey, aid and assistance programmes for refugees were also distinct by citizenship and re-enforced this differentiation, characterising the response by a condition of nationality-based aid.
Erbb4Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes
Authors: Kiemes Amanda , Serrano Navacerrada Maria Elisa , Kim Eugene , Randall Karen , Simmons Camilla , Rojo Gonzalez Loreto , Petrinovic Marija-Magdalena , Lythgoe David J , Rotaru Diana , Di Censo Davide , Hirschler Lydiane , Barbier Emmanuel L , Vernon Anthony C , Stone James M , Davies Cathy , Cash Diana , Modinos Gemma 
Published: December 2022

AbstractBackground and HypothesisConverging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice.Study DesignHere, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography.ResultsErbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified.ConclusionsThese findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.
The Effects of Tinnitus and Tinnitus Annoyance on Need for Recovery After Work: Results of the Netherlands Longitudinal Study on Hearing
Authors: Simons Iris A. , Goderie Thadé , Lissenberg-Witte Birgit I. , Versfeld Niek J. , Kramer Sophia E. , van Wier Marieke F. 
Published: December 2022

Objectives:
The first aim of this study was to examine the relationship between having tinnitus and the need for recovery after work (NFR). The second aim was to investigate whether the level of tinnitus annoyance is associated with NFR.

Design:
Data from the 5- and 10-year follow-up measurement rounds of the Netherlands Longitudinal Study on Hearing (NL-SH) were used in a cross-sectional analyses. The NL-SH is a web-based prospective cohort study and includes participants aged 18 to 70 years at baseline. For this study, we included only participants who worked at least 12 hours/week and were under the age of 65 years. Participants completed questionnaires on demographic, socioeconomic, psychosocial, hearing-related, and work-related characteristics. In addition, participants answered questions about hearing ability and tinnitus and performed an online digit-triplet speech recognition in noise test to measure the speech reception threshold (SRT) in noise. Participants were asked if (1) they suffer from tinnitus and (2) to rate tinnitus annoyance on a 0-100 numeric rating scale. A linear mixed model was used (1) to estimate the overall (i.e., cross-sectional) association between having tinnitus and NFR and (2) to estimate the overall association between the level of tinnitus annoyance and NFR. The models were checked for effect modification and confounding of factors known to be associated with either tinnitus or NFR and available in the NL-SH.

Results:
The study sample comprised 770 unique participants in total; 686 and 335 participants at 5- and 10-year follow-up, respectively. Distress, somatization, and self-reported hearing disability appeared to be confounding factors in the analysis of having tinnitus and NFR. After adjusting for these factors, participants with tinnitus had a 2.5% higher NFR (95% confidence interval: −0.9 to 5.9; p = 0.15). In the analysis of tinnitus annoyance and NFR, SRT was an effect modifier. Distress, somatization, depression, and self-reported hearing disability were confounders. After adjustment for effect modification and confounding, tinnitus annoyance was not significantly associated with NFR (p = 0.79 for tinnitus annoyance).

Conclusions:
This study showed that having tinnitus was not associated with a higher NFR. Also, higher levels of tinnitus annoyance were not associated with a higher NFR. NFR was associated with the psychological factors distress, somatization, and depression, which are known to be intricately related to tinnitus. A longitudinal study design is recommended as it can assess the sequence of events, which might help disentangle the association between tinnitus, NFR, and psychological factors.
The changes that occur in the immune system during immune activation in pre-diabetic patients of all ethnicities, from the age of 25- to 45-years: A systematic review and meta-analysis
Authors: Mzimela Nomusa Christina , Sosibo Aubrey Mbulelo , Ngubane Phikelelani Siphosethu , Khathi Andile 
Published: December 2022

Background:
Pre-diabetes is an intermediate state between normoglycaemia and type 2 diabetes (T2D). This condition has been shown to be asymptomatic thus making it hard to investigate the changes that occur in the body during this state. Recent findings stipulate that in this state, there are changes that are often associated with T2D. These include changes in concentration of immune cells and inflammatory markers. This systematic review will provide a synthesis of the data that is available reporting on the changes in the concentration of immune cells and selected markers during prediabetes. It will also give clarity of the variation of the complications of the condition among the various demographic groups.

Methods:
The assembly of this systematic review was through strict adherance to the PRISMA 2020 guidelines for reporting systematic reviews. This systematic review has been registered with the International Prospective Registry of Systematic Reviews (PROSPERO), registration number “CRD42020184828” dated 05-07-2020). In this systematic review, published clinical studies articles that involve observational reports, whether it is case-control, cross-sectional, and comparative cross-sectional will be used. Cohort study designs that involve normal/non-diabetic and pre-diabetes reports will be used in this systematic review and meta-analysis. Clinical MeSH headings to search on MEDLINE, COCHRANE library, EMBASE, and ICTRP and African Journal Online will be a tool used to achieve the required report. Reviewers (NCM, AMS, and AK) will screen all the results and select the studies that will be eligible by guidance according to eligibility criteria. Downs and Black Checklist will be used to check the risk of bias and then for meta-analysis Review Manager v5.4 Forrest plot will be used. Additionally, the Forrest plot will also be used for sensitivity analysis. The strength of evidence will then be assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results:
Only 4 reports were eligible and risk of bias checked. The results indicated the outcomes even though there were only few reports.

Discussion and conclusion:
This systematic review will give an indication on the available data on this research area and lay a foundation for future studies.