bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of lifestyle risk factors on admission to nursing home care: a cohort study of 127 108 people aged 60 years and over
Authors: Gibson Alice A , Gale Joanne , Stamatakis Emmanuel , Lindley Richard I , Fontana Luigi , Cistulli Peter A , Nassar Natasha 
Published: August 2023

BackgroundLittle is known on how lifestyle factors, individually or in combination, may relate to nursing home admission, an outcome of great societal and economic importance with increased population ageing. The aim of this study was to determine the association of lifestyle risk factors with nursing home admission.MethodsThis prospective cohort study linked data from the 45 and Up Study, Australia, to health records. 127 108 men and women, aged ≥60 years, were recruited between 2006 and 2009. A healthy lifestyle score categorised participants into three risk groups based on five equally contributing risk factors: smoking status, physical activity, sedentary behaviour, sleep duration and diet quality. HRs for incident nursing home admission were estimated using multivariable Cox proportional hazards model.ResultsOne-quarter of participants were in the low-risk lifestyle group, 62% were in the medium-risk group and 14% in the high-risk (least healthy) group. During a median (IQR) follow-up of 11.3 years, 23 094 (18%) participants were admitted to a nursing home. Compared with those in the low-risk group, risk of nursing home admission was 43% higher among participants in the high-risk group (multivariable adjusted HR (aHR) 1.43; 95% CI 1.36 to 1.50); and participants in the medium-risk group had an intermediate 12% greater risk (aHR 1.12; 95% CI 1.08 to 1.16). Participants aged 60–64 years in the high-risk (aHR 2.15; 95% CI 1.82 to 2.54) lifestyle group had the greatest risk of nursing home admission.ConclusionAn unhealthy lifestyle was associated with a marked increased risk of admission to a nursing home in adults aged 60+ years. Interventions focused on lifestyle modifications may prevent or delay nursing home admission.
Effect of oculomotor exercises in patients with non-specific chronic neck pain and associated visual complaints
Authors: Aggarwal Amita , Thakur Jidnyasa , Palekar Tushar J 
Published: August 2023

Background: Neck pain is a common musculoskeletal disorder, the most common type being non-specific chronic neck pain. It usually involves postural or mechanical causes. In Individuals with neck pain, a notable prevalence of visual complaints has been predominantly reported. It can be linked to the mismatch in the cervical afferent output. Objective: This study aimed to assess the effect of oculomotor exercises on neck pain, neck disability, gaze stability and visual complaints among individuals with non-specific chronic neck pain and associated visual complaints. Methods: A total of 32 individuals with non-specific chronic neck pain and associated visual complaints were equally randomised into two groups. To receive either: stretching to the sternocleidomastoid and anterior scalene along with neck Isometric exercises (Group A, conventional) or the conventional protocol along with oculomotor exercises (Group B, experimental). The protocol was given for three alternate days a week for three weeks, a total of nine sessions. The outcome measures were the Visual Analogue Scale (VAS) for pain, Neck Disability Index (NDI) for disability, Dynamic Visual Acuity (DVA) test for gaze stability and Visual Complaints Index (VCI) for visual complaints. Results: Significant results were seen for the DVA ([Formula: see text]) and VCI ([Formula: see text]), suggesting improvements in gaze stability and visual complaints using oculomotor exercises. Conclusion: From this study, we highlighted that oculomotor exercises along with conventional treatment led to improvement in visual complaints and gaze stability in patients with non-specific chronic neck pain and associated visual complaints.
The Application of Teachings by the International Court of Justice, 2016–2022
Authors: Helmersen Sondre Torp 
Published: August 2023

Abstract
This article examines the application of teachings by the International Court of Justice between 2016 and 2022. The Court did not cite teachings in its majority opinions during this period. It did cite works from the International Law Commission, which suggests that these are considered different from teachings and possibly have more weight. Judges cited teachings in their individual opinions. Judge Cançado Trindade stands out as a judge with a particularly high citation rate. Teachings played a wide variety of functions in individual opinions, from the classical functions of aiding the interpretation of a treaty and the ascertainment of a rule of customary international law, to a range of other specialized functions such as the interpretation of other texts, in particular judicial decisions, methodological and historical points, and showing the purpose of a rule of instrument, in addition to providing reflections on the role of the international judiciary itself. The article also examines the demographics of the most-cited writers, finding that most of them are men from Western States. The article compares the judges’ practice with findings from prior to 2016 and other international courts and tribunals.
Fact-Finding by Trade-off: Questions of Evidence and Its Interactions with Valuation in Compensation Cases before the International Court of Justice
Authors: Nakajima Kei 
Published: August 2023

Abstract
This article discusses the evidentiary issues that arise at the compensation phase of the proceedings in the International Court of Justice (‘the Court’), with special reference to the intersection of the rules of evidence and the law of State responsibility concerning reparations. It identifies a sequence of interactions between the two sets of norms throughout the compensation phase and even the prior merits stage. Various notions and approaches indicated by the Court that fall into either of the two sets of rules, such as the reversal of the burden of proof, lowering the standards of proof, equitable considerations and the global sum, should thus be read in conjunction with each other and not in isolation. Such an interplay aims ultimately to bring about a financial outcome that may afford minimum satisfaction to both parties in a dispute, even at the sacrifice of the coherence of judicial reasoning to some extent. In particular, the trade-off between the questions of proof and the reduction of the amount of compensation is seen as a practical adjustment of the financial outcome that could otherwise be unacceptable for the responsible State in the situation of evidentiary uncertainties. The remedies brought to the injured party might be minimal, but an invented alternative to nothing, which could have been the case had the rules of evidence and compensation been ordinarily applied.
Revisiting the Standard of Proof for Charges of Exceptional Gravity before the International Court of Justice
Authors: Bills Amanda 
Published: August 2023

Abstract
The International Court of Justice has consistently required a stricter standard of proof for ‘charges of exceptional gravity’. The Bosnia Genocide and Croatia Genocide cases saw the Court require the high standard of ‘fully conclusive’ evidence across all elements of the allegations of genocide. Despite the difficulties associated with obtaining the necessary evidence of the intent of the perpetrators to destroy, in whole or in part, a protected group to establish the commission of genocide, the Court allowed little flexibility in the application of that standard in what may have been a departure from its previous cases relating to grave charges. The Court emphasized the gravity of the allegations and the high stigmatization attached to a finding of responsibility for genocide, suggesting a strong emphasis on the consequences of a finding of responsibility for the wrongdoing State over other interests that may also have been present in the proceedings. The Court has yet to explain the rationale for the high standard of proof applied to charges of exceptional gravity in international judicial proceedings, or why it required a particularly stringent standard of proof in the Genocide cases. This raises questions about the Court’s approaches to the standard of proof and the process by which it balances different interests in judicial proceedings. As States seek out the Court’s jurisdiction for serious breaches of international law – including, for example, the pending Rohingya Genocide case – the Court’s strict approach to the standard of proof risks imposing a high bar to the enforcement of these obligations.
Convection-Permitting Simulations of Precipitation over the Peruvian Central Andes: Strong Sensitivity to Planetary Boundary Layer Parameterization
Authors: Huang Yongjie , Xue Ming , Hu Xiao-Ming , Martin Elinor , Novoa Hector Mayol , McPherson Renee A. , Perez Andres , Morales Isaac Yanqui 
Published: August 2023

Abstract
Regional climate dynamical downscaling at convection-permitting resolutions is now practical and has the potential to significantly improve over coarser-resolution simulations, but the former is not necessarily free of systematic biases. The evaluation and optimization of model configurations are therefore important. Twelve simulations at a grid spacing of 3 km using the WRF Model with different microphysics, planetary boundary layer (PBL), and land surface model (LSM) schemes are performed over the Peruvian central Andes during the austral summer, a region with particularly complex terrain. The simulated precipitation is evaluated using rain gauge data and three gridded precipitation datasets. All simulations correctly capture four precipitation hotspots associated with prevailing winds and terrain features along the east slope of the Andes, though they generally overestimate the precipitation intensity. The simulation using Thompson microphysics, Asymmetric Convection Model version 2 (ACM2) PBL, and Noah LSM schemes has the smallest bias. The simulated precipitation is most sensitive to PBL, followed by microphysics, and least sensitive to LSM schemes. The simulated precipitation is generally stronger in simulations using the YSU rather than the MYNN and ACM2 schemes. All simulations successfully capture the diurnal precipitation peak time mainly in the afternoon over the Peruvian central Andes and in the early morning along the east slope. However, there are significant differences over the western Amazon basin, where the precipitation peak occurs primarily in the late afternoon. Simulations using YSU exhibit a 4–8-h delay in the precipitation peak over the western Amazon basin, consistent with their stronger and more persistent low-level jets. These results provide guidance on the optimal configuration of a dynamical downscaling of global climate projections for the Peruvian central Andes.
A Comparison of the Impacts of Inner-Core, In-Vortex, and Environmental Dropsondes on Tropical Cyclone Forecasts during the 2017–20 Hurricane Seasons
Authors: Ditchek Sarah D. , Sippel Jason A. 
Published: August 2023

Abstract
This study conducts the first large-sample comparison of the impact of dropsondes in the tropical cyclone (TC) inner core, vortex, and environment on NWP-model TC forecasts. We analyze six observing-system experiments, focusing on four sensitivity experiments that denied dropsonde observations within annuli corresponding with natural breakpoints in reconnaissance sampling. These are evaluated against two other experiments detailed in a recent parallel study: one that assimilated and another that denied dropsonde observations. Experiments used a basin-scale, multistorm configuration of the Hurricane Weather Research and Forecasting (HWRF) Model and covered active periods of the 2017–20 North Atlantic hurricane seasons. Analysis focused on forecasts initialized with dropsondes that used mesoscale error covariance derived from a cycled HWRF ensemble, as these forecasts were where dropsondes had the greatest benefits in the parallel study. Some results generally support findings of previous research, while others are novel. Most notable was that removing dropsondes anywhere, particularly from the vortex, substantially degraded forecasts of maximum sustained winds. Removing in-vortex dropsondes also degraded outer-wind-radii forecasts in many instances. As such, in-vortex dropsondes contribute to a majority of the overall impacts of the dropsonde observing system. Additionally, track forecasts of weak TCs benefited more from environmental sampling, while track forecasts of strong TCs benefited more from in-vortex sampling. Finally, inner-core-only sampling strategies should be avoided, supporting a change made to the U.S. Air Force Reserve’s sampling strategy in 2018 that added dropsondes outside of the inner core.

Significance Statement
This study uses a regional hurricane model to conduct the most comprehensive assessment to date of the impact of dropsondes at different distances away from the center of a tropical cyclone (TC) on TC forecasts. The main finding is that in-vortex dropsondes are most important for intensity and outer-wind-radii forecasts. Particularly notable is the impact of dropsondes on TC maximum wind speed forecasts, as reducing sampling anywhere would degrade those forecasts.
A randomized, open-label, cross-over pilot study investigating metabolic product kinetics of the palatable novel ketone ester, bis-octanoyl (R)-1,3-butanediol, and bis-hexanoyl (R)-1,3-butanediol ingestion in healthy adults
Authors: Stubbs Brianna J , Cook Chad , Blonquist Traci M , Taggart Kristen , Beckman Dawn , Kruger Claire , Conze Dietrich , Boileau Amy C 
Published: August 2023

Introduction Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel, palatable ketone ester that, when consumed, is hydrolyzed in the gastrointestinal tract into octanoic acid (OCT) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Metabolism of BO-BD is hypothesized to be similar to bis-hexanoyl (R)-1,3-butanediol (BH-BD), apart from release of octanoic acid instead of hexanoic acid (HEX). Methods As part of the safety assessment for BO-BD a randomized, cross-over, open-label study in middle-aged, healthy adults ( n = 12) was undertaken to provide a qualitative comparison of plasma BHB, OCT, HEX and BDO concentrations for 8 h following consumption of 12.5 or 25 g of BO-BD and 12.5 g of BH-BD. Results All study products increased plasma BHB and BDO up to 4 h post-consumption. BH-BD increased HEX, whereas BO-BD increased OCT. All kinetic parameters for BHB and BDO were similar between 12.5 g servings of BH-BD and BO-BD while Cmax and AUC for OCT were higher following 12. 5 g servings of BO-BD as compared to HEX with 12.5 g of BH-BD. All metabolites returned to baseline by 8 h post-consumption. BHB, BDO and OCT Cmax and AUC were increased with serving size of BO-BD from 12.5 to 25 g. Sensory acceptability scores of BO-BD were significantly higher than for BH-BD. An in vitro hydrolysis experiment using human blood plasma further confirmed that plasma esterases possess the ability to break down the novel ketone esters into BDO, and OCT or HEX. Discussion The two novel ketone ester molecules exhibit similar metabolic breakdown to BHB and BDO and result in transiently higher concentrations of the plasma fatty acids, OCT and HEX, in vivo. Conclusions Given the similar ketone delivery with greater acceptability, BO-BD may offer a more broadly translatable tool to induce physiologic ketosis than BH-BD.
Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments
Authors: Adams David , Algalarrondo Vincent , Echaniz-Laguna Andoni 
Published: August 2023

Abstract
Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR, also known as prealbumin. ATTRv survival ranges from 3 to 10 years, and peripheral nervous system and heart are usually the 2 main tissues affected, although central nervous system and eye may also be involved. Because the liver is the main TTR protein secretor organ, it has been the main target of treatments developed these last years, including liver transplantation, which has been shown to significantly increase survival in a subset of patients carrying the so-called “early-onset Val30Met” TTR gene mutation. More recently, treatments targeting hepatic TTR RNA have been developed. Hepatic TTR RNA targeting is performed using RNA interference (RNAi) and antisense oligonucleotide (ASO) technologies involving lipid nanoparticle carriers or N-acetylgalactosamine fragments. RNAi and ASO treatments induce an 80% decrease in TTR liver production for a period of 1 to 12 weeks. ASO and RNAi phase 3 trials in patients with TTR-related polyneuropathy have shown a positive impact on neuropathy clinical scores and quality of life end points, and delayed RNAi treatment negatively affects survival. Clinical trials specifically investigating RNAi therapy in TTR cardiomyopathy are underway. Hepatic RNA targeting has revolutionized ATTRv treatment and may allow for the transforming a fatal disease into a treatable disorder. Because retina and choroid plexus secrete limited quantities of TTR protein, both tissues are now seen as the next targets for fully controlling the disease.
Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia
Authors: Zhang Qi , Li He , Chen Xuelan , Gu Fan , Zhang Lanxin , Zhang Lu , Chen Tong , Chen Qiang , Meng Wentong , Wu Yu , Chang Hong , Liu Ting , Chen Chong , Ma Hongbing , Liu Yu 
Published: August 2023

Abstract
Here we report a new fusion gene, STRN3-RARA, in acute promyelocytic leukemia (APL). It cooperates with UTX deficiency to drive full-blown APL in mice. Although STRN3-RARA leukemia quickly relapses after all-trans retinoic acid treatment, it can be restrained by cepharanthine.
The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor
Authors: Stanger Livia , Yamaguchi Adriana , Yalavarthi Pooja , Lambert Sylviane , Gilmore Devin , Rickenberg Andrew , Luke Catherine , Kumar Kiran , Obi Andrea T. , White Andrew , Bergh Niklas , Dahlöf Björn , Holinstat Michael 
Published: August 2023

Abstract
Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.
Treatment strategy for acquired pure red cell aplasia: a systematic review and meta-analysis
Authors: Lobbes Hervé , Lega Jean-Christophe , Le Guenno Guillaume , Ruivard Marc , Mainbourg Sabine 
Published: August 2023

Abstract
The treatment of autoimmune acquired pure red cell aplasia (aPRCA) is challenging. Guidelines are based on expert recommendations in the absence of controlled trials. We assessed the efficacy of the main treatment strategy through a systematic review and meta-analysis using MEDLINE, EMBASE, and the Cochrane Library up to September 2022. The overall response rate (ORR) was pooled using random-effects models. In total, 24 observational studies (19 retrospective, median follow-up of 48 months) encompassing 753 patients (49% male) were included. Primary aPRCA represented 57% of the cases. The risk of bias was moderate to high using the ROBINS-I tool. Substantial heterogeneity (I2 &gt; 50%) was retrieved. Corticosteroids as monotherapy as first-line treatment (186 patients, 13 studies) provided an ORR of 47% (95% confidence interval [CI], 34-60). Cyclosporine A was the most frequently used immunosuppressant agent (384 patients, 18 studies), providing an ORR of 74% (95% CI, 66-82) with a similar ORR in first- (73%) and second-line (76%) treatment and when cyclosporin was used as monotherapy (83%) or with corticosteroids (77%). A total of 112 patients (10 studies) received cyclophosphamide, with an ORR of 49% (95% CI, 35-64), which was higher when cyclophosphamide was combined with corticosteroids (48%) and used in second-line treatment (58%) than in monotherapy (31%), and in first-line treatment (44%). Sirolimus use was reported only after cyclosporine A failure and provided an ORR of 87% (95% CI, 68-100; 64 patients, 3 studies). Substantial uncertainty remains regarding the best treatment strategy in the absence of high-quality evidence. This study was registered on the PROPERO database as #CRD42022360452.
Elevated galectin-3 levels detected in women with hyperglycemia during early and mid-pregnancy antagonizes high glucose − induced trophoblast cells apoptosis via galectin-3/foxc1 pathway
Authors: Deng Yu , Jin Hongyan , Ning Jie , Cui Dong , Zhang Muqiu , Yang Huixia 
Published: August 2023

Abstract
Objective
This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure.

Methods
The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein–protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry.

Results
Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose − induced apoptosis.

Conclusion
Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy.

Graphical Abstract