bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration
Authors: Öztürk Muhammet M , Emgård Jakob , García-Revilla Juan , Fernández-Calle Rosalía , Yang Yiyi , Deierborg Tomas , Roos Tomas T 
Published: February 2025

Abstract
Numerous neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS (amyotrophic lateral sclerosis) share a neuropathological hallmark: aberrant protein aggregation in the CNS (central nervous system). Microglia, the brain’s innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer’s disease, Parkinson’s disease, and ALS. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighboring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.
Global, regional, and national burden of pulmonary arterial hypertension and related heart failure from 1990 to 2021, with predictions to 2050: insights from the global burden of disease study 2021
Authors: Liu Ke , Zeng Yi , Wang Hualing , Yang Huiping , Liu Lida , Chen Xingyu , Yang Xiuli , Liu Yufei , Zhu Yi , Zhang Chuantao 
Published: February 2025

Abstract

Background
Pulmonary arterial hypertension (PAH) and PAH-related heart failure (PAH-HF) have undergone significant epidemiological changes since 1990. However, large-scale studies are scarce. This study evaluates global epidemiologic trends from 1990 to 2021 and projects them to 2050 to inform public health policies.

Methods
Data on the incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of PAH and PAH-HF were analyzed using models like joinpoint regression, bayesian age-period-cohort and decomposition analysis. Trends were reported by sex, age group, and geographic region, with projections extending to 2050.

Results
In 2021, the global age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate (ASDR) for PAH were 0.52, 2.28, 0.27, and 8.24 per 100 000 population, respectively. Compared to 1990, ASIR and ASPR increased, while ASDR and ASMR declined. Females showed higher burdens in nearly all outcomes. In 2021, Zambia and Switzerland had the highest ASIR and ASPR of PAH, while Mongolia recorded the highest ASMR and ASDR. For PAH-HF, the number of prevalent cases and years lived with disability from 1990 to 2021, though most heart failure subtypes showed declines in ASPR. Decomposition analysis attributed increases in PAH incidence, prevalence, and DALYs primarily to population growth, while aging primarily drove increases in deaths. Future projections suggest continued growth in ASIR but declines in other burden indicators after 2021.

Conclusions
From 1990 to 2021, the global burden of PAH and PAH-HF increased, with significant gender disparities. These results provide valuable guidance for healthcare strategies and resource allocation.
The Patient Journey in Chronic Coronary Syndromes with/without Obstructive Coronary Arteries
Authors: La Sarena , Tavella Rosanna , Wu Jing , Spertus John A , Pasupathy Sivabaskari , Girolamo Olivia , Zeitz Christopher , Worthley Matthew , Arstall Margaret , Sinhal Ajay , Beltrame John 
Published: February 2025

Abstract

Background
In patients undergoing invasive coronary angiography for the investigation of angina, the management pathways for obstructive coronary artery disease (CAD) are well described, whereas the clinical and diagnostic journey of patients with ANOCA has largely been inferred, as there is limited quantitative data.

Objectives
To compare the journey of patients with ANOCA versus Obstructive CAD, particularly in relation to (i) clinical presentation and (ii) diagnostic assessment, (iii) 12 month patient-reported outcome measures (PROMs) and (iv) three year composite MACE

Methods
A total of 2,285 ANOCA and 4,087 Obstructive CAD consecutive patients were included from the CADOSA (Coronary Angiogram Database of South Australia) registry between 2012-2018.

Results
At presentation for elective invasive angiography, the chest pain features and non-invasive ischemic markers were indistinguishable between patients with Obstructive CAD and ANOCA, although the latter were younger (67±11 vs. 61 ± 11 years, p&lt;0.001), more likely to be female (27% vs. 58%, p&lt;0.001) and have fewer traditional cardiac risk factors. However, following angiography (compared to those with Obstructive CAD) patients with ANOCA were less likely to attain a cardiac discharge diagnosis (100% vs. 22%) or receive anti-anginal therapy (76% vs. 57%), despite the same prevalence of persistent angina (weekly angina: 10% vs 11% over 12 months).

Conclusions
Although the pre-angiography journey (symptoms & non-invasive ischemic investigations) of patients with Obstructive CAD and ANOCA is indistinguishable, the post-angiography journey is portrayed by a vast diagnostic and treatment gap in those with ANOCA, which needs to be addressed.
Multiple domestication centres of the Indian pig population
Authors: Desai Shailesh , Singh Prajjval Pratap , Pandey Rudra Kumar , Mishra Rahul Kumar , Chaubey Akhilesh Kumar , Kumar Ajit , Tiwary Sachin Kr , Gupta Sandeep , Achilli Alessandro , Rambaldi Migliore Nicola , Chaubey Gyaneshwer 
Published: February 2025

Abstract
The domestication of animals is a major milestone in human history and has been studied in various fields. Pig domestication, in particular, has been widely studied, and it is believed that India is one of at least six domestication centers. However, there is a lack of systematic studies using high-resolution genetic markers, including complete mitogenomes, to investigate the domestication and genetic roots of pigs in India. In the present study, we investigated the origin and evolution of Indian pigs using mitochondrial genetic data to complement archaeological datasets. The phylogenetic status of Indian pig breeds was determined by analyzing all available mitochondrial data, incorporating a global dataset of 239 mitogenomes. The Bayesian and maximum likelihood tree analyses unveiled at least eight haplogroups diverging from three main branches, two of which are geographically restricted to India. We propose that the North Indian domestic haplogroup might represent an independent in-situ domestication event in North India, probably dating before ∼5,000 YBP. An additional North East Indian domestic haplogroup is nested within a widespread Asian clade that also includes Indian mitogenomes from the Andaman and Nicobar Islands that diverged more recently from distinct East and Southeast Asian roots. In conclusion, we propose that North Indian farmers could have been responsible for the independent domestication of local wild boars giving rise to the current domestic lineage identified in North India. At least one additional domestic lineage arrived in India more recently and remained mainly localized in the northeast. Domestic mitogenomes from the Indian islands show a notable connection with pig populations from Vietnam, and their arrival might be related to Austroasiatic-speaking human populations. Overall, this study provides valuable insights into the complex dynamics of pig domestication in India.
Ethylene positively regulates anthocyanin synthesis in 'Viviana' lily via the LvMYB5-LvERF113-LvMYB1 module
Authors: Zhang Yibing , Sun Yibo , Du Weifeng , Sun Shaokun , Zhang Shimiao , Nie Mengyao , Liu Yudong , Irfan Muhammad , Zhang Li , Chen Lijing 
Published: February 2025

Abstract
Ethylene (ET) influences the synthesis of anthocyanins, although its regulatory effects can differ significantly across various plant species. In apples (Malus domestica), ET promotes anthocyanin synthesis, whereas in Arabidopsis thaliana, it inhibits its accumulation. Our research showed that ethephon (Eth), an ET derivative, promotes anthocyanin synthesis in 'Viviana' lilies, which has great potential in the cut flower industry. The regulatory mechanism whereby ethylene influences anthocyanin synthesis in lilies remains unclear. In this study, we screened and characterized an ET-induced ET response factors (ERFs), LvERF113, with inhibitory function. Our analyses suggested that LvERF113 could inhibit the negative regulatory function of LvMYB1 at transcriptional and posttranslational levels, promoting anthocyanin synthesis in 'Viviana' lily tepals. In addition, LvERF113 is positively regulated by LvMYB5, forming the LvMYB5-LvERF113-LvMYB1 module controlling anthocyanin synthesis by ET in 'Viviana' lily. These findings offer new insights into the ET regulatory network of anthocyanin synthesis and provide a theoretical basis for the application of ET derivatives in the cut flower industry.
Building Reparations: Key Factors for Success in Transitional Justice Efforts
Authors: Southey Safia K 
Published: February 2025

ABSTRACT
Amidst the focus on traditional postconflict justice mechanisms, the significance of financial compensation warrants reevaluation. This research investigates the dearth of literature on reparations, seeking to unravel the circumstances that led to successful administrative reparation programs for intrastate human rights violations. Through an analysis of 32 historical cases across 20 countries, this study highlights political motivations and financial stability as key factors shaping reparations’ success, using Argentina and Nepal to illustrate how reparations can be implemented across different contexts. Recognizing that political calculations underpin the birth of nearly all implemented programs, a novel categorization system emerges, encompassing three overlapping motivators: legal obligation, protection of power and personal/political gain. Within this framework, understanding these motivators becomes imperative for the establishment of effective policies.
Molecular Evolution of Nucleoside Deoxyribosyl Transferase (NDT) to Enhance the Activity towards 2’-Fluoro-2’-Deoxynucleoside
Authors: Yang Su-Been , Yoo Yeon-Jin , Choi Kanghyun , Kim Byungkyun , Choi Si-Sun , Kang Seung-Hoon , Kim Eung-Soo 
Published: February 2025

Abstract
Nucleoside deoxyribosyl transferase (NDT) is an enzyme that catalyzes the transfer of purine and pyrimidine bases between 2'-deoxyribonucleosides and is widely used for synthesizing nucleoside analogs in various biotechnological applications. While NDT exhibits high activity toward natural nucleosides, its activity toward unnatural nucleoside analogs is significantly lower. Previously, the NDT mutant named fNDT(L59Q) was identified displaying 4.4-fold higher activity toward 2'-fluoro-2'-deoxyuridine (2FDU). In this study, molecular evolution strategies using error-prone PCR were employed to further generate mutant enzymes with enhanced activity toward 2FDU. After two rounds of mutational screening, two mutant clones that exhibited high activity against 2FDU were identified as fNDT-i1 (V52A) and fNDT-i2 (L28I), respectively. A double mutant fNDT-i4, was subsequently constructed by combining the V52A and L28I mutations. Whole-cell-based activity measurements showed that fNDT-i4 exhibited 4.0-fold and 20.6-fold higher activity at 40°C and 50°C, respectively, compared to the wild-type NDT. The detailed characterization of the purified enzymes conducted under various conditions, including temperature, pH, thermal stability, and enzyme kinetics experiments, showed that fNDT-i1 and fNDT-i4 exhibited 3.1- and 3.7-fold higher catalytic efficiency, respectively than wild-type NDT. The L59Q mutation was identified as a key factor in improving the thermal stability, whereas the V52A and L28I mutations were critical for improving substrate affinity and reaction efficiency. These findings provide the potential of fNDT-i1 and fNDT-i4 as highly efficient biocatalysts for developing industrially relevant nucleoside analog synthesis.
Obinutuzumab maintenance versus observation for patients with newly diagnosed high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy: a multicenter, randomized, phase III study (JCOG2008, MAIN study)
Authors: Kobayashi Tsutomu , Ishizawa Kenichi , Machida Ryunosuke , Sadachi Ryo , Sasaki Keita , Kim Haryoon , Kataoka Keisuke , Munakata Wataru , Fukuhara Noriko , Nagai Hirokazu ,   Lymphoma Study Group of the Japan Clinical Oncology Group
Published: February 2025

Abstract
Maintenance therapy with monoclonal anti-CD20 antibody is the standard approach in patients with follicular lymphoma who initially treated and achieved response to immunochemotherapy. Maintenance therapy reduces the risk of lymphoma progression, but the risk of late or delayed fatal treatment-emergent adverse events is a clinically important issue. The aim of this randomized phase III study is to confirm the non-inferiority of observation compared to obinutuzumab maintenance therapy in patients with untreated high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy (JCOG2008, MAIN study). The first registration is performed before obinutuzumab plus bendamustine administration. Those who achieved complete metabolic response at the end of induction are included in the second registration and randomized to an obinutuzumab maintenance arm or observation only. This study has been registered in the Japan Registry for Clinical Trials as jRCT1031210379.
Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved
Authors: Ouimet Charlotte , Fodor Bianca , Del Paggio Joseph C , Kimmelman Jonathan 
Published: February 2025

Abstract

Background
Many patients enroll in phase 1 dose expansion cohorts or phase 2 clinical trials (together referred to below as “phase 2”) seeking access to novel treatments. Little is known about the extent to which they benefit by enrolling. Herein, we use a novel metric of benefit—therapeutic proportion—to assess the probability that patients in phase 2 trials receive treatment that eventually advances to FDA (Food and Drug Administration) approval for their condition.

Methods
We randomly sampled 400 trials identified in a search of Clinicaltrials.gov for cancer phase 2 trials initiated between November 1, 2012 and November 1, 2015. We determined whether the drug/dose/indication tested in each trial advanced to FDA approval within 7.5 years. We determined whether the drug/dose/indication presented substantial clinical benefit using the ESMO-MCBS (European Society for Medical Oncology - Magnitude of Clinical Benefit Scale), or whether it received off-label recommendation in NCCN (National Comprehensive Cancer Network) guidelines.

Results
Collectively, trials in our sample enrolled 25 002 patient-participants in 608 specific treatment cohorts. A total of 4045 patients received a treatment that advanced to FDA approval (16.2%; 95% CI = 10.3 to 22.7). The therapeutic proportion increased to 19.4% (95% CI = 14.1 to 25.8) when considering NCCN off-label recommendations and decreased to 9.3% (95% CI = 4.7 to 14.6) for FDA-approved regimens considered being of substantial clinical benefit by ESMO-MCBS. Bootstrap test of mean difference showed no statistical difference in proportions based on drug class, trial phase, or sponsorship.

Conclusion
One in 6 patients in phase 2 clinical trials receives treatments that are eventually approved. This represents a higher therapeutic value than phase 1 trials.
Assessment of TB Infection-Related Outpatient Clinical Outcomes Across Neighborhood-Level Deprivation Quartiles
Authors: Day Melissa E , Duan Qing , Burkhardt Mary Carol , Klein Melissa , Schlaudecker Elizabeth P , Beck Andrew F 
Published: February 2025

Abstract

Background
Pediatric tuberculosis infection (TBI) disproportionately affects those in complex social situations. Neighborhood characteristics may influence access to care and TBI-related outcomes. We sought to examine links between neighborhood-level socioeconomic deprivation and clinical outcomes.

Methods
In this retrospective cohort study, we identified children with TBI treated at our pediatric infectious diseases clinics between 2012-2023. We geocoded each child’s address to identify neighborhood-level material community deprivation index (MCDI) scores. Outcomes included missed clinic visits, missed antibiotic doses, and changes in antibiotic therapy due to adherence concerns. We assessed time between referral and first visit, first and second visits, and first and last visits. Kruskal-Wallis rank sum test and chi-squared tests examined relationships between DI quartile and clinical outcomes. Log-rank testing and Cox proportional hazard regression models evaluated time-to-event analyses.

Results
We identified 150 children with TBI. There were no differences across MCDI quartiles in rates of missed clinic visits, missed antibiotic doses, changed therapy, or therapy completion. Higher deprivation was associated with longer time between referral and first visit (median 12 days for low/moderate-low deprivation quartiles vs. 24 days for high/moderate-high deprivation quartiles, p=0.004). The high/moderate-high deprivation category had a 39% lower hazard of getting to the first clinic visit after referral compared to the low/moderate-low deprivation category (HR 0.61; 95%CI 0.43, 0.85) after adjustment for race, insurance, and language.

Conclusions
Children with TBI from socioeconomically deprived neighborhoods have longer times from referral to first clinical evaluation. Exploring drivers of differences could promote more equitable TBI care.
Resettlement vs. spontaneous applications. Canadians’ attitudes to asylum policy in a comparative perspective
Authors: Van Wolleghem Pierre Georges 
Published: February 2025

Abstract
Increasing irregular crossings into Canada have put the asylum issue at the forefront of the political debate. This article explores Canadian citizens’ attitudes toward two distinct asylum policies: the long-established resettlement policy endorsed by the federal government, and spontaneous applications, which have sparked public debate over the past seven years. Analyzing original survey data from 2021, I show that a majority of Canadians support asylum policies, irrespective of type. Delving into opposition to these policies, I identify welfare chauvinism as the primary factor, although attitudes to international collaboration on refugee matters and to the United Nations also correlate with policy preferences. A comparative analysis of attitudes in Canada, the USA, the UK, and the Netherlands reveals similar influences on asylum policy preferences. By shifting the focus from attitudes to refugees to attitudes to asylum policy, this study provides novel evidence of an important dimension of Canadians’ attitudes toward refugee-related matters.
High-resolution urban air quality monitoring from citizen science data with echo-state transformer networks
Authors: Bonas Matthew , Castruccio Stefano 
Published: February 2025

Abstract
Citizen science data for monitoring air pollution have recently emerged as a powerful yet under-explored resource to complement expensive and sparse national air quality monitors. In urban environments, these new data have the potential to allow for high-resolution and high-frequency forecasts, and thereby to provide an assessment of population exposure at neighbourhood level. The complex spatio-temporal structure of these data, however, requires new flexible methods that are also able to provide timely forecasts. In this work, we propose a novel method that first provides forecasts with a reservoir computing approach, an echo-state network, adjusts the forecast with a transformer network with attention mechanism and then merges the echo-state and transformer forecast into a combined network. The stochastic nature of the method allows for a fast and more accurate forecast then individual predictors as well as standard statistical methods. Simulation and application to San Francisco air pollution show how the proposed method is able to produce high-resolution urban maps of air quality. Additionally, we show how these forecasts can be used to provide neighbour-level exposure assessment using population data, a task that would not be achievable with sparse government-sponsored air quality networks.
Identifying regions of concomitant compound precipitation and wind speed extremes over Europe
Authors: Boulin Alexis , Di Bernardino Elena , Laloë Thomas , Toulemonde Gwladys 
Published: February 2025

Abstract
The task of simplifying the complex spatio-temporal variables associated with climate modelling is of utmost importance and comes with significant challenges. In this research, our primary objective is to develop a clustering framework to handle compound extreme events within gridded climate data across Europe. Specifically, we intend to identify subregions that display asymptotic independence between precipitation and wind speed extremes, meaning that occurrences of extreme rain and wind speed in one subregion do not affect those in the other. To achieve this, we utilize daily precipitation sums and daily maximum wind speed data derived from the ERA5 reanalysis dataset spanning from 1979 to 2022. Our approach hinges on a tuning parameter and the application of a divergence measure to spotlight disparities in extremal dependence structures without relying on specific parametric assumptions. We propose a data-driven approach to determine the tuning parameter. This enables us to generate clusters that are spatially concentrated, which can provide more insightful information about the regional distribution of compound precipitation and wind speed extremes. The proposed method is able to extract valuable information about extreme compound events while also significantly reducing the size of the dataset within reasonable computational timeframes.