bluuebunny/crossref_metadata_2025_split huggingface dataset:
A conserved lysine/arginine-rich motif is essential for the autophagic degradation of potyviral 6K1 protein and virus infection
Authors: Hu Weiyao , Deng Changhui , Qin Li , Liu Peilan , Wang Linxi , Wang Xaioqing , Shi Wei , Aziz Asma , Li Fangfang , Cheng Xiaofei , Wang Aiming , Dai Zhaoji , Xiang Xiaohua , Cui Hongguang 
Published: February 2025

ABSTRACT

Potyviruses possess one positive-sense single-stranded RNA genome, mainly dependent on polyprotein processing as the expression strategy. The resulting polyproteins are proteolytically processed by three virus-encoded proteases into 11 or 12 mature proteins. One such factor, 6 kDa peptide 1 (6K1), is an understudied viral factor. Its function in viral infection remains largely mysterious. This study is to reveal part of its roles by using pepper veinal mottle virus (PVMV) as the model. Alanine substitution screening analysis revealed that 15 of 17 conserved residues across potyviral 6K1 sequences are essential for PVMV infection. However, 6K1 protein is less accumulated in virus-infected cells, although P3-6K1 and 6K1-CI junctions are efficiently processed by NIa-Pro for its release, indicating that 6K1 undergoes a self-degradation event. Mutating the cleavage site to prevent NIa-Pro processing abolishes viral infection, suggesting that the generation of 6K1 along with its degradation might be important for viral multiplication. We corroborated that cellular autophagy is engaged in 6K1’s degradation. Individual engineering of the 15 6K1 variants into PVMV allows their expression along with viral infection. Five of such variants, D30A, V32A, K34A, L36A, and L39A, significantly interfere with viral infection. The five residues are enclosed in a conserved lysine/arginine-rich motif; four of them appear crucial in engaging autophagy-mediated self-degradation. Based on these data, we envisaged a scenario which potyviral 6K1s interact with an unknown anti-viral component to be co-degraded by autophagy to promote viral infection.

IMPORTANCE

Potyvirus
is the largest genus of plant-infecting RNA viruses, which encompasses socio-economically important virus species, such as
Potato virus Y
,
Plum pox virus
, and
Soybean mosaic virus
. Like all picorna-like viruses, potyviruses express their factors mainly via polyprotein processing. Theoretically, viral factors P3 through CP, including 6K1, should share an equivalent number of molecules. The 6K1 is small in size (~6 kDa) and conserved across potyviruses but less accumulated in virus-infected cells. This study demonstrates that cellular autophagy is engaged in the degradation of 6K1 to promote viral infection. In particular, we found a conserved lysine/arginine-rich motif in 6K1s across potyviruses that is engaged in this degradation event. This finding reveals one facet of a small protein that helps understand the pro-viral role of cellular autophagy in viral infection.
A New C-Peptide Minimal Model to Assess β-Cell Responsiveness to Glucagon in Individuals With and Without Type 2 Diabetes
Authors: Boscolo F. , Faggionato E. , Welch A. A. , Farahani R. A. , Egan A. M. , Vella A. , Dalla Man C. 
Published: February 2025

Glucagon regulates its own secretion indirectly by stimulating β-cells to secrete insulin. This may serve as a compensatory mechanism to enhance β-cell function in individuals with, or predisposed to, type 2 diabetes. However, tools to quantify glucagon-induced C-peptide secretion (SR) are lacking. To bridge this gap, we developed a novel model-based method to provide quantitative indices of β-cell function in response to a glucagon bolus in individuals without and with type 2 diabetes (T2D). Eight individuals without diabetes (3M, age=55±9 yrs, BMI=32±4 kg/m2) and 6 with T2D (1M, age=59±5 yrs, BMI=35±6 kg/m2) underwent a 210-min hyperglycemic clamp (~9 mmol/L). After 180 min, a 1 mg bolus of glucagon was administered over 1 min and plasma glucagon and C-peptide concentrations were frequently measured over 30 min. We tested a battery of mathematical models and selected the best one based on standard criteria. The optimal model assumes that C-peptide SR is made up of two components, one proportional to the above basal glucagon, through parameter Γs (static), and one proportional to glucagon rate of change, through parameter Γd (dynamic responsivity to the hormone). An index of total β-cell responsivity to glucagon, Γ, was also derived from Γs and Γd. Model estimated Γs and Γ were significantly higher in individuals without diabetes compared to T2D (p<0.05), while Γd was not. Our findings reveal notable differences in both static and total insulin secretory response to glucagon in people with diabetes as compared to those without diabetes.
Experimentações democráticas sociocentradas na descolonização de práticas de participação: o caso do Conselho da Juventude Pataxó da Bahia
Authors: Ferrarini Adriane Vieira , Giannella Valéria , Felberg Altemar 
Published: February 2025

El ciclo de participación inaugurado por la Constitución Federal de 1988 allanó el camino para movimientos sociales que invirtieron en acciones institucionalizadas, pero resultaron incapaces de captar demandas de diferentes capas de la población históricamente excluida. Ante esto, pretendemos comprender las prácticas insurgentes que, al no orbitar alrededor del Estado, permanecen invisibles o poco teorizadas en su potencial de expansión democrática. Este es el caso del Consejo Juvenil Pataxó de Bahía, analizado desde una etnografía militante, con el debido sustento teórico-conceptual. Teóricamente, utilizamos perspectivas descolonizadoras para una expansión ontoepistémica de la política, para reconstruir, sobre esta base, un marco teórico y analítico centrado en la categoría de “experimentación democrática sociocéntrica (EDS)”. Concluimos que las EDS crean, restauran y reinventan simultáneamente prácticas y conocimientos de una democracia sustancialmente vivida, revelando poderes políticos e innovaciones públicas para la descolonización de las prácticas participativas. CONJUPAB invita a abrirse a la capacidad revolucionaria de los movimientos sociobiocéntricos y las culturas políticas tradicionales en la búsqueda de soluciones a los problemas públicos, con/a pesar/contra/más allá del Estado.
International Law of Regional Organizations: A Comparative Perspective
Authors: Bordin Fernando Lusa , Odermatt Jed 
Published: February 2025

Abstract
This article provides a comparative analysis of the law and practice of regional international organizations (rio s). Drawing upon the International Law Association (ila) study and individual regional reports, the article offers a cross-regional account of organizations located in Europe, Eurasia, the Middle East, Africa, Latin America and the Caribbean, and the Asia-Pacific. The article focuses on the main conceptual questions that emerged during the study and reflects on some of the main insights gleaned from the cross-cutting comparisons. The article discusses the concept of ‘regional international organization’ and the debates about the appropriate definition to be used in the Study. The article discusses how international law applies to, and within, regional international organizations, examining issues such as the autonomy of the organization’s internal law. The article shows how regional international organizations have influenced the development of international law, by concluding treaties, contributing or catalysing relevant practice to the formation of customary international law, and producing authoritative ‘subsidiary means’ to identify the law. The comparative assessment allows us to offer reflections on the ‘openness’ of regional international organizations and the conditions under which they can shape, and be shaped by, international law. The article concludes with some starting points for further research on the place of regional international organizations.
The European Union and Other Regional International Organizations: Tales of Solidarity
Authors: Kassoti Eva 
Published: February 2025

Abstract
Regional International Organizations (rio s) are an important part of the modern international legal landscape. Yet, thus far, they have largely remained at the margins of scholarly attention. This contribution argues that, inter alia, the rio s’ lens provides valuable insights since rio s’ law casts in legal terms regional narratives of emancipation and solidarity that are central to bringing into existence and sustaining the legitimacy of new regional (legal) orders. The article then proceeds to trace the development of the principle of solidarity in international law and in the legal orders of two rio s, namely the European Union (EU) and the African Union (AU) with a view to providing concrete examples of the potential and limits of rio s to act as vehicles for realising regional narratives of solidarity. The article concludes by emphasising the importance of taking regional (legal) space seriously by highlighting the potential of rio s’ law to increase accountability and pluralise the geographies of international law.
To evaluate repaired rotator cuff morphologically and quantitatively in one GRAPPATINI MRI examination
Authors: Xie Yuxue , Cai Jiajie , Li Qing , Kober Tobias , Hilbert Tom , Chen Shuang , Tao Hongyue 
Published: February 2025

Background GRAPPATINI is capable of originating synthetic T2 images (T2synth) and T2 maps in one magnetic resonance imaging (MRI) scan. Purpose To evaluate GRAPPATINI's performance in providing simultaneous morphological assessment of repaired rotator cuffs (RC) using T2synth images and quantitative evaluation of the postoperative clinical outcomes on T2 maps. Material and Methods A total of 45 individuals after repair surgery for at least 2 years were prospectively examined with GRAPPATINI MRI. Clinical scores were also collected. Image quality was measured using contrast-to-noise ratio (CNR) of the repaired tendons on the T2synth and compared to conventional T2-weighted (T2W) images. Two blinded readers independently graded the repaired RCs based on the Sugaya classification on both T2synth and T2W images to calculate intra- and inter-rater agreements. In addition, T2 values of repaired RCs from the T2 maps generated by GRAPPATINI were correlated with clinical scores. Results GRAPPATINI successfully provided both synthetic T2W and quantitative T2 map in a clinically feasible acquisition time of 2:18 min for the shoulder. There were no significant differences in mean CNR ( P = 0.9) between conventional T2W and T2synth images. The inter-rater agreement for the Sugaya classification did not differ significantly between T2W and T2synth images ( P = 0.8). Furthermore, T2 values of the attached RC showed significant correlations with functional outcomes (r = 0.39–0.52; P < 0.05). Conclusion This study concludes that GRAPPATINI offers a comprehensive assessment of the shoulder by providing both morphological and quantitative evaluations in a single scan. It is an efficient tool for assessing repair status and predicting functional outcomes in patients after arthroscopic RC repair.
OnabotulinumtoxinA for primary new daily persistent headache and comparison to chronic migraine
Authors: Cheema Sanjay , Lagrata Susie , Rantell Khadija Rerhou , Ahmed Maha , Kamourieh Salwa , Matharu Manjit Singh 
Published: February 2025

Background New daily persistent headache (NDPH) is an often treatment-refractory primary headache disorder with a lack of evidence base for treatment. Methods We performed an observational study using prospectively collected data in consecutive patients with NDPH, chronic migraine with daily headache (daily-CM) and without daily headache (non-daily-CM). Patients were treated with two cycles of OnabotulinumtoxinA. Propensity score matching was used to control for imbalances between the groups. The primary outcome measure was the proportion who experienced a ≥ 30% improvement in monthly moderate-to-severe headache days at 24 weeks. Results We included 58 patients with NDPH, 148 with daily-CM, and 84 with non-daily-CM. In NDPH, 34.5% of patients experienced a ≥ 30% improvement in monthly moderate-to-severe headache days, compared to 43.2% in daily-CM and 51.2% in non-daily CM. In NDPH, 6.9% experienced an improvement in monthly headache days, 27.6% an improvement in headache severity, 25.9% a ≥ 6 point improvement in HIT-6 score, and 59% a patient reported improvement. There was no significant difference in response rates between the three groups. Adverse event rates were similar in all groups and there were no serious adverse events. Conclusion OnabotulinumtoxinA is effective in approximately 1/3 patients with NDPH and has a favourable safety profile.
Differentiating Functional Connectivity Patterns in ADHD and Autism Among the Young People: A Machine Learning Solution
Authors: Sütçübaşı Bernis , Ballı Tuğçe , Roeyers Herbert , Wiersema Jan R. , Çamkerten Sami , Öztürk Ozan Cem , Metin Barış , Sonuga-Barke Edmund 
Published: February 2025

Objective: ADHD and autism are complex and frequently co-occurring neurodevelopmental conditions with shared etiological and pathophysiological elements. In this paper, we attempt to differentiate these conditions among the young people in terms of intrinsic patterns of brain connectivity revealed during resting state using machine learning approaches. We had two key objectives: (a) to determine the extent to which ADHD and autism could be effectively distinguished via machine learning from one another on this basis and (b) to identify the brain networks differentially implicated in the two conditions. Method: Data from two publicly available resting-state functional magnetic resonance imaging (fMRI) resources—Autism Brain Imaging Data Exchange (ABIDE) and the ADHD-200 Consortium—were analyzed. A total of 330 participants (65 females and 265 males; mean age = 11.6 years), comprising equal subgroups of 110 participants each for ADHD, autism, and healthy controls (HC), were selected from the data sets ensuring data quality and the exclusion of comorbidities. We identified region-to-region connectivity values, which were subsequently employed as inputs to the linear discriminant analysis algorithm. Results: Machine learning models provided strong differentiation between connectivity patterns in participants with ADHD and autism—with the highest accuracy of 85%. Predominantly frontoparietal network alterations in connectivity discriminate ADHD individuals from autism and neurotypical group. Networks contributing to discrimination of autistic individuals from neurotypical group were more heterogeneous. These included language, salience, and frontoparietal networks. Conclusion: These results contribute to our understanding of the distinct neural signatures underlying ADHD and autism in terms of intrinsic patterns of brain connectivity. The high level of discriminability between ADHD and autism, highlights the potential role of brain based metrics in supporting differential diagnostics.
Urinary Incontinence Following Transurethral Prostatectomy: Current Status and Nursing Strategies
Authors: He Mingjie , Mao Chen , Shu Yongxia , Liu Xue 
Published: February 2025

Background: Urinary incontinence is a prevalent condition among patients who have undergone transurethral prostatectomy (TURP). The objective of this study was to assess the current status and the factors influencing the development of urinary incontinence following TURP. Methods: This retrospective study enrolled patients diagnosed with Benign Prostatic Hyperplasia (BPH) who underwent TURP at our hospital from November 1, 2022, to October 30, 2024. We analyzed the demographic and clinical characteristics of patients who developed postoperative urinary incontinence with those who did not. Results: A total of 242 patients who underwent TURP was enrolled, the incidence rate of postoperative urinary incontinence was 36.4%. There were correlations between postoperative urinary incontinence and the following factors: age (r = 0.601), diabetes (r = 0.589), and duration of surgery (r = 0.578), preoperative pelvic floor muscle training (r = −0.626). Multivariate logistic regression analysis revealed that age ≥65 years (OR = 1.941, 95% CI: 1.220∼2.403), diabetes (OR = 2.488, 95% CI: 2.192∼3.070), and surgery duration ≥60 minutes (OR = 1.995, 95% CI: 1.542∼2.426) are independent risk factors for the development of postoperative urinary incontinence in patients undergoing TURP. Preoperative pelvic floor muscle training (OR = 0.604, 95%CI: 0.319∼0.902) was a protective factor against postoperative urinary incontinence. Conclusion: The incidence of postoperative urinary incontinence following TURP is relatively high and is influenced by multiple factors. It is recommended that preventive and nursing measures be implemented to mitigate the occurrence of postoperative urinary incontinence. These measures should include the stringent control of blood glucose levels, optimization of surgical duration, and the standardization of preoperative pelvic floor muscle training.
Hearing loss and cognitive decline in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) during eight years of follow-up
Authors: Samelli Alessandra Giannella , Gonçalves Natalia Gomes , Padilha Fernanda Yasmin Odila Maestri Miguel , Guesser Vitor Martins , Matas Carla Gentile , Rabelo Camila Maia , Moreira Renata Rodrigues , Santos Itamar S , Lotufo Paulo Andrade , Bensenõr Isabela J , Gilsanz Paola , Suemoto Claudia Kimie 
Published: February 2025

Background Hearing loss (HL) of moderate or higher grades is common in older adults with increasing prevalence as people age, rising from 12% at the age of 60 years to over 58% at 90 years. HL in midlife is one of the main potentially modifiable risk factors for dementia. It is estimated that 7% of dementia cases globally could be avoided if this risk factor was eliminated. However, much of the research conducted has been in high-income countries even though low- and middle-income countries have the highest prevalence of dementia. Objective To study the association between HL and cognitive decline during eight years of follow-up in a Brazilian sample. Methods Participants from the São Paulo center of the Brazilian Longitudinal Study of Adult Health were evaluated in three study waves (2008–10, 2012–14, and 2017–19). HL was defined as pure-tone audiometry above 25 dB in the better ear. Cognitive performance was evaluated with six tests related to memory, verbal fluency, and trail-making tests. A global cognitive z-score was derived from these tests. The association between HL and cognitive decline was evaluated with linear mixed-effects models adjusted for sociodemographic, lifestyle, and clinical factors. Results Of 805 participants (mean age 51 ± 9 years, 52% women, 60% White), 62 had HL. During follow-up, HL was associated with faster global cognitive decline (β = −0.012, 95% CI = −0.023; 0.000, p = 0.039). Conclusions HL was significantly associated with a faster rate of global cognitive decline after a median follow-up of eight years in a sample of middle-income country.
Perceived risk of Alzheimer's disease: Insights into the Black and African American male perspective
Authors: Williams Lilcelia A , Terhorst Lauren , Williams Ishan C , Skidmore Elizabeth , Lingler Jennifer H 
Published: February 2025

Background Non-Hispanic Black and African American men are more likely to have Alzheimer's disease (AD) than non-Hispanic White peers. Despite this, little is known about how Black and African American men perceive dementia risk, which is foundational to prevention. Objective Acknowledging that personal vantage point influences behavior, our study examined Black and African American male perceptions about their anticipated risk for AD. Methods We conducted a secondary analysis of Black and African American adult male responses to the Recruitment Innovations for Diversity Enhancement electronic survey study. We examined associations between perceived risk of AD and age, education, employment status, household income adequacy, marital status, living status, prior experience with AD, and subjective memory performance using generalized linear models. Results Respondents ( n = 112) were age 18 to 79 years ( M = 51.05, SD = 13.44), and 35% reported prior experience with AD through a friend or family member. Respondents’ perceived risk of developing AD ranged from 0 to 100% ( M = 33.46, SD = 28.29). Spearman rho correlations revealed modest but significant correlations between perceived risk and age (r = 21, p = 0.03) and marital status (r = -0.22 p = 0.02). The best fitting generalized linear model revealed low perceived risk for AD was associated with younger age, income adequacy and being married or living as married (χ 2 = 8.76, p = 0.03). Conclusion Selected social determinants of health were associated with perceived risk. Future studies should examine additional social determinants of health (e.g., social and physical environment) and measures of cognitive and physical health to further explore relationships with perceived risk of AD in Black and African American males.
Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study
Authors: Ziemssen Tjalf , Bass Ann D. , Van Wijmeersch Bart , Eichau Sara , Richter Stephan , Hoffmann Frank , Armstrong Nicole M. , Chirieac Magdalena , Cunha-Santos Janete , Singer Barry A. 
Published: February 2025

Background: Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. Objectives: To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13 years of TOPAZ data and TREAT-MS interim data. Design: TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12 mg/day, 3 consecutive days; ⩾12 months apart) for 11–13 years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4 years after last alemtuzumab treatment phase. Methods: Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (⩾2 relapses in the year prior to baseline and ⩾1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed. Results: More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3–13) and in TREAT-MS (0.24, >2 years). Stable/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS. Conclusion: Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals. Trial registration: ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281).