bluuebunny/crossref_metadata_2025_split huggingface dataset:
The IMPACT Survey: the humanistic impact of osteogenesis imperfecta in adults
Authors: van Welzenis Taco , Westerheim Ingunn , Hart Tracy , Wekre Lena Lande , Semler Oliver , Rauch Frank , Dewavrin Laetitia , Dadzie Ruby , Prince Samantha , Raggio Cathleen 
Published: November 2024

Abstract
Background
The IMPACT Survey explored the humanistic, clinical, and economic burden of osteogenesis imperfecta (OI) on individuals with OI, their families, caregivers, and wider society. Two previous publications report research methodology, initial insights of the survey, and cost of illness of OI. Here, we present data on the impact of OI on the quality of life (QoL) of adults with OI and explore potential drivers of this impact.

Methods
The IMPACT Survey was an international mixed methods online survey in eight languages (fielded July–September 2021), aimed at adults (aged ≥ 18 years) or adolescents (aged 12–17 years) with OI, caregivers (with or without OI) of individuals with OI, and other close relatives. Survey domains included demographics, socioeconomic factors, clinical characteristics, treatment patterns, QoL, and health economics. We conducted a descriptive analysis of the QoL data, as well as exploratory regression analyses to identify drivers of impact of OI on QoL (independent associations between patient characteristics and the impact on QoL).

Results
1,440 adults with OI participated in the survey. The proportion who reported an impact of OI on their QoL across individual areas in the physical, socioeconomic, and mental well-being domains ranged between 49 and 84%. For instance, 84% of adults reported an impact of OI on the types of leisure activities they could do and 74% on the type of job they could do. More severe self-reported OI and higher fracture frequency were consistently identified as drivers of OI’s impact on QoL. The proportion of adults who reported worrying about different aspects of their lives due to their OI, such as mobility loss, future fractures, and ageing, ranged between 31 and 97%.

Conclusion
IMPACT provides insights into the humanistic burden of OI on adults, revealing that OI has a substantial impact on the QoL of adults. OI severity and fracture frequency were consistently identified as drivers of impact on QoL across all domains. Understanding these drivers may aid in identifying areas for targeted interventions, such as fracture prevention.
Costing curative outpatient care for the poorest in Burkina Faso: informing universal health coverage and leaving no one behind
Authors: Beaugé Yvonne , Ridde Valéry , Souleymane Sidibé , Kiendrébéogo Joël Arthur , Nguyen Hoa Thi , Bonnet Emmanuel , De Allegri Manuela 
Published: November 2024

Abstract
Introduction
The poorest in Burkina Faso face numerous barriers to healthcare access, including financial and geographic obstacles, as well as a high burden of chronic conditions and multimorbidity. This study estimates the average cost of providing curative outpatient consultations at first-level healthcare facilities to the poorest in Burkina Faso. It also estimates the budgetary impact of scaling up free access to these services nationwide. The findings provide essential evidence on cost structures to inform decision-makers in developing policies aimed at achieving universal health coverage and ensuring that no one is left behind.

Methods
We conducted a micro-costing study to estimate the economic costs of providing curative outpatient healthcare services to the poorest at first-level healthcare facilities, considering a health system perspective. We measured the consumption of capital costs (building and equipment) using survey data from 32 primary health facilities and recurrent costs (drugs and consumables) from medical records of 1380 poor patients in Diébougou district. These individuals were targeted and exempted from user fees through a community-based targeting approach. We obtained unit costs from official price lists, pharmacy registries, and expert interviews. We calculated the national budget for providing curative care services to the exempted poorest based on the average cost per first-level consultation.

Results
The estimated capital and recurrent costs of providing curative care services ranged between USD 0.59 - USD 0.61 and USD 2.58 - USD 5.00, respectively. The total cost ranged between USD 3.17 - USD 5.61 per first-level consultation. Providing curative care to the bottom 20% of the population, assuming 0.25 healthcare contacts per person per year, would result in an annual expense ranging from USD 2.77 M to USD 5.38 M (0.74-1.43% of the healthcare budget in 2019). With 2 healthcare contacts per person per year, costs increase to USD 22.19 M to USD 43.05 M (5.91-11.45% of the healthcare budget).

Conclusion
The results can inform policies aimed at expanding access to curative care for the poorest in Burkina Faso, contributing to the goals of universal health coverage and leaving no one behind. Further research is needed to enhance cost estimation and budgeting for higher-level care in the country.
Whole-genome DNA methylomes of tree shrew brains reveal conserved and divergent roles of DNA methylation on sex chromosome regulation
Authors: Son Dongmin R. , Kong Yifan , Tan Yulian , Hu Ting , Shi Lei , Yi Soojin V. 
Published: November 2024

Abstract
Background
The tree shrew (Tupaia belangeri) is a promising emerging model organism in biomedical studies, notably due to their evolutionary proximity to primates. To enhance our understanding of how DNA methylation is implicated in regulation of gene expression and the X chromosome inactivation (XCI) in tree shrew brains, here we present their first genome-wide, single-base-resolution methylomes integrated with transcriptomes from prefrontal cortices.

Results
Genome-wide relationships between DNA methylation and gene expression are consistent with those in other mammals. Interestingly, we observed a clear and significant global reduction (hypomethylation) of DNA methylation across the entire female X chromosome compared to male X. Female hypomethylation does not directly contribute to the gene silencing of the inactivated X chromosome nor does it significantly drive sex-specific gene expression in tree shrews. However, we identified a putative regulatory region in the 5′ end of the X-inactive-specific transcript (Xist) gene, whose pattern of differential DNA methylation strongly relate to its sex-differential expression in tree shrews. Furthermore, differential methylation of this region is conserved across different species. We also provide evidence suggesting that the observed difference between human and tree shrew X-linked promoter methylation is associated with the difference in genomic CpG contents.

Conclusions
Our study offers novel information on genomic DNA methylation of tree shrews as well as insights into the evolution of sex chromosome regulation in mammals. Specifically, we show conserved role of DNA methylation in regulation of Xist expression and propose genomic CpG contents as a factor in driving sex-differential DNA methylation of X-linked promoters.
Pin1 promotes human CaV2.1 channel polyubiquitination by RNF138: pathophysiological implication for episodic ataxia type 2
Authors: Fu Ssu-Ju , Cheng Kai-Min , Hsiao Cheng-Tsung , Fang Ya-Ching , Jeng Chung-Jiuan , Tang Chih-Yung 
Published: November 2024

AbstractLoss-of-function mutations in the human gene encoding the neuron-specific Ca2+ channel CaV2.1 are linked to the neurological disease episodic ataxia type 2 (EA2), as well as neurodevelopmental disorders such as developmental delay and developmental epileptic encephalopathy. Disease-associated CaV2.1 mutants may exhibit defective proteostasis and promote endoplasmic reticulum (ER)-associated degradation of their wild-type (WT) counterpart in a dominant-negative manner. The E3 ubiquitin ligase RNF138 was previously shown to mediate EA2-related aberrant degradation of CaV2.1 at the ER. Herein we aimed to elucidate the ER proteostasis mechanism of CaV2.1. The peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) was identified as a novel neuronal CaV2.1 binding partner that promoted polyubiquitination and proteasomal degradation of CaV2.1. Suppression of endogenous Pin1 level with either shRNA knockdown or the Pin1 inhibitor all-trans retinoic acid (ATRA) enhanced endogenous CaV2.1 protein level in neurons, and attenuated ER-associated degradation of CaV2.1 WT and EA2-causing mutants. Detailed mutation analyses suggested that Pin1 interacted with specific phosphorylated serine/threonine-proline motifs in the intracellular II-III loop and the distal carboxy-terminal region of human CaV2.1. We further generated Pin1-insensitive CaV2.1 constructs and demonstrated that, during ER quality control, Pin1 served as an upstream regulator of CaV2.1 polyubiquitination and degradation by RNF138. Pin1 regulation was required for the dominant-negative effect of EA2 missense mutants, but not nonsense mutants, on CaV2.1 WT protein expression. Our data are consistent with the idea that CaV2.1 proteostasis at the ER, as well as dominant-negative suppression of disease-causing loss-of-function mutants on CaV2.1 WT, entail both Pin1/RNF138-dependent and -independent mechanisms.
NOTCH2NLC GGC intermediate repeat with serine induces hypermyelination and early Parkinson’s disease-like phenotypes in mice
Authors: Tu Haitao , Yeo Xin Yi , Zhang Zhi-Wei , Zhou Wei , Tan Jayne Yi , Chi Li , Chia Sook-Yoong , Li Zhihong , Sim Aik Yong , Singh Brijesh Kumar , Ma Dongrui , Zhou Zhidong , Bonne Isabelle , Ling Shuo-Chien , Ng Adeline S.L. , Jung Sangyong , Tan Eng-King , Zeng Li 
Published: November 2024

Abstract
Background
The expansion of GGC repeats (typically exceeding 60 repeats) in the 5’ untranslated region (UTR) of the NOTCH2NLC gene (N2C) is linked to N2C-related repeat expansion disorders (NREDs), such as neuronal intranuclear inclusion disease (NIID), frontotemporal dementia (FTD), essential tremor (ET), and Parkinson’s disease (PD). These disorders share common clinical manifestations, including parkinsonism, dementia, seizures, and muscle weakness. Intermediate repeat sizes ranging from 40 to 60 GGC repeats, particularly those with AGC-encoded serine insertions, have been reported to be associated with PD; however, the functional implications of these intermediate repeats with serine insertion remain unexplored.

Methods
Here, we utilized cellular models harbouring different sizes of N2C variant 2 (N2C2) GGC repeat expansion and CRISPR-Cas9 engineered transgenic mouse models carrying N2C2 GGC intermediate repeats with and without serine insertion to elucidate the underlying pathophysiology associated with N2C intermediate repeat with serine insertion in NREDs.

Results
Our findings revealed that the N2C2 GGC intermediate repeat with serine insertion (32G13S) led to mitochondrial dysfunction and cell death in vitro. The neurotoxicity was influenced by the length of the repeat and was exacerbated by the presence of the serine insertion. In 12-month-old transgenic mice, 32G13S intensified intranuclear aggregation and exhibited early PD-like characteristics, including the formation of α-synuclein fibers in the midbrain and the loss of tyrosine hydroxylase (TH)-positive neurons in both the cortex and striatum. Additionally, 32G13S induced neuronal hyperexcitability and caused locomotor behavioural impairments. Transcriptomic analysis of the mouse cortex indicated dysregulation in calcium signaling and MAPK signaling pathways, both of which are critical for mitochondrial function. Notably, genes associated with myelin sheath components, including MBP and MOG, were dysregulated in the 32G13S mouse. Further investigations using immunostaining and transmission electron microscopy revealed that the N2C intermediate repeat with serine induced mitochondrial dysfunction-related hypermyelination in the cortex.

Conclusions
Our in vitro and in vivo investigations provide the first evidence that the N2C-GGC intermediate repeat with serine promotes intranuclear aggregation of N2C, leading to mitochondrial dysfunction-associated hypermyelination and neuronal hyperexcitability. These changes contribute to motor deficits in early PD-like neurodegeneration in NREDs.
Allergic rhinitis management: a Delphi Consensus promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP)
Authors: Miraglia del Giudice Michele , Marseglia Gian Luigi , Peroni Diego G. , Zicari Anna Maria , Dinardo Giulio , Ciprandi Giorgio 
Published: November 2024

AbstractAllergic rhinitis (AR) is the most frequent IgE-mediated disease, mainly in children and adolescents. Management of AR in the pediatric age may be heterogeneous, and the available guidelines do not adequately consider this issue. As a result, the Italian Society of Pediatric Allergy and Immunology (SIAIP) promoted a Delphi Consensus to define and evaluate the most relevant aspects of AR management in the pediatric setting in Italy. A qualified board of experts prepared a list of statements that a panel of Italian experts voted on using a web platform. Forty-two pediatricians participated. The results showed that all statements had consensus (> 80% of scores 4 + 5). In particular, there was awareness that AR is a type 2 inflammatory disease requiring adequate treatment. Topical drugs should be preferred, as they are better with cycles. Combined antihistamine/corticosteroid is also considered effective and safe in adolescents. In conclusion, AR deserves adequate attention and care. Current medications are safe and effective; treatment should be addressed to dampen type 2 inflammation and relieve complaints.
Emerging models of human and non-human primate placental development – Centre for Trophoblast Research 17th annual meeting 2024
Authors: Aye Irving L. M. H. 
Published: November 2024

ABSTRACT
The 17th annual meeting of the Centre for Trophoblast Research (CTR) took place at the University of Cambridge, UK, on 1-2 July 2024. This year's meeting provided an opportunity to reflect on the significant advancements made recently in modelling the human placenta in vitro. The meeting featured 12 invited speakers and attracted 260 participants from 25 countries. Many of the speakers were leading figures who have developed methods to derive human trophoblast stem cells or organoids from first trimester and term placentas, and from pluripotent stem cells. Accompanying the invited presentations were flash talks selected from the abstract submissions and poster presentations. The meeting concluded with a stimulating panel discussion to evaluate the current human trophoblast models. This Meeting Review aims to capture the spirit of the event and highlight the key themes and take-home messages that emerged.
Confrontation experience against escaping bait improves pursuit strategy in mice
Authors: Wang Jincheng , Zhang Yueting , Lv Songyan , Pang Ruiqi , Zhang Yanjie , Liu Xue , Deng Qiyue , Zhou Yi 
Published: November 2024

ABSTRACT
Confrontations between predator and prey, driven by the innate survival instincts in both predator and prey, constitute the most significant form of competition in evolution. Yet, understanding how survival skills can benefit from such confrontations remains limited, despite its critical importance for animal survival. We have developed an interactive platform to investigate confrontations between a hungry mouse and an escaping bait. This robotic bait is controlled magnetically through a closed-loop system to continually evade the approaching mouse. Meanwhile, the mouse must capture the escaping bait to receive a food reward. Through analysis of angles, speeds and other kinematic parameters of both the mouse and the bait, we observed that confrontation experiences can notably enhance mice performance. Compared with novice mice, veteran mice enhanced predation efficiency primarily by optimizing the pursuit phase, significantly reducing time costs, mainly by minimizing pauses in movement. Additionally, experience strengthened the navigation strategies used by mice to better track evading bait. Finally, we validated the impact of empirically induced changes in speed distribution and pursuit methods on predation efficiency through modeling of the pursuit phase. In conclusion, this study reveals that confrontation experience could improve pursuit strategy in mice by altering the speed control and pursuit method, providing new insights into these crucial behavioral interactions in nature.
Desenvolvimento de simulador de baixo custo para ensino em cricotireoidostomia
Authors: Tavares Fernandes Vieira Francisco Matheus , Martins Neto Francisco , Cesar Silva Oliveira Leonardo , Valente Acrisio 
Published: November 2024

Introdução: A cricotireoidostomia é um procedimento pouco realizado e que costuma ser feito em situações de estresse pois, comumente, é indicado quando não se consegue estabelecer uma via aérea adequada em situações de insuficiência respiratória, condições que prejudicam o treinamento. Objetivo: Desenvolvimento de um simulador de fácil replicação e baixo custo para o ensino na técnica da cricotireoidostomia. Método: Para o desenvolvimento do simulador foi pensando em 3 conceitos fundamentais: baixo custo de fabricação, facilidade de replicabilidade e realismo. Após a realização de pesquisa sobre modelos tridimensionais existentes, definiu-se pelo desenvolvimento de um simulador realístico e funcional em impressora tridimensional baseado em partes anatômicas reais através de modelo tomográfico. Diversos testes relacionados à impressora, material e funcionalidade foram realizados para a definição da concepção final. Resultados: O produto final foi um simulador realístico impresso em impressora de filamento com movimento em 3 eixos, sendo composto por modelo representando parte inferior da face com o mento, região cervical e início do tórax em tamanho real, placa removível e intercambeável representando modelos de cartilagens tireóide e cricóide com membrana cricotireóide e pele, sendo estas duas partes descartáveis. Os materiais empregados no simulador foram ácido polilático, poliuretano termoplástico, borracha de silicone e esparadrapo impermeável. O conjunto foi disposto em base sintética emborrachada. Todo o modelo levou cerca de 70 horas para ser construído e teve custo final de materiais inferior à R$ 150,00. Conclusão: Foi desenvolvido um simulador mecânico para treinamento em cricotireoidostomia de aspecto realístico, baixo custo e simples construção.
Structure of BiHom-pre-Poisson algebras
Authors: Aloulou Walid , Jebli Mansour 
Published: November 2024

In the current research paper, we define and investigate the structure of a BiHom-pre-Poisson algebra. This algebraic structure is defined by two products "Λ", "◊" and two linear maps f, g on A. In particular, (A, Λ, f, g) is a BiHom-Zinbiel algebra and (A, ◊, f, g) is a BiHom-pre-Lie algebra. Additionally two compatibility conditions between Λ and ◊ are verified. Our first main results are devoted to demonstrating that if A is a BiHom-pre-Lie algebra, then a tensorial algebra of A has a structure of a BiHom-pre-Poisson algebra. Furthermore, we prove that any BiHom-Poisson algebra together with a Rota–Baxter operator defines a BiHom-pre-Poisson algebra. Finally, we define the structure of a dual BiHom-pre-Poisson algebra and we demonstrate that an averaging operator on a BiHom-Poisson algebra gives rise to a dual BiHom-pre-Poisson algebra.
Should Individuals Choose Their Own Incentives? Evidence from a Mindfulness Meditation Intervention
Authors: Woerner Andrej , Romagnoli Giorgia , Probst Birgit M. , Bartmann Nina , Cloughesy Jonathan N. , Lindemans Jan Willem 
Published: November 2024

Traditionally, incentives to promote behavioral change are assigned rather than chosen. In this paper, we theoretically and empirically investigate the alternative approach of letting people choose their own incentives from a menu of increasingly challenging and rewarding options. When individuals are heterogeneous and have private information about their costs and benefits, we theoretically show that leaving them the choice of incentives can improve both adherence and welfare. We test the theoretical predictions in a field experiment based on daily meditation sessions. We randomly assign some participants to one of two incentive schemes and allow others to choose between the two schemes. As predicted, participants sort into schemes in (partial) agreement with the objectives of the policymaker. However, in contrast to our prediction, participants who could choose complete significantly fewer sessions than participants that were randomly assigned. Because the results are not driven by poor selection, we infer that letting people choose between incentive schemes may bring in psychological effects that discourage adherence. This paper was accepted by Axel Ockenfels, behavioral economics and decision analysis. Funding: This work was supported by Zilveren Kruis Zorgverzekeringen N.V. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.04157 .
Severe cutaneous toxicity in a 67-year-old patient with metastatic urothelial carcinoma undergoing therapy with enfortumab vedotin and pembrolizumab
Authors: Müller Benjamin , Curatolo Riccardo , Juratli Hazem , Husic Almir , Nehring Josephine , Potlukova Eliska , Kohler Angela 
Published: November 2024

Introduction: Enfortumab vedotin (EV) combined with pembrolizumab (EV+P) is a promising first-line therapy for metastatic urothelial carcinoma. While it has shown significant efficacy, severe cutaneous adverse events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. We present this case as another example of severe skin off-target toxicity associated with this treatment, emphasising the importance of recognising this potential complication. Case description: A 67-year-old male with metastatic urothelial carcinoma, chronic kidney failure and liver cirrhosis presented with fever, respiratory symptoms and a pruritic rash after two doses of EV+P. The rash rapidly worsened, leading to extensive skin desquamation affecting 20–30% of his body surface area. Skin biopsies confirmed SJS with early-stage TEN (SJS/TEN overlap). The patient was treated with high-dose intravenous steroids, empirical antibiotics for neutropenia and intensive topical care. Significant re-epithelialisation occurred by day 13, and the patient was discharged on day 15 with cessation of EV+P therapy. Conclusion: This case demonstrates the potential for severe cutaneous toxicity in patients receiving EV+P, especially those with complex comorbidities. Early recognition and prompt, aggressive management with systemic corticosteroids are essential for improving outcomes. The case highlights the need for vigilance in monitoring for such adverse events and reporting them to improve patient safety.