bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deleterious variant of INTS1 leads to disrupted sleep–wake cycles
Authors: Confino Shir , Wexler Yair , Medvetzky Adar , Elazary Yotam , Ben-Moshe Zohar , Reiter Joel , Dor Talya , Edvardson Simon , Prag Gali , Harel Tamar , Gothilf Yoav 
Published: August 2024

ABSTRACT
Sleep disturbances are common among children with neurodevelopmental disorders. Here, we report a syndrome characterized by prenatal microcephaly, intellectual disability and severe disruption of sleep–wake cycles in a consanguineous family. Exome sequencing revealed homozygous variants (c.5224G&gt;A and c.6506G&gt;T) leading to the missense mutations E1742K and G2169V in integrator complex subunit 1 (INTS1), the core subunit of the Integrator complex. Conservation and structural analyses suggest that G2169V has a minor impact on the structure and function of the complex, while E1742K significantly alters a negatively charged conserved patch on the surface of the protein. The severe sleep–wake cycles disruption in human carriers highlights a new aspect of Integrator complex impairment. To further study INTS1 pathogenicity, we generated Ints1-deficient zebrafish lines. Mutant zebrafish larvae displayed abnormal circadian rhythms of locomotor activity and sleep, as is the case with the affected humans. Furthermore, Ints1-deficent larvae exhibited elevated levels of dopamine β-hydroxylase (dbh) mRNA in the locus coeruleus, a wakefulness-inducing brainstem center. Altogether, these findings suggest a significant, likely indirect, effect of INTS1 and the Integrator complex on maintaining circadian rhythms of locomotor activity and sleep homeostasis across vertebrates.
An exploration of cardiopulmonary resuscitation discussions with ethnically diverse patients and their families
Authors: Islam Zoebia , Pollock Kristian , Patterson Anne , Hanjari Matilda , Faull Christina 
Published: August 2024

Background/Aims Little is known about how current UK policy for end-of-life care planning fits with the social, cultural and religious values and beliefs of ethnic minority communities. This study aimed to explore the perspectives of patients and family caregivers from ethnically diverse backgrounds, as well as the views of health professionals, regarding end-of-life care planning, including discussions about cardiopulmonary resuscitation. Methods A qualitative study was conducted, including comparative thematic and cross-case analysis from 18 longitudinal patient case studies and 19 interviews with bereaved family members. A total of 112 interviews were conducted across patients, family caregivers and health professionals. Topics included experiences of talking about illness, discussions about choices and decisions about future care, such as cardiopulmonary resuscitation decision making. Results Health professionals sought to identify when patients were ‘ready’ for end-of-life care discussions before initiating these conversations. However, little clarity was given around the characteristics that constituted this readiness by any of the health professionals. Issues around translation, such as mistranslation, confidentiality issues with external translators and the potential for family caregivers to misconstrue information in translation were also highlighted. Religious and cultural beliefs played significant roles in patients' do not attempt cardiopulmonary resuscitation decisions, with anxieties around whether the system adequately valued these beliefs. Conclusions Health professionals played a significant role in seeking an agreement on do not attempt cardiopulmonary resuscitation. Participants' accounts of the discussions highlight the importance of insightful professional recognition of ‘readiness’ to broach the topic, as well as a good knowledge of family dynamics. It also raises concerns about the risk of the patient's voice being unduly influenced by health professionals and/or family caregivers, especially in cases where an interpreter is required to mediate communication.
Reaching adolescents with health services: Systematic development of an adolescent health check-ups and wellbeing programme in Ghana (Y-Check, Ghana)
Authors: Weobong Benedict , Glozah Franklin N. , Taylor-Abdulai Hannah B. , Koka Eric , Addae Nancy , Alor Stanley , Kohl Kid , Banati Prerna , Adongo Philip B. , Ross David A. 
Published: August 2024

Background
Routine health check-ups may improve adolescent health, but global guidelines are lacking. Phase 1 of the WHO-coordinated Y-Check Research Programme involved three African cities to co-produce a programme of adolescent health check-ups. We describe a systematic approach to developing a routine adolescent health check-ups and wellbeing programme (Y-Check) to contribute evidence on whether adolescent health check-ups should be part of routine health services in Ghana.

Methods
Y-Check Phase 1 was conducted in four communities in Cape Coast Ghana, over two stages using a variety of methods: (a) needs assessment and landscape analysis on the health of adolescents (existing policies/programmes, school system, adolescent health conditions) was conducted through desk-review and interviews with key informants to identify the potential content, delivery strategy and settings for adolescent health check-ups in this context; (b) co-designing the Y-Check intervention framework through person-centred participatory workshops and a consensus-building workshop with multiple stakeholders, including adolescents (10–19 years) and their parents. The study was conducted between January 2020 and October 2020.

Results
The Y-Check intervention consists of two check-ups with content that is tailored to the needs of younger adolescents and older adolescents; delivered at both school and community settings by a team of trained staff in multiple steps involving up to four stations. Y-Check includes a referral system for adolescents with any problems that cannot be investigated or treated on-the-spot.

Conclusions
Our systematic approach to co-producing Y-Check has resulted in an intervention whose content and structure is determined by the local context, and which was adjudged by multiple stakeholders to be likely to be both useful and acceptable, and which builds on best practice. As a logical next step, the Y-Check will be subjected to pilot testing and implementation research to rigorously evaluate the feasibility, acceptability, coverage, yield of previously undiagnosed conditions and cost of these health check-ups.
Could breaks reduce general practitioner burnout and improve safety? A daily diary study
Authors: Hall Louise H. , Johnson Judith , Watt Ian , O’Connor Daryl B. 
Published: August 2024

Background
Rates of burnout are currently at record high levels, and GPs experience higher burnout than many other specialties. Organisational interventions may reduce burnout, but few studies have investigated these in primary care.

Aim
The current study investigated whether breaks, both with and without social interactions, were associated with burnout and patient safety perceptions in GPs.

Design
A within-subjects, interval contingent, quantitative daily diary design.

Setting
UK GP practices.

Method
Participants completed questionnaires at baseline measuring demographic variables, burnout and patient safety perceptions. They then completed a questionnaire in the evening each day for a week which captured whether they had taken a break that day, whether it involved a positive social interaction, burnout (comprising subscales of disengagement and exhaustion), positive and negative affect and patient safety perceptions. The data were analysed using hierarchical linear modelling to assess same-day and next-day associations.

Results
We included 241 responses from 58 GPs for analysis. Taking at least one break (involving any or no social interactions) was associated with lower disengagement that day and lower exhaustion the next day. Taking at least one break involving a positive interaction was associated with 1) lower disengagement, exhaustion, overall burnout and negative affect on the same day, as well as higher positive affect and improved perceptions of patient safety, and 2) lower exhaustion and improved patient safety perceptions on the next day.

Conclusion
Organizing daily team or practice breaks where staff can socialise may help to reduce burnout and improve perceptions of patient safety.
The management of unused and expired medications in Thai households: Influencing factors and prevailing practices
Authors: Srijuntrapun Patranit , Maluangnon Kusawadee 
Published: August 2024

Objective
Although the improper disposal of unused and expired medications represents a global environmental concern, its significance is often underestimated. This research delves into the practices and factors related to the management of unused and expired medications.

Methods
Data was collected through a comprehensive survey of Thai households, with 400 structured questionnaires. Multiple regression was then employed to analyze the data.

Results
Findings show an intriguing paradox. The participants in the survey demonstrated commendable knowledge regarding the appropriate management of unused or expired medications. Yet, this knowledge was not sufficiently put into practice. This study identifies the factors that have a positive influence on proper medication disposal practices, such as age, level of education, attitude, and perception. Surveyed participants exhibited a tendency to retain unused medications and discard expired ones with household waste. Most of them showed a low degree of medication management, pointing to the need for targeted interventions.

Conclusion
This research provides tangible benefits for policymakers, healthcare practitioners, and researchers addressing waste management paradigms. In terms of policy, the study highlights the need for comprehensive interventions, including medication take-back systems, infrastructure development, and educational initiatives. Policymakers are urged to bridge the gap between knowledge and behavior by promoting access to collection points for proper medication disposal to avoid perpetuating the cycle of suboptimal medication management. This research informs strategies to encourage responsible medication management practices globally, addressing the adverse environmental and health impacts associated with the improper accumulation of medications.
Upregulation of Metrnl improves diabetic kidney disease by inhibiting the TGF-β1/Smads signaling pathway: A potential therapeutic target
Authors: Lin Lu , Huang Shulin , Lin Xin , Liu Xiaoling , Xu Xiangjin , Li Chunmei , Chen Pin 
Published: August 2024

Purpose
This study comprises an investigation of the role of meteorin-like (Metrnl) in an experimental model of diabetic kidney disease (DKD).

Methods
Twenty-four db/db mice were randomly assigned to one of the following groups: DKD, DKD + Metrnl-/-, and DKD + Metrnl+/+. Plasma Metrnl concentrations were measured using ELISA. Kidney tissues were examined via western blotting, qRT-PCR, and immunohistochemistry to determine the expression levels of inflammatory factors. Electron microscopy was employed to observe stained kidney sections.

Results
Compared with the NC group, FBG, BW, and UACR were elevated in the DKD and Metrnl-/- groups, with severe renal pathological injury, decreased serum Metrnl concentration, decreased renal Metrnl expression, and increased expression levels of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA. In contrast, the Metrnl+/+ group showed decreased FBG and UACR, BUN, TC and TG, increased HDL-C and serum Metrnl concentration, increased renal Metrnl expression, and decreased expression of TNF-α, TGF-β1, TGF-R1, pSmad2, pSmad3, and α-SMA, compared to the DKD and Metrnl-/- groups. A Pearson bivariate correlation analysis revealed a negative correlation between UACR and Metrnl, and a positive correlation between UACR and TGF-β1.

Conclusion
Upregulation of renal Metrnl expression can improve renal injury by downregulating the expression of molecules in the TGF-β1/Smads signaling pathway in the renal tissues of type 2 diabetic mice; and by reducing the production of fibrotic molecules such as α-SMA.
Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set
Authors: Elmunzer B. Joseph , Zhang Jingwen , Coté Gregory A. , Edmundowicz Steven A. , Wani Sachin , Shah Raj , Bang Ji Young , Varadarajulu Shyam , Singh Vikesh K. , Khashab Mouen , Kwon Richard S. , Scheiman James M. , Willingham Field F. , Keilin Steven A. , Papachristou Georgios I. , Chak Amitabh , Slivka Adam , Mullady Daniel , Kushnir Vladimir , Buxbaum James , Keswani Rajesh , Gardner Timothy B. , Forbes Nauzer , Rastogi Amit , Ross Andrew , Law Joanna , Yachimski Patrick , Chen Yen-I , Barkun Alan , Smith Zachary L. , Serrano Jose , Petersen Bret , Wang Andrew Y. , Saltzman John R. , Spitzer Rebecca L. , Ordiah Collins , Spino Cathie , Foster Lydia D. , Durkalski-Mauldin Valerie ,   on behalf of the SVI Study Group*
Published: August 2024

INTRODUCTION:
Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain.

METHODS:
In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP).

RESULTS:
Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37–1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73–3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63–1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65–1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49–1.41).

DISCUSSION:
The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.
Heiliggeistkirche
Authors: Mell Ulrich 
Published: August 2024

Zusammenfassung
Da Heiligkeit in urchristlicher Zeit personal wie sozial durch Einwohnung des heiligen Geistes konstruiert wurde, konnten christliche Kultfeiern in vorhandenen privaten Wohn- oder Wirtschaftsgebäuden praktiziert werden. Räumlichkeiten, die christlichen Heiligen zum Medium wurden, dürften ihre Sakralität nur abgeleitet von ihrer Benutzung besessen haben.
»Der Ort ist wol leiblich«
Authors: Saarinen Risto 
Published: August 2024

Zusammenfassung
Die aristotelische Physik kennt keinen Begriff des absoluten Raumes. Sie lehrt, dass die Außenflächen der anderen Dinge, die mich umschließen, meinen Ort und Raum bestimmen. Der Raum ist also relativ und setzt die körperlichen Dinge voraus. Am Beispiel von Paulus, Pseudo-Klemens und Luther wird gezeigt, dass diese klassische Raumlehre auch für die Theologie des Körpers und des Raumes bedeutsam ist.
Zur digital vermittelten Abendmahlsfeier
Authors: Wüthrich Matthias D. 
Published: August 2024

Zusammenfassung
In der Diskussion zum digital vermittelten Abendmahl wird sehr häufig das Abendmahl »im digitalen Raum« demjenigen im »realen Raum« entgegengesetzt. Diese problematische, essentialistische Rede von zwei Räumen ist ein Indiz dafür, dass die räumlichen Erfahrungen von Menschen während des digital vermittelten Abendmahls noch nicht hinreichend erfasst sind. Der Beitrag entfaltet darum eine Raumtheorie, die es ermöglicht, räumliche Erfahrungen partizipativer leiblicher Ko-Präsenz und Gemeinschaft im Vollzug des digital vermittelten Abendmahls zu beschreiben.
Wahrnehmungsroutinen statt heilige Räume
Authors: Keller Sonja 
Published: August 2024

Zusammenfassung
Der Beitrag fragt, welche Beschreibungen von evangelischen Kirchengebäuden angesichts der Absenz der Deutekategorie »heilig« diskursiv entstanden sind. Er skizziert raum- und materialitätstheoretische, wissenssoziologische, ästhetische, phänomenologische und nutzungsorientierte Zugänge sowie die architektonische Resakralisierungstendenz des Kirchenbaus im 19. Jahrhundert.
Heilige Stätten im Judentum
Authors: van Voolen Edward 
Published: August 2024

Zusammenfassung
Die Bedeutung der heiligen Stätten des Judentums und ihre Rolle im jüdischen Leben haben sich im Laufe der Zeit erheblich verändert. In diesem Aufsatz geht es um die Frage, wie sich ihre Bedeutung im Laufe der Jahrhunderte verändert hat. Neben heiligen Orten entstanden ortsbezogene heilige Zeiten und die Zahl der Stätten vervielfachte sich. Die Säkularisierung und Politisierung vieler heiliger Orte in den letzten Jahrzehnten vergrößerten ihre Bedeutung. Vergleiche mit dem Christentum und Islam, die sich beide auf das Judentum beziehen, werden gelegentlich mit einbezogen.
»Neutrale« Heiligkeit?
Authors: Radosh-Hinder Silke 
Published: August 2024

Zusammenfassung
Wenn gegenwärtig zunehmend multireligiöse Räume und Gebäude entstehen, fragt die Autorin in diesem Artikel nach Möglichkeiten, ob und inwiefern sich Konzepte von »Heiligkeit« in diesen neuen Räumen erkennen lassen. Ein bislang wenig beachteter Aspekt ist die kommunikative Raumkonstruktion, bei der die Aushandlungsprozesse der Beteiligten daraufhin untersucht werden, wie über die gemeinsame kommunikative Interaktion multireligiöse Gebäude sozial konstruiert werden. Dass ein Konzept von Heiligkeit und Bundesschluss im Rahmen solcher Aushandlungsprozesse auftaucht, wird an einem Datenausschnitt erläutert und eröffnet eine neue Perspektive zur Frage von Heiligkeit multireligiöser Gebäude.
Sakralisierungsprozesse in der Erinnerungskultur
Authors: Eschebach Insa 
Published: August 2024

Zusammenfassung
Sakralisierung kann man als eine Kulturtechnik beschreiben. In Hinblick auf eine gewaltvolle Vergangenheit stellen Sakralisierungsprozesse Handlungsmuster und ein Vokabular zur Verfügung, das das geschehene Unheil in einer sinnvollen, scheinbar überirdisch legitimierten Ordnung aufgehen lässt. Der vorliegende Aufsatz diskutiert Sakralisierung am Beispiel des Umgangs mit Orten wie Oradour-sur-Glane und das Frauen-Konzentrationslager Ravensbrück nach 1945 und schildert erinnerungskulturelle Praktiken der Gegenwart.
The Chow ring of the moduli space of degree 2 quasi-polarized K3 surfaces
Authors: Canning Samir , Oprea Dragos , Pandharipande Rahul 
Published: August 2024

Abstract
We study the Chow ring with rational coefficients of the moduli space

F
2

\mathcal{F}_{2}

of quasi-polarized K3 surfaces of degree 2.
We find generators, relations, and calculate the Chow Betti numbers.
The highest nonvanishing Chow group is

A
17

⁢

(

F
2

)

≅
Q

\mathsf{A}^{17}(\mathcal{F}_{2})\cong{\mathbb{Q}}

.
We prove that the Chow ring consists of tautological classes and is isomorphic to the even cohomology.
The Chow ring is not generated by divisors and does not satisfy duality with respect to the pairing into

A
17

⁢

(

F
2

)

\mathsf{A}^{17}(\mathcal{F}_{2})

.
The kernel of the pairing is a 1-dimensional subspace of

A
9

⁢

(

F
2

)

\mathsf{A}^{9}(\mathcal{F}_{2})

which we calculate explicitly.
In the appendix, we revisit Kirwan–Lee’s calculation of the Poincaré polynomial of

F
2

\mathcal{F}_{2}

.
The Impact of the Global Minimum Tax Reform on China and Its Countermeasures
Authors: Liang Yufei 
Published: August 2024

Abstract
Significant corporate tax reform was agreed upon by more than 140 nations in 2021, with implementation set for 2023 and beyond. Many people throughout the globe are discussing the possible effects of the Organization for Economic Cooperation and Development (OECD) planned adjustment to the global minimum tax (GMT) on their respective economies. The OECD has formulated a “two-pillar” scheme for international tax rules for 137 countries and regions within the overall framework. Pillar 2 is to set the tax rate at 15%, the world’s lowest corporate tax. The GMT is a reclassification of the taxing authority mechanism for the profits of multinational corporations, which has made significant adjustments to the global tax coordination and governance mechanism. People living in China and earning money from China must pay university fees, which are all of a nationality. Progressive rates ranging from 3 to 45% apply to the complete income. Therefore, taking the initiative in policy is crucial to address this challenge actively. This article makes an in-depth assessment and prediction of the impact of the GMT reform on China’s tax system and enterprises and proposes countermeasures. However, approximately 20% of the earnings can be exposed to the 15% tax rate that governments can apply. If the entire process is mixed in tandem, the tax rate equals 0.2%. Hence, an important amount of tax revenue can proceed down the drain. From the numerical outcomes, the minimum tax with jurisdictional blending was set at 12.5% under Pillar 2; the disparity between the sample’s top and lowest EATRs would decrease by 2.8% points.
Effect of designations of index date in externally controlled trials: an empirical example
Authors: Van Le Hoa , De Benedetti Marc , Yue Lihua , Fang Lorraine , Van Naarden Braun Kim , Lin Po-Chun , Yang Yanhui , Yang Ling , Li Daniel 
Published: August 2024

Abstract

Objectives
To create an external control arm (ECA) for a single arm trial, the choice of index date – when a patient becomes eligible for a study, is a complex issue. In real world data (RWD), patients commonly have multiple qualifying lines of therapy (LOT) which can be used to determine the index date. This study assessed the impact of different methods to assign the index date on the effectiveness estimates of the target drug versus conventional therapies and explored the impact of seven methods to assign the index date on the effectiveness estimates of the target drug versus conventional therapies.

Methods
A study using RWD was conducted in which patients received varied number of LOTs before qualifying for entry into the ECA. Two novel and five established indexing methods were examined for the ECA in this comparative effectiveness research. Baseline characteristics were adjusted by using stabilized inverse probability of treatment weighting (sIPTW). Cox proportional hazards (PH) model was used for time-to-event endpoints and risk ratio (RR) was estimated from a binomial regression for response-based end points.

Results
Five methods (first eligible line [FEL], restricted-line, all eligible lines, random line, and stratified random line) demonstrated close clinical outcome estimates after adjustment of baseline differences via sIPTW. The FEL resulted in an inability to adjust for number of prior LOTs due to poor overlap of line distribution in this study. The last and second last eligible line cannot be recommended due to their inability to adjust for immortal time bias.

Conclusions
Multiple methods are available for selecting the most appropriate index date for an ECA, and this empirical study has indicated that certain methods yield comparable outcomes when the treatment effect and sample size are large. It is important for researchers to carefully assess the specifics of their studies and justify their selection of the most appropriate indexing method. Future research including simulations to evaluate the two novel stratified random line and SLEL methods is necessary.