bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Adaptive Introgression From Dogs in Iberian Grey Wolves (Canis lupus)
Authors: Sarabia Carlos , Salado Isabel , Fernández‐Gil Alberto , vonHoldt Bridgett M. , Hofreiter Michael , Vilà Carles , Leonard Jennifer A.
Published: January 2025

Invading species along with increased anthropogenization may lead to hybridization events between wild species and closely related domesticates. As a consequence, wild species may carry introgressed alleles from domestic species, which is generally assumed to yield adverse effects in wild populations. The opposite evolutionary consequence, adaptive introgression, where introgressed genes are positively selected in the wild species, is possible but has rarely been documented. Grey wolves (Canis lupus) are widely distributed across the Holarctic and frequently coexist with their close relative, the domestic dog (C. familiaris). Despite ample opportunity, hybridization rarely occurs in most populations. Here we studied the geographically isolated grey wolves of the Iberian Peninsula, who have coexisted with a large population of loosely controlled dogs for thousands of years in a human‐modified landscape. We assessed the extent and impact of dog introgression on the current Iberian grey wolf population by analysing 150 whole genomes of Iberian and other Eurasian grey wolves as well as dogs originating from across Europe and western Siberia. We identified almost no recent introgression and a small (< 5%) overall ancient dog ancestry. Using a combination of single scan statistics and ancestry enrichment estimates, we identified positive selection on six genes (DAPP1, NSMCE4A, MPPED2, PCDH9, MBTPS1, and CDH13) for which wild Iberian wolves carry alleles introgressed from dogs. The genes with introgressed and positively selected alleles include functions in immune response and brain functions, which may explain some of the unique behavioural phenotypes in Iberian wolves such as their reduced dispersal compared to other wolf populations.
Elevated CO2 alters soybean physiology and defense responses, and has disparate effects on susceptibility to diverse microbial pathogens
Authors: Bredow Melissa , Khwanbua Ekkachai , Sartor Chicowski Aline , Qi Yunhui , Breitzman Matthew W. , Holan Katerina L. , Liu Peng , Graham Michelle A. , Whitham Steven A.
Published: January 2025

Increasing atmospheric CO2 levels have a variety of effects that can influence plant responses to microbial pathogens. However, these responses are varied, and it is challenging to predict how elevated CO2 (eCO2) will affect a particular plant–pathogen interaction. We investigated how eCO2 may influence disease development and responses to diverse pathogens in the major oilseed crop, soybean.

Soybean plants grown in ambient CO2 (aCO2, 419 parts per million (ppm)) or in eCO2 (550 ppm) were challenged with bacterial, viral, fungal, and oomycete pathogens. Disease severity, pathogen growth, gene expression, and molecular plant defense responses were quantified.

In eCO2, plants were less susceptible to Pseudomonas syringae pv. glycinea (Psg) but more susceptible to bean pod mottle virus, soybean mosaic virus, and Fusarium virguliforme. Susceptibility to Pythium sylvaticum was unchanged, although a greater loss in biomass occurred in eCO2. Reduced susceptibility to Psg was associated with enhanced defense responses. Increased susceptibility to the viruses was associated with reduced expression of antiviral defenses.

This work provides a foundation for understanding how future eCO2 levels may impact molecular responses to pathogen challenges in soybean and demonstrates that microbes infecting both shoots and roots are of potential concern in future climatic conditions.
External DC Shocks of Symptomatic Supraventricular Tachycardia during Screw‐In Leadless Pacemaker Implant: A Case Report
Authors: Liccardo Mattia , Cipolletta Ersilia , Arezzi Emma , Sicuranza Monica , Rea Maria , Ricciardi Pietro , Napolitano Giovanni
Published: January 2025

We present the case of a 64‐year‐old man who, during the implantation of an active‐fixation leadless pacemaker (LP, Aveir VR, Abbott, USA), underwent several external defibrillation shocks up to 240 Joules, due to symptomatic sustained supraventricular tachycardia at 160 bpm. The shocks, delivered both before and after the screwing of the device in the low interventricular septum, did not cause any technical damage to the device, and no complications were observed. The device was then deployed successfully. To our knowledge, this is the first documented case of external cardioversion (ECV) in a patient with an active‐fixation LP. The results suggest that ECV in these patients appears to be safe and feasible.
LbHKT1;1 Negatively Regulates Salt Tolerance of Limonium bicolor by Decreasing Salt Secretion Rate of Salt Glands
Authors: Zhu Zhihui , Liu Xiuyue , Meng Fanxia , Jiang Aijuan , Zhou Yuqing , Yuan Fang , Chen Min
Published: January 2025

The HKT‐type proteins have been extensively studied and have been shown to play important roles in long‐distance Na+ transport, maintaining ion homoeostasis and improving salt tolerance in plants. However, there have been no reports on the types, characteristics and functions of HKT‐type proteins in Limonium bicolor, a recretohalophyte species with the typical salt gland structure. In this study, five LbHKT genes were identified in L. bicolor, all belonging to subfamily 1 (HKT1). There are many cis‐acting elements related to abiotic/biotic stress response on the promoters of the LbHKT genes. LbHKT1;1 was investigated in detail. Subcellular localization results showed that LbHKT1;1 is targeted to the plasma membrane. Functional analysis in yeast showed that LbHKT1;1 has a higher tolerance than AtHKT1;1 under high Na+ conditions. Silencing and overexpression of the LbHKT1;1 gene in L. bicolor showed that LbHKT1;1 negatively regulates salt secretion by the salt glands. Further experiments showed that LbbZIP52 can specifically bind to the ABRE element in the LbHKT1;1 promoter and regulate the expression of the LbHKT1;1 gene and is involved in the negative regulation of the salt secretion capacity of L. bicolor. This study demonstrates for the first time that the HKT‐type protein is involved in salt secretion by salt glands and provides a new perspective on the function of HKT‐type proteins under salt stress conditions.
Reproductive capacity of Meristotheca papulosa (Solieriaceae, Rhodophyta) and effects of temperature on carpospore release and sporeling growth
Authors: Kim Bo Yeon , Ko Jun‐Cheol , Shan Tifeng , Choi Han Gil
Published: January 2025

Meristotheca papulosa is an economically important red alga with extensive applications in the food, phycocolloid, and pharmaceutical industries. In Korea, this species has only been observed along the coast of Jeju Island. M. papulosa has been intensively harvested for export throughout history as it is more expensive than other seaweeds, which has substantially decreased its natural resources. To restore the destroyed natural algal populations and meet commercial demands that have continuously increased, we evaluated the reproductive capacity of M. papulosa. Also, the effects of temperature on carpospore release and growth were examined at 16, 18, 20, 22, 24, and 26°C. The reproductive capacity of thalli with cystocarps was higher in August (5.2 × 107 spores m−2). The number of carpospores released from M. papulosa was maximum at 24°C (782 ± 93 spores cystocarp−1). Temperature also significantly affected sporeling growth and development. Carpospores grew from 17.16 to 159.18 μm in diameter with maximal growth rate of 10.57% day−1 at 24°C after 21 days. Also, sporelings produced erect thalli at 22–24°C after 28 days. These results provide valuable information for not only the protection and recovery of natural resources but also the establishment of a spore‐based cultivation method for this commercially important alga.
Choosing the right crowdsourcing strategy: Implications for governments' crowdsourcing initiatives
Authors: Colovic Ana , Bagherzadeh Mehdi , Liévin Jean‐Louis
Published: January 2025

Building on recent advances in crowdsourcing research, we argue that, when using crowdsourcing, governments should accurately select the crowd they wish to engage with, depending on the problem to be solved. While targeting a large crowd may be common, it is not always the most appropriate: it can waste significant resources without necessarily producing satisfactory results. We contend that the nature of the problem should determine the crowdsourcing strategy. We propose a typology of problems based on their scope and technicity: specific nontechnical, specific technical, broad nontechnical, and broad technical. We introduce the main crowdsourcing strategies—fishing, hunting, and collective production—explain the rationale for each, and offer a practitioner's perspective on their costs and benefits. We then discuss how each strategy is suited for solving diverse problems and propose guidelines for governments on using crowdsourcing more effectively.
Ammonia emissions and nitrogen use efficiency of untreated and plasma treated liquid organic materials
Authors: Rollett A. J. , Williams J. R. , Priest H.
Published: January 2025

Manure management is a significant source of ammonia emissions in the EU. Ammonia emissions can damage sensitive habitats, pose a risk to human health and reduce crop available nitrogen supply from organic materials and manufactured fertilizers. Total ammoniacal‐nitrogen in liquid organic materials consists of both un‐ionized ammonia gas and ammonium in solution which are at an equilibrium that is pH and temperature dependant. At pH <6 the proportion of ammonia gas is very low, and acidification is recognized as a technique for reducing ammonia emissions from liquid organic materials. Air plasma treatment, which fixes nitrogen from air using a strong electric current, lowers the pH of liquid organic materials to around 5.5, from pH 7–8 for untreated materials. A series of seven replicated field experiments were used to compare the effects of plasma treated and untreated liquid organic materials on ammonia emissions, crop yield and nitrogen use efficiency following application to winter wheat. Results from the field experiments showed that ammonia emissions following the application of plasma treated liquid organic materials were 28%–83% lower than from the untreated materials and similar to emissions from mineral ammonium nitrate in the same experiments. The lower ammonia emissions increased the fertilizer value of the plasma treated liquid organic materials (compared with the untreated materials) by 45%. The increased crop available nitrogen supply from the plasma treated materials reduced the requirement for purchased nitrogen fertilizer applications to meet optimum crop demand.
Task design to support preservice teacher development of statistical graphic critical thinking skills
Authors: Casas‐Rosal José Carlos , León‐Mantero Carmen , Gutiérrez‐Rubio David , Arencibia Orlando
Published: January 2025

Critical thinking is a skill that people must develop to navigate skillfully the information they receive through media channels. The cultivation of this skill must begin in the early stages of education and continue uninterrupted through the completion of academic training. For this reason, the search for tools to promote critical thinking in the classroom is crucial. To address this situation, it is essential that the initial training of educators provides them with valuable resources, offering them a tool for supporting critical thinking in their own future classrooms. This paper presents an activity to cultivate statistical graphic critical thinking (SGCT task) of preservice teachers, offering them a tool for their future teaching role. This approach is implemented dynamically, incorporating real‐world information and simulating individuals' everyday situations. The proposal, implemented with a cohort of 60 preservice teachers, has proven beneficial in improving the critical thinking skills of participating preservice teachers.
Strategic Interaction in Kantian Utopia: The Prisoner's Dilemma
Authors: Roussel Edward , Demey Lorenz
Published: January 2025

What does the Kantian realm of ends look like? To partially answer that question, game theory will be used to analyse how Kantians would handle situations of strategic interaction. Starting from a thorough understanding of Kant's categorical imperative, three purportedly Kantian game theoretical models will be analysed and argued to be inconsistent with the categorical imperative. As these existing models are unfit for analysing strategic interaction in the realm of ends, a genuinely Kantian model will be constructed by adding the concepts of ‘moral field’, ‘moral range’ and ‘Kantian utility function’ to the standard game‐theoretical model. Throughout the paper, the prisoner's dilemma will be used both as a case study and as a ground for argumentation.
Detection of sensory deficits in fine nerve fibres in leprosy diagnosis
Authors: Rodrigues Júnior Ismael Alves , Chaves Ana Thereza , de Andrade Luciana Cardoso , Lyon Sandra , de Faria Grossi Maria Aparecida , de Medeiros Brito Ramayana Morais , de Oliveira Ana Laura Grossi , de Figueiredo Villarroel Manoel , da Costa Rocha Manoel Otávio
Published: January 2025

Objectives

The purpose of this study was to determine reference points for thermal perception in cutaneous lesions of leprosy, a disease caused by Mycobacterium leprae characterised by hypoesthesia in skin lesions due to nerve and Schwann cell infection. Early diagnosis is essential to control transmission and effectively treat the disease.

Methods

Quantitative thermal testing (QTT) has been proposed as a valuable tool for early detection of the disease, initiation of treatment, and monitoring of nerve damage. A thermal analyser was used to determine warm and cold perception thresholds (WPT and CPT, respectively) in skin lesions of 42 leprosy patients and 22 healthy controls.

Results

The thresholds were determined using a 0.25 cm2 thermal stimulator, the method of limits, and the receiver operating characteristic (ROC) curve. Thermal thresholds were higher in patients’ skin lesions compared to unaffected areas and controls. The reference points calculated for the WPT and CPT were 36.55 and 26.35°C, respectively, with high sensitivity and specificity.

Conclusion

The nerve fibres affected by leprosy caused altered thermal sensitivity in the patients’ lesions, especially in warm sensation. A smaller thermal stimulator and the method of limits were effective in detecting early sensory deficits in nerve fibres, demonstrating the potential for early detection of the disease.
Style or accent?: Gendered perceptions of English among young Bahrainis
Authors: Al‐Alawi Wafa
Published: January 2025

Although both are recognized as different speech types, an accent is generally understood as unintentional, whereas style is performative. This study argues that with increasing rates of contact in globalization between people, resources, and cultures, ‘accent’ can be reconceptualized as closely intersected with ‘style’ in Expanding Circle contexts. My analysis of metacommentaries from English‐dominant young Bahrainis shows that the interaction of English with local (gendered) ideologies leads to the perception of English, especially with a foreign American(ized) accent, as ‘emasculating’ and the prevalence of locally accented English ideals in Bahraini men. Applying a scalar‐chronotopic approach, I show how the notion of a foreign English ‘accent’ may overlap with ‘style’ as opposed to being, as commonly understood, an unintentional manner of pronunciation. The analysis clearly shows that Expanding Circle contexts are not entirely norm‐dependent on Inner Circle contexts and has further implications for our understandings of prestige, language, and gender.
Effect of a Nurse‐Led Support Program Using Mobile Application Versus Nurse Phone Advice on Patients at Risk of Coronary Artery Disease: A Randomized Controlled Trial
Authors: Wong Eliza M. L. , Leung Doris Y. P. , Lam Simon C. , Suen Lorna K. P. , Tang Anson C. Y. , Ko Shuk Y. , Leung Angela Y. M.
Published: January 2025

Background

Coronary artery disease (CAD) is a major health problem of atherosclerotic cardiovascular (CV) disease and early intervention is regarded important. Given the proven effect of a lifestyle intervention with nursing telephone counselling and mHealth use in health care, yet the comparisons of both support are lacking, this study is proposed.

Objectives

This study aimed to compare the effects of a coronary artery disease (CAD) support program using a mobile application versus nurse phone advice on exercise amount and physical and psychological outcomes for clients at risk of CAD.

Methods

A prospective randomized controlled trial was conducted. Ethical approval was obtained. Two‐hundred and twenty‐six clients were screened, and a total of 168 clients who were at risk of CAD and routinely used smartphones were randomized into the app support group (App group) or the nurse phone advice (NPA) group. Although all participants received the same health talk delivered by a cardiac nurse at the community center, the App group received additional CAD app support, whereas the NPA group received nurse phone advice for 20 min monthly. The app content comprised (1) CAD knowledge in 10 modules, (2) individual exercise records with their own goals and health measures, and (3) a chest pain action list. The intervention lasted for 3 months. Health outcome data were collected at baseline (T0) and after 1 (T1) and 3 (T2) months. The outcomes were the total amount of exercise (primary outcome), self‐efficacy in illness management, perceived stress, and CAD risk profile (body weight, body mass index, and lipid concentration). Generalized estimating equation models were used to assess differential changes in all outcomes within 3 months.

Results

The attrition rates at 3 months were 3.49% and 9.30% for the App and NPA groups, respectively. The App support group was superior to the NPA group in significantly increasing total exercise amount and reducing body weight, waist circumference, triglycerides, and increased self‐efficacy in illness management.

Linking Evidence to Action

The result provides further insights of app development to support health promotion programs for community‐dwelling adults at risk of CAD.
Landscape Design as Art: An Experimental Methodology with the Use of Neurographic Art and Metaball Geometry
Authors: Agirbas Asli , Sabyrova Roza , Kirhalli Tarik Emre
Published: January 2025

With the use of new technological solutions, non-Euclidean forms can be created in various software platforms and can be produced or fabricated in order to be parts of real world design works. Therefore, new methodology proposals for creation of non-Euclidean forms can be helpful to both designers and design students. In this study, an experimental landscape design methodology which is carried out within the scope of Ozyegin University, Department of Architecture, Architectural Design Studio V and Parametric Design courses, is presented and discussed. Neurographic art is used as a manual art case and metaball script is used as a digital art case of this method. This method has been evaluated and discussed from the perspective of the educators and students. As a result, it has been concluded that the proposed landscape design methodology can be used for the creation of non-Euclidean landscape design forms.
Enhancing Electricity Consumption Forecasting in Limited Dataset: A Simple Stacked Ensemble Approach Incorporating Simple Linear and Support Vector Regression for Malaysia
Authors: Chuan Zun Liang , Ong Shao Jie , Tham Yim Hin , Mat Zain Siti Nur Syamimi , Abdul Rashid Yunalis Amani , Kamarudin Ainur Naseiha
Published: January 2025

Rapid population growth and urbanization, coupled with technological advancements, have driven higher electricity demand, predominantly sourced from contributors to climate change. This article introduces a novel artificial intelligence (AI) time-series algorithm, a simple stacked ensemble of simple linear regression (SLR) and Support Vector Regression (SVR), designed to forecast Malaysia’s annual electricity consumption, particularly in scenarios with limited datasets utilizing the Cross Industry Standard Process for Data Mining (CRISP-DM) data science methodology. Analysis revealed that this simple stacked ensemble SVR-based time-series algorithm, employing an -insensitive loss function with a third-degree polynomial kernel, outperformed 71 other SVR-based algorithms, including four time-series algorithms from the previous study. The algorithm’s forecasting insights from the formulated algorithm could guide policymakers in establishing more effective regulations aligned with Sustainable Development Goals (SDGs) such as affordable and clean energy (SDG7), decent work and economic growth (SDG8), industry, innovation and infrastructure (SDG9), sustainable cities and communities (SDG11), responsible consumption and production (SDG12), and climate action (SDG13), which benefit economic, environmental, human, and social.
Effectiveness of Green Space in Improving Mental Health: A Review
Authors: Baskaran Shastitharran , Ab. Azis Shazmin Shareena , Ab Rahman Nur Hannani , Aziz Nursyuhaida
Published: January 2025

Increasing urbanisation throughout the world has increased the number of mental health cases in citizens, especially in metropolitan areas. Various studies have conveyed the positive linkage between increased green space exposure in the daily life of urban citizens and mental health improvement. However, the current state of knowledge has limited information on percentage of effectiveness of green spaces in improving mental health. Apart from that, the contributions of green space attributes that enhance the improvement of mental health remains unclear. Thus, this study aims to discover the percentage of efficiency of green spaces in improving mental health through systematic review and meta-analysis. The formula for calculating confidence interval of odds ratio is used to calculate the standard error of each study and the random effect inverse-variance approach was used in the meta-analysis to identify the combined effect of the studies. Results from meta-analysis indicated that green spaces can provide an average of 17% [OR (95%CI): 0.83 (0.78–0.88)] improvement in the mental health of a person in terms of stress, depression, and anxiety. Apart from that, green space effectiveness in improving mental health varies with the influence of attributes such as bigger size, better accessibility, and higher tree density. The findings of this review provide evidence that green space exposure can improve the mental health of urban citizens. This study is significant to government bodies and developers as a guideline to implement more green spaces in urban areas that are filled with dense buildings. Overall, this review provides insights on social benefits of green space in improving mental health of citizens, indicating that green space that is accessible, big and has high density of greenness can be beneficial for urban citizen’s mental health.
Delphi Study on the Difficulties of Safety Practice Implementation in Indonesia: A Case of Transportation Infrastructure Projects
Authors: Utama Wahyudi P , Sesmiwati Sesmiwati , Zaitul Zaitul , Peli Martalius , Mohd Isa Haryati , Mohd Kamar Izatul F
Published: January 2025

Despite the fact that health and safety practice at work has been promoted over decades, occupational injuries and fatalities continue to plague the construction industry particularly in developing economies like Indonesia. What are the major difficulties in implementing safety practices in Indonesian, and how do these challenges differ from those identified in previous research? This study aims at investigating the difficulties of implementing safety practices in Indonesian, specifically in the case of transportation infrastructure projects (TIPs). A perusal of past research successfully identified 16 fundamental difficulties to implement safety practices, mostly in the field of construction industry. Based on the expert’s opinions, two difficulties were added by considering the characteristic of TIPs and domestic issue. A two-round Delphi survey was employed to obtain 16 experts’ consensus on major fundamental difficulties in implementing safety practice at TIPs. The experts were academia, government agencies and practitioners having national occupational safety certificate and TIPs experienced. Most of experts agreed that difficulty in changing the workers’ mindset and unsafe outward demeanour, the uniqueness of TIPs (complexity, massive heavy equipment and adverse site condition), adversity of conducting safety supervision on TIP’s sites, lack of safety awareness of workers (ignorance and disobey) and difficulty to enforce national standard and regulation as the five topmost difficulties of safety practice implementation at TIPs. The findings on the key issues hampering the implementation of safety practices in TIPs are very important for the project’s stakeholders in designing strategy or program to improved safety implementation in similar projects. This study contributes to the existing literature by providing a detailed analysis of safety challenges specific to Indonesian transportation infrastructure projects, which have unique characteristics such as large-scale operations and complex infrastructure. While the Delphi survey method is effective for obtaining expert consensus, it may be subject to biases.
The punctuated evolution of the Venusian atmosphere from a transition in mantle convective style and volcanic outgassing
Authors: Weller Matthew B. , Kiefer Walter S.
Published: January 2025

A key question in the planetary sciences centers on the divergence between the sibling planets, Venus and Earth. Venus currently does not operate with plate tectonics, and its thick atmosphere has led to extreme greenhouse conditions. It is unknown if this state was set primordially or if Venus was once more Earth-like. Here, we explore Venus as an example of a planet that recently transitioned between tectonic regimes. Our results show that transitions naturally lead to substantial resurfacing and melt-generated outgassing from lithosphere-breaking events and overturns, with 3 to 10 bars of atmosphere generated per overturn over ~60–million year timescales and ~10 to 100 bars outgassed over billion-year time frames. We find that the observation of Venus with a thick greenhouse atmosphere and the inferences of currently low volcanic rates and previous prodigious volcanic rates are consistent with a planet that has undergone a transition in tectonics, suggesting that Venus once hosted clement surface conditions and was more Earth-like.
Perivascular cells function as key mediators of mechanical and structural changes in vascular capillaries
Authors: Franca Cristiane M. , Lima Verde Maria Elisa , Silva-Sousa Alice Correa , Mansoorifar Amin , Athirasala Avathamsa , Subbiah Ramesh , Tahayeri Anthony , Sousa Mauricio , Fraga May Anny , Visalakshan Rahul M. , Doe Aaron , Beadle Keith , Finley McKenna , Dimitriadis Emilios , Bays Jennifer , Uroz Marina , Yamada Kenneth M. , Chen Christopher , Bertassoni Luiz E.
Published: January 2025

A hallmark of chronic and inflammatory diseases is the formation of a fibrotic and stiff extracellular matrix (ECM), typically associated with abnormal, leaky microvascular capillaries. Mechanisms explaining how the microvasculature responds to ECM alterations remain unknown. Here, we used a microphysiological model of capillaries on a chip mimicking the characteristics of healthy or fibrotic collagen to test the hypothesis that perivascular cells mediate the response of vascular capillaries to mechanical and structural changes in the human ECM. Capillaries engineered in altered fibrotic collagen had abnormal migration of perivascular cells, reduced pericyte differentiation, increased leakage, and higher regulation of inflammatory/remodeling genes, all regulated via
NOTCH3
, a known mediator of endothelial-perivascular cell communication. Capillaries engineered either with endothelial cells alone or with perivascular cells silenced for
NOTCH3
expression showed a minimal response to ECM alterations. These findings reveal a previously unknown mechanism of vascular response to changes in the ECM in health and disease.
Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system
Authors: Almassalha Luay M. , Carignano Marcelo , Liwag Emily Pujadas , Li Wing Shun , Gong Ruyi , Acosta Nicolas , Dunton Cody L. , Gonzalez Paola Carrillo , Carter Lucas M. , Kakkaramadam Rivaan , Kröger Martin , MacQuarrie Kyle L. , Frederick Jane , Ye I Chae , Su Patrick , Kuo Tiffany , Medina Karla I. , Pritchard Josh A , Skol Andrew , Nap Rikkert , Kanemaki Masato , Dravid Vinayak , Szleifer Igal , Backman Vadim
Published: January 2025

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains. Instead, packing domains exist across a structure-function life cycle that couples heterochromatin and transcription in situ, explaining how heterochromatin enzyme inhibition can produce a paradoxical decrease in transcription by destabilizing domain cores. Applied to development and aging, we show the pairing of heterochromatin and transcription at myogenic genes that could be disrupted by nuclear swelling. In sum, packing domains represent a foundation to explore the interactions of chromatin and transcription at the single-cell level in human health.
Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation–dependent mechanisms
Authors: Sun Yilun , Jenkins Lisa M. , El Touny Lara H. , Zhu Linying , Yang Xi , Jo Ukhyun , Escobedo Lauren , Maity Tapan K. , Saha Liton Kumar , Uribe Isabel , Saha Sourav , Takeda Shunichi , Leung Anthony K. L. , Cheng Ken , Pommier Yves
Published: January 2025

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown. Here, we profiled the proteome of FA-induced DPCs and found that flap endonuclease 1 (FEN1) resolves FA-induced DPCs. We revealed that FA also damages DNA bases adjoining the DPCs, leading to DPC-conjugated 5′ flap structures via the base excision repair (BER) pathway. We also found that FEN1 repairs enzymatic topoisomerase II (TOP2)–DPCs. Furthermore, we report that both FA-induced and TOP2-DPCs are adenosine diphosphate (ADP) ribosylated by poly(ADP-ribose) polymerase 1 (PARP1). PARylation of the DPCs in association with FEN1 PARylation at residue E285 is required for the recruitment of FEN1. Our work unveils the identity of proteins forming FA-induced DPCs and a previously unrecognized PARP1-FEN1 nuclease pathway repairing both FA- and TOP2-DPCs.
Large enhancement of ferroelectric properties of perovskite oxides via nitrogen incorporation
Authors: Wang Tao , Gong Fenghui , Ma Xue , Pan Shen , Wei Xian-Kui , Kuo Changyang , Yoshida Suguru , Ku Yu-Chieh , Wang Shuai , Yang Zhenni , Hazra Sankalpa , Zhang Kelvin H. L. , Liu Xingjun , Tang Yunlong , Zhu Yin-Lian , Chang Chun-Fu , Das Sujit , Ma Xiuliang , Chen Lang , Xu Bin , Gopalan Venkatraman , Bellaiche Laurent , Martin Lane W. , Chen Zuhuang
Published: January 2025

Perovskite oxides have a wide variety of physical properties that make them promising candidates for versatile technological applications including nonvolatile memory and logic devices. Chemical tuning of those properties has been achieved, to the greatest extent, by cation-site substitution, while anion substitution is much less explored due to the difficulty in synthesizing high-quality, mixed-anion compounds. Here, nitrogen-incorporated BaTiO
3
thin films have been synthesized by reactive pulsed-laser deposition in a nitrogen growth atmosphere. The enhanced hybridization between titanium and nitrogen induces a large ferroelectric polarization of 70 μC/cm
2
and high Curie temperature of ~1213 K, which are ~2.8 times larger and ~810 K higher than in bulk BaTiO
3
, respectively. These results suggest great potential for anion-substituted perovskite oxides in producing emergent functionalities and device applications.
High-performance ternary logic circuits and neural networks based on carbon nanotube source-gating transistors
Authors: Zhu Xuehao , Xi Meiqi , Wang Jianyu , Zhang Panpan , Li Yi , Luo Xiao , Bai Lan , Chen Xingxing , Peng Lian-mao , Cao Yu , Li Qiliang , Liang Xuelei
Published: January 2025

Multi-valued logics (MVLs) offer higher information density, reduced circuit and interconnect complexity, lower power dissipation, and faster speed over conventional binary logic system. Recent advancement in MVL research, particularly with emerging low-dimensional materials, suggests that breakthroughs may be imminent if multistates transistors can be fabricated controllably for large-scale integration. Here, a concept of source-gating transistors (SGTs) is developed and realized using carbon nanotubes (CNTs). By extending the source electrode into the channel of conventional CNT transistors, a controllable p-n homojunction is formed, allowing CNT-SGTs to reliably switch between three distinct states. Capitalizing on the straightforward fabrication process of CNT-SGTs, ternary inverters, NMIN and NMAX logic gates, ternary SRAM cells, and a ternary neural network achieving 100% image classification accuracy have been successfully implemented. This study represents the most advanced and highest-performing ternary circuits realized with low-dimensional materials to date. This progress highlights the potential of CNT-SGTs in driving the future of MVL architectures.
Avoidable factors associated with maternal death from postpartum haemorrhage: a national Malawian surveillance study
Authors: Riches Jennifer , Jafali James , Twabi Hussein H , Chimwaza Yamikani , Onrust Marthe , Bilesi Rosemary , Gadama Luis , Kachale Fannie , Kuyere Annie , Makhaza Lumbani , Makuluni Regina , Munthali Laura , Musopole Owen , Ndamala Chifundo , Phiri Deborah A , Coomarasamy Arri , Merriel Abi , Waitt Catriona , Odland Maria Lisa , Lissauer David
Published: January 2025

Background

Despite strong evidence-based strategies for prevention and management, global efforts to reduce deaths from postpartum haemorrhage (PPH) have failed, and it remains the leading cause of maternal mortality. We conducted a detailed review of all maternal deaths from 33 facilities in Malawi to identify health system weaknesses leading to deaths from PPH.

Methods

Data were collected regarding every maternal death occurring across all district and central hospitals in Malawi. Deaths occurring from August 2020 to December 2022 were reviewed by multidisciplinary facility-based teams who compiled case narratives from clinical notes and then subsequently reviewed by obstetricians to confirm the cause of death according to international criteria. Data were summarised using proportions/frequencies, comparisons made using χ2or Wilcoxon rank sum tests, and logistic regression conducted to calculate ORs with CIs.

Results

PPH was the cause of 20.4% of maternal deaths. Most deaths from PPH occurred within 24 hours of birth (80.0%), among women who had been referred to a higher-level facility (57.0%) and were admitted in stable condition (60.0%). Vacuum births carried an increased risk of death from PPH (OR 4.25 (95% CI 1.15 to 20.13, p=0.039)). Detailed reviews identified that deaths from PPH were more likely to be associated with factors such as ‘lack of obstetric lifesaving skills’ (26.7% vs 10.1%, p<0.001), ‘inadequate monitoring’ (51.5% vs 40.7%, p=0.012) and ‘communication problems between facilities’ (11.5% vs 6.2%, p=0.019) than deaths from other causes.

Conclusions

Our analysis represents the largest published review of maternal deaths from PPH. We demonstrate that key health system weaknesses are contributing to these preventable maternal deaths. Case reviews conducted by multidisciplinary facility-based teams identified common and recurrent avoidable factors associated with deaths from PPH. Global efforts must now be focused on strategies that address these weaknesses, strengthening health systems and empowering healthcare workers to reduce maternal deaths from PPH.
Virtual reality-based neuroproprioceptive physiotherapy in multiple sclerosis: a protocol for a double-arm randomised assessor-blinded controlled trial on upper extremity function, postural function and quality of life, with molecular and functional MRI assessment
Authors: Miznerova Barbora , Reissigova Jindra , Vasa Libor , Frank Jakub , Hudec Michael , Rodina Lubomir , Herynkova Anna , Havlik Jan , Tintera Jaroslav , Rydlo Jan , Ibrahim Ibrahim , O’Leary Valerie B , Cerna Marie , Jurickova Iva , Pokorna Marketa , Philipp Tom , Hlinovska Jana , Stetkarova Ivana , Rasova Kamila
Published: January 2025

Introduction

Upper limb (UL) impairment is common in people with multiple sclerosis (pwMS), and functional recovery of the UL is a key rehabilitation goal. Technology-based approaches, like virtual reality (VR), are increasingly promising. While most VR environments are task-oriented, our clinical approach integrates neuroproprioceptive ‘facilitation and inhibition’ (NFI) principles. To advance this, we developed immersive VR software based on NFI principles targeting UL function and sit-to-stand ability. This study aims to evaluate the effectiveness of this VR therapy compared with conventional NFI-based physical therapy in pwMS. Our study uniquely applies advanced imaging techniques, along with biological molecular assessments, to explore adaptive processes induced by VR rehabilitation.

Methods and analysis

This double-arm, randomised, assessor-blinded, controlled trial runs over 2 months (1 hour, 2 times per week). PwMS with mild to severe disability will receive either VR therapy or real-world physical therapy. Primary outcomes include the nine-hole peg test, box and block test, handgrip strength, tremor and five times sit-to-stand test. Secondary measures include the Multiple Sclerosis Impact Scale, the 5-level EQ-5D questionnaire and kinematic analysis. Adaptive processes will be monitored using imaging techniques (functional MRI and tractography), molecular genetic methods (long non-coding RNAs) and immune system markers (leukocytes, dendritic cells). The International Classification of Functioning, Disability and Health brief set for MS will map the bio-psycho-social context of participants.

Ethics and dissemination

This project and its amendments were approved by the Ethics Committee of the Institute for Clinical and Experimental Medicine and Thomayer Hospital (1983/21+4772/21 (G-21–02) and the Ethics Committee of Kralovske Vinohrady University Hospital (EK-VP/38/0/2021) in Prague, Czechia (with single enrolment). The findings of this project will be disseminated through scientific publications, conferences, professional networks, public engagement, educational materials and stakeholder briefings to ensure a broad impact across clinical, academic and public domains.

Trial registration number

clinicaltrials.gov (NCT04807738).
Exploring undergraduate medical students and faculty perspectives on blended learning: a qualitative study in China
Authors: Li Sisi , Zhang Chunhui , Chen Xi , Liao Xunchen , Yu Xi , Wu Shaoyu , Zhou Lei , Lv Lin
Published: January 2025

Objectives

This study aimed to explore the views and expectations of medical students and faculty members on blended learning following university-wide teaching reforms, focusing on its influence on self-directed learning (SDL) and educational effectiveness.

Design

A qualitative study employing grounded theory methodology with semistructured individual and group interviews.

Setting

A tertiary medical university after institution-wide educational reforms.

Participants

One administrator, 11 faculty members and 30 third-year preclinical medical students were recruited to participate in the study.

Results

The analysis of faculty and student perceptions yielded two core categories from faculty and three from students. Faculty highlighted the comparison between face-to-face and online instruction, emphasising the influence of students’ learning attitudes, SDL abilities, teachers' beliefs and teaching strategies on blended learning outcomes. Students shared their learning preferences and challenges with SDL, identifying learning attitudes, teaching management and learning methods as key factors impacting blended learning success.

Conclusions

The study highlights that teachers’ positive beliefs enhance blended learning success, while fostering students’ self-directed skills and learning attitudes, along with addressing challenges and needs, is key to effective strategies.
Impact of pandemic service changes on ethnic inequalities in maternal and perinatal outcomes in England: a population-based study
Authors: Ibrahim Buthaina , Jardine Jennifer Elizabeth , Lenguerrand Erik , Judge Andrew , Khalil Asma , Draycott Tim , Iliodromiti Stamatina
Published: January 2025

Objective

In the UK and worldwide, there are substantial ethnic inequalities in maternal and perinatal care and outcomes. We aim to assess the impact of the unprecedented change in care provision during the COVID-19 pandemic on inequalities in adverse maternity outcomes.

Design

Retrospective cohort study using structured electronic health record data.

Setting

English hospital trusts providing maternity care.

Participants

Women giving birth and babies born in the National Health Service (NHS) in England between 1 April 2018 and 31 March 2021, in three time groups: prepandemic, the first pandemic wave (26 March 2020 to 30 June 2020) and second pandemic wave (1 July 2020 to 31 March 2021). Self-reported ethnicity was grouped into White, South-Asian, Black, Mixed and Other.

Main outcome measures

Composite and component measures of maternal (emergency caesarean section, obstetric anal sphincter injury, hysterectomy, sepsis, anaesthetic complications and prolonged hospital stay) and perinatal (stillbirth, neonatal death, preterm birth, brain injury, small for gestational age and prolonged hospital stay). Poisson regression was used to compare relative risks between different ethnic groups.

Findings

1.54 million maternal and 1.43 million neonatal records were included. The overall incidence of adverse outcomes per 1000 births initially decreased maternal: from 308.0 (95% CI 307.0 to 309.0) to 291.0 (95% CI 311.4 to 314.9) (p<0.001); perinatal: from 133.0 (95% CI 132.3 to 133.7) to 111.9 (95% CI 110.1 to 113.7) (p<0.001)), but then increased in the second pandemic period (maternal: 313.2 (95% CI 311.4 to 314.9) (p<0.001); perinatal 118.9 (95% CI 117.7 to 120.0) (p<0.001)). The risk of adverse outcomes was higher in women and babies from all ethnic minority groups compared with White women in both pandemic periods. Black and South-Asian women and babies were approximately 25% more likely to sustain adverse outcomes. While similar overall changes in adverse outcomes were seen in all groups, existing inequalities were sustained throughout the pandemic periods.

Interpretation

Existing inequalities in adverse maternal and perinatal/neonatal outcomes were maintained, not tempered, during the pandemic, despite substantial changes to maternity services and care. Further research on possible interventions to reduce inequality is needed.
Study protocol for a single-centre non-inferior double-blinded randomised controlled trial in China comparing the efficacy and safety of high-frequency irreversible electroporation with transurethral resection of the prostate in treating lower urinary tract symptoms and benign prostatic obstruction (the GIANT trial)
Authors: He Bi-Ming , Shi Zhen-Kai , Chen Rui , Wang Hai-Feng
Published: January 2025

Introduction

Transurethral resection of the prostate (TURP) is the gold standard surgical treatment to lower urinary tract symptoms and benign prostatic obstruction (LUTS/BPO). Although it has been proven to have substantial efficacy in improving functional outcomes, it has shown a high incidence of complications, including transurethral resection syndrome, massive bleeding, urinary incontinence and sexual dysfunction. High-frequency irreversible electroporation (H-FIRE) is a novel non-thermal ablation technique that delivers pulsed high-voltage but low-energy electric current to the cell membrane, thereby leading to cell death. H-FIRE has been reported to be tissue-selective, which leads to fewer side effects. However, no data are available on whether H-FIRE is non-inferior compared with TURP in treating patients with LUTS/BPO regarding safety and efficacy.

Methods and analysis

This trial is a prospective, single-centre, randomised controlled, double-blinded and non-inferiority study in which all men with LUTS/BPO are included. This study aims to determine whether the HI-FIRE is non-inferior to TURP for achieving better functional outcomes as measured by the co-primary outcome of the change from baseline in maximal flow rate (Qmax) and the urinary symptoms by questionnaire of International Prostate Symptom Score (IPSS) scoring at 3 months after surgical treatment. The main inclusion criteria are men with prostatic volume range 30 to 100 mL, Qmax<15 mL/s and IPSS>8. A sample size of 118 participants is required, accounting for a 20% loss. All participants will be randomly allocated at a ratio of 1:1 to the H-FIRE arm (n=59) and the TURP arm (n=59). The primary outcome is to assess the change from baseline in Qmaxand IPSS scoring at 3 months after surgical treatment.

Ethics and dissemination

Ethical approval was obtained from the ethics committee of Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. The results of the study will be disseminated and published in international peer-reviewed journals.

Trial registration number

ClinicalTrials.gov:NCT05306145.
Leveraging International Health Regulations (2005) to enhance health security in the Eastern Mediterranean Region: a retrospective analysis from 2016 to 2023
Authors: Elhakim Mohamed , Hamid Mahgoub , Elkholy Amgad , Samhouri Dalia
Published: January 2025

Introduction

The WHO Eastern Mediterranean Region (EMR), consisting of 22 member states, faces significant health security challenges exacerbated by socioeconomic, political and environmental factors. This study aims to assess the efforts to enhance health security in the EMR from 2016 to 2023 through the implementation of the International Health Regulations (IHR) (2005) core capacities.

Methods

A narrative review was conducted using IHR Monitoring and Evaluation Framework (MEF) tools, such as the State Party Self-Assessment Annual Report (SPAR) and the Joint External Evaluation (JEE), to evaluate the region’s preparedness and response capabilities. Other assessments, such as the Universal Health and Preparedness Review (UHPR), after-action and intra-action reviews and simulation exercises, were included.

Results

The evaluations identified critical gaps in health security infrastructure, highlighting the need for comprehensive strategies and external support, including the Pandemic Fund and National Action Plans for Health Security. While progress has been made, challenges remain due to emerging and re-emerging diseases and regional humanitarian crises.

Conclusion

Despite improvements, the EMR continues to face significant health security challenges. Increased advocacy, capacity building and multisectoral collaboration, particularly through the One Health approach, are essential for future preparedness.