bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of an uncharacterized mitochondrial methionine tRNA-synthetase induces mitochondrial unfolded protein response inCaenorhabditis elegans
Authors: Thapa Bharat Vivan , Das Mohit , Held James P , Patel Maulik R 
Published: February 2025

AbstractAminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen for mitochondrial unfolded protein response (UPRmt) activators inC. elegans, we identified a missense mutation (P447V) in the previously uncharacterized gene Y105E8A.20, which encodes a dually localized methionine tRNA synthetase (MetRS). Here, we characterize the UPRmtinduction by Y105E8A.20, which we callmars-2, and demonstrate that the P447V allele is a loss-of-function mutation. Furthermore, we show impairedmars-2activity in the mitochondria triggers UPRmt. This strain provides a valuable tool for studying mitochondrial translation and understanding how aaRSs are involved in mitochondrial homeostasis.
Clinical Evaluation of an AI System for Streamlined Variant Interpretation in Genetic Testing
Authors: Ruzicka Jiri , Ravel Jean-Marie , Audoux Jérôme , Boulat Alexandre , Thévenon Julien , Yauy Kévin , Dancer Marine , Raymond Laure , Lombardi Yannis , Philippe Nicolas , Blum Michael GB , Duforet-Frebourg Nicolas , Mesnard Laurent 
Published: February 2025

AbstractBackgroundThe growing use of whole exome/genome sequencing for diagnosing hereditary diseases has increased the interpretive workload for clinical laboratories. Efficient methods are needed to identify pathogenic variants and maximize diagnostic yield without overwhelming resources.MethodsWe developed DiagAI, an AI-powered system trained on 2.5 million ClinVar variants to predict ACMG pathogenicity classes. DiagAI ranks variants, proposes diagnostic shortlists, and identifies probands likely to receive molecular diagnoses. It integrates molecular features, inheritance patterns, and phenotypic data when available. We retrospectively analyzed 966 exomes from a nephrology cohort, including 196 with causal variants and 770 undiagnosed cases.ResultsDiagAI identified 94.9% of causal variants in diagnostic exomes with HPO terms, compared to 90.8% without, with median shortlist sizes of 12 and 9 variants, respectively. It achieved a sensitivity of 57.1% and a specificity of 92.6% in tagging exomes likely to contain a diagnostic variant. With HPO terms, 74% of top-ranked (top 1) variants were diagnostic, versus 42% without, and DiagAI outperformed Exomiser and AIMARRVEL in this setting.ConclusionDiagAI generates accurate shortlists of variants that streamline the variant interpretation process. It provides a scalable solution for managing growing diagnostic test volumes without compromising quality.
Cervicovaginal inflammation and HIV target cell activation in adolescent girls and young women with asymptomaticChlamydia trachomatisinfections
Authors: Dabee Smritee , Barnabas Shaun , Kullin Brian , Versteeg Bart , Mkhize Nonhlanhla , Muller Etienne , Maseko Venessa , Lewis David A. , Dietrich Janan , Gray Glenda , Gill Katherine , Bekker Linda-Gail , Sinkala Musalula , Martin Darren P. , Bruisten Sylvia M. , Jaspan Heather B. , Passmore Jo-Ann S. 
Published: February 2025

AbstractBackgroundAdolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected byChlamydia trachomatis(CT) infections, a leading cause of pelvic inflammatory disease (PID), infertility, and increased HIV susceptibility. CT-induced genital inflammation disrupts mucosal barriers and activates HIV target cells, compounding reproductive and immunological risks. We investigated the impact of CT infection in AGYW from two South African regions, focusing on genital inflammation and immune activation.MethodsAn observational cohort of 298 sexually active AGYW (16–22 years) from Cape Town and Johannesburg was enrolled. Those in Johannesburg attended one visit while those in Cape Town were followed for three visits over 6-8 months. Cytokine profiling of cervicovaginal samples assessed inflammatory responses, while cervical cytobrush-derived CD4+ T cells were analyzed for CD38, Ki67 and CCR5 expression. CTompAgenotyping examined strain diversity.ResultsCT prevalence was 2.4 times higher in Cape Town (41.6%) than in Johannesburg (17.4%). Infection with CT led to an upregulation of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, with a stronger inflammatory response observed in Johannesburg. Genotypic analysis revealed regional variations: genovar D, which was predominant in Cape Town, was associated with lower IFN-γ levels, whereas genovar E, prevalent in Johannesburg, was linked to higher IFN-γ levels. AGYW who experienced CT infection across multiple study visits did not exhibit elevated genital tract cytokine levels compared to those with a single infection. However, they did show an increase in activated and proliferating cervical CD4+ T cells, which may contribute to heightened HIV susceptibility.ConclusionsCT genotypic diversity and regional variations significantly influence immune responses in AGYW. Region-specific vaccines and integrated sexual health services would support mitigating STI and HIV risks in this vulnerable population.
Klebsiella pneumoniaedisrupts vasodilation by targeting eNOS post translational modifications via the type VI secretion system and the capsule polysaccharide
Authors: Rehman Safi , sa Pessoa Joana , Buckley Charlotte , Lancaster Rebecca , Ross Ciara , Zhang Xun , McCarron John G. , Curtis Tim M. , Bengoechea Jose A. 
Published: February 2025

SUMMARYVasodilation is a crucial protective response to inflammation and infection. Endothelial cells control vasodilation through the bioavailability of eNOS-produced nitric oxide (NO), and the generation of endothelium-dependent hyperpolarization (EDH). Here, we demonstrate thatKlebsiella pneumoniae, one of the most prevalent blood stream infection pathogens, inhibits agonist-induced vasodilation by blunting the NO-dependent pathway and attenuating the EDH pathway. The type VI secretion system (T6SS) effector VgrG4 licences the kinase PKCβ in an NLRX1-controlled mitochondria reactive oxygen species (mtROS)-dependent manner to phosphorylate the eNOS inhibitory site Thr495, effectively dampening eNOS activity. The capsule polysaccharide, on the other hand, limits the phosphorylation of the eNOS activation site Ser1177by inducing the phosphatase PP2Ac upon activation of an EGF receptor-dependent pathway. VgrG4-induced mtROS attenuates the EDH pathway. Overall, this work reveals a new anti-host activity of the T6SS and illustrates how pathogens can control vascular biology by targeting eNOS post translational modifications.
Combined effects of mechanical loading and Piezo1 chemical activation on 22-months-old female mouse bone adaptation
Authors: Meslier Quentin A. , Oehrlein Robert , Shefelbine Sandra J. 
Published: February 2025

AbstractWith age, bones mechanosensitivity is reduced, which limits their ability to adapt to loading. The exact mechanism leading to this loss of mechanosensitvity is still unclear, making developing effective treatment challenging. Current treatments mostly focus on preventing bone mass loss (such as bisphosphonates) or promoting bone formation (such as Sclerostin inhibitors) to limit the decline of bones mass. However, treatments do not target the cause of bone mass loss which may be, in part, due to the bone’s inability to initiate a normal bone mechanapdatation response. In this work, we investigated the effects of 2 weeks of tibia loading, and Piezo1 agonist injectionin vivoon 22-month-old mouse bone adaptation response. We used an optimized loading profile, which induced high fluid flow velocity and low strain magnitude in adult mouse tibia. We found that tibia loading and Yoda2 injection have an additive effect on increasing cortical bone parameters in 22-month-old mice. This combination of mechanical and chemical stimulation could be a promising treatment strategy to help promote bone formation in patients who have low bone mass due to aging.
Adaptive stratified mixture importance sampling for efficiently estimating extremely small failure probability with high-dimensional inputs and multiple failure domains
Authors: Yan Yuhua , Lu Zhenzhou 
Published: February 2025

PurposeThis study aims to efficiently estimate the extremely small failure probability with high-dimensional inputs and multiple failure domains.Design/methodology/approachThis paper proposed an adaptive stratified mixture importance sampling method. The proposed method first constructs an explicit and regular mixture importance sampling probability density function (M-IS-PDF) by taking the clustering centroids as the density centers. Then by the constructed M-IS-PDF, the proposed method explores the rare multiple failure domains by adaptively stratifying, thereby addressing the issue of estimating extremely small failure probability robustly and efficiently.FindingsCompared with the existing cross-entropy based IS method, the constructed M-IS-PDF not only covers the domains significantly contributing to the failure probability through clustering centroids to reduce the variance of failure probability estimation, but also has no undetermined parameter set to optimize, enhancing the adaptability in high-dimensional problems. Compared with the subset simulation method, the adaptive stratified M-IS-PDF constructed is explicit, regular and easy sampling. It not only has high sampling efficiency but also avoids estimating conditional failure probabilities layer by layer, improving the algorithmic robustness for estimating extremely small failure probability.Originality/valueBoth numerical and engineering examples indicate that, under the similar failure probability estimation accuracy, the proposed method requires significantly smaller sample size and lower computational cost than subset simulation and cross-entropy based IS methods, demonstrating higher efficiency and robustness in addressing intractable reliability analysis problems with high-dimensional inputs, multiple failure domains and rare failure.
Stable isotope analysis reveals individual variations in feeding habits among wild Japanese macaques
Authors: Funakawa Kazuho , Suzumura Takafumi , Koba Keisuke 
Published: February 2025

AbstractWe employed stable isotope ratio analysis to quantitatively assess the feeding behaviors of individual macaques within a wild group of Japanese macaques (Macaca fuscata). The primary objective was to evaluate macaque's feeding habits at the individual scale and to clarify the relationship between feeding habits and social factors, including age, sex, and social rank. The study population consisted of the Main group of Japanese macaques on Koshima Island. We collected 78 body hair samples and 29 food resource samples for isotopic analysis. The variability in carbon, nitrogen, and sulfur isotope ratios among individuals in the Main group has ranges of 5.5‰, 6.5‰, and 6.8‰, respectively. Furthermore, the Bayesian mixture model revealed that there were individual differences in the utilization of forest‐derived (62.3%–90.5%), marine‐derived (6.1%–27.6%), and human‐derived (1.7%–23.4%) food resources, driven by the effect of sex, rank, and year. These findings particularly emphasize the utility of sulfur stable isotope ratios and demonstrate how the combined use of three stable isotope ratios enables effective analysis of the relationships between Japanese macaques and their food resources. Furthermore, our results provide a valuable opportunity for the advancement of future research that integrates stable isotope approaches with field investigations. This study not only highlights the applicability of sulfur isotope ratios as a tool for uncovering the use of marine resources by primates in other regions but also shows the potential of using isotopic techniques to distinguish human‐derived resources, such as wheat, and to develop strategies for managing crop‐raiding by macaques.
Nectar traits and their responses to herbivory in Solidago altissima as a dominant introduced flowering herb in Japan
Authors: Ikemoto Mito , Hashimoto Koya , Katayama Noboru 
Published: February 2025

AbstractThis study investigates the nectar characteristics of the tall goldenrod (Solidago altissima L.), an introduced dominant fall‐flowering herb in Japan. We found that the nectar volume of S. altissima peaked at approximately 13:00 before decreasing. Glucose and fructose were identified as the primary sugar components, followed by sucrose. The average sugar amount per panicle of naturally growing plants was estimated as 229.0 mg. Herbivory by the exotic lacebug (Corythucha marmorata) reduced the nectar volume per floret but did not affect the total sugar amount per floret. However, the sugar amount per panicle decreased substantially because C. marmorata reduced both the number of disc florets (i.e., nectar‐secreting florets) per head and the number of heads per panicle. Plant genotypes also influenced some nectar traits, interacting with the effects of herbivory. As the distribution of C. marmorata continues to expand across Japan, the nectar resources provided by S. altissima may be diminishing nationwide.
The views and course practices of science teachers on the psychological resilience of students with learning disabilities
Authors: Özen Altınkaynak Şenay , Erginsoy Osmanoğlu Devrim , Inaltekin Tufan , Kirman Bilgin Arzu , Erdağı Selma 
Published: February 2025

AbstractIt is crucial for students with learning disabilities (SLDs) to possess psychological resilience in order to pursue their careers as entrepreneurial individuals. One of the areas where entrepreneurship skills are taught in middle school is in science courses. This shows the importance of teaching psychological resilience in science courses. On the basis of this idea, the present study aims to determine the views and suggestions of science teachers on the psychological resilience of SLDs as well as the course processes they carry out in order to foster this trait. Individual and focus group interviews were conducted with 15 science teachers and observations were recorded with two science teachers. Interview and observation forms were developed, taking into account the indicators of the four dimensions of resilience: coping with stress, communication, assertiveness and problem‐solving skills. The study revealed that science teachers did not implement teaching processes to develop the psychological resilience of SLDs and that they considered themselves professionally inadequate in this regard. The science teachers suggested that activities based on learning by practice and experience, collaboration with different businesses and project‐based teaching could be effective in improving the psychological resilience of SLDs.
PRODUCING THE GHATS OF BANARAS AS WORLD‐CLASS SPACES: The Mobilization of Nishad Boatmen
Authors: Shahi Ishan 
Published: February 2025

AbstractThe mobilization of boatmen of the Nishad community on the riverfront of Varanasi, also known as Banaras, against the introduction of a cruise service between September 2018 and the initial months of 2019 reveals the confluence of forces such as Hindu nationalism and the neoliberal pursuit of a world‐class aesthetic, which articulate themselves in the urban developments in Banaras. These include the smart cities mission at the level of the city, which has a cruise service among its constituent world‐class practices, and the protest at the ghat (the riverfront steps that lead to the Ganga river) by the Nishads—the community of fishermen and boatmen in Varanasi, India—at a community level. Meanwhile, at the national and global level, the Hindu nationalist Bhartiya Janata Party (BJP) government has been trying to transform and showcase the city of Banaras as a world‐class city with a Hindu nationalist flavour since 2014. The article shows how different dimensions of Henri Lefebvre's dialectic of the production of space undergo changes through state interventions that are seemingly limited to one dimension, that of conceived space or representation of space.
Better Transcriptomic Stability and Broader Transcriptomic Thermal Response Range Drive the Greater Thermal Tolerance in a Global Invasive Turtle Relative to Native Turtle
Authors: Zhang Changyi , Jiang Shufen , Storey Kenneth B. , Zhang Wenyi 
Published: February 2025

ABSTRACTGreater thermal tolerance of invasive species benefits their survival and spread under extreme climate events, especially under global warming. Revealing the mechanisms underlying the interspecific differences in thermal tolerance between invasive and native species can help understand the invasion process and predict potential invaders. Here, we link the changes in global transcriptomics and antioxidant defense at multiple temperatures with the differences in thermal limits in the juveniles of a successful globally invasive turtle, Trachemys scripta elegans, and a native turtle in China, Mauremys reevesii. The two species show different thermal tolerances and have co‐existed in habitats with the risk of overheating. The majority of the transcriptional response to thermal stress is conserved in the two turtle species, including protein folding or DNA damage responses activated under relatively moderate thermal stress and regulation of the cell cycle and apoptosis during severe thermal stress. Greater thermal tolerance of T. scripta elegans can be associated with a more stable global transcriptome during thermal stress, except for necessary stress responses, and a broader thermal range of continuous up‐regulation of the core mechanisms promoting survival under thermal stress, mainly protein folding and negative regulation of apoptosis. Under extreme hot conditions, the opposite change trends of genes involved in survival mechanisms during thermal stress between invasive and native turtles can be due to differences in energy turnover. The present study provides insights into the mechanisms of physiological differences between invasive and native species given global transcriptional changes and helps understand successful invasion and predict potential invasive species.
Transparency and Policymaking with Endogenous Information Provision
Authors: Li Hanzhe 
Published: February 2025

ABSTRACTHow does the politician's reputation concern affect information provision when the information is endogenously provided by a biased lobbyist? I develop a model to study this problem and show that the answer depends on the transparency design. When the lobbyist's preference is publicly known, the politician's reputation concern induces the lobbyist to provide more information. When the lobbyist's preference is unknown, the politician's reputation concern may induce the lobbyist to provide less information. One implication of the result is that given transparent preferences, the transparency of decision consequences can impede information provision by moderating the politician's reputational incentive.
Experiences of accessing injury prevention, treatment and rehabilitation services for older Māori
Authors: Hikaka Joanna , Ihimaera Louise , Vercoe Hariata , Parsons John 
Published: February 2025

AbstractObjectiveUnintentional injuries cause significant morbidity and mortality for older adults. Māori, the Indigenous people of Aotearoa New Zealand (NZ), experience inequitable access to injury treatment and care services; however, the extent to which this impacts older Māori is unknown. Our objective was to explore older Māori, family and stakeholders' perceptions and experiences of injury‐related care and access for older Māori.MethodsConvenience sampling was used to recruit three participant groups: older Māori (aged ≥55, and living in two regional areas of NZ); family/support network members (whānau) of older Māori; stakeholders (roles in injury prevention/care, health professionals, injury policy, health navigators or Indigenous health service development). Data were collected through demographic questionnaires and in‐person interviews or focus groups. A general inductive approach to thematic analysis was utilised, guided by Māori research theory to situate the findings in the relevant social, political and cultural context for Māori.ResultsForty‐four people participated between September and November 2021 (n = 23 older Māori; n = 21 stakeholders). The findings generated four themes. First, quality of care impacts holistic well‐being. Second, informed advocates and advocacy to access and connect injury‐related care. Third, culturally safe and Māori‐led care. Fourth, the role of family and self in injury‐related care.ConclusionsUnintentional injury‐related care in older Māori is difficult to access and navigate, often not meeting the multidimensional well‐being needs of older Māori. Solutions that support advocacy and navigation through the health system are required to respond to mental health and social, as well as physical needs.
Smoking Cessation Practices in Australian Oncology Settings: A Cross‐Sectional Study of Who, How, and When
Authors: Young Alison Luk , McEnallay Melissa , Day Fiona , Vinod Shalini K. , Stone Emily , Morris Sarah , Stefanovska Elena , Devitt Bianca , Yip Po Yee , Kukard Craig , Pal Abhijit , Thawal Vaibhav , Wright Gavin , Hofman Alison , Sareen Heena , McLennan James , Wong Shuet Oi , Rubio Cassandra , Liu Jennifer , Smith Alexandra , Betts Dimity , Mack Jane , Donnelly Jennifer , Paul Christine 
Published: February 2025

ABSTRACTPurposePatients who smoke tobacco during and after a cancer diagnosis have poorer health outcomes. Oncology healthcare providers (HCPs) are crucial to providing smoking cessation support. The study examined the characteristics associated with differences in HCPs’ smoking cessation practices.MethodsAs part of the Care to Quit trial, a cross‐sectional survey exploring smoking cessation practices was completed by HCPs across nine cancer centers in New South Wales and Victoria, Australia.ResultsOne hundred and seventy‐seven HCPs completed the survey. Over half of the HCP respondents reported asking patients their smoking status, but fewer than half advised patients about the benefits of quitting, referred patients to behavioral support such as Quitline, or offered pharmacotherapy medication. All components of the “3A's” model (Ask, Advise, Act) were more likely to be completed by doctors compared to registered nurses (OR: 7.86, 95% CI: 3.64, 16.95, p<0.001), by those with more years of practice (OR: 0.26, 95% CI: 0.07−0.93, p = 0.039), and those who had received smoking cessation training (OR: 3.91, 95% CI: 1.80, 8.48, p = 0.001). Multivariate analyses also identified differences in the amount of cancer‐specific advice provided between occupation type (p<0.001) and years of practice (p = 0.021).ConclusionThe need for smoking cessation care training in oncology continues to be apparent. Training in prescribing pharmacotherapies (for doctors) or supporting the use of pharmacotherapies (for nurses) is a particular “gap.” Differences between the roles and engagement of doctors and nurses in relation to smoking cessation care should be carefully considered when developing site‐specific models of cessation care and providing training.