bluuebunny/crossref_metadata_2025 huggingface dataset:
Wearable smart glasses for first‐person video analysis to evaluate nursing skills: A pilot study with a mixed method design
Authors: Kim Sun Kyung , Lee Youngho , Hwang Hye Ri , Kim Oe Nam
Published: October 2024

Background

Comprehensive assessment of skills and performance are necessary to improve the quality of care in nursing education. Various factors pose challenges to accurate assessments, including high student–teacher ratio and observer bias.

Objectives

To establish an assessment system based on first‐person video of smart glasses and validate its usability and feasibility.

Methods

We used two cameras (smart glasses for first‐person perspective and a web cam) to perform video analysis for skill and performance assessments. Usability tests were conducted using quantitative and qualitative questionnaires for the usefulness and acceptability of the current assessment system. Data from standardised checklists for three clinical nursing skills (intramuscular injection, endotracheal suction, and Levin tube feeding) were used to analyse the inter‐rater reliability in addition to Fleiss' Kappa coefficient analysis. A total of 22 participants (18 students and 4 reviewers) were recruited. They completed the study. Apart from physical discomfort component, the proposed smart glasses‐based first‐person video assessment system achieved good usability scores from both students and reviewers.

Results and Conclusions

Fleiss' Kappa values for individual items ranged from 0.450 to 0.808, with an overall average value of 0.592. Results of this study validated the potential of smart glasses‐based assessment system where a set of beneficial mechanisms may meaningfully support the formative learning process. However, issues regarding upgrading the device and need for guidelines for roles of raters and students still remain.
Caffeic acid inhibits Staphylococcus aureus‐induced endometritis through regulating AMPKα/mTOR/HIF‐1α signalling pathway
Authors: Cao Lu , Liu Junbao , Ye Cong , Hu Yubo , Qin Rui
Published: October 2024

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti‐inflammatory, and anti‐infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus‐induced endometritis. The contents of TNF‐α and IL‐1β were detected by ELISA in S. aureus‐induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF‐1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus‐induced uterine injury, MPO activity, the contents of inflammatory factors TNF‐α and IL‐1β, and NF‐κB activation. Meanwhile, CA significantly inhibited S. aureus‐induced ferroptosis, as confirmed by decreased MDA and iron concentration and up‐regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus‐induced HIF‐1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF‐1α signalling pathway to alleviate S. aureus‐induced endometritis in mice.
KRAS mutation promotes the colonization of Fusobacterium nucleatum in colorectal cancer by down‐regulating SERTAD4
Authors: Chen Yizhen , Zheng Yuanyuan , Liu Shaolin
Published: October 2024

This study explores and verifies potential molecular targets through which KRAS mutations regulate the colonization of Fusobacterium nucleatum (FN) in colorectal cancer (CRC). This study combined multiple bioinformatics methods and biological assays. Through The Cancer Genome Atlas, Gene Expression Omnibus, Human Protein Atlas, immunohistochemistry, and co‐culture assays, we further confirmed the differential expression of SERTAD4 in CRC. We delved deeper into examining how expression of SERTAD4 is linked with immune cell infiltration and the enrichment of potential pathways. Lastly, through bacterial phenotypic assays, we validated the function of SERTAD4. As a molecule associated with KRAS mutations and FN infection, the expression levels of SERTAD4 were downregulated in CRC. The diagnostic efficacy of SERTAD4 for CRC is not inferior to that of CEA. Low expression of SERTAD4 is associated with poorer overall survival in CRC. Correlation analysis found that increased expression of SERTAD4 is associated with various immune cell infiltrations and immune checkpoint genes. Finally, bacterial adhesion and invasion assays verify that SERTAD4 inhibits the adhesion and invasion abilities of FN in CRC. This study demonstrates that SERTAD4 exerts a protective role in CRC by inhibiting the colonization of FN.
Food choice and neural reward systems in adolescents with anorexia nervosa and atypical anorexia nervosa
Authors: Lloyd E. Caitlin , Posner Jonathan , Schebendach Janet , Muratore Alexandra F. , Hong Susie , Ojeda Jessica , Rafanello Elizabeth , Steinglass Joanna E. , Foerde Karin
Published: October 2024

Background

Adolescence is a critical developmental period for the study of anorexia nervosa (AN), an illness characterized by extreme restriction of food intake. The maturation of the reward system during adolescence combined with recent neurobiological models of AN led to the hypothesis that early on in illness, restrictive food choices would be associated with activity in nucleus accumbens reward regions, rather than caudate regions identified among adults with AN.

Methods

Healthy adolescents (HC, n = 41) and adolescents with AN or atypical AN (atypAN, n = 76) completed a Food Choice Task during fMRI scanning. Selection of high‐fat foods and choice‐related activation in nucleus accumbens and anterior caudate regions‐of‐interest (ROIs) were compared between individuals with AN/atypAN and HC. Associations were examined between choice‐related activation and choice preferences among the AN group. Exploratory analyses examined associations between choice‐related activation and psychological assessments among the patient group.

Results

Adolescents with AN or atypAN selected fewer high‐fat foods than HC (t = −5.92, p < .001). Counter to predictions, there were no significant group differences in choice‐related activation in the ROIs. Among individuals with AN or atypAN, choice‐related neural activity in the anterior caudate was significantly negatively associated with high‐fat food selections in the task (r = −.32, p = .024). In exploratory analyses, choice‐related anterior caudate activation was positively associated with psychological measures of illness severity among patients (p's < .05, uncorrected).

Conclusions

In this large cohort of adolescents with AN/atypAN, there was no evidence of altered reward system engagement during food choice. While there was no group difference in choice‐related caudate activation, the associations with choices and psychological measures continue to suggest that this neural region is implicated in illness. Longitudinal analyses will clarify whether neural variability relates to longer‐term course.
Efficacy of Subdermal Poly‐d,l‐Lactic Acid Injections for the Treatment of Melasma
Authors: Wan Jovian , Yi Kyu‐Ho
Published: October 2024

Background

Melasma is a chronic, recurrent skin disorder with limited long‐term treatment success using conventional therapies like hydroquinone and laser treatments, which primarily target epidermal components while leaving dermal aspects untreated.

Objective

To evaluate the efficacy and safety of poly‐d,l lactic acid (PDLLA) subdermal injections for treating moderate melasma.

Methods

Three female patients (age range: 45–59 years) with Fitzpatrick skin types III and IV received three PDLLA injection sessions at 3‐week intervals. Treatment outcomes were assessed using the Melasma Area and Severity Index (MASI) and patient satisfaction scores at 12‐week follow‐up.

Results

All patients showed significant MASI score improvements (reduction range: 3.60–6.30 points). Patient satisfaction ratings ranged from 3 to 4 out of 4. Temporary side effects included mild edema and bruising, resolving within 72 h.

Conclusions

PDLLA subdermal injections showed promising results in melasma treatment, potentially due to its biostimulatory effects on collagen production and dermal remodeling. Further research, including histopathological analysis, is needed to confirm long‐term efficacy and safety, and understand underlying mechanisms.
Patient experiences of narcolepsy and idiopathic hypersomnia in the Nordics: a patient journey map
Authors: Vesinurm Märt , Dünweber Christina , Rimestad Jesper , Landtblom Anne‐Marie , Jennum Poul Jørgen
Published: October 2024

Central disorders of hypersomnolence (CDH) are chronic diseases that significantly impact the lives of affected individuals. We aimed to explore the perspectives of individuals with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), and the challenges they encounter in their daily lives and within the healthcare systems in the Nordics. Interviews with patients (N = 41) and healthcare professionals (n = 14) and a patient survey (n = 70) were conducted in 2022 in Denmark, Sweden, Finland, and Norway to develop a patient journey map that visualises the patient with CDH journey and provides insights into the difficulties faced by these individuals. The patient journey mapping approach was chosen to focus on the processes and experiences of patients, highlighting the challenges they confront. Our findings revealed that the process of receiving a CDH diagnosis, as well as subsequent misdiagnoses and treatment, can be protracted and burdensome. CDH diagnoses remain poorly understood by neurologists, general practitioners, and the public, resulting in adverse consequences, with patients reporting a mean (standard deviation [SD]) time from symptom onset to diagnosis of 8.4 (5.11) years and a mean (SD) of 5.5 (4.17) productive hours lost/day. The available non‐pharmaceutical support for patients with CDH, encompassing medical, psychological, educational, and professional assistance, was insufficient. The generalisability of the findings to one specific diagnosis is limited due to the collective analysis of the CDH. These findings are invaluable for identifying disruptions in the patient with CDH journeys and for designing improved pathways for those with NT1, NT2, and IH in the future.
Comparative Pharmacokinetics of Intravenous and Subcutaneous Omeprazole in Sheep and Goats
Authors: Serih Firas , Fadel Charbel , Łebkowska‐Wieruszewska Beata , Lisowski Andrzej , Poapolathep Amnart , Giorgi Mario
Published: October 2024

Abomasal ulcers are a challenge in animal farming, affecting health, welfare, and productivity. Omeprazole's (OPZ) efficacy in treating these ulcers is known, but data on its pharmacokinetics (PK) in adult goats and sheep are lacking. The purpose of this research was to investigate and contrast OPZ's PK in these animals following a single intravenous (IV, 1 mg/kg) and subcutaneous (SC, 2 mg/kg) doses. Sheep and goats had similar exposure levels for all administration routes, with no significant AUC(0‐∞)D variations. Half‐life was short in both species (sheep: 0.20 h; goats: 0.31 h). Goats had a higher volume of distribution after IV administration. Clearance was rapid, and extraction ratio values were high for both goats and sheep (43% and 30%, respectively). SC administration showed similarities in Cmax and Tmax values between species. Both goats and sheep had high bioavailability (about 80%) levels and comparable mean absorption times (MAT). Despite some PK parameters' variances, systemic exposure to OPZ is similar in sheep and goats. SC administration's high bioavailability suggests it as a convenient field application route. Further investigations are needed to understand OPZ's effectiveness in small ruminants with abomasal ulcers and improve dosing regimens for clinical use.
Developmental eye movement test results of Hebrew‐speaking children with cross‐linguistic comparisons
Authors: Ben‐Eli Hadas , Blique Hadas , Scheiman Mitchell , Eichler Rachel
Published: October 2024

Introduction and Purpose

The developmental eye movement (DEM) test is designed to assess saccadic eye movements and visual‐verbal automaticity in children. This study aimed to assess whether there is a need for independent DEM Hebrew norms and to compare DEM results for Hebrew‐speaking children with eight other language norms.

Methods

The DEM test was administered to 224 Hebrew‐speaking children aged 6–13 years who met the inclusion criteria and read the numbers in Hebrew. Test C of the DEM was performed twice, once from right (R) to left (L) and once from L to R, in random order. Age group and language comparisons, including vertical and horizontal reading speeds, errors and horizontal/vertical (H/V) ratios in both directions were analysed.

Results

The participants were almost evenly distributed between the sexes (46.8% female). Statistically significant differences were found between age groups (6–9 and 10–13 years) for vertical and horizontal reading speeds and H/V ratios in both directions (p < 0.001). Older children, as compared to younger children, exhibited faster vertical and horizontal times, with fewer errors, as well as lower ratios (p < 0.001). No significant difference was noted between reading directions for horizontal time and H/V ratio within both age groups (6–9 year olds: p = 0.27 and p = 0.06; 10–13 year olds: p = 0.89 and p = 0.49, respectively). Comparison of DEM norms across languages showed significant differences, with post‐hoc analysis revealing specific language‐related variations. DEM results for Hebrew‐speaking children had similar outcomes to both original English and French values.

Conclusions

This study compared DEM results of Hebrew‐speaking children and scores across nine languages. DEM test values for Hebrew‐speaking children aligned with norms from other languages, particularly the French and original English norms, with consistent ratio scores. It is recommended for practitioners who test Hebrew‐speaking children to continue using the original English norms and to enable the children to read using their preferred reading direction.
Exploring the Combinatorial Effects of Collaborative Factors Leading to Higher Degree of Co‐Production
Authors: Wang Huanming , Zhang Sihan , Ran Bing
Published: October 2024

This study investigates the collaborative factors conducive to co‐production in public services, utilizing Ansell and Gash's framework and fuzzy set qualitative comparative analysis (fsQCA) across 18 cases from the Collaborative Governance Case Database (CGCD). It identifies incentive as a necessary condition for co‐production, revealing three sufficient pathways to co‐production: managed, led, and self‐organized co‐production. The findings advance our understanding of the specific collaborative configurations that can achieve higher degree of co‐production, offering an “incentive‐structure‐behavior” framework and practical insights for policy makers seeking to enhance public service co‐production.
The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State
Authors: Johns Eleanor , Ma Yilun , Louphrasitthiphol Pakavarin , Peralta Christopher , Hunter Miranda V. , Raymond Jeremy H. , Molina Henrik , Goding Colin R. , White Richard M.
Published: October 2024

Lipid droplets are fat storage organelles composed of a protein envelope and lipid‐rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all‐trans‐retinal to all‐trans‐retinol, is upregulated in the MITFLO/undifferentiated/neural crest‐like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid‐mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling.
Multiple genotypes of a quarantine plant pathogen detected in New Zealand indigenous plants located in a botanical garden overseas
Authors: Visnovsky Sandra B. , Kahn Alexandra K. , Nieto‐Jacobo Fernanda , Panda Preeti , Thompson Sarah , Teulon David A. J. , Bojanini Molina Isabel , Marroni M. Virginia , Groenteman Ronny , Rigano Luciano A. , Taylor Robert K. , Forbes Holly , Almeida Rodrigo P. P.
Published: October 2024

Xylella fastidiosa is a xylem‐limited bacterial plant pathogen transmitted by insect vectors. It infects a wide range of plant species and causes devastating diseases. Botanical gardens are global repositories of plant diversity exposed to local biotic and abiotic stresses. We used molecular diagnostic tools for the detection of X. fastidiosa in a collection of New Zealand indigenous plants grown in a X. fastidiosa‐infected Californian area to determine if any species were infected with this bacterial pathogen and to help inform biosecurity responses. To this end, 130 New Zealand indigenous plant species comprising 72 genera, growing in the University of California Botanical Garden at Berkeley, California, were screened for X. fastidiosa. Multiple PCR‐based methods were used to detect the pathogen at the subspecies and sequence‐type levels directly from plant material; nine plant species tested positive by at least two PCR‐based methods. All nine infections were identified as X. fastidiosa subsp. multiplex sequence types 6 or 7 by the amplification of seven housekeeping genes. Three strains were cultured in vitro and their whole genome sequences were obtained; these strains belonged to three distinct clades within subspecies multiplex, indicating that the infections were not transmitted among these New Zealand indigenous plant species. The information gathered in this study will help to assess the risk of X. fastidiosa to New Zealand indigenous flora and the potential spillover to crops of agricultural importance. The work also shows the applied value of botanical garden collections as sentinels for international plant pathogen biosecurity risk assessment.
The integration of the ecosystem approach in the BBNJ agreement—An initial assessment of limits and opportunities
Authors: De Lucia Vito
Published: October 2024

This paper carries out an initial assessment of the integration of the ecosystem approach in the recently adopted agreement on the conservation and sustainable use of marine biodiversity in areas beyond national jurisdiction (BBNJ). The analysis seeks to assess whether or not such integration is likely to be effective. In this respect, this paper follows up on earlier analyses offered during the negotiating process and aims at offering some initial considerations on, and reactions to, the final text of the BBNJ agreement, in order to map the limits of this integration and the opportunities it may offer, for an effective implementation of the ecosystem approach in the context of the BBNJ agreement, focussing especially on article 7 (on general principles and approaches), on part III (on area‐based management tools, including marine protected areas) and part IV (on environmental impact assessments) with specific focus on strategic environmental assessment.
Inter‐Individual Variability in Muscle Fiber–Type Distribution Affects Running Economy but Not Running Gait at Submaximal Running Speeds
Authors: Swinnen Wannes , Lievens Eline , Hoogkamer Wouter , De Groote Friedl , Derave Wim , Vanwanseele Benedicte
Published: October 2024

Running economy is an important determinant of endurance running performance, yet insights into characteristics contributing to its inter‐individual variability remain limited. Although slow‐twitch muscle fibers are more energy‐efficient than fast‐twitch fibers during the (near‐)isometric contractions common during submaximal running, current literature lacks a consensus on whether a relationship between muscle fiber–type distribution and running economy exists. This study aims to resolve the ongoing debate by addressing potential confounding factors often overlooked in prior research, such as the effect of different running speeds, the homogeneity of investigated groups, and the potential impact of the adopted running gait. We selected two groups with predetermined distinct muscle fiber–type distribution in their triceps surae muscle by measurement of carnosine via 1H‐MRS, one predominantly slow (ST; n = 11; carnosine z‐score = −1.31) and the other predominantly fast (FT; n = 10; z‐score = 0.83). Across a range of running speeds (2–4 m/s), we measured running economy (W/kg) through indirect calorimetry, along with running kinematics, kinetics and muscle activity of the lower limb. The ST‐group exhibited, on average, 7.8% better running economy than the FT‐group (p = 0.01) and this difference was consistent across speeds. Both groups demonstrated almost identical kinematics, kinetics, and muscle activity patterns across submaximal running speeds. Overall, our findings indicate that distinct muscle fiber–type distribution explains some of the observed variability in running economy, for which a predominance of energy‐efficient slow‐twitch fibers appear beneficial. In contrast, muscle fiber–type distribution does not affect running gait substantially.
Genomic full‐length sequence of the HLA‐B*40:96 allele was identified by full length group‐specific sequencing
Authors: Zhou Jiyong , Duan Yi , Yuan Ke , Feng Zhihui , Liu Xiuxiang
Published: October 2024

Genomic full‐length sequence of HLA‐B*40:96 was identified by a group‐specific sequencing approach in a Chinese individual.
Are Low‐Income Groups More Dependent on Community Space? A Case Study of Nanjing
Authors: Wang Hui , Kwan Mei‐Po , Hu Mingxing , Qiu Bing
Published: October 2024

Community dependence reflects individuals' daily needs for community space and facilities and is closely related to the accurate allocation of social resources and human quality of life. This study examines the differences in community use and dependence among different income groups at the overall and community levels from the perspective of the microscale individual activity space. Compared with non‐low‐income groups, low‐income groups are generally more dependent on their communities during their daily lives. However, these differences are diverse among different communities; they are more moderate among different income groups in communities located in central city areas and significant among different income groups in suburban affordable housing communities. The regression models reveal that in addition to income, the characteristics of activities and built environment attributes also affect individuals' community dependence. Social policies should prioritize the quality and quantity of community resources for vulnerable suburban groups.
New Municipalism and the Challenges of Design: Context, Instruments and Implementation
Authors: Ahn Byeongsun , Kazepov Yuri
Published: October 2024

This contribution adds a design approach to our understanding of emancipatory epistemologies within new municipalism. So far, the extant research has rarely discussed its specific opportunities and limitations, regarding their context‐bound formulation and real‐world implementation as a policy process. In contrast, the following article situates their emancipatory potential within the place‐specific ways in which multiple stakeholders define problems, set objectives, choose instruments and convert them into actions, intersecting with significant capacity constraints of the municipal scale. The case of participatory budgeting in Vienna illustrates our approach and theoretical reflection. It shows how and to what extent the design of the relational process influences new municipalism in practice and its outcome with respect to agenda‐setting, formulation and implementation. It concludes by highlighting the contribution of a design approach to the production of emancipatory knowledge and practices in democratic transformation and its analytical value added for comparative research on new municipalism.
A transcriptome atlas of zygotic and somatic embryogenesis in Norway spruce
Authors: Stojkovič Katja , Canovi Camilla , Le Kim‐Cuong , Ahmad Iftikhar , Gaboreanu Ioana , Johansson Sofie , Delhomme Nicolas , Egertsdotter Ulrika , Street Nathaniel R.
Published: October 2024

Somatic embryogenesis (SE) is a powerful model system for studying embryo development and an important method for scaling up availability of elite and climate‐adapted genetic material of Norway spruce (Picea abies L. Karst). However, there are several steps during the development of the somatic embryo (Sem) that are suboptimal compared to zygotic embryo (Zem) development. These differences are poorly understood and result in substantial yield losses during plant production, which limits cost‐effective large‐scale production of SE plants. This study presents a comprehensive data resource profiling gene expression during zygotic and somatic embryo development to support studies aiming to advance understanding of gene regulatory programmes controlling embryo development. Transcriptome expression patterns were analysed during zygotic embryogenesis (ZE) in Norway spruce, including separated samples of the female gametophytes and Zem, and at multiple stages during SE. Expression data from eight developmental stages of SE, starting with pro‐embryogenic masses (PEMs) up until germination, revealed extensive modulation of the transcriptome between the early and mid‐stage maturing embryos and at the transition of desiccated embryos to germination. Comparative analysis of gene expression changes during ZE and SE identified differences in the pattern of gene expression changes and functional enrichment of these provided insight into the associated biological processes. Orthologs of transcription factors known to regulate embryo development in angiosperms were differentially regulated during Zem and Sem development and in the different zygotic embryo tissues, providing clues to the differences in development observed between Zem and Sem. This resource represents the most comprehensive dataset available for exploring embryo development in conifers.
Identification of lineage‐specific cis–trans regulatory networks related to kiwifruit ripening initiation
Authors: Kuwada Eriko , Takeshita Kouki , Kawakatsu Taiji , Uchida Seiichi , Akagi Takashi
Published: October 2024

Previous research on the ripening process of many fruit crop varieties typically involved analyses of the conserved genetic factors among species. However, even for seemingly identical ripening processes, the associated gene expression networks often evolved independently, as reflected by the diversity in the interactions between transcription factors (TFs) and the targeted cis‐regulatory elements (CREs). In this study, explainable deep learning (DL) frameworks were used to predict expression patterns on the basis of CREs in promoter sequences. We initially screened potential lineage‐specific CRE–TF interactions influencing the kiwifruit ripening process, which is triggered by ethylene, similar to the corresponding processes in other climacteric fruit crops. Some novel regulatory relationships affecting ethylene‐induced fruit ripening were identified. Specifically, ABI5‐like bZIP, G2‐like, and MYB81‐like TFs were revealed as trans‐factors modulating the expression of representative ethylene signaling/biosynthesis‐related genes (e.g., ACS1, ERT2, and ERF143). Transient reporter assays and DNA affinity purification sequencing (DAP‐Seq) analyses validated these CRE–TF interactions and their regulatory relationships. A comparative analysis with co‐expression networking suggested that this DL‐based screening can identify regulatory networks independently of co‐expression patterns. Our results highlight the utility of an explainable DL approach for identifying novel CRE–TF interactions. These  imply that fruit crop species may have evolved lineage‐specific fruit ripening‐related cis–trans regulatory networks.
All convex bodies are in the subdifferential of some everywhere differentiable locally Lipschitz function
Authors: Daniilidis Aris , Deville Robert , Tapia‐García Sebastián
Published: October 2024

We construct a differentiable locally Lipschitz function in with the property that for every convex body there exists such that coincides with the set of limits of derivatives of sequences converging to . The technique can be further refined to recover all compact connected subsets with nonempty interior, disclosing an important difference between differentiable and continuously differentiable functions. It stems out from our approach that the class of these pathological functions contains an infinite‐dimensional vector space and is dense in the space of all locally Lipschitz functions for the uniform convergence.
Exposure to sugar rationing in the first 1000 days of life protected against chronic disease
Authors: Gracner Tadeja , Boone Claire , Gertler Paul J.
Published: October 2024

We examined the impact of exposure to sugar restrictions within 1000 days after conception on type 2 diabetes and hypertension, leveraging quasi-experimental variation from the end of the United Kingdom’s sugar rationing in September 1953. Rationing restricted sugar intake to levels within current dietary guidelines, and consumption nearly doubled immediately after rationing ended. Using an event study design with UK Biobank data comparing adults conceived just before or after rationing ended, we found that early-life rationing reduced type 2 diabetes and hypertension risk by about 35 and 20% and delayed disease onset by 4 and 2 years, respectively. Protection was evident with in utero exposure and increased with postnatal sugar restriction, especially after 6 months, when eating of solid foods likely began. In utero sugar rationing alone accounted for about one-third of the risk reduction.
Acoustic cognitive map–based navigation in echolocating bats
Authors: Goldshtein Aya , Chen Xing , Amichai Eran , Boonman Arjan , Harten Lee , Yinon Omer , Orchan Yotam , Nathan Ran , Toledo Sivan , Couzin Iain D. , Yovel Yossi
Published: October 2024

Bats are known for their ability to use echolocation for obstacle avoidance and orientation. However, the extent to which bats utilize their highly local and directional echolocation for kilometer-scale navigation is unknown. In this study, we translocated wild Kuhl’s pipistrelle bats and tracked their homing abilities while manipulating their visual, magnetic, and olfactory sensing and accurately tracked them using a new reverse GPS system. We show that bats can identify their location after translocation and conduct several-kilometer map-based navigation using solely echolocation. This proposition was further supported by a large-scale echolocation model disclosing how bats use environmental acoustic information to perform acoustic cognitive map–based navigation. We also demonstrate that navigation is improved when using both echolocation and vision.
Shrub cover declined as Indigenous populations expanded across southeast Australia
Authors: Mariani Michela , Wills Alastair , Herbert Annika , Adeleye Matthew , Florin S. Anna , Cadd Haidee , Connor Simon , Kershaw Peter , Theuerkauf Martin , Stevenson Janelle , Fletcher Michael-Shawn , Mooney Scott , Bowman David , Haberle Simon
Published: October 2024

Wildfires in forests globally have become more frequent and intense because of changes in climate and human management. Shrub layer fuels allow fire to spread vertically to forest canopy, creating high-intensity fires. Our research provides a deep-time perspective on shrub fuel loads in fire-prone southeastern Australia. Comparing 2833 records for vegetation cover, past climate, biomass burning, and human population size across different phases of human occupation, we demonstrated that Indigenous population expansion and cultural fire use resulted in a 50% reduction in shrub cover, from approximately 30% from the early to mid-Holocene (12 to 6 thousand years ago) to 15% during the late to mid-Holocene (6 to 1 thousand years ago). Since the start of British colonization to the present, shrub cover has increased to the highest ever recorded (mean of 35% land cover), increasing the risk of high-intensity fires.
Gender parity in African science
Authors: Asare Kwabena Boahen , Stanford Fatima Cody
Published: October 2024

Africa has seen a notable increase in young women’s participation in science, technology, engineering, and mathematics (STEM) fields over the past two decades. In 2019, the continent boasted the greatest share of female STEM students globally—47% across 49 universities—according to a report from the United Nations Educational, Scientific and Cultural Organization. Sadly, much of this talent is underutilized. Traditional gender expectations and domestic roles pose substantial obstacles, restricting African women from accessing STEM career opportunities. In sub-Saharan Africa, for example, only 31% of professional researchers are women. Without closing the gender gap in African science, progress on widespread problems such as maternal and child health, and food security, is unlikely.
First responders have it covered
Authors: Green Miranda , Foster Jane A.
Published: October 2024

Meningeal innate lymphoid cells guide inhibitory neurons in early life
Bacteria divide to conquer antibiotics
Authors: Harrison Ewan
Published: October 2024

High-level resistance to methicillin requires a distinct form of cell division
A field’s dilemmas
Authors: Kupferschmidt Kai
Published: October 2024

Misinformation research has exploded. But scientists are still grappling with fundamental challenges
In Science Journals
Authors: Vignieri Sacha , Yashinski Melisa , Szuromi Phil , Walia Ankit , Jiang Di , Lopez Bianca , Grocholski Brent , Berry Brandon , Ross Sarah H. , Simonti Corinne , Funk Michael A. , Yeston Jake S. , Maroso Mattia , Ash Caroline , Osborne Ian S. , Fogg Christiana N. , VanHook Annalisa M.
Published: October 2024

Highlights from the
Science
family of journals
Cornerstone medical ethics guidelines get a major update
Authors: O’Grady Cathleen
Published: October 2024

Revised Declaration of Helsinki stresses need to avoid inequities and protect healthy trial volunteers
Exploration of novel mechanisms of azole resistance in
Candida auris
Authors: Li Jizhou , Brandalise Danielle , Coste Alix T. , Sanglard Dominique , Lamoth Frederic
Published: October 2024

Candida auris
is a pathogenic yeast of particular concern because of its ability to cause nosocomial outbreaks of invasive candidiasis (IC) and to develop resistance to all current antifungal drug classes. Most
C. auris
clinical isolates are resistant to fluconazole, an azole drug that is used for the treatment of IC. Azole resistance may arise from diverse mechanisms, such as mutations of the target gene (
ERG11
) or upregulation of efflux pumps via gain of function mutations of the transcription factors
TAC1
and/or
MRR1
. To explore novel mechanisms of azole resistance in
C. auris
, we applied an
in vitro
evolutionary protocol to induce azole resistance in a
TAC1A
/
TAC1B
/
MRR1
triple-deletion strain. Azole-resistant isolates without
ERG11
mutations were further analyzed. In addition to a whole chromosome aneuploidy of chromosome 5, amino acid substitutions were recovered in the transcription factor Upc2 (N592S, L499F), the ubiquitin ligase complex consisting of Ubr2 (P708T, H1275P) and Mub1 (Y765*), and the mitochondrial protein Mrs7 (D293H). Genetic introduction of these mutations in an azole-susceptible wild-type
C. auris
isolate of clade IV resulted in significantly decreased azole susceptibility. Real-time reverse transcription PCR analyses were performed to assess the impact of these mutations on the expression of genes involved in azole resistance, such as
ERG11
, the efflux pumps
CDR1
and
MDR1
or the transcription factor
RPN4
. In conclusion, this work provides further insights in the complex and multiple pathways of azole resistance of
C. auris
. Further analyses would be warranted to assess their respective role in azole resistance of clinical isolates.
Application of sodium hypochlorite for human norovirus and hepatitis A virus inactivation in groundwater
Authors: Jeon Eun Bi , Roy Anamika , Park Shin Young
Published: October 2024

In this study, the effect of sodium hypochlorite (10–200 ppm of Cl
2
) on the inactivation of human norovirus (HuNV) GII.4 and hepatitis A virus (HAV) in groundwater was investigated using propidium monoazide (PMA)/reverse transcription quantitative real-time PCR (RT-qPCR). Initially, 4.00 log
10
genome copies/μL of HuNV GII.4 or 5.50 log
10
genome copies/μL of HAV were artificially inoculated in groundwater. The titers of HuNV GII.4 and HAV decreased significantly (
P
< 0.05) with increasing Cl
2
concentrations. Groundwater was treated with 10, 30, 50, 100, 150, and 200 ppm of Cl
2
, and the viable HuNV GII.4 was significantly (
P
< 0.05) reduced to 3.28 (0.21-log reduction), 3.18 (0.31-log reduction), 3.01 (0.48 log reduction), 2.75 (0.74 log reduction), 2.54 (0.95 log reduction), and 2.34 (1.15 log reduction) log
10
genome copies/μL, respectively. The viable HAV was also significantly (
P
< 0.05) reduced to 4.99 (0.23 log reduction), 4.76 (0.46 log reduction), 4.55 (0.67 log reduction), 4.21 (1.01-log reduction), 3.89 (1.33 log reduction), and 3.64 (1.58 log reduction) log
10
genome copies/μL, respectively. The decimal reduction times (
D
values) (1-log
10
genome reduction) of HuNV GII.4 and HAV infectivity in groundwater were predicted as 116.7 and 98.9 ppm of Cl
2
, respectively, using the first-order kinetics model (HuNV GII.4:
y
= −0.0054
x
+ 3.3585, correlation coefficient (
R
2
) = 0.97; HAV:
y
= −0.0091
x
+ 5.0470,
R
2
= 0.97). The result specifically suggests that 150- to 200-ppm Cl
2
can potentially be used for the inactivation of >1-log
10
genome copy/μL HuNV GII.4 and HAV in groundwater.

IMPORTANCE

Groundwater represents a vital component of the global water supply, serving as a crucial source of potable water for humans. It serves as a source of potable water for up to 50% of the global population and accounts for 43% of all water used for irrigation. It thus follows that the sustainable management of groundwater represents a pivotal solution. However, the regrowth of pathogens in water that is not treated with chlorine or where proper residual chlorine is not maintained represents a risk to public health.
PEDV evades MHC-I-related immunity through nsp1-mediated NLRC5 translation inhibition
Authors: Liu Xiang , Zhang Meng , Yin Lingdan , Kang Li , Luo Yi , Wang Xiaodong , Ren Li , Zhang Guozhong , Yao Yao , Liu Pinghuang
Published: October 2024

Major histocompatibility complex class I (MHC-I) plays crucial roles against viral infections not only by initiating CD8
+
T cell immunity but also by modulating natural killer (NK) cell cytotoxicity. Understanding how viruses precisely regulate MHC-I to optimize their infection is important; however, the manipulation of MHC-I molecules by porcine epidemic diarrhea virus (PEDV) remains unclear. In this study, we demonstrate that PEDV infection promotes the transcription of NLRC5, a key transactivator of MHC-I, in several porcine cell lines and
in vivo
. Paradoxically, no increase in MHC-I expression is observed after PEDV infection both
in vitro
and
in vivo
. Mechanistic studies revealed that PEDV infection inhibits the translation of PEDV-elicited NLRC5 mRNA and the expression of downstream MHC-I proteins, without affecting the expression of physiological NLRC5 and MHC-I proteins. Through viral protein screening, we identified PEDV nonstructural protein 1 (nsp1) as the critical antagonist that inhibits NLRC5-mediated upregulation of MHC-I, and the nsp1’s inhibitory effect on MHC-I requires the motif of 15 amino acids at its C-terminus. Notably, our results revealed that the cytotoxic ability of NK cells against PEDV-infected cells is similar to that against healthy cells. Collectively, our findings uncover an immune evasion mechanism by which PEDV-infected cells masquerade as healthy cells to evade NK and T cell immunity. This is achieved by targeting NLRC5, a key MHC-I transcriptional regulator, via nsp1.

IMPORTANCE

Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that inflicts substantial financial losses on the swine industry. Major histocompatibility complex class I (MHC-I) is a critical factor influencing both CD8
+
T cell and natural killer (NK) cell immunity. However, how PEDV manipulates MHC-I expression to optimize its infection process remains largely unknown. In this study, we demonstrate that PEDV’s nonstructural protein 1 (nsp1) inhibits virus-mediated induction of MHC-I expression by directly targeting NLRC5, a key MHC-I transactivator. Intriguingly, nsp1 does not reduce physiological NLRC5 and MHC-I expression. This selective inhibition of virus-elicited NLRC5 mRNA translation allows PEDV-infected cells to masquerade as healthy cells, thereby evading CD8
+
T cell and NK cell cytotoxicity. Our findings provide unique insights into the mechanisms by which PEDV evades CD8
+
T cell and NK cell immunity.
SydR, a redox-sensing MarR-type regulator of
Sinorhizobium meliloti
, is crucial for symbiotic infection of
Medicago truncatula
roots
Authors: Nazaret Fanny , Farajzadeh Davoud , Mejias Joffrey , Pacoud Marie , Cosi Anthony , Frendo Pierre , Alloing Geneviève , Mandon Karine
Published: October 2024

Rhizobia associate with legumes and induce the formation of nitrogen-fixing nodules. The regulation of bacterial redox state plays a major role in symbiosis, and reactive oxygen species produced by the plant are known to activate signaling pathways. However, only a few redox-sensing transcriptional regulators (TRs) have been characterized in the microsymbiont. Here, we describe SydR, a novel redox-sensing TR of
Sinorhizobium meliloti
that is essential for the establishment of symbiosis with
Medicago truncatula
. SydR, a MarR-type TR, represses the expression of the adjacent gene SMa2023 in growing cultures, and this repression is alleviated by NaOCl,
tert-
butyl hydroperoxide, or H
2
O
2
treatment. Transcriptional
psydR-gfp
and
p
SMa2023-
gfp
fusions, as well as gel shift assays, showed that SydR binds two independent sites of the
sydR
-SMa2023 intergenic region. This binding is redox-dependent, and site-directed mutagenesis demonstrated that the conserved C16 is essential for SydR redox sensing. The inactivation of
sydR
did not alter the sensitivity of
S. meliloti
to NaOCl,
tert
-butyl hydroperoxide, or H
2
O
2
, nor did it affect the response to oxidants of the roGFP2-Orp1 redox biosensor expressed within bacteria. However,
in planta
, Δ
sydR
mutation impaired the formation of root nodules. Microscopic observations and analyses of plant marker gene expression showed that the Δ
sydR
mutant is defective at an early stage of the bacterial infection process. Altogether, these results demonstrated that SydR is a redox-sensing MarR-type TR that plays a key role in the regulation of nitrogen-fixing symbiosis with
M. truncatula
.

IMPORTANCE

The nitrogen-fixing symbiosis between rhizobia and legumes has an important ecological role in the nitrogen cycle, contributes to nitrogen enrichment of soils, and can improve plant growth in agriculture. This interaction is initiated in the rhizosphere by a molecular dialog between the two partners, resulting in plant root infection and the formation of root nodules, where bacteria reduce the atmospheric nitrogen into ammonium. This symbiosis involves modifications of the bacterial redox state in response to reactive oxygen species produced by the plant partner. Here, we show that SydR, a transcriptional regulator of the
Medicago
symbiont
Sinorhizobium meliloti
, acts as a redox-responsive repressor that is crucial for the development of root nodules and contributes to the regulation of bacterial infection in
S. meliloti/Medicago truncatula
symbiotic interaction.
Emerging mosquito-borne flaviviruses
Authors: Nelson Amy N. , Ploss Alexander
Published: October 2024

Flaviviruses comprise a genus of enveloped, positive-sense, single-stranded RNA viruses typically transmitted between susceptible and permissive hosts by arthropod vectors. Established flavivirus threats include dengue viruses (DENV), yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), which continue to cause over 400 million infections annually and are significant global health and economic burdens. Additionally, numerous closely related but largely understudied viruses circulate in animals and can conceivably emerge in human populations. Previous flaviviruses that were recognized to have this potential include ZIKV and WNV, which only became extensively studied after causing major outbreaks in humans. More than 50 species exist within the flavivirus genus, which can be further classified as mosquito-borne, tick-borne, insect-specific, or with no known vector. Historically, many of these flaviviruses originated in Africa and have mainly affected tropical and subtropical regions due to the ecological niche of mosquitoes. However, climate change, as well as vector and host migration, has contributed to geographical expansion, thereby posing a potential risk to global populations. For the purposes of this minireview, we focus on the mosquito-borne subgroup and highlight viruses that cause significant pathology or lethality in at least one animal species and/or have demonstrated an ability to infect humans. We discuss current knowledge of these viruses, existing animal models to study their pathogenesis, and potential future directions. Emerging viruses discussed include Usutu virus (USUV), Wesselsbron virus (WSLV), Spondweni virus (SPOV), Ilheus virus (ILHV), Rocio virus (ROCV), Murray Valley encephalitis virus (MVEV), and Alfuy virus (ALFV).
Draft genome of
Schizophyllum
sp. strain F4_1A, a novel white-rot fungus isolated in Gauteng Province, South Africa
Authors: Ijoma Grace Nkechinyere , Ogola Henry Joseph Oduor , Mafuna Thendo
Published: October 2024

We present a draft genome of
Schizophyllum
sp. F4_1A, a basidiomycete isolated from decaying wood in Gauteng Province, South Africa, sequenced using the MGISEQ-2000RS platform. This draft genome will serve as a valuable genomic resource, enhancing our understanding of white rot fungi and facilitating future comparative genomic analyses.