bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients
Authors: Wang Tianming , Gong Min , Lu Yingfei , Zhao Chengcheng , Ling Ling , Chen Jianquan , Ju Rong 
Published: March 2024

AbstractSquamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.
Ultrawide-field fluorescein angiography features in patients with anterior uveitis
Authors: Nguyen Nam V. , Oyeniran Enny , Zeleny Alexander , Chen Michelle , Sherif Noha A. , Konstantinou Eleni , Vitale Susan , Sen H. Nida , Kodati Shilpa 
Published: March 2024

Abstract
Purpose
To evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management.

Study design/materials and methods
Patients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted.

Results
A total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 – 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients.

Conclusion
Our results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.
Parental kinship coefficient but not paternal coloration predicts early offspring growth in lake char
Authors: Garaud Laura , Nusbaumer David , Marques da Cunha Lucas , de Guttry Christian , Ançay Laurie , Atherton Audrey , Lasne Emilien , Wedekind Claus 
Published: March 2024

AbstractThe ‘good genes’ hypotheses of sexual selection predict that females prefer males with strong ornaments because they are in good health and vigor and can afford the costs of the ornaments. A key assumption of this concept is that male health and vigor are useful predictors of genetic quality and hence offspring performance. We tested this prediction in wild-caught lake char (Salvelinus umbla) whose breeding coloration is known to reveal aspects of male health. We first reanalyzed results from sperm competition trials in which embryos of known parenthood had been raised singly in either a stress- or non-stress environment. Paternal coloration did not correlate with any measures of offspring performance. However, offspring growth was reduced with higher kinship coefficients between the parents. To test the robustness of these first observations, we collected a new sample of wild males and females, used their gametes in a full-factorial in vitro breeding experiment, and singly raised about 3000 embryos in either a stress- or non-stress environment (stress induced by microbes). Again, paternal coloration did not predict offspring performance, while offspring growth was reduced with higher kinship between the parents. We conclude that, in lake char, the genetic benefits of mate choice would be strongest if females could recognize and avoid genetically related males, while male breeding colors may be more relevant in intra-sexual selection.
Quantifying the potential renal acid load of edible mushrooms
Authors: Storz Maximilian Andreas 
Published: March 2024

AbstractThe capability of any food to alter net endogenous acid or base production can be estimated using the potential renal acid load (PRAL) estimation method. The PRAL of edible mushrooms has been rarely examined; thus a quantification study ofn = 37 edible mushroom species was performed. Results revealed a heterogeneous picture: although the most commonly consumed mushrooms (e.g.,Agaricus bisporus,Lentinula edodes, andPleurotus ostreatus(white)) have alkalizing properties, several acidifying species (Volvariella volvacea,Pleurotus flabellatus) were identified, which may be attributable to their high phosphorus content.
Enhanced attenuation of chikungunya vaccines expressing antiviral cytokines
Authors: Chuong Christina , Cereghino Chelsea N. , Rai Pallavi , Bates Tyler A. , Oberer Megan , Weger-Lucarelli James 
Published: March 2024

AbstractAlphaviruses are vector-borne, medically relevant, positive-stranded RNA viruses that cause disease in animals and humans worldwide. Of this group, chikungunya virus (CHIKV) is the most significant human pathogen, responsible for generating millions of infections leading to severe febrile illness and debilitating chronic joint pain. Currently, there are limited treatments to protect against alphavirus disease; thus, there is a tremendous need to generate safe and effective vaccines. Live-attenuated vaccines (LAVs) are cost-effective and potent immunization strategies capable of generating long-term protection in a single dose. However, LAVs often produce systemic viral replication, which can lead to unwanted post-vaccination side effects and pose a risk of reversion to a pathogenic phenotype and transmission to mosquitoes. Here, we utilized a chimeric infectious clone of CHIKV engineered with the domain C of the E2 gene of Semliki Forest virus (SFV) to express IFNγ and IL-21—two potent antiviral and immunomodulatory cytokines—in order to improve the LAV’s attenuation while maintaining immunogenicity. The IFNγ- and IL-21-expressing vaccine candidates were stable during passage and significantly attenuated post-vaccination, as mice experienced reduced footpad swelling with minimal systemic replication and dissemination capacity compared to the parental vaccine. Additionally, these candidates provided complete protection to mice challenged with WT CHIKV. Our dual attenuation strategy represents an innovative way to generate safe and effective alphavirus vaccines that could be applied to other viruses.
Suppression of Dexter transfer by covalent encapsulation for efficient matrix-free narrowband deep blue hyperfluorescent OLEDs
Authors: Cho Hwan-Hee , Congrave Daniel G. , Gillett Alexander J. , Montanaro Stephanie , Francis Haydn E. , Riesgo-Gonzalez Víctor , Ye Junzhi , Chowdury Rituparno , Zeng Weixuan , Etherington Marc K. , Royakkers Jeroen , Millington Oliver , Bond Andrew D. , Plasser Felix , Frost Jarvist M. , Grey Clare P. , Rao Akshay , Friend Richard H. , Greenham Neil C. , Bronstein Hugo 
Published: March 2024

AbstractHyperfluorescence shows great promise for the next generation of commercially feasible blue organic light-emitting diodes, for which eliminating the Dexter transfer to terminal emitter triplet states is key to efficiency and stability. Current devices rely on high-gap matrices to prevent Dexter transfer, which unfortunately leads to overly complex devices from a fabrication standpoint. Here we introduce a molecular design where ultranarrowband blue emitters are covalently encapsulated by insulating alkylene straps. Organic light-emitting diodes with simple emissive layers consisting of pristine thermally activated delayed fluorescence hosts doped with encapsulated terminal emitters exhibit negligible external quantum efficiency drops compared with non-doped devices, enabling a maximum external quantum efficiency of 21.5%. To explain the high efficiency in the absence of high-gap matrices, we turn to transient absorption spectroscopy. It is directly observed that Dexter transfer from a pristine thermally activated delayed fluorescence sensitizer host can be substantially reduced by an encapsulated terminal emitter, opening the door to highly efficient ‘matrix-free’ blue hyperfluorescence.
Single-protein optical holography
Authors: Thiele Jan Christoph , Pfitzner Emanuel , Kukura Philipp 
Published: March 2024

AbstractLight scattering by nanoscale objects is a fundamental physical property defined by their scattering cross-section and thus polarizability. Over the past decade, a number of studies have demonstrated single-molecule sensitivity by imaging the interference between scattering from the object of interest and a reference field. This approach has enabled mass measurement of single biomolecules in solution owing to the linear scaling of image contrast with molecular polarizability. Nevertheless, all implementations so far are based on a common-path interferometer and cannot separate and independently tune the reference and scattered light fields, thereby prohibiting access to the rich toolbox available to holographic imaging. Here we demonstrate comparable sensitivity using a non-common-path geometry based on a dark-field scattering microscope, similar to a Mach–Zehnder interferometer. We separate the scattering and reference light into four parallel, inherently phase-stable detection channels, delivering a five orders of magnitude boost in sensitivity in terms of scattering cross-section over state-of-the-art holographic methods. We demonstrate the detection, resolution and mass measurement of single proteins with mass below 100 kDa. Separate amplitude and phase measurements also yield direct information on sample identity and experimental determination of the polarizability of single biomolecules.
Global supply chains amplify economic costs of future extreme heat risk
Authors: Sun Yida , Zhu Shupeng , Wang Daoping , Duan Jianping , Lu Hui , Yin Hao , Tan Chang , Zhang Lingrui , Zhao Mengzhen , Cai Wenjia , Wang Yong , Hu Yixin , Tao Shu , Guan Dabo 
Published: March 2024

AbstractEvidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input–output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)–0.05 ± 0.03 (SSP 585) percentage points during 2030–2040 to 0.05 ± 0.01–0.15 ± 0.04 percentage points during 2050–2060. By 2060, the expected global economic losses reach a total of 0.6–4.6% with losses attributed to health loss (37–45%), labour productivity loss (18–37%) and indirect loss (12–43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0–3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.
Last-mile delivery increases vaccine uptake in Sierra Leone
Authors: Meriggi Niccolò F. , Voors Maarten , Levine Madison , Ramakrishna Vasudha , Kangbai Desmond Maada , Rozelle Michael , Tyler Ella , Kallon Sellu , Nabieu Junisa , Cundy Sarah , Mobarak Ahmed Mushfiq 
Published: March 2024

AbstractLess than 30% of people in Africa received a dose of the COVID-19 vaccine even 18 months after vaccine development1. Here, motivated by the observation that residents of remote, rural areas of Sierra Leone faced severe access difficulties2, we conducted an intervention with last-mile delivery of doses and health professionals to the most inaccessible areas, along with community mobilization. A cluster randomized controlled trial in 150 communities showed that this intervention with mobile vaccination teams increased the immunization rate by about 26 percentage points within 48–72 h. Moreover, auxiliary populations visited our community vaccination points, which more than doubled the number of inoculations administered. The additional people vaccinated per intervention site translated to an implementation cost of US $33 per person vaccinated. Transportation to reach remote villages accounted for a large share of total intervention costs. Therefore, bundling multiple maternal and child health interventions in the same visit would further reduce costs per person treated. Current research on vaccine delivery maintains a large focus on individual behavioural issues such as hesitancy. Our study demonstrates that prioritizing mobile services to overcome access difficulties faced by remote populations in developing countries can generate increased returns in terms of uptake of health services3.
The evolution of menopause in toothed whales
Authors: Ellis Samuel , Franks Daniel W. , Nielsen Mia Lybkær Kronborg , Weiss Michael N. , Croft Darren P. 
Published: March 2024

AbstractUnderstanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan1,2. Although progress has been made in understanding the adaptive value of menopause in humans3,4, the generality of these findings remains unclear. Toothed whales are the only mammal taxon in which menopause has evolved several times5, providing a unique opportunity to test the theories of how and why menopause evolves in a comparative context. Here, we assemble and analyse a comparative database to test competing evolutionary hypotheses. We find that menopause evolved in toothed whales by females extending their lifespan without increasing their reproductive lifespan, as predicted by the ‘live-long’ hypotheses. We further show that menopause results in females increasing their opportunity for intergenerational help by increasing their lifespan overlap with their grandoffspring and offspring without increasing their reproductive overlap with their daughters. Our results provide an informative comparison for the evolution of human life history and demonstrate that the same pathway that led to menopause in humans can also explain the evolution of menopause in toothed whales.
Mitochondrial complex I activity in microglia sustains neuroinflammation
Authors: Peruzzotti-Jametti L. , Willis C. M. , Krzak G. , Hamel R. , Pirvan L. , Ionescu R.-B. , Reisz J. A. , Prag H. A. , Garcia-Segura M. E. , Wu V. , Xiang Y. , Barlas B. , Casey A. M. , van den Bosch A. M. R. , Nicaise A. M. , Roth L. , Bates G. R. , Huang H. , Prasad P. , Vincent A. E. , Frezza C. , Viscomi C. , Balmus G. , Takats Z. , Marioni J. C. , D’Alessandro A. , Murphy M. P. , Mohorianu I. , Pluchino S. 
Published: March 2024

AbstractSustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.
Substrate-induced condensation activates plant TIR domain proteins
Authors: Song Wen , Liu Li , Yu Dongli , Bernardy Hanna , Jirschitzka Jan , Huang Shijia , Jia Aolin , Jemielniak Wictoria , Acker Julia , Laessle Henriette , Wang Junli , Shen Qiaochu , Chen Weijie , Li Pilong , Parker Jane E. , Han Zhifu , Schulze-Lefert Paul , Chai Jijie 
Published: March 2024

AbstractPlant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR–NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.
Geographical distribution of radon and associated health risks in drinking water samples collected from the Mulazai area of Peshawar, Pakistan
Authors: Shah Syed Samran Ali , Asif Abdul Rahim , Ilahi Manzoor , Haroon Haseeb , Islam Ihtisham , Qadir Adnan , Nisar Irfan , Sani Malik Muhammad Usman , Iqbal Rashid , Rahman Muhammed Habib ur , Arslan Muhammad , Alwahibi Mona S. , Elshikh Mohamed S. , Ditta Allah 
Published: March 2024

AbstractGeospatial methods, such as GIS and remote sensing, map radon levels, pinpoint high-risk areas and connect geological traits to radon presence. These findings direct health planning, focusing tests, mitigation, and policies where radon levels are high. Overall, geospatial analyses offer vital insights, shaping interventions and policies to reduce health risks from radon exposure. There is a formidable threat to human well-being posed by the naturally occurring carcinogenic radon (222Rn) gas due to high solubility in water. Under the current scenario, it is crucial to assess the extent of 222Rn pollution in our drinking water sources across various regions and thoroughly investigate the potential health hazards it poses. In this regard, the present study was conducted to investigate the concentration of 222Rn in groundwater samples collected from handpumps and wells and to estimate health risks associated with the consumption of 222Rn-contaminated water. For this purpose, groundwater samples (n = 30) were collected from handpumps, and wells located in the Mulazai area, District Peshawar. The RAD7 radon detector was used as per international standards to assess the concentration of 222Rn in the collected water samples. The results unveiled that the levels of 222Rn in the collected samples exceeded the acceptable thresholds set by the US Environmental Protection Agency (US-EPA) of 11.1 Bq L−1. Nevertheless, it was determined that the average annual dose was below the recommended limit of 0.1 mSv per year, as advised by both the European Union Council and the World Health Organization. In order to avoid the harmful effects of such excessive 222Rn concentrations on human health, proper ventilation and storage of water in storage reservoirs for a long time before use is recommended to lower the 222Rn concentration.
Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine
Authors: Jmel Haifa , Sarno Stefania , Giuliani Cristina , Boukhalfa Wided , Abdelhak Sonia , Luiselli Donata , Kefi Rym 
Published: March 2024

AbstractAdverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in SLC22A1, HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.
Adaptation to numerosity affects the pupillary light response
Authors: Caponi Camilla , Castaldi Elisa , Burr David Charles , Binda Paola 
Published: March 2024

AbstractWe recently showed that the gain of the pupillary light response depends on numerosity, with weaker responses to fewer items. Here we show that this effect holds when the stimuli are physically identical but are perceived as less numerous due to numerosity adaptation. Twenty-eight participants adapted to low (10 dots) or high (160 dots) numerosities and subsequently watched arrays of 10–40 dots, with variable or homogeneous dot size. Luminance was constant across all stimuli. Pupil size was measured with passive viewing, and the effects of adaptation were checked in a separate psychophysical session. We found that perceived numerosity was systematically lower, and pupillary light responses correspondingly smaller, following adaptation to high rather than low numerosities. This is consistent with numerosity being a primary visual feature, spontaneously encoded even when task irrelevant, and affecting automatic and unconscious behaviours like the pupillary light response.