bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a novel estrogenic perfluoroalkyl substance on reproductive endocrinology and function in the fathead minnow (Pimephales promelas)
Authors: Ankley Gerald T , Jensen Kathleen M , Cavallin Jenna E , Baettig Camille , Balgooyen Sarah , Blackwell Brett R , Blanksma Chad A , Collins Jacob , Ellman Michael , Hoang John , Kahl Michael D , Santana-Rodriguez Kelvin , Schaupp Christopher M , Stacy Emma , Villeneuve Daniel L
Published: January 2025

Effects data are lacking for the majority of poly- and perfluoroalkyl substances (PFAS). Recent in vitro work with around 140 data-poor PFAS showed that several could affect signaling pathways associated with estrogen receptor-α (ER). Subsequent short-term gene expression studies with adult male fathead minnows (Pimephales promelas) using a subset of the ER-active PFAS confirmed their estrogenic properties in vivo. Herein, we evaluated the effects of the most potent of these, 1H, 1H, 10H, 10H-perfluorodecane-1,10-diol (FC10-diol), in a multi-endpoint fathead minnow reproduction assay designed for endocrine-disrupting chemicals. Fish were exposed for 21 days to five water concentrations of FC10-diol, ranging from 0.68 to 68 µg/L, or 17β-estradiol as a positive control. Data confirmed FC10-diol as an ER agonist. Responses in males included changes in expression of four hepatic genes controlled by ER, induction of plasma vitellogenin (VTG; egg yolk protein precursor), decreased expression of male secondary sexual characteristics, histopathological changes in the testis and kidney, and mortality in the highest FC10-diol treatment group. Effects in females from the high treatment included altered ovarian expression of genes involved in steroid synthesis, decreased plasma steroids, elevated plasma VTG, histological changes in the ovary and kidney, and decreased egg production. In addition to generating baseline toxicological data, study results enabled evaluation and expansion of two adverse outcome pathways (AOPs) for predicting the effects of ER agonists in fish. One of the AOPs links activation of the ER to abnormal production of VTG, resulting in kidney dysfunction and death, whereas the second connects ER activation to altered gonadotropin signaling, resulting in decreased synthesis of maturation-inducing steroids and consequent effects on oocyte development and release.
Taking a stand, ready or not: navigating sensitive end-of-life care conversations in patients with end-stage heart failure
Authors: Róin Tóra , Jurlander Birgit , Juhl Gitte Irene , Dieperink Karin B , Sjøgren Per , Bergenholtz Heidi , Zwisler Ann-Dorthe , Kurita Geana Paula , Larsen Sille , Tønder Niels , Høyer Lene Vibe , Lykke Camilla
Published: January 2025

Aims

Patients with heart failure (HF) often experience delayed identification of palliative care needs. While communication with HF patients and their caregivers is increasingly stressed, systematic conversations about end-of-life care wishes remain a gap. This study explores a dyad experience of Advance Care Planning (ACP) conversations in an HF outpatient clinic.

Methods and results

A qualitative interview study with 15 patients diagnosed with end-stage HF and 14 caregivers. Through qualitative content analysis and investigator triangulation, three subthemes emerged: ‘ACP as a harsh reality’, ‘ACP as a catalyst for crucial conversations’, and ‘ACP conversations help appreciating life’s small moments and adjusting hope’. Despite significant symptom burden, many patients lacked awareness of their end-stage HF prognosis. Following an initial ‘reality shock’, ACP conversations facilitated open discussions about end-of-life care wishes. Especially spousal caregivers experienced a significant caregiving load, generating complex emotions for both patients and their families. Notably, patients prioritized self-care, daily activities, and social interaction for maintaining quality of life.

Conclusion

This study highlights a gap between patients with end-stage HF disease status and their comprehension of disease severity. Early integration of ACP may address knowledge gaps, enable informed decision-making, and alleviate caregiver burden. The study also emphasizes the patient-and family-centred care to support self-care, daily life activities, and social connections for improved quality of life throughout the disease trajectory.

Registration

ClinicalTrials.gov: NCT05269875
Comparison of blood pressure measurements between a smartphone application and the upper arm automated cuff: a prospective study with an invasive reference
Authors: Lakhal Karim , Dauvergne Jérôme E , Audran Alexia , Normand Gurvan , Rozec Bertrand , Boulain Thierry
Published: January 2025

Registration  ClinicalTrials.gov: NCT06032169.
Population Genomics of Japanese Macaques (Macaca fuscata): Insights Into Deep Population Divergence and Multiple Merging Histories
Authors: Higashino Atsunori , Nakamura Katsuki , Osada Naoki
Published: January 2025

The influence of long-term climatic changes such as glacial cycles on the history of living organisms has been a subject of research for decades, but the detailed population dynamics during the environmental fluctuations and their effects on genetic diversity and genetic load are not well understood on a genome-wide scale. The Japanese macaque (Macaca fuscata) is a unique primate adapted to the cold environments of the Japanese archipelago. Despite the past intensive research for the Japanese macaque population genetics, the genetic background of Japanese macaques at the whole-genome level has been limited to a few individuals, and the comprehensive demographic history and genetic differentiation of Japanese macaques have been underexplored. We conducted whole-genome sequencing of 64 Japanese macaque individuals from 5 different regions, revealing significant genetic differentiation and functional variant diversity across populations. In particular, Japanese macaques have low genetic diversity and harbor many shared and population-specific gene loss, which might contribute to population-specific phenotypes. Our estimation of population demography using phased haplotypes suggested that, after the strong population bottleneck shared among all populations around 400 to 500 kya, the divergence among populations initiated around 150 to 200 kya, but there has been the time with strong gene flow between some populations after the split, indicating multiple population split and merge events probably due to habitat fragmentation and fusion during glacial cycles. These findings not only present a complex population history of Japanese macaques but also enhance their value as research models, particularly in neuroscience and behavioral studies. This comprehensive genomic analysis sheds light on the adaptation and evolution of Japanese macaques, contributing valuable insights to both evolutionary biology and biomedical research.
Reconciling aging and slip state evolutions from laboratory-derived canons of rate-and-state friction
Authors: Sato Dye S K , Nakatani Masao , Ando Ryosuke
Published: January 2025

The aging law and the slip law are two representative evolution laws of the rate- and state-dependent friction (RSF) law, based on canonical behaviours in three types of laboratory experiments: slide-hold-slide (SHS), velocity-step (VS) and steady-state (SS) tests. The aging law explains the SHS canon but contradicts the VS canon, and vice versa for the slip law. The later proposed composite law, which switches these two laws according to the slip rate V, explains both canons but contradicts the SS canon. This study constructs evolution laws satisfying all three canons throughout the range of variables where experiments have confirmed the canons. By recompiling the three canons, we have derived constraints on the evolution law and found that the evolution rates in the strengthening phases of the SHS and VS canons are so different that complete reconciliation throughout the entire range of variables is mathematically impossible. However, for the limited range of variables probed by experiments so far, we have found that the SHS and VS canons can be reconciled without violating the SS canon by switching the evolution function according to $\Omega$, the ratio of the state $\theta$ to its steady-state value $\theta _{\rm SS}$ for the instantaneous slip rate. We could generally show that, as long as the state evolution rate $\dot{\theta }$ depends only on the instantaneous values of V and $\theta$, simultaneous reproduction of the three canons, throughout the experimentally confirmed range, requires the aging-law-like evolution for $\Omega$ sufficiently below a threshold $\beta$ and the slip-law-like evolution for $\Omega$ sufficiently above $\beta$. The validity of the canons in existing experiments suggests $\beta \lesssim 0.01$.
The evolution of fault orientation in the 2019 Ridgecrest earthquake sequence with a new long-term catalogue of seismicity and moment tensors
Authors: Atterholt James , Wilding John D , Ross Zachary E
Published: January 2025

Throughout an earthquake sequence, perturbations to the stress field may lead to changes in the distribution of active fault orientations. Resolving such changes for narrow spatiotemporal windows requires high-quality seismicity catalogues and objective techniques to measure fault orientations. We investigate the evolution of fault orientations throughout the 2019 Ridgecrest earthquake sequence using a new seismicity catalogue that captures the sequence over several years. We generate this catalogue using a state-of-the-art workflow for event detection, absolute and relative relocation, and moment tensor inversion. With this catalogue, we measure high-resolution, time-dependent changes in the orientations of active faults using a technique from spatial statistics that quantifies anisotropic features in point processes. We evaluate the results alongside those of more standard techniques based on focal mechanisms. Near the centroid of the mainshock, we observe a substantial shift in the distribution of fault orientations, whereas to the south of the mainshock centroid, we observe only a moderate transient change in the distribution of fault orientations. Compared with results derived from focal mechanisms alone, our findings suggest a smaller background differential stress and a distinct response of the stress state to post-seismic deformation.
Illustrating the structures of bias from immortal time using directed acyclic graphs
Authors: Yang Guoyi , Burgess Stephen , Schooling Catherine Mary
Published: January 2025

Background

Immortal time is a period of follow-up during which death or the study outcome cannot occur by design. Bias from immortal time has been increasingly recognized in epidemiological studies. However, the fundamental causes and structures of bias from immortal time have not been explained systematically.

Methods

We use an example ‘Does winning a Nobel Prize prolong lifespan?’ for illustration. We illustrate how immortal time arises and present structures of bias from immortal time using directed acyclic graphs that specify time-varying variables. We further explore the structures of bias with the exclusion of immortal time and with the presence of competing risks. We discuss how these structures are shared by different study designs in pharmacoepidemiology and provide solutions, where possible, to address the bias.

Results

The fundamental cause of immortal time is misalignment of exposure allocation and eligibility. Specifically, immortal time arises from using post-eligibility information to define exposure or using post-exposure information to define eligibility. The structures of bias from immortal time are confounding by survival until exposure allocation or selection bias from selecting on survival until eligibility. Excluding immortal time from follow-up does not fully address this confounding or selection bias, and the presence of competing risks can worsen the bias. Bias from immortal time may be avoided by aligning baseline, exposure allocation and eligibility, and by excluding individuals with prior exposure.

Conclusions

Understanding bias from immortal time in terms of confounding or selection bias helps researchers identify and thereby avoid or ameliorate this bias.
Finite element analysis of hygrothermal interactions in date palm concrete, autoclaved aerated concrete, and gypsum walls using the Künzel model under arid and hot Climate
Authors: Bendekhis Mourad , Fezzioui Naima , Benyamine Mébirika , Osra Oumr Adnan , Alkhafaji Mohammed Ayad , Dikandé Alain M , Kaid Noureddine , Menni Younes , Chamkha Ali J
Published: January 2025

This paper assesses the hygrothermal performance of date palm concrete (DPC), autoclaved aerated concrete (AAC), and gypsum walls for arid climates using the Künzel model and finite element method. The profiles of temperature, relative humidity, and water content were determined under different boundary conditions. Among them, DPC exhibited the highest thermal conductivity and retained more moisture; therefore, cooling occurred much faster in the case of DPC when compared with AAC and gypsum. The temperature profiles were linearly varied, humidity relative humidity profile expressed the superior hygroscopic property of DPC. These findings guide material selection for arid climates and highlight DPC for its superior thermal and moisture management.
High-Dose Inactivated Influenza Vaccine Inconsistently Improves Heterologous Antibody Responses in an Older Human Cohort
Authors: Billings W Zane , Ge Yang , Knight Jessica H , Hemme Hayley , Hammerton Savannah M , Skarlupka Amanda L , Cao Wangnan , Shen Ye , Bahl Justin , Thomas Paul G , Ross Ted M , Handel Andreas
Published: January 2025

Background

Older adults often mount a weak immune response to standard inactivated influenza vaccines. To induce a stronger response and better protection, a high-dose (HD) version of the inactivated Fluzone vaccine is recommended for individuals >65 years of age. While better immunogenicity and protection against the vaccine strain have been shown, it is not known if the HD vaccine also induces a robust antibody response to heterologous strains.

Methods

We fit bayesian multilevel regression models to hemagglutination inhibition antibody data from an influenza vaccine cohort spanning the influenza seasons of 2013–2014 to 2021–2022. We used this model to estimate the average causal effect of obtaining the HD vaccine relative to the standard-dose vaccine.

Results

We show that while there is generally a benefit derived from the HD vaccine, the impact is small and inconsistent. For some strains, the HD vaccine might even result in less robust heterologous responses.

Conclusions

We suggest that further increases in dose might be worth investigating to help induce a stronger broad response.
Availability of pesticide-treated seeds and bird occurrence in freshly drilled onion and carrot fields in Brazil
Authors: Souza Santos Gustavo , Casallanovo Fábio , Cione Ana Paola , Artal Mariana Coletty , Felici José Paulo , Paniago Mario del Giudice , von Blanckenhagen Felix , Vallon Martin , Ludwigs Jan-Dieter , Farrelly Eamonn , Kragten Steven , Maul Jonathan D
Published: January 2025

Agricultural landscapes in Brazil provide habitat to various bird species, which may be exposed to pesticide-treated seeds that have not been incorporated into the soil during drilling. Understanding the dynamics and interactions between birds and drilled fields is crucial for developing sustainable farming practices that balance agricultural food production with wildlife conservation. This study focused on the attractivity of freshly drilled onion and carrot fields to birds and the potential exposure of birds to the pesticide-treated onion and carrot seeds available on the soil surface after drilling in Minas Gerais, Brazil. Bird surveys were conducted using scan sampling and point count methods to assess diversity and behavior before, on the day of drilling, and after drilling. Carrot fields showed a decrease in observed species and individuals on the day of drilling, with an increase in bird sightings after drilling. Similar trends were observed in onion fields, with the species composition changing after drilling and a significant decrease in abundance on the day of drilling. None of the species found foraging in the field after drilling were granivorous or omnivorous. Seed exposure was assessed by counting available seeds on the soil surface at different time points after drilling. Seed exposure was higher in the field border than in the field center. These findings indicate that carrot and onion fields offer limited food sources for granivore bird species probably due to low seed availability and intensive seedbed preparation. The research also suggests that freshly drilled carrot and onion crops are unattractive to foraging birds, with low seed exposure and a reduced likelihood of contact with pesticides applied as a seed treatment.
AI as an intervention: improving clinical outcomes relies on a causal approach to AI development and validation
Authors: Joshi Shalmali , Urteaga Iñigo , van Amsterdam Wouter A C , Hripcsak George , Elias Pierre , Recht Benjamin , Elhadad Noémie , Fackler James , Sendak Mark P , Wiens Jenna , Deshpande Kaivalya , Wald Yoav , Fiterau Madalina , Lipton Zachary , Malinsky Daniel , Nayan Madhur , Namkoong Hongseok , Park Soojin , Vogt Julia E , Ranganath Rajesh
Published: January 2025

The primary practice of healthcare artificial intelligence (AI) starts with model development, often using state-of-the-art AI, retrospectively evaluated using metrics lifted from the AI literature like AUROC and DICE score. However, good performance on these metrics may not translate to improved clinical outcomes. Instead, we argue for a better development pipeline constructed by working backward from the end goal of positively impacting clinically relevant outcomes using AI, leading to considerations of causality in model development and validation, and subsequently a better development pipeline. Healthcare AI should be “actionable,” and the change in actions induced by AI should improve outcomes. Quantifying the effect of changes in actions on outcomes is causal inference. The development, evaluation, and validation of healthcare AI should therefore account for the causal effect of intervening with the AI on clinically relevant outcomes. Using a causal lens, we make recommendations for key stakeholders at various stages of the healthcare AI pipeline. Our recommendations aim to increase the positive impact of AI on clinical outcomes.
On Being Simultaneously Arab and “Modern”: Saloua Raouda Choucair’s Design Between Science and Sufism
Authors: Taan Yasmine Nachabe
Published: January 2025

This article discusses Saloua Raouda Choucair’s commitment to design through her combined interest in science and Sufism. Her artistic and design accomplishments portray her as a resolute and determined woman who actively pursued education, independence, and progress throughout her career. By looking into Saloua’s engagement with science, technology, and mysticism, this study seeks to unravel the nuanced intersections between tradition and modernity, craftsmanship, and technology in the realm of design production. The aim is to illuminate how her utilization of scientific knowledge and Sufism shaped her design thinking, challenging prevailing norms and contributing to a broader understanding of the dynamic relationship between gender, education, and design practice in Lebanon. This research aims to interrogate the intricacies of design production by challenging the conventional dichotomy that juxtaposes tradition against modernity and craftsmanship against technology.
Effects of Metarhizium anisopliae on lethality, transfer, behavior, and physiology in Eucryptorrhynchus scrobiculatus and E. brandti (Coleoptera: Curculionidae)
Authors: Sun Xuewen , Wen Chao , Yang Danhui , Zhang Genzhuang , Zhang Bohan , Wen Junbao
Published: January 2025

Eucryptorrhynchus scrobiculatus (Motschulsky) and E. brandti (Harold) are 2 serious pests inflicting damage on Ailanthus altissima (Mill.) Swingle. In the field, these species exhibit aggregation behavior. We hypothesized that this behavior facilitated the contact and horizontal transfer of Metarhizium anisopliae (Metschn.) Sorokin in weevil species. Little or no mortality in both E. scrobiculatus and E. brandti adult individuals exposed to low concentrations M. anisopliae (1 × 105, 1 × 106 conidia/ml). A mortality rate of 100% was observed in both E. scrobiculatus and E. brandti adults after 3 and 5 d of treatment with M. anisopliae at concentrations of 1 × 109 and 1 × 108 conidia/ml. The aggregation behavior of E. scrobiculatus and E. brandti adults was unaffected by M. anisopliae. In the transfer test of M. anisopliae, the mortality rate of recipients mixed with donors treated with M. anisopliae conidia was significantly higher compared to untreated donors and control recipients in laboratory and field experiments. Furthermore, the mortality of secondary recipients in both E. scrobiculatus and E. brandti was significantly higher than that of the control group. The findings suggested that horizontal transfer of M. anisopliae occurred in both species, which was further supported by microscopy observation and the activity of immune-related enzymes in the donor, recipient, and secondary recipient. Our findings demonstrated a specific method for improving pest control by combining aggregation behavior with the use of biopesticides, thereby enhancing the understanding of biological management strategies.
Remaking trade for a sustainable future
Authors: Trachtman Joel , Remy Jan Yves , Esty Daniel C
Published: January 2025

The articles in this Special Feature have been developed as part of the Remaking Trade for a Sustainable Future Project and are a part of the research and analysis that formed the background for the Villars Framework 2.0 report prepared through that project to develop a vision for reform of the international trade system in order to promote sustainable development.
Fisheries subsidies, the WTO, and sustainability
Authors: De Gama Mustaqeem
Published: January 2025

This article analyses the World Trade Organization (WTO) fisheries subsidies mandate and the outcomes of the 12th and 13th Ministerial Conferences. It assesses the relative merits of outcomes under the various pillars of negotiations and recommends a greater focus on addressing issues such as special and differential treatment, overfishing, and overcapacity. In order to address overfishing and overcapacity, WTO members that subsidize long-range fishing must drastically reduce such subsidies due to their deleterious impact on fish stocks, the marine environment, and the livelihoods of millions of low resource fishers.
Topical review: sleep regulation as a novel target for treating preschool-aged children with attention-deficit/hyperactivity disorder symptoms
Authors: Lunsford-Avery Jessica R , Wu Jade Q , French Alexis , Davis Naomi O
Published: January 2025

Objective

Elevated attention-deficit/hyperactivity disorder (ADHD) symptoms in preschoolers are a risk factor for poorer psychiatric health, cognitive deficits, and social and academic impairment across the lifespan. The first-line treatment for these preschoolers, behavioral parent training (BPT), reduces children’s disruptive behaviors and parenting stress, yet its impact on core ADHD symptoms is inconsistent. Early interventions targeting biological mechanisms linked to core ADHD pathophysiology are critically needed.

Methods

This topical review explores sleep dysregulation as a potential key target for early intervention for ADHD symptoms among preschoolers.

Results

Sleep dysregulation is common in school-aged children with ADHD, and treating sleep improves core ADHD symptoms in older children. Cross-sectional and prospective research with preschoolers offers compelling evidence that sleep dysregulation and ADHD symptoms are closely linked over the course of early development. BPT and behavioral sleep medicine (BSM) interventions share an underlying theoretical framework and could be streamlined to target sleep in addition to daytime behaviors.

Conclusions

Novel early interventions targeting underlying biological mechanisms linked to core ADHD pathophysiology are critically needed to improve the trajectories of ADHD symptoms, comorbidity, and functional deficits for preschoolers with elevated ADHD symptoms. Sleep regulation is a promising mechanistic treatment target for this population, and future interventions may draw from the shared behavioral principles of BPT and BSM to target behaviors across the 24-hr period and employ scalable formats to optimize the number of families who can benefit from parent-based interventions targeting ADHD symptoms and sleep in early development.
Persistent ascending mesocolon: an unexpected content in a giant and complex paraumbilical hernia of a 48-year-old obese woman
Authors: Naabo Nuhu N , Maalman Raymond S , Adamu Aishah F , Naabo Mohammed N , Mensah Samuel
Published: January 2025

Persistent ascending mesocolon (PAM) is a rare congenital anomaly in ⁓2%–4% of individuals. PAM is associated with various complications, including volvulus of the colon and caecum, bowel perforation, intestinal obstruction, and adhesions. This case is reported on a 48-year-old woman who reported to the Ho Teaching Hospital specialist clinic with a 13-year history of initial painless and reducible paraumbilical swelling. Management was based on a surgical approach. The content of the hernia sac was unusual with a viable appendix, caecum, ascending and transverse colons inclusive, and ascending mesocolon was persistent. The repair was done through an anterior component separation technique. An onlay mesh repair was fashioned with a 30 cm × 30 cm polypropylene mesh. This case report highlights the complexities of managing a giant paraumbilical hernia in a morbidly obese patient with a PAM, a rare congenital anomaly.
Increased burstiness at high redshift in multiphysics models combining supernova feedback, radiative transfer, and cosmic rays
Authors: Dome Tibor , Martin-Alvarez Sergio , Tacchella Sandro , Yuan Yuxuan , Sijacki Debora
Published: January 2025

We study star formation variability, or burstiness, as a method to constrain and compare different galaxy formation models at high redshift using the azahar simulation suite. The models range from magnetohydrodynamics with turbulence-driven star formation to more sophisticated set-ups incorporating radiative transfer and cosmic ray physics. Analysing a sample of galaxies at redshifts $z=4-10$, we find that including both radiative transfer and cosmic rays results in more regular star formation periodicity, as revealed by the Lomb–Scargle periodogram. While both radiative transfer and cosmic rays amplify star formation stochasticity, their combination leads to the largest scatter in burst intensity and the most pronounced deviations from the star-forming main sequence. To compare this comprehensive model against observations, we generate a mock spectrum of a low-mass galaxy during a mini-quenching event at $z=7.5$. The resulting spectrum aligns well with the low-mass quiescent galaxy JADES-GS-z7-01-QU observed at $z=7.3$, though discrepancies attributed to stellar metallicity suggest it may have a composite nature. Our findings highlight the importance of including complex physical processes like cosmic rays and radiative transfer in simulations to accurately capture the bursty nature of star formation in early galaxy formation. Future JWST observations, particularly of the scatter around the star-forming main sequence, might provide critical constraints for numerical models of galaxy formation at high redshift.
Selection Can Favor a Recombination Landscape That Limits Polygenic Adaptation
Authors: Parée Tom , Noble Luke , Roze Denis , Teotónio Henrique
Published: January 2025

Modifiers of recombination rates have been described but the selective pressures acting on them and their effect on adaptation to novel environments remain unclear. We performed experimental evolution in the nematode Caenorhabditis elegans using alternative rec-1 alleles modifying the position of meiotic crossovers along chromosomes without detectable direct fitness effects. We show that adaptation to a novel environment is impaired by the allele that decreases recombination rates in the genomic regions containing fitness variation. However, the allele that impairs adaptation is indirectly favored by selection, because it increases recombination rates and reduces the associations among beneficial and deleterious variation located in its chromosomal vicinity. These results validate theoretical expectations about the evolution of recombination but suggest that genome-wide polygenic adaptation is of little consequence to indirect selection on recombination rate modifiers.
Interplay between the Xer recombination system and the dissemination of antibioresistance in Acinetobacter baumannii
Authors: Blanchais Corentin , Pages Carine , Campos Manuel , Boubekeur Kenza , Contarin Rachel , Orlando Mathias , Siguier Patricia , Laaberki Maria-Halima , Cornet François , Charpentier Xavier , Rousseau Philippe
Published: January 2025

Antibiotic-resistant infections are a pressing clinical challenge. Plasmids are known to accelerate the emergence of resistance by facilitating horizontal gene transfer of antibiotic resistance genes between bacteria. We explore this question in Acinetobacter baumannii, a globally emerging nosocomial pathogen responsible for a wide range of infections with a worrying accumulation of resistance, particularly involving plasmids. In this species, plasmids of the Rep_3 family harbor antibiotic resistance genes within variable regions flanked by potential site-specific recombination sites recognized by the XerCD recombinase. We first show that the Xer system of A. baumannii functions as described in Escherichia coli, resolving chromosome dimers at the dif site and recombining plasmid-carried sites. However, the multiple Xer recombination sites found in Rep_3 plasmids do not allow excision of plasmid fragments. Rather, they recombine to cointegrate plasmids, which could then evolve to exchange genes. Cointegrates represent a significant fraction of the plasmid population and their formation is controlled by the sequence of recombination sites, which determines the compatibility between recombination sites. We conclude that plasmids in A. baumannii frequently recombine by Xer recombination, allowing a high level of yet controlled plasticity in the acquisition and combination of antibiotic resistance genes.
SProtFP: a machine learning-based method for functional classification of small ORFs in prokaryotes
Authors: Khanduja Akshay , Mohanty Debasisa
Published: January 2025

Small proteins (≤100 amino acids) play important roles across all life forms, ranging from unicellular bacteria to higher organisms. In this study, we have developed SProtFP which is a machine learning-based method for functional annotation of prokaryotic small proteins into selected functional categories. SProtFP uses independent artificial neural networks (ANNs) trained using a combination of physicochemical descriptors for classifying small proteins into antitoxin type 2, bacteriocin, DNA-binding, metal-binding, ribosomal protein, RNA-binding, type 1 toxin and type 2 toxin proteins. We have also trained a model for identification of small open reading frame (smORF)-encoded antimicrobial peptides (AMPs). Comprehensive benchmarking of SProtFP revealed an average area under the receiver operator curve (ROC-AUC) of 0.92 during 10-fold cross-validation and an ROC-AUC of 0.94 and 0.93 on held-out balanced and imbalanced test sets. Utilizing our method to annotate bacterial isolates from the human gut microbiome, we could identify thousands of remote homologs of known small protein families and assign putative functions to uncharacterized proteins. This highlights the utility of SProtFP for large-scale functional annotation of microbiome datasets, especially in cases where sequence homology is low. SProtFP is freely available at http://www.nii.ac.in/sprotfp.html and can be combined with genome annotation tools such as ProsmORF-pred to uncover the functional repertoire of novel small proteins in bacteria.
Long-read structural and epigenetic profiling of a kidney tumor-matched sample with nanopore sequencing and optical genome mapping
Authors: Margalit Sapir , Tulpová Zuzana , Detinis Zur Tahir , Michaeli Yael , Deek Jasline , Nifker Gil , Haldar Rita , Gnatek Yehudit , Omer Dorit , Dekel Benjamin , Baris Feldman Hagit , Grunwald Assaf , Ebenstein Yuval
Published: January 2025

Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural variants (SVs) and copy number variations (CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing [Oxford Nanopore Technologies (ONT)] bridge this resolution gap and offer enhanced performance for cytogenetic applications. Additionally, both methods can capture epigenetic information as they profile native, individual DNA molecules. We compared the effectiveness of the two methods in characterizing the structural, copy number and epigenetic landscape of a clear cell renal cell carcinoma tumor. Both methods provided comparable results for basic karyotyping and CNVs, but differed in their ability to detect SVs of different sizes and types. ONT outperformed OGM in detecting small SVs, while OGM excelled in detecting larger SVs, including translocations. Differences were also observed among various ONT SV callers. Additionally, both methods provided insights into the tumor’s methylome and hydroxymethylome. While ONT was superior in methylation calling, hydroxymethylation reports can be further optimized. Our findings underscore the importance of carefully selecting the most appropriate platform based on specific research questions.
Mapping glioma’s impact on cognition: Insights from macrostructure, microstructure, and beyond
Authors: Cayuela Nuria , Izquierdo Cristina , Vaquero Lucía , Càmara Estela , Bruna Jordi , Simó Marta
Published: January 2025

Background

Cognitive impairment (CI) significantly impacts the quality of life of glioma patients. The main contributing risk factors include tumor characteristics, treatment-related factors, and their complex interplay. This review explores the role of advanced structural neuroimaging techniques in understanding CI in glioma patients.

Methods

A literature search was conducted in PubMed, PsycINFO, and ISI Web of Knowledge using specific keywords. We included studies with advanced magnetic resonance imaging techniques and objective neuropsychological exams.

Results

At diagnosis, during the pre-surgery phase, associations between glioma characteristics and cognitive outcomes have been described. Specifically, patients with isocitrate dehydrogenase (IDH)-wild-type gliomas exhibit more adverse cognitive outcomes, accompanied by disruptions in gray (GM) and white matter (WM) networks when compared to IDH-mutant. In addition, pre- and post-surgery imaging analyses highlight the importance of preserving specific WM tracts, such as the inferior longitudinal and arcuate fasciculus, in mitigating verbal memory and language processing decline. Furthermore, examining gliomas in perisylvian regions emphasizes deleterious effects on various cognitive domains. Additionally, it has been suggested that neuroplastic reorganization could serve as a compensatory mechanism against CI. Lastly, a limited number of studies suggest long-term CI linked to GM atrophy and leukoencephalopathy induced by radiotherapy ± chemotherapy in glioma survivors, highlighting the need for improving treatment approaches, particularly for patients with extended survival expectations.

Conclusion

This review underscores the need for nuanced understanding and an individual approach in the management of glioma patients. Neuroplastic insights offer clinicians valuable guidance in surgical decision-making and personalized therapeutic approaches thus improving patient outcomes in neuro-oncology.
Construction of the Gene Tagging and Knock Out system for reliable genetic analysis of nuclear genes in Cyanidioschyzon merolae
Authors: Bora Prerna , Tanaka Kan
Published: January 2025

The unicellular red alga Cyanidioschyzon merolae is a eukaryotic photosynthetic model organism used for basic and applied cell biology studies. Its nuclear genome can be modified by homologous recombination with exogenously introduced DNA. The comparison of mutants with isogenic strains is critical for reliable genetic analyses; however, this has been impossible thus far. Strain construction and genetic complementation studies take a long time and give rise to unstable phenotypes. In this study, we modified the pMKT vector system described in Takemura et al. (Takemura, T., Imamura, S., Kobayashi, Y. and Tanaka, K. (2018) Construction of a selectable marker recycling system and the use in epitope tagging of multiple nuclear genes in the unicellular red alga Cyanidioschyzon merolae. Plant Cell Physiol. 59: 2308–2316.) by adding an upstream sequence of the target gene, after the URA5.3 T marker, to create a double sandwich of repeat elements at the target gene genomic loci after transformation. 5-Fluoroorotic acid selection-based DNA excision yields two mutants simultaneously: an epitope-tagged mutant with only the URA5.3 marker eliminated and a knockout mutant with both URA5.3 T and the target gene’s open reading frame eliminated. This system can provide multiple sets of isogenic controls in parallel, and further reveal the essentialness of a gene. Here, we introduce the multifunctional mutant design system Gene Tagging and Knock Out (GTKO), and demonstrate its utility by creating GTKO mutants of the CmBTB1 and CmBTB2 genes in C. merolae.
Natural variation in a molybdate transporter confers salt tolerance in tomato
Authors: Wang Zhen , Hong Yechun , Guo Zhaojun , Li Dianjue , Chao Zhen-Fei , Zhu Guangtao , Zhu Jian-Kang
Published: January 2025

Natural variation in a molybdate transporter-encoding gene is associated with molybdenum accumulation, which reduces hypocotyl growth and improves salt tolerance in tomato.
Genetic insights into visceral obesity with health conditions, from disease susceptibility to therapeutic intervention
Authors: Zhang Genshan , Han Baolin , Chen Yanghui , Jiang Wei , Fu Jie , Xu Xiangshang , Luo Xuelai , Cao Zhixin
Published: January 2025

Purpose

This study aimed to investigate the relationship between visceral obesity and various disease traits, as well as to identify potential safe targets for the prevention and treatment of visceral obesity.

Study Design

Univariable and multivariable Mendelian randomization (MR) analyses were performed to examine the associations between visceral obesity and 1883 disease traits. Furthermore, we assessed the potential effect of 1684 protein expressions on visceral obesity using the available quantitative trait locus data for plasma proteins. To evaluate the potential safety profiles associated with biomarker intervention, we conducted phenome-wide MR using 1883 outcomes, focusing on the significant biomarkers.

Results

Visceral obesity was significantly associated with elevated risks of 183 disease traits across multiple systems, such as endocrine, cardiovascular, respiratory, digestive, musculoskeletal, and genitourinary systems. Higher genetically predicted levels of GCKR, CYB5A, ITPKA, and ENTPD6 were found to increase the risk of visceral obesity, while 1433B, SEMA3G, FOXO3, and HAPLN4 were associated with a decreased risk of visceral obesity. The results of the phenome-wide MR analysis indicate that CYB5A, ENTPD6, 1433B, and HAPLN4 can potentially be safe and effective drug targets for visceral obesity treatment.

Conclusions

This study indicates visceral obesity is associated with an increased risk of diseases within various physiological systems, such as cardiovascular, respiratory, and endocrine systems. The circulatory proteome reveals eight novel biomarkers for visceral obesity intervention, with CYB5A, ENTPD6, 1433B, and HAPLN4 displaying particular potential as safe and effective drug targets.
Dependence of the Critical Temperature and Disorder in Holographic Superconductors on Superfluid Density
Authors: Wang Zhenguo , Ge Xian-Hui , Ishigaki Shuta
Published: January 2025

Recent experiments strongly indicate deep connections between transports of strange metal and high-$T_c$ superconductors. For instance, it is known that the dependence of the zero-temperature phase stiffness on the critical superconducting temperature becomes linear in underdoped materials. In this paper, we investigate meticulously the relation between the phase stiffness and the critical superconducting temperature for the Gubser–Rocha holographic superconductor model in the probe limit. The superfluid density (or phase stiffness) can be extracted from the low-frequency dependence of the AC conductivity. More importantly, we find linear dependence of zero-temperature superfluid density on the critical superconducting temperature, which bears a similarity to a recent experiment in a film cuprate. In addition, we also provide some approximate formulas for the critical temperatures and the AC conductivity.
The association between residing in regions with population decline and receiving management education or treatment in patients with hypertension
Authors: Kim Woorim , Han Jina , Lee Soon Young , Ju Yeong Jun
Published: January 2025

Background

Many districts in rural areas of Korea are facing population decline due to the aging population phenomenon. This study examined the associations of rural residency with the likelihood of receiving hypertension management education and nonpharmacological and pharmacological treatment.

Methods

Data from the 2022 Korea Community Health Survey were used to identify individuals aged 19 years or above diagnosed with hypertension. Rural residency was defined based on the population decline index, which categorizes districts into those with, at risk of, or without population decline. The association between rurality and the likelihood of receiving hypertension management education, with nonpharmacological treatment, and with pharmacological treatment were analyzed using multilevel logistic regression.

Results

Of the 68 183 individuals diagnosed with hypertension, 13 246 (19.4%) received hypertension management education, 17 488 (25.6%) received nonpharmacological treatment, and 65 418 (95.9%) received pharmacological treatment. Individuals residing in areas with population decline were less likely to receive hypertension management education [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.59–0.94] and nonpharmacological treatment (OR, 0.54; 95% CI, 0.42–0.69), but more likely to receive pharmacological treatment (OR, 1.39; 95% CI, 1.17–1.64).

Conclusions

The findings highlight the importance of providing adequate hypertension management education and nonpharmacological treatment to patients residing in rural areas.
Preferences for Selecting and Initiating Long-Acting Injectable Antipsychotic Agents for the Treatment of Patients With Schizophrenia: Results From the US DECIDE Survey
Authors: Velligan Dawn , Salinas Gregory D , Belcher Emily , Franzenburg Kelli R , Suett Mark , Thompson Stephen , Hansen III Rolf T
Published: January 2025

Background

Long-acting injectable antipsychotics (LAIs) improve adherence and reduce schizophrenia relapse rates. Data on which LAI attributes drive clinician preference are limited.

Methods

In the DECIDE survey, 380 psychiatric clinicians (psychiatrists, psychiatric nurse practitioners, physician assistants) were surveyed regarding preferences when selecting and initiating LAIs for patients with schizophrenia. Responses were analyzed by clinician use of LAIs (high [≥31% of their patients using LAIs] or low [≤14% of their patients using LAIs]) and mindset toward LAI use (early, severity reserved, adherence reserved, LAI hesitant).

Results

Overall and across subgroups, side effects were the most important consideration when selecting a particular LAI, with 33% of clinicians ranking this as most important (26%–46% across subgroups). Clinician preference for the molecule was most often ranked least important (47% overall; 39%–59% across subgroups). A significantly higher proportion of clinicians with high vs low LAI use ranked product attributes as the most important consideration (26% vs 13%; P < .01). Across subgroups, multiple injection site options, small/on par needle, and price made at least two-thirds of clinicians somewhat/much more likely to use a particular LAI, and 63%–82% of clinicians reported being somewhat/much more likely to select an LAI dosed once monthly or less often vs 6%–11% being somewhat/much more likely to select an LAI dosed once every 2 weeks.

Conclusions

Overall, results from DECIDE provide insight into the decision-making process of psychiatric clinicians when selecting an LAI and highlight opportunities to help clinicians deliver optimal care for patients with schizophrenia.
Prognostic value of Chagas heart disease on short- and long-term clinical outcomes in patients hospitalized for COVID-19
Authors: Magalhães Bianca K , Silva Vinicius P S , Machado Maurício N , Nakazone Marcelo A
Published: January 2025

Background

Immunological similarities led us to explore potential interactions between Chagas heart disease (CHD) and coronavirus disease 2019 (COVID-19). We evaluated CHD's impact on the short- and long-term clinical courses of COVID-19 patients.

Methods

The CHD group comprised consecutive hospitalized patients (March 2020–March 2022), while the controls were selected through genetic matching based on COVID complications predictors. Cox proportional hazards models were used to assess the predictive value of CHD.

Results

Among 114 patients (50.9% male, 82.5% Caucasian, median age 66 y), prevalent comorbidities included cardiovascular diseases (84.2%) and type 2 diabetes (15.8%). Over a 22-month follow-up, no significant difference in the composite outcome (death and decompensated heart failure) was found between CHD patients (68.4%) and controls (72.6%, p=0.709). In-hospital and post-discharge clinical courses showed similarities in presentation, exams, respiratory support, long-COVID manifestations and death (p>0.05). Cox models identified age (every 10 y) (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.31 to 2.20], p<0.001) and normal lymphocyte count (800–1600/mm3) (HR 0.94 [95% CI 0.89 to 0.98], p=0.007) as independent predictors of mortality.

Conclusions

CHD does not significantly impact clinical presentation, in-hospital outcomes or long-COVID manifestations. Age and lymphocyte count are independent predictors of mortality, emphasizing their prognostic significance in COVID-19 complications, regardless of comorbidities.