bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rethinking asexuality: the enigmatic case of functional sexual genes inLepraria(Stereocaulaceae)
Authors: Doellman Meredith M. , Sun Yukun , Barcenas-Peña Alejandrina , Thorsten Lumbsch H. , Grewe Felix 
Published: June 2024

AbstractBackgroundThe ubiquity of sex across eukaryotes, given its high costs, strongly suggests it is evolutionarily advantageous. Asexual lineages can avoid, for example, the risks and energetic costs of recombination, but suffer short-term reductions in adaptive potential and long-term damage to genome integrity. Despite these costs, lichenized fungi have frequently evolved asexual reproduction, likely because it allows the retention of symbiotic algae across generations. The relatively speciose lichenized fungal genusLeprariais thought to be exclusively asexual, while its sister genusStereocauloncompletes a sexual reproductive cycle. A comparison of sister sexual and asexual clades should shed light on the evolution of asexuality in lichens in general, as well as the apparent long-term maintenance of asexuality inLepraria, specifically.ResultsIn this study, we assembled and annotated representative long-read genomes from the putatively asexualLeprariagenus and its sexual sister genusStereocaulon, and added short-read assemblies from an additional 22 individuals across both genera. Comparative genomic analyses revealed that both genera were heterothallic, with intact mating-type loci of both idiomorphs present across each genus. Additionally, we identified and assessed 29 genes involved in meiosis and mitosis and 45 genes that contribute to formation of fungal sexual reproductive structures (ascomata). All genes were present and appeared functional in nearly allLepraria, and we failed to identify a general pattern of relaxation of selection on these genes across theLeprarialineage. Together, these results suggest thatLeprariamay be capable of sexual reproduction, including mate recognition, meiosis, and production of ascomata.ConclusionsDespite apparent maintenance of machinery essential for fungal sex, over 200 years of careful observations by lichenologists have produced no evidence of canonical sexual reproduction inLepraria. We suggest thatLeprariamay have instead evolved a form of parasexual reproduction, perhaps by repurposingMATand meiosis-specific genes. This may, in turn, allow these lichenized fungi to avoid long-term consequences of asexuality, while maintaining the benefit of an unbroken bond with their algal symbionts.
Painting cell-cell interactions by horseradish peroxidase and endogenously generated hydrogen peroxide
Authors: Jeong Inyoung , Kim Kwang-eun , Rhee Hyun-Woo 
Published: June 2024

ABSTRACTCell-Cell interactions are fundamental in biology for maintaining physiological conditions, with direct contact being the most straightforward mode of interaction. Recent advancements have led to the development of various chemical tools for detecting or identifying these interactions. However, the use of exogenous cues, such as toxic reagents, bulky probes, and light irradiations, can disrupt normal cell physiology. For example, the toxicity of hydrogen peroxide (H2O2) limits the applications of peroxidases in proximity labeling field. In this study, we aimed to address this limitation by demonstrating that membrane-localized Horseradish Peroxidase (HRP-TM) efficiently utilizes endogenously generated extracellular H2O2. By harnessing endogenous H2O2, we observed that HRP-TM-expressing cells can effectively label contacting cells without the need for exogenous H2O2treatment. Furthermore, we confirmed that HRP-TM labels proximal cells in an interaction-dependent manner. These findings offer a novel approach for studying cell-cell interactions under more physiological conditions, without the confounding effects of exogenous stimuli. Our study contributes to elucidating cell-cell interaction networks in various model organisms, providing valuable insights into the dynamic interplay between cells in their native network.
A genetically encoded sensor for real-time monitoring of poly-ADP-ribosylation dynamics in-vitro and in cells
Authors: Thomas Alix , Upadhyaya Kapil , Bejan Daniel , Adoff Hayden , Cohen Michael , Schultz Carsten 
Published: June 2024

ABSTRACTADP-ribosylation, the transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) groups to proteins, is a conserved post-translational modification (PTM) that occurs most prominently in response to DNA damage. ADP-ribosylation is a dynamic PTM regulated by writers (PARPs), erasers (ADPr hydrolases), and readers (ADPR binders). PARP1 is the primary DNA damage-response writer responsible for adding a polymer of ADPR to proteins (PARylation). Real-time monitoring of PARP1-mediated PARylation, especially in live cells, is critical for understanding the spatial and temporal regulation of this unique PTM. Here, we describe a genetically encoded FRET probe (pARS) for semi-quantitative monitoring of PARylation dynamics. pARS feature a PAR-binding WWE domain flanked with turquoise and Venus. With a ratiometric readout and excellent signal-to-noise characteristics, we show that pARS can monitor PARP1-dependent PARylation temporally and spatially in real-time. pARS provided unique insights into PARP1-mediated PARylation kinetics in vitro and high-sensitivity detection of PARylation in live cells, even under mild DNA damage. We also show that pARS can be used to determine the potency of PARP inhibitors in vitro and, for the first time, in live cells in response to DNA damage. The robustness and ease of use of pARS make it an important tool for the PARP field.
COVID-19 advocacy bias in theBMJ: meta-research evaluation
Authors: Kepp Kasper P. , Cristea Ioana Alina , Muka Taulant , Ioannidis John P.A. 
Published: June 2024

ABSTRACTObjectivesDuring the COVID-19 pandemic,BMJ, the premier journal on evidence-based medicine worldwide, published many views by advocates of specific COVID-19 policies. We aimed to evaluate the presence and potential bias of this advocacy.Design and MethodsScopus was searched for items published until April 13, 2024 on “COVID-19 OR SARS-CoV-2”.BMJpublication numbers and types before (2016−2019) and during (2020−2023) the pandemic were compared for a group of advocates favoring aggressive measures (leaders of both the Independent Scientific Advisory Group for Emergencies (indieSAGE) and the Vaccines-Plus initiative) and four control groups: leading members of the governmental Scientific Advisory Group for Emergencies (SAGE), UK-based key signatories of the Great Barrington Declaration (GBD) (favoring more restricted measures), highly-cited UK scientists, and UK scientists who published the highest number of COVID-19-related papers in the entire scientific literature (n=16 in each group).Results122 authors published more than 5 COVID-19-related items each inBMJ. Of those, 18 were leading members/signatories of aggressive measures advocacy groups publishing 231 COVID-19 related BMJ documents, 53 were editors/journalists, and 51 scientists were not identified as associated with any advocacy. Of 41 authors with >10 publications inBMJ, 8 were scientists advocating for aggressive measures, 7 were editors, 23 were journalists, and only 3 were non-advocate scientists. Some aggressive measures advocates already had strongBMJpresence pre-pandemic. During pandemic years, the studied indieSAGE/Vaccines-Plus advocates outperformed inBMJpresence leading SAGE members by 16.0-fold, UK-based GBD advocates by 64.2-fold, the most-cited scientists by 16.0-fold, and the authors who published most COVID-19 papers overall by 10.7-fold. The difference was driven mainly by short opinion pieces and analyses.ConclusionsBMJappears to have favored and massively promoted specific COVID-19 advocacy views during the pandemic, thereby strongly biasing the scientific picture on COVID-19.Summary boxSection 1: What is already known on this topicAdvocacy is intensely debated for its merits to science and policy.Many journals increasingly publish pieces by advocates and it is thus important to understand the nature, scale and impact of this phenomenon.Section 2: What this study addsThis study provides a detailed quantitative assessment of journal-promoted advocacy, focusing on the world’s premier evidence-based medical journal, theBMJ.We show thatBMJhad massive bias towards specific COVID-19-related advocacy favoring aggressive measures.Our study reveals a need for editorial guidelines on journal-promoted advocacy.
Comparing lagged impacts of mobility changes and environmental factors on COVID-19 waves in rural and urban India: a Bayesian spatiotemporal modelling study
Authors: Cleary Eimear , Atuhaire Fatumah , Sorcihetta Alessandro , Ruktanonchai Nick , Ruktanonchai Cori , Cunningham Alexander , Pasqui Massimiliano , Schiavina Marcello , Melchiorri Michele , Bondarenko Maksym , Shepherd Harry E R , Padmadas Sabu S , Wesolowski Amy , Cummings Derek A T , Tatem Andrew J , Lai Shengjie 
Published: June 2024

AbstractPrevious research in India has identified urbanisation, human mobility and population demographics as key variables associated with higher district level COVID-19 incidence. However, the spatiotemporal dynamics of mobility patterns in rural and urban areas in India, in conjunction with other drivers of COVID-19 transmission, have not been fully investigated. We explored travel networks within India during two pandemic waves using aggregated and anonymized weekly human movement datasets obtained from Google, and quantified changes in mobility before and during the pandemic compared with the mean baseline mobility for the 8-week time period at the beginning of 2020. We fit Bayesian spatiotemporal hierarchical models coupled with distributed lag non-linear models (DLNM) within the integrated nested Laplace approximate (INLA) package in R to examine the lag-response associations of drivers of COVID-19 transmission in urban, suburban, and rural districts in India during two pandemic waves in 2020-2021. Model results demonstrate that recovery of mobility to 99% that of pre-pandemic levels was associated with an increase in relative risk of COVID-19 transmission during the Delta wave of transmission. This increased mobility, coupled with reduced stringency in public intervention policy and the emergence of the Delta variant, were the main contributors to the high COVID-19 transmission peak in India in April 2021. During both pandemic waves in India, reduction in human mobility, higher stringency of interventions, and climate factors (temperature and precipitation) had 2-week lag-response impacts on theRtof COVID-19 transmission, with variations in drivers of COVID-19 transmission observed across urban, rural and suburban areas. With the increased likelihood of emergent novel infections and disease outbreaks under a changing global climate, providing a framework for understanding the lagged impact of spatiotemporal drivers of infection transmission will be crucial for informing interventions.
Vestibular afferent neurons develop normally in the absence of quantal/glutamatergic input
Authors: Núñez Katherine Regalado , Bronson Daniel , Chang Ryan , Kalluri Radha 
Published: June 2024

AbstractThe vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons’ membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons. To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined the maturation of the vestibular epithelium and ganglion neurons inVglut3-komice whose hair cell synapses lack glutamate. Despite lacking glutamatergic input, the knockout mice showed no notable balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of theVglut3-kovestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wildtype animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in theVglut3-komice is comparable to that found in wildtype controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type. Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.
JAK inhibition decreases the autoimmune burden in Down syndrome
Authors: Rachubinski Angela L. , Wallace Elizabeth , Gurnee Emily , Enriquez Estrada Belinda A. , Worek Kayleigh R. , Smith Keith P. , Araya Paula , Waugh Katherine A. , Granrath Ross E. , Britton Eleanor , Lyford Hannah R. , Donovan Micah G. , Eduthan Neetha Paul , Hill Amanda A. , Martin Barry , Sullivan Kelly D. , Patel Lina , Fidler Deborah J. , Galbraith Matthew D. , Dunnick Cory A. , Norris David A. , Espinosa Joaquin M. 
Published: June 2024

AbstractIndividuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier:NCT04246372.
Development of self-phenotyping tools to empower patients and improve diagnostics
Authors: Shefchek Kent , Ziniel Sonja , McMurry Julie A. , Brownstein Catherine A , Brownstein John S. , Riggs Erin Rooney , Might Matthew , Smedley Damian , Clugston Amy , Beggs Alan H , Paterson Heather , Robinson Peter N. , Vasilevsky Nicole A. , Holm Ingrid A. , Haendel Melissa 
Published: June 2024

ABSTRACTDeep phenotyping is important for improving diagnostics and rare diseases research and is especially effective when standardized using Human Phenotype Ontology (HPO). Patients are an under-utilized source of information, so to facilitate self-phenotyping we previously “translated” HPO into plain language (“layperson HPO”). Another self-phenotyping survey, GenomeConnect, asks patient-friendly questions that map to HPO. However, self-reported data has not been assessed. Since not all HPO terms are translated to layperson HPO or in the GenomeConnect survey, we created theoretical maximum-accuracy phenotype profiles for each disease for each instrument, representing the theoretical maximum performance. Both instruments performed well in analyses of semantic similarity (area under the curve 0.991 and 0.954, respectively). To explore the real-world implications, we randomized participants with diagnosed genetic diseases to complete the GenomeConnect, Phenotypr, or both instruments. For each diagnosed disease, we compared the derived disease profile to the patient-completed profile for each instrument. Profiles resulting from participant responses to the GenomeConnect survey were more accurate than to the Phenotypr instrument. The Phenotypr instrument had a tighter distribution of scores for respondents who did both instruments and was therefore more precise. We evaluated the ability of each known Mendelian disease HPO phenotype profile to retrieve the corresponding disease. We conducted interviews and generally participants preferred the GenomeConnect multiple choice format over the autocomplete Phenotypr format. Our results demonstrate that individuals can provide rich HPO phenotype data. These results suggest that self-phenotyping source of information could be used to support diagnostics or supplement profiles created by clinicians.
What is the effectiveness of antiracist interventions for ethnic minority healthcare staff? A systematic review
Authors: Lalli Kismet , Adewole Oluwatomisin , Peters Holly , Price Chris , Lumb Blanche , Gal Micaela , Cooper Alison 
Published: June 2024

AbstractBackgroundThe National Health Service (NHS) has the most diverse workforce in the United Kingdom (UK), 25% (n= 309,532/1,200,000) of staff belong to ethnic minority groups. However, there is evidence of longstanding issues of racism within the NHS and discrimination towards ethnic minority healthcare staff has been rising since 2016. In the first wave of the COVID-19 pandemic, 95% of COVID-19 deaths among doctors were in an ethnic minority group. There has been no definitive answer for the disproportionate COVID-19 mortality but socioeconomic factors due to structural racism have been suggested as the main drivers. No studies have assessed the effectiveness of antiracist interventions for healthcare staff.MethodsWe conducted a systematic review; databases searched included: AMED, Medline via OVID, CINAHL, APA Pyscinfo, Web of Science and OVID Emcare 25th– 31stJanuary 2022. The interventions were structured using a model of antiracist interventions and analysed using narrative synthesis methods.Results16 papers were reviewed with interventions at different levels: personally mediated (n=9), multilevel (n=4) and institutional (n=3). Personally mediated interventions were workshops (n=8) and a mentorship scheme (n=1). Institutional interventions were policies (n=2) and increasing diversity initiative (n=1). Multilevel interventions were a mix of both. Study designs and risk of bias tools indicated that the quality of evidence was of low quality. Only two studies included control groups. Countries included the USA (n=11), Canada (n=1) and the UK (n=4).ConclusionThere is a lack of robust evidence for antiracist interventions for healthcare staff, especially at an institutional level. High quality research is required to evaluate the long-term effects of interventions.Funding statementThe Wales COVID-19 Evidence Centre was funded for this work by Health and Care Research Wales on behalf of Welsh Government.
Proposed Mammography Protocol and Pre-Mammography Survey for Transgender Patients
Authors: Godoy Carlos Carrasco , Fernández Diego Muñoz , Urzúa Sergio Quitral , Zulueta Elizabeth Cañipa , Herrera Marco Jiménez , Miranda Jeannette Soto 
Published: June 2024

AbstractBackgroundEarly detection of breast cancer reduces the risk of mortality, with mammography being the gold standard for detecting breast cancer. Currently, there is no consensus on breast screening in transgender patients, with only recommendations from various international health organizations, which differ from one another. The objective of this research was to determine the mammographic projections applicable to transgender patients, in order to propose a mammography protocol and a pre-mammography survey focused on this patient group.MethodologyA semi-structured survey with both closed and open-ended questions was conducted, which was answered by radiologists specializing in mammography. To propose mammographic projections, the survey included questions about the transitional phase, hormone use, surgeries, and breast tissue development. To propose a pre-mammography survey for transgender patients, questions about risk factors and surgical treatments were included.ConclusionsA mammographic protocol is proposed according to the transitional phase, along with a pre-mammography survey for transgender patients, based on information gathered from a survey answered by 20 radiologists specializing in mammography. This contributes significantly to the screening process for this patient group.