bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of nonfatal suicidal behavior preceding suicide death reveals differences in clinical risks
Authors: Coon Hilary , Shabalin Andrey , DiBlasi Emily , Monson Eric T. , Han Seonggyun , Kaufman Erin A. , Chen Danli , Kious Brent , Molina Nicolette , Yu Zhe , Staley Michael , Crockett David K. , Colbert Sarah M. , Mullins Niamh , Bakian Amanda V. , Docherty Anna R. , Keeshin Brooks 
Published: June 2024

ABSTRACTNonfatal suicidality is the most robust predictor of suicide death. However, only ∼10% of those who survive an attempt go on to die by suicide. Moreover, ∼50% of suicide deaths occur in the absence of prior known attempts, suggesting risks other than nonfatal suicide attempt need to be identified. We studied data from 4,000 population-ascertained suicide deaths and 26,191 population controls to improve understanding of risks leading to suicide death. This study included 2,253 suicide deaths and 3,375 controls with evidence of nonfatal suicidality (SUI_SI/SB and CTL_SI/SB) from diagnostic codes and natural language processing of electronic health records notes. Characteristics of these groups were compared to 1,669 suicides with no prior nonfatal SI/SB (SUI_None) and 22,816 controls with no lifetime suicidality (CTL_None). The SUI_None and CTL_None groups had fewer diagnoses and were older than SUI_SI/SB and CTL_SI/SB. Mental health diagnoses were far less common in both the SUI_None and CTL_None groups; mental health problems were less associated with suicide death than with presence of SI/SB. Physical health diagnoses were conversely more often associated with risk of suicide death than with presence of SI/SB. Pending replication, results indicate highly significant clinical differences among suicide deaths with versus without prior nonfatal SI/SB.
Gender based disparities in Medicare physician reimbursement persist across years and specialty
Authors: Sekimitsu Sayuri , Halawa Omar Alaa , Boland Michael V. , Zebardast Nazlee 
Published: June 2024

AbstractIntroductionThe gender pay gap is wide in medicine but the extent of this disparity across specialties and over time have not been elucidated. Here we evaluate differences in Medicare reimbursement between men and women physicians over time and by specialty, controlling for physician and practice characteristics.MethodsThe Centers for Medicare & Medicaid Services Payment Data was used to determine total reimbursements and number of services submitted by physicians practicing in the US between 2013 and 2019. Data from the American Community Survey (ACS) were used to determine average income, unemployment rates, poverty rates, income, and educational attainment levels by zip code for each physician’s practice location.ResultsAmong the 3,831,504 physicians included in this analysis from 2013-2019, 2,712,545 (70.8%) were men and 1,118,859 (29.2%) were women. Overall, men received more in Medicare reimbursements ($58,815 ± $104,772 vs. $32,205 ± $60,556, p<0.001) and billed more services (864 ± 1,780 vs. 505 ± 1,007, p<0.001) compared to women. The median Medicare reimbursement for men decreased from 2013 to 2019 from $59,710 to $57,874, while the median Medicare reimbursement for women increased from $30,575 to $33,456. Men were reimbursed more than women across all specialties with the greatest disparity in procedure-heavy specialties. The specialties with the highest difference in median Medicare reimbursement between men and women were ophthalmology ($99,452), dermatology ($84,844), cardiology ($64,112), nephrology ($62,352), and pulmonary medicine ($47,399). In linear regression models controlling for calendar year, years of experience, total number of services, and ACS zip-code-level variables, men received a higher amount of Medicare reimbursement in all specialties, as compared to women (p<0.01 for all). The percentage of top earning men (range: 65.0%-99.5%) surpassed the proportion of men in each specialty (range: 46.1%-94.6%), except public health and preventive medicine.Conclusions and RelevanceWomen physicians continue to receive lower total Medicare reimbursements than men physicians, particularly in procedure-heavy specialties. Lower clinical volume and fewer procedural services among women physicians partially contribute to the disparities in reimbursement.
Functional and structural maturation of auditory cortex from 2 months to 2 years old
Authors: Chen Yuhan , Green Heather L. , Berman Jeffery I. , Putt Mary E. , Otten Katharina , Mol Kylie L. , McNamee Marybeth , Allison Olivia , Kuschner Emily S. , Kim Mina , Bloy Luke , Liu Song , Yount Tess , Roberts Timothy P.L. , Edgar J. Christopher 
Published: June 2024

AbstractIn school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.
Structural basis for synthase activation and cellulose modification in theE. coliType II Bcs secretion system
Authors: Anso Itxaso , Zouhir Samira , Sana Thibault G. , Krasteva Petya Violinova 
Published: June 2024

AbstractBacterial cellulosic polymers constitute a prevalent class of biofilm matrix exopolysaccharides that rely on conserved cyclic diguanylate (c-di-GMP)-dependent cellulose synthases. Polymer structure and modifications, however, depend on the ensemble of synthase modules and accessory subunits, thus defining several types of bacterial cellulose secretion (Bcs) systems. InE. coli, a BcsRQABEFG macrocomplex, encompassing the inner membrane and cytosolic subunits, and an outer membrane porin, BcsC, secure the biogenesis of phosphoethanolamine (pEtN)-modified cellulose. Resolution-limited studies have proposed different macrocomplex stoichiometries and its assembly and regulation have remained elusive. Using cryo-EM, we visualize the molecular mechanisms of BcsA-dependent recruitment and stabilization of a trimeric BcsG pEtN-transferase for polymer modification and a dimeric BcsF-dependent recruitment of an otherwise cytosolic BcsE2R2Q2regulatory complex. We further demonstrate that BcsE, a secondary c-di-GMP sensor, remains dinucleotide-bound and retains the essential-for-secretion BcsRQ partners onto the synthase even in the absence of direct c-di-GMP-synthase complexation, likely lowering the threshold for c-di-GMP-dependent synthase activation. Such ‘activation-by-proxy’ mechanism could allow Bcs secretion system activation even in the absence of dramatic intracellular c-di-GMP increase and is reminiscent of other widespread synthase-dependent polysaccharide secretion systems where c-di-GMP sensing and/or synthase stabilization are carried out by key co-polymerase subunits.
Locally released somatostatin triggers cAMP and Ca2+signaling in primary cilia to modulate pancreatic β-cell function
Authors: Incedal Nilsson Ceren , Dumral Özge , Sanchez Gonzalo , Xie Beichen , Müller Andreas , Solimena Michele , Ren Huixia , Idevall-Hagren Olof 
Published: June 2024

ABSTRACTSomatostatin is produced and released from δ-cells within pancreatic islets of Langerhans and constitutes one of the most important negative regulators of islet hormone secretion. Somatostatin receptors (SSTR) are abundantly expressed in the islet cells and coupled to Gαi and lowering of intracellular cAMP. We find that both SSTR3 and SSTR5 localize to primary cilia of β-cells, and that activation of these receptors lowers the ciliary cAMP concentration. cAMP produced in the cytosol can enter the cilium through diffusion, but activation of ciliary SSTR3 specifically counteracts the rise of cAMP in the cilium. Moreover, we find that islet δ-cells are positioned near primary cilia of the other islet cell types and that somatostatin secretion is directed towards primary cilia. While acute exposure to somatostatin caused a rapid lowering of ciliary cAMP, sustained exposure promoted nuclear entry of the cilia-dependent transcription factor GLI2 through a mechanism that operated in parallel with the canonical Hedgehog pathway and depended on ciliary Ca2+signaling. We also find that primary cilia length is reduced in islets from human donors with type-2 diabetes, which is associated with a reduction in cilia-δ-cell interactions. Our findings show that islet cell primary cilia constitute an important target of somatostatin action that endows it with the ability to regulate islet cell function beyond the acute suppression of hormone release.
TheCaenorhabditis elegansbacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion
Authors: El Jarkass Hala Tamim , Castelblanco Stefanie , Kaur Manpreet , Wan Yin Chen , Ellis Abigail E. , Sheldon Ryan D. , Lien Evan C. , Burton Nick O. , Wright Gerard D. , Reinke Aaron W. 
Published: June 2024

AbstractMicrosporidia are eukaryotic obligate intracellular parasites that infect most animals including humans. To understand how the microbiome can impact microsporidia infection, we tested how bacterial isolates that naturally occur withCaenorhabditis elegansinfluence infection by the microsporidianNematocida parisii. Nematodes exposed to two of these bacteria,Chryseobacterium scopthalmumandSphingobacterium multivorum, exhibit reduced pathogen loads. Using untargeted metabolomics, we show that unsaturated fatty acid levels are disrupted by growth on these bacteria and that supplementation with the polyunsaturated fatty acid linoleic acid can restore full parasite growth in animals cultured onS. multivorum. We also found that two isolates,Pseudomonas luridaandPseudomonas mendocina,secrete molecules that inactivateN. parisiispores. We determined thatP. luridainhibitsN. parisiithrough the production of massetolides. We then measured 53 additionalPseudomonasstrains, 64% of which significantly reducedN. parisiiinfection. A mixture ofPseudomonasspecies can greatly limit the amount of infection inC. eleganspopulations over many generations. Our findings suggest that interactions between bacteria andN. parisiiare common and that these bacteria both modulate host metabolism and produce compounds that inhibit microsporidia infection.
Subgenomic flaviviral RNAs and human proteins:in silicoexploration of anti-host defense mechanisms
Authors: Ponti Riccardo Delli , Vandelli Andrea , Tartaglia Gian Gaetano 
Published: June 2024

AbstractBackgroundFlaviviruses pose significant global health threats, infecting over 300 million people annually. Among their evasion strategies, the production of subgenomic flaviviral RNAs (sfRNAs) from the 3’ UTR of viral genomes is particularly notable. These sfRNAs interact with human proteins, disrupting key cellular processes such as RNA splicing and the interferon response.ResultsUtilizing a comprehensivein silicoapproach with thecatRAPID algorithm, we analyzed over 300,000 interactions between sfRNAs and human proteins derived from more than 8,000 flavivirus genomes, including Dengue, Zika, Yellow Fever, West Nile, and Japanese Encephalitis viruses. Our study not only validated known interactions but also revealed novel human proteins that could be involved in sfRNA-mediated host defense evasion, including helicases, splicing factors, and chemokines. We propose that sfRNAs function as molecular sponges, sequestering specific proteins indicative of sfRNA-forming regions across flaviviruses. These findings represent a valuable resource for diagnostic and therapeutic developments.ConclusionsOur findings significantly expand the known interactome of sfRNAs with human proteins, underscoring their role in modulating host cellular pathways. By providing the first extensive atlas of sfRNA interactions, we offer new insights into how flaviviruses can manipulate host cellular machinery to facilitate viral survival and persistence. Intriguingly, we predict interaction with stress granules, a critical component of the cellular response to viral infection, suggesting a mechanism by which flaviviruses inhibit their formation to evade host defenses. This atlas not only serves as a resource for exploring therapeutic targets but also aids in the identification of sfRNA biomarkers for improved flavivirus diagnostics.
Expression and regulation of SETBP1 in the song system of male zebra finches (Taeniopygia guttata) during singing
Authors: Grönberg Dana , Pinto de Carvalho Sara Luisa , Dernerova Nikola , Norton Phillip , Wong Maggie M. K. , Mendoza Ezequiel 
Published: June 2024

AbstractRarede novoheterozygous loss-of-functionSETBP1variants lead to a neurodevelopmental disorder characterized by speech deficits, indicating a potential involvement of SETBP1 in human speech. However, the expression pattern of SETBP1 in brain regions associated with language remains poorly understood, along with the underlying molecular mechanisms linking it to speech. In this study, we examined SETBP1 expression in the brain of male zebra finches, a well-established model for studying vocal production learning. We demonstrated that zebra finch SETBP1 exhibits a greater number of exons and isoforms compared to its human counterpart. We characterized a SETBP1 antibody and showed that SETBP1 colocalized with FoxP1, FoxP2, and Parvalbumin in key song nuclei. Moreover, SETBP1 expression in neurons in Area X is significantly higher in zebra finches singing alone, than those singing courtship song to a female, or non-singers. Importantly, we found a distinctive neuronal protein expression of SETBP1 and FoxP2 in Area X only in zebra finches singing alone, but not in the other conditions. We demonstrated SETBP1’s regulatory role on FoxP2 promoter activityin vitro. Taken together, these findings provide compelling evidence for SETBP1 expression in brain regions to be crucial for vocal learning and its modulation by singing behavior.
A combinatorial neural code for long-term motor memory
Authors: Kim Jae-Hyun , Daie Kayvon , Li Nuo 
Published: June 2024

AbstractMotor skill repertoire can be stably retained over long periods, but the neural mechanism underlying stable memory storage remains poorly understood. Moreover, it is unknown how existing motor memories are maintained as new motor skills are continuously acquired. Here we tracked neural representation of learned actions throughout a significant portion of a mouse’s lifespan, and we show that learned actions are stably retained in motor memory in combination with context, which protects existing memories from erasure during new motor learning. We used automated home-cage training to establish a continual learning paradigm in which mice learned to perform directional licking in different task contexts. We combined this paradigm with chronic two-photon imaging of motor cortex activity for up to 6 months. Within the same task context, activity driving directional licking was stable over time with little representational drift. When learning new task contexts, new preparatory activity emerged to drive the same licking actions. Learning created parallel new motor memories while retaining the previous memories. Re-learning to make the same actions in the previous task context re-activated the previous preparatory activity, even months later. At the same time, continual learning of new task contexts kept creating new preparatory activity patterns. Context-specific memories, as we observed in the motor system, may provide a solution for stable memory storage throughout continual learning. Learning in new contexts produces parallel new representations instead of modifying existing representations, thus protecting existing motor repertoire from erasure.
Sero-epidemiological investigation and risk factors associated with camelpox in pastoral areas of Somali region, eastern Ethiopia: a cross-sectional study
Authors: Arog Hassan Abdi , Ahad Abdullahi Adan , Fesseha Haben 
Published: June 2024

AbstractCamelpox is a highly significant viral disease that has a major economic impact on camels in Ethiopia. However, the epidemiology of the disease in the country, particularly in Somali region, is currently not well understood. The objective of this study was to estimate the prevalence of camelpox and identify associated risk factors in order to implement effective disease control measures in the study area. A cross-sectional design was employed from January 2023 to July 2023, involving a sample of 374 camels from 75 households in two districts and six peasant associations (PAs). Serum samples were tested using a competitive enzyme immunoassay (c-ELISA) to detect camelpox-specific antibodies. The overall seroprevalence of camelpox infection in the study area was found to be 16.0%. We administered structured questionnaires to camel owners to gather additional information on potential risk factors. Variables such as age, sex, and seasonal patterns were found to have a significant association with camelpox seropositivity. Female camels exhibited 3.2 times higher odds of infection compared to male camels, while young dromedaries aged between 6 months and 4 years were found to have a 2.3 times higher risk of infection than adults, indicating susceptibility to the age factor. Furthermore, the risk of infection was found to be 26 times higher during the rainy season than to the dry period. Thus, by identifying contributing factors, effective preventative measures, such as an appropriate vaccination strategy, can be developed to reduce the spread of camelpox and the associated economic losses. This study provides valuable insights for disease control and management practices.
Herbicidal interference: glyphosate drives both the ecology and evolution of plant-herbivore interactions
Authors: Zhang Grace M. , Baucom Regina S. 
Published: June 2024

AbstractThe coevolution of plants and their insect herbivores reflects eco-evolutionary dynamics at work— ecological interactions influence adaptive traits, which feed back to shape the broader ecological community. However, novel anthropogenic stressors like herbicide, which are strong selective agents, can disrupt these dynamics. Little is known about how the evolution of herbicide resistance may impact plant-herbivore interactions. We performed a common garden field experiment usingIpomoea purpurea(common morning glory) and the herbicide glyphosate (Roundup) to investigate the ecological effects of herbicide exposure on insect herbivory patterns and assess the potential evolutionary consequences. We find that plants treated with glyphosate experienced higher levels of herbivory and altered chewing herbivory damage patterns. Additionally, we found that glyphosate resistance is positively associated with herbivory resistance, and uncovered positive selection for increased glyphosate resistance, suggesting that selection for increased glyphosate resistance has the potential to lead to increased herbivory resistance. Positive selection for glyphosate resistance, coupled with the detection of genetic variation for this trait, suggests there is potential for glyphosate resistance—and herbivory resistanceviahitchhiking— to further evolve. Our results show that herbicides can not just influence, but potentially drive the eco-evolutionary dynamics of plant-herbivore interactions.
Transcription templated assembly of the nucleolus in theC. elegansembryo
Authors: Kodan Nishant , Hussaini Rabeya , Weber Stephanie C. , Kondev Jane , Mohapatra Lishibanya 
Published: June 2024

AbstractThe nucleolus is a multicomponent structure made of RNA and proteins that serves as the site of ribosome biogenesis within the nucleus. It has been extensively studied as a prototype of a biomolecular condensate whose assembly is driven by phase separation. While the steady-state size of the nucleolus is quantitatively accounted for by the thermodynamics of phase separation, we show that experimental measurements of the assembly dynamics are inconsistent with a simple model of a phase-separating system relaxing to its equilibrium state. Instead, we show that the dynamics are well described by a model in which the transcription of ribosomal RNA actively drives nucleolar assembly. We find that our model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early embryos at different developmental stages, and for different RNAi perturbations of embryo size. Our model predicts a scaling of the time to assembly with the volume of the nucleus to the one-third power, which is confirmed by experimental data. Our study highlights the role of active processes such as transcription in controlling the placement and timing of assembly of membraneless organelles.Significance statementHow membraneless organelles like nucleolus assemble within cells is not well understood. Recent experiments suggest that transcription of ribosomal RNA actively drives nucleolar assembly. Our proposed model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early worm embryos at different developmental stages. Further, it predicts a scaling of the time to assembly with the volume of the nucleus that is confirmed by experimental data. This work describes how active processes such as transcription can control the placement and timing of assembly of membraneless organelles.