bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct measurements of luminal Ca2+with endo-lysosomal GFP-aequorin reveal functional IP3receptors
Authors: Calvo B , Torres-Vidal P , Delrio-Lorenzo A , Rodriguez C , Aulestia FJ , Rojo-Ruiz J , McVeigh BM , Moiseenkova-Bell V , Yule DI , Garcia-Sancho J , Patel S , Alonso MT 
Published: July 2023

ABSTRACTEndo-lysosomes are considered acidic Ca2+stores but direct measurements of luminal Ca2+within them are limited. Here we report that the Ca2+-sensitive luminescent protein aequorin does not reconstitute with its cofactor at highly acidic pH but that a significant fraction of the probe is functional within a mildly acidic compartment when targeted to the endo-lysosomal system. We leveraged this probe (ELGA) to report Ca2+dynamics in this compartment. We show that Ca2+uptake is ATP-dependent and sensitive to blockers of endoplasmic reticulum Ca2+pumps. We find that the Ca2+mobilizing messenger IP3which typically targets the endoplasmic reticulum evokes robust luminal responses in wild type cells, but not in IP3receptor knock-out cells. Responses were comparable to those evoked by activation of the endo-lysosomal ion channel TRPML1. Stimulation with IP3-forming agonists also mobilized the store in intact cells. Super-resolution microscopy analysis confirmed the presence of IP3receptors within the endo-lysosomal system, both in live and fixed cells. Our data reveal a physiologically-relevant, IP3-sensitive store of Ca2+within the endo-lysosomal system.
Chromosomal-level genome assembly ofPopulus davidiana
Authors: Chen Liyang , Jiang Yuanzhong , Shi Tingting , Jia Changfu , Long Zhiqin , Zhang Xinxin , Sang Yupeng , Liu Jianquan , Wang Jing 
Published: July 2023

AbstractDespite the population structure and genetic differentiation ofP. davidianahas been reported, little is known about theP. davidianagenome characterization with the genomes assembled at the chromosome level. As one of the most widely distributed and ecologically important tree species in China,P. davidianais an excellent resource to understand population adaption to climate and environment change. Here we present a high-quality assembly based on long-read sequences and Hi-C data. This assembly is assembled into 19 contiguous chromosomes which provides a powerful tool for future association studies.
Evolutionary genomics predicts adaptive genetic and plastic gene expression responses to climate change in a key alpine forest tree species
Authors: Long Zhiqin , Sang Yupeng , Feng Jiajun , Zhang Xinxin , Shi Tingting , Zhang Lushui , Mao Kangshan , Rieseberg Loren H. , Liu Jianquan , Wang Jing 
Published: July 2023

ABSTRACTDespite widespread biodiversity loss, our understanding of how species and populations will respond to accelerated climate change remains limited. In this study, we predict the evolutionary responses ofPopulus lasiocarpa, a key alpine forest tree species primarily found in the mountainous regions of a global biodiversity hotspot, to climate change. We accomplish this by generating and integrating a new reference genome forP. lasiocarpa, re-sequencing data for 200 samples, and gene expression profiles for leaf and root tissue following exposure to heat and waterlogging. Analyses of the re-sequencing data indicate that demographic dynamics, divergent selection, and long-term balancing selection have shaped and maintained genetic variation within and between populations over historical timescales. In examining genomic signatures of contemporary climate adaptation, we found that haplotype blocks, characterized by inversion polymorphisms that suppress recombination, play a crucial role in clustering environmentally adaptive variations. Comparison of evolved and plastic gene expression show that genes with expression plasticity generally align with evolved responses, highlighting the adaptive role of plasticity. Lastly, we incorporated local adaptation, migration, genetic load, and plasticity responses into our predictions of population-level climate change risks. Our findings reveal that western populations, primarily distributed in the Hengduan Mountains—a region known for its environmental heterogeneity and significant biodiversity—are the most vulnerable to climate change and should be prioritized for conservation and management. Overall, our study advances understanding of the relative roles of long-term natural selection, local environmental adaptation, and immediate plasticity responses in driving evolutionary adaptation to climate change in keystone species.
Does enforcing glenohumeral joint stability matter? A new rapid muscle redundancy solver highlights the importance of non-superficial shoulder muscles
Authors: Belli Italo , Joshi Sagar , Prendergast J. Micah , Beck Irene , Santina Cosimo Della , Peternel Luka , Seth Ajay 
Published: July 2023

AbstractThe complexity of the human shoulder girdle enables the large mobility of the upper extremity, but also introduces instability of the glenohumeral (GH) joint. Shoulder movements are generated by coordinating large superficial and deeper stabilizing muscles spanning numerous degrees-of-freedom. How shoulder muscles are coordinated to stabilize the movement of the GH joint remains widely unknown. Musculoskeletal simulations are powerful tools to gain insights into the actions of individual muscles and particularly of those that are difficult to measure. In this study, we analyze how enforcement of GH joint stability in a musculoskeletal model affects the estimates of individual muscle activity during shoulder movements. To estimate both muscle activity and GH stability from recorded shoulder movements, we developed a Rapid Muscle Redundancy (RMR) solver to include constraints on joint reaction forces (JRFs) from a musculoskeletal model. The RMR solver yields muscle activations and joint forces by minimizing the weighted sum of squared-activations, while matching experimental motion. We implemented three new features: first, computed muscle forces include active and passive fiber contributions; second, muscle activation rates are enforced to be physiological, and third, JRFs are efficiently formulated as linear functions of activations. Muscle activity from the RMR solver without GH stability was not different from the computed muscle control (CMC) algorithm and electromyography of superficial muscles. The efficiency of the solver enabled us to test 3600 trials sampled within the uncertainty of the experimental movements to test the differences in muscle activity with and without GH joint stability enforced. We found that enforcing GH stability significantly increases the estimated activity of the rotator cuff muscles but not of most superficial muscles. Therefore, a comparison of shoulder model muscle activity to EMG measurements of superficial muscles alone is insufficient to validate the activity of rotator cuff muscles estimated from musculoskeletal models.
Skeletal progenitor LRP1-mediated endocytosis is critical for synovial joint formation and bone growth
Authors: Alhashmi Mohammad , Gremida Abdulrahman ME , Al-Maslamani Noor A , Liu Ke , Sutherland Hazel , Wilson Peter , Clegg Peter , van ’t Hof Robert J , Bou-Gharios George , Yamamoto Kazuhiro 
Published: July 2023

AbstractThe layer of stem cells surrounding developing limbs is essential for bone formation and regeneration. Our work addresses the critical question of how these stem cells and bone template communicate to ensure that limbs form correctly. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose mutations are linked to bone and joint pathologies. Here, we show the abundant expression of LRP1 in skeletal progenitor cells, especially in the perichondrium – the dense layer of fibrous connective tissue enveloping the cartilage of the developing limb bud. Our mouse models reveal that LRP1 deficiency in these stem cells (Lrp1flox/flox/Prrx1Cre) but not in chondrocytes (Lrp1flox/flox/AcanCreERT2) causes disrupted articulation and cavitation starting at as early as embryonic stage 16.5. LRP1 deficiency is also associated with aberrant accumulation of LRP1 ligands including tissue-inhibitor of metalloproteinase 3 and CCN2. These early abnormalities result in severe defects in multiple joints, plus markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Ourin vitroexploration shows unique regulation of non-canonical WNT components by LRP1 that may explain the malformation of long bones. Mechanistically, we found that LRP1 facilitates cell-association, endocytic recycling but not degradation, and graded distribution of Wnt5a in the developing limbs. We propose that LRP1-mediated endocytic regulation of availability and distribution of extracellular signalling molecules play a critical role in limb development. This provides a novel mechanism for crosstalk among skeletal elements.
Beyond the (geometric) mean: stochastic models undermine deterministic predictions of bet hedger evolution
Authors: Weissman Maya , Raynes Yevgeniy , Weinreich Daniel 
Published: July 2023

AbstractBet hedging is a ubiquitous strategy for risk reduction in the face of unpredictable environmental change where a lineage lowers its variance in fitness across environments at the expense of also lowering its arithmetic mean fitness. Classically, the benefit of bet hedging has been quantified using geometric mean fitness (GMF); bet hedging is expected to evolve if and only if it has a higher GMF than the wild-type. We build upon previous research on the effect of incorporating stochasticity in phenotypic distribution, environment, and reproduction to investigate the extent to which these sources of stochasticity will impact the evolution of real-world bet hedging traits. We utilize both individual-based simulations and Markov chain numerics to demonstrate that modeling stochasticity can alter the sign of selection for the bet hedger compared to deterministic predictions. We find that bet hedging can be deleterious at small population sizes and beneficial at larger population sizes. This non-monotonic dependence of the sign of selection on population size, known as sign inversion, exists across parameter space for both conservative and diversified bet hedgers. We apply our model to published data of bet hedging strategies to show that sign inversion exists for biologically relevant parameters in two study systems:Papaver dubium, an annual poppy with variable germination phenology, andSalmonella typhimurium, a pathogenic bacteria that exhibits antibiotic persistence. Taken together, our results suggest that GMF is not enough to predict when bet hedging is adaptive.
Associations of schooling type, qualification type, and subsequent health in mid-adulthood: Evidence from the 1970 British Cohort Study
Authors: Deng Keyao , Wright Liam , Silverwood Richard , Sullivan Alice , Bann David 
Published: July 2023

AbstractBackgroundEducation is thought to benefit subsequent health. However, existing studies have predominantly focused on educational attainment while the type of educational institution attended has been overlooked, despite being important indictors of education resource, quality, and influencing subsequent socioeconomic outcomes. In this study, we investigated associations between type of high school or university attended and multiple subsequent health outcomes in mid-adulthood.MethodsData from the 1970 British Cohort Study were used (N=8 107). Type of high school attended (comprehensive; grammar; private) was ascertained at age 16 and type of university (classified as higher (Russell Group) or normal-status) was reported at age 42. We investigated ten health measures that capture cardiometabolic risks, physical capabilities, and cognitive function measured at age 46. Multivariable regression models were used, adjusting for sex and childhood socioeconomic, health and cognitive factors.ResultsIn unadjusted models, private school and higher-status university attendance were favourably associated with most health outcomes. After adjusting for potential confounders, associations between private school attendance and cardiometabolic risks remained; associations for higher-status university attendance and cognitive function remained, while the association with other health outcomes were largely attenuated. For example, private school attendance was associated with 0.14 standard deviation (SD) (95% confidence interval (CI): 0.04, 0.23) lower body mass index (BMI) while higher-status university attendance was associated with a 0.16 SD (0.07, 0.26) better performance in memory (word list recall task) compared with normal-status university attendance.ConclusionsThe type of educational institution attended was associated with multiple health outcomes—it could therefore be an important under-researched component of health inequalities. Further research is warranted to test the causal nature of this relationship and its generalisability to more recently born cohorts given changes in secondary education and the expansion of higher education.
PATIENT-ASSESSED QUALITY OF CARE AND LEVEL OF SATISFACTION IN HEALTHCARE FACILITIES IN CROSS RIVER STATE, NIGERIA
Authors: Etim John John , Nja Glory M. , Ejemot-Nwadiaro Regina Idu 
Published: July 2023

AbstractBackgroundPatients’ experiences with health care professionals are a central component of quality of care, complementing more technical aspects of care such as the appropriate use of medications and procedures.AimsThis study sought to assess patients’ quality of care and level of satisfaction in healthcare facilities in Cross River State, Nigeria.MethodsThe study adopted a descriptive cross sectional survey employing quantitative data collection method that utilized a semi-structured questionnaire to collect data from patients. A multi-stage sampling procedure was used where 405 respondents were selected through simple random sampling. A 27 items semi-structured questionnaire was used to elicit data from respondents. Data collected were analyzed and presented using descriptive statistics.ResultsOn a multi response options, the study showed that more than half 294(72.8%) respondents were satisfied with the services provided by healthcare professionals on their current admission; more than half of the respondents 235(58.2%) were satisfied with previous care received; about half 197(48.8%) of the respondents complained about long waiting time to be seen on admission; more than half 209(51.7%) of the respondents strongly disagreed that the hospital/ward environment into which they were admitted was clean and conducive, with a significant proportion 335(82.9%) who were unable to get all the prescribed drugs from the facility, while just 69(17.2%) of those not satisfied could recall some instances/aspects of healthcare they were not satisfied with where 49(12.2%) recalled poor attitude of healthcare professionals.ConclusionsTimely care and better communication between patient and healthcare providers were recommended among others.What is already known on this topicThere is a recorded level of patients’ dissatisfaction with healthcare in the study setting.What this study addsPoor attitude of healthcare workers has been associated with patients’ dissatisfaction with healthcare.Poor attitude of healthcare workers has been associated with poor work environment which by extension affect the mental health of healthcare staff.How this study might affect research, practice or policyThis study outlines the implication of poor work environment on mental health of workers as by extension affects patients’ quality of care and as such calls better healthcare management by trained experts.
Injury incidence, severity and type across the menstrual cycle in elite female professional footballers: a prospective three season cohort study
Authors: Barlow Ally , Blodgett Joanna M , Williams Sean , Pedlar Charles R , Bruinvels Georgie 
Published: July 2023

AbstractObjectivesThe aim of the study was to assess the influence of menstrual cycle phase on injury incidence, severity and type in elite female professional footballers over three seasons.MethodsTime-loss injuries and menstrual cycle data were prospectively recorded for 26 elite female football players across three seasons. The menstrual cycle was categorised into four phases using a standardised model: menstruation (phase 1; P1), remainder of follicular phase (phase 2; P2), early luteal (phase 3; P3), and pre-menstrual phase (phase 4; P4). Injury incidence rates (IRR) and ratios (IIRR) were calculated for overall injuries, injury type, contact vs non-contact, game/training and severity of injury.Results593 cycles across 13,390 days were tracked during the study and 74 injuries from 26 players were eligible for analysis. Muscle injuries were the most prevalent sub-type (n=41). When comparing IRR between phases (reference: P1), injury rates were highest in P4 for overall (IIRR: 2.30 [95% CI: 0.99-5.34; p=0.05]), muscle-specific (6.07 [1.34-27.43; p=0.02]), non-contact (3.05 [1.10-8.50; p=0.03]) and ≤7 day’s time-loss injuries (4.40 [0.93-20.76; p=0.06]). Muscle-specific (IIRR P3:P1: 5.07 [1.16-22.07; p=0.03]) and ≤7 day’s time-loss (4.47 [1.01-19.68; p=0.05]) injury risk were also significantly higher in P3. No anterior cruciate ligament injuries were recorded across the monitoring period.ConclusionInjury risk was significantly elevated during the luteal phase of the menstrual cycle (P3 and P4) among elite female professional footballers. Further research is urgently needed to better understand the influence of the menstrual cycle on injury risk and to develop interventions to mitigate risk.What are the new findings?Injury risk was lowest in phase 1, during menstruation.Rate of overall injuries was highest in the luteal phase (phases 3 and 4), specifically for non-contact and lower severity injuries (e.g. 1-7 days missed training).Muscle injury risk increased across the menstrual cycle, with a greater incidence in the luteal phase (phases 3 and 4).Conversely to current perceptions, squad availability is significantly impacted by a wide range of injuries that are related to menstrual cycle phase, not just significant ligament injuries.How might it impact on clinical practice in the near future?When reviewing injury occurrence, mechanism and prevention guidelines, it is crucial to consider menstrual cycle day and phase.Longitudinal menstrual cycle monitoring provides an additional, potentially useful factor to support female athletes.The results of this study demonstrate that there is an urgent need to collect menstrual cycle data alongside standardised injury data to allow for further exploration in a larger sample.
Focal transcranial direct current stimulation of auditory cortex in chronic tinnitus: A randomized controlled mechanistic trial
Authors: Leaver Amber M. , Chen Yufen J. , Parrish Todd B. 
Published: July 2023

ABSTRACTObjectiveThe goal of this pilot MRI study was to understand how focal transcranial direct current stimulation (tDCS) targeting auditory cortex changes brain function in chronic tinnitus.MethodsPeople with chronic tinnitus were randomized to active or sham tDCS on five consecutive days in this pilot mechanistic trial (n=10/group). Focal 4×1 tDCS (central anode, surround cathodes) targeted left auditory cortex, with single-blind 2mA current during twenty-minute sessions. Arterial spin-labeled and blood oxygenation level dependent MRI occurred immediately before and after the first tDCS session, and tinnitus symptoms were measured starting one week before the first tDCS session and through four weeks after the final session.ResultsAcute increases in cerebral blood flow and functional connectivity were noted in auditory cortex after the first active tDCS session. Reduced tinnitus loudness ratings after the final tDCS session correlated with acute change in functional connectivity between an auditory network and mediodorsal thalamus and prefrontal cortex. Reduced tinnitus intrusiveness also correlated with acute change in connectivity between precuneus and an auditory network.ConclusionsFocal auditory-cortex tDCS can influence function in thalamus, auditory, and prefrontal cortex, which may associate with improved tinnitus.SignificanceWith future refinement, noninvasive brain stimulation targeting auditory cortex could become a viable intervention for tinnitus.HIGHLIGHTSFocal transcranial direct current stimulation (tDCS) of auditory cortex changes cerebral blood flow and connectivity in tinnitusTinnitus loudness ratings decreased on average after five sessions of active focal tDCSAcute changes in auditory, thalamic, and prefrontal function may predict quieter tinnitus after five sessions
Safety and protection of plasma donors: A scoping review and evidence (gap) map
Authors: Schroyens Natalie , D’aes Tine , Buck Emmy De , Mikkelsen Susan , Tiberghien Pierre , van den Hurk Katja , Erikstrup Christian , Compernolle Veerle , Remoortel Hans Van 
Published: July 2023

AbstractBackground and objectivesAs part of a large-scale European project aiming to safely increase plasma collection in Europe, the current scoping review identifies the existing evidence (gaps) on adverse events (AEs) and other health effects in plasmapheresis donors, as well as factors that may be associated with such events/effects.Materials and methodsWe searched 6 databases and 3 registries. Study characteristics (publication type and language, study design, population, outcomes, associated factors, time of assessment, duration of follow-up, number and frequency of donations within the study period, convalescent plasma (y/n), study setting, and location) were charted in duplicate and in consultation with a content expert group. Results were synthesized narratively and in an interactive evidence gap map (EGM).ResultsNinety-four research articles and 5 registrations focused on AEs (n = 38) and/or other health effects (n = 77) in plasmapheresis donors. Around 90% were observational studies (57 controlled; 33 uncontrolled), and most of them were performed in Europe (55%) or the USA (20%). Factors studied in association with donor health included donor characteristics (e.g., sex, age) (n = 27), cumulative number of donations (n = 21), donation frequency (n = 11), plasma collection device or program (n = 11), donor status (first-time versus repeat) (n = 10), donation volume per session (n = 8), time in donation program (n = 3), preventive measures (n = 2), or other (n = 9).ConclusionThe current scoping review and EGM provide accessible tools for researchers and policy-makers to identify the available evidence and existing research gaps concerning plasmapheresis donation safety. Controlled, prospective studies with long-term donor follow-up are scarce. Furthermore, additional experimental studies comparing the health effects of different donation frequencies are required to inform a safe upper limit for donation frequency.