bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Viability of Magnetic Bead Implants in Muscle
Authors: Taylor Cameron R. , Clark William H. , Clarrissimeaux Ellen G. , Yeon Seong Ho , Carty Matthew J. , Lipsitz Stuart R. , Bronson Roderick T. , Roberts Thomas J. , Herr Hugh M. 
Published: August 2022

AbstractHuman movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body’s surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post- versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses, exoskeletons, and in closed-loop neuroprosthetics to aid recovery from neurological disorders.
Absence of atrial smooth muscle in the heart of the loggerhead sea turtle (Caretta caretta): a re-evaluation of its role in diving physiology
Authors: Costello Leah M. , García-Párraga Daniel , Crespo-Picazo Jose Luis , Codd Jonathan , Shiels Holly A. , Joyce William 
Published: August 2022

AbstractContraction of atrial smooth muscle in the hearts of semi-aquatic emydid turtles regulates ventricular filling, and it has been proposed that it could regulate stroke volume during characteristic rapid transitions in cardiac output associated with diving. For this hypothesis to be supported, atrial smooth muscle should be widely distributed in diving Testudines. To further understand the putative function and evolutionary significance of endocardial smooth muscle in Testudines, we studied the hearts of loggerhead sea turtles, Caretta caretta (n=7), using immunohistochemistry and histology. Surprisingly, we found no evidence of prominent atrial smooth muscle in C. caretta. However, smooth muscle was readily identified in the sinus venosus. Our results suggest atrial smooth muscle does not contribute to the diving capabilities of C. caretta, indicating that the possible roles of smooth muscle in emydid turtle hearts requires a re-evaluation. In sea turtles, the sinus venosus may instead contribute to regulate cardiac filling.
Harmful self-pollination drives gynodioecy in European chestnut, a self-incompatible tree
Authors: Larue Clément , Petit Rémy J. 
Published: August 2022

SummaryGynodioecy is a rare sexual system in which two genders, cosexuals and females, coexist. It provides the opportunity to compare individuals having both sexual functions with individuals lacking the male function, an ideal situation to understand how sexes interact within individual plants.We report gynodioecy in the European chestnut, an outcrossing self-incompatible Fagaceae tree species. This finding was unexpected because gynodioecy is often interpreted as an outbreeding mechanism. To understand how female chestnuts compensate for their lack of siring capacity, we compared key female fitness components between genders and performed emasculation experiments.Genders have similar basal area and number of flowers but different fruit set. Following the removal of nectar-producing catkins on branches or entire trees, fruit set increased in cosexual trees but decreased in female trees.These results show that self-pollination impairs fruit set in cosexual trees, a likely effect of self-pollen interference caused by late-acting self-incompatibility and by early inbreeding depression. Female trees escape from self-pollen interference but continue to attract pollinators thanks to their sterile but rewarding male catkins, resulting in a much higher fruit set than cosexuals. This demonstrates that even entirely outcrossed plants can benefit from the cessation of self-pollination.
Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients
Authors: Ho Minh , Nguyen Huynh-Nga , Hoang Minh Van , Bui Tien Thuy Thi , Vu Bao-Quoc , Dinh Truc Huong Thi , My Vo Hoa Thi , Blaydon Diana , Eldirany Sherif A. , Bunick Christopher G. , Bui Chi-Bao 
Published: August 2022

AbstractCutaneous ichthyosis (CI) is a collective group of monogenetic disorders of cornification demonstrating epidermal scaling, fissuring, chronic skin inflammation, and increased susceptibility to infection. In healthy individuals the skin microbiome limits growth of pathogenic organisms; however, the microbiome signature in CI is poorly characterized. To rectify this, we investigated the microbiome signature across 7 subtypes of CI in 43 individuals of Southeast Asian ethnicity, of which exome sequencing revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis revealed distinct microbial populations, reduced commensal microbiota, and higher colonization by pathogenic species. This correlated with increased production of inflammatory cytokines, including Th17 and JAK/STAT signaling, in peripheral blood mononuclear cells. Moreover, we identified microbiota and inflammation alterations in wounds of CI patients responsible for impaired wound healing. Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI patients and provides critical information for improving therapeutic management.
Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning
Authors: Neumann Alexander , Ohlei Olena , Küçükali Fahri , Bos Isabelle J , Vos Stephanie , Prokopenko Dmitry , Tijms Betty M , Andreasson Ulf , Blennow Kaj , Vandenberghe Rik , Scheltens Philip , Teunissen Charlotte E , Engelborghs Sebastiaan , Frisoni Giovanni B , Blin Oliver , Richardson Jill C , Bordet Régis , Lleó Alberto , Alcolea Daniel , Popp Julius , Clark Christopher , Peyratout Gwendoline , Martinez-Lage Pablo , Tainta Mikel , Dobson Richard JB , Legido-Quigley Cristina , Van Broeckhoven Christine , Tanzi Rudolph E , ten Kate Mara , Lill Christina M , Barkhof Frederik , Lovestone Simon , Streffer Johannes , Zetterberg Henrik , Visser Pieter Jelle , Sleegers Kristel , Bertram Lars ,   EMIF-AD & ADNI study group
Published: August 2022

ABSTRACTGenome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to: 1. identify common genetic variants associated with these CSF profiles; 2. assess the role of associated variants in AD pathophysiology and 3. explore potential sex differences. We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n=205 controls, n=546 mild cognitive impairment, n=222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed sex-specific effects. Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 and GRIN2D) and three were previously described (APOE, TMEM160B and CHI3L). GRIN2D was associated with synaptic functioning, whereas rs145791381 was associated with biomarker evidence of inflammation. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers. These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.
Opportunities for shared decision-making about major surgery: findings from a multi-method qualitative study of decision-making about orthopaedic, colorectal and cardio thoracic surgery with high risk patients
Authors: Shaw Sara E , Hughes Gemma L , Pearse Rupert , Avagliano Ester , Day James R , Edsell Mark E , Edwards Jennifer A , Everest Leslie , Stephens Timothy J 
Published: August 2022

ABSTRACTBackgroundLittle is known about the opportunities for shared decision-making when high-risk patients (over 60 years, with co-morbidities) are offered major surgery. This paper examines when and why clinicians and patients can share decision-making about major surgery.MethodsMulti-method qualitative study, combining video-recordings of pre-operative consultations, interviews and focus groups (with a maximum variation sample of 31 patients, 19 relatives, 37 clinicians), with observations of clinics in five UK hospitals undertaking major joint, colorectal and/or cardiac surgery.ResultsThree opportunities for shared decision making about major surgery were identified. Resolution-focused consultations (cardiac/colorectal) resulted in a single agreed preferred option related to a potentially life-threatening problem, with limited opportunities for shared decision-making. Evaluative and deliberative consultations offered more opportunity. The former focused on assessing the likelihood of benefits of surgery for a presenting problem that was not a threat to life for the patient (e.g. orthopaedic consultations) and the later (largely colorectal) involving discussion of a range of options while also considering significant comorbidities and patient preferences. The extent to which opportunities for shared decision-making were available, and taken up by surgeons, was influenced by nature of the presenting problem, clinical pathway and patient trajectory.Conclusion and relevanceDecisions about major surgery are not always shared between patients and doctors. The nature of the presenting problem, comorbidities, clinical pathways and patient trajectories all inform the type of consultation and opportunities for sharing decision-making. This has implications for clinicians, with shared decision-making about major surgery most feasible when the focus is on life-enhancing rather than life-saving treatment.
Healthcare workers’ worries and Monkeypox vaccine advocacy during the first month of the WHO Monkeypox alert: Cross-sectional survey in Saudi Arabia
Authors: Aljamaan Fadi , Alenezi Shuliweeh , Alhasan Khalid , Saddik Basema , Alhaboob Ali , Altawil Esraa S. , Alshahrani Fatimah , Alrabiaah Abdulkarim , Alaraj Ali , Alkriadees Khaled , Alshammari Yousef , Alharbi Homood , Jamal Amr , Halwani Rabih , AlZamil Fahad , Al-Subaie Sarah , Barry Mazin , Memish Ziad A , Al-Tawfiq Jaffar A. , Temsah Mohamad-Hani 
Published: August 2022

AbstractBackgroundMonkeypox virus re-surged in May 2022 as a new potential global health threat with outbreaks bursting in multiple countries across different continents. This study was conducted during the first month of the WHO announcement to assess the healthcare workers (HCWs) within Saudi Arabia, exploring their perception, worries, and vaccine acceptance for Monkeypox in-line with the resolving COVID-19 pandemic.MethodsA national cross-sectional survey was conducted between May 27 and June 10, 2022, in Saudi Arabia. Data were collected on the sociodemographic and job-related characteristics, COVID-19 infection status, HCWs’ worry levels of Monkeypox compared to COVID-19 and its sources, their perceptions, awareness, and HCWs’ Monkeypox vaccination advocacy.ResultsAmong the 1130 HCWs who completed survey, 41.6% already developed COVID-19. Still, 56.5% were more worried from COVID-19 compared to Monkeypox, while the rest were more worried of Monkeypox disease. The main reason for their worry among 68.8% of the participants was development of another worldwide pandemic post COVID-19, followed by their worry of acquiring the infection themselves or their families (49.6%). Most HCWs (60%) rated their self-awareness of Monkeypox disease as moderate to high.Males and those who previously developed COVID-19 were significantly less likely to worry about Monkeypox. The worry about Monkeypox developing into a pandemic and the perception of Monkeypox being a severe disease correlated significantly positively with the odds of high worry from the disease.Regarding participants’ advocacy for HCWs’ vaccination against Monkeypox disease, those who developed COVID-19 previously and those who supported application of tighter infection control measures compared to the current ones to combat the disease were significantly predicted to agree for vaccination. 74.2% of the surveyed HCWs perceived that they need to read more about the Monkeypox disease after the survey.ConclusionDuring the first month of the WHO’s Monkeypox international alert, about half of HCWs in this study were more worried about Monkeypox disease as compared to COVID-19, and its possible progression into another pandemic. In addition, the majority were in favor of applying tighter infection prevention measures to combat the disease. The current study highlights areas needed for healthcare administrative about the HCWs’ perceptions and readiness for Monkeypox especially in the event of any occurrence of local or international pandemic.
Exposure-Response Relation for Vibration-Induced White Finger: Inferences from a Published Meta-Analysis of Population Groups
Authors: Scholz Magdalena F. , Brammer Anthony J. , Marburg Steffen 
Published: August 2022

AbstractPurposeIt is questioned whether the exposure-response relation for the onset of vibration-induced white finger (VWF) in ISO 5349-1:2001 needs to be revised based on the epidemiologic studies identified by Nilsson et al., (2017) (https://doi.org/10.1371/journal.pone.0180795), and whether the relation they derive improves the prediction of VWF in vibrationexposed populations.MethodsA pooled analysis has been performed using pidemiologic studies that complied with selection rules and reported a VWF prevalence of 10% or more, and exposure constructed according to the provisions of ISO 5349-1:2001. The lifetime exposure at 10% prevalence was calculated for various data sets using linear interpolation. They were then compared to both the model from the standard and that developed by Nilsson et al.ResultsRegression analyses reveal excluding extrapolation to adjust group prevalences to 10% produce models with 95-percentile confidence intervals that include the ISO exposure-response relation but not that in Nilsson et al. (2017). Different curve fits are obtained for studies involving daily exposure to single or multiple power tools and machines. Studies with similar exposure magnitudes and lifetime exposure durations but markedly different prevalences are observed to cluster.ConclusionsA range of exposures and A(8)-values is predicted within which the onset of VWF is most likely to occur. The exposure-response relation in ISO 5349-1:2001, but not that proposed by Nilsson et al., falls within this range and provides a conservative estimate for the development of VWF. Additionally, the analyses demonstrate that the method for evaluating vibration exposure contained in ISO 5349-1:2001 needs revision.
Acute respiratory distress syndrome and shunt detection with bubble studies: a systematic review and meta-analysis
Authors: Odenbach Jeffrey , Dhanoa Sumeet , Sebastianski Meghan , Milovanovic Lazar , Robinson Andrea , Mah Graham , Rewa Oleksa G. , Bagshaw Sean M. , Buchanan Brian , Lau Vincent I. 
Published: August 2022

ABSTRACTObjectivesAcute respiratory distress syndrome (ARDS) is a life-threatening respiratory injury with multiple physiological sequalae. Shunting of deoxygenated blood through intra and extra-pulmonary shunts is one consequence that may complicate ARDS management. Therefore, we conducted a systematic review to determine the prevalence of sonographically detected shunt and its association with oxygenation and mortality in patients with ARDS.Data SourcesWe searched MEDLINE, EMBASE, Cochrane Library and DARE databases on March 26, 2021Study SelectionArticles relating to respiratory failure and sonographic shunt detection.Data ExtractionArticles were independently screened and extracted in duplicate. Data pertaining to study demographics and shunt detection were compiled for mortality and oxygenation outcomes. Risk of bias was appraised using the Joanna Briggs Institute and Newcastle-Ottawa Scale tools with evidence rating certainty using GRADE methodology.Data SynthesisFrom 4,617 citations, 10 observational studies met eligibility criteria. Sonographic detection of right-to-left shunt was present in 21.8% of patients (range:14.4-30.0%) amongst included studies using transthoracic, transesophageal and transcranial bubble Doppler sonography. Shunt prevalence may be associated with increased mortality (risk ratio: 1.22, 95% CI: 1.01-1.49, p=0.04, very low certainty evidence) with no difference in oxygenation as measured by PaO2:FiO2ratio (mean difference -0.7, 95% CI: -18.6 to 17.2, p=0.94, very low certainty evidence).ConclusionsIntra- and extra-pulmonary shunts are detected frequently in ARDS with ultrasound techniques. Shunts may increase mortality amongst patients with ARDS, but its association with oxygenation is uncertain. Future research should explore the role of shunt in ARDS, their association with mortality, and whether targeted precision medicine interventions can improve outcomes.PROSPERO Registration Number: CRD42021245194 (March 26, 2021)Key PointsQuestion:In adult critically ill ARDS patients, what is the prevalence of right-to-left shunts, and what are their effects on mortality and/or oxygenation?Findings:In this systematic review and meta-analysis, shunts be may prevalent in ∼1 in 5 ARDS patients. They may be associated with a statistically significant increase in mortality, with no difference in oxygenation parameters.Meaning:Intra- and extra-pulmonary shunts are detected frequently in ARDS with ultrasound techniques, and may increase mortality amongst patients with ARDS (although its association with oxygenation is uncertain).
Neural Network-Derived Potts Models for Structure-Based Protein Design using Backbone Atomic Coordinates and Tertiary Motifs
Authors: Li Alex J. , Lu Mindren , Desta Israel , Sundar Vikram , Grigoryan Gevorg , Keating Amy E. 
Published: August 2022

AbstractDesigning novel proteins to perform desired functions, such as binding or catalysis, is a major goal in synthetic biology. A variety of computational approaches can aid in this task. An energy-based framework rooted in the sequence-structure statistics of tertiary motifs (TERMs) can be used for sequence design on pre-defined backbones. Neural network models that use backbone coordinate-derived features provide another way to design new proteins. In this work, we combine the two methods to make neural structure-based models more suitable for protein design. Specifically, we supplement backbone-coordinate features with TERM-derived data, as inputs, and we generate energy functions as outputs. We present two architectures that generate Potts models over the sequence space: TERMinator, which uses both TERM-based and coordinate-based information, and COORDinator, which uses only coordinate-based information. Using these two models, we demonstrate that TERMs can be utilized to improve native sequence recovery performance of neural models. Furthermore, we demonstrate that sequences designed by TERMinator are predicted to fold to their target structures by AlphaFold. Finally, we show that both TERMinator and COORDinator learn notions of energetics, and these methods can be fine-tuned on experimental data to improve predictions. Our results suggest that using TERM-based and coordinate-based features together may be beneficial for protein design and that structure-based neural models that produce Potts energy tables have utility for flexible applications in protein science.CodeCode will be made publically available at https://github.com/alexjli/terminator_public
Taxonomic, genomic, and functional variation in the gut microbiomes of wild spotted hyenas across two decades of study
Authors: Rojas Connie A. , Holekamp Kay E. , Jasso Mariette Viladomat , Souza Valeria , Eisen Jonathan A. , Theis Kevin R. 
Published: August 2022

AbstractThe gut microbiome provides vital functions for mammalian hosts, yet research on the variability and function of the microbiome across adult lifespans and multiple generations is limited in large mammalian carnivores. Here we use 16S rRNA gene and metagenomic sequencing to profile the taxonomic composition, genomic diversity, and metabolic function of the gut microbiome of 12 wild spotted hyenas (Crocuta crocuta) residing in the Masai Mara National Reserve, Kenya over a 23-year period spanning three generations. We determined the extent to which host factors predict variation in the gut microbiome and identify the core microbes present in the guts of hyenas. We also investigate novel genomic diversity in the mammalian gut by reporting the first metagenome-assembled genomes (MAGs) for hyenas. We found that gut microbiome taxonomic composition was highly variable across the two decades of sampling, but despite this, a core set of 14 bacterial genera and 19 amplicon sequence variants were identified. The strongest predictors of microbiome alpha and beta-diversity were host identity and age, suggesting that hyenas possess individualized microbiomes, and that these may change with age during adulthood. Gut microbiome functional profiles were also individual-specific, and were moderately correlated with antelope prey abundance, indicating that the functions of the gut microbiome vary with host diet. We recovered 149 high-quality MAGs from the hyena gut, spanning 25 bacterial orders and 51 genera. Some MAGs were classified as taxa previously reported for other carnivores, but many were novel and lacked species level matches to genomes in existing reference databases.ImportanceThere is a gap in knowledge regarding the genomic diversity and variation of the gut microbiome across a host’s lifespan and across multiple generations of hosts in wild mammals. Using two types of sequencing approaches, we demonstrate that although gut microbiomes are individualized and temporally variable among hyenas, they correlate similarly to large-scale changes in their host’s ecological environment. We also recovered 149 high-quality MAGs from the hyena gut, greatly expanding the microbial genome repertoire known for hyenas, carnivores and wild mammals in general. Some MAGs came from genera abundant in the gastrointestinal tracts of canid species and other carnivores but over 80% of MAGs were novel and from species previously not represented in genome databases. Collectively, our novel body of work illustrates the importance of surveying the gut microbiome of non-model wild hosts, using multiple sequencing methods and computational approaches, and at distinct scales of analysis.