bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower Extremity Pediatric Tissue Expansion
Authors: Yusuf Cynthia T. , Lopez Christopher D. , Girard Alisa O. , Khoo Kimberly H. , Yang Robin , Redett Richard J. 
Published: October 2023

Background
Tissue expansion is a well-established approach to soft tissue reconstruction in the pediatric population for lower extremity pathologies. Unfortunately, complication rates range from 19% to 40% in literature, including infection and implant extrusion, leading to delays in reconstruction. These challenges have prompted investigation toward categorizing risk factors for lower extremity tissue expander placement.

Methods
A retrospective study of pediatric patients who underwent lower extremity tissue expander placement by the senior author (R.J.R.) was performed over a 16-year period. Patient charts were reviewed to categorize baseline and operative characteristics. Primary outcome variables were surgical-site infection, expander extrusion, and expander deflation. Univariate and multivariate logistic regressions were performed (α < 0.05).

Results
There were 59 tissue expanders in our cohort. The overall complication rate was 27.1% with a 77.2% successful reconstruction rate. Greater number of expanders placed during 1 operation is associated with 2.5 increased odds of having any complication and is associated with 0.4 decreased odds of having a successful reconstruction. Incisions made in scar tissue for expander placement appear to be associated with a greater than 7 times increased odds of readmission.

Conclusions
Reconstruction of soft tissue pathologies using lower extremity tissue expanders in the pediatric population is an effective yet challenging technique. This study identified that the number of expanders inserted during 1 operation, incisions made over scar tissue, and expanders placed in the anterior thigh were correlated with having a negative impact on reconstructive outcomes. Extra care should be taken with patients who require multiple expanders during 1 operation and with choosing the location and incision of expander placement.
Critical systolic blood pressure threshold for endovascular aortic occlusion – A multinational analysis to determine when to place a REBOA
Authors: Ordoñez Carlos A. , Parra Michael W. , Caicedo Yaset , Rodríguez-Holguín Fernando , García Alberto F. , Serna José J. , Serna Carlos , Franco María Josefa , Salcedo Alexander , Padilla-Londoño Natalia , Herrera-Escobar Juan P. , Zogg Cheryl , Orlas Claudia P. , Palacios Helmer , Saldarriaga Luis , Granados Marcela , Scalea Thomas , McGreevy David T. , Kessel Boris , Hörer Tal M. , Dubose Joseph , Brenner Megan ,   AAST-AORTA Investigators*; ABO Trauma Registry Group*
Published: October 2023

ABSTRACT

Background
Systolic blood pressure (SBP) is a potential indicator that could guide when to use a resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma patients with life-threatening injuries. This study aims to determine the optimal SBP threshold for REBOA placement by analyzing the association between SBP pre-REBOA and 24-hour mortality in severely injured hemodynamically unstable trauma patients.

Methods
We performed a pooled analysis of the Aortic Balloon Occlusion (ABO) trauma and AORTA registries. These databases record the details related to the use of REBOA and include data from 14 countries worldwide. We included patients who had suffered penetrating and/or blunt trauma. Patients who arrived at the hospital with a SBP pre-REBOA of 0 mm Hg and remained at 0 mm Hg after balloon inflation were excluded. We evaluated the impact that SBP pre-REBOA had on the probability of death in the first 24 hours.

Results
A total of 1107 patients underwent endovascular aortic occlusion, of these, 848 met inclusion criteria. The median age was 44 years [IQR, 27-59 years] and 643(76%) were male. The median injury severity score was 34 [IQR, 25-45]. The median SBP pre-REBOA was 65 mm Hg [IQR: 49-88 mm Hg]. Mortality at 24-hours was reported in 279 (32%) patients. Math modelling shows that predicted probabilities of the primary outcome increased steadily in SBP pre-REBOA below 100 mm Hg. Multivariable mixed-effects analysis shows that when SBP pre-REBOA was lower than 60 mm Hg, the risk of death was more than 50% (relative risk, 1.5; 95%CI, 1.17-1.92; P = .001)

Discussion
In patients who do not respond to initial resuscitation, the use of REBOA in SBP’s between 60- and 80-mm Hg may be a useful tool in resuscitation efforts before further decompensation or complete cardiovascular collapse. The findings from our study are clinically important as a first step in identifying candidates for REBOA.

Study Type
Observational Study

Level of Evidence
Level IV
Marker effect p-values for single-step GWAS with the algorithm for proven and young in large genotyped populations
Authors: Leite Natália Galoro , Bermann Matias , Tsuruta Shogo , Misztal Ignacy , Lourenco Daniela 
Published: October 2023

AbstractBackgroundAlthough single-step GBLUP (ssGBLUP) is a breeding value method, single-nucleotide polymorphism (SNP) effects can be backsolved from ssGBLUP genomic estimated breeding values (GEBV), and p-values can be obtained as a measure of estimation certainty. This enables single-step genome-wide association studies (ssGWAS). However, obtaining p-values for ssGWAS relies on the inversion of dense matrices, which poses computational limitations in large genotyped populations. In this study, we present an algorithm to approximate p-values for SNP in ssGWAS with many genotyped animals. The approximation relies on the algorithm for proven and young (APY) and submatrices for core animals. To test that, we first compared SNP p-values obtained with an exact inversion using the genomic relationship matrix (G−1) for 50K genotyped animals to those estimated with an exact inversion usingand those obtained with the proposed approximation based on. Then, we compared these results with those obtained with the proposed approximation using 450K genotyped animals.ResultsThe same genomic regions in chromosomes 7 and 20 were identified with p-values obtained withG−1,, and the approximation based onwhen using 50k genotyped animals and 1.5M in the pedigree. In terms of computational requirements, obtaining p-values with the approximation based onrepresented a reduction of 38 times in wall-clock time and ten times in memory requirement compared to using the exact inversion with. When the approximation was applied to a population of 450K genotyped animals and 1.8 in the pedigree, apart from the two genomic regions in chromosomes 7 and 20 previously identified with the smaller genotyped population, two new significant regions on chromosomes 6 and 14 were uncovered, indicating an increase in GWAS detection power when including more genotypes in the analyses. The process of obtaining p-value with the approximation and 450K genotyped individuals took 24.5 wall-clock hours and 87.66 GB of memory, which is expected to increase linearly with the addition of noncore genotyped individuals.ConclusionsWith an algorithm that approximates the prediction error variance of SNP effects based on APY, ssGWAS with p-values for SNP is possible in large genotyped populations. The computational cost of obtaining p-values in ssGWAS is no longer a limitation in extensive populations with many genotyped animals.
A gene with a thousand alleles: the HYPer-variable effectors of plant-parasitic nematodes
Authors: Sonawala Unnati , Beasley Helen , Thorpe Peter , Varypatakis Kyriakos , Senatori Beatrice , Jones John T. , Derevnina Lida , den Akker Sebastian Eves-van 
Published: October 2023

AbstractPathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms, including effectors and immune receptors, are part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the HYPer-variable (HYP) effectors of plant-parasitic nematodes.We discovered single effector gene loci that can harbour potentially thousands of allelic variants. These alleles vary in the number, but principally in the organisation, of motifs within a central Hyper Variable Domain (HVD). Using targeted long-read sequencing, we dramatically expand the HYP repertoire of two plant-parasitic nematodes,Globodera pallidaandG. rostochiensis,such that we can define distinct sets of species-specific “rules” underlying the apparently flawless genetic rearrangements. Finally, by analysing the HYP complement of 68 individual nematodes we made the unexpected finding that despite the huge number of alleles, most individuals are homozygous. Taken together, these data point to a novel mechanism of programmed genetic variation, termed HVD-editing, where alterations are locus-specific, strictly governed by rules, and can theoretically produce thousands of variants without errors.
Predicting functional consequences of recent natural selection in Britain
Authors: Poyraz Lin , Colbran Laura L. , Mathieson Iain 
Published: October 2023

AbstractAncient DNA can directly reveal the contribution of natural selection to human genomic variation. However, while the analysis of ancient DNA has been successful at identifying genomic signals of selection, inferring the phenotypic consequences of that selection has been more difficult. Most trait-associated variants are non-coding, so we expect that a large proportion of the phenotypic effects of selection will also act through non-coding variation. Since we cannot measure gene expression directly in ancient individuals, we used an approach (Joint-Tissue Imputation; JTI) developed to predict gene expression from genotype data. We tested for changes in the predicted expression of 17,384 protein coding genes over a time transect of 4500 years using 91 present-day and 616 ancient individuals from Britain. We identified 28 genes at seven genomic loci with significant (FDR < 0.05) changes in predicted expression levels in this time period. We compared the results from our transcriptome-wide scan to a genome-wide scan based on estimating per-SNP selection coefficients from time series data. At five previously identified loci, our approach allowed us to highlight small numbers of genes with evidence for significant shifts in expression from peaks that in some cases span tens of genes. At two novel loci (SLC44A5andNUP85), we identify selection on gene expression not captured by scans based on genomic signatures of selection. Finally we show how classical selection statistics (iHS and SDS) can be combined with JTI models to incorporate functional information into scans that use present-day data alone. These results demonstrate the potential of this type of information to explore both the causes and consequences of natural selection.
Membrane Mimetic-Dependence of GPCR Energy Landscapes
Authors: Thakur Naveen , Ray Arka Prabha , Lyman Edward , Gao Zhan-Guo , Jacobson Kenneth A. , Eddy Matthew T. 
Published: October 2023

SummaryProtein function strongly depends on temperature, which is related to temperature-dependent changes in the equilibria of protein conformational states. We leveraged variable-temperature19F-NMR spectroscopy to interrogate the temperature dependence of the conformational landscape of the human A2Aadenosine receptor (A2AAR), a class A GPCR. Temperature-induced changes in the conformational equilibria of A2AAR in lipid nanodiscs were markedly dependent on the efficacy of bound drugs. While antagonist complexes displayed only modest changes as the temperature rose, both full and partial agonist complexes exhibited substantial increases in the active state population. Importantly, the temperature-dependent response of complexes with both full and partial agonists exhibited a pronounced sensitivity to the specific membrane mimetic employed. In striking contrast to observations within lipid nanodiscs, in detergent micelles the active state population exhibited different behavior for A2AAR complexes with both full and partial agonists. This underscores the importance of the protein environment in understanding the thermodynamics of GPCR activation.HighlightsActive A2AAR population increases with increasing temperature in lipid nanodiscsActive A2AAR population exhibits different temperature dependence in detergentsPartial agonist complexes present a unique conformational state in nanodiscsTemperature dependence of partial agonist equilibria depends on membrane mimetic
Early syphilis in Guangzhou, China: presentation, molecular detection ofTreponema pallidum, and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing
Authors: Yang Ligang , Zhang Xiaohui , Chen Wentao , Seña Arlene C. , Zheng Heping , Jiang Yinbo , Zhao Peizhen , Chen Rongyi , Wang Liuyuan , ke Wujian , Salazar Juan C. , Parr Jonathan B. , Tucker Joseph D. , Hawley Kelly L. , Caimano Melissa J. , Hennelly Christopher M. , Aghakanian Farhang , Zhang Feifei , Chen Jane S. , Moody M. Anthony , Radolf Justin D. , Yang Bin 
Published: October 2023

AbstractBackgroundThe global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) ofTreponema pallidum(TPA) using different specimen types is essential for vaccine development.MethodsPatients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China. We collected ulcer exudates and blood from PS participants, and skin biopsies and blood from SS participants forTPA polApolymerase chain reaction (PCR); ulcer exudates and blood were also used to isolateTPAstrains by rabbit infectivity testing (RIT).TPAWGS was performed on 52 ulcer exudates and biopsy specimens and 25 matched rabbit isolates.ResultsWe enrolled 18 PS and 51 SS participants from December 2019 to March 2022. Among PS participants,TPADNA was detected in 16 (89%) ulcer exudates and three (17%) blood specimens. Among SS participants,TPADNA was detected in 50 (98%) skin biopsies and 27 (53%) blood specimens.TPA was isolated from 48 rabbits, with a 71% (12/17) success rate from ulcer exudates and 69% (36/52) from SS bloods. Twenty-three matched SS14 clade genomes were virtually identical, while two Nichols clade pairs had discordanttprKsequences. Forty-two of 52 uniqueTPAgenomes clustered in an SS14 East Asia subgroup, while ten fell into two East Asian Nichols subgroups.ConclusionsOurTPAdetection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS whole blood, with RIT isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.SummaryWe performedTreponema pallidummolecular detection and genome sequencing from multiple specimens collected from early syphilis patients and isolates obtained by rabbit inoculation. Our results support the use of whole genome sequencing from rabbit isolates to inform syphilis vaccine development.
Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced ECG analysis
Authors: Hughes Rebecca K. , Thornton George D. , Malcolmson James W. , Pierce Iain , Khoury Shafik , Hornell Amanda , Knott Kristopher , Captur Gabriella , Moon James C. , Schlegel Todd T. , Ugander Martin 
Published: October 2023

ABSTRACTBackgroundTypical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM.MethodsA-ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM (n=75 overt, n=32 relative [<15mm hypertrophy]), a subgroup of which underwent cardiovascular magnetic resonance, n=92), and comparator subjects (n=2449), including healthy volunteers (n=1672), patients with coronary artery disease (n=372), left ventricular electrical remodelling (n=108), ischemic (n=114) or non-ischemic cardiomyopathy (n=57), and asymmetrical septal hypertrophy (ASH) HCM (n=126).ResultsMultivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy (area under the receiver operating characteristics curve (AUC) [bootstrapped 95% confidence interval] 0.982 [0.965– 0.993]. Linear discriminant analysis also diagnosed ApHCM with high accuracy (AUC 0.989 [0.986–0.991]).ConclusionExplainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting future diagnostic and management strategies may incorporate both features.
Microtubule reorganization during mitotic cell division in the dinoflagellateOstreospiscf.ovata
Authors: Velasquez-Carvajal David , Garampon Flavie , Lemée Rodolphe , Schaub Sebastian , Castagnetti Stefania 
Published: October 2023

AbstractDinoflagellates are marine organisms that undergo seasonal explosive proliferation events known as algal blooms. Vegetative cell proliferation is a main contributing factor in these events. However, mechanistical understanding of mitosis and cytokinesis in dinoflagellate remains rudimentary. Using an optimized immunofluorescence protocol, we analysed changes in microtubule organization occurring during the mitotic cycle of the toxic dinoflagellateOstreopsiscf.ovata.This study revealed important features of dinoflagellate cell division. We find that the two flagella and the cortical microtubule array persist throughout the mitotic cycle. Two microtubule bundles are present in the cytoplasm originating from the ventral area, where the basal bodies are located: a cortical bundle and a cytoplasmic ventral bundle. The latter associates with the nucleus in the cell centre in preparation for mitosis and with the acentrosomal extranuclear spindle during mitosis. Analysis of tubulin post-translational modifications identifies two populations of spindle microtubules: polar acetylated microtubules whose length is stable throughout mitosis and central tyrosinated microtubules which elongate during chromosome segregation. During cell division a microtubule rich structure forms along the dorsal-ventral axis, associated with the site of cytokinesis, consistent with a cytokinetic mechanism independent of the actomyosin ring typical of animal and yeast cells.Summary statementOur study describes special features of mitosis and cytokinesis in dinoflagellates and uncovers a new alternative mechanism for cell division, highlighting the plasticity of cell biological process in eukaryotic cells.
Implementation of Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD) for improving treatment adherence amongst drug-resistant Tuberculosis patients in Ahmedabad City, Gujarat
Authors: Travedi Poonam , Raval Devang , Malik Danish , Saha Somen , Saxena Deepak , Halkarni Nishad , Doshi Rahul , Rajpurohit Sukan , Rao Raghavendra , Joshi Madhav 
Published: October 2023

AbstarctBackgroundTreatment Adherence among Tuberculosis (TB) patients is a critical challenge globally and in India. Digital technology has appeared as a tool for providing patient centric monitoring support to improve TB patients’ drug adherence. However, there is a paucity of evidence on the acceptability and effectiveness of such devices for enhancing adherence among drug-resistant TB (DRTB). The present study aims to document the feasibility of using the Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD) and treatment adherence amongst DRTB patients.MethodsA longitudinal follow-up study of DRTB patients was conducted in Ahmedabad. A total of 22 Tuberculosis Units (TUs) from Ahmedabad’s rural and urban regions were included in the study based on the high load of DR-TB patients. Two hundred patients were enrolled per the inclusion criteria, and the TMEAD device was deployed to the enrolled patients and followed up monthly for six months to document drug adherence and various challenges.ResultMore than 80.5% of the patients used the device, and the point drug adherence was 92% among the patients who used the device. About 19.5% did not use the device, and the reasons for the non-use of the device include non-functional devices and alarms, charging, and incomplete refilling with prescribed drugs. The other significant issues include the social stigma regarding the disease and the fear of disclosure of TB.ConclusionThe present study revealed that the acceptability of TMEAD and patient reported drug adherence were high. However, there were various disease and device related challenges. The implementation of TMEAD can be improved through the design modification. Further large-scale research is required to document the effectiveness of the device and scale up.
Excess deaths in China during SARS-CoV-2 viral waves in 2022-2023
Authors: Jha Prabhat , Brown Patrick E , Lam Teresa , Morawski Ed , Reid Angus 
Published: October 2023

BackgroundThe extent to which the Omicron variant of SARS-CoV-2 raised death rates in China during its viral wave of December 2022-January 2023 remains undocumented.MethodsWe worked with an established national survey organization to survey 8,004 adults in all 31 administrative areas of China to ask about deaths in families since January 2020. We examined agespecific death rates, focusing on deaths above age 60 years, and at 15-59 years. We compared these to the United Nations (UN) estimates of age-specific mortality in 2019.FindingsThe survey participants were broadly similar to the 2020 census and other national surveys in age, sex, region, and smoking status, but had lower SARS-CoV-2 vaccination rates and higher education levels. There were no differences between reporting of deaths during the Omicron period versus earlier. The survey captured 456 deaths, of which 329 occurred at ages 60+ years and 212 were women. At ages 60+ years, death rates per 1000 rose 242% (95%CI 128-398%) during December 2022-January 2023. Deaths at ages 15-59 years did not rise appreciably. The UN estimates approximately 675,000 deaths per month at ages 60+ years in 2019. If rates doubled nationally as in our survey, China had approximately 1·35 million excess deaths over the two months.InterpretationChina experienced a sharp but short increase in excess deaths among its elderly during the Omicron wave. If death registry data corroborate our estimates of substantial excess deaths in China, the worldwide estimates of excess deaths to 2023 may need upward adjustment.FundingCanadian Institutes of Health Research
Bidirectional relationship between olfaction and Parkinson’s disease
Authors: Kim Jonggeol J. , Bandres-Ciga Sara , Heilbron Karl ,   23andMe Research Team, Blauwendraat Cornelis , Noyce Alastair J. 
Published: October 2023

AbstractBackgroundHyposmia (loss of smell) is a common early symptom of Parkinson’s disease (PD). The shared genetic architecture between hyposmia and PD is unknown.MethodsWe leveraged genome-wide association study (GWAS) results for self-assessment of ‘ability to smell’ and PD diagnosis. Linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA) were used to identify genome-wide and local genetic correlations. Mendelian randomization was used to identify potential causal relationships.ResultsLDSC found that sense of smell negatively correlated at a genome-wide level with PD. LAVA found negative correlations in four genetic loci nearGBA1, ANAPC4, SNCA, andMAPT. Using Mendelian randomization we found evidence for strong causal relationship between PD and liability towards poorer sense of smell, but weaker evidence for the reverse direction.ConclusionsHyposmia and PD share genetic liability in only a subset of the major PD risk genes. While there was definitive evidence that PD can lower the sense of smell, there was only suggestive evidence for the reverse. This work highlights the heritability of olfactory function and its relationship with PD heritability and provides further insight into the association between PD and hyposmia.