bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
Authors: Hariharan Praveen , Dupuis Josée 
Published: August 2021

AbstractCoronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary ARtery DIsease Genome wide Replication and Meta-analysis consortium Exome (n = 120,575) and multi ancestry pan UK Biobank study (n = 442,574) summary data using versatile gene-based association study (VEGAS2) and Multi-marker analysis of genomic annotation (MAGMA) to identify novel genes and pathways associated with CAD. We included only exonic SNVs and excluded regulatory regions. VEGAS2 and MAGMA ranked genes and pathways based on aggregated SNV test statistics. We used Bonferroni corrected gene and pathway significance threshold at 3.0 × 10–6 and 1.0 × 10–5, respectively. We also report the top one percent of ranked genes and pathways. We identified 17 top enriched genes with four genes (PCSK9, FAM177, LPL, ARGEF26), reaching statistical significance (p ≤ 3.0 × 10–6) using both GBA tests in two GWAS studies. In addition, our analyses identified ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8) with previously unreported associations with CAD, although none of the single SNV associations within the genes were genome-wide significant. Among the top 1% non-lipid pathways, we detected pathways regulating coagulation, inflammation, neuronal aging, and wound healing.
Cross reactivity of neutralizing antibodies to the encephalitic California Serogroup orthobunyaviruses varies by virus and genetic relatedness
Authors: Evans Alyssa B. , Peterson Karin E. 
Published: August 2021

AbstractThe California Serogroup (CSG) of Orthobunyaviruses comprises several viruses capable of causing neuroinvasive disease in humans, including La Crosse (LACV), Snowshoe Hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses. Diagnosis of specific CSG viruses is complicated by the high degree of antibody cross-reactivity between them, with laboratory standards requiring a fourfold higher titer of neutralizating antibody (NAb) activity to positively identify the etiologic virus. To help elucidate NAb relationships between neuroinvasive CSG viruses, we directly compared the cross-reactivity of NAb between LACV, SSHV, TAHV, JCV, and INKV. Mice were inoculated with individual viruses and the NAb activity of plasma samples was compared by plaque reduction neutralization tests against all five viruses. Overall, the results from these studies show that the CSG viruses induced high levels of NAb against the inoculum virus, and differing amounts of cross-reactive NAb against heterologous viruses. LACV, SSHV, and INKV elicited the highest amount of cross-reactive NAb. Interestingly, a fourfold difference in NAb titer between the inoculum virus and the other CSG viruses was not always observed. Thus, NAb titers, which are the gold-standard for diagnosing the etiologic agent for viral encephalitis, may not clearly differentiate between different CSG viruses.
Reduced order modelling and experimental validation of a MEMS gyroscope test-structure exhibiting 1:2 internal resonance
Authors: Gobat Giorgio , Zega Valentina , Fedeli Patrick , Guerinoni Luca , Touzé Cyril , Frangi Attilio 
Published: August 2021

AbstractMicro-Electro-Mechanical Systems revolutionized the consumer market for their small dimensions, high performances and low costs. In recent years, the evolution of the Internet of Things is posing new challenges to MEMS designers that have to deal with complex multiphysics systems experiencing highly nonlinear dynamic responses. To be able to simulate a priori and in real-time the behavior of such systems it is thus becoming mandatory to understand the sources of nonlinearities and avoid them when harmful or exploit them for the design of innovative devices. In this work, we present the first numerical tool able to estimate a priori and in real-time the complex nonlinear responses of MEMS devices without resorting to simplified theories. Moreover, the proposed tool predicts different working conditions without the need of ad-hoc calibration procedures. It consists in a nonlinear Model Order Reduction Technique based on the Implicit Static Condensation that allows to condense the high fidelity FEM models into few degrees of freedom, thus greatly speeding-up the solution phase and improving the design process of MEMS devices. In particular, the 1:2 internal resonance experienced in a MEMS gyroscope test-structure fabricated with a commercial process is numerically investigated and an excellent agreement with experiments is found.
Multimorbidity prediction using link prediction
Authors: Aziz Furqan , Cardoso Victor Roth , Bravo-Merodio Laura , Russ Dominic , Pendleton Samantha C. , Williams John A. , Acharjee Animesh , Gkoutos Georgios V. 
Published: August 2021

AbstractMultimorbidity, frequently associated with aging, can be operationally defined as the presence of two or more chronic conditions. Predicting the likelihood of a patient with multimorbidity to develop a further particular disease in the future is one of the key challenges in multimorbidity research. In this paper we are using a network-based approach to analyze multimorbidity data and develop methods for predicting diseases that a patient is likely to develop. The multimorbidity data is represented using a temporal bipartite network whose nodes represent patients and diseases and a link between these nodes indicates that the patient has been diagnosed with the disease. Disease prediction then is reduced to a problem of predicting those missing links in the network that are likely to appear in the future. We develop a novel link prediction method for static bipartite network and validate the performance of the method on benchmark datasets. By using a probabilistic framework, we then report on the development of a method for predicting future links in the network, where links are labelled with a time-stamp. We apply the proposed method to three different multimorbidity datasets and report its performance measured by different performance metrics including AUC, Precision, Recall, and F-Score.
Incident stroke in patients with Alzheimer’s disease: systematic review and meta-analysis
Authors: Pinho João , Quintas-Neves Miguel , Dogan Imis , Reetz Kathrin , Reich Arno , Costa Ana Sofia 
Published: August 2021

AbstractVascular mechanisms are increasingly recognized in the pathophysiology of Alzheimer’s disease (AD), but less is known about the occurrence of stroke in AD patients. We aimed to quantify the risk of stroke in patients with AD and compare the incidence rates (IR) of stroke in individuals without AD. Systematic search of Embase and MEDLINE between 1970 and 2020. Inclusion criteria: reports with ≥ 50 patients with non-familial AD, which reported the occurrence of stroke (all types) and/or ischemic stroke and/or intracerebral hemorrhage (ICH) during follow-up. Meta-analyses of pooled data using random-effects model were performed. IR were calculated for each study. Incidence rate ratios (IRR) were calculated for studies presenting a control-group without AD. Among 5109 retrieved studies, 29 (0.6%) fulfilled the inclusion criteria, reporting a total of 61,824 AD patients. In AD patients the IR were 15.4/1000 person-years for stroke (all types), 13.0/1000 person-years for ischemic stroke and 3.4/1000 person-years for ICH. When compared to controls without AD, incidence rate for ICH in AD patients was significantly higher (IRR = 1.67, 95%CI 1.43–1.96), but similar for ischemic stroke. Incident stroke is not a rare event in AD population. AD is associated with an increased risk of intracerebral hemorrhage which warrants further clarification.
Adequacy of antibiotic prophylaxis and incidence of surgical site infections in neck surgery
Authors: Alonso-García M. , Toledano-Muñoz A. , Aparicio-Fernández J. M. , De-la-Rosa-Astacio F. M. , Rodríguez-Villar D. , Gil-de-Miguel A. , Durán-Poveda M. , Rodríguez-Caravaca G. 
Published: August 2021

AbstractHealth care-related infections are frequent and among them surgical site infection (SSI) are the most frequent in hospitals. The objective was to evaluate the adequacy of antibiotic prophylaxis in patients undergoing neck surgery and its relationship with the incidence of surgical site infection (SSI). Prospective cohort study. The adequacy of antibiotic prophylaxis in patients undergoing neck surgery was evaluated. Antibiotic prophylaxis was considered adequate when it conformed to all items of the protocol (antibiotic used, time of administration, administration route, dose and duration). The cumulative incidence of SSI was calculated, and the relationship between SSI and antibiotic prophylaxis adequacy was determined using adjusted relative risk (RR). Antibiotic prophylaxis was administered in 63 patients and was adequate in 85.7% (95% CI 75.0–92.3) of them. The cumulative incidence of SSI was 6.4% (95% CI 3.4–11.8). There was no significant relationship between antibiotic prophylaxis inadequacy and the incidence of SSI (RR = 2.4, 95% CI 0.6–10.6). Adequacy of antibiotic prophylaxis was high and it did not affect the incidence of SSIs.
Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients
Authors: Kappler Paula , Morgan Michael A. , Ivanyi Philipp , Brunotte Stefan J. , Ganser Arnold , Reuter Christoph W. M. 
Published: August 2021

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.
Integrated computational and experimental pipeline for quantifying local cell–matrix interactions
Authors: Xiao Hugh , Nguyen Ryan Y. , LaRanger Ryan , Herzog Erica L. , Mak Michael 
Published: August 2021

AbstractCellular interactions with the extracellular matrix (ECM) play a key role in modulating biological processes. While studies have identified key molecular factors of these interactions, the mechanical regulation associated with these interactions is not well characterized. To address this, we present an image analysis platform to analyze time-dependent dynamics observed in lung fibroblasts embedded in a 3D collagen matrix. Combining drug studies with quantitative analysis of cell–matrix interactions, our results are able to provide cellular level quantitative insights for mechanical and biophysical phenomena relevant to cell-ECM interactions. This system overall represents an initial pipeline for understanding cell mechanics in a 3D collagen gel and their implications in a physiologically relevant context.
Fitness consequences of biochemical adaptation in Drosophila melanogaster populations under simultaneous selection for faster pre-adult development and extended lifespan
Authors: Sharma Khushboo , Shakarad Mallikarjun N. 
Published: August 2021

AbstractIn holometabolous insects like Drosophila melanogaster, critical size is an important time point during larval life, for irreversible commitment to metamorphosis. Here, we studied the impact of restricted growth duration in terms of selection for faster pre-adult development in Drosophila melanogaster populations which resulted in the evolution of reduced critical size on adult life history traits. Selection for faster pre-adult development resulted in biochemical adaptation in larval physiology with no compromise in major biomolecules at critical size time point. The flies from the selected populations seem to not only commit to metamorphosis on the attainment of critical size but also seem to channelize resources to reproduction as indicated by similar life-time fecundity of CS and NS flies from selected populations, while the Control CS flies significantly lower life-time fecundity compared to Control NS flies. The flies from selected populations seem to achieve longevity comparable to control flies despite being significantly smaller in size-thus resource constrained due to faster pre-adult development.
Manual kidney stone size measurements in computed tomography are most accurate using multiplanar image reformatations and bone window settings
Authors: Reimer Robert Peter , Klein Konstantin , Rinneburger Miriam , Zopfs David , Lennartz Simon , Salem Johannes , Heidenreich Axel , Maintz David , Haneder Stefan , Große Hokamp Nils 
Published: August 2021

AbstractComputed tomography in suspected urolithiasis provides information about the presence, location and size of stones. Particularly stone size is a key parameter in treatment decision; however, data on impact of reformatation and measurement strategies is sparse. This study aimed to investigate the influence of different image reformatations, slice thicknesses and window settings on stone size measurements. Reference stone sizes of 47 kidney stones representative for clinically encountered compositions were measured manually using a digital caliper (Man-M). Afterwards stones were placed in a 3D-printed, semi-anthropomorphic phantom, and scanned using a low dose protocol (CTDIvol 2 mGy). Images were reconstructed using hybrid-iterative and model-based iterative reconstruction algorithms (HIR, MBIR) with different slice thicknesses. Two independent readers measured largest stone diameter on axial (2 mm and 5 mm) and multiplanar reformatations (based upon 0.67 mm reconstructions) using different window settings (soft-tissue and bone). Statistics were conducted using ANOVA ± correction for multiple comparisons. Overall stone size in CT was underestimated compared to Man-M (8.8 ± 2.9 vs. 7.7 ± 2.7 mm, p < 0.05), yet closely correlated (r = 0.70). Reconstruction algorithm and slice thickness did not significantly impact measurements (p > 0.05), while image reformatations and window settings did (p < 0.05). CT measurements using multiplanar reformatation with a bone window setting showed closest agreement with Man-M (8.7 ± 3.1 vs. 8.8 ± 2.9 mm, p < 0.05, r = 0.83). Manual CT-based stone size measurements are most accurate using multiplanar image reformatation with a bone window setting, while measurements on axial planes with different slice thicknesses underestimate true stone size. Therefore, this procedure is recommended when impacting treatment decision.
Effect of antibiotic treatment on Oxalobacter formigenes colonization of the gut microbiome and urinary oxalate excretion
Authors: Nazzal Lama , Francois Fritz , Henderson Nora , Liu Menghan , Li Huilin , Koh Hyunwook , Wang Chan , Gao Zhan , Perez Guillermo Perez , Asplin John R. , Goldfarb David S , Blaser Martin J 
Published: August 2021

AbstractThe incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.
Aerosol, chemical and physical properties of dry powder synthetic lung surfactant for noninvasive treatment of neonatal respiratory distress syndrome
Authors: Walther Frans J. , Chan Holly , Smith Jacob R. , Tauber Mike , Waring Alan J. 
Published: August 2021

AbstractInhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40 °C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.
Machine learning using clinical data at baseline predicts the efficacy of vedolizumab at week 22 in patients with ulcerative colitis
Authors: Miyoshi Jun , Maeda Tsubasa , Matsuoka Katsuyoshi , Saito Daisuke , Miyoshi Sawako , Matsuura Minoru , Okamoto Susumu , Tamura Satoshi , Hisamatsu Tadakazu 
Published: August 2021

AbstractPredicting the response of patients with ulcerative colitis (UC) to a biologic such as vedolizumab (VDZ) before administration is an unmet need for optimizing individual patient treatment. We hypothesized that the machine-learning approach with daily clinical information can be a new, promising strategy for developing a drug-efficacy prediction tool. Random forest with grid search and cross-validation was employed in Cohort 1 to determine the contribution of clinical features at baseline (week 0) to steroid-free clinical remission (SFCR) with VDZ at week 22. Among 49 clinical features including sex, age, height, body weight, BMI, disease duration/phenotype, treatment history, clinical activity, endoscopic activity, and blood test items, the top eight features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were selected for logistic regression to develop a prediction model for SFCR at week 22. In the validation using the external Cohort 2, the positive and negative predictive values of the prediction model were 54.5% and 92.3%, respectively. The prediction tool appeared useful for identifying patients with UC who would not achieve SFCR at week 22 during VDZ therapy. This study provides a proof-of-concept that machine learning using real-world data could permit personalized treatment for UC.
Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis
Authors: Conteduca Vincenza , Ku Sheng-Yu , Fernandez Luisa , Dago-Rodriquez Angel , Lee Jerry , Jendrisak Adam , Slade Megan , Gilbertson Cole , Manohar Jyothi , Sigouros Michael , Wang Yipeng , Dittamore Ryan , Wenstrup Rick , Mosquera Juan Miguel , Schonhoft Joseph D. , Beltran Himisha 
Published: August 2021

AbstractNeuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.
Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis
Authors: Jin Meihua , Jin Xiaocen , Homma Hidenori , Fujita Kyota , Tanaka Hikari , Murayama Shigeo , Akatsu Hiroyasu , Tagawa Kazuhiko , Okazawa Hitoshi 
Published: August 2021

AbstractMultiple gene mutations cause familial frontotemporal lobar degeneration (FTLD) while no single gene mutations exists in sporadic FTLD. Various proteins aggregate in variable regions of the brain, leading to multiple pathological and clinical prototypes. The heterogeneity of FTLD could be one of the reasons preventing development of disease-modifying therapy. We newly develop a mathematical method to analyze chronological changes of PPI networks with sequential big data from comprehensive phosphoproteome of four FTLD knock-in (KI) mouse models (PGRNR504X-KI, TDP43N267S-KI, VCPT262A-KI and CHMP2BQ165X-KI mice) together with four transgenic mouse models of Alzheimer’s disease (AD) and with APPKM670/671NL-KI mice at multiple time points. The new method reveals the common core pathological network across FTLD and AD, which is shared by mouse models and human postmortem brains. Based on the prediction, we performed therapeutic intervention of the FTLD models, and confirmed amelioration of pathologies and symptoms of four FTLD mouse models by interruption of the core molecule HMGB1, verifying the new mathematical method to predict dynamic molecular networks.