bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival by race in men with chemotherapy-naive enzalutamide- or abiraterone-treated metastatic castration-resistant prostate cancer
Authors: George Daniel J. , Ramaswamy Krishnan , Huang Ahong , Russell David , Mardekian Jack , Schultz Neil M. , Janjan Nora , Freedland Stephen J. 
Published: November 2021

Abstract
Background
Black men are more likely to be diagnosed with aggressive prostate cancer (PC) and die from PC than white men. However, black men with metastatic castration-resistant PC (mCRPC) had longer overall survival (OS) than white men when treated with certain agents in clinical trials. We analyzed claims data from the Veterans Health Administration (VHA) database to evaluate OS in black and white men treated with enzalutamide or abiraterone (novel hormonal therapy [NHT]) for chemotherapy-naïve mCRPC.

Methods
Patients with mCRPC aged ≥18 years were identified in the VHA database by diagnosis codes, evidence of surgical/medical castration, and a prescription claim for enzalutamide or abiraterone after castration from April 2014–March 2017. Cox models assessed associations between race and OS. Unadjusted and multivariable analyses were performed on the entire population and subsets based on the type of therapy received (if any) after NHT.

Results
In total, 2910 patients were identified (787 black, mean 71.7 years; 2123 white, mean 74.0 years). Median follow-up was 19.0 and 18.7 months in blacks and whites, respectively. Black men had better survival versus white men: hazard ratios (95% CIs) were 0.89 (0.790–0.996; P = 0.044) and 0.67 (0.592–0.758; P < 0.0001) in the unadjusted and multivariable models, respectively. Statistically significantly longer OS was seen in black versus white men regardless of subsequent treatment, including no subsequent treatment.

Conclusions
In the VHA, black men with chemotherapy-naïve mCRPC initiating NHT may have better outcomes than similarly treated white men.
Application of long-read sequencing to elucidate complex pharmacogenomic regions: a proof of principle
Authors: van der Lee Maaike , Rowell William J. , Menafra Roberta , Guchelaar Henk-Jan , Swen Jesse J. , Anvar Seyed Yahya 
Published: November 2021

AbstractThe use of pharmacogenomics in clinical practice is becoming standard of care. However, due to the complex genetic makeup of pharmacogenes, not all genetic variation is currently accounted for. Here, we show the utility of long-read sequencing to resolve complex pharmacogenes by analyzing a well-characterised sample. This data consists of long reads that were processed to resolve phased haploblocks. 73% of pharmacogenes were fully covered in one phased haploblock, including 9/15 genes that are 100% complex. Variant calling accuracy in the pharmacogenes was high, with 99.8% recall and 100% precision for SNVs and 98.7% precision and 98.0% recall for Indels. For the majority of gene-drug interactions in the DPWG and CPIC guidelines, the associated genes could be fully resolved (62% and 63% respectively). Together, these findings suggest that long-read sequencing data offers promising opportunities in elucidating complex pharmacogenes and haplotype phasing while maintaining accurate variant calling.
Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy
Authors: Farrokhi Vahid , Walsh Jason , Palandra Joe , Brodfuehrer Joanne , Caiazzo Teresa , Owens Jane , Binks Michael , Neelakantan Srividya , Yong Florence , Dua Pinky , Le Guiner Caroline , Neubert Hendrik 
Published: November 2021

AbstractDuchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction. We demonstrated the validation and application of a novel peptide immunoaffinity liquid chromatography–tandem mass spectrometry (IA-LC-MS/MS) assay. Data showed that dystrophin expression in Becker muscular dystrophy and DMD tissues, normalized against the mean of non-dystrophic control tissues (n = 20), was 4–84.5% (mean 32%, n = 20) and 0.4–24.1% (mean 5%, n = 20), respectively. In a DMD rat model, biceps femoris tissue from dystrophin-deficient rats treated with AAV9.hCK.Hopti-Dys3978.spA, an adeno-associated virus vector containing a mini-dystrophin transgene, showed a dose-dependent increase in mini-dystrophin expression at 6 months post-dose, exceeding wildtype dystrophin levels at high doses. Validation data showed that inter- and intra-assay precision were ≤20% (≤25% at the lower limit of quantification [LLOQ]) and inter- and intra-run relative error was within ±20% (±25% at LLOQ). IA-LC-MS/MS accurately quantifies dystrophin/mini-dystrophin in human and preclinical species with sufficient sensitivity for immediate application in preclinical/clinical trials.
A new method for sampling African swine fever virus genome and its inactivation in environmental samples
Authors: Kosowska Aleksandra , Barasona Jose A. , Barroso-Arévalo Sandra , Rivera Belén , Domínguez Lucas , Sánchez-Vizcaíno Jose M. 
Published: November 2021

AbstractAfrican swine fever (ASF) is currently the most dangerous disease for the global pig industry, causing huge economic losses, due to the lack of effective vaccine or treatment. Only the early detection of ASF virus (ASFV) and proper biosecurity measures are effective to reduce the viral expansion. One of the most widely recognized risks as regards the introduction ASFV into a country is infected animals and contaminated livestock vehicles. In order to improve ASF surveillance, we have assessed the capacity for the detection and inactivation of ASFV genome by using Dry-Sponges (3 M) pre-hydrated with a new surfactant liquid. We sampled different surfaces in ASFV-contaminated facilities, including animal skins, and the results were compared to those obtained using a traditional sampling method. The surfactant liquid successfully inactivated the virus, while ASFV DNA was well preserved for the detection. This is an effective method to systematically recover ASFV DNA from different surfaces and skin, which has a key applied relevance in surveillance of vehicles transporting live animals and greatly improves animal welfare. This method provides an important basis for the detection of ASFV genome that can be assessed without the biosafety requirements of a BSL-3 laboratory at least in ASF-affected countries, which may substantially speed up the early detection of the pathogen.
A multicenter Spanish study of atropine 0.01% in childhood myopia progression
Authors: Pérez-Flores Inés , Macías-Murelaga Beatríz , Barrio-Barrio Jesús ,   Multicenter Group of Atropine Treatment for Myopia Control (GTAM), Pérez Flores Inés , Valcárcel Vizcaíno Marta , García Arias Marta , Catalán López Sara , Rodríguez Enríquez Manuel , Iglesias Álvarez María , Lorente Bulnes Betty , García-Anllo Reinoso Matías , Carnero José María , de Rojas Silva Victoria , Barrio Barrio Jesús , Macías-Murelaga Beatríz , Rodríguez Feijoo David , Rodríguez Sánchez Javier , Calvo Robles Argentina Rosario , López-Romero Moraleda Sonia , Barrajón Rodríguez Ángela , Gálvez Martínez Javier , Mesa Carina Diana Victoria , Galán Risueño Elena , Rodríguez Domingo Esther 
Published: November 2021

AbstractTo evaluate the efficacy and safety of atropine 0.01% eye drops for myopia control in a multicentric pediatric Spanish cohort. An interventional, prospective, multicenter study was designed. Children aged between 6 and 14 years, with myopia between − 2.00 D to − 6.00 D, astigmatism < 1.50 D and documented previous annual progression greater than − 0.5 D (cycloplegic spherical equivalent, SE) were included. Once nightly atropine 0.01% eye drops in each eye were prescribed to all participants for 12 months. Age, gender, ethnicity and iris color were registered. All patients underwent the same follow-up protocol in every center: baseline visit, telephone consultation 2 weeks later and office controls at 4, 8 and 12 months. At each visit, best-corrected visual acuity, and cycloplegic autorefraction were assessed. Axial length (AL), anterior chamber depth and pupil diameter were measured on an IOL Master (Carl Zeiss Meditec, Inc, Dublin, CA). Adverse effects were registered in a specific questionnaire. Mean changes in cycloplegic SE and AL in the 12 months follow-up were analyzed. SE progression during treatment was compared with the SE progression in the year before enrollment for each patient. Correlation between SE and AL, and annual progression distribution were evaluated. Progression risk factors were analyzed by multivariate logistic regression analyses. Of the 105 recruited children, 92 completed the treatment. Mean SE and AL changes were − 0.44 ± 0.41 D and 0.27 ± 0.20 mm respectively. Mean SE progression was lower than the year before treatment (− 0.44 ± 0.41 D versus − 1.01 ± 0.38 D; p < 0.0001). An inverse correlation between SE progression and AL progression (r: − 0.42; p < 0.0001) was found. Fifty-seven patients (62%) had a SE progression less than − 0.50 D. No risk factors associated with progression could be identified in multivariate analyses. Mean pupil diameter increment at 12-months visit was 0.74 ± 1.76 mm. The adverse effects were mild and infrequent, and decreased over the time. Atropine 0.01% is effective and safe for myopia progression control in a multicentric Spanish children cohort. We believe this efficacy might be extensible to the myopic pediatric population from Western countries with similar social and demographic features. More studies about myopia progression risk factors among atropine treated patients are needed.
Understanding complex multiple sublattice magnetism in double double perovskites
Authors: Halder Anita , Das Shreya , Sanyal Prabuddha , Saha-Dasgupta Tanusri 
Published: November 2021

AbstractUnderstanding magnetism in multiple magnetic sublattice system, driven by the interplay of varied nature of magnetic exchanges, is on one hand challenging and on other hand intriguing. Motivated by the recent synthesis of AA$$^{\prime }$$

′

BB$$^{\prime }$$

′

O$$_6$$

6

double double perovskites with multiple magnetic ions both at A- and B-sites, we investigate the mechanism of magnetic behavior in these interesting class of compounds. We find that the magnetism in such multiple sublattice compounds is governed by the interplay and delicate balance between two distinct mechanisms, (a) kinetic energy-driven multiple sublattice double exchange mechanism and (b) the conventional super-exchange mechanism. The derived spin Hamiltonian based on first-principles calculations is solved by classical Monte Carlo technique which reproduces the observed magnetic properties. Finally, the influence of off-stoichiometry, as in experimental samples, is discussed. Some of these double double perovskite compounds are found to possess large total magnetic moment and also are found to be half-metallic with reasonably high transition temperature, which raises the hope of future applications of these large magnetic moment half-metallic oxides in spintronics and memory devices.
Infrared reflectance image-guided laser photocoagulation of telangiectatic capillaries in persistent diabetic macular edema
Authors: Roh Hyeon Cheol , Lee Chaeyeon , Kang Se Woong , Choi Kyung Jun , Eun Jun Soo , Hwang Sungsoon 
Published: November 2021

AbstractThis study aimed to assess detection rate of telangiectatic capillaries (TelCaps) with infrared reflectance (IR) and optical coherence tomography (OCT) images and to evaluate the clinical efficacy of IR image-guided focal laser photocoagulation of TelCaps in persistent diabetic macular edema (DME). This retrospective case series included 28 eyes of 28 patients with TelCap and persistent DME refractory to intravitreal anti-vascular endothelial growth factor or corticosteroids. The presence of TelCaps was confirmed using IR and OCT images. All patients were followed up for more than 12 months after direct focal laser photocoagulation of the TelCaps. The TelCap closure rate, changes in best-corrected visual acuity, and central subfield thickness were analyzed. On IR imaging, TelCap appeared as a characteristic hyperreflectivity within a hyporeflective spherical lesion in 85.7% of the eyes. After focal laser photocoagulation, the TelCap closure rate was 57.1% at 3 months and 71.4% at 12 months. A significant improvement in visual acuity and reduction in central subfield thickness were observed at three and 12 months after focal laser photocoagulation (all p < 0.05). The characteristic hyperreflectivity within hyporeflective lesions on the IR image in conjunction with OCT helps identify the TelCap. Our results suggest that IR imaging and OCT-guided focal laser photocoagulation of TelCaps can improve functional and anatomical outcomes in persistent DME.
Genome-wide association mapping and genomic prediction for adult stage sclerotinia stem rot resistance in Brassica napus (L) under field environments
Authors: Roy Jayanta , Shaikh T. M. , del Río Mendoza Luis , Hosain Shakil , Chapara Venkat , Rahman Mukhlesur 
Published: November 2021

AbstractSclerotinia stem rot (SSR) is a fungal disease of rapeseed/canola that causes significant seed yield losses and reduces its oil content and quality. In the present study, the reaction of 187 diverse canola genotypes to SSR was characterized at full flowering stage using the agar plug to stem inoculation method in four environments. Genome-wide association study (GWAS) using three different algorithms identified 133 significant SNPs corresponding with 123 loci for disease traits like stem lesion length (LL), lesion width (LW), and plant mortality at 14 (PM_14D) and 21 (PM_21D) days. The explained phenotypic variation of these SNPs ranged from 3.6 to 12.1%. Nineteen significant SNPs were detected in two or more environments, disease traits with at least two GWAS algorithms. The strong correlations observed between LL and other three disease traits evaluated, suggest they could be used as proxies for SSR resistance phenotyping. Sixty-nine candidate genes associated with disease resistance mechanisms were identified. Genomic prediction (GP) analysis with all the four traits employing genome-wide markers resulted in 0.41–0.64 predictive ability depending on the model specifications. The highest predictive ability for PM_21D with three models was about 0.64. From our study, the identified resistant genotypes and stable significant SNP markers will serve as a valuable resource for future SSR resistance breeding. Our study also suggests that genomic selection holds promise for accelerating canola breeding progress by enabling breeders to select SSR resistance genotypes at the early stage by reducing the need to phenotype large numbers of genotypes.
Modelling the growth, development and yield of Triticum durum Desf under the changes of climatic conditions in north-eastern Europe
Authors: Bożek Kamila S. , Żuk-Gołaszewska Krystyna , Bochenek Anna , Gołaszewski Janusz , Kalaji Hazem M. 
Published: November 2021

AbstractHow agricultural ecosystems adapt to climate change is one of the most important issues facing agronomists at the turn of the century. Understanding agricultural ecosystem responses requires assessing the relative shift in climatic constraints on crop production at regional scales such as the temperate zone. In this work we propose an approach to modeling the growth, development and yield of Triticum durum Desf. under the climatic conditions of north-eastern Poland. The model implements 13 non-measurable parameters, including climate conditions, agronomic factors, physiological processes, biophysical parameters, yield components and biological yield (latent variables), which are described by 33 measurable predictors as well as grain and straw yield (manifest variables). The agronomic factors latent variable was correlated with nitrogen fertilization and sowing density, and biological yield was correlated with grain yield and straw yield. An analysis of the model parameters revealed that a one unit increase in agronomic factors increased biological yield by 0.575. In turn, biological yield was most effectively determined by climate conditions (score of 60–62) and biophysical parameters (score of 60–67) in the 2nd node detectable stage and at the end of heading. The modeled configuration of latent and manifest variables was responsible for less than 70% of potential biological yield, which indicates that the growth and development of durum wheat in north-eastern Europe can be further optimized to achieve high and stable yields. The proposed model accounts for local climate conditions and physiological processes in plants, and it can be implemented to optimize agronomic practices in the cultivation of durum wheat and, consequently, to expand the area under T. durum to regions with a temperate climate.
Detection of heteroplasmy and nuclear mitochondrial pseudogenes in the Japanese spiny lobster Panulirus japonicus
Authors: Chow Seinen , Yanagimoto Takashi , Takeyama Haruko 
Published: November 2021

AbstractPartial mtDNA cytochrome oxidase subunit I (COI) fragments and near entire stretch of 12S rDNA (12S) and control region (Dloop) of the Japanese spiny lobster (Panulirus japonicus) (n = 3) were amplified by PCR and used for direct nucleotide sequencing and for clone library-based nucleotide sequence analysis. Nucleotide sequences of a total of 75 clones in COI, 77 in 12S and 92 in Dloop were determined. Haplotypes of the clones matched with those obtained by direct sequencing were determined to be genuine mtDNA sequence of the individual. Phylogenetic analysis revealed several distinct groups of haplotypes in all three regions. Genuine mtDNA sequences were observed to form a group with their closely related variables, and most of these variables may be due to amplification error but a few to be heteroplasmy. Haplotypes determined as nuclear mitochondrial pseudogenes (NUMTs) formed distinct groups. Nucleotide sequence divergence (K2P distance) between genuine haplotypes and NUMTs were substantial (7.169–23.880% for COI, 1.336–23.434% for 12S, and 7.897–71.862% for Dloop). These values were comparable to or smaller than those between species of the genus Panulirus, indicating that integration of mtDNA into the nuclear genome is a continuous and dynamic process throughout pre- and post-speciation events. Double peaks in electropherograms obtained by direct nucleotide sequencing were attributed to common nucleotides shared by multiple NUMTs. Information on the heteroplasmy and NUMTs would be very important for addressing their impact on direct nucleotide sequencing and for quality control of nucleotide sequences obtained.
Identification of stress response proteins through fusion of machine learning models and statistical paradigms
Authors: Alzahrani Ebraheem , Alghamdi Wajdi , Ullah Malik Zaka , Khan Yaser Daanial 
Published: November 2021

AbstractProteins are a vital component of cells that perform physiological functions to ensure smooth operations of bodily functions. Identification of a protein's function involves a detailed understanding of the structure of proteins. Stress proteins are essential mediators of several responses to cellular stress and are categorized based on their structural characteristics. These proteins are found to be conserved across many eukaryotic and prokaryotic linkages and demonstrate varied crucial functional activities inside a cell. The in-vivo, ex vivo, and in-vitro identification of stress proteins are a time-consuming and costly task. This study is aimed at the identification of stress protein sequences with the aid of mathematical modelling and machine learning methods to supplement the aforementioned wet lab methods. The model developed using Random Forest showed remarkable results with 91.1% accuracy while models based on neural network and support vector machine showed 87.7% and 47.0% accuracy, respectively. Based on evaluation results it was concluded that random-forest based classifier surpassed all other predictors and is suitable for use in practical applications for the identification of stress proteins. Live web server is available athttp://biopred.org/stressprotiens, while the webserver code available is athttps://github.com/abdullah5naveed/SRP_WebServer.git
Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis
Authors: Ma Dennis , Hernandez Grace A. , Lefebvre Austin E. Y. T. , Alshetaiwi Hamad , Blake Kerrigan , Dave Kushal R. , Rauf Maha , Williams Justice W. , Davis Ryan T. , Evans Katrina T. , Longworth Aaron , Masoud Madona Y. G. , Lee Regis , Edwards Robert A. , Digman Michelle A. , Kessenbrock Kai , Lawson Devon A. 
Published: November 2021

AbstractMetastasis is a fatal disease where research progress has been hindered by a lack of authentic experimental models. Here, we develop a 3D tumor sphere culture-transplant system that facilitates the growth and engineering of patient-derived xenograft (PDX) tumor cells for functional metastasis assays in vivo. Orthotopic transplantation and RNA sequencing (RNA-seq) analyses show that PDX tumor spheres maintain tumorigenic potential, and the molecular marker and global transcriptome signatures of native tumor cells. Tumor spheres display robust capacity for lentiviral engineering and dissemination in spontaneous and experimental metastasis assays in vivo. Inhibition of pathways previously reported to attenuate metastasis also inhibit metastasis after sphere culture, validating our approach for authentic investigations of metastasis. Finally, we demonstrate a new role for the metabolic enzyme NME1 in promoting breast cancer metastasis, providing proof-of-principle that our culture-transplant system can be used for authentic propagation and engineering of patient tumor cells for functional studies of metastasis.
A population-specific reference panel for improved genotype imputation in African Americans
Authors: O’Connell Jared , Yun Taedong , Moreno Meghan , Li Helen , Litterman Nadia , Kolesnikov Alexey , Noblin Elizabeth , Chang Pi-Chuan , Shastri Anjali , Dorfman Elizabeth H. , Shringarpure Suyash ,   23andMe Research Team, Aslibekyan Stella , Babalola Elizabeth , Bell Robert K. , Bielenberg Jessica , Bryc Katarzyna , Bullis Emily , Coker Daniella , Partida Gabriel Cuellar , Dhamija Devika , Das Sayantan , Elson Sarah L. , Filshtein Teresa , Fletez-Brant Kipper , Fontanillas Pierre , Freyman Will , Gandhi Pooja M. , Heilbron Karl , Hernandez Alejandro , Hicks Barry , Hinds David A. , Jewett Ethan M. , Jiang Yunxuan , Kukar Katelyn , Lin Keng-Han , Lowe Maya , McCreight Jey , McIntyre Matthew H. , Micheletti Steven J. , Mountain Joanna L. , Nandakumar Priyanka , Petrakovitz Aaron A. , Poznik G. David , Schumacher Morgan , Shelton Janie F. , Shi Jingchunzi , Tchakouté Christophe Toukam , Tran Vinh , Tung Joyce Y. , Wang Xin , Wang Wei , Weldon Catherine H. , Wilton Peter , Wong Corinna , Auton Adam , Carroll Andrew , McLean Cory Y. 
Published: November 2021

AbstractThere is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals. With the exception of the TOPMed imputation server (which notably cannot be downloaded), our panel substantially outperformed other available panels when imputing African American individuals. The raw sequencing data, variant calls and imputation panel for this cohort are all freely available via dbGaP and should prove an invaluable resource for further study of admixed African genetics.