bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of unique ROH regions with unfavorable effects on production and fertility traits in Canadian Holsteins
Authors: Makanjuola Bayode O. , Maltecca Christian , Miglior Filippo , Marras Gabriele , Abdalla Emhimad A. , Schenkel Flavio S. , Baes Christine F. 
Published: August 2021

AbstractBackgroundThe advent of genomic information and the reduction in the cost of genotyping have led to the use of genomic information to estimate genomic inbreeding as an alternative to pedigree inbreeding. Using genomic measures, effects of genomic inbreeding on production and fertility traits have been observed. However, there have been limited studies on the specific genomic regions causing the observed negative association with the trait of interest. Our aim was to identify unique run of homozygosity (ROH) genotypes present within a given genomic window that display negative associations with production and fertility traits and to quantify the effects of these identified ROH genotypes.MethodsIn total, 50,575 genotypes based on a 50K single nucleotide polymorphism (SNP) array and 259,871 pedigree records were available. Of these 50,575 genotypes, 46,430 cows with phenotypic records for production and fertility traits and having a first calving date between 2008 and 2018 were available. Unique ROH genotypes identified using a sliding-window approach were fitted into an animal mixed model as fixed effects to determine their effect on production and fertility traits.ResultsIn total, 133 and 34 unique ROH genotypes with unfavorable effects were identified for production and fertility traits, respectively, at a 1% genome-wise false discovery rate. Most of these ROH regions were located on bovine chromosomes 8, 13, 14 and 19 for both production and fertility traits. For production traits, the average of all the unfavorably identified unique ROH genotypes effects were estimated to decrease milk yield by 247.30 kg, fat yield by 11.46 kg and protein yield by 8.11 kg. Similarly, for fertility traits, an average 4.81-day extension in first service to conception, a 0.16 increase in number of services, and a − 0.07 incidence in 56-day non-return rate were observed. Furthermore, a ROH region located on bovine chromosome 19 was identified that, when homozygous, had a negative effect on production traits. Signatures of selection proximate to this region have implicatedGH1as a potential candidate gene, which encodes the growth hormone that binds the growth hormone receptor. This observed negative effect could be a consequence of unfavorable alleles in linkage disequilibrium with favorable alleles.ConclusionsROH genotypes with unfavorable effects on production and fertility traits were identified within and across multiple traits on most chromosomes. These identified ROH genotypes could be included in mate selection programs to minimize their frequency in future generations.
Genome-wide association study for deoxynivalenol production and aggressiveness in wheat and rye head blight by resequencing 92 isolates of Fusarium culmorum
Authors: Miedaner Thomas , Vasquez Andrea , Castiblanco Valheria , Castillo Hilda Elena , Foroud Nora , Würschum Tobias , Leiser Willmar 
Published: August 2021

Abstract
Background
Fusarium culmorum is an important pathogen causing head blight of cereals in Europe. This disease is of worldwide importance leading to reduced yield, grain quality, and contamination by mycotoxins. These mycotoxins are harmful for livestock and humans; therefore, many countries have strict regulatory limits for raw materials and processed food. Extensive genetic diversity is described among field populations of F. culmorum isolates for aggressiveness and production of the trichothecene mycotoxin deoxynivalenol (DON). However, the causes for this quantitative variation are not clear, yet. We analyzed 92 isolates sampled from different field populations in Germany, Russia, and Syria together with an international collection for aggressiveness and DON production in replicated field experiments at two locations in two years with two hosts, wheat and rye. The 30x coverage whole-genome resequencing of all isolates resulted in the identification of 130,389 high quality single nucleotide polymorphisms (SNPs) that were used for the first genome-wide association study in this phytopathogenic fungus.

Results
In wheat, 20 and 27 SNPs were detected for aggressiveness and DON content, respectively, of which 10 overlapped. Additionally, two different SNPs were significantly associated with aggressiveness in rye that were among those SNPs being associated with DON production in wheat. Most of the SNPs explained only a small proportion of genotypic variance (pG), however, four SNPs were associated with major quantitative trait loci (QTLs) with pG ranging from 12 to 48%. The QTL with the highest pG was involved in DON production and associated with a SNP most probably located within the Tri4 gene.

Conclusions
The diversity of 92 isolates of F. culmorum were captured using a heuristic approach. Key phenotypic traits, SNPs, and candidate genes underlying aggressiveness and DON production were identified. Clearly, many QTLs are responsible for aggressiveness and DON content in wheat, both traits following a quantitative inheritance. Several SNPs involved in DON metabolism, among them the Tri4 gene of the trichothecene pathway, were inferred as important source of variation in fungal aggressiveness. Using this information underlying the phenotypic variation will be of paramount importance in evaluating strategies for successful resistance breeding.
Aortic root aortopathy in bicuspid aortic valve associated with high genetic risk
Authors: Ma Mingjia , Li Zongzhe , Mohamed Mohamed Abdulkadir , Liu Ligang , Wei Xiang 
Published: August 2021

Abstract
Background
The bicuspid aortic valve (BAV) is prone to ascending aortic dilatation (AAD) involving both the tubular segment and the aortic root. The genetic factor was proposed as one of the most important mechanisms for AAD. We hypothesized that the rare genetic variants mainly contribute to the pathogenesis of aortic roots in affected individuals.

Methods
The diameter of aortic root or ascending aorta ≥ 40 mm was counted as AAD. The targeted next-generation sequencing of 13 BAV-associated genes were performed on a continuous cohort of 96 unrelated BAV patients. The rare variants with allele frequency < 0.05% were selected and analyzed. Variants frequency was compared against the Exome aggregation consortium database. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics guidelines.

Results
A total of 27 rare nonsynonymous coding variants involving 9 genes were identified in 25 individuals. The burden analysis revealed that variants in GATA5, GATA6, and NOTCH1 were significantly associated with BAV. Eighty percent of the pathogenic variants were detected in root group. The detection rate of rare variants was higher in root dilatation group (71.4%) compared with normal aorta (29.0%) and tubular dilatation groups (29.6%) (P = 0.018). The rare variant was identified as the independent risk factor of root dilatation [P = 0.014, hazard ratio = 23.9, 95% confidence interval (1.9–302.9)].

Conclusions
Our results presented a broad genetic spectrum in BAV patients. The rare variants of BAV genes contribute the most to the root phenotype among BAV patients.
Evaluation of Tp-e interval, Tp-e/QT ratio and index of cardiac-electrophysiological balance in patients with tinnitus
Authors: Kaya Hakan , Suner Arif , Koparal Mehtap , Yucetas S. Cem , Kafadar Safiye 
Published: August 2021

Abstract
Background
Tinnitus is a common auditory symptom. Dysfunction in the autonomic nervous system (ANS) is an essential part of the etiopathogenesis of tinnitus. ANS regulates heart rate and heart rhythm and can lead to ventricular repolarization changes, which can cause malignant ventricular arrhythmias. T wave peak-to-end T(p-e) interval and T(p-e)/QT ratio are known ventricular arrhythmia indexes, and the index of cardiac-electrophysiological balance (iCEB) is a novel index that can be used to predict the risk of malignant ventricular arrhythmia. The goal of the study was to investigate these ventricular arrhythmia indexes in patients with tinnitus.

Methods
The study population consisted of 240 patients with tinnitus and 240 healthy subjects. A standard 12-channel surface electrocardiogram was applied to both groups. T(p-e) interval, QT interval and QRS duration were determined. Corrected QT (QTc) was determined via Bazett’s formula. To predict ventricular arrhythmia, iCEB (QT/QRS), T(p-e)/QT, corrected iCEB (QTc/QRS) and T(p-e)/QTc values were determined and compared between groups.

Results
Compared to the control group, QT (376.46 ± 36.54 vs 346.52 ± 24.51 ms), QTc (426.68 ± 24.68 vs 390.42 ± 24.04 ms), T(p-e) (75.86 ± 14.68 vs 62.42 ± 8.64 ms), T(p-e)/QT (0.201 ± 0.06 vs 0.180 ± 0.01) and T(p-e)/QTc (0.177 ± 0.06 vs 0.159 ± 0.02) were significantly higher in patients with tinnitus (p < 0.001 for all). QT/QRS (3.92 ± 0.68 vs 3.56 ± 0.32) and QTc/QRS (4.44 ± 1.03 vs 4.01 ± 0.64) were also significantly higher in patients with tinnitus (p = 0.018 and p = 0.008, respectively). In addition, significant positive correlations were found between T(p-e), T(p-e)/QTc ratio and disease duration (r = 0.792, p < 0.001; r = 0.500, p < 0.001, respectively).

Conclusion
As a result, patients with tinnitus may have an increased risk of malignant ventricular arrhythmia.
Duration of SARS-CoV-2 sero-positivity in a large longitudinal sero-surveillance cohort: the COVID-19 Community Research Partnership
Authors:   The COVID-19 Community Research Partnership Study Group, Herrington David M. , Sanders John W. , Wierzba Thomas F. , Alexander-Miller Martha , Espeland Mark , Bertoni Alain G. , Mathews Allison , Seals Austin L. , Munawar Iqra , Runyon Michael S. , McCurdy Lewis H. , Gibbs Michael A. , Kotloff Karen , Friedman-Klabanoff DeAnna , Weintraub William , Correa Adolfo , Uschner Diane , Edelstein Sharon , Santacatterina Michele 
Published: August 2021

AbstractBackgroundEstimating population prevalence and incidence of prior SARS-CoV-2 infection is essential to formulate public health recommendations concerning the COVID-19 pandemic. However, interpreting estimates based on sero-surveillance requires an understanding of the duration of elevated antibodies following SARS-CoV-2 infection, especially in the large number of people with pauci-symptomatic or asymptomatic disease.MethodsWe examined > 30,000 serology assays for SARS-CoV-2 specific IgG and IgM assays acquired longitudinally in 11,468 adults between April and November 2020 in the COVID-19 Community Research Partnership.ResultsAmong participants with serologic evidence for infection but few or no symptoms or clinical disease, roughly 50% sero-reverted in 30 days of their initial positive test. Sero-reversion occurred more quickly for IgM than IgG and for antibodies targeting nucleocapsid protein compared with spike proteins, but was not associated with age, sex, race/ethnicity, or healthcare worker status.ConclusionsThe short duration of antibody response suggests that the true population prevalence of prior SARS-CoV-2 infection may be significantly higher than presumed based on earlier sero-surveillance studies. The impact of the large number of minimally symptomatic COVID-19 cases with only a brief antibody response on population immunity remains to be determined.
Associations of CKD risk factors and longitudinal changes in urine biomarkers of kidney tubules among women living with HIV
Authors: Muiru Anthony N. , Scherzer Rebecca , Ascher Simon B. , Jotwani Vasantha , Grunfeld Carl , Shigenaga Judy , Spaulding Kimberly A. , Ng Derek K. , Gustafson Deborah , Spence Amanda B. , Sharma Anjali , Cohen Mardge H. , Parikh Chirag R. , Ix Joachim H. , Estrella Michelle M. , Shlipak Michael G. 
Published: August 2021

Abstract
Background
Novel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear.

Methods
We assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women’s Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels.

Results
Of the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin [IL]-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 [YKL-40]). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 [KIM-1] and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher β2-microglobulin [β2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively).

Conclusions
CKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting.
Comparison of tumor mutation burden of 300 various non-Hodgkin lymphomas using panel based massively parallel sequencing
Authors: Cho Junhun , Yoon Sang Eun , Kim Seok Jin , Ko Young Hyeh , Kim Won Seog 
Published: August 2021

Abstract
Background
Tumor mutation burden is an emerging biomarker for immunotherapy. Although several clinical trials for immunotherapy in lymphoma have been carried out, the mutation burden of various lymphomas is not well known yet. Thus, the objective of this study was to compare tumor mutation burden of various non-Hodgkin lymphomas using panel based massively parallel sequencing.

Methods
We conducted 405 gene panel based massively parallel sequencing of 300 non-Hodgkin lymphomas and investigate the number of SNV/Indel in each lymphoma.

Results
The number of SNV/Indel was higher in mature B-cell lymphoma than in mature T- and NK-cell lymphoma. (P < 0.001) The number of SNV/Indel in primary mediastinal large B-cell lymphoma and primary diffuse large B-cell lymphoma of the central nervous system was the highest, which was significantly higher than that in diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS).(P = 0.030 and P = 0.008, respectively) The SNV/Indel number in EBV-positive DLBCL NOS was significantly lower than that in DLBCL NOS. (P = 0.048) Peripheral T-cell lymphoma, NOS showed no significant difference in the number of SNV/Indel from extranodal NK/T-cell lymphoma, nasal type (P = 0.942) or angioimmunoblastic T-cell lymphoma (P = 0.739). The number of SNV/Indel in anaplastic large cell lymphoma, ALK-positive was significantly lower than that in anaplastic large cell lymphoma, ALK-negative (P = 0.049). It was the lowest among all the lymphomas considered.

Conclusion
Various lymphomas have different mutation burdens. Thus, tumor mutation burden can be used as a promising biomarker for immunotherapy in lymphomas.
Radiological and mid- to long-term patient-reported outcome after stabilization of traumatic thoraco-lumbar spinal fractures using an expandable vertebral body replacement implant
Authors: Lang Siegmund , Neumann Carsten , Schwaiger Christina , Voss Andreas , Alt Volker , Loibl Markus , Kerschbaum Maximilian 
Published: August 2021

Abstract
Background
For the treatment of unstable thoraco-lumbar burst fractures, a combined posterior and anterior stabilization instead of a posterior-only instrumentation is recommend in the current literature due to the instability of the anterior column. Data on restoring the bi-segmental kyphotic endplate angle (BKA) with expandable vertebral body replacements (VBR) and on the mid- to long-term patient-reported outcome measures (PROM) is sparse.

Methods
A retrospective cohort study of patients with traumatic thoraco-lumbar spinal fractures treated with an expandable VBR implant (Obelisc™, Ulrich Medical, Germany) between 2001 and 2015 was conducted. Patient and treatment characteristics were evaluated retrospectively. Radiological data acquisition was completed pre- and postoperatively, 6 months and at least 2 years after the VBR surgery. The BKA was measured and fusion-rates were assessed. The SF-36, EQ-5D and ODI questionnaires were evaluated prospectively.

Results
Ninety-six patients (25 female, 71 male; age: 46.1 ± 12.8 years) were included in the study. An AO Type A4 fracture was seen in 80/96 cases (83.3%). Seventy-three fractures (76.0%) were located at the lumbar spine. Intraoperative reduction of the BKA in n = 96 patients was 10.5 ± 9.4° (p < 0.01). A loss of correction of 1.0 ± 2.8° at the first follow-up (t1) and of 2.4 ± 4.0° at the second follow-up (t2) was measured (each p < 0.05). The bony fusion rate was 97.9%. The total revision rate was 4.2%. Fifty-one patients (53.1% of included patients; age: 48.9 ± 12.4 years) completed the PROM questionnaires after 106.4 ± 44.3 months and therefore were assigned to the respondent group. The mean ODI score was 28.2 ± 18.3%, the mean EQ-5D VAS reached 60.7 ± 4.1 points. Stratified SF-36 results (ISS < and ≥ 16) were lower compared to a reference population.

Conclusion
The treatment of traumatic thoraco-lumbar fractures with an expandable VBR implant lead to a high rate of bony fusion. A significant correction of the BKA could be achieved and no clinically relevant loss of reduction occurred during the follow-up. Even though health related quality of life did not reach the normative population values, overall satisfactory results were reported.
Evaluation of three methods of suture for skin closure in total knee arthroplasty: a randomized trial
Authors: Vieira Rodrigo Barreiros , Waldolato Gustavo , Fernandes João Sequeira , de Carvalho Thiago Gontijo , Moreira Pedro Augusto Maciel , Moreira Guilherme Barbosa , Vieira Jorge Suman 
Published: August 2021

Abstract
Background
There are several studies comparing techniques and different materials, yet the results are not unanimous. We compared three methods of skin closure in total knee arthroplasty (TKA), including suture with single stitches and unabsorbable MonoNylon®, as well as continuous subcuticular suture with Monocryl® or barbed Stratafix® absorbable suture.

Methods
A prospective, randomized study was conducted with 63 patients undergoing TKA between March 2016 and December 2016. Patients were divided into three groups: traditional suture MonoNylon® (n 22), subcuticular continuous suture with Monocryl® (n 20), and another barbed with Stratafix® (n 21). The closure time, length of wire used, pain intensity, possible complications, and cosmeses were evaluated.

Results
Subcuticular continuous suture using Monocryl® was superior to traditional suture using MonoNylon® as less thread was used (p 0.01) and a better cosmetic effect was achieved (p < 0.01), which was equal to Stratafix® aspects analyzed (p > 0.05). Complications were observed mostly in patients who used Stratafix®.

Conclusions
This study concluded that the subcuticular suture with absorbable monofilament Monocryl® proved to be advantageous compared to the others because it presented results equal to the barbed Stratafix®, however with fewer complications. Furthermore, Monocryl® was shown to be equal or superior to traditional MonoNylon® suture regarding in relation pain intensity, aesthetic result, and effective cost.

Trial registration
WHO ICTRP identifier RBR78dh5d. Retrospectively registered: 07/29/2020.
Applying the Plan-Do-Study-Act cycle in medical education to refine an antibiotics therapy active learning session
Authors: Rose Stacey , Hamill Richard , Caruso Andrew , Appelbaum Nital P. 
Published: August 2021

Abstract
Background
Active learning improves learner engagement and knowledge retention. The application of continuous quality improvement methodologies, such as the Plan-Do-Study-Act (PDSA) framework, may be useful for optimizing medical education, including active learning sessions. We aimed to enhance student satisfaction and achievement of learning outcomes by applying the PDSA framework to an antibiotic utilization curriculum for medical students.

Methods
Guided by the Plan-Do-Study-Act framework, between February 2017 and July 2019, we developed, implemented, and revised an active learning session for medical students, focused on appropriate utilization of antibiotics during their Internal Medicine clerkship.

Results
Across twelve sessions, 367 students (83.4%) completed the post-evaluation survey. Although baseline ratings were high (97% of respondents enjoyed the “active learning” format), constructive comments informed iterative improvements to the session, such as modifying session timing, handouts and organization of the gaming component. Intervention 3, the last improvement cycle, resulted in more favorable ratings for the active learning format (p = 0.015) improvement in understanding antibiotics and their clinical application (p = 0.001) compared to Baseline ratings.

Conclusions
This intervention suggests that active learning, with regular incorporation of student feedback vis-à-vis a PDSA cycle, was effective in achieving high student engagement in an Internal Medicine core clerkship session on antibiotic therapy. Iterative interventions based on student feedback, such as providing an antibiotic reference table and answer choices for each case, further improved student receptivity and perceived educational value. The study findings have potential implications for medical education and suggest that the application of the PDSA cycle can optimize active learning pedagogies and outcomes.