bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody and T cell responses to COVID-19 vaccination in patients receiving anticancer therapies
Authors: Rouhani Sherin Juliet , Yu Jovian , Olson Daniel , Zha Yuanyuan , Pezeshk Apameh , Cabanov Alexandra , Pyzer Athalia R , Trujillo Jonathan , Derman Benjamin A , O'Donnell Peter , Jakubowiak Andrzej , Kindler Hedy L , Bestvina Christine , Gajewski Thomas F 
Published: June 2022

BackgroundPatients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination.MethodsAntibodies to the SARS-CoV-2 receptor binding domain (RBD) and spike protein were assessed in patients with cancer (n=118) and healthy donors (HD, n=22) after 1, 2 or 3 mRNA vaccine doses. CD4+and CD8+T cell reactivity to wild-type (WT) or B.1.617.2 (delta) spike peptides was measured by intracellular cytokine staining.ResultsOncology patients without prior COVID-19 infections receiving immunotherapy (n=36), chemotherapy (n=15), chemoimmunotherapy (n=6), endocrine or targeted therapies (n=6) and those not on active treatment (n=26) had similar RBD and Spike IgG antibody titers to HDs after two vaccinations. Contrary to our hypothesis, PD-1 blockade did not augment antibody titers or T cell responses. Patients receiving B-cell directed therapies (n=14) including anti-CD20 antibodies and multiple myeloma therapies had decreased antibody titers, and 9/14 of these patients were seronegative for RBD antibodies. No differences were observed in WT spike-reactive CD4+and CD8+T cell generation between treatment groups. 11/13 evaluable patients seronegative for RBD had a detectable WT spike-reactive CD4+T cell response. T cells cross-reactive against the B.1.617.2 variant spike peptides were detected in 31/59 participants. Two patients with prior immune checkpoint inhibitor-related adrenal insufficiency had symptomatic hypoadrenalism after vaccination.ConclusionsCOVID-19 vaccinations are safe and immunogenic in patients with solid tumors, who developed similar antibody and T cell responses compared with HDs. Patients on B-cell directed therapies may fail to generate RBD antibodies after vaccination and should be considered for prophylactic antibody treatments. Many seronegative patients do develop a T cell response, which may have an anti-viral effect. Patients with pre-existing adrenal insufficiency may need to take stress dose steroids during vaccination to avoid adrenal crisis.
Phenotypical changes and clinical significance of CD4+/CD8+T cells in SLE
Authors: Yuan Shiwen , Zeng Yanting , Li Jiawei , Wang Cuicui , Li Weinian , He Zhixiang , Ye Jinghua , Li Fangfei , Chen Yi , Lin Xiaojun , Yu Na , Cai Xiaoyan 
Published: June 2022

ObjectiveT cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.MethodsPeripheral blood CD4+and CD8+T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed.ResultsThere was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+and CD28−cells in CD4+T cells was observed in patients with SLE. We found that the expanded CD4+CD28−T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28−T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+T cells and Treg cells in this study. Increased CD8+HLADR+T cell and CD8+CD38+HLADR+T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+T cells in SLE. Additionally, we found that CD8+CD38+HLADR+T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+CXCR5−PD1+T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study.ConclusionThe proportions of CD4+CD28−T cells, CD4+CXCR5−PD1+T cells, CD8+HLADR+T cells and CD8+CD38+HLADR+T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.
Quantification of Cardiac Adipose Tissue in Failing and Nonfailing Human Myocardium
Authors: Peczkowski Kyra K. , Mashali Mohammed A. , Saad Nancy S. , Hare Austin , Campbell Courtney M. , Whitson Bryan A. , Mokadam Nahush A. , Janssen Paul M. L. 
Published: June 2022

Background
Because body mass index (BMI) is generally used clinically to define obesity and to estimate body adiposity, BMI likely is positively correlated with epicardial adipose tissue (EAT) level. Based on echocardiography, previous outcomes on this matter have varied from almost absent to rather strong correlations between BMI and EAT. The purpose of our study was to unambiguously examine EAT content and determine if correlations exist between EAT content and BMI, cause of heart failure, or contractile force.

Methods and Results

We qualitatively scored 150 human hearts ex vivo on EAT distribution. From each heart, multiple photographs of the heart were taken, and both atrial and ventricular adipose tissue levels were semiquantitatively scored. Main findings include a generally higher EAT content on nonfailing hearts compared with end‐stage failing hearts (atrial adipose tissue level 5.70±0.13 vs. 5.00±0.12,
P
<0.001; ventricular adipose tissue level 5.14±0.16 vs. 4.57±0.12,
P
=0.0048). The results also suggest that EAT quantity is not strongly correlated with BMI in nonfailing (atrial adipose tissue level
r
=0.069, ventricular adipose tissue level
r
=0.14) or failing (atrial adipose tissue level
r
=−0.022, ventricular adipose tissue level
r
=0.051) hearts. Atrial EAT is closely correlated with ventricular EAT in both nonfailing (
r
=0.92,
P
<0.001) and failing (
r
=0.87,
P
<0.001) hearts.

Conclusions
EAT volume appears to be inversely proportional to severity of or length of time with heart failure based on our findings. Based on a lack of correlation with BMI, it is incorrect to assume high EAT volume given high body fat percentage.
Understanding the Role of Rainfall Intensity on Relative Car Crash Risk in the Carolinas
Authors: Eck Montana A. , Konrad Charles E. , Rayne Sandra , Black Alan W. 
Published: June 2022

Abstract
As a significant detriment to physical and mental health, millions of motor vehicle crashes occur in the United States each year, with approximately 23% of these crashes linked to adverse weather conditions. This study builds upon a strong knowledge base to provide a deeper understanding of how rainfall intensity influences relative crash risk. Gridded precipitation and temperature data were aggregated to the county level and analyzed alongside motor vehicle crash data for all 146 counties in the Carolinas (North Carolina and South Carolina) for the period 2003–19. A matched-pair analysis routine linked unique time steps of rainfall (daily, 6-h, and hourly) to corresponding dry periods to evaluate relative crash risk across each state. Risk estimates were calculated on the basis of precipitation thresholds (light, moderate, heavy, and very heavy). Results indicate a statistically significant increase in crash risk during periods of rainfall in the Carolinas. As a baseline, the relative risk of experiencing a crash increases by 11.6% during days with accumulating rainfall and as much as 81.0% during heavy rainfall events over a 6-h period. In general, estimates of risk increase relative to the intensity of the rainfall event and the temporal delineation of the matched-pair routine. However, these relationships have unique spatiotemporal patterns indicating that, although hourly risk estimates may be beneficial for urban counties, daily relative risk estimates may be the only way to accurately capture risk in rural areas.

Significance Statement
Each year, more than 1 000 000 motor vehicle crashes in the United States are linked to adverse weather conditions in police reports, with rainfall events being among the largest contributors to increased crash risk. In this study, crash frequencies are evaluated to better understand how the intensity of rainfall events (light vs heavy) influences the risk of experiencing a collision on roadways in North Carolina and South Carolina. The results of statistical analyses revealed that risk increases significantly during rainfall events in both states and that the risk of experiencing a crash is highest during the heaviest rainfall events. However, even during light precipitation events, the risk of experiencing a crash is significantly higher than when driving during dry conditions. These results are helpful to transportation stakeholders and emergency responders in the hope of reducing crash risk in our changing climate.
The implementation and validation of the NoMAD during a complex primary care intervention
Authors: Lamarche Larkin , Clark Rebecca E. , Parascandalo Fiona , Mangin Dee 
Published: June 2022

Abstract
Background
Normalization process theory (NPT) has been widely used to better understand how new interventions are implemented and embedded. The NoMAD (Normalization Measurement Development questionnaire) is a 23-item NPT instrument based on NPT. As the NoMAD is a relatively new instrument, the objectives of this paper are: to describe the experience of implementing the NoMAD, to describe it being used as a feedback mechanism to gain insight into the normalization process of a complex health intervention, and to further explore the psychometric properties of the instrument.

Methods
Health TAPESTRY was implemented in six Family Health Teams (total of seven sites) across Ontario. Healthcare team members at each site were invited to complete the NoMAD, and three general questions about normalization, six times over a 12-month period. Each site was then provided a visual traffic light summary (TLS) reflecting the implementation of the Health TAPESTRY. The internal consistency of each sub-scale and validity of the NoMAD were assessed. Learnings from the implementation of the NoMAD and subsequent feedback mechanism (TLS) are reported descriptively.

Results
In total, 56 diverse health care team members from six implementation sites completed the NoMAD. Each used it at least once during the 12-month study period. The implementation of the NoMAD and TLS was time consuming to do with multiple collection (and feedback) points. Most (60%) internal consistency values of the four subscales (pooled across site) across each collection point were satisfactory. All correlations were positive, and most (86%) were statistically significant among NoMAD subscales. All but one correlation between the NoMAD subscales and the general questions were positive, and most (72%) were significant. Generally, scores on the subscales were higher at 12-month than baseline, albeit did not follow a linear pattern of change across implementation. Generally, scores were higher for experienced sites compared to first-time implementors.

Conclusion
Our experience would suggest fewer collection points; three timepoints spaced out by several months are adequate, if repeated administration of the NoMAD is used for feedback loops. We provide additional evidence of the psychometric properties of the NoMAD.

Trial Registration
Registered at ClinicalTrials.gov: NCT03397836.
Genetics education in primary care residency training: satisfaction and current barriers
Authors: Falah Nadia , Umer Amna , Warnick Emilea , Vallejo Manuel , Lefeber Timothy 
Published: June 2022

Abstract
Background
Genetics education can be integrated into general care medicine through primary care residency programs. A study of primary care residents was done to evaluate quality, satisfaction, and barriers in genetics education in residency training programs. Thus, providing more evidence for the necessity for its development and progress.

Methods
A cross-sectional descriptive self-administered questionnaire survey was delivered to four primary care West Virginia University (WVU) residency training programs in 2020–2021. The anonymous 14-item survey included the following questionnaire domains: general data, genetics training satisfaction, and genetics education barriers.

Results
The survey response rate was 52% (70/123) and 59 participants completed the survey. Overall, respondents viewed genetic education as critical to their chosen specialty (90%). Trainees at all educational levels obtained their education mostly from class based educational curricula (77% from lectures, 65% from didactic and 49% from grand rounds). The majority of survey respondents indicated insufficient experience with genetic patient care (34% ward genetic consultation, 5% clinic experience, 0% genetic department rotation). The percentage of residents who were satisfied with genetic topics were as follows: basic genetics (57%), capturing family history (82%), initiating basic genetic workup (15%), a basic understanding of the genetic report (23%), basic management surveillance in the genetic patient (18%), understanding the genetic referral and explaining it to a patient (47%).
Residents reported barriers to genetic interest included complexity of the field (87%), followed by limited utility of genetics testing (41%). The most common suggestions for improving the genetic education component were to provide more lectures (61%), followed by enhanced advertisement of genetic education resources specifically rotations in the genetics department (22%). Other suggestions include the integration of genetic education in inpatient learning (20%) and providing research experience (7%).

Conclusion
Primary care residents were satisfied with their genetic knowledge in the classroom and stated a clear need for enhanced hands-on clinical skills and research experience in their current residency training. The survey suggestions for improvement can enhance primary care residents’ genetic training that can lead to advances in rare disease recognition, precision medicine, and improve access to genetics testing.
Investigation of target sequencing of SARS-CoV-2 and immunogenic GWAS profiling in host cells of COVID-19 in Vietnam
Authors: Hoang Tham H. , Vu Giang M. , Tran Mai H. , Tran Trang T. H. , Le Quang D. , Tran Khanh V. , Nguyen Tue T. , Nguyen Lan T. N. , Tran Thinh H. , Ta Van T. , Vo Nam S. 
Published: June 2022

Abstract
Background
A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam.

Method
In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity.

Result
We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models’ predictive capabilities.

Conclusion
We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes.
Postoperative complications after gastrointestinal pediatric surgical procedures: outcomes and socio-demographic risk factors
Authors: Brock Robert , Chu Angel , Lu Shengjie , Brindle Mary Elizabeth , Somayaji Ranjani 
Published: June 2022

Abstract
Background
Several socio-demographic characteristics are associated with complications following certain pediatric surgical procedures. In this comprehensive study, we sought to determine socio-demographic risk factors and resource utilization of children with complications after common pediatric surgical procedures.

Methods
We performed a population-based cohort study utilizing the 2016 Healthcare Cost and Use Project Kids’ Inpatient Database (KID) to identify and characterize pediatric patients (age 0–21 years) in the United States with common inpatient pediatric gastrointestinal surgical procedures: appendectomy, cholecystectomy, colonic resection, pyloromyotomy and small bowel resection. Multivariable logistic regression modeling was used to identify socio-demographic predictors of postoperative complications. Length of stay and hospitalization costs for patients with and without postoperative complications were compared.

Results
A total of 66,157 pediatric surgical hospitalizations were identified. Of these patients, 2,009 had postoperative complications. Male sex, young age, African American and Native American race and treatment in a rural hospital were associated with significantly greater odds of postoperative complications. Mean length of stay was 4.58 days greater and mean total costs were $11,151 (US dollars) higher in the complication cohort compared with patients without complications.

Conclusions
Postoperative complications following inpatient pediatric gastrointestinal surgery were linked to elevated healthcare-related expenditure. The identified socio-demographic risk factors should be considered in the risk stratification before pediatric surgical procedures. Targeted interventions are required to reduce preventable complications and surgical disparities.
Novel copy number variations within SYCE1 caused meiotic arrest and non-obstructive azoospermia
Authors: Huang Yuhua , Tian Ruhui , Xu Junwei , Ji Zhiyong , Zhang Yuxiang , Zhao Liangyu , Yang Chao , Li Peng , Zhi Erlei , Bai Haowei , Han Sha , Luo Jiaqiang , Zhao Jingpeng , Zhang Jing , Zhou Zhi , Li Zheng , Yao Chencheng 
Published: June 2022

Abstract
Background
Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for majority of NOA remain unknown.

Methods
Two Chinese NOA-affected patients were recruited to identify the genetic causal factor of infertility. Whole-exome sequencing (WES) was conducted in the two patients with NOA. Sanger sequencing and CNV array were used to ascertain the WES results. Hematoxylin and eosin (H&E) staining and immunofluorescence (IF) were carried out to evaluate the stage of spermatogenesis arrested in the affected cases.

Results
Novel heterozygous deletion (LOH) within SYCE1 (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous loss of function (LoF) variant in SYCE1 (NM_001143763: c.689_690 del:p.F230fs) were identified in one NOA-affected patient. While homozygous deletion within SYCE1 (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del) was detected in the other patient with meiotic arrest. H&E and IF staining demonstrated that the spermatogenesis was arrested at pachytene stage in the two patients with NOA, suggesting these two novel CNVs within SYCE1 could lead to meiotic defect and NOA.

Conclusions
We identified that two novel CNVs within SYCE1 are associated with meiotic arrest and male infertility. Thus, our study expands the knowledge of variants in SYCE1 and provides a new insight to understand the genetic etiologies of NOA.
Metabolomics of bronchoalveolar lavage in children with persistent wheezing
Authors: Liang Lingfang , Hu Minfei , Chen Yuanling , Liu Lingke , Wu Lei , Hang Chengcheng , Luo Xiaofei , Xu Xuefeng 
Published: June 2022

Abstract
Background
Recent studies have demonstrated the important role of metabolomics in the pathogenesis of asthma. However, the role of lung metabolomics in childhood persistent wheezing (PW) or wheezing recurrence remains poorly understood.

Methods
In this prospective observational study, we performed a liquid chromatography/mass spectrometry-based metabolomic survey on bronchoalveolar lavage samples collected from 30 children with PW and 30 age-matched infants (control group). A 2-year follow-up study on these PW children was conducted.

Results
Children with PW showed a distinct characterization of respiratory metabolome compared with control group. Children with PW had higher abundances of choline, oleamide, nepetalactam, butyrylcarnitine, l-palmitoylcarnitine, palmitoylethanolamide, and various phosphatidylcholines. The glycerophospholipid metabolism pathway was the most relevant pathway involving in PW pathophysiologic process. Additionally, different gender, prematurity, and systemic corticoids use demonstrated a greater impact in airway metabolite compositions. Furthermore, for PW children with recurrence during the follow-up period, children who were born prematurely had an increased abundance of butyrylcarnitine relative to those who were carried to term.

Conclusions
This study suggests that the alterations of lung metabolites could be associated with the development of wheezing, and this early alteration could also be correlated with wheezing recurrence later in life.