bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Priors When Using Bayesian Regression to Estimate Oral Reading Fluency Slopes
Authors: Solomon Benjamin G. , Forsberg Ole J. , Thomas Monelle , Penna Brittney , Weisheit Katherine M.
Published: August 2021

Bayesian regression has emerged as a viable alternative for the estimation of curriculum-based measurement (CBM) growth slopes. Preliminary findings suggest such methods may yield improved efficiency relative to other linear estimators and can be embedded into data management programs for high-frequency use. However, additional research is needed, as Bayesian estimators require multiple specifications of the prior distributions. The current study evaluates the accuracy of several combinations of prior values, including three distributions of the residuals, two values of the expected growth rate, and three possible values for the precision of slope when using Bayesian simple linear regression to estimate fluency growth slopes for reading CBM. We also included traditional ordinary least squares (OLS) as a baseline contrast. Findings suggest that the prior specification for the residual distribution had, on average, a trivial effect on the accuracy of the slope. However, specifications for growth rate and precision of slope were influential, and virtually all variants of Bayesian regression evaluated were superior to OLS. Converging evidence from both simulated and observed data now suggests Bayesian methods outperform OLS for estimating CBM growth slopes and should be strongly considered in research and practice.
Obstacle Avoidance and Dual-Tasking During Reaching While Standing in Patients With Mild Chronic Stroke
Authors: Mullick Aditi A. , Baniña Melanie C. , Tomita Yosuke , Fung Joyce , Levin Mindy F.
Published: August 2021

Background. Poststroke individuals use their paretic arms less often than expected in daily life situations, even when motor recovery is scored highly in clinical tests. Real-world environments are often unpredictable and require the ability to multitask and make decisions about rapid and accurate arm movement adjustments. Objective. To identify whether and to what extent cognitive–motor deficits in well-recovered individuals with stroke affect the ability to rapidly adapt reaching movements in changing cognitive and environmental conditions. Methods. Thirteen individuals with mild stroke and 11 healthy controls performed an obstacle avoidance task in a virtual environment while standing. Subjects reached for a virtual juice bottle with their hemiparetic arm as quickly as possible under single- and dual-task conditions. In the single-task condition, a sliding glass door partially obstructed the reaching path of the paretic arm. A successful trial was counted when the subject touched the bottle without the hand colliding with the door. In the dual-task condition, subjects repeated the same task while performing an auditory–verbal working memory task. Results. Individuals with stroke had significantly lower success rates than controls in avoiding the moving door in single-task (stroke: 51.8 ± 21.2%, control: 70.6 ± 12.7%; P = .018) and dual-task conditions (stroke: 40.0 ± 27.6%, control: 65.3 ± 20.0%; P = .015). Endpoint speed was lower in stroke subjects for successful trials in both conditions. Obstacle avoidance deficits were exacerbated by increased cognitive demands in both groups. Individuals reporting greater confidence using their hemiparetic arm had higher success rates. Conclusion. Clinically well-recovered individuals with stroke may have persistent deficits performing a complex reaching task.
Toward a hybrid causal framework for autonomous vehicle safety analysis
Authors: Thomas Stephen , Groth Katrina M
Published: August 2021

Autonomous Vehicles (AVs), also known as self-driving cars, are a potentially transformative technology, but developing and demonstrating AV safety remains an open question. AVs offer some unique challenges that stretch the limits of traditional safety engineering practices. Most current safety standards and methodologies in the AV industry were not originally intended for application to autonomous vehicles, and they have significant limitations and shortcomings. In this article, we analyze the literature to first build an argument that a new safety framework is needed for AVs. We then use the identified limitations of current methodologies as a basis to formulate a set of fundamental requirements that must be met by any proposed AV safety framework. We propose a new AV safety framework based on the Hybrid Causal Logic (HCL) methodology, which combines Event Sequence Diagrams (ESDs), Fault Tree Analysis (FTA), and Bayesian Networks (BNs). The HCL framework is developed at a conceptual level and then evaluated versus the identified fundamental requirements. To further illustrate how the framework may meet the requirements, a simple example of an AV perception system scenario is developed using the HCL framework and evaluated. The results demonstrate that the HCL framework provides an integrated approach that has the potential to satisfy more completely the fundamental requirements than the current methodologies.
Aggressive osteoblastoma with a secondary aneurysmal bone cyst treated with denosumab
Authors: Wong Karlton , Chantharasamee Jomjit , Nelson Scott , Eckardt Mark A , Motamedi Kambiz , Hornicek Francis J , Singh Arun S
Published: August 2021

Osteoblastomas and aneurysmal bone cysts (ABC) are rare benign bone tumors that make up about 1%–2% of primary bone malignancies, typically occurring in young patients with a median age of 20 years, most commonly effecting the axial skeleton. ABCs may develop independently as primary lesions, or secondary to other bony lesions including osteoblastomas, chondroblastomas, and giant cell tumors. Treatment of unresectable or extensive osteoblastomas can be challenging. In 2013, the Food and Drug Administration (FDA) approved denosumab for the treatment of giant cell tumors of the bone due to its efficacy in these morbid bony lesions. Various case reports have shown that osteoblastomas can respond to denosumab. Furthermore, numerous ABC case reports have described the efficacy of denosumab in these situations. We herein describe a unique case of a young patient with an aggressive osteoblastoma and secondary ABCs who was successfully treated with denosumab.
Cardiovascular disease is a leading cause of mortality among TTP survivors in clinical remission
Authors: Sukumar Senthil , Brodsky Max , Hussain Sarah , Yanek Lisa , Moliterno Alison , Brodsky Robert , Cataland Spero R. , Chaturvedi Shruti
Published: August 2021

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors experience high rates of adverse health sequelae and increased mortality over long-term follow-up. We conducted this multicenter cohort study to evaluate long-term mortality and causes of death in iTTP survivors. Between 2003 and 2020, 222 patients were enrolled in the Ohio State University and Johns Hopkins TTP registries and followed for a median of 4.5 (interquartile range [IQR], 75 0.4-11.5) years. Nine patients died during their first iTTP episode, and 29 patients died during follow-up. Mortality rate was 1.8 times higher than expected from an age-, sex-, and race-adjusted reference population. Cardiovascular disease was a leading primary cause of death (27.6%) tied with relapsed iTTP (27.6%), followed by malignancy (20.7%), infection (13.8%), and other causes (10.3%). Male sex (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.65-8.48), increasing age (HR, 1.04; 95% CI, 1.01-1.07), and number of iTTP episodes (HR, 1.10; 95% CI, 1.01-1.20) were associated with mortality in a model adjusted for African American race (HR, 0.70; 95% CI, 0.30-1.65), hypertension (HR, 0.47; 95% CI, 0.20-1.08), chronic kidney disease (HR 1.46; 95% CI, 0.65-3.30), and site (HR, 1.46; 95% CI, 0.64–3.30). There was a trend toward shorter survival in patients with lower ADAMTS13 activity during remission (P = .078). Our study highlights the need for survivorship care and investigation focused on cardiovascular disease and early mortality in TTP survivors.
Late-occurring venous thromboembolism in allogeneic blood or marrow transplant survivors: a BMTSS-HiGHS2 risk model
Authors: Gangaraju Radhika , Chen Yanjun , Hageman Lindsey , Wu Jessica , Francisco Liton , Kung Michelle , Weisdorf Daniel J. , Forman Stephen J. , Arora Mukta , Armenian Saro H. , Bhatia Smita
Published: August 2021

Allogeneic blood or marrow transplant (BMT) recipients are at risk for venous thromboembolism (VTE) because of high-intensity therapeutic exposures, comorbidities, and a proinflammatory state due to chronic graft-versus-host disease (GVHD). The long-term risk of VTE in allogeneic BMT survivors remains unstudied. Participants were drawn from the Blood or Marrow Transplant Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived ≥2 years after BMT. We analyzed the risk of VTE in 1554 2-year survivors of allogeneic BMT compared with 907 siblings. Using backward variable selection guided by minimizing Akaike information criterion, we created a prediction model for risk of late-occurring VTE. Allogeneic BMT survivors had a 7.3-fold higher risk of VTE compared with siblings (95% CI, 4.69-11.46; P < .0001). After a median follow-up of 11 years, conditional on surviving the first 2 years after BMT, the cumulative incidence of late-occurring VTE was 2.4% at 5 years, 4.9% at 10 years, and 7.1% at 20 years after BMT. The final model for VTE risk at 2 years post-BMT included History of stroke, chronic GVHD, Hypertension, Sex (male vs female) and Stem cell source (peripheral blood stem cells vs other) (“HiGHS2”) (corrected C-statistics: 0.73; 95% CI = 0.67-0.79). This model was able to classify patients at high and low VTE risk (10-year cumulative incidence, 9.3% vs 2.4% respectively; P < .0001). The BMTSS HiGHS2 risk model when applied at 2 years post-BMT can be used to inform targeted prevention strategies for patients at high risk for late-occurring VTE.
Suboptimal iron deficiency screening in pregnancy and the impact of socioeconomic status in a high-resource setting
Authors: Teichman Jennifer , Nisenbaum Rosane , Lausman Andrea , Sholzberg Michelle
Published: August 2021

Iron deficiency (ID) anemia in pregnancy is associated with poor maternal and childhood outcomes, yet ferritin testing, the standard test for ID, is not considered part of routine prenatal bloodwork in Canada. We conducted a retrospective cohort study of 44 552 pregnant patients with prenatal testing at community laboratories in Ontario, Canada, to determine the prevalence of ferritin testing over 5 years. Secondary objectives were to determine the prevalence and severity of ID and to identify clinical and demographic variables that influence the likelihood of ID screening. A total of 59.4% of patients had a ferritin checked during pregnancy; 71.4% were ordered in the first trimester, when the risk of ID is lowest. Excluding patients with abnormally elevated ferritins, 25.2% were iron insufficient (30-44 µg/L) and 52.8% were iron deficient (≤29 µg/L) at least once in pregnancy. A total of 8.3% were anemic (hemoglobin <105 g/L). The proportion of anemic patients with a subsequent ferritin test in pregnancy ranged from 22% to 67% in the lowest and highest anemia severity categories, respectively. Lower annual household income was negatively associated with the odds of a ferritin test; compared with those in the fifth (ie, highest) income quintile, the odds of ferritin testing for patients in the first, second, and fourth quintiles were 0.83 (95% confidence interval [CI], 0.74-0.91), 0.82 (95% CI, 0.74-0.91), and 0.86 (95% CI, 0.77-0.97), respectively. These data highlight gaps in prenatal care and issues of health equity that warrant harmonization of obstetrical guidelines to recommend routine ferritin testing in pregnancy.
Peripheral blood cytopenias in the aging general population and risk of incident hematological disease and mortality
Authors: van Zeventer Isabelle A. , de Graaf Aniek O. , van der Klauw Melanie M. , Vellenga Edo , van der Reijden Bert A. , Schuringa Jan Jacob , Diepstra Arjan , Malcovati Luca , Jansen Joop H. , Huls Gerwin
Published: August 2021

Peripheral blood cytopenias may precede the development of hematological malignancies and frequently pose clinical challenges in the older population. The natural course of (mild) cytopenias during aging and their association with hematological disorders in community-dwelling individuals are not well studied. Within the population-based Lifelines cohort (n = 167729), we studied changes in peripheral blood counts, occurrence of cytopenias, and associated hematological outcomes in the context of aging. Development of hematological malignancies and (cause-specific) mortality were evaluated by linkage to nationwide registries. Anemia and thrombocytopenia emerged with older age, in line with a general age-related decline in these blood counts. For neutropenia, no increase in prevalence with older age was observed. Using standard reference limits to define cytopenias, anemia (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.59-2.12), thrombocytopenia (HR, 1.58; 95% CI, 1.32-1.89), and, especially the concomitant presence of anemia and thrombocytopenia (HR, 4.75; 95% CI, 2.98-7.55) were associated with inferior overall survival. Only a minor proportion of deaths was explained by diagnosed hematological malignancies, with the majority attributable to other causes. Neutropenia, either isolated (HR, 0.88; 95% CI, 0.73-1.06) or combined with another cytopenia, did not affect overall survival. For individuals aged ≥60 years, 5-year cumulative incidence of hematological malignancies was 0.60% (95% CI, 0.50-0.70), with higher incidences among those with anemia (P < .001) or thrombocytopenia (P < .001) but not neutropenia (P = .201). Highest cumulative incidences of diagnoses and mortality from hematological malignancies were observed in individuals with >1 cytopenia. We conclude that anemia and thrombocytopenia, but not neutropenia, are associated with inferior overall survival of community-dwelling individuals. Hematological malignancies develop in a small fraction of these cases.
Comparison of haploidentical and umbilical cord blood transplantation after myeloablative conditioning
Authors: Wagner John E. , Ballen Karen K. , Zhang Mei-Jie , Allbee-Johnson Mariam , Karanes Chatchada , Milano Filippo , Verneris Michael R. , Eapen Mary , Brunstein Claudio G.
Published: August 2021

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as an important treatment modality. Most reports comparing haplo-HSCT with posttransplant cyclophosphamide (PTCy) and other donor sources have focused on outcomes in older adults treated with reduced intensity conditioning. Therefore, in the current study, we evaluated outcomes in patients with hematological malignancy treated with myeloablative conditioning prior to haplo- (n = 375) or umbilical cord blood (UCB; n = 333) HSCT. All haplo recipients received a 4 of 8 HLA-matched graft, whereas recipients of UCB were matched at 6-8/8 (n = 145) or ≤5/8 (n = 188) HLA antigens. Recipients of 6-8/8 UCB transplants were younger (14 years vs 21 and 29 years) and more likely to have lower comorbidity scores compared with recipients of ≤5/8 UCB and haplo-HSCT (81% vs 69% and 63%, respectively). UCB recipients were more likely to have acute lymphoblastic leukemia and transplanted in second complete remission (CR), whereas haplo-HSCT recipients were more likely to have acute myeloid leukemia in the first CR. Other characteristics, including cytogenetic risk, were similar. Survival at 3 years was similar for the donor sources (66% haplo- and 61% after ≤5/8 and 58% after 6-8/8 UCB). Notably, relapse at 3 years was lower in recipients of ≤5/8 UCB (21%, P = .03) compared with haplo- (36%) and 6-8/8 UCB (30%). However, nonrelapse mortality was higher in ≤5/8 UCB (21%) compared with other groups (P < .0001). These data suggest that haplo-HSCT with PTCy after myeloablative conditioning provides an overall survival outcome comparable to that after UCB regardless HLA match group.
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

Background

The 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.

Methods

In 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.

Results

In 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.

Conclusions

ROH 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

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

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

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

Background

Estimating 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.

Methods

We 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.

Results

Among 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.

Conclusions

The 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

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

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

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

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

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.
YouTube as a source of information during the Covid-19 pandemic: a content analysis of YouTube videos published during January to March 2020
Authors: Parabhoi Lambodara , Sahu Ramani Ranjan , Dewey Rebecca Susan , Verma Manoj Kumar , Kumar Seth Arbind , Parabhoi Damodar
Published: August 2021

Background

Institutions, government departments, and healthcare professionals engage in social media because it facilitates reaching a large number of people simultaneously. YouTube provides a platform whereby anyone can upload videos and gain feedback on their content from other users. Many YouTube videos are related to health and science, and many people search YouTube for health-related information. YouTube has been acknowledged as a key public information source in recent crises caused by Zika, H1N1, swine flu, and most recently, COVID-19.

Methods

YouTube videos were collected from the YouTube Application Programming Interface (API) using the search terms COVID-19, coronavirus, COVID19, and corona. The search was conducted on April 4 and 5, 2020. The initial investigation found a total of 1084 videos. The second step involved identifying and verifying the videos for their relationship to COVID-19 information and excluding videos that did not relate to COVID-19 or were in a language other than English and Hindi.

Results

An analysis of YouTube videos covering COVID-19, uploaded in early 2020, in English and Hindi. The sample comprised 349 videos (n = 334 English). Videos were characterized by contributor, duration, content, and reception (views/likes/dislikes/comments). The majority contained general information, with only 4.01% focusing on symptoms and 11.17% on treatment and outcomes. Further, the majority (n = 229) were short videos of under 10 min duration. Videos provided by government and health care professionals comprised 6.87% and 5.74% % of the sample, respectively. News channels uploaded 71.63% of videos.

Conclusions

YouTube may provide a significant resource for disseminating of information on public health issues like outbreaks of viral infections and should be utilized by healthcare agencies for this purpose. However, there is currently no way to determine whether a video has been produced or verified by authorized healthcare professionals. This limitation needs to be addressed so that the vital distribution services offered by platforms like YouTube can be fully utilized for increasing public understanding of healthcare science, particularly during a crisis such as a pandemic.
Transfluthrin eave-positioned targeted insecticide (EPTI) reduces human landing rate (HLR) of pyrethroid resistant and susceptible malaria vectors in a semi-field simulated peridomestic space
Authors: Tambwe Mgeni M. , Moore Sarah , Hofer Lorenz , Kibondo Ummi A. , Saddler Adam
Published: August 2021

Background

Volatile pyrethroids (VPs) are proven to reduce human–vector contact for mosquito vectors. With increasing resistance to pyrethroids in mosquitoes, the efficacy of VPs, such as transfluthrin, may be compromised. Therefore, experiments were conducted to determine if the efficacy of transfluthrin eave-positioned targeted insecticide (EPTI) depends on the resistance status of malaria vectors.

Methods

Ribbons treated with 5.25 g transfluthrin or untreated controls were used around the eaves of an experimental hut as EPTI inside a semi-field system. Mosquito strains with different levels of pyrethroid resistance were released simultaneously, recaptured by means of human landing catches (HLCs) and monitored for 24-h mortality. Technical-grade (TG) transfluthrin was used, followed by emulsifiable concentrate (EC) transfluthrin and additional mosquito strains. Generalized linear mixed models with binomial distribution were used to determine the impact of transfluthrin and mosquito strain on mosquito landing rates and 24-h mortality.

Results

EPTI treated with 5.25 g of either TG or EC transfluthrin significantly reduced HLR of all susceptible and resistantAnophelesmosquitoes (Odds Ratio (OR) ranging from 0.14 (95% Confidence Interval (CI) [0.11–0.17], P < 0.001) to 0.57, (CI [0.42–0.78]P < 0.001). Both TG and EC EPTI had less impact on landing for the resistantAnopheles arabiensis(Mbita strain) compared to the susceptibleAnopheles gambiae(Ifakara strain) (OR 1.50 [95% CI 1.18–1.91]P < 0.001) and (OR 1.67 [95% CI 1.29–2.17]P < 0.001), respectively. The EC EPTI also had less impact on the resistantAn. arabiensis(Kingani strain) (OR 2.29 [95% CI 1.78–2.94]P < 0.001) compared to the control however the TG EPTI was equally effective against the resistant Kingani strain and susceptible Ifakara strain (OR 1.03 [95% CI 0.82–1.32]P = 0.75). Finally the EC EPTI was equally effective against the susceptibleAn. gambiae(Kisumu strain) and the resistantAn. gambiae(Kisumu-kdr strain) (OR 0.98 [95% CI 0.74–1.30]P = 0.90).

Conclusions

Transfluthrin-treated EPTI could be useful in areas with pyrethroid-resistant mosquitoes, but it remains unclear whether stronger resistance to pyrethroids will undermine the efficacy of transfluthrin. At this dosage, transfluthrin EPTI cannot be used to kill exposed mosquitoes.
Patients’ preferences for antiretroviral therapy service provision: a systematic review
Authors: Belay Yihalem Abebe , Yitayal Mezgebu , Atnafu Asmamaw , Taye Fitalew Agimass
Published: August 2021

Background

Achieving global targets of adherence to treatment, retention in care, and treatment success remains a challenge. Health system investment to make antiretroviral therapy services more responsive to patients’ needs and values could address these impediments. Appropriate resource allocation to implement differentiated HIV treatment services demands research evidence. This study aimed to provide an overview of the patients’ preferences for antiretroviral therapy service delivery features.

Methods

Electronic databases (PubMed, Web of Science, Embase, and CINAHL) and search engines (Google and Google Scholar) were searched. This review has followed a convergent segregated approach to synthesis and integration. Data from the included studies were systematically extracted, tabulated, and summarised in a narrative review. Studies that analysed preferences for antiretroviral therapy regardless of the method used and published in the English language in any year across the world and HIV positive clients who were 15 years and above on 4th February 2021 were included for this review. The quality of the included studies was assessed using the mixed methods appraisal tool. A thematic synthesis of the data from the findings section of the main body of the qualitative study was undertaken. ATLAS.ti software version 7 was used for qualitative synthesis.

Results

From the 1054 retrieved studies, only 23 studies (16 quantitative, three qualitative, and four mixed-methods) fulfilled the inclusion criteria. The median number of attributes used in all included quantitative studies was 6 (Inter Quartile Range 3). In this review, no study has fulfilled the respective criteria in the methodological quality assessment. In the quantitative synthesis, the majority of participants more valued the outcome, whereas, in the qualitative synthesis, participants preferred more the structure aspect of antiretroviral therapy service. The thematic analysis produced 17 themes, of which ten themes were related to structure, three to process, and four to outcome dimension of Donabedian’s quality of care model. The findings from individual quantitative and qualitative syntheses complement each other.

Conclusions

In this review, participants’ value for antiretroviral therapy service characteristics varied across included studies. Priorities and values of people living with HIV should be incorporated in the policy, practice, research, and development efforts to improve the quality of antiretroviral therapy service hence avoid poor patient outcomes.
TFH cells in systemic sclerosis
Authors: Beurier Pauline , Ricard Laure , Eshagh Deborah , Malard Florent , Siblany Lama , Fain Olivier , Mohty Mohamad , Gaugler Béatrice , Mekinian Arsène
Published: August 2021

Systemic sclerosis is an autoimmune disease characterized by excessive dermal fibrosis with progression to internal organs, vascular impairment and immune dysregulation evidenced by the infiltration of inflammatory cells in affected tissues and the production of auto antibodies. While the pathogenesis remains unclear, several data highlight that T and B cells deregulation is implicated in the disease pathogenesis. Over the last decade, aberrant responses of circulating T follicular helper cells, a subset of CD4 T cells which are able to localise predominantly in the B cell follicles through a high level of chemokine receptor CXCR5 expression are described in pathogenesis of several autoimmune diseases and chronic graft-versus-host-disease. In the present review, we summarized the observed alteration of number and frequency of circulating T follicular helper cells in systemic sclerosis. We described their role in aberrant B cell activation and differentiation though interleukine-21 secretion. We also clarified T follicular helper-like cells involvement in fibrogenesis in both human and mouse model. Finally, because T follicular helper cells are involved in both fibrosis and autoimmune abnormalities in systemic sclerosis patients, we presented the different strategies could be used to target T follicular helper cells in systemic sclerosis, the therapeutic trials currently being carried out and the future perspectives from other auto-immune diseases and graft-versus-host-disease models.