bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Readability of Patient Education Materials on Breast Reconstruction by Major US Academic Hospitals as Compared With Nonacademic Sites
Authors: Powell Lauren E. , Andersen Emily S. , Pozez Andrea L. 
Published: November 2020

Purpose
Women undergoing postmastectomy breast reconstruction face many complex choices. A myriad of online patient education materials exist to assist in decision making. Understanding of these materials, termed health literacy, affects surgical decision making and outcomes. The National Institutes of Health recommends writing patient education materials at a sixth- to seventh-grade reading level. The primary goal of this study was to assess readability of online breast reconstruction materials.

Methods and Materials
Resources were collected from every academic hospital with a plastic surgery residency program, 97 in total. These data were compared with the top nonacademic Web sites ranked by search engine results, 14 in total. Materials were analyzed using 3 validated readability assessment scales: Coleman-Liau Index, SMOG (Simplified Measure of Gobbledygook) Readability Formula, and Flesch-Kincaid Grade Level. Average readability was analyzed, and results were compared using a 1-way analysis of variance to assess for significance between the different tools and a 2-sided t test to assess for significance between academic and nonacademic readability results.

Results
The mean readability scores across the academic programs were a Coleman-Liau Index of 13.38 (standard Deviation [SD] 2.81, 13th to 14th grade), Flesch-Kincaid Grade Level of 13.04 (SD = 3.9, 13th grade), and SMOG Readability of 13.64 (SD = 2.99, 13th to 14th grade). For the 14 nonacademic sites, results showed a Coleman-Liau Index of 11.93 (SD = 1.14, 12th grade), Flesch-Kincaid of 11.82 (SD = 2.33, 11th to 12th grade), and SMOG Readability of 10.91 (SD = 1.79, 11th grade). One-way analysis of variance demonstrated no significant differences in mean readability scores across the 3 readability tools used (academic F = 2.7804, P = 0.06; nonacademic F = 1.14, P = 0.33). Two-tailed t test results demonstrated that there was statistical significance between readability of the academic in comparison with nonacademic search engine results (t = 2.04, P = 0.04).

Conclusions
Average readability across all Web sites were much higher than the recommended reading level, at a 13th to 14th grade reading level for academic institutions, and an 11th to 12th grade for nonacademic Web sites. Plastic surgeons may contribute to improving patient understanding and perioperative outcomes through revising patient education materials.
State of Microsurgery Training in 2020
Authors: Morrison Kerry A. , Verzella Alexandra , Hacquebord Jacques H. 
Published: November 2020

Background
Given the current national conundrum of decreasing microsurgery case volume performed by hand surgery fellows despite interest, program directors were surveyed to evaluate opinions of exposure gaps in training and to determine the current state of microsurgery training in 2020.

Methods
Anonymous national surveys were distributed to hand surgery fellowship program directors by the American Society for Surgery of the Hand. Subgroups were compared by training location and size of the fellowship program. Accreditation Council for Graduate Medical Education public national data on graduate case log procedures by hand surgery fellows were reviewed.

Results
Eighty-eight surveys were distributed by the American Society for Surgery of the Hand to hand surgery fellowship program directors with a 44% (n = 39) response rate. Hand surgery fellowship programs from 19 US states participated. Most program's fellows had previous orthopedic surgery residency training with 41.03% of programs surveyed having 100% orthopedic surgery–trained fellows. The average number of weekly vascular microsurgical cases ranged from 25% of fellowships having no microsurgery cases per week, 46.2% having 1 per week, and only 7.7% having 5 or more cases per week. However, 60.5% of program directors prioritized a microvascular surgery case as the most valuable educational opportunity for fellows. Most program directors agreed (79.5%) that a 1-year hand surgery fellowship is sufficient to train a competent hand surgeon, who is proficient in microsurgery. In contrast, the majority disagreed (53.8%) that hand surgery microsurgery skills after a 1-year hand surgery fellowship are equivalent among graduates, regardless of a prior plastic surgery or orthopedic surgery residency training. There was a statistically significant difference in program directors’ responses by geographic location regarding prior residency background impacting microsurgical skills (Kendall τ, −0.439; P = 0.001). Graduate case log data revealed an increasing trend in the number of microsurgery procedures performed by orthopedic hand surgery fellows until 2014, with a decline in cases per year and stagnating trend at 7% thereafter.

Conclusions
In 2020, most hand surgery fellowship program directors highly value and prioritize microsurgery exposure for their hand surgery fellows' education despite the decrease in case volume for hand surgery fellows.
Modafinil Induced Spontaneous Ejaculation Without Orgasm: A Case Report
Authors: Aras Neriman 
Published: November 2020

Abstract
Modafinil is used for the treatment of narcolepsy and obstructive sleep apnea syndrome, and as add-on therapy for psychiatric diseases such as attention-deficit/hyperactivity disorder, schizophrenia, depression, cocaine addiction. The exact mechanism of action is unknown. Modafinil may be helpful for the treatment of erectile dysfunction and premature ejaculation. The addition of modafinil to antidepressant treatment may provide positive effects on sexual dysfunction. However, side effects such as hypersexuality and unwanted orgasm have been reported with modafinil treatment. In this article, a patient who had developed spontaneous ejaculations after the addition of modafinil for the treatment of depression with venlafaxine is discussed. Although venlafaxine treatment continued after the discontinuation of modafinil, spontaneous ejaculation did not continue. It should be kept in mind that agents with dopaminergic and noradrenergic effects, such as modafinil, can cause undesirable sexual side effects.
The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
Authors: Abdulrahman Abdulkarim , AlSayed Islam , AlMadhi Marwa , AlArayed Jumana , Mohammed Sara Jaafar , Sharif Aesha Khalid , Alansari Khadija , AlAwadhi Abdulla I , AlQahtani Manaf 
Published: November 2020

ABSTRACTBackgroundHydroxychloroquine is an antimalarial drug that received worldwide news and media attention in the treatment of COVID-19 patients. This drug was used based on its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using Hydroxychloroquine in treatment of COVID-19 patients who are admitted in acute care hospitals in Bahrain.MethodologyWe conducted retrospective cohort study on a random sample of admitted COVID19 patients between 24 February and 31 July 2020. The study was conducted in four acute care COVID19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression and matched propensity score analysis.ResultsA random sample of 1571 patients were included, 440 of which received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43 95% CI 0.85 to 2.37, P value=0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7 95% CI 0.82 to 8.85 P value =0.10). HCQ was found to be associated with increased risk of hypoglycemia (OR 10.9 95% CI 1.72 - 69.49, P value =0.011) and diarrhea(OR 2.8, 95% CI 1.4-5.5, P value =0.003), but not QT prolongation(OR=1.92, 95% CI 0.95-3.9, P value =0.06) or cardiac arrhythmia.(OR=1.06, 95% CI 0.55-2.05, P value =0.85).ConclusionOur results showed no significant beneficial effect of using hydroxychloroquine on the outcome of COVID-19 patients. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out of hospital use.
T cell and antibody functional correlates of severe COVID-19
Authors: Yu Krystle K.Q. , Fischinger Stephanie , Smith Malisa T. , Atyeo Caroline , Cizmeci Deniz , Wolf Caitlin R. , Layton Erik D. , Logue Jennifer K. , Aguilar Melissa S. , Shuey Kiel , Loos Carolin , Yu Jingyou , Franko Nicholas , Choi Robert Y. , Wald Anna , Barouch Dan H. , Koelle David M. , Lauffenburger Douglas , Chu Helen Y. , Alter Galit , Seshadri Chetan 
Published: November 2020

ABSTRACTComorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2 which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19. Our data suggest that isolated measurements of the magnitudes of spike-specific immune responses are likely insufficient to anticipate vaccine efficacy in high-risk populations.
Genetic Mutations Associated with Hormone-Positive Breast Cancer in Ethiopian Women
Authors: Schwartz Alyssa D. , Adusei Afua , Tsegaye Solomon , Moskaluk Christopher A. , Schneider Sallie S. , Platt Manu O. , Seifu Daniel , Peyton Shelly R. , Babbitt Courtney C. 
Published: November 2020

AbstractIn Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER +) breast cancer. This is surprising given 1) the aggressive nature of the disease, 2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and 3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched normal and tumor tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and White patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.
Optimal shutdown strategies for COVID-19 with economic and mortality costs: BC as a case study
Authors: Barlow M.T. , Marshall N.D. , Tyson R.C. 
Published: November 2020

AbstractDecision makers with the responsibility of managing policy for the COVID-19 epidemic have faced difficult choices in balancing the competing claims of saving lives and the high economic cost of shutdowns. In this paper we formulate a model with both epidemiological and economic content to assist this decision making process. We consider two ways to handle the balance between economic costs and deaths. First, we use the statistical value of life, which in Canada is about C$7 million, to optimise over a single variable, which is the sum of the economic cost and the value of lives lost. Our second method is to calculate the Pareto optimal front when we look at the two variables – deaths and economic costs.In both cases we find that, for most parameter values, the optimal policy is to adopt an initial shutdown level which reduces the reproduction number of the epidemic to close to 1. This level is then reduced once a vaccination program is underway. Our model also indicates that an oscillating policy of strict and mild shutdowns is less effective than a policy which maintains a moderate shutdown level.
Automated Western immunoblotting detection of anti-SARS-CoV-2 serum antibodies
Authors: Edouard S. , Jaafar R. , Orain N. , Parola P. , Colson P. , La Scola B. , Fournier P-E. , Raoult D. , Drancourt M. 
Published: November 2020

ABSTRACTELISA and chemiluminescence serological assays for COVID-19 are currently incorporating only one or two SARS-CoV-2 antigens. We developed an automated Western immunoblotting as a complementary serologic assay for COVID-19. The Jess™ Simple Western system, an automated capillary-based assay was used, incorporating an inactivated SARS-CoV-2 lineage 20a strain as antigen, and IgT detection. In total, 602 sera were tested including 223 from RT-PCR-confirmed COVID-19 patients, 76 from patients diagnosed with seasonal HCoVs and 303 from coronavirus-negative control sera. We also compared this assay with the EUROIMMUN® SARS-CoV-2 IgG ELISA kit. Among 223 sera obtained from RT-PCR-confirmed COVID-19 patients, 180/223 (81%) exhibited reactivity against the nucleocapsid and 70/223 (31%) against the spike protein. Nucleocapsid reactivity was further detected in 9/76 (14%) samples collected from patients diagnosed with seasonal HCoVs and in 15/303 (5%) coronavirus-negative control samples. In the subset of sera collected more than 2 weeks after the onset of symptoms, the sensitivity was 94% and the specificity 93%, the latter value probably reflecting cross-reactivity of SARS-CoV-2 with other coronaviruses. The automated Western immunoblotting presented a substantial agreement (90%) with the compared ELISA (Cohen’s Kappa=0.64). Automated Western immunoblotting may be used as a second line test to monitor exposition of people to HCoVs including SARS-CoV-2.
Using Whole Genome Sequences to Investigate Adenovirus Outbreaks, Including Five Deaths in a Haematopoietic Stem Cell Transplant Unit
Authors: Myers Chloe E. , Houldcroft Charlotte J. , Roy Sunando , Margetts Ben K. , Best Timothy , Venturini Cristina , Guerra-Assunção José A. , Williams Charlotte A. , Williams Rachel , Dunn Helen , Hartley John C. , Rolfe Kathryn J. , Breuer Judith 
Published: November 2020

AbstractBackgroundHuman mastadenoviruses (HAdV) are associated with significant morbidity and mortality amongst the immunocompromised population. A recent surge in HAdV cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate.MethodsTo gain a complete transmission picture, we compared outbreak and non-outbreak sequences (54 sequences from 37 patients) with GenBank sequences and our own database of previously sequenced HAdVs (132 sequences from 37 patients). An improved bait set for WGS was used. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships paired with epidemiological data from routine Infection, Prevention and Control (IPC) activity.ResultsNine monophyletic clusters were identified, seven of which were corroborated by epidemiological evidence and by comparison of single nucleotide polymorphisms. Two incomplete patient clusters were identified by IPC over the same time period. Of the five patients who died, one had a mixed HAdV infection and two were the source of transmission events.ConclusionsThe clinical consequences of unmitigated HAdV transmission events are high. Focusing on two high risk wards using WGS we identified six transmission events, over prolonged periods, that would have gone unnoticed using traditional polymerase chain reaction and epidemiology. Mixed infection is frequent (10% of patients), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harbouring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into a clinical algorithm to prevent transmission and influence IPC policy in real-time.SummaryWhole genome sequencing of adenovirus, direct from clinical samples, can be used to identify cryptic health care associated transmission events, and to resolve transmission suspected by traditional epidemiology. It can also identify mixed genotype infections in immunocompromised patient populations.
Changing case fatality risk for COVID-19 over time in selected European countries
Authors: Becher Heiko , Olszewski Katharina , Wiegel Sarah , Mueller Olaf 
Published: November 2020

Objectives	To illustrate the development of the case fatality risk (CFR) for COVID-19 over time using different assumptions for calculating the CFR.
Design	Observational study.
Setting	Selected European countries, 28 January to October 29 2020.
Participants	Laboratory-confirmed COVID-19 cases and deaths due to COVID-19
Main outcome measure	case fatality risk (CFR)
Results	We show that the CFR has considerably decreased over time. This seems to be driven not only by increased testing but also by a reduced CFR among cases older than 60 years. Our data also confirm a significantly higher fatality risk for men than for women. The decline in the CFR is even more pronounced when only cases and deaths occurring in a specified time window are considered. This alternative estimation method has the advantage that early data where the bias due to the incomplete ascertainment of cases was arguably largest do not affect CFR estimates later on. We find similar results for other European countries.
Conclusion	CFR estimates vary considerably depending on the underlying assumptions concerning their calculation. Reliable CFR estimates should not be based on cumulative numbers from the beginning of the pandemic but rather be based on more recent data only.
The evolving worldwide dynamic state of the COVID-19 outbreak
Authors: Vilar Jose M. G. , Saiz Leonor 
Published: November 2020

ABSTRACTThe dynamic characterization of the COVID-19 outbreak is critical to implement effective actions for its control and eradication but the information available at a global scale is not sufficiently reliable to be used directly. Here, we integrate multiple data sources through dynamical constraints to quantify its temporal evolution and controllability around the world and within the United States. Overall, the numbers of actively infectious individuals have remained high beyond targeted controllability, with worldwide estimates of 10.24 million on November 24, 2020, totaling in 266.1 million cumulative infections growing at a rate of 11.12 million new infections per week. The actively infectious population reached a local maximum of 7.33 million on July 16, 2020 and remained virtually stagnant at a global scale, with growth rates for most countries around zero that compensated each other, until reverting to net growth on September 22, 2020. We validated the approach, contrasting with prevalence data and the effects of nonpharmaceutical interventions, and we identified general patterns of recession, stabilization, and resurgence. The diversity of dynamic behaviors of the outbreak across countries is paralleled by those of states and territories in the United States, converging to remarkably similar global states in both cases. Our results offer precise insights into the dynamics of the outbreak and an efficient avenue for the estimation of the prevalence rates over time.
Auricular Vagus Neuromodulation – A Systematic Review on Quality of Evidence and Clinical Effects
Authors: Verma Nishant , Mudge Jonah D , Kasole Maïsha , Chen Rex C , Blanz Stephan L , Trevathan James K , Lovett Eric , Williams Justin C , Ludwig Kip A 
Published: November 2020

ABSTRACTThis review is intended to identify key gaps in the mechanistic knowledge and execution of aVNS studies, to be addressed in future works, and aid the successful translation of neuromodulation therapies.BackgroundThe auricular branch of the vagus nerve runs superficial to the surface of the skin, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. For this reason, there have been many early-stage clinical trials on a diverse range of conditions. These trials often report conflicting results for the same indication.MethodsUsing the Cochrane Risk of Bias tool we conducted a systematic review of auricular vagus nerve stimulation (aVNS) randomized controlled trials (RCTs) to identify the factors that led to these conflicting results. As is common for early-stage studies, the majority of aVNS studies were assessed as having ‘some’ or ‘high’ risk of bias, which makes it difficult to interpret their results in a broader context.ResultsThere is evidence of a modest decrease in heart rate during higher stimulation dosages, sometimes at above the level of sensory discomfort. Findings on heart rate variability conflict between studies and are hindered by trial design, including inappropriate washout periods, and multiple methods used to quantify heart rate variability. There is early-stage evidence to suggest aVNS may reduce circulating levels and endotoxin-induced levels of inflammatory markers. Studies on epilepsy reached primary endpoints similar to previous RCTs testing implantable vagus nerve stimulation (VNS) therapy, albeit with concerns over quality of blinding. Preliminary evidence shows that aVNS ameliorated pathological pain but not evoked pain.DiscussionBased on results of the Cochrane analysis we list common improvements for the reporting of results, which can be implemented immediately to improve the quality of evidence. In the long term, existing data from aVNS studies and salient lessons from drug development highlight the need for direct measures of local neural target engagement. Direct measures of neural activity around the electrode will provide data for the optimization of electrode design, placement, and stimulation waveform parameters to improve on-target engagement and minimize off-target activation. Furthermore, direct measures of target engagement, along with consistent evaluation of blinding success, must be used to improve the design of controls in the long term – a major source of concern identified in the Cochrane analysis.ConclusionThe need for direct measures of neural target engagement and consistent evaluation of blinding success is applicable to the development of other paresthesia-inducing neuromodulation therapies and their control designs.