bluuebunny/crossref_metadata_2025 huggingface dataset:
Megadepth: efficient coverage quantification for BigWigs and BAMs
Authors: Wilks Christopher , Ahmed Omar , Baker Daniel N , Zhang David , Collado-Torres Leonardo , Langmead Ben
Published: March 2021

Motivation

A common way to summarize sequencing datasets is to quantify data lying within genes or other genomic intervals. This can be slow and can require different tools for different input file types.

Results

Megadepth is a fast tool for quantifying alignments and coverage for BigWig and BAM/CRAM input files, using substantially less memory than the next-fastest competitor. Megadepth can summarize coverage within all disjoint intervals of the Gencode V35 gene annotation for more than 19 000 GTExV8 BigWig files in approximately 1 h using 32 threads. Megadepth is available both as a command-line tool and as an R/Bioconductor package providing much faster quantification compared to the rtracklayer package.

Availability and implementation

https://github.com/ChristopherWilks/megadepth, https://bioconductor.org/packages/megadepth.

Supplementary information

Supplementary data are available at Bioinformatics online.
Super-delta2: an enhanced differential expression analysis procedure for multi-group comparisons of RNA-seq data
Authors: Cui Zihan , Liu Yuhang , Zhang Jinfeng , Qiu Xing
Published: March 2021

Motivation

We developed super-delta2, a differential gene expression analysis pipeline designed for multi-group comparisons for RNA-seq data. It includes a customized one-way ANOVA F-test and a post-hoc test for pairwise group comparisons; both are designed to work with a multivariate normalization procedure to reduce technical noise. It also includes a trimming procedure with bias-correction to obtain robust and approximately unbiased summary statistics used in these tests. We demonstrated the asymptotic applicability of super-delta2 to log-transformed read counts in RNA-seq data by large sample theory based on Negative Binomial Poisson (NBP) distribution.

Results

We compared super-delta2 with three commonly used RNA-seq data analysis methods: limma/voom, edgeR and DESeq2 using both simulated and real datasets. In all three simulation settings, super-delta2 not only achieved the best overall statistical power, but also was the only method that controlled type I error at the nominal level. When applied to a breast cancer dataset to identify differential expression pattern associated with multiple pathologic stages, super-delta2 selected more enriched pathways than other methods, which are directly linked to the underlying biological condition (breast cancer).

Conclusions

In conclusion, by incorporating trimming and bias-correction in the normalization step, super-delta2 was able to achieve tight control of type I error. Because the hypothesis tests are based on asymptotic normal approximation of the NBP distribution, super-delta2 does not require computationally expensive iterative optimization procedures used by methods such as edgeR and DESeq2, which occasionally have convergence issues.

Availability and implementation

Our method is implemented in a R-package, ‘superdelta2’, freely available at: https://github.com/fhlsjs/superdelta2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Omixer: multivariate and reproducible sample randomization to proactively counter batch effects in omics studies
Authors: Sinke Lucy , Cats Davy , Heijmans Bastiaan T
Published: March 2021

Motivation

Batch effects heavily impact results in omics studies, causing bias and false positive results, but software to control them preemptively is lacking. Sample randomization prior to measurement is vital for minimizing these effects, but current approaches are often ad hoc, poorly documented and ill-equipped to handle multiple batches and outcomes.

Results

We developed Omixer—a Bioconductor package implementing multivariate and reproducible sample randomization for omics studies. It proactively counters correlations between technical factors and biological variables of interest by optimizing sample distribution across batches.

Availabilityand implementation

Omixer is available from Bioconductor at http://bioconductor.org/packages/release/bioc/html/Omixer.html. Scripts and data used to generate figures available upon request.

Supplementary information

Supplementary data are available at Bioinformatics online.
Hummingbird: efficient performance prediction for executing genomic applications in the cloud
Authors: Bahmani Amir , Xing Ziye , Krishnan Vandhana , Ray Utsab , Mueller Frank , Alavi Amir , Tsao Philip S. , Snyder Michael P. , Pan Cuiping
Published: March 2021

Motivation

A major drawback of executing genomic applications on cloud computing facilities is the lack of tools to predict which instance type is the most appropriate, often resulting in an over- or under- matching of resources. Determining the right configuration before actually running the applications will save money and time. Here, we introduce Hummingbird, a tool for predicting performance of computing instances with varying memory and CPU on multiple cloud platforms.

Results

Our experiments on three major genomic data pipelines, including GATK HaplotypeCaller, GATK Mutect2 and ENCODE ATAC-seq, showed that Hummingbird was able to address applications in command line specified in JSON format or workflow description language (WDL) format, and accurately predicted the fastest, the cheapest and the most cost-efficient compute instances in an economic manner.

Availability and implementation

Hummingbird is available as an open source tool at: https://github.com/StanfordBioinformatics/Hummingbird.

Supplementary information

Supplementary data are available at Bioinformatics online.
Expression of Genes in the 16p11.2 Locus during Development of the Human Fetal Cerebral Cortex
Authors: Morson Sarah , Yang Yifei , Price David J , Pratt Thomas
Published: March 2021

The 593 kbp 16p11.2 copy number variation (CNV) affects the gene dosage of 29 protein coding genes, with heterozygous 16p11.2 microduplication or microdeletion implicated in about 1% of autism spectrum disorder (ASD) cases. The 16p11.2 CNV is frequently associated with macrocephaly or microcephaly indicating early defects of neurogenesis may contribute to subsequent ASD symptoms, but it is unknown which 16p11.2 transcripts are expressed in progenitors and whose levels are likely, therefore, to influence neurogenesis. Analysis of human fetal gene expression data revealed that KIF22, ALDOA, HIRIP3, PAGR1, and MAZ transcripts are expressed in neural progenitors with ALDOA and KIF22 significantly enriched compared to post-mitotic cells. To investigate the possible roles of ALDOA and KIF22 proteins in human cerebral cortex development we used immunohistochemical staining to describe their expression in late first and early second trimester human cerebral cortex. KIF22 protein is restricted to proliferating cells with its levels increasing during the cell cycle and peaking at mitosis. ALDOA protein is expressed in all cell types and does not vary with cell-cycle phase. Our expression analysis suggests the hypothesis that altered neurogenesis in the cerebral cortex contributes to ASD in 16p11.2 CNV patients.
Detecting Cyberbullying across Social Media Platforms in Saudi Arabia Using Sentiment Analysis: A Case Study
Authors: Fati Suliman Mohamed
Published: March 2021

Twitter has become an open space for the users’ interactions and discussions on diverse trending topics. One of the issues raised on social media platforms is the misunderstanding of ‘freedom of speech’, which in turn, leads us to a new social and behavioral attack: cyberbullying. Cyberbully affects both individuals and societies. Despite tough sanctions globally and locally, cyberbullying is still a serious issue, which needs further consideration. Thus, this research aims to address this issue by proposing a framework, based on sentiment analysis, to detect cyberbullying in the tweets stream. The proposed framework in this paper extracts the tweets from Twitter. Then, the preprocessing through tweets tokenization was applied to remove noise from tweets and also symbols and phrases such as http, emoji faces, hash tag symbols, mention symbols and retweet. After data tokenization, the proposed system classifies the tweets, based on extracted keywords from both experts and potential victims, using deep-learning classification algorithm with 70% of dataset samples used for the training purpose, and 30% of the dataset samples used for the testing purpose. The experimental results show the ability of proposed methodology to detect cyberbullying effectively with accuracy 81%.
Linguistic but Not Cognitive Weaknesses in Deaf or Hard-of-Hearing Poor Comprehenders
Authors: Deng Qinli , Tong Shelley Xiuli
Published: March 2021

This study examined the reading comprehension profiles, and the related linguistic and cognitive skills, of 146 Chinese students in Grades 3–9 who are deaf or hard of hearing (d/Dhh). Employing a rigorous regression approach, the current study identified 19 unexpected poor comprehenders, 24 expected average comprehenders, and 16 unexpected good comprehenders. Compared to the expected average and unexpected good comprehenders, the unexpected poor comprehenders performed worse in broad linguistic skills (i.e., Chinese sign language comprehension, vocabulary, and segmental and suprasegmental phonological awareness), but their weaknesses in cognitive skills (i.e., working memory and executive function) were less severe. These findings suggest that weak linguistic skills are possible indicators of reading comprehension difficulties for students who are d/Dhh.
Pathological assessment of very late bare metal stent thrombosis in the left main coronary artery: a case report
Authors: Yuki Haruhito , Naganuma Toru , Nakazawa Gaku , Nakamura Sunao
Published: March 2021

Background

Late catch-up phenomenon following stent implantation is a well-known complication. However, no report has evaluated thrombosis after 9 years with multi-modality and pathological evaluation.

Case summary

A 71-year-old man with stable angina underwent elective percutaneous intervention of the left main coronary artery with implantation of a bare metal stent (BMS) 9 years ago. At the 9-year follow-up, coronary computed tomography (CCT) and coronary angiography (CAG) findings revealed a thrombus-like structure in the BMS slightly protruding into the sinus of Valsalva. Therefore, the previously prescribed double-antiplatelet therapy was replaced with an anticoagulant and clopidogrel, and a potent statin treatment was initiated. After the changes in drug treatment, follow-up examinations with CCT at 1 and 3 months suggested a decrease in the size of the thrombus; however, it appeared to increase after 6 months. Subsequently, the patient underwent surgical intervention. Pathological assessment of the explanted stent showed a proteoglycan-dominated extracellular matrix with few smooth muscle cells suggesting an organized thrombus.

Discussion

It should be emphasized that multiple factors might be responsible for very late stent thrombosis, such as peri-stent strut chronic inflammation involving proteoglycans, stent protrusion, and poorly controlled type 2 diabetes mellitus, possibly further inducing inflammatory cells.
The Antibiotic Dosage of Fastest Resistance Evolution: Gene Amplifications Underpinning the Inverted-U
Authors: Reding Carlos , Catalán Pablo , Jansen Gunther , Bergmiller Tobias , Wood Emily , Rosenstiel Phillip , Schulenburg Hinrich , Gudelj Ivana , Beardmore Robert
Published: March 2021

To determine the dosage at which antibiotic resistance evolution is most rapid, we treated Escherichia coli in vitro, deploying the antibiotic erythromycin at dosages ranging from zero to high. Adaptation was fastest just below erythromycin’s minimal inhibitory concentration (MIC) and genotype-phenotype correlations determined from whole genome sequencing revealed the molecular basis: simultaneous selection for copy number variation in three resistance mechanisms which exhibited an “inverted-U” pattern of dose-dependence, as did several insertion sequences and an integron. Many genes did not conform to this pattern, however, reflecting changes in selection as dose increased: putative media adaptation polymorphisms at zero antibiotic dosage gave way to drug target (ribosomal RNA operon) amplification at mid dosages whereas prophage-mediated drug efflux amplifications dominated at the highest dosages. All treatments exhibited E. coli increases in the copy number of efflux operons acrAB and emrE at rates that correlated with increases in population density. For strains where the inverted-U was no longer observed following the genetic manipulation of acrAB, it could be recovered by prolonging the antibiotic treatment at subMIC dosages.
Four lenses on people management in the public sector: an evidence review and synthesis
Authors: Ali Aisha J , Fuenzalida Javier , Gómez Margarita , Williams Martin J
Published: March 2021

We review the literature on people management and performance in organizations across a range of disciplines, identifying aspects of management where there is clear evidence about what works as well as aspects where the evidence is mixed or does not yet exist. We organize our discussion by four lenses, or levels of analysis, through which people management can be viewed: (i) individual extrinsic, intrinsic, and psychological factors; (ii) organizational people management, operational management, and culture; (iii) team mechanisms, composition and structural features; and (iv) relationships, including networks, leadership, and individuals’ relationships to their job and tasks. Each of these four lenses corresponds not only to a body of literature but also to a set of management tools and approaches to improving public employees’ performance; articulating the connections across these perspectives is an essential frontier for research. We find that existing people management evidence and practice have overemphasized formal management tools and financial motivations at the expense of understanding how to leverage a broader range of motivations, build organizational culture, and use informal and relational management practices. We suggest that foregrounding the role of relationships in linking people and performance—relational public management—may prove a fertile and interdisciplinary frontier for research and practices.
Fueling the Covid-19 pandemic: summer school holidays and incidence rates in German districts
Authors: Plümper Thomas , Neumayer Eric
Published: March 2021

Background

The Robert-Koch-Institute reports that during the summer holiday period a foreign country is stated as the most likely place of infection for an average of 27 and a maximum of 49% of new SARS-CoV-2 infections in Germany.

Methods

Cross-sectional study on observational data. In Germany, summer school holidays are coordinated between states and spread out over 13 weeks. Employing a dynamic model with district fixed effects, we analyze the association between these holidays and weekly incidence rates across 401 German districts.

Results

We find effects of the holiday period of around 45% of the average district incidence rates in Germany during their respective final week of holidays and the 2 weeks after holidays end. Western states tend to experience stronger effects than Eastern states. We also find statistically significant interaction effects of school holidays with per capita taxable income and the share of foreign residents in a district’s population.

Conclusions

Our results suggest that changed behavior during the holiday season accelerated the pandemic and made it considerably more difficult for public health authorities to contain the spread of the virus by means of contact tracing. Germany’s public health authorities did not prepare adequately for this acceleration.
Phenotypic analysis of pyrin-associated autoinflammation with neutrophilic dermatosis patients during treatment
Authors: Van Nieuwenhove Erika , De Langhe Ellen , Dooley James , Van Den Oord Joost , Shahrooei Mohammad , Parvaneh Nima , Ziaee Vahid , Savic Sinisa , Kacar Mark , Bossuyt Xavier , Humblet-Baron Stephanie , Liston Adrian , Wouters Carine
Published: March 2021

Objective

In 2016 specific heterozygous gain-of-function mutations in the Mediterranean fever gene MEFV were reported as causal for a distinct autoinflammatory disease coined pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). We sought to provide an extended report on clinical manifestations in PAAND patients to date and evaluate the efficacy and safety of treatment with the IL-1-blocking agent anakinra.

Methods

We undertook an open-label pilot study with anakinra. Three patients were recruited in a preliminary phase of the study with the intention to expand the treatment cohort in case of a favourable response. Acute-phase reactants and plasma cytokine levels were monitored throughout. Skin biopsies at baseline and at week 12 were stained for relevant cytokines. Available clinical data on treatment responses were retrospectively collected on additional patients.

Results

The three patients from the preliminary phase of the study [patients 1–3 (P1–P3)] demonstrated one failed and two partial treatment responses, where one patient opted to continue treatment with anakinra and the other favoured adalimumab. While a partial systemic response was observed, there was no appreciable effect of anakinra on the prominent cutaneous manifestations, reflected in residual local inflammatory cytokine expression in lesional skin. These observations did not warrant further expansion of the treatment cohort. Clinical data was retrospectively collected on an additional eight patients (P4–P11), highlighting both dominant and recessive inheritance with variable penetrance in PAAND and common gastrointestinal involvement that was not previously appreciated.

Conclusion

In our experience, while anakinra appears safe, it was not superior to biologicals targeting TNF-α in PAAND despite evidence directly implicating dysregulated IL-1β signalling.
“Everyone has the right to their opinion”: “Gender Ideology” Rhetoric and Epistemic Struggles in Slovak Policymaking
Authors: Valkovičová Veronika , Meier Petra
Published: March 2021

Through the case study of the Slovak Committee on Gender Equality, a governmental advisory body, this article draws upon the growing literature on “gender ideology” rhetoric in Central and Eastern Europe to study the efforts of advocates of that rhetoric to gain access to policymaking structures. With the aid of narrative research, we examine the Committee’s struggles over appropriate terminology and discourse, data and research, and ultimately the status of experts. This shows how “gender ideology” rhetoric serves to delegitimize gender knowledge, and how it eventually turns into knowledge itself.
Considérations sur le droit de rétention du transporteur routier de marchandises en droit OHADA
Authors: Tchamgwe Innocent
Published: March 2021

En raison de son caractère synallagmatique, le contrat de transport met à la charge de l’expéditeur ou du destinataire, selon le cas, l’obligation de payer le prix du déplacement des marchandises. Ainsi, en cas de refus de paiement du prix du transport le transporteur a le droit de retenir les marchandises transportées jusqu’à complet paiement de sa créance. Mais malgré que le droit de rétention du transporteur ait été érigé au rang de sûreté, c’est parfois avec peine que son exercice par le transporteur débouche sur un paiement spontané du débiteur du prix du transport. La réalisation de la sûreté n’étant pas en principe possible, le désintéressement du transporteur ne peut être assuré que grâce au secours des autres moyens qui lui sont offerts par la loi. Et là encore, c’est à prendre avec des réserves.

Due to its synallagmatic nature, the transport contract places the responsibility of the sender or the recipient, as the case may be, with the obligation to pay the price of moving the goods. Thus, in the event of refusal to pay the price of the transport, the carrier has the right to withhold the goods transported until full payment of his debt. But despite the fact that the carrier's lien has been raised to the rank of security, it is sometimes with difficulty that its exercise by the carrier leads to a spontaneous payment by the debtor of the transport price. The realization of the security is not in principle possible; the disinterestedness of the carrier can be assured only thanks to the help of the other means which are offered to him by the law. And there again, it is to be taken with reservations.
Screening of Commercially Available Satsuma (Citrus unshiu and C. reticulata) Cultivars for Their Susceptibility to Citrus Canker Caused by Xanthomonas axonopodis pv. citri
Authors: de Souza Monique , Singh Raghuwinder , Khanal Churamani , Rankins Ansel , Laird Brett
Published: March 2021

Citrus canker presents major challenges in citrus production worldwide. The disease spreads and develops rapidly under conducive environmental conditions, and Louisiana’s hot and humid weather provides highly favorable conditions for citrus canker development in both commercial and backyard citrus production. Despite being considered eradicated in late 1940s, citrus canker was reconfirmed in Louisiana in 2013. Citrus is the most popular fruit tree grown commercially and in backyards in Louisiana, and satsumas dominate with 63% of total citrus acreage. The results from an annual citrus cooperative agricultural pest survey from 2014 to 2016 revealed that satsumas are highly tolerant to citrus canker with only 2.5% disease incidence, but the survey lacked information on the types of satsuma cultivar. The main objective of this study was to screen commercially available satsuma cultivars including Brown’s Select, Louisiana Early, Miho, Owari, and St. Ann for their susceptibility to citrus canker under natural field disease inoculum conditions with a goal to provide citrus growers with alternate disease management tactics. The results showed that there were significant differences in disease severity (average number of lesions per leaf) among the satsuma cultivars. Of the five satsuma cultivars, Brown’s Select and Miho consistently showed less disease severity with delayed incidence. Additionally, both Brown’s Select and Miho exhibited significantly smaller lesion size, which could lower canker inoculum production for secondary infections. This work provides Louisiana growers with scientific field-based data to make sound decisions in selecting less-susceptible satsuma cultivars for future plantings to mitigate disease spread and development in the state.
Where Did All the Appendicitis Go? Impact of the COVID-19 Pandemic on Volume, Management, and Outcomes of Acute Appendicitis in a Nationwide, Multicenter Analysis
Authors: Rosenthal Martin G. , Fakhry Samir M. , Morse Jennifer L. , Wyse Ransom J. , Garland Jeneva M. , Duane Therese M. , Slivinski Andrea , Wilson Nina Y. , Watts Dorraine D. , Shen Yan , Tabrizi Maryam Bita
Published: March 2021

Objective:

The study objective was to evaluate effects of the COVID-19 pandemic on rates of emergency department (ED) acute appendicitis presentation, management strategies, and patient outcomes.

Summary Background Data:

Acute appendicitis is the most commonly performed emergency surgery in the United States and is unlikely to improve without medical or surgical intervention. Dramatic reductions in ED visits prompted concern that individuals with serious conditions, such as acute appendicitis, were deferring treatment for fear of contracting COVID-19.

Methods:

Patients from 146 hospitals with diagnosed appendicitis and arrival between March 2016 and May 2020 were selected. Electronic medical records data were retrospectively reviewed to retrieve patient data. Daily admissions were averaged from March 2016 through May 2019 and compared with March 2020. April-specific admissions were compared across the 5-year pre-COVID-19 period to April 2020 to identify differences in volume, demographics, disease severity, and outcomes.

Results:

Appendicitis patient admissions in 2020 decreased throughout March into April, with April experiencing the fewest admissions. April 2020 experienced a substantial decrease in patients who presented with appendicitis, dropping 25.4%, from an average of 2030 patients (2016–2019) to 1516 in 2020. An even greater decrease of 33.8% was observed in pediatric patients (age <18). Overall, 77% of the 146 hospitals experienced a reduction in appendicitis admissions. There were no differences between years in percent of patients treated nonoperatively (P = 0.493) incidence of shock (P = 0.95), mortality (P = 0.24), or need for postoperative procedures (P = 0.81).

Conclusions:

Acute appendicitis presentations decreased significantly during the COVID-19 pandemic, while overall management and patient outcomes did not differ from previous years. Further research is needed focusing on putative explanations for decreased hospital presentations unrelated to COVID-19 infection and possible implications for surgical management of uncomplicated acute appendicitis.

Keywords: acute appendicitis, COVID-19, decreasing volumes, multicenter study
Multistakeholder Collaborative Effort to Enhance Long-Term Follow-Up in the Abdominal Core Health Quality Collaborative
Authors: Poulose Benjamin K. , Schwartzman Harriet , Huang Li-Ching , Chouinard Scott , Coelho Donald , Macarios David , Master Sundeep , Rosen Michael J.
Published: March 2021

Objective:

To determine the effectiveness of a clinical call center in performing focused long-term patient reported outcome (PRO)-based follow-up for ventral hernia patients in routine practice.

Background:

Long-term follow-up remains the mainstay of assessing quality of care in hernia management. Achieving acceptable rates of long-term follow-up outside of clinical trials in the routine care of patients has been very difficult to achieve.

Methods:

A prospective quality improvement intervention using a clinical call center in 1000 random patients eligible for long-term (1 year or greater) follow-up after ventral hernia repair in the Abdominal Core Health Quality Collaborative was performed. The primary outcome measure was the proportion of patients with successfully completed PRO-based long-term follow-up.

Results:

Between 2013 and 2017, the baseline long-term follow-up PRO completion rate was 2167/13,950 (15.5%). For the Focus on Follow-Up initiative, 890 patients were eligible for contact; a completion rate of 450/890 (50.6%, P < 0.001) was achieved.

Conclusions:

Clinical call center-based patient contact can greatly facilitate the completion of PROs utilized for long-term follow-up in ventral hernia repair. This has important implications for quality improvement programs and postmarket device surveillance.
Targeting the IL-2 inducible kinase in melanoma; a phase 2 study of ibrutinib in systemic treatment-refractory distant metastatic cutaneous melanoma: preclinical rationale, biology, and clinical activity (NCI9922)
Authors: Moschos Stergios J. , Eroglu Zeynep , Khushalani Nikhil I. , Kendra Kari L. , Ansstas George , In Gino K. , Wang Peng , Liu Glenn , Collichio Frances A. , Googe Paul B. , Carson Craig C. , McKinnon Karen , Wang Hsing-Hui , Nikolaishvilli-Feinberg Nana , Ivanova Anastasia , Arrowood Christy C. , Garrett-Mead Nancy , Conway Kathleen C. , Edmiston Sharon N. , Ollila David W. , Serody Jonathan S. , Thomas Nancy E. , Ivy S. Percy , Agrawal Lokesh , Dees Elizabeth C. , Abbruzzese James L.
Published: March 2021

Background

IL-2 inducible kinase (ITK) is highly expressed in metastatic melanomas and its inhibition suppresses melanoma cell proliferation. We hypothesize that ibrutinib has a direct antitumor effect in melanoma cell lines and that treatment of metastatic melanomas with ibrutinib induces antitumor responses.

Methods

We assessed the ibrutinib effect on melanoma cell proliferation, apoptosis, and motility. Patients with metastatic melanoma refractory to PD-1 and MAPK inhibitors (if BRAFV600-mutant) were treated with ibrutinib, 840 mg PO QD, as part of a phase II clinical trial (clinicaltrials.gov NCT02581930).

Results

Melanoma cell lines frequently express ITK, YES1, and EGFR. Ibrutinib suppressed cell motility and proliferation in most cell lines. Eighteen patients (13 male; median age 63.5 years, range 37–82; 12 with ipilimumab resistance) were enrolled. The most frequent side effects were fatigue (61%), anorexia (50%), hyponatremia (28%), nausea, and vomiting (22% each). No antitumor responses were seen. At a median follow-up of 6 months (0.3–35.8 months), the median progression-free survival was 1.3 months (range 0.2–5.5 months). Fifteen patients were discontinued from the study due to progression, and 14 patients had died from metastatic melanoma. All archived tumors expressed ITK, 41% had no expression of p16 and PTEN, and 61% had absent tumor-infiltrating lymphocytes (TILs). Ibrutinib significantly suppressed proliferating (Ki67+) CD19+ peripheral blood mononuclear cells and had no significant effect on other lymphocyte subsets.

Conclusion

Ibrutinib did not induce any meaningful clinical benefit. ITK expression may not be clinically relevant. Treatment-refractory metastatic melanomas have other fundamental defects (i.e. absent PTEN and p16 expression, absent TILs) that may contribute to an adverse prognosis.
Association of Self-Paced Physical and Cognitive Activities Across the First Week Postconcussion With Symptom Resolution in Youth
Authors: Yang Jingzhen , Yeates Keith Owen , Shi Junxin , Sullivan Lindsay , Xun Pengcheng , Taylor H. Gerry , Tiso Michael , Pommering Thomas , MacDonald James , Cohen Daniel M. , Hautmann Amanda , Asa Nicole , Singichetti Bhavna , Bailey Matthew , Lu Zhong-lin
Published: March 2021

Objective:

To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth.

Setting:

Emergency department or concussion clinics.

Participants:

Youth aged 11 to 17 years with physician-confirmed concussion.

Design:

Prospective cohort with repeated measures.

Main Measure(s):

Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively.

Results:

A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27).

Conclusion:

Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.
Total keratometry for determination of true corneal power after myopic small-incision lenticule extraction
Authors: Lischke Roman , Mayer Wolfgang J. , Feucht Nikolaus , Siedlecki Jakob , Wiltfang Rainer , Kook Daniel , Priglinger Siegfried G. , Luft Nikolaus
Published: March 2021

Purpose:

To gauge the value of total keratometry (TK) to estimate corneal power change in eyes that underwent small-incision lenticule extraction (SMILE) for treatment of myopia or myopic astigmatism.

Setting:

Department of Ophthalmology, Ludwig-Maximilians-University, and SMILE Eyes Clinic Munich Airport, Munich, Germany.

Design:

Prospective cross-sectional trial.

Methods:

A total of 40 eyes of 40 patients who had undergone myopic SMILE were enrolled in this prospective study. Total corneal refractive power (TCRP; Pentacam HR) and TK (IOLMaster 700, Carl Zeiss Meditec AG) values were compared with the clinical history method (CHM). The surgically induced changes in TCRP (ΔTCRP) and TK (ΔTK) were also compared with the changes in spherical equivalent on the corneal plane (ΔSEco).

Results:

Of the 40 eyes analyzed, the correlation between TK and CHM (R
2 = 0.91, P < .001) was stronger than that between TCRP and CHM (R
2 = 0.87, P < .001). When compared with the CHM, TCRP underestimated corneal power by a mean relative error of 0.59 diopter (D) and TK by 0.17 D. Linear regression analysis of ΔTCRP/ΔTK and the difference between preoperative and postoperative manifest refraction spherical equivalent at the corneal plane (ΔSEco) showed stronger correlation in ΔTK (R
2 = 0.88) than that in ΔTCRP (R
2 = 0.82).

Conclusions:

The findings endorse TK as an accurate measure for corneal power after myopic SMILE.
Accuracy of Vaginal pH Testing Before and After Addition of Sterile Saline
Authors: Bakir Sarah , Elas Diane , Stockdale Colleen K. , Zimmerman M. Bridget , Hardy-Fairbanks Abbey
Published: March 2021

Objective

Complaints of vaginal discharge are common, and vaginal pH is important diagnostically. Vaginal pH is measured either directly using pH paper or after wet mount analysis. This study aims to analyze whether a significant change in vaginal pH after saline addition exists.

Methods

This prospective, diagnostic accuracy study included 97 persons with a vagina between the ages of 18–80 years who received care at an academic center. Two samples of vaginal discharge were collected, with pH measured by direct application to pH paper and after wet prep analysis. Outcome measurements included pH measurements and demographic variables collected from electronic medical records. A Wilcoxon signed-rank test was performed, with a p value less than .05 considered significant. It was hypothesized that addition of saline to vaginal discharge increases pH artificially.

Results

Primary outcome included pH difference between both samples. Sixty four (66%) of the subjects had a pH difference of 0.50 and 3 (3%) had a difference of 1.0. Twenty nine (30%) of the subjects had no difference. One subject (1%) had a decrease of 0.50 in pH after saline. Reproductive age and nonuse of vaginal medications were significantly associated with a pH difference of 0.50 or higher after saline addition. Of the demographic variables, reproductive age and nonuse of vaginal medications within the past week or the day of collection were associated with a significant pH difference after saline addition (79%, p = .025; 79%, p = .001; 76%, p = .002, respectively).

Conclusions

It may be reasonable to subtract 0.50 from final pH reading in patients of reproductive age and in those who have not used vaginal medications recently.
Knowledge, Attitudes, and Experiences of Anal Cancer and Anal Cancer Screening Among a Clinical Sample of Hispanic Women
Authors: Ortiz Ana P. , García-Camacho Sandra I. , Ramos-Cartagena Jeslie M. , Colón-López Vivian , Estremera-Rodríguez Lianeris M. , Berríos-Toledo Kyara M. , Romaguera Josefina
Published: March 2021

Objective

Anal cancer screening has been recommended for women with lower genital tract neoplasia, lupus, Crohn disease, HIV, and/or organ transplantation recipients. This study described and compared knowledge, attitudes, and experiences related to anal cancer and anal cancer screening between women at high risk for anal cancer and their counterparts.

Methods

This is a cross-sectional study within colposcopy and gynecology oncology clinics in Puerto Rico; 278 women 21 years or older and with prior diagnosis of gynecological neoplasia completed an interviewer-administered questionnaire. Women were categorized according to their medical history as being high risk or non–high risk for anal cancer. The high-risk group included women with a history of lower genital tract neoplasia, lupus, Crohn disease, HIV, and/or organ transplantation.

Results

Overall, 40.7% of the study population were at high risk for developing anal cancer. History of anal cancer screening was low among high-risk and non–high-risk women (11.5% vs 5.6%, p > .05). Less than 1% of all women reported to have had a high-resolution anoscopy. Most women (87.6%) had little knowledge about anal Pap test but were willing to have one if their doctors recommended it (96.5%). No major differences in knowledge, attitudes, or screening history were observed between high-risk and non–high-risk women.

Conclusions

Although experts do not recommend routine anal cancer screening for the general population, they do recommend it for women within certain high-risk groups. Study findings highlight the importance of increasing education and awareness of anal cancer among high-risk patients and physicians, to promote better preventive methods, achieve early detection, and improve disease outcomes.
Follow-up After Loop Electrosurgical Excision of Cervical Intraepithelial Neoplasia: The Use of Combined Cytology and Human Papillomavirus Testing
Authors: Anderson Kristi Bøgh , Frandsen Anna Poulsgaard , Sandal Preben , Søgaard-Andersen Erik
Published: March 2021

Objectives

The aims of the study were to investigate how many women after 1 or 2 follow-up examinations, based on combined cervical cytology and human papillomavirus (HPV) testing, could finish posttreatment follow-up and continue with the general screening program and to determine the 5-year risk of recurrence in this group.

Methods

This is a prospective observational study that includes women, who underwent loop electrosurgical excision procedure (LEEP) in the North Denmark Region, from January 1, 2012, to May 31, 2014. All included women had histologically verified diagnosis of high-grade cervical intraepithelial neoplasia (CIN 2+) or adenocarcinoma in situ (AIS) before LEEP and posttreatment follow-up with cervical cytology and HPV combination testing. Study period was until October 2019.

Results

Totally, 563 women were included in the study. After finishing the posttreatment follow-up, 439 (78%) could continue to the general screening program and 362 of them had a screening during the study period. Six women (1.7%) had either cervical dysplasia and/or HPV infection in the cervical screening, and of these, 3 (0.8%) had high-grade dysplasia corresponding to CIN 2. None was diagnosed with CIN 3, AIS, or invasive carcinoma. One hundred twenty-one women (36%) chose to be screened sooner than recommended in the national guidelines.

Conclusions

Human papillomavirus and cytology combination test after LEEP allows women, irrespective of margin status, safely to continue with the general screening program after a short posttreatment follow-up period. Improved information is mandatory to reduce “opportunistic” screening after finishing posttreatment follow-up.
A Novel Capacitive Cochlear Implant Electrode Array Sensing System to Discriminate Failure Patterns
Authors: Hou Lei , Du Xinli , Boulgouris Nikolaos , Coulson Chris , Irving Richard , Begg Philip , Brett Peter
Published: March 2021

Objectives:

The research is to propose a sensing system to ensure the electrode array being correctly placed inside the cochlea. Instead of applying extra sensors to the array, the capacitive information from multiple points of the array is gathered and analyzed to determine the state and behavior of the electrode array.

Methods:

The sensing system measures electrode bipolar capacitances between multiple pairs of electrodes during the insertion. The principal component analysis (PCA) method is then applied to analysis the recorded data to discriminate insertion patterns.

Results:

In total, 384 capacitance profiles from electrode pair (1, 2), and electrode pair (15, 16) were analyzed and compared. In an account of both the electrode pairs, the threshold distance was examined to be d = 1.99 at the average comparison type. The experiment results showed the success rate is over 80% to identify buckling during the insertion on a 2D cochlear model.

Conclusion:

This early-stage investigation shows great potential compared with the current practice, which does not provide any feedback to surgeons. The system demonstrates the feasibility of a sensing method for auto-reoccupation electrodes behavior, and it will help surgeons to avoid misplacement of the electrode array inside the cochlea.
Adaptation of the Standardized Hearing Outcomes Scattergram to Hearing Preservation in Cochlear Implantation
Authors: Perkins Elizabeth L. , Manzoor Nauman F. , Haynes David S. , O’Malley Matthew , Gifford René , Rivas Alejandro
Published: March 2021

Objective:

Encourage adaptation of a standardized format for reporting hearing preservation outcomes in cochlear implantation (CI).

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

One hundred seventy-eight postlingually deafened adults with bilateral SNHL and a preoperative low-frequency pure-tone average (LFPTA) 80 dB HL or better at 125, 250, and 500 Hz in the ear to be implanted.

Interventions:

Subjects underwent unilateral CI from 2013 to 2019 at a large referral center. Pre- versus postoperative LPFTA was used to generate a scattergram.

Main Outcomes Measures:

Pre- versus postoperative activation LPFTA, percentage of patients fit with electric and acoustic stimulation, scattergram plot.

Results:

Average postoperative LFPTA was 68.6 dB HL (range 18–68) compared with 48.7 dB (range 5–80), preoperatively. At activation, the average LFPTA shift at CI activation was 20.5 dB HL (range 0–60) and 83.5% (n = 137) patients had hearing preserved, of whom 41.6% were fit with electric and acoustic stimulation throughout the study period. The scattergram successfully illustrates the distribution and number of patients with their respective audiometric outcomes.

Conclusions:

The scattergram developed for reporting hearing outcomes in clinical trials is highly adaptable to reporting hearing preservation results in cochlear implant surgery. It represents a transparent and accessible option for reporting outcomes that can be used as a consistent format to allow for interstudy comparison and future meta-analysis.
Does Sinusitis Affect Lateralization of a Tuning Fork Weber Test?
Authors: Ungar Omer J. , Wengier Anat , Cavel Oren , Abergel Avraham , Safadi Ahmad , Warshavsky Anton , Horowitz Gilad , Handzel Ophir , Oron Yahav , Shilo Shahaf
Published: March 2021

Objective:

To describe the effect of sinusitis on Weber test lateralization which normally lateralizes toward the ear of a conductive hearing loss and away from the ear of a sensorineural hearing loss; to investigate whether the presence of an extra-aural condition might affect Weber test results.

Study Design:

Descriptive study.

Setting:

Tertiary referral center.

Subjects and Methods:

Consecutive adult patients with maxillary and/or frontal sinusitis were included (study group), as well as patients with normal sinus structure and function (control group) were enrolled between February and September 2019. Presence or absence of paranasal disease and middle ear aeration was confirmed by computerized tomography. Subjects with otologic condition were excluded. The physical examinations, tympanograms, and audiograms were unremarkable. The Weber test consisted of 512, 1024, and 2048 Hz tuning forks that were applied on the central incisors and frontal midline, and lateralization patterns were compared with the extent of paranasal pathology.

Results:

There were 44 participants (M:F=26:18), age 19 to 63 years (average 51). The cohort included 39 patients with sinusitis, affecting the frontal and/or maxillary sinus(es), as well as 5 controls without evidence of paranasal disease. There was a match between the extent of paranasal disease and the results of all 3 Weber test frequencies in 35 patients (80%). Omission of the 2048 and 1024 Hz tuning forks from the analysis yielded a match in 40 (91%) and 43 (98%) patients, respectively. No Weber test lateralized to the nondiseased sinus in any subject. Weber test lateralization was observed in 11% of patients, after the sinonasal pathology was successfully addressed.

Conclusion:

Weber test lateralization in the absence of aural pathology may be explained by asymmetry related to paranasal disease and may alert to its presence.
Comparison of Medial Underlay and Lateral Underlay Endoscopic Type I Tympanoplasty for Anterior Perforations of the Tympanic Membrane
Authors: Choi Sung-Won , Kim Hwabin , Na Han-Seul , Lee Jung Woo , Lee Seokhwan , Oh Se-Joon , Kong Soo-Keun
Published: March 2021

Objectives:

To compare the outcomes of medial and lateral underlay endoscopic type I tympanoplasty for anterior tympanic membrane (TM) perforations.

Study Design:

Retrospective chart review.

Setting:

Tertiary care academic referral center.

Patients:

Patients who were diagnosed with either chronic otitis media with dry and stable anterior TM perforations or traumatic anterior TM perforations and underwent endoscopic type I tympanoplasty between 2017 and 2019.

Interventions:

Medial or lateral underlay type I endoscopic tympanoplasty.

Main Outcome Measures:

Patient demographics, size, and location of TM perforation, graft success rate, and hearing outcome.

Results:

Of the 170 patients, 68 and 102 patients underwent the medial and lateral underlay techniques, respectively. Patient demographics were not significantly different between groups, except the middle ear mucosa status. Graft success rates were significantly different between groups regardless of the perforation size (85.3 and 95.1%, p < 0.001). The lateral underlay group had a significantly better outcome (p < 0.001) when anterior superior quadrant TM perforation was included than the medial underlay group (p = 0.552). Hearing outcomes did not significantly differ between groups, but a significant audiological improvement was observed in both groups (p < 0.05).

Conclusion:

Lateral underlay type I endoscopic tympanoplasty can be challenging as it requires dissection of the malleus. However, the lateral underlay group had a high graft success rate without sensorineural hearing loss in the repair of anterior TM perforations. Thus, lateral underlay type I endoscopic tympanoplasty should be considered for repairing anterior TM perforations, especially when the anterior superior quadrant is involved.
Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization
Authors: Badulak Jenelle , Antonini M. Velia , Stead Christine M. , Shekerdemian Lara , Raman Lakshmi , Paden Matthew L. , Agerstrand Cara , Bartlett Robert H. , Barrett Nicholas , Combes Alain , Lorusso Roberto , Mueller Thomas , Ogino Mark T. , Peek Giles , Pellegrino Vincent , Rabie Ahmed A. , Salazar Leonardo , Schmidt Matthieu , Shekar Kiran , MacLaren Graeme , Brodie Daniel
Published: March 2021

Disclaimer:

This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19–related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19–related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.