bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heptad stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core
Authors: Marchetti Chiara , Vaglietti Serena , Rizzo Francesca , Di Nardo Giovanna , Colnaghi Luca , Ghirardi Mirella , Fiumara Ferdinando 
Published: November 2021

Abstract
The fusion of the SARS-CoV-2 virus with cells, a key event in the pathogenesis of Covid-19, depends on the assembly of a six-helix fusion core (FC) formed by portions of the spike protein heptad repeats (HRs) 1 and 2. Despite the critical role in regulating infectivity, its distinctive features, origin, and evolution are scarcely understood. Thus, we undertook a structure-guided positional and compositional analysis of the SARS-CoV-2 FC, in comparison with FCs of related viruses, tracing its origin and ongoing evolution. We found that clustered amino acid substitutions within HR1, distinguishing SARS-CoV-2 from SARS-CoV-1, enhance local heptad stereotypy and increase sharply the FC serine-to-glutamine (S/Q) ratio, determining a neat alternate layering of S-rich and Q-rich subdomains along the post-fusion structure. Strikingly, SARS-CoV-2 ranks among viruses with the highest FC S/Q ratio, together with highly syncytiogenic respiratory pathogens (RSV, NDV), whereas MERS-Cov, HIV, and Ebola viruses display low ratios, and this feature reflects onto S/Q segregation and H-bonding patterns. Our evolutionary analyses revealed that the SARS-CoV-2 FC occurs in other SARS-CoV-1-like Sarbecoviruses identified since 2005 in Hong Kong and adjacent regions, tracing its origin to &gt;50 years ago with a recombination-driven spread. Finally, current mutational trends show that the FC is varying especially in the FC1 evolutionary hotspot. These findings establish a novel analytical framework illuminating the sequence/structure evolution of the SARS-CoV-2 FC, tracing its long history within Sarbecoviruses, and may help rationalize the evolution of the fusion machinery in emerging pathogens and the design of novel therapeutic fusion inhibitors.
Precise Conclusions Regarding the Influence of Age Stereotypes Require Precise Operationalizations Thereof
Authors: Rudolph Cort W , Friedrich Jack C , Zacher Hannes 
Published: November 2021

Abstract
Murphy and DeNisi (2021) offer that there is scant evidence that age-based stereotypes affect personnel judgments and decisions. However, this conclusion is drawn from evidence that assumes that biased judgments follow from stereotypes, rather than from evidence suggesting that stereotypes precede biased judgments. In this reply to Murphy and DeNisi (2021), we point out the flaws in this argument and offer the counterpoint that we know very little about the influence that age-based stereotypes have for such judgments and decisions. Moreover, given this lack of evidence, we argue that any conclusions regarding the influence of age-based stereotypes in this regard are, at best, premature.
Updates on treatment options in aspirin exacerbated respiratory disease
Authors: Ramos Courtney L. , Woessner Katharine M. 
Published: November 2021

Purpose of review
The aim is to describe why this review is timely and relevant. Acetylsalicylic acid exacerbated respiratory disease (AERD) is a clinically significant disease affecting approximately 7% of all asthmatics or around 1,400,000 persons in the United States alone. A large portion of these patients remain undiagnosed. This review summarizes up to date knowledge on the pathophysiology, treatment opinions and provides an expert opinion on how to approach the AERD patient.

Recent findings
Findings describe the main themes in the literature covered by the article. Review of the current knowledge in terms of the key cells, cytokines/chemokines contributing to the acquired disease state of AERD. It also provides clinical approach toward the AERD patient with regards to current treatment options.

Summary
Summary describes the implications of the findings for clinical practice or research. This is an up-to-date review of the current literature, with insight into how to approach the management of an AERD patient.
Surgical Management of Ocular Cicatricial Pemphigoid in a Pediatric Patient
Authors: Ollero Rafael , Soldevila Anna , Fideliz de la Paz María , Martínez-Grau Ainhoa 
Published: November 2021

Purpose:
The purpose of the report was to describe the first successful tarsal fracture surgery in a 1-year-old boy diagnosed with cicatricial ocular pemphigoid whose visual and psychomotor development were notably limited.

Methods:
We present the case of a 1-year-old boy diagnosed with mucous membrane pemphigoid by biopsy who was treated with rituximab (375 mg/m2 intravenous infusion at 2-week interval administered twice) and stable with oral dapsone (2 mg·kg−1·d−1). His eyelid cicatricial entropion and trichiasis in both eyes prevented him from opening his eyes, impeding visual development. After 1 year of clinical stability, we performed a tarsal fracture procedure in both eyes to restore eyelid anatomy and functionality, with the aim to prevent an inflammatory reaction, administrating intravenous dexamethasone before and after surgery.

Results:
The intervention was successfully performed without postoperative complications. Excellent anatomic and functional results allowed him to develop normally in his daily life the first week after surgery. He is currently taking oral dapsone (2 mg·kg−1·d−1) as a maintenance treatment to stop the progression of the disease.

Conclusions:
Tarsal fracture surgery may be considered part of the treatment in pediatric patients with stable ocular cicatricial pemphigoid presenting with severe entropion and trichiasis.
The Quality of Otology and Neurotology Research in Otology Journals
Authors: O’ Byrne Lisa , Copperthwaite Amy , Rente Madalena , Fenton John E. , Coelho Daniel H. 
Published: November 2021

Objective:
To establish the level of evidence and publishing trends in otology-specific journals over a 20-year period.

Design:
Retrospective analysis.

Methods:
The three O/N specific journals with the highest Eigenfactor scores were identified. All articles published in the years 1998, 2008, and 2018 were reviewed and level of evidence (LoE) based on standards set by the Oxford Centres for Evidence Based Medicine was assigned by two independent reviewers. One way analysis of variance and 95% bootstrap sensitivity analysis were performed.

Results:
A total of 1,062 studies were published over 20 years, of these 809 (76.2%) were eligible for inclusion in the present study. The average number of publications per year increased over time. The average LoE improved significantly over the total interval (–0.235, p = 0.027, [CI –0.45, –0.019]), however did not between 1998 and 2008 (p = 0.111) or between 2008 and 2018 (p = 1). When looking at just LoE 1 or 2, the number and percentage of higher quality papers improves over time—48/158 (30.4%) in 1998, rising to 94/250 (37.6%) in 2008, and 158/401 (39.4%) in 2008.

Conclusions:
Over the past two decades there has been an overall increase in the quantity and quality (as measured by LoE) of publications in O/N-specific journals. In general, quality of O/N studies is slightly better in O/N-specific journals compared with general OHNS journals. However, there are still improvements to be had in the proportion of high-evidence publications, as they still number less than half of all total publications in the subspecialty.
Using Functional Outcomes to Predict Vestibular Loss in Children
Authors: Janky Kristen L. , Thomas Megan LA. , Patterson Jessie , Givens Diane 
Published: November 2021

Objective:
The purpose of this study was to determine: (1) the relationship between vestibular loss severity and functional performance, (2) which functional performance outcomes best predict vestibular loss, and (3) which vestibular rate sensors (canals vs. otoliths) provide the most weighting during different functional measures.

Study Design:
Prospective.

Setting:
Tertiary referral center.

Patients:
Fifty-seven children with normal hearing (mean age: 12.3 years, 32 males) and 55 children with cochlear implants (mean age 12.8 years, 29 males).

Intervention:
Diagnostic.

Main Outcome Measures:
Video head impulse test, cervical vestibular evoked myogenic potential (cVEMP), ocular VEMP (oVEMP), single leg stance, Standing Balance Test, active and passive dynamic visual acuity, and the balance subtest of the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2).

Results:
Performance worsened as vestibular loss severity worsened for all functional outcomes except the standing balance test conditions 1 and 2. The best outcomes for classifying children with vestibular loss were the single leg stance (cut-off criterion: 5 seconds; sensitivity and specificity of 88% and 86%) and the BOT-2 balance subtest (cut-off criterion of 27.5 points; sensitivity and specificity of 88% and 88%). Average horizontal canal vHIT gain was a significant predictor of all functional outcomes while neither corrected cVEMP amplitude nor oVEMP amplitude predicted performance.

Conclusion:
Functional performance declines as vestibular loss severity worsens. Single leg stance is fast and efficient for predicting vestibular loss in school age children. Average horizontal canal vHIT best predicts functional performance; if using a tiered approach, horizontal canal vHIT should be completed first.
Using the Gensini score to estimate severity of STEMI, NSTEMI, unstable angina, and anginal syndrome
Authors: Charach Lior , Blatt Alex , Jonas Michael , Teodorovitz Nick , Haberman Dan , Gendelman Gera , Grosskopf Itamar , George Jacob , Charach Gideon 
Published: November 2021

Abstract
Gensini score (GS) provides valuable information on severity and prognosis of coronary artery disease (CAD).
To evaluate the relationship between the severity of CAD determined by the GS and relation to ST-elevation myocardial infarction, non-ST segment elevation myocardial infarction (NSTEMI), unstable angina pectoris, chest pain (suspected angina syndrome on admission) and risk-factors for CAD and predictors of severity.
Observational cross-sectional study.
Consecutive patients who underwent clinically-indicated coronary angiography for ST-elevation myocardial infarction, NSTEMI, unstable angina pectoris or chest pain were enrolled.
Among 600 patients, 417 (average age 67.8 ± 12.2 years) had CAD–related symptoms. Mean GS was 66.7 ± 63.8. Patients presenting with NSTEMI had the highest GS (81.3 ± 42.3; P < .001) Regression analysis of risk-factors showed the best association of GS with multivessel disease and coronary artery bypass graft. Regression analysis of medications showed that clopidogrel, had the best association with low GS.
GS correlated with the severity of CAD, multivessel disease, coronary artery bypass graft, and troponin. GS was related to the cardiovascular risk-factors of diabetes, hypertension, and high-density cholesterol.
Polymyositis in a child with thalassemia after hematopoietic stem cell transplantation
Authors: Tan Yonghong , Lin Jinzong , Hong Xiuli , Lu Jingyuan , Lu Quanyi 
Published: November 2021

Abstract

Rationale:
Polymyositis (PM) is a rare neuromuscular phenotype of chronic graft-versus-host disease (cGVHD). Although glucocorticoids have been shown to be effective in the treatment of PM, most people experience poor treatment response and poor prognosis.

Patient concerns:
A six-year-old boy with thalassemia received allogeneic hematopoietic stem cell transplantation (HSCT) and consequently developed sudden myasthenia of limbs 17 months after the transplant.

Diagnoses:
Medical history, current symptoms, laboratory examinations, and imaging findings of the patient indicated cGVHD complicated with PM.

Interventions:
He was then given high-dose corticosteroid therapy, including tacrolimus, ruxolitinib, and rituximab.

Outcomes:
Twenty-three months after transplantation, creatine kinase levels returned to normal range, and the MRI showed that the original muscle edema signal was significantly improved. The patient's muscle weakness continued to improve, and his overall condition was good.

Lessons:
This report suggests that glucocorticoids combined with immunosuppressants may be effective against polymyositis. Rituximab and ruxolitinib may be a good choice in treating polymyositis.
Comparison of therapeutic effects of different acupuncture and moxibustion therapies on constipation after stroke treatment
Authors: Shang Jingwen , He Yongyang , Wang Rui , Xu Yifan , Xu Jia 
Published: November 2021

AbstractBackground:Constipation is a common complication after stroke, which seriously affects patients’ quality of life and recovery. Many evidences show that acupuncture and moxibustion therapy has advantages in the treatment of constipation after stroke. But different types of acupuncture and moxibustion have different effects, and there is no research to prove which one is more effective.Methods:According to the search strategy, we will retrieve the randomized controlled studies of acupuncture and moxibustion in the treatment of constipation after stroke from China Knowledge Network, Wanfang, VIP, China Biomedical medicine, PubMed, Embase, Web of Science, and The Cochrane Library databases. The retrieval time was from the establishment of the database to July 2021. Studies will be screened according to inclusion and exclusion criteria, and the quality of the studies will be assessed using the Cochrane Risk Bias Assessment Tool. All data analyses will be performed using Revman 5.4, Gemtc 0.14.3, and Stata 14.0. Finally, we will evaluate the strength of evidence using the Grading of Recommendations Assessment, Development, and Evaluation method.Results:In this study, the efficacy of different acupuncture and moxibustion therapies in the treatment of constipation after stroke will be evaluated by evaluating defecation frequency, stool property score, constipation symptom score, quality of life score, adverse reactions, etc.Conclusions:This study will provide reliable evidence-based evidence for selecting the best acupuncture and moxibustion therapy for constipation after stroke.
Favorable colorectal cancer mortality-to-incidence ratios in countries with high expenditures on health and development index
Authors: Wang Chi-Chih , Sung Wen-Wei , Yan Pei-Yi , Ko Po-Yun , Tsai Ming-Chang 
Published: November 2021

Abstract

Background:
Global variation in the incidence and outcomes of colorectal cancer (CRC) is associated with many factors, among which screening policies and early treatment play substantial roles. However, screening programs and intense treatment are expensive and require good health care systems. For CRC, no clear association has yet been established between clinical outcomes and health care disparities.

Method:
We used the mortality-to-incidence ratio (MIR) of CRC as a measure of clinical outcomes for comparison with the Human Development Index (HDI), current health expenditure (CHE), and current health expenditure as a percentage of gross domestic product (CHE/GDP) using linear regression analyses. We included 171 countries based on data from the GLOBOCAN 2018 database.

Results:
We found that the regions with the lowest MIRs for CRC are Oceania and North America. A significant correlation was observed between incidence, mortality and HDI, CHE, and CHE/GDP among the countries enrolled. Furthermore, lower MIRs of CRC significantly correlated with higher HDI, CHE, and CHE/GDP (P < 0.001, P < 0.001, and P < 0.001, respectively).

Conclusion
: CRC MIRs tend to be most favorable in countries with high health care expenditures and a high HDI.
Growth arrest-specific 5 (GAS5) insertion/deletion polymorphism and cancer susceptibility in Asian populations
Authors: Gao Gan , Liu Chunming , Li Xueli , Guan Xiaoyong , Yang Xingxing , Qin Peixu 
Published: November 2021

Abstract

Background:
Previous studies have reported the association of an insertion/deletion (Ins/Del) polymorphism (rs145204276 AGGCA/-) in the promoter region of growth arrest-specific 5 (GAS5) with the risk of cancer, such as breast cancer, gastric cancer, and hepatocellular carcinoma. However, the results are still controversial. We aimed to clarify the association of GAS5 rs145204276 polymorphism with cancer risk by meta-analysis.

Methods:
PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and Cochrane Library were searched for studies concerning GAS5 and cancer published up to November 25, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate cancer risk.

Results:
A total of 12 case–control studies with 8729 cases and 10,807 controls were included in this meta-analysis. We found that the GAS5 rs145204276 polymorphism was not significantly associated with cancer risk (Del vs Ins: OR = 0.96, 95% CI: 0.81–1.13; Del/Del vs Ins/Ins: OR = 1.00, 95% CI: 0.70–1.43; Ins/Del vs Ins/Ins: OR = 0.92, 95% CI: 0.78–1.08; Ins/Del and Del/Del vs Ins/Ins: OR = 0.93, 95% CI: 0.76–1.13; Del/Del vs Ins/Del and Ins/Ins: OR = 1.04, 95% CI: 0.78–1.38). In the stratified analyses, significant effects on gastric cancer were found (Del vs Ins: OR = 0.79, 95% CI: 0.72–0.86; Del/Del vs Ins/Ins: OR = 0.65, 95% CI: 0.52–0.82; Ins/Del vs Ins/Ins: OR = 0.76, 95% CI: 0.68–0.86; Ins/Del + Del/Del vs Ins/Ins: OR = 0.74, 95% CI: 0.66–0.83; Del/Del vs Ins/Ins + Ins/Del: OR = 0.74, 95% CI: 0.59–0.91).

Conclusion:
Our meta-analysis showed that GAS5 rs145204276 polymorphisms were not related to overall cancer risk. However, the GAS5 rs145204276 polymorphism may be a protective factor for gastric cancer in the stratification analyses.
Patient-reported outcomes after operative versus nonoperative treatment of pediatric lateral humeral condyle fractures
Authors: Ikwuezunma Ijezie A. , Suresh Krishna V. , Nhan Derek T. , Bryant Barry R. , Kotian Ronak N. , Lee R. Jay 
Published: November 2021

Abstract
Lateral humeral condyle fractures in children are treated with several approaches, yet it is unclear which has the best treatment outcomes. We hypothesized that functional outcomes would be equivalent between treatment types, reduction approaches, and fixation types. Our purpose was to assess patient-reported outcomes and complications by treatment type (operative versus nonoperative), reduction approach (open versus percutaneous), and fixation type (cannulated screws versus Kirschner wires).
We retrospectively reviewed data from acute lateral humeral condyle fractures treated at our level-1 pediatric trauma center from 2008 to 2017. Patients were included if they were 8 years or older and had completed clinical follow-up. Fractures were categorized by fracture severity as mild (<2-mm displacement), moderate (isolated, 2- to 5-mm displacement), or severe (isolated, >5-mm displacement or >2-mm displacement with concomitant elbow dislocation or other elbow fracture). We extracted data on patient age, sex, treatment type, reduction approach, fixation type, patient-reported outcomes (shortened Disabilities of the Arm, Shoulder, and Hand and Patient Reported Outcome Measurement Information System upper extremity), treatment complications, and follow-up duration. Patients in the operative versus nonoperative group and across fracture severity subgroups did not differ significantly by age, sex, or follow-up duration. Bivariate analysis was performed to determine whether outcomes differed by intervention. Alpha = 0.05.
No differences were observed in patient-reported outcomes between operative versus nonoperative groups for the mild and severe fracture subgroups. No differences were observed between approach (open versus percutaneous) or instrumentation (cannulated screw versus Kirschner wire fixation) for any outcome measure within the operative group. Patients whose fractures were stabilized with screws versus wires had significantly higher rates of return to the operating room (94% versus 8.3%, P < .001). The overall complication rate for our cohort was low, with no differences by treatment type or fracture severity.
In our cohort, patient-reported outcomes were similar across fracture severity categories, irrespective of treatment or fixation type. Patients who underwent internal fixation with cannulated screws experienced significantly higher rates of return to the operating room compared with those treated with Kirschner wires but otherwise had similar complication rates and patient-reported outcomes.

Level of Evidence: 3
Molecular evaluation of mutations in acute myeloid leukemia patients from Turkey
Authors: Merdin Alparslan , Dal Mehmet Sinan , Kizil Çakar Merih , Bahsi Taha , Düzkale Neslihan , Yildiz Jale , Bakirtaş Mehmet , Başçi Semih , Darçin Tahir , Şahin Derya , Tetik Ayşegül , Uncu Ulu Bahar , İskender Dicle , Yiğenoğlu Tuğçe Nur , Altuntaş Fevzi 
Published: November 2021

Abstract
Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.
This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.
It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.
Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.
Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway
Authors: Wang Guangying , Shen Dayue , Zhang Xilan , Ferrini Monica G. , Li Yuanping , Liao Hui 
Published: November 2021

Abstract

Background:
Erectile dysfunction is a disease commonly caused by diabetes mellitus (DMED) and cavernous nerve injury (CNIED). Bioinformatics analyses including differentially expressed genes (DEGs), enriched functions and pathways (EFPs), and protein-protein interaction (PPI) networks were carried out in DMED and CNIED rats in this study. The critical biomarkers that may intervene in nitric oxide synthase (NOS, predominantly nNOS, ancillary eNOS, and iNOS)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway, an important mechanism in erectile dysfunction treatment, were then explored for potential clinical applications.

Methods:
GSE2457 and GSE31247 were downloaded. Their DEGs with a |logFC (fold change)| > 0 were screened out. Database for Annotation, Visualization and Integrated Discovery (DAVID) online database was used to analyze the EFPs in Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes networks based on down-regulated and up-regulated DEGs respectively. PPI analysis of 2 datasets was performed in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. Interactions with an average score greater than 0.9 were chosen as the cutoff for statistical significance.

Results:
From a total of 1710 DEGs in GSE2457, 772 were down-regulated and 938 were up-regulated, in contrast to the 836 DEGs in GSE31247, from which 508 were down-regulated and 328 were up-regulated. The 25 common EFPs such as aging and response to hormone were identified in both models. PPI results showed that the first 10 hub genes in DMED were all different from those in CNIED.

Conclusions:
The intervention of iNOS with the hub gene complement component 3 in DMED and the aging process in both DMED and CNIED deserves attention.