bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenoma detection rate is not influenced by the time of day in computer-aided detection colonoscopy
Authors: Lei Shan , Wang Zhilan , Tu Mengtian , Liu Peixi , Lei Lei , Xiao Xun , Zhou GuanYu , Liu Xiaogang , Li Liangping , Wang Pu
Published: December 2020

Because of endoscopist fatigue, the time of colonoscopy have been shown to influence adenoma detection rate (ADR). Computer-aided detection (CADe) provides simultaneous visual alerts on polyps during colonoscopy and thus to increase adenoma detection rate. This is attributable to the strengthening of endoscopists diagnostic level and alleviation of fatigue. The aim of the study was to investigate whether CADe colonoscopy could eliminate the influence of the afternoon fatigue on ADR.

We retrospectively analyzed the recorded data of patients who were performed CADe colonoscopy from September 2017 to February 2019 in Endoscopy Center of Sichuan Provincial People's Hospital. Patients demographic as well as baseline data recorded during colonoscopy were used for the analysis. Morning colonoscopy was defined as colonoscopic procedures starting between 8:00 am and 12:00 noon. Afternoon colonoscopy was defined as procedures starting at 2:00 pm and thereafter. The primary outcome was ADR. Univariate analysis and multivariate regression analysis were also performed.

A total of 484 CADe colonoscopies were performed by 4 endoscopists in the study. The overall polyp detection rate was 52% and overall ADR was 35.5%. The mean number of adenomas detected per colonoscopy (0.62 vs 0.61, P > .05) and ADR (0.36 vs 0.35, P > .05) were similar in the am and pm group. Multivariable analysis shows that the ADR of CADe colonoscopy was influenced by the age (P < .001), gender (P = .004) and withdrawal time (P < .001), no correlation was found regarding bowel preparation (P = .993) and endoscopist experience (P = .804).

CADe colonoscopy could eliminate the influence of the afternoon fatigue on ADR. The ADR during CADe colonoscopy is significantly affected by age, gender and withdrawal time.
Metronomic capecitabine as maintenance treatment after first line induction with XELOX for metastatic colorectal cancer patients
Authors: Geng Rui , Wang Gang , Qiu Lei , Liu Bing , Yang Fan , Zhang Jingyu , Miao Yongchang
Published: December 2020

Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.

In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.

Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25–6.07) months vs 3.98 (95%CI 3.71–4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04–0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38–25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23–23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21–1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.

Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.
Acupoint catgut embedding for obesity
Authors: Huang Wei , Chen Xia , Zhang Yanji , Wang Lihua , Wang Jiajie , Zhang Yingrong , Wei Dan , Zhou Zhongyu
Published: December 2020

Background:

Obesity is a chronic metabolic disease in which patients are overweight due to the excessive accumulation of fat in the body. As a subtype of acupuncture, catgut embedding at acupoints has increased in clinical application for obesity. The aim of this study is to evaluate the effectiveness and safety of acupoint catgut embedding therapy for simple obesity.

Methods and analysis:

Electronic searches of the Cochrane Library, PubMed, Springer Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-Fang Data (WANFANG), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP databases) will be performed. The Chinese Clinical Trial Registry Center and the ClinicalTrials.gov registry will also be searched for ongoing trials. Databases will be searched from inception to August 2020.Randomized controlled clinical trials (RCTs) will be included if acupoint catgut embedding was evaluated as the sole treatment (diet or exercise therapy as the control group will be allowed) for simple obesity. The primary outcomes will consist of the improvement rate and reduction in body weight (BW). The secondary outcomes will include body mass index (BMI), waist circumference (WC), fat percentage (F %) and adverse effects. Two reviewers will undertake the study selection, data extraction and assessments of study quality. After screening the studies, the quality of the included studies will be assessed according to the quality criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software.

Results:

According to the data of improvement rate and reduction in BW, BMI, WC, and F %, this study will provide an evidence-based review of acupoint catgut embedding therapy for simply.

Conclusions:

This systematic review will present the current evidence for acupoint catgut embedding therapy for obesity.

Ethics and dissemination:

Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.

Trial registration number:

INPLASY2020110045.
Adult split liver transplantation
Authors: Kong Lingxiang , Lv Tao , Yang Jian , Jiang Li , Yang Jiayin
Published: December 2020

Although pediatric split liver transplantation (SLT) has been proven safe and the waitlist mortality rate has been successfully reduced, the safety of adult SLT has not been confirmed.

Using 1:2 matching, 47 recipients who underwent adult SLT were matched to 94 of 743 recipients who underwent adult whole graft liver transplantation (WGLT). Eventually, 141 recipients were included in the case-control study. Subgroup analysis of 43 recipients in the SLT group was performed based on the presence of the middle hepatic vein (MHV) in the grafts.

No significant differences in 5-year survival (80.8% vs 81.6%, P = .465) were observed between the adult SLT and WGLT groups. However, compared to recipients in the WGLT group, those in the SLT group had more Clavien–Dindo grade III-V complications, longer hospitalization duration, and higher mortality within 45 days. Furthermore, on multivariate analysis, 45-day postoperative mortality in recipients in the SLT group was mainly affected by hyperbilirubinemia within postoperative day (POD) 7–14, surgery time, and intraoperative blood loss. Subgroup analysis showed no significant differences in hyperbilirubinemia within POD 7–14, complications, and survival rate between SLTMHV(+) and SLTMHV [−].

Adult SLT is safe and effective based on long-term survival rates; however, a reduction in the incidence of short-term complications is required. Non-obstructive hyperbilirubinemia within POD 7 to 14 is an independent predictor of short-term mortality after SLT.
A DNA methylation-associated nomogram predicts the overall survival of osteosarcoma
Authors: Shi Jun , Huang Daijuan , Zhang Gao , Zhao Feng , Yang Lin
Published: December 2020

Numerous reports have demonstrated that DNA methylation may be underlying prognostic biomarkers of cancer. However, few studies indicated that DNA methylation was independent biomarker for osteosarcoma prognosis. We aimed to discover and validate a novel DNA methylation signature for prediction of osteosarcoma patients’ overall survival (OS).

The DNA methylation data of osteosarcoma patients was researched from The Cancer Genome Atlas (TCGA) database. Overall, 80 samples with 485,577 DNA methylation sites were enrolled in our study. The 80 samples were randomly allocated into training dataset (first two-thirds) and validation dataset (remaining one-third). Initially, the univariate Cox proportional hazard analysis was performed in the training dataset to determine methylation sites significantly (P < .05) relevant to osteosarcoma patients’ OS as underlying indicators. Subsequently, the underlying indicators were employed to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis for further selecting the candidate methylation sites. Then, the selected candidate methylation sites were employed as covariates to perform multivariate Cox proportional hazard model for identifying the predictor of OS in osteosarcoma patients. The validation dataset was used to validate the predictive accuracy by receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis.

We discovered a 7-DNA methylation signature closely relevant to OS of osteosarcoma patients. AUC at 1, 3, 5 years in training dataset (0.951, 0.922, 0.925, respectively), testing dataset (0.952, 0.918, 0.925, respectively), and entire dataset (0.952, 0.968, 0.968, respectively). Suggesting high predictive values for OS of osteosarcoma patients. In addition, a methylation-associated nomogram suggested good predictive value and clinical application.

We discovered and validated a novel 7-DNA methylation-associated nomogram for predicting OS of osteosarcoma patients.
Background styles in systematic review articles are not related to the publication in high-impact-factor journals
Authors: Kataoka Yuki , Taito Shunsuke , Yamamoto-Kataoka Sachiko , Tsujimoto Yasushi , Yamazaki Hajime , Furukawa Toshi A.
Published: December 2020

Objectives:

To clarify the styles used in background sections of systematic reviews (SR) and to identify which styles if any were related to the publication in high-impact-factor (HIF) medical journals.

Method:

This was a cross-sectional study for original SR articles published in top 50 journals in MEDICINE, GENERAL & INTERNAL category in Journal Citation Reports 2018. We randomly included 90 articles from top 10 HIF journals and 90 from others, respectively. We conducted a content analysis to classify the background styles. We assessed the factors associated with the publication in HIF journals.

Results:

We found 6 categories. We defined 6 categories as follows: Update of prior SR, New in scope than prior SR, Higher quality than prior SR, Completely new SR, Limitations of primary studies only, and Not presenting unknown in prior SR or primary studies. All 6 categories were not related to the publication in HIF journals.

Conclusions:

We found 6 categories of styles in background sections of SR, none of which however were related to publication in HIF journals. SR authors may wish to use any of these categories to communicate the importance of their research questions.
Clinical efficacy of Qi Di laxative decoction in the treatment of functional constipation
Authors: Wang Jian-Fang , Sun Zhong-Mei , Li Jun-Xiang
Published: December 2020

Background:

Functional constipation (FC) is a common gastrointestinal disorder characterized by slow bowel movement and defecation difficulties, significantly impacting patients’ quality of life and exerting heavy financial burden to whole society. However, more than 50% FC patients are not completely satisfied with current therapies and alternative therapies are urgently required. Increasing evidences have demonstrated that traditional Chinese medicine has a good therapeutic effect on FC, which is well known for its multitarget and multimode effects on diverse diseases as well as less side effects. Furthermore, studies proved that Qi Di Laxative Decoction was an effective treatment for FC. Its safety and effectiveness should be verified by further studies.

Methods:

We will search the following electronic databases for randomized controlled trials to evaluate the clinical efficacy of Qi Di Laxative Decoction in treating FC: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to November 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses.

Results:

This proposed study will evaluate the clinical efficacy of Qi Di Laxative Decoction for patients with FC. The outcomes will include changes in FC relief and adverse effect.

Conclusion:

This proposed systematic review will evaluate the existing evidence on the clinical efficacy of Qi Di Laxative Decoction in treating FC.

Dissemination and ethics:

The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

OSF Registration Number:

DOI 10.17605/OSF.IO/M2ESR
The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome
Authors: Liu Zhimin , Song Ying , Xu Yuanfang , Wang Jing , Hu Hongyuan , Weng Yingchun
Published: December 2020

Background:

Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS.

Methods:

Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study.

Results:

This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals.

Conclusion:

The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease.

Ethics and dissemination:

In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics.

OSF Registration DOI:

10.17605/OSF.IO/8GW9M.
Comparison between open reduction and internal fixation and minimally invasive surgery in management of Sanders type II calcaneal fracture
Authors: Xue Dingshan , Lou Baozhen , Tan Rongrong , Yu Hongchang
Published: December 2020

Background:

The minimally invasive surgery possesses an essential and growing function in treating the calcaneal fractures, but the related literature on this topic is limited. For our study, the main purpose was to compare the early prognosis of a group of the patients with Sanders type II fracture of calcaneus treated via minimally invasive surgery and open reduction and internal fixation (ORIF).

Methods:

This is a prospective randomized controlled trial in the patients who suffer from displaced intra-articular calcaneal fractures. This current study was carried out in accordance with the guidelines of “CONSORT statement” for the randomized controlled studies. All patients were randomly assigned into 2 groups on the basis of a random number table, namely the minimally invasive treatment group and the ORIF group using conventional methods. Inclusion criteria included the followings: aged between 18 to 59 years old; closed and unilateral fracture; patients with displaced intra-articular calcaneal fracture (>2 mm) involving Sanders Type IIC and Type IIB; and patients have enough mental capacity to understand and answer questions in the evaluation scale. In the process of outpatient follow-up, the radiographs were taken at 1, 3, 6, and 12 months. The functional results involved the American Orthopaedic Foot and Ankle Score, Foot Function Index, and the pain score.

Conclusions:

This protocol will give us research directions in future work.

Trial registration:

This study protocol was registered in Research Registry (researchregistry6261).
Response evaluation after immunotherapy in NSCLC
Authors: Park Sohyun , Lee Youngjoo , Kim Tae-Sung , Kim Seok-ki , Han Ji-Youn
Published: December 2020

The present study aimed to evaluate the role of early F-18 2-deoxy-2-[fluorine-18] fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in non-small cell lung cancer patients undergoing immune checkpoint inhibitor (ICI) treatment.

Twenty-four non-small cell lung cancer patients who received nivolumab or pembrolizumab and underwent FDG PET/CT as an interim analysis after 2 or 3 cycles of ICI treatment were retrospectively enrolled. Tumor response was assessed using the PET Response Criteria in Solid Tumors 1.0 (PERCIST) and the European Organization for Research and Treatment of Cancer (EORTC) criteria after 2 or 3 cycles of ICI treatment (SCAN-1) and after an additional 2 cycles of ICI treatment (SCAN-2). The best overall response was determined by FDG PET/CT or chest CT at ≥ 3 months after therapy initiation, and the clinical benefit was investigated. progression-free survival was investigated, and its correlation with clinicopathologic and metabolic parameters was examined using a Cox multivariate proportional hazards model.

In the interim analysis, 4 patients achieved a complete metabolic response (CMR), 1 patient exhibited a partial metabolic response (PMR), and 14 patients had Progressive metabolic disease (PMD) according to the PERCIST and EORTC criteria. Four patients showed stable metabolic disease (SMD) according to the PERCIST criteria, and 2 patients showed different responses (i.e., PMR) according to the EORTC criteria. Patients with a CMR or PMR at SCAN-1 had a clinical benefit. Among the 4 patients with SMD at SCAN-1, only 1 experienced a clinical benefit regardless of the percent change in the peak standardized uptake value. Two patients with discordant response assessments between the PERCIST and EORTC criteria showed conflicting clinical benefits. Among the 14 patients with PMD, none experienced any clinical benefit. Only metabolic parameters were significant factors for predicting progression in the multivariate analysis (peak standardized uptake value and metabolic tumor volume, HRs of 1.18 and 1.00, respectively).

Based on early F-18 FDG PET/CT after ICI treatment, metabolic parameters could predict post-treatment progression. Responses after ICI treatment were correctly assessed in patients with a CMR, a PMR, and PMD, but patients with SMD required a meticulous follow-up because of varying clinical benefits.
Effectiveness comparisons of Chinese patent medicine on sciatica
Authors: An Hongqiang , Li Bing , Zhao Jifeng , Ao Zhijian , Zhong Xiaohui , Zhu Pengfei , Wu Jianlin
Published: December 2020

Background:

Sciatica is one of the common clinical diseases. Studies have proved the efficacy of Chinese patent medicine (CPM) in the treatment of sciatica, so far, there has not been a complete systematic review of its effectiveness and safety, and the comparative efficacy and safety of CPM have not been ranked. Therefore, it is necessary to evaluate the efficacy and safety of these CPM by means of systematic review and network meta-analysis (NMA), and to compare them in order.

Methods:

We will search PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, CBM and other databases for RCTs of CPM in the treatment of sciatica, (database established until December 30, 2020). In addition, we will manually search the “Pharmaceutical Information”, “National Essential Drug List”, “Chinese Pharmacopoeia”, etc. to inquire about drug instructions, and screen the market circulation and clinically commonly used CPM. We will use RevMan software, gemtc package, GeMTC software for statistical analysis, and draw the surface under cumulative ranking area (SUCRA) to predict the order of curative effect of treatment measures.

Results:

Our study will compare and evaluate the effectiveness of CPM in the treatment of sciatica, and rank different CPM. The outcome indicators will include clinical efficacy, pain degree, lumbar spine function and adverse events.

Conclusion:

Our research will provide support for clinical practice.

INPLASY registration number:

INPLASY2020110073.
Herbal medicine for cervicogenic dizziness
Authors: Oh Hyunjoo , Shin Seungwon , Lee Euiju
Published: December 2020

Background:

Herbal medicines are empirically used to treat cervicogenic dizziness. However, till date there have been no systematic review to evaluate the efficacy and safety of these medicines. Therefore, this study protocol describes the methods for evaluating the efficacy and safety of herbal medicine for cervicogenic dizziness.

Methods and analysis:

The following electronic academic databases will be searched up to December 2019 without language or publication status restrictions: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL), together with Korean, Chinese, and Japanese databases. Any randomized controlled trials related to herbal medicine for cervicogenic dizziness will be included. The functional outcomes and the vertebrobasilar artery hemodynamic states will be evaluated as primary outcomes. The total effective rate, hematological conditions, and adverse events will be assessed as secondary outcomes. Study selection, data extraction, quality assessment of studies, and qualitative evaluation of clinical evidence will be performed by 2 independent reviewers. The methodological quality of the included studies will be evaluated using a revised Cochrane risk-of-bias tool for randomized trials. The strength of evidence from the included data will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data synthesis will be performed as either a fixed-effects or a random-effects model using Review Manager software version 5.3. The results will be reported as a risk ratio for dichotomous outcomes and as a mean difference or standardized mean difference for continuous outcomes.

Ethics and dissemination:

No ethical approval is required since the individual clinical information of the patient is not used. The findings of this systematic review will be disseminated through the peer-reviewed publications or conference presentations.

Review Registry Unique Identifying Number:

reviewregistry1036.
Diagnosis of Schaaf-Yang syndrome in Korean children with developmental delay and hypotonia
Authors: Ahn Hyunji , Seo Go Hun , Oh Arum , Lee Yena , Keum Changwon , Heo Sun Hee , Kim Taeho , Choi Jeongmin , Kim Gu-Hwan , Ko Tae-Sung , Yum Mi-Sun , Lee Beom Hee , Choi In Hee
Published: December 2020

Schaaf-Yang syndrome (SYS) is a recently identified disorder caused by a loss-of-function mutation in a maternally imprinted gene, MAGEL2, at 15q11.2q13. Due to its extreme rarity and wide range of clinical severity, clinical suspicion is difficult for a physician. In the current study, its frequency among the Korean pediatric patients with developmental delay (DD) or intellectual disability (ID) was assessed. As the first report of Korean patients with SYS, our study aims to increase the awareness of this condition among the physicians taking care of the pediatric patients with DD/ID and hypotonia.

The patients diagnosed with SYS by whole-exome sequencing (WES) among the 460 Korean pediatric patients with DD/ID were included, and their clinical and molecular features were reviewed.

Four patients (0.9%) were diagnosed with SYS. Profound DD (4 patients), multiple anomalies including joint contractures and facial dysmorphism (4 patients), generalized hypotonia (3 patients), and severe respiratory difficulty requiring mechanical ventilation (3 patients) were noted in most cases, similar to those in previous reports. Sleep apnea (2 patients), autistic features (2 patients), a high grade of gastroesophageal reflux (1 patient), and seizures (1 patient) were found as well. A total of 3 different truncating MAGEL2 mutations were identified. A previously-reported mutation, to be the most common one, c.1996dupC, was found in 2 patients. The other 2 mutations, c.2217delC and c.3449_3450delTT were novel mutations. As MAGEL2 is maternally imprinted, 2 patients had inherited the MAGEL2 mutation from their respective healthy fathers.

SYS is an extremely rare cause of DD/ID. However, hypotonia, joint contractures, profound DD/ID and facial dysmorphism are the suggestive clinical features for SYS. As a maternally imprinted disorder, it should be reminded that SYS may be inherited in form of a mutation from a healthy father.
PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline
Authors: Tew William P. , Lacchetti Christina , Ellis Annie , Maxian Kathleen , Banerjee Susana , Bookman Michael , Jones Monica Brown , Lee Jung-Min , Lheureux Stéphanie , Liu Joyce F. , Moore Kathleen N. , Muller Carolyn , Rodriguez Patricia , Walsh Christine , Westin Shannon N. , Kohn Elise C.
Published: December 2020

(Abstracted from J Clin Oncol 2020;38:3468–3493)

Despite advances in diagnosis and therapy, an individual with ovaries carries an approximate 1 in 108 lifetime chance to die due to ovarian cancer (OC). Primary therapy typically involves surgical cytoreduction and a combination regimen of platinum and a taxane.
Organ Donation Authorization After Brain Death Among Patients Admitted to PICUs in the United States, 2009–2018*
Authors: Spaulding Alicen B. , Zagel Alicia L. , Cutler Gretchen J. , Brown Angela , Zier Judith L.
Published: December 2020

Objectives:

To identify trends in and factors associated with pediatric organ donation authorization after brain death.

Design:

Retrospective cohort study of data from Virtual Pediatric Systems, LLC (Los Angeles, CA).

Setting:

Data from 123 PICUs reporting to Virtual Pediatric Systems from 2009 to 2018.

Patients:

Patients less than 19 years old eligible for organ donation after brain death.

Measurements and Main Results:

Of 2,777 eligible patients, 1,935 (70%) were authorized for organ donation; the authorization rate remained unchanged over time (ptrend = 0.22). In a multivariable logistic regression model, hospitalizations lasting greater than 7 days had lower odds of authorization (adjusted odds ratio, 0.5; p < 0.001 vs ≤ 1 d) and White patients had higher odds than other race/ethnicity groups. Authorization was higher for trauma-related encounters (adjusted odds ratio, 1.5; p < 0.001) and when donation was discussed with an organ procurement organization coordinator (adjusted odds ratio, 1.7; p < 0.001). Of 123 hospitals, 35 (28%) met or exceeded a 75% organ donation authorization target threshold; these hospitals more often had an organ procurement organization coordinator discussing organ donation (85% vs 72% of encounters; p < 0.001), but no difference was observed by PICU bed size.

Conclusions:

Organ donation authorization after brain death among PICU patients was associated with length of stay, race/ethnicity, and trauma-related encounter, and authorization rates were higher when an organ procurement organization coordinator was involved in the donation discussion. This study identified factors that could inform initiatives to improve the authorization process and increase pediatric organ donation rates.
The origins of G12P[6] rotavirus strains detected in Lebanon
Authors: Reslan Lina , Mishra Nischay , Finianos Marc , Zakka Kimberley , Azakir Amanda , Guo Cheng , Thakka Riddhi , Dbaibo Ghassan , Lipkin W. Ian , Zaraket Hassan
Published: December 2020

The G12 rotaviruses are an increasingly important cause of severe diarrhoea in infants and young children worldwide. Seven human G12P[6] rotavirus strains were detected in stool samples from children hospitalized with gastroenteritis in Lebanon during a 2011–2013 surveillance study. Complete genomes of these strains were sequenced using VirCapSeq-VERT, a capture-based high-throughput viral-sequencing method, and further characterized based on phylogenetic analyses with global RVA and vaccine strains. Based on the complete genomic analysis, all Lebanese G12 strains were found to have Wa-like genetic backbone G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Phylogenetically, these strains fell into two clusters where one of them might have emerged from Southeast Asian strains and the second one seems to have a mixed backbone between North American and Southeast Asian strains. Further analysis of these strains revealed high antigenic variability compared to available vaccine strains. To our knowledge, this is the first report on the complete genome-based characterization of G12P[6] emerging in Lebanon. Additional studies will provide important insights into the evolutionary dynamics of G12 rotaviruses spreading in Asia.
Effect of mutations in capsid shell protein on the assembly of BmCPV virus-like particles
Authors: Ren Feifei , Swevers Luc , Lu Qiuyuan , Zhao Yongchao , Yan Jiming , Li Haiyun , Sun Jingchen
Published: December 2020

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a typical single-layer capsid dsRNA virus belonging to the genus Cypovirus in the family Reoviridae. The results of cryo-electron microscopy showed that the BmCPV capsid consists of 60 asymmetric units, and each asymmetric unit contains one turret protein (TP), two large protrusion proteins (LPP) and two capsid shell proteins (CSP). CSP has the ability to self-assemble into virus-like particles (VLPs), and the small protrusion domain (SPD) in CSP may play an essential role in the assembly of viral capsids. In this study, three critical amino acid sites, D828, S829 and V945, in the SPD were efficiently mutated (point mutation) based on the principle of PCR circular mutagenesis. Moreover, a multi-gene expression system, Ac-MultiBac baculovirus, was used to produce eight different recombinant VLPs in vitro. Transmission electron microscopy showed that the single site and double site mutations had little effect on the efficiency and morphology of the assembly of VLPs. Still, the simultaneous mutation of the three sites had a significant impact. The experimental results demonstrate that the SPD of CSP plays an essential role in assembly of the viral capsid, which lays the foundation for further analysis of the molecular and structural mechanism of BmCPV capsid assembly.
Understanding the outcomes of COVID-19 – does the current model of an acute respiratory infection really fit?
Authors: Simmonds Peter , Williams Sarah , Harvala Heli
Published: December 2020

Although coronavirus disease 2019 (COVID-19) is regarded as an acute, resolving infection followed by the development of protective immunity, recent systematic literature review documents evidence for often highly prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory and faecal samples, periodic recurrence of PCR positivity in a substantial proportion of individuals and increasingly documented instances of reinfection associated with a lack of protective immunity. This pattern of infection is quite distinct from the acute/resolving nature of other human pathogenic respiratory viruses, such as influenza A virus and respiratory syncytial virus. Prolonged shedding of SARS-CoV-2 furthermore occurs irrespective of disease severity or development of virus-neutralizing antibodies. SARS-CoV-2 possesses an intensely structured RNA genome, an attribute shared with other human and veterinary coronaviruses and with other mammalian RNA viruses such as hepatitis C virus. These are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit for example in the susceptible–infected–recovered (SIR) model used for epidemic prediction, should be rigorously re-evaluated.
DksA coordinates bile-mediated regulation of virulence-associated phenotypes in type three secretion system-positive Vibrio cholerae
Authors: Sofia Madeline K. , Dziejman Michelle
Published: December 2020

In order to cause disease, pathogenic strains of

Vibrio cholerae

rely on intricate regulatory networks to orchestrate the transition between their native aquatic environment and the human host. For example, bacteria in a nutrient-starved environment undergo a metabolic shift called the stringent response, which is mediated by the alarmone ppGpp and an RNA-polymerase binding transcriptional factor, DksA. In O1 serogroup strains of V. cholerae, which use the toxin co-regulated pilus (TCP) and cholera toxin (CT) as primary virulence factors, DksA was reported to have additional functions as a mediator of virulence gene expression. However, little is known about the regulatory networks coordinating virulence phenotypes in pathogenic strains that use TCP/CT-independent virulence mechanisms. We therefore investigated whether functions of DksA outside of the stringent response are conserved in type three secretion system (T3SS)-positive

V. cholerae

. In using the T3SS-positive clinically isolated O39 serogroup strain AM-19226, we observed an increase in dksA expression in the presence of bile at 37 °C. However, DksA was not required for wild-type levels of T3SS structural gene expression, or for colonization in vivo. Rather, data indicate that DksA positively regulates the expression of master regulators in the motility hierarchy. Interestingly, the ΔdksA strain forms a less robust biofilm than the WT parent strain at both 30 and 37 °C. We also found that DksA regulates the expression of hapR, encoding a major regulator of biofilm formation and protease expression. Athough DksA does not appear to modulate T3SS virulence factor expression, its activity is integrated into existing regulatory networks governing virulence-related phenotypes. Strain variations therefore may take advantage of conserved ancestral proteins to expand regulons responding to in vivo signals and thus coordinate multiple phenotypes important for infection.
Simulation-Based Study on the COVID-19 Airborne Transmission in a Restaurant
Authors: Liu Han , He Sida , Shen Lian , Hong Jiarong
Published: December 2020

COVID-19 has shown a high potential of transmission via virus-carrying aerosols as supported by growing evidence. However, detailed investigations that draw direct links between aerosol transport and virus infection are still lacking. To fill in the gap, we conducted a systematic computational fluid dynamics (CFD)-based investigation of indoor air flow and the associated aerosol transport in a restaurant setting, where likely cases of airborne infection of COVID-19 caused by asymptomatic individuals were widely reported by the media. We employed an advanced in-house large eddy simulation (LES) solver and other cutting-edge numerical methods to resolve complex indoor processes simultaneously, including turbulence, flow–aerosol interplay, thermal effect, and the filtration effect by air conditioners. Using the aerosol exposure index derived from the simulation, we are able to provide a spatial map of the airborne infection risk under different settings. Our results have shown a remarkable direct linkage between regions of high aerosol exposure index and the reported infection patterns in the restaurant, providing strong support to the airborne transmission occurring in this widely-reported incidence. Using flow structure analysis and reverse-time tracing of aerosol trajectories, we are able to further pinpoint the influence of environmental parameters on the infection risks and highlight the needs for more effective preventive measures, e.g., placement of shielding according to the local flow patterns. Our research, thus, has demonstrated the capability and value of high-fidelity CFD tools for airborne infection risk assessment and the development of effective preventive measures.
A rapid, high-sensitivity SARS-CoV-2 nucleocapsid immunoassay to aid diagnosis of acute COVID-19 at the point of care
Authors: Drain Paul K. , Ampajwala Madhavi , Chappel Christopher , Gvozden Andre B. , Hoppers Melanie , Wang Melody , Rosen Robert , Young Stephen , Zissman Edward , Montano Michalina
Published: December 2020

Background

The LumiraDx SARS-CoV-2 antigen test, which uses a high-sensitivity, microfluidic immunoassay to detect the nucleocapsid protein of SARS-CoV-2, was evaluated for diagnosing acute COVID-19 in adults and children across point-of-care settings.

Methods

Two paired anterior nasal swabs or two paired nasopharyngeal swabs were collected from each participant. Swabs were tested by the LumiraDx SARS-CoV-2 antigen test and compared with real-time PCR (rt-PCR; Roche cobas 6800 platform). Positive- and negative predictive values and likelihood ratios were calculated. Results stratified based on gender, age, duration of symptoms, and rt-PCR cycle threshold.

Results

Out of the 512 participants, aged 0-90 years, of this prospective validation study, 414 (81%) were symptomatic for COVID-19 and 123 (24%) swabs were positive for SARS-CoV-2 based on rt-PCR testing. Compared with rt-PCR, the 12-minute swab test had 97.6% sensitivity and 96.6% specificity within 12 days of symptom onset, representing the period of infectivity. All (100%) samples detected within 33 rt-PCR cycles were also identified using the antigen test. Results were consistent across age and gender. Despite being performed by minimally trained healthcare workers, the user error rate of the test system was 1%.

Conclusion

The rapid high-sensitivity assay using nasopharyngeal or anterior nasal sampling may offer significant improvements for diagnosing acute SARS-CoV-2 infection in clinic- and community-based settings.

A 12-minute nasal swab test detects 97.6% of COVID-19 infections, compared to gold standard real-time PCR testing, up to 12 days following symptom onset using a microfluidic immunoassay for SARS-CoV-2 nucleocapsid protein.
Changes in cardiovascular disease monitoring in English primary care during the COVID-19 pandemic: an observational cohort study
Authors: Bankhead Clare R , Lay-Flurrie Sarah , Nicholson Brian D , Sheppard James P , Gale Chris P , Liyanage Harshana , McGagh Dylan , Minchin Mark , Perera Rafael , Sherlock Julian , Smith Margaret , Thomas Nicholas PB , Drakesmith Cynthia Wright , de Lusignan Simon , Hobbs FD Richard
Published: December 2020

Objective

To quantify the impact and recovery in cardiovascular disease monitoring in primary care associated with the first COVID-19 lockdown.

Design

Retrospective nationwide primary care cohort study, utilising data from 1st January 2018 to 27th September 2020.

Setting

We extracted primary care electronic health records data from 514 primary care practices in England contributing to the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID). These practices were representative of English primary care across urban and non-urban practices.

Participants

The ORCHID database included 6,157,327 active patients during the study period, and 13,938,390 patient years of observation (final date of follow-up 27th September 2020). The mean (SD) age was 38±24 years, 49.4% were male and the majority were of white ethnicity (65% [21.9% had unknown ethnicity])

Exposure

The primary exposure was the first national lockdown in the UK, starting on 23rd March 2020.

Main outcome measures

Records of cholesterol, blood pressure, HbA1c and International Normalised Ratio (INR) measurement derived from coded entries in the primary care electronic health record.

Results

Rates of cholesterol, blood pressure, HbA1c and INR recording dropped by 23-87% in the week following the first UK national lockdown, compared with the previous week. The largest decline was seen in cholesterol (IRR 0.13, 95% CI 0.11 to 0.15) and smallest for INR (IRR 0.77, 95% CI 0.72 to 0.81).

Following the immediate drop, rates of recorded tests increased on average by 5-9% per week until 27th September 2020. However, the number of recorded measures remained below that expected for the time of year, reaching 51.8% (95% CI 51.8 to 51.9%) for blood pressure, 63.7%, (95% CI 63.7% to 63.8%) for cholesterol measurement and 70.3% (95% CI 70.2% to 70.4%) for HbA1c. Rates of INR recording declined throughout the previous two years, a trend that continued after lockdown. There were no differences in the times series trends based on sex, age, ethnicity or deprivation.

Conclusions

Cardiovascular disease monitoring in English primary care declined substantially from the time of the first UK lockdown. Despite a consistent recovery in activity, there is still a substantial shortfall in the numbers of recorded measurements to those expected. Strategies are required to ensure cardiovascular disease monitoring is maintained during the COVID-19 pandemic.
Social Media Study of Public Opinions on Potential COVID-19 Vaccines: Informing Dissent, Disparities, and Dissemination
Authors: Lyu Hanjia , Wang Junda , Wu Wei , Duong Viet , Zhang Xiyang , Dye Timothy D. , Luo Jiebo
Published: December 2020

The current development of vaccines for SARS-CoV-2 is unprecedented. Little is known, however, about the nuanced public opinions on the coming vaccines. We adopt a human-guided machine learning framework (using more than 40,000 rigorously selected tweets from more than 20,000 distinct Twitter users) to capture public opinions on the potential vaccines for SARS-CoV-2, classifying them into three groups: pro-vaccine, vaccine-hesitant, and anti-vaccine. We aggregate opinions at the state and country levels, and find that the major changes in the percentages of different opinion groups roughly correspond to the major pandemic-related events. Interestingly, the percentage of the pro-vaccine group is lower in the Southeast part of the United States. Using multinomial logistic regression, we compare demographics, social capital, income, religious status, political affiliations, geo-locations, sentiment of personal pandemic experience and non-pandemic experience, and county-level pandemic severity perception of these three groups to investigate the scope and causes of public opinions on vaccines. We find that socioeconomically disadvantaged groups are more likely to hold polarized opinions on potential COVID-19 vaccines. The anti-vaccine opinion is the strongest among the people who have the worst personal pandemic experience. Next, by conducting counterfactual analyses, we find that the U.S. public is most concerned about the safety, effectiveness, and political issues regarding potential vaccines for COVID-19, and improving personal pandemic experience increases the vaccine acceptance level. We believe this is the first large-scale social media-based study to analyze public opinions on potential COVID-19 vaccines that can inform more effective vaccine distribution policies and strategies.
Screening for high amounts of SARS-CoV-2 identifies pre-symptomatic subjects among healthy healthcare workers
Authors: Dillner Joakim , Elfström K. Miriam , Blomqvist Jonas , Engstrand Lars , Uhlén Mathias , Eklund Carina , Boulund Fredrik , Lagheden Camilla , Hamsten Marica , Nordqvist-Kleppe Sara , Seifert Maike , Hellström Cecilia , Olofsson Jennie , Andersson Eni , Falk August Jernbom , Bergström Sofia , Hultin Emilie , Pin Elisa , Pimenoff Ville N. , Hassan Sadaf , Månberg Anna , Nilsson Peter , Hedhammar My , Hober Sophia , Mattsson Johan , Mühr Laila Sara Arroyo , Lundgren Kalle Conneryd
Published: December 2020

Background

Pre-symptomatic subjects are spreaders of SARS-CoV-2 infection, and strategies that could identify these subjects, particularly in hospital settings, are needed.

Methods

We tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the screening results to sick leave records and examined the association between screening results and past or future sick leave using multinomial logistic regression.

Results

We found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11·97 (CI 95% 6·29-22·80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6·31 (4·38-9·08)). Only 2·5% of employees were SARS-CoV-2 positive while 10·5% were positive by serology and 1·2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1·06 (95% CI, 0·71-1·57)), but virus-positive subjects had a 7·23 fold (95% CI, 4·52-11·57)) increased risk for sick leave within two weeks post testing.

Conclusions

Screening of asymptomatic healthcare workers for high amounts of SARS-CoV-2 virus using Ct values will identify pre-symptomatic subjects who will develop disease in the next few weeks. Identification of potentially contagious, pre-symptomatic subjects is likely critical for protecting patients and healthcare workers.

Main point

Healthy healthcare workers with low amounts of SARS-CoV-2 nucleic acids will previously have had the disease. Presence of a high amount of SARS-CoV-2 nucleic acids predicts future symptomatic disease.