bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric analysis of acute pancreatitis in Web of Science database based on CiteSpace software
Authors: Sun Wenjie , Huang Pinxian , Song Hualing , Feng Dianxu
Published: December 2020

Objectives:

Recent years have witnessed some controversial viewpoints in clinical and basic research, which exert a great influence on the research trend of acute pancreatitis (AP). We aimed to analyze the literature on AP by metrology, co-occurrence, co-citation, and visualization, and to explore the research status and trend in this field in the past 5 years.

Methods:

The relevant literature collected in Web of Science Core Collection (WoSCC) database from 2015 to 2019 was searched using “acute pancreatitis” as the title word, and the co-occurrence analysis of authors, institutions, countries, and keywords was carried out by using CiteSpace V. On this basis, the keywords were clustered and analyzed by using VOSviewer 1.6.8 and Carrot 2 software, and a visual map was drawn.

Results:

A total of 2035 articles were included, with an average annual volume of more than 400. The high-yield authors were mainly Chinese, among which Li WQ was the most prominent. Most of these articles were from universities and institutions of high-yielding countries including China, the United States, and India. The main sources of journals were professional journals, among which Pancreas and Pancreatology have the most literature collection volume (both over 100), including clinical and basic research. Among the funds, the National Natural Science Foundation of China and NIH were the main 2 sponsors. Disciplinary attributes involved multiple subjects such as gastroenterology, internal medicine, and surgery. Keyword co-occurrence and clustering results showed that the classification, mortality, and risk factors of AP were still more concerned, and the research trend of this disease was the molecular mechanism of the severity of AP.

Conclusions:

CiteSpace can be used to analyze the knowledge graph of AP, to show its development status initially and intuitively, and to provide a reference for topic content and its further development.
Arthroscopy versus nonoperative treatment of symptomatic femoroacetabular impingement syndrome
Authors: Kim Chul-Ho , Moon Jun-Ki , Yoon Jae Youn , Lee Sunhyung , Kim Won Jun , Kim Han Soul , Lee Soong Joon , Yoon Pil Whan
Published: December 2020

Background:

Presently, hip arthroscopy is a widely adopted surgical intervention for the treatment of femoroacetabular impingement (FAI). However, there is insufficient evidence regarding which between arthroscopy and nonoperative treatment is more optimal for symptomatic FAI.

Methods:

MEDLINE, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that compared arthroscopy and nonoperative interventions for FAI treatment from inception to August 4, 2020. We included studies that directly compared surgical and nonsurgical treatment for symptomatic FAI and excluded those that did not use arthroscopic treatment as a surgical technique and studies performed on patients with concomitant diagnoses instead of pure FAI. We compared the following clinical outcome scores at 6 and 12 months of follow-up: International Hip Outcome Tool 33 (iHOT-33), hip outcome score (HOS), EuroQol-visual analog scale (EQ-VAS), modified Harris hip score (mHHS), and nonarthritic hip score (NAHS).

Results:

Five studies totaling 838 patients were included in the qualitative and quantitative synthesis; 382 patients underwent hip arthroscopy, and 456 patients were treated by nonoperative interventions. At 6 months of follow-up, there were no statistically significant differences in iHOT-33 ratings (mean difference [MD] = 7.92, P = .15), HOS (MD of HOS-ADL = 5.15, P = .26 and MD of HOS-Sports = 2.65, P = .79, respectively), and EQ-VAS (MD = 1.22, P = .76) between the 2 treatment strategies. At 12 months of follow-up, the arthroscopy group had a greater mean improvement in iHOT-33 score than the conservative treatment group (MD = 8.42, P = .002), but there was no difference between the groups in terms of mHHS rating (MD = −0.24, P = .83) and NAHS (MD = −2.08, P = .09).

Conclusion:

Despite arthroscopy being associated with significantly superior iHOT-33 scores after 12 months of follow-up, we were unable to discern the difference between the treatment strategies using other scoring methods, such as HOS, EQ-VAS, mHHS, and NAHS. Further studies will be needed to conclusively determine if 1 strategy is superior to the other for treating FAI.
Effect and safety of Chinese patent medicine capsules for recurrent angina pectoris after percutaneous coronary intervention
Authors: Sun Yize , Wang Zheyi , Wang Chao , Tang Zhuoran , Shi Jinyu , Zhao Haibin
Published: December 2020

Introduction:

Recurrent angina pectoris after percutaneous coronary intervention (PCI) is a common clinical syndrome, which seriously reduces the quality of life and health of patients, increases medical costs, and causes the risk of cardiogenic death. The efficacy of various western medicine improving angina symptoms has not been fully confirmed at the moment, whereas Chinese patent medicine capsules (CPMC) have been generally used in clinical practice due to the therapeutic efficacy and safety. This study evaluates the efficacy and safety of CPMC for stable angina after PCI, designed to provide more evidence for clinical treatment.

Methods:

This protocol was based on the previous reporting items. We will search 3 English databases (PubMed, Excerpta Medica Database, and the Cochrane Library) and 3 Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and Chinese Biomedicine) until January 2020. RCTs to evaluate the efficacy and safety of CPMC for recurrent stable angina pectoris after PCI will be included. The primary outcome will be assessed by major adverse cardiovascular events and angina attack frequency. We will use the criteria provided by Cochrane risk of bias tool for quality evaluation and risk assessment, and use the Revman 5.3 for meta-analysis.

Ethics and Dissemination:

Ethical approval is not required for systematic review and meta-analysis. The results of this review will be disseminated in a peer-review journal.

PROSPERO registration number:

CRD42020164005.
Bringing prevost's sign into the third dimension: Artificial intelligence estimation of conjugate gaze adjusted length (CGAL) and correlation with acute ischemic stroke
Authors: Maresky Hillel S. , Rootman Joseph M. , Klar Miriam M. , Levitt Max , Kossar Alexander P. , Zucker David , Glazier Michael , Kalmanovich-Avnery Shani , Aviv Richard , Ertl-Wagner Birgit , Tal Sigal
Published: December 2020

Conjugate gaze deviation is associated with acute ischemic stroke (AIS), although previously only measured on a 2D plane. The current study evaluates 3D imaging efficacy to assess conjugate gaze deviation and correlate direction and strength of deviation to neuro-clinical findings.

A retrospective analysis of 519 patients who had CT scans for suspected AIS at our institution. Direction and angle of eye deviation were calculated based on 2D axial images. Volumetric reconstruction of CT scans allowed for calculation of 3D conjugate gaze adjusted length (CGAL). Angle, direction, and vector strength of both 2D and 3D scans were calculated by an artificial intelligence algorithm and tested for agreement with hemispheric ischemia location. CGAL measurements were correlated to NIHSS scores. Follow up MRI data was used to evaluate the sensitivity and specificity of CGAL in the identification of AIS.

The final analysis included 122 patients. A strong agreement was found between 3D gaze direction and hemispheric ischemia location. CGAL measurements were highly correlated with NIHSS score (r = .72, P = .01). A CGAL >0.25, >0.28, and >0.35 exhibited a sensitivity of 91%, 86%, and 82% and specificity of 66%, 89%, and 89%, respectively, in AIS identification. A CGAL >0.28 has the best sensitivity-specificity balance in the identification of AIS. A CGAL >0.25 has the highest sensitivity.

Given CED's correlation with NIHSS score a 1/4 deviation in the ipsilateral direction is a sensitive ancillary radiographic sign to assist radiologists in making a correct diagnosis even when not presented with full clinical data.
Contraceptive and reproductive health practices of unmarried women globally, 1999 to 2018
Authors: Wang Meng-yao , Temmerman Marleen , Zhang Wei-hong , Fan Yu , Mu Yi , Mo Si-ping , Zheng Ai , Li Jin-ke
Published: December 2020

Background:

Premarital sex practices and contraceptive prevalence rate (CPR) among unmarried women worldwide remain unclear, even though unmarried women tend to have multiple sex partners over time, which makes their sexual behaviors particularly important to the sexual and reproductive health of society more broadly.

Methods:

We searched the MEDLINE, PubMed, and Google Scholar databases for relevant articles published between January 1, 1999 and December 31, 2018. Data on prevalence of premarital sexual intercourse, use of highly prevalent contraceptive methods, as well as CPR overall and at first sexual intercourse were extracted and estimated using a DerSimonian– Laird random effects model.

Results:

Of the 3918 articles identified, 37 covering 19 countries were included. The estimated overall prevalence of premarital sexual intercourse was 41.9% (95%CI 34.2–49.6%). Pooled CPR was 57.0% (95%CI 44.3–69.8%) overall and 57.6% (95% CI 39.5– 75.6%) at first intercourse. The overall prevalence of condom use was 51.2% (95%CI 42.7–59.7%), followed by oral contraceptives (20.5%, 95%CI 13.7–27.3%), withdrawal (12.7%, 95%CI 9.4–15.9%), and rhythm (12.1%, 95%CI 6.7–17.4%).

Conclusion:

The findings of this global study indicate worrying trends in unprotected intercourse and contraceptive practices, suggesting the need for greater attention and resources aimed at educating unmarried adolescent women about sexual and reproductive health.

Systematic review registration number:

CRD42019132736.
Gemcitabine, cisplatin, and dexamethasone and ifosfamide, carboplatin, and etoposide regimens have similar efficacy as salvage treatment for relapsed/refractory aggressive lymphoma
Authors: Mi Mi , Zhang Caijiao , Liu Zijian , Wang Ye , Li Juan , Zhang Liling
Published: December 2020

In this study, our aim was to compare the efficacy and toxicity profiles of gemcitabine, cisplatin, and dexamethasone (GDP) and ifosfamide, carboplatin, and etoposide (ICE) regimens in the salvage treatment of relapsed/refractory lymphoma. A total of 110 patients with refractory/relapsed classical Hodgkin lymphoma (n = 22) or non-Hodgkin lymphoma (n = 88) who received GDP or ICE salvage regimens from January 2011 to July 2018 were retrospectively analyzed. Of the 110 patients, 50 patients received GDP, and 60 patients received ICE. The response could be evaluated in all patients. In the GDP group, 30 (60.0%) patients achieved overall response rate (ORR), and in the ICE group, the ORR was 56.6%. Of the classical Hodgkin lymphoma patients, the ORR were 72.8% and 54.6% in the GDP and ICE groups, respectively. Of the non-Hodgkin lymphoma patients, the ORR were 56.4% and 57.1% in the GDP and ICE groups, respectively. Grade I-II toxicity occurred in 16 (32.0%) patients in the GDP group and 18 patients (30.0%) in the ICE group; 14 (28.0%) patients had Grade III-IV toxicity in the GDP group, as did 20 (33.3%) patients in the ICE group. As a result, both GDP and ICE regimens are suitable for the treatment of recurrent/refractory lymphoma. The overall adverse reactions of both regimens are acceptable.
The association study of Apolipoprotein E polymorphisms and chronic obstructive pulmonary disease in the Chinese population
Authors: Zhang Yuan , Li Xiao-hui , Zhou Yu-tian , Xiang Lu , Xiao Meng , Guo Jian-shu , Zhang Jing-wei , Chen Guo
Published: December 2020

Chronic obstructive pulmonary disease (COPD) patients have increased cardiovascular morbidity and mortality. Apolipoprotein E (ApoE) is involved in chronic inflammation which is the common characteristic of emphysema and cardiovascular disease. ApoE polymorphisms are associated with cardiovascular disorders and atherosclerosis. There is no report about the association between ApoE polymorphism and COPD.

A total of 480 COPD patients and 322 controls who were unrelated Chinese Han individuals were enrolled. Rs429358 and rs7412 were genotyped and the associations between ApoE polymorphisms and COPD risk were analyzed by logistic regression analysis. Online software SHEsis were applied to perform linkage disequilibrium (LD) and haplotypes analysis. The interactions of ApoE and environmental factor on COPD susceptibility was analyzed by software MDR3.0.2.

No significant association was found between rs429358, rs7412 and COPD under different genetic models. Rs429358 and smoking formed the best model in the MDR analysis. The frequency of E2/E2 phenotype was the lowest in 2 groups. E3/E3 was the most common phenotype, accounting for 69.8% of COPD patients and 68.9% of controls. No statistically difference was identified between the cases and controls under different phenotypes.

This was the first genetic association study between ApoE and COPD. No positive association was found in the Chinese Han population. Rs429358 and smoking status existed significant interaction, indicating that both of ApoE and smoking may be involved in the development of COPD disease.
Unicompartmental knee replacement and high tibial osteotomy for medial unicompartmental knee osteoarthritis
Authors: Yin Yongqiang , Zhang Xu , Zhang Kaiming , He Xiang
Published: December 2020

Background:

Many clinical studies have been published in the literature to compare the outcomes of unicompartmental knee replacement (UKR) and high tibial osteotomy (HTO), but reached different conclusions. Therefore, the relative merits and demerits of these 2 procedures remain under debate. The purpose of the present protocol was to design a retrospective comparative study to further investigate the clinical effectiveness of HTO compared to UKR in the medial unicompartmental osteoarthritis of knee patients.

Methods:

This is an observational retrospective research, which prospectively collected the data from several surgeons in our center and utilized the above 2 methods to treat the unicompartmental osteoarthritis of knee. In our single hospital, we reviewed unicompartmental knee osteoarthritis patients treated using UKR or HTO from June 2016 to February 2018. For the HTO, its criteria included:

For the UKR, its inclusion criteria contained

In our cohorts, the clinical investigations of the knee were composed of the objective parameters, which were recorded and then documented through utilizing the Function Score and Orthopedic American Knee Society Knee Score. The extra clinical findings evaluated involved operative time, postoperative requirements of blood transfusion, possible postoperative complications, as well as the range of motion.

Conclusion and discussion:

The results of this study will provide clinical evidence on appropriate surgical treatment for patients with medial unicompartmental knee osteoarthritis.

Trial registration:

This study protocol was registered in Research Registry (researchregistry6152).
A randomized, multi-center, open-label study to compare the safety and efficacy between afatinib monotherapy and combination therapy of afatinib and HAD-B1 for the locally advanced or metastatic NSCLC patients with EGFR mutations
Authors: Song Si-Yeon , Ha Su-Jeong , Park Ji-Hye , Park So-Jung , Shin Seong Hoon , Oak Chulho , Choi Jun-Yong , Yoon Seong Woo , Kim Jung-A , Yoon Seong Hoon , Son Ji Woong , Kim Seung Joon , Yoo Hwa-Seung
Published: December 2020

Background:

Afatinib is an epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy for treating patients with advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, responses are limited by acquired resistance. Because traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy, the aim of our study is to elucidate the efficacy and safety of afatinib plus HangAmDan-B1 (HAD-B1) combination therapy in the treatment of patients with NSCLC, as well as EGFR mutations, who need afatinib therapy.

Methods/design:

This study is a randomized, multi-center, open clinical trial. A total of 142 eligible subjects, recruited at 8 centers, are randomly assigned to take Afatinib (20–40 mg) ± HAD-B1 (0.972 g/day) for 16 weeks. In the test group, HAD-B1 and afatinib will be used in combination. The primary outcome is a comparison of starting dose maintenance rate as well as the disease control rate (DCR) between afatinib monotherapy and afatinib plus HAD-B1 combination therapy in patients with local advanced or metastatic (Stage IIIA, B, C/IV) NSCLC. Secondary outcomes are the Progression Free Survival (PFS), Time to progression (TTP), Overall survival rate, ORR based on RESIST 1.1, tumor size reduction, health-related quality of life (HRQoL), and Tumor marker.

Discussion:

The result of this clinical trial will provide evidence for the efficacy and safety of using HAD-B1 in the treatment of EGFR-positive patients with locally advanced or metastatic NSCLC who require afatinib therapy.

Trial registration:

Clinical Research Information Service (CRIS), Republic of Korea (ID: KCT0005414), on September 23, 2020.
Effects of glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors on major adverse cardiovascular events in type 2 diabetes by race, ethnicity, and region
Authors: Qiu Mei , Ding Liangliang , Wei Xubin , Wei Wei , Zhou Hairong
Published: December 2020

Background:

The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists on major adverse cardiovascular events (MACE) in type 2 diabetic subgroups defined by race, ethnicity, and region are unestablished.

Methods:

We searched PubMed and Embase for related randomized controlled trials. We conducted random-effects meta-analysis, stratified by drug class, on MACE in various subgroups defined by 3 factors of interest (ie, race, ethnicity, and region) to estimate pooled hazard ratio (HR) and 95% confidence interval. Random-effects meta-regression was conducted to evaluate the differences between 2 drug classes.

Results:

We included 11 randomized controlled trials for pooled analysis. Compared with placebo, SGLT2is and GLP-1 RAs significantly reduced the risk of MACE (HR ranged from 0.76 to 0.93) in most diabetic subgroups defined by 3 factors of interest. The 2 drug classes did not significantly reduced this risk in the Black race group (HR 0.92, 95% confidence interval 0.70–1.20). The effect of the 2 drug classes on MACE was not significantly different in all diabetic subgroups of interest (P-value for subgroup differences ranged from .101 to .971).

Conclusions:

SGLT2is and glucagon-like peptide 1 receptor agonists can significantly reduce the risk of MACE in most type 2 diabetic subgroups defined by race, ethnicity, and region, whereas they fail to do it in Black individuals.
Aerobic, resistance and combined training for adults with chronic kidney disease
Authors: Zeng Rong , Lai Honghao , Li Zhuoyan , Chen Beibei , Wang Lu , Zhang Yali
Published: December 2020

Background:

Chronic kidney disease (CKD) as a disease that poses a great threat to human health, which has become a public health issue of great concern. Studies have found that exercise training has a positive effect on improving the condition of chronic kidney disease. We will conduct a network meta-analysis to assess the effects of aerobic training, resistance training and combined aerobic and resistance training in treating CKD patients.

Methods:

We will search PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science to identify randomized control trails (RCTs) that assessed the effect of different exercise training for CKD patients. Cochrane Handbook will be used to evaluate the risk of bias of included articles. We will use Stata or R software to perform data analysis.

Results and Conclusion:

Our systematic review and network meta-analysis will be the first study that investigates the effect of different exercise training for CKD patients, and will provide evidence for management of chronic kidney disease.

Ethics and dissemination:

The data involved in this study are from published articles. For this reason, there is no need for ethical approval or patient consent.

Trial registration:

the registration number was: CRD42020157280
Infrared thermography in the diagnosis of musculoskeletal injuries
Authors: Li Xiaoyu , Zhang Yajun , Sun Haiju , Jiang Yongliang , Lou Jiali , He Xiaofen , Fang Jianqiao
Published: December 2020

Background:

Musculoskeletal injuries (MSDs) have become a major public health problem worldwide. Current diagnosis techniques for MSDs are often associated with radiation exposure, expensive cost, or contraindication. Infrared thermography (IRT) is becoming a proposed tool to assist in diagnosing MSDs, but current evidence is inconclusive. Thus, herein we aimed to evaluate the diagnostic accuracy of IRT for MSDs.

Methods:

We will search EMBASE, MEDLINE, EBSCO, Cochrane Library, SCOPUS, Web of Science, CNKI, SinoMed, and Wangfang. Two researchers will independently screen eligible studies. Study quality will be evaluated based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data synthesis will be completed using STATA 14.0 software. A bivariate random-effects analysis will be utilized to estimate the pooled estimation of the diagnostic odds ratio (DOR) and the summary receiver operating characteristics (SROC) curve. Subgroup analyses will be performed to determine heterogeneity sources.

Results:

This systematic review and meta-analysis will provide reliable evidence about the diagnostic accuracy of IRT for MSDs.

Conclusion:

The conclusion of this study will be published in a peer-reviewed journal.

Ethics and Communication:

Given that this is a systematic review of published research, patient consent and ethical approval are not relevant. The findings of this study will be disseminated through conference presentations and publication in peer-reviewed journals.

Prospero registration number:

CRD42020184867.
Hyperbaric oxygen therapy for spinal cord injury
Authors: Li Tong , Wang Yiran , Feng Chaoqun , Li Qianchun , Ran Qiang , Chen Botao , Yu Yang , Jiang Leiming , Fan Xiaohong
Published: December 2020

Background:

Hyperbaric oxygen (HBO) therapy can prevent further spinal cord injury (SCI) caused by spinal cord ischemia-reperfusion injury to the maximum extent, which has been reported increasingly in recent years. However its security and effectiveness still lack of high-quality medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials (RCTs) to evaluate the efficacy and safety of HBO therapy for SCI.

Methods:

All potential RCTs on HBO therapy for SCI will be searched from the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang database and Chinese Biomedical Literature Database. We will search all electronic databases from their initiation to the September 30, 2020 in spite of language and publication date. Two contributors will independently select studies from all searched literatures, extract data from included trials, and evaluate study quality for all eligible RCTs using Cochrane risk of bias tool, respectively. Any confusion will be resolved by consulting contributor and a consensus will be reached. We will utilize RevMan 5.3 software to pool the data and to conduct the data analysis.

Results:

The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals.

Conclusion:

This study will provide evidence to evaluate the efficacy and safety of HBO therapy for SCI at evidence-based medicine level.

Trial registration number:

INPLASY 2020100084.
Association between functional polymorphisms in the flanking region of miR-143/145 and risk of papillary thyroid carcinoma
Authors: Wang Yichao , Zhou Shengliang , Zhao Wanjun , Li Zhihui , Zhu Jingqiang , Wei Tao , Song Haolan
Published: December 2020

MiR-143 and miR-145 were down-regulated in papillary thyroid carcinoma (PTC) involving in cell proliferation, apoptosis, migration, invasion, and epithelial to mesenchymal transition. In this study, we aimed to investigate the association between 2 functional polymorphisms (ie, rs4705342 and rs353292) in the flanking region of miR-143/145 and risk of PTC.

A case-control study including 316 PTC patients and 347 controls was performed. The rs4705342 and rs353292 were genotyped by using the TaqMan allelic discrimination. The results were confirmed by DNA sequencing.

For the rs4705342, a reduced risk of PTC was observed in heterozygous comparison, dominant genetic model and allele comparison (CC vs TT: adjusted OR = 0.37, 95% CI = 0.19–0.74, P = .003; CT/CC vs TT: adjusted OR = 0.64, 95% CI = 0.47–0.87, P = .005; C vs T: adjusted OR = 0.66, 95% CI = 0.52–0.85, P = .001, respectively). No significant difference was found in the genotypic distributions of the rs353292 between cases and controls.

These findings indicate that the rs4705342 in the flanking region of miR-143/145 may be a protective factor against the occurrence of PTC. Further study is therefore required to investigate the correlation between the genotype and V-raf murine sarcoma viral oncogene homolog B1 V600E, rat sarcoma viral oncogene homolog mutations, rearranged in transformation/PTC1 and rearranged in transformation/PTC3.
Evaluation of an Osteoporosis Outreach Program for Men With a Fragility Fracture and Their Physicians
Authors: Pasquale Margaret K. , Sheer Richard L. , Yehoshua Alon , McFadden Adrienne , Chines Arkadi , Caloyeras John
Published: December 2020

Background:

Many health plans have outreach programs aimed at appropriately screening, evaluating, and treating women experiencing fragility fractures; however, few programs exist for men.

Objective:

The objective of this study was to develop, implement, and evaluate an osteoporosis outreach program for men with a recent fragility fracture and their physicians.

Research Design and Subjects:

A total of 10,934 male patients enrolled in a Medicare Advantage with Prescription Drug Plan with a recent fragility fracture were randomized to a program or control group. Patients and their physicians received letters followed by phone calls on osteoporosis and the importance of screening and treatment. The evaluation compared bone mineral density (BMD) test utilization and osteoporosis medication treatment (OPT) among patients who received the outreach versus no outreach at 12 months. The effect of the program was estimated through univariate and multivariable logistic regressions.

Results:

The program had a significant impact on BMD evaluation and OPT initiation. At 12 months, 10.7% of participants and 4.9% of nonparticipants received a BMD evaluation. The odds ratio (OR) (95% confidence interval) was 2.31 (1.94, 2.76), and the number needed to outreach to receive a BMD test was 18. OPT was initiated in 4.0% of participants and 2.5% of nonparticipants. The OR (95% confidence interval) of receiving OPT was 1.60 (1.24, 2.07), and the number needed to outreach was 69. Adjusted ORs were similar in magnitude and significance.

Conclusion:

The program was highly effective by more than doubling the rate of BMD evaluation; however, more intensive interventions may yield an even higher screening rate.
Drivers of Cost Differences Between Nurse Practitioner and Physician Attributed Medicare Beneficiaries
Authors: Razavi Moaven , O’Reilly-Jacob Monica , Perloff Jennifer , Buerhaus Peter
Published: December 2020

Background:

Although recent research suggests that primary care provided by nurse practitioners costs less than primary care provided by physicians, little is known about underlying drivers of these cost differences.

Research Objective:

Identify the drivers of cost differences between Medicare beneficiaries attributed to primary care nurse practitioners (PCNPs) and primary care physicians (PCMDs).

Study Design:

Cross-sectional cost decomposition analysis using 2009–2010 Medicare administrative claims for beneficiaries attributed to PCNPs and PCMDs with risk stratification to control for beneficiary severity. Cost differences between PCNPs and PCMDs were decomposed into payment, service volume, and service mix within low-risk, moderate-risk and high-risk strata.

Results:

Overall, the average PCMD cost of care is 34% higher than PCNP care in the low-risk stratum, and 28% and 21% higher in the medium-risk and high-risk stratum. In the low-risk stratum, the difference is comprised of 24% service volume, 6% payment, and 4% service mix. In the high-risk stratum, the difference is composed of 7% service volume, 9% payment, and 4% service mix. The cost difference between PCNP and PCMD attributed beneficiaries is persistent and significant, but narrows as risk increases. Across the strata, PCNPs use fewer and less expensive services than PCMDs. In the low-risk stratum, PCNPs use markedly fewer services than PCMDs.

Conclusions:

There are differences in the costs of primary care of Medicare beneficiaries provided by nurse practitioners and MDs. Especially in low-risk populations, the lower cost of PCNP provided care is primarily driven by lower service volume.
Fecal Microbiota Transplantation for Treatment of Severe Clostridioides difficile Colitis in a Pediatric Patient With Non-Hodgkin Lymphoma
Authors: Sabus Ashley , Merrow Mya , Heiden Alyssa , Boster Julia , Koo Jane , Franklin Anna R.K.
Published: December 2020

Background:

Patients with malignant diseases are at high risk for refractory Clostridioides difficile infections (CDI). Fecal microbiota transplantation (FMT) restores the gastrointestinal microbiome and may be an effective treatment for patients who fail pharmacotherapy. However, FMT is not commonly used in the oncology population because of risk for donor-derived infection.

Observations:

The authors report successful use of FMT in a pediatric patient with refractory CDI actively receiving chemotherapy. The patient’s symptoms improved 1 day following FMT. He did not experience infectious complications or other adverse effects.

Conclusions:

FMT may be a feasible option for treatment of refractory CDI in pediatric oncology patients.
Translatability of WGS typing results can simplify data exchange for surveillance and control of Listeria monocytogenes
Authors: Lüth Stefanie , Deneke Carlus , Kleta Sylvia , Al Dahouk Sascha
Published: December 2020

Where classical epidemiology has proven to be inadequate for surveillance and control of foodborne pathogens, molecular epidemiology, using genomic typing methods, can add value. However, the analysis of whole genome sequencing (WGS) data varies widely and is not yet fully harmonised. We used genomic data on 494

Listeria monocytogenes

isolates from ready-to-eat food products and food processing environments deposited in the strain collection of the German National Reference Laboratory to compare various procedures for WGS data analysis and to evaluate compatibility of results. Two different core genome multilocus sequence typing (cgMLST) schemes, different reference genomes in single nucleotide polymorphism (SNP) analysis and commercial as well as open-source software were compared. Correlation of allele distances from the different cgMLST approaches was high, ranging from 0.97 to 1, and unified thresholds yielded higher clustering concordance than scheme-specific thresholds. The number of detected SNP differences could be increased up to a factor of 3.9 using a specific reference genome compared with a general one. Additionally, specific reference genomes improved comparability of SNP analysis results obtained using different software tools. The use of a closed or a draft specific reference genome did not make a difference. The harmonisation of WGS data analysis will finally guarantee seamless data exchange, but, in the meantime, knowledge on threshold values that lead to comparable clustering of isolates by different methods may improve communication between laboratories. We therefore established a translation code between commonly applied cgMLST and SNP methods based on optimised clustering concordances. This code can work as a first filter to identify WGS-based typing matches resulting from different methods, which opens up a new perspective for data exchange and thereby accelerates time-critical analyses, such as in outbreak investigations.
Fas-threshold signalling in MSCs causes tumour progression and metastasis
Authors: Mohr Andrea , Tianyuan Chu , Clarkson Christopher T. , Brooke Greg N. , Teif Vladimir B. , Zwacka Ralf M.
Published: December 2020

Mesenchymal stem cells (MSCs) are part of the tumour microenvironment and have been implicated in tumour progression. We found the number of MSCs significantly increased in tumour-burdened mice driven by Fas-threshold signalling. Consequently, MSCs lacking Fas lost their ability to induce metastasis development in a pancreatic cancer model. Mixing of MSCs with pancreatic cancer cells led to sustained production of the pro-metastatic cytokines CCL2 and IL6 by the stem cells. The levels of these cytokines depended on the number of MSCs, linking Fas-mediated MSC-proliferation to their capacity to promote tumour progression. Furthermore, we discovered that CCL2 and IL6 were induced by pancreatic cancer cell-derived IL1. Analysis of patient transcriptomic data revealed that high FasL expression correlates with high levels of MSC markers as well as increased IL6 and CCL2 in pancreatic tumours. Moreover, both FasL and CCL2 are linked to elevated levels of markers specific for monocytes known to possess further pro-metastatic activities. These results confirm our experimental findings of a FasL-MSC-IL1-CCL2/IL6 axis in pancreatic cancer and highlight the role MSCs play in tumour progression.
In VitroAnalysis of the Anti-viral Potential of nasal spray constituents against SARS-CoV-2
Authors: Cannon Mark L , Westover Jonna B. , Bleher Reiner , Sanchez-Gonzalez Marcos A. , Ferrer Gustavo
Published: December 2020

Viral pandemics have taken a significant toll on humanity and the world now is contending with the SARS-CoV-2 epidemic. Readily available economical preventive measures should be immediately explored. Xylitol has been reported to reduce the severity of viral infections as well as the severity of pneumonia, and increase the survivability of animal subjects. Since pneumonia and acute respiratory distress syndrome are potentially fatal complications of COVID-19, the present study tested thein vitroeffectiveness of xylitol against SARS-CoV-2. Virus titers and LRV of SARS-CoV-2, were incubated with a single concentration of nasal spray. Toxicity was observed in the top dilution (1/10). Virus was seen below that dilution so it did not affect calculations of virus titer or LRV. After a 25-minute contact time, the nasal spray (11% Pure Xylitol, 0.85%NaCL (Saline), and 0.20% grapefruit seed extract) reduced virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction (P<0.001) of 2.5 log10 CCID50. STEM Images obtained at the BIoCryo Laboratory revealed virus contained on the cell wall but none intra-cellular, possibly due to D-xylose (xylitol) production of glycoaminoglycans decoy targets. Xylitol and grapefruit seed extract are not exotic nor expensive rare high technology answers to viral epidemics. The potential in saving lives and the economies of the world by using X-GSE combination therapy should inspire large clinical trials, especially in those nations whereas the healthcare system would be dangerously compromised by the adoption of less effective and significantly more financially demanding therapies. Because there are no risk factors in using the X/GSE combination therapy, and the nasal spray is over the counter available without a prescription, and the spray allows for comfortable long term mask-wearing, adoption of this preventive anti-viral therapy should be encouraged.
A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters
Authors: Bricker Traci L. , Darling Tamarand L. , Hassan Ahmed O. , Harastani Houda H. , Soung Allison , Jiang Xiaoping , Dai Ya-Nan , Zhao Haiyan , Adams Lucas J. , Holtzman Michael J. , Bailey Adam L. , Case James Brett , Fremont Daved H. , Klein Robyn , Diamond Michael S. , Boon Adrianus C. M.
Published: December 2020

The development of an effective vaccine against SARS-CoV-2, the etiologic agent of COVID-19, is a global priority. Here, we compared the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in Golden Syrian hamsters. While immunization with ChAd-SARS-CoV-2-S induced robust spike protein specific antibodies capable or neutralizing the virus, antibody levels in serum were higher in hamsters immunized by an intranasal compared to intramuscular route. Accordingly, ChAd-SARS-CoV-2-S immunized hamsters were protected against a challenge with a high dose of SARS-CoV-2. After challenge, ChAd-SARS-CoV-2-S-immunized hamsters had less weight loss and showed reductions in viral RNA and infectious virus titer in both nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-Control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provided superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.
Microarthropod contributions to fitness variation in the common mossCeratodon purpureus
Authors: Shortlidge Erin E. , Payton Adam C. , Carey Sarah B. , McDaniel Stuart F. , Rosenstiel Todd N. , Eppley Sarah M.
Published: December 2020

The evolution of mutualism depends critically upon genetic variation in the fitness benefit to both partners. Estimates of these quantities are rare, however, because genetic variation for the interaction may be absent, aspects of the interaction may not be amenable to experimental manipulation, or the benefits to one partner may be unknown. In vitro experiments show that female mosses produce odors which attract sperm-dispersing microarthropods, but the fitness consequences of this interaction for either partner are unknown. Here we established experimental mesocosms to test for a commensal effect of sperm-dispersing microarthropods on moss reproduction. We found that of moss grown with microarthropods showed increased moss reproductive rates by five times, relative to control mesocosms, but remarkably also increased the number of reproducing genotypes, and changed the rank-order of fitness for both male and female genotypes. These results provide an estimate of the fitness benefit for mosses in the presence of microarthropods, and highlight the potential for biotic dispersal agents to alter fitness among moss genotypes in this relationship.
Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses
Authors: Xiong Kun , Gerstein Mark , Masel Joanna
Published: December 2020

Transcriptional regulatory networks (TRNs) are enriched for certain “motifs”. Motif usage is commonly interpreted in adaptationist terms, i.e. that the optimal motif evolves. But certain motifs can also evolve more easily than others. Here, we computationally evolved TRNs to produce a pulse of an effector protein. Two well-known motifs, type 1 incoherent feed-forward loops (I1FFLs) and negative feedback loops (NFBLs), evolved as the primary solutions. Which motif evolves more often depends on selection conditions, but under all conditions, either motif achieves similar performance. I1FFLs generally evolve more often than NFBLs, unless we select for a tall pulse. I1FFLs are more evolutionarily accessible early on, before the effector protein evolves high expression; when NFBLs subsequently evolve, they tend to do so from a conjugated I1FFL-NFBL genotype. In the empiricalS. cerevisiaeTRN, output genes of NFBLs had higher expression levels than those of I1FFLs. These results suggest that evolutionary accessibility, and not relative functionality, shapes which motifs evolve in TRNs, and does so as a function of the expression levels of particular genes.
Functional and genomic adaptations of blood monocytes to pregravid obesity during pregnancy
Authors: Sureshchandra Suhas , Marshall Nicole E. , Mendoza Norma , Jankeel Allen , Zulu Michael Z. , Messaoudi Ilhem
Published: December 2020

Pre-pregnancy obesity is associated with several adverse maternal health outcomes, notably increased risk of infection as well as the incidence of gestational diabetes, preeclampsia, and preterm birth. However, the mechanisms by which pregravid obesity disrupts the pregnancy associated “immune clock” are still unknown. To address this question, we collected blood samples from women during the first and third trimesters and determined the impact of both pregnancy and pregravid obesity on circulating immune mediators, immune cell subset frequencies, and peripheral immune responses. While regardless of BMI, pregnancy was associated with an elevation in both Th1 and Th2 cytokines, pregravid obesity was associated with a dysregulation in circulating myeloid factors at term. Moreover, pregnancy in lean subjects was associated with enhanced monocyte activation, augmented chromatin accessibility at inflammatory loci, and heightened responses to LPS. Pregravid obesity disrupted this trajectory and was accompanied by a lack of transcriptional and epigenetic changes and alterations in metabolic status strongly suggesting a skewing towards immunotolerance. These findings provide novel insight into the increased susceptibility to infections observed with obesity during pregnancy.

A healthy pregnancy is associated with progressive innate immune activation. Maternal factors such as obesity compromise this myeloid cell activation trajectory at genomic, epigenomic, functional, and metabolic levels, resulting in stagnant immune responses, suggestive of a state of tolerance.
Genome-wide association of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) plasma levels in the ELSA-Brasil study
Authors: Bensenor Isabela , Padilha Kallyandra , Lima Isabella Ramos , Santos Raul Dias , Lambert Gilles , Ramin-Mangata Stéphane , Bittencourt Marcio S , Goulart Alessandra C , Santos Itamar S. , Mill Jose G , Krieger Jose E , Lotufo Paulo A. , Pereira Alexandre C.
Published: December 2020

Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genome-wide genetic variation in a healthy sample from the general population.

We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the ELSA-Brasil cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array and imputation used the TOPMED multi-ancestry sample panel. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit.

We observed two genome-wide significant loci and seven loci that reached the pre-definedpvalue threshold of 1 × 10−6. Significant variants were nearKCNA5andKCNA1, andLINC00353. Genetic variation at thePCSK9locus was able to explain approximately 4% of the overall interindividual variation in PCSK9 levels. Colocalization analysis using eQTL data suggestedRWDD3,ATXN7L1,KCNA1, andFAM177A1to be potential mediators of some of the observed associations.

Our results suggest that PCSK9 levels may be modulated bytransgenetic variation outside of thePCSK9gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identifying new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.
Accuracy and precision of citizen scientist animal counts from drone imagery
Authors: Wood Sarah A. , Robinson Patrick W. , Costa Daniel P. , Beltran Roxanne S.
Published: December 2020

Repeated counts of animal abundance can reveal changes in local ecosystem health and inform conservation strategies. Unmanned aircraft systems (UAS) such as drones are commonly used to photograph animals in remote locations; however, counting animals in images is a laborious task. Crowd-sourcing can reduce the time required to conduct these censuses considerably, but must first be validated against expert counts to measure sources of error. Our objectives were to assess the accuracy and precision of citizen science counts and make recommendations for future citizen science projects. We uploaded drone imagery from Año Nuevo Island (California, USA) to a curated Zooniverse website that instructed citizen scientists to count seals and sea lions. Across 212 days, over 1,500 volunteers counted animals in 90,000 photographs. We quantified the error associated with several descriptive statistics to extract a single citizen science count per photograph from the 15 repeat counts and then compared the resulting citizen science counts to expert counts. Although proportional error was relatively low (9% for sea lions and 5% for seals during the breeding seasons) and improved with repeat sampling, the 12+ volunteers required to reduce error was prohibitively slow, taking on average 6 weeks to estimate animals from a single drone flight covering 25 acres, despite strong public outreach efforts. The single best algorithm was ‘Median without the lowest two values’, demonstrating that citizen scientists tended to under-estimate the number of animals present. Citizen scientists accurately counted adult seals, but accuracy was lower when sea lions were present during the summer and could be confused for seals. We underscore the importance of validation efforts and careful project design for researchers hoping to combine citizen science with drone imagery.
SARS-CoV-2 D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability
Authors: Chen Chiung-Ya , Chou Yu-Chi , Hsueh Yi-Ping
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) exhibits two major variants based on mutations of its spike protein, i.e., the D614 prototype and G614 variant. Although neurological symptoms have been frequently reported in patients, it is still unclear whether SARS-CoV-2 impairs neuronal activity or function. Here, we show that expression of both D614 and G614 spike proteins is sufficient to induce phenotypes of impaired neuronal morphology, including defective dendritic spines and shortened dendritic length. Using spike protein-specific monoclonal antibodies, we found that D614 and G614 spike proteins show differential S1/S2 cleavage and cell fusion efficiency. Our findings provide an explanation for higher transmission of the G614 variant and the neurological manifestations observed in COVID-19 patients.