bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of a WeChat-based multimodal nursing program for women with breast cancer
Authors: Zhao Na , Yin Fang , Wu Xiaofang , Zhong Yuxia
Published: December 2020

Background:

Breast cancer is one of the most familiar malignant tumor all over the world in women. The main treatment for the early breast cancer is surgery accompanied by the adjuvant therapy. Nevertheless, these treatments can lead to adverse reactions including sleep disturbances, fatigue, and pain. For our research, the objective is to assess the therapeutic effect of nursing program based on WeChat for the female breast cancer.

Methods:

This is a randomized controlled research, and it will be carried out from November 2020 to May 2021, which was granted via the Ethics Committee of the Second Affiliated Hospital of Hainan Medical University (LW2020056). In this study, patients meeting the following criteria will be included:

And patients with

In intervention group, the patients are given multi-mode nursing program based on WeChat and routine nursing. In control group, patients are given routine nursing, involving vital signs monitoring, the education of health, the monitoring of postoperative complications, as well as postoperative drainage tube nursing. The main outcomes are the change of Functional Assessment of Cancer Therapy-Breast version 4.0 (FACT-Bv4.0) score. While the secondary result is the numerical rating scale (NRS).

Results:

Table 1 shows the clinical results between study group and control group.

Conclusion:

This paper has guided nurses to develop an evidence-based protocol to improve patient care for postoperative women with breast cancer.

Trial registration:

This study protocol was registered in Research Registry (researchregistry6180).
How about the quality and recommendation on prevention, diagnosis, and treatment of HIV/AIDS guidelines developed by WHO
Authors: Zhu Qingshuang , Fang Pengzhong , Zhao Yadong , Dai Dingmei , Luo Xiaofeng
Published: December 2020

Background:

Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) has become a pandemic that has infected millions of people around the world and brings a tremendous economic burden. There are numerous guidelines for prevention, diagnosis, and treatment of HIV/AIDS published in recent years, but the quality of these guidelines is still unknown. Therefore, we conducted this study to evaluate the quality of prevention, diagnosis, and treatment of HIV/AIDS published by World Health Organization (WHO) as well as perform a comparison of recommendations between those guidelines. And we also hope our finding could provide suggestions to enhance the quality of future guidelines in this area.

Methods:

We obtained guidelines from WHO Guidelines approved by the Guidelines Review Committee (GRC). Two reviewers will independently select eligible guidelines. The quality of included guidelines will be appraised by at least four reviewers through AGREE II and RIGHT tools. The results will be checked for discrepancies. Differences between them than two reviewers will be considered as discrepant and the final discrepancies will be resolved by consensus. The results will be presented in tables and the descriptive statistics will be calculated for all domains of the AGREE II instrument as standard score and median (range) as the reporting quality result of eligible guidelines will also be evaluated through RIGHT criteria. In this study, we will also compare the differences and similarities of recommendations among different guidelines.

Results:

The results of this study will increase the knowledge about the development of recommendations guidelines for HIV/AIDS of high methodological rigor and reporting quality. This study may also identify potential limitations for future research in this area.

Conclusion:

This study may guide health professionals, policy makers, and health policy managers in choosing the guidelines for recommendation to better to achieve the 90–90–90 targets.

INPLASY registration number:

INPLASY2020110010
Vestibulo-ocular reflex tests may reflect unilateral Ménière disease progression
Authors: Zhou Renhong , Leng Yangming , Liu Bo
Published: December 2020

Vestibular disorders can manifest several patterns of horizontal vestibulo-ocular reflex (VOR) impairment, which can be detected by caloric test and video head impulse test (vHIT). Several studies have examined the patterns of caloric-vHIT response in Ménière disease (MD). The purpose of this study was to investigate the diversity of caloric-vHIT response and its related factors in unilateral MD patients. We also explore the possibility of assessing the progression of unilateral MD by using the horizontal VOR tests.

Ninety-eight patients with unilateral MD were enrolled and underwent a battery of audio-vestibular evaluations, including the pure tone audiogram, caloric test, and horizontal vHIT. Some patients received the electrocochleography and glycerol test. The combined results of caloric test and horizontal vHIT were categorized qualitatively into 4 patterns: Pattern I: normal caloric and vHIT responses; Pattern II: abnormal caloric and normal vHIT responses; Pattern III: normal caloric and abnormal vHIT response; and Pattern IV: abnormal caloric and vHIT responses. The abnormal caloric results were semi-quantitatively subdivided into sub-patterns as mild, moderate, and severe abnormality. The associations between these patterns/sub-patterns and related factors were analyzed.

Pattern I was found in 35 cases (35.7%), Pattern II in 57 (58.2%), and Pattern IV in 6 (6.1%). No patient had Pattern III. No significant differences were found between the patterns/sub-pattern distribution and age, electrocochleography, and glycerol test results. Disease duration was not associated with the pattern distribution, while remained a relation with sub-pattern distribution. The pattern/sub-pattern distribution varied significantly across MD stages. The proportion of pattern II or pattern IV increased with the stage of unilateral MD.

MD can manifest several patterns of horizontal VOR impairment, of which the impaired caloric response with normal vHIT is the most common pattern. With the progression of unilateral MD, the caloric-vHIT pattern tends to shift, which may reflect the deterioration of endolymphatic hydrops and vestibular hair cells impairments.
Hemostasis after percutaneous transfemoral access
Authors: Reich Rejane , Helal Lucas , Mantovani Vanessa Monteiro , Rabelo-Silva Eneida Rejane
Published: December 2020

Background:

Access site hemostasis after percutaneous procedures done in the catheterization laboratory still needs to be better studied in relation to such aspects as the different results achieved with different hemostasis strategies, the impact of different introducer sheath sizes, and arterial versus venous access. The objective of this review is to synthesize the available scientific evidence regarding different techniques for hemostasis of femoral access sites after percutaneous diagnostic and therapeutic procedures.

Methods:

This review is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The primary outcomes will include the following vascular complications: hematoma, pseudoaneurysm, bleeding, minor, and major vascular complications. The secondary outcomes will include the following: time to hemostasis, repetition of manual compression, and device failure. A structured strategy will be used to search the PubMed/ MEDLINE, Embase, CINAHL, and CENTRAL databases. In addition, a handsearch of the reference lists of selected studies will be conducted. The ERIC research database will be queried for the gray literature and ClinicalTrials.gov, for potential results not yet published in indexed journals. Two reviewers will independently screen citations and abstracts, identify full-text articles for inclusion, extract data, and appraise the quality and risk of bias of included studies. If possible, a meta-analysis will be carried out. All estimations will be made using Review Manager 5.3. Statistical heterogeneity will be assessed by considering the I
2 proxy, accompanied with qualitative indicators such as differences in procedures, interventions, and outcomes among the studies. If synthesis proves inappropriate, a narrative review will be undertaken.

Results:

This protocol adheres to the PRISMA-P guideline to ensure clarity and completeness of reporting at all phases of the systematic review.

Conclusion:

This study will provide synthesized information on different methods used to achieve hemostasis after femoral access.

Ethics and dissemination:

Ethical approval number CAAE 19713219700005327. The results of the systematic review will be disseminated via publication in a peer-reviewed journal and through conference presentations.

Systematic review registration:

PROSPERO CRD42019140794.
Dizziness handicap and anxiety depression among patients with benign paroxysmal positional vertigo and vestibular migraine
Authors: Zhu Cuiting , Li Yiqing , Ju Yi , Zhao Xingquan
Published: December 2020

To investigate the dizziness handicap and anxiety depression among patients with benign paroxysmal positional vertigo (BPPV) and vestibular migraine (VM).

A prospective cohort study in which patients came from the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University was conducted. Patients were diagnosed with BPPV and VM from September 2016 to December 2017. Dizziness handicap inventory (DHI) scale and hospital anxiety and depression scale (HADS) were assessed among subjects before treatment and 3 months follow-up.

We used the Mann–Whitney U test to compare the DHI and HADS scores of BPPV and VM patients before and after 3 months and found significantly statistical difference. Before treatment, the median DHI scores of BPPV and VM were 34 and 60, with a Z = −5.643 (P = .001); The median HADS scores were 6 and 14, with Z = −4.807 (P = .001). After 3 months follow-up, the median DHI scores of BPPV and VM were 0 and 22, with a Z = −8.425 (P = .001); The median HADS scores were 6 and 14, with Z = −7.126 (P = .001) 51.11% VM patients and 12.21% BPPV patients have anxiety and depression. A Spearman correlation revealed a significantly moderate positive correlation (r = .455, P < .001) between DHI and HADS scores.

The emotional, functional and physical effects of vertigo on VM patients were more significant than BPPV patients. The change of DHI scores in BPPV and VM patients was positively correlated with changes in the anxiety and depression in the HADS.
Prognostic value of microRNA-21 in epithelial ovarian carcinoma
Authors: Ji Kun , Wang Xiaohua , Zhang Anqi , Wen Hongwei
Published: December 2020

Backgroud:

The expression of microRNA-21 has been shown to be associated with the prognosis in patients with malignant tumors. However, its prognostic value in epithelial ovarian carcinoma (EOC) remains controversial. This meta-analysis aimed to synthesize available data to clarify the association between microRNA-21 expression levels and clinical prognosis in EOC patients.

Methods:

Eligible literatures were searched from Embase, Google Scholar, PubMed, Web of Science, Medline, Cochrane Library, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese BioMedical Database and Wanfang Database to identify eligible studies. Papers in English or Chinese published from their inception to November 2020 will be included. Methodological quality for each eligible trial will be assessed by using the Newcastle-Ottawa Quality Assessment Scale. Odds ratios or hazards ratios with corresponding 95% confidence intervals were pooled to estimate the prognosis value of microRNA-21 by using Stata 14.0 and Review Manager 5.3 software.

Results:

This study will provide a high-quality evidence-based medical evidence of the correlations between microRNA-21 expression and overall survival and disease-free survival.

Conclusion:

The findings of this systematic review will show the effect of high expression of microRNA-21 on the prognosis of EOC patients.

Trial registration number:

INPLASY2020110064
The efficacy of Tuina for asthma
Authors: Wang Changhong , Jiang Yong , Fan Zhipeng , Zhao Mao , Jiang Yuchang , Wang Zhaodi , Chen Zhaoxing
Published: December 2020

Background:

Asthma is one of the most common chronic diseases in the world, with ∼100 million asthma patients worldwide. China has become one of the countries with the highest asthma death rate in the world. Asthma is a chronic airway inflammatory disease. Patients with this disease may have symptoms such as cough, wheezing, and difficulty breathing. For many years, Western medicine has mainly used anti-inflammatory, anti-bronchial spasm, asthma, cough, and oxygen to treat this disease, but the effect is not good. Tuina is a common treatment for asthma in China. But at present, there is no systematic evaluation report on its therapeutic effectiveness and safety. This protocol aims to reveal the efficacy and safety of Tuina for treating asthma.

Methods:

The following databases will be searched by electronic methods: PubMed, EBASE, WHO International Clinical Trials Registry Platform, Embase, the Chinese Biomedical Literature Database (CBM), Wan-fang Data (WANFANG), the China National Knowledge Infrastructure (CNKI), and other sources from inception to November 2020. Bias risk, subgroup analysis, data synthesis, and meta-analyses will be assessed with RevMan V.5.3 software if the data is met inclusion conditions.

Results:

This study will present a quality evidence of Tuina for the treatment of astma patients.

Conclusion:

The systematic review will present reliable evidence to judge whether or not Tuina is a safe and effective intervention for asthma patients. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number: INPLASY2020110100.
Pre-radiofrequency ablation MRI imaging features predict the local tumor progression in hepatocellular carcinoma
Authors: Hu Zhouchao , Yu Nannan , Wang Heping , Li Shibo , Yan Jingang , Zhang Guoqiang
Published: December 2020

To investigate whether MRI features could preoperatively predict local tumor progression (LTP) in patients with hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) as the first-line treatment and improve a novel predictive model through developing a nomogram including various conventional MRI parameters. 105 patients with HCCs who had received RFA were enrolled. All patients had undergone conventional MRI before RFA. Uni- and multivariable analyses for LTP were assessing using a Cox proportional hazards model. The developed MRI-based nomogram was further designed based on multivariable logistic analysis in our study and the usefulness of the developed model was validated according to calibration curves and the C-index. Rim enhancement (hazard ratio: 2.689, P = .044) and the apparent diffusion coefficient (ADC) values (hazard ratio: 0.055, P = .038) were statistically significant independent predictors of LTP after RFA at multivariable analysis. The performance of the nomogram incorporating two MRI parameters (with a C-index of 0.782) was improved compared with that based on rim enhancement and ADC alone (with C-index values of 0.630 and 0.728, respectively). The calibration curve of the MRI-based nomogram showed good conformance between evaluation and observation at 0.5, 1, and 1.5 years after RFA. The preliminary predictive model based on MRI findings including rim enhancement and ADC value could be used preoperatively to estimate the risk of LTP of HCC after RFA as the first-line treatment.
Prognostic Value of Positive Presurgical FDG PET/CT in the Evaluation of Tumor-Induced Osteomalacia
Authors: Wang Peipei , Zhang Shu , Huo Li , Jing Hongli , Li Fang
Published: December 2020

Objectives

Tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome, is curable by excision or destruction of the causative tumor. However, occasionally, TIO may relapse after surgical intervention. We aimed to investigate the roles of 18F-FDG PET/CT in the prognosis of TIOs.

Methods

Seventy-six patients who had surgically removed tumors that caused osteomalacia were included in this retrospective investigation. All patients underwent both 18F-FDG and 68Ga-DOTATATE PET/CT prior to surgery. The prognostic value of presurgical FDG PET/CT study was determined with 5-year follow-up.

Results

In the presurgical evaluation, 68Ga-DOTATATE detected lesions in all 76 patients. However, FDG PET/CT was positive in only 25 among all 76 patients. Following surgical removal of the causative tumor, all 76 patients had symptomatic relief and normalization of the serum phosphate level initially. However, 15 of 76 cases (19.7%) had recurrent hypophosphatemia and became symptomatic again during the follow-up. Among these 15 patients with recurrence, 11 (73.3%) had recurrent lesions at the original location of the resected causative tumors, whereas 4 were in other locations due to malignant nature of the primary tumor. Interestingly, 14 of these 15 patients with recurrent disease had positive presurgical FDG PET/CT findings with an incident ratio of 56.0% (14 of 25). In contrast, only 1 patient with recurrent disease had negative presurgical FDG PET/CT scan with an incident ratio of 1.9% (1 of 51), significantly less than the positive presurgical FDG PET/CT group (P < 0.05).

Conclusions

A positive presurgical FDG PET/CT suggests increased likelihood for possible recurrence of TIO after surgical resection. In contrast, when a causative tumor detected by 68Ga-DOTATATE PET/CT does not have elevated activity on FDG PET/CT, the chance of recurrence is very small.
Intense Diffuse Uptake of 68Ga-FAPI-04 in the Breasts Found by PET/CT in a Patient With Advanced Nasopharyngeal Carcinoma
Authors: Wang Li-juan , Zhang Yin , Wu Hu-bing
Published: December 2020

The physiological uptake of 68Ga-FAPI-04 due to the change of the internal environment is little known. We report the case of a 45-year-old woman who was highly suspected to have advanced nasopharyngeal carcinoma. 18F-FDG and 68Ga-FAPI-04 PET/CT was performed for evaluating the disease. Both PET and CT with different tracers detected the primary nasopharyngeal carcinoma and metastases in right neck lymph nodes, liver, and bones. To our surprise, intense diffuse uptake of 68Ga-FAPI-04 was found in both breasts, which might be due to the hormone stimulation because the patient received 68Ga-FAPi-04 PET/CT just at the period of ovulation.
Circulating Cell-free DNA in Patients With Acute Biliary Pancreatitis: Association With Disease Markers and Prolonged Hospitalization Time—A Prospective Cohort Study
Authors: Gibor Udit , Perry Zvi , Netz Uri , Kirshtein Boris , Mizrahi Solly , Czeiger David , Sebbag Gilbert , Douvdevani Amos
Published: December 2020

Objective:

To evaluate cfDNA as an indicator of pancreatitis severity.

Background:

Acute pancreatitis severity scores have limited proficiency, and are complex and challenging to use clinically. Elevation of circulating cfDNA concentration has been shown to be associated with hospital length of stay (LOS) and mortality.

Methods:

In a prospective study, cfDNA concentration was measured by a simple fluorometric test, at admission and for 2 consecutive days, in patients with acute biliary pancreatitis (ABP). Ranson and APACHE II scores were used as measures of pancreatitis severity. Hospital LOS and mortality were used as outcome measures.

Results:

Seventy-eight patients were included. Patients with severe disease according to Ranson's Criteria (n = 24) had elevated median admission cfDNA compared to patients with mild disease (n = 54, 2252ng/ml vs 1228 ng/ml, P < 0.05). Admission cfDNA levels correlated with Ranson and APACHE II scores and markers of bile duct obstruction. LOS did not differ between patients with mild and severe disease according to Ranson and APACHE II scores. Patients with cfDNA at 24 hours concentrations above the cutoff value of healthy patients (>850 ng/ml) had a significantly longer LOS compared to those with normal cfDNA levels (P < 0.001).

Conclusions:

cfDNA, measured by a rapid simple assay, proved a valuable early marker of severity in ABP with clear advantages for prediction of LOS over Ranson and APACHE II. Measurement of cfDNA has the potential to be an effective practical approach to predict the course of ABP and should be further evaluated in larger trials.
Conventional Surgical Management of Bile Duct Stones
Authors: Nassar Ahmad H. M. , Ng Hwei J. , Katbeh Tarek , Cannings Elizabeth
Published: December 2020

Objective:

The primary aim of this study was to describe the service model of one-session management, with a limited role for preoperative endoscopic clearance. The secondary aim was to review the outcomes and long term follow up in comparison to available studies on LCBDE.

Background:

The laparoscopic era brought about a decline in the conventional surgical management of common bile duct stones. Preoperative endoscopic removal became the primary method of managing choledocholithiasis. Although LCBDE deals with gallstones and ductal stones in onw session, the limited availability of such an advanced procedure perpetuated the reliance on the endoscopic approach.

Methods:

Prospective data was entered into a single surgeon’s database containing 5739 laparoscopic cholecystectomy over 28 years and analyzed.

Results:

One thousand eighteen consecutive LCBDE were included (23% of the series). Intraoperative cholangiography was performed in 1292 (98.0%). The median age was 60 years, male to female ratio 1:2 and 75% were emergency admissions. Most patients (43.4%) presented with jaundice. 66% had transcystic explorations and one third through a choledochotomy with 2.1% retained stones, 1.2% conversion, 18.7% morbidity, and 0.2% mortality. Postoperative ERCPs were needed in 3.1%. Recurrent stones occurred in 3%.

Conclusions:

One stage LCBDE is a safe and cost-effective treatment where the expertise and equipment are available. Endoscopic treatment has a role for specific indications but remains the first-line treatment in most units. This study demonstrates that establishing specialist services through training and logistic support can optimize the outcomes of managing common bile duct stones.
Personalization improves the biomechanical efficacy of foot progression angle modifications in individuals with medial knee osteoarthritis
Authors: Uhlrich Scott D , Kolesar Julie A , Kidziński Łukasz , Boswell Melissa A , Silder Amy , Gold Garry E , Delp Scott L , Beaupre Gary S
Published: December 2020

Objectives

The goal of this study was to evaluate the importance of personalization when selecting foot progression angle modifications that aim to reduce the peak knee adduction moment in individuals with medial knee osteoarthritis.

Design

One hundred seven individuals with medial knee osteoarthritis walked on an instrumented treadmill with biofeedback instructing them to toe-in and toe-out by 5° and 10° relative to their self-selected foot progression angle. We selected individuals’ personalized foot progression angle as the modification that maximally reduced their larger knee adduction moment peak. Additionally, we used lasso regression to identify which secondary changes in kinematics made a 10° toe-in gait modification more effective at reducing the first knee adduction moment peak.

Results

Sixty-six percent of individuals reduced their larger knee adduction moment peak by at least 5% with a personalized foot progression angle modification, which is more than (p<0.001) the 54% and 23% of individuals who reduced it with a uniformly-assigned 10° toe-in or toe-out modification, respectively. When toeing-in, greater reductions in the first knee adduction moment peak were related to an increased frontal-plane tibia angle (knee more medial than ankle), a more valgus knee abduction angle, reduced contralateral pelvic drop, and a more medialized center of pressure in the foot reference frame.

Conclusions

Personalization increases the proportion of individuals with medial knee osteoarthritis who may benefit from modification of their foot progression angle.
Whole Genome Rare-Variant Association Study of HIV-1 Progression in a Southern African Population
Authors: Thami Prisca K. , Choga Wonderful , Mulisa Delesa D. , Dandara Collet , Shevchenko Andrey K. , Leteane Melvin M. , Novitsky Vlad , O’Brien Stephen J. , Essex Myron , Gaseitsiwe Simani , Chimusa Emile R.
Published: December 2020

Despite the high burden of HIV-1 in Botswana, the population of Botswana is significantly underrepresentation in host genetics studies of HIV-1. Furthermore, the bulk of previous genomics studies evaluated common human genetic variations, however, there is increasing evidence of the influence of rare variants in the outcome of diseases which may be uncovered by comprehensive complete and deep genome sequencing. This research aimed to evaluate the role of rare-variants in susceptibility to HIV-1 and progression through whole genome sequencing. Whole genome sequences (WGS) of 265 HIV-1 positive and 125 were HIV-1 negative unrelated individuals from Botswana were mapped to the human reference genome GRCh38. Population joint variant calling was performed using Genome Analysis Tool Kit (GATK) and BCFTools. Cumulative effects of rare variant sets on susceptibility to HIV-1 and progression (CD4+ T-cell decline) were determined with optimized Sequence Kernel Association Test (SKAT-O).In silicofunctional analysis of the prioritized variants was performed through gene-set enrichment using databases in GeneMANIA and Enrichr. Novel rare-variants within theANKRD39(8.48 × 10−8),LOC105378523(7.45 × 10−7) andGTF3C3(1.36 × 10−6) genes were significantly associated with HIV-1 progression. Functional analysis revealed that these genes are involved in viral translation and transcription. These findings highlight the significance of whole genome sequencing in pinpointing rare-variants of clinical relevance. The research contributes towards a deeper understanding of the host genetics HIV-1 and offers promise of population specific interventions against HIV-1.
Covid-19 Vaccine Efficacy: Accuracy, Uncertainty and Projection of Cases
Authors: Fu Wenjiang , Li Jieni , Scheet Paul
Published: December 2020

Background

Two vaccine candidates for coronavirus disease 2019 (Covid-19) have been announced by Pfizer-BioNTech and Moderna with above 90% efficacy. The efficacy of each vaccine changes between reports with no accuracy assessment.

Methods

We examined data in both vaccine trials, provided 95% confidence intervals, and projected the cases that would be prevented in communities of multi-million population.

Results

The 95% confidence intervals reveal that the true vaccine efficacy could be as low as 86% for stated efficacy of 94.4% in an interim report, indicating the inaccuracy and uncertainty of efficacy point estimate. Both vaccines achieve an efficacy above 89% by the 95% confidence interval in updated reports. The Moderna vaccine would prevent more than 50,260 cases in communities of 1 million people with 1 year exposure.

Conclusions

Point estimates of vaccine efficacy transmit limited information. Corresponding statements of uncertainty, such as confidence intervals, should be provided and included in discussions of societal impact. The Covid-19 vaccines announced to date would prevent a substantial number of cases even at lower ends of the intervals.
Development of intra-oral automated landmark recognition (ALR) for dental and occlusal outcome measurements
Authors: Woodsend Brénainn , Koufoudaki Eirini , Lin Ping , McIntyre Grant , El-Angbawi Ahmed , Aziz Azad , Shaw William , Semb Gunvor , Reesu Gowri Vijay , Mossey Peter A.
Published: December 2020

Previous studies embracing digital technology and automated methods of scoring dental arch relationships have shown that such technology is valid and accurate. To date, however there is no published literature on artificial intelligence and machine learning to completely automate the process of dental landmark recognition.

This study aimed to develop and evaluate a fully automated system and software tool for the identification of landmarks on human teeth using geometric computing, image segmenting and machine learning technology.

239 digital models were used in the automated landmark recognition (ALR) validation phase, 161 of which were digital models from cleft palate subjects aged 5 years. These were manually annotated to facilitate qualitative validation. Additionally, landmarks were placed on 20 adult digital models manually by three independent observers. The same models were subjected to scoring using the ALR software and the differences (in mm) were calculated. All the teeth from the 239 models were evaluated for correct recognition by the ALR with a breakdown to find which stages of the process caused the errors.

The results revealed that 1526 out of 1915 teeth (79.7%) were correctly identified, and the accuracy validation gave 95% confidence intervals for the geometric mean error of [0.285, 0.317] for the humans and [0.269, 0.325] for ALR – a negligible difference.

It is anticipated that ALR software tool will have applications throughout Dentistry and anthropology and in research will constitute an objective tool for handling large datasets without the need for time intensive employment of experts to place landmarks manually.
Sensitive and quantitative detection of MHC-I displayed neoepitopes using a semi-automated workflow and TOMAHAQ mass spectrometry
Authors: Pollock Samuel B. , Rose Christopher M. , Darwish Martine , Bouziat Romain , Delamarre Lélia , Blanchette Craig , Lill Jennie R.
Published: December 2020

Advances in several key technologies, including MHC peptidomics, has helped fuel our understanding of basic immune regulatory mechanisms and identify T cell receptor targets for the development of immunotherapeutics. Isolating and accurately quantifying MHC-bound peptides from cells and tissues enables characterization of dynamic changes in the ligandome due to cellular perturbations. This multi-step analytical process remains challenging, and throughput and reproducibility are paramount for rapidly characterizing multiple conditions in parallel. Here, we describe a robust and quantitative method whereby peptides derived from MHC-I complexes from a variety of cell lines, including challenging adherent lines, can be enriched in a semi-automated fashion on reusable, dry-storage, customized antibody cartridges. TOMAHAQ, a targeted mass spectrometry technique that combines sample multiplexing and high sensitivity, was employed to characterize neoepitopes displayed on MHC-I by tumor cells and to quantitatively assess the influence of neoantigen expression and induced degradation on neoepitope presentation.
Voxel-level forecast system for lesion development in patients with COVID-19
Authors: Jin Cheng , Duan Yongjie , Cao Yukun , Yu Jinyang , Xu Zhanwei , Chen Weixiang , Han Xiaoyu , Liu Jia , Zhou Jie , Shi Heshui , Feng Jianjiang
Published: December 2020

The global spread of COVID-19 seriously endangers human health and even lives. By predicting patients’ individualized disease development and further performing intervention in time, we may rationalize scarce medical resources and reduce mortality. Based on 1337 multi-stage (≥3) high-resolution chest computed tomography (CT) images of 417 infected patients from three centers in the epidemic area, we proposed a random forest + cellular automata (RF+CA) model to forecast voxel-level lesion development of patients with COVID-19. The model showed a promising prediction performance (Dice similarity coefficient [DSC] = 71.1%, Kappa coefficient = 0.612, Figure of Merit [FoM] = 0.257, positional accuracy [PA] = 3.63) on the multicenter dataset. Using this model, multiple driving factors for the development of lesions were determined, such as distance to various interstitials in the lung, distance to the pleura, etc. The driving processes of these driving factors were further dissected and explained in depth from the perspective of pathophysiology, to explore the mechanism of individualized development of COVID-19 disease. The complete codes of the forecast system are available athttps://github.com/keyunj/VVForecast_covid19.
Co-infection withToxoplasma gondiileads to a loss of resistance inHeligmosomoides bakeritrickle-infected mice due to ineffective granulomas
Authors: Fougere Breton , Ariyaratne Anupama , Chege Naomi , Perera Shashini , Forrester Emma , Luzzi Mayara de Cassia , Bowron Joel , Coria Aralia Leon , Szabo Edina , Finney Constance A. M.
Published: December 2020

The intestinal roundwormHeligmosomoides bakericauses chronic infection in susceptible (C57Bl/6) mice; however, repeat (trickle) infection confers immunity and facilitates worm clearance. We previously showed that this acquired immunity is associated with a strong Th2 response, notably the enhanced production of intestinal granulomas. Here we demonstrate that elevated proportions of IgG1-bound eosinophils and macrophages are observed around the developing tissue worms of trickle-infected female C57Bl/6 mice compared to bolus infected animals. Levels of IgG2c, IgA or IgE were not detected in the granulomas. Increased proportions of SiglecF+and CD206+cells, but not Ly6G+and/or NK1.1+cells, were also found in the granulomas of trickle-infected mice. However, in the natural world rather than the laboratory setting, immune environments are more nuanced. We examined the impact of a mixed immune environment on trickle infection-induced immunity, using a pre-infection withToxoplasma gondii. The mixed immune environment resulted in fewer and smaller granulomas with a lack of IgG -bound cells as well as reduced proportions of SiglecF+and CD206+cells, measured by immunofluorescence and flow cytometry. This was associated with a higher worm burden in the co-infected animals. Our data confirm the importance of intestinal granulomas and parasite-specific antibody for parasite clearance. They highlight why it may be more difficult to clear worms in the field than in the laboratory.

AUTHOR’S SUMMARY

Despite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used models of trickle infection (multiple low doses of parasites) and co-infection (two intestinal parasites) to simulate how people/animals get infected in the real world. Using these models, we have confirmed the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the host’s ability to clear worms. The lack of specific immune cells and antibodies within the granuloma was associated with chronic infection. Our results help explain why intestinal parasitic worms are so prevalent and why it may be difficult to clear worms in natural settings.
Behavioral gain following isolation of attention
Authors: Edwards Grace , Berestova Anna , Battelli Lorella
Published: December 2020

Stable sensory perception is achieved through balanced excitatory-inhibitory interactions of lateralized sensory processing. In real world experience, sensory processing is rarely equal across lateralized processing regions, resulting in continuous rebalancing. Using lateralized attention as a case study, we predicted rebalancing lateralized processing following prolonged spatial attention imbalance could cause a gain in attention the opposite direction. In neurotypical human adults, we isolated covert attention to one visual field with a 30-minute attention-demanding task and found anincreasein attention in the opposite visual field after manipulation. We suggest a gain in lateralized attention in the previously unattended visual field is due to an overshoot through attention rebalancing. The offline post-manipulation effect is suggestive of long-term potentiation affecting behavior. Our finding of visual field specific attention rebound could be critical for the development of clinical rehabilitation for patients with a unilateral lesion and lateralized attention deficits. This proof-of-concept study initiates the examination of overshoot following the release of imbalance in other lateralized control and sensory domains, important in our basic understanding of lateralized processing.
A cryo-EM structure of metazoan TRAPPIII, the multisubunit complex that activates the GTPase Rab1
Authors: Galindo Antonio , Planelles-Herrero Vicente J. , Degliesposti Gianluca , Munro Sean
Published: December 2020

The TRAPP complexes are highly conserved nucleotide exchange factors, with TRAPPIII activating Rab1 and TRAPPII acting primarily on Rab11. The two complexes share a core of small subunits that affect nucleotide exchange, but are distinguished by additional large subunits that are essential for activity in vivo, and are mutated in a range of human disorders. Crystal structures of the core subunits have revealed the mechanism of Rab activation, but how and why the large subunits associate with the core remains unclear. We report here a cryo-EM structure of the entire TRAPPIII complex fromDrosophila. The TRAPPIII-specific subunits TRAPPC8 and TRAPPC11 hold the catalytic core like a pair of tongs, with TRAPPC12 and TRAPPC13 positioned at the joint between them. TRAPPC2 and TRAPPC2L link the core to the two large arms, with the interfaces containing residues affected by disease-causing mutations. The TRAPPC8 arm is positioned such that it would contact bound Rab1, indicating how the arms could alter the Rab specificity of the core. A lower resolution structure of TRAPPII shows a similar architecture, and suggests that the TRAPP complexes evolved from a single ur-TRAPP.
Dextran sulfate sodium salt corrupted colonic crypts declined the smooth muscle tension in mouse large intestine
Authors: Yiwei Sun , Aihua Hu , shouyan Fan , Lusi Wei , Yuechuan Shi , Lu Wen , Aden Cham Mohamed , Lingfeng Gao , Yang Wang
Published: December 2020

Ulcerative colitis is one kind of colonic mucosa damage, shows high number of inflammatory epithelial cells. Dextran sulfate sodium salt (DSS) induce a milder onset of colitis or a more aggressive response. It may damage the protective effects on intestinal barrier. In this study, we investigated the damaging of colon crypts, evaluated the smooth muscle tension beneath corrupted crypts in DSS exposed mice.

Methods

female specific-pathogen-freeBALB/Cmice (n=16) are randomly divided as: group A: control mice (n=4); group B: DSS-mice (colitis, 5% DSS in drink water, days 1 to 7, n = 12). The DSS is replaced every 2 days. On day 8, mice colons are excised from the colon-cecal junction to the anus. The distal colon segment is longitude incision and aberrant crypt area are determined by methylene blue staining method. The smooth muscle strip is separated and prepared for passive tension tests. The rest segment is fixed with 10% formalin and embedded in paraffin. Histological scores are evaluated in hematoxylin-eosin staining section: crypt damage (none = 0, basal 1/3 damaged = 1, basal 2/3 damaged = 2, only the surface epithelium is intact = 3, and entire crypt and epithelium are lost = 4). The smooth muscle passive tension beneath the aberrant crypt area in DSS-mice are tested and compared with the preparations from control mice.

Results

In DSS uptake mice, the inflammation in large intestine mucosa damaged crypts with architectural distortions on day 7 (n=7). In crypts damage area, the smooth muscle passive tension and relative myogenic spontaneous contraction parameters are significantly reduced under the high preload conditions. The maximum rate of change of velocity of spontaneous contraction was noticeable attenuated.

Conclusion

Our findings demonstrate that low dosage DSS water drink result in corrupted colonic crypts. The corrupted crypts damage the large intestinal epithelium barrier, affect the smooth muscle functions, which declined in myogenic spontaneous contraction under the preload. This further may reduce the peristalsis in large intestine.
BART Cancer: a web resource for transcriptional regulators in cancer genomes
Authors: Thomas Zachary V. , Wang Zhenjia , Zang Chongzhi
Published: December 2020

Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10,000 gene expression profiling RNA-seq datasets from TCGA with over 7,000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.
Rectal bacteria produce sex pheromones in the male oriental fruit fly
Authors: Ren Lu , Yingao Ma , Xie Mingxue , Lu Yongyue , Cheng Daifeng
Published: December 2020

In recent decades, a growing body of literature has indicated that microbial symbionts of insects can modulate their hosts’ chemical profiles and mate choice decisions. However, there is currently little direct evidence indicate that insect pheromones can be produced by symbionts. UsingBactrocera dorsalisas a model system, we demonstrate thatBacillus sp.in the rectum of maleB. dorsalisplays a pivotal role in sex pheromones production. We demonstrate that 2,3,5-trimethylpyrazine (TMP) and 2,3,5,6-tetramethylpyrazine (TTMP) are sex pheromones produced in the male rectums. Mature virgin females can be strongly attracted by TMP and TTMP. TMP and TTMP contents in male rectums can be decreased when rectal bacteria are inhibited with antibiotics. Moreover,Bacillussp. isolated from male rectum can produce TMP and TTMP when providing with substrates-glucose and threonine, for which the contents are significantly higher in rectums of mature males. These findings highlight the influence of microbial symbionts on insect pheromones and provide an example of direct bacterial production of pheromones in insects.
SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19
Authors: de Campos Mata Leire , Piñero Janet , Vaquero Sonia Tejedor , Tachó-Piñot Roser , Kuksin Maria , Aldea Itziar Arrieta , Melero Natalia Rodrigo , Carolis Carlo , Furlong Laura , Cerutti Andrea , Villar-García Judit , Magri Giuliana
Published: December 2020

The production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.
Let the DOCTOR Decide Whom to Test: Adaptive Testing Strategies to Tackle the COVID-19 Pandemic
Authors: Liang Yu , Yadav Amulya
Published: December 2020

A robust testing program is necessary for containing the spread of COVID-19 infections before a vaccine becomes available. However, due to an acute shortage of testing kits (especially in low-resource developing countries), designing an optimal testing program/strategy is a challenging problem to solve. Prior literature on testing strategies suffers from two major limitations: (i) it does not account for the trade-off between testing of symptomatic and asymptomatic individuals, and (ii) it primarily focuses on static testing strategies, which leads to significant shortcomings in the testing program’s effectiveness. In this paper, we address these limitations by making five novel contributions. (i) We formally define the optimal testing problem and propose the DOCTOR POMDP model to tackle it. (ii) We solve the DOCTOR POMDP using a scalable Monte Carlo tree search based algorithm. (iii) We provide a rigorous experimental analysis of DOCTOR’s testing strategies against static baselines - our results show that when applied to the city of Santiago in Panama, DOCTOR’s strategies result in ∼40% fewer COVID-19 infections (over one month) as compared to state-of-the-art static baselines. (iv) In addition, we analyze DOCTOR’s testing policy to derive insights about the reasons behind the optimality of DOCTOR’s testing policy. (v) Finally, we characterize conditions (of the real world) under which DOCTOR’s optimization would be of most benefit to government policy makers, and thus requires significant attention from researchers in this area. Our work complements the growing body of research on COVID-19, and serves as a proof-of-concept that illustrates the benefit of having an AI-driven adaptive testing strategy for COVID-19.
Biomimetic, smart and multivalent ligands for G-quadruplex isolation and bioorthogonal imaging
Authors: Sperti Francesco Rota , Charbonnier Thibaut , Lejault Pauline , Zell Joanna , Bernhard Claire , Valverde Ibai E. , Monchaud David
Published: December 2020

G-quadruplexes (G4s) continue to gather wide attention in the field of chemical biology as their prevalence in the human genome and transcriptome strongly suggests that they may play key regulatory roles in cell biology. G4-specific, cell-permeable small molecules (G4-ligands) innovately permit the interrogation of cellular circuitries in order to assess to what extent G4s influence cell fate and functions. Here, we report on multivalent, biomimetic G4-ligands referred to as TASQs that enable both the isolation and visualization of G4s in human cells. Two biotinylated TASQs,BioTASQandBioCyTASQ, are indeed efficient molecular tools to fish out G4s of mixtures of nucleic acids through simple affinity capture protocols and to image G4s in cellsviaa biotin/avidin pretargeted imaging system first applied here to G4s, found to be a reliable alternative toin situclick chemistry.

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