bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study of mandibular expansion in combination with a fixed-appliance for increasing the effective space of the mandibular arch
Authors: Zhao Bingjing , Zhao Guizhi , Shen Tao , Wang Chao , Xiao Yihan , Han Yichen , Ke Jie
Published: March 2021

Techniques for enhancing the effective space of the mandibular arch are urgently needed. Therefore, this study aimed to perform mandibular expansion in combination with a fixed-appliance technique, with preliminary monitoring by finite element analysis and 3-dimensional cone-beam computed tomography (CBCT).

Finite element models were structured according to CBCT images of a 14-year-old girl. The von Mises stress of the alveolar bone and tooth displacement were assessed in different models. The technique was also applied in an 11-year-old boy. CBCT was performed at post-expansion, post-retention, post-treatment and 2 years after treatment. Tooth movement and alveolar bone stress were assessed by the CAD software.

Finite element analysis suggested that the teeth tended to stand upright in the buccal side in the expander model compared with the expander-remove model. However, minimum tooth change was observed in the normal model, indicating highest stability. The von Mises stress of the alveolar bone was decreased in the normal model compared with the expander model, suggesting that buccal-inclined teeth could more easily lead to alveolar bone stress than normal ones. Based on CBCT data and the 3D mandibular dentition model fitting, mandibular teeth tended to be upright in the buccal side after retention compared with the post-expansion condition, which somewhat differed from finite element analysis results. Furthermore, dehiscence and fenestration were not observed.

This expansion technique is expected to increase the effective space after mandibular expansion and reduce buccal alveolar bone stress.
Meta-analysis: combination of meropenem vs ceftazidime and amikacin for empirical treatment of cancer patients with febrile neutropenia
Authors: Wang Ying , Du Zhichao , Chen Yongdong , Liu Yugang , Yang Zhitang
Published: March 2021

Background:

Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial.

Methods:

Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants’ characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria.

Result:

The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93–1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91–1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52–1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin.

Conclusion:

Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.
Risk factors of prehypertension and hypertension among workers at public elderly welfare facilities in Taiwan
Authors: Lin Pei-Ying , Chang Chia-Chen , Tung Chen-Yin , Chu Wan-Hsia , Tong Fu-Guan
Published: March 2021

The prevalence and factors that influence prehypertension and hypertension in workers at elderly welfare facilities remain unknown. This study investigated prehypertension and hypertension as well as the relevant factors affecting the development of these conditions in workers at elderly welfare facilities.

A cross-sectional survey was conducted among 242 workers at 3 elderly welfare facilities in northern Taiwan. A structured questionnaire survey comprising demographic characteristics, job characteristics, burnout inventory, and health information was employed for data collection. Chi-Squared tests and multinomial logistic regression were adopted to analyze the correlation between research variables and blood pressures as well as relevant factors influencing prehypertension and hypertension.

The results indicated that sex, age, education level, type of work shift, work-related burnout, and body mass index of the research participants were significantly correlated with prehypertension and hypertension. The results of multinominal logistic regression demonstrated that being male, being older, being a nonnurse assistant, being obese, working in shifts, and having moderate or severe work-related burnout were associated with higher risks of prehypertension and hypertension. The interaction between age and being a nonnurse assistant was statistically significant. Compared with nonnurse assistants, nurse assistants aged ≥55 years had a relatively low risk of prehypertension and hypertension.

Age, job characteristics, work-related burnout, and obesity of workers in elderly welfare facilities were the major risk factors for prehypertension and hypertension.
Carbon dioxide: the cause of devastating stroke without hemodynamic compromise during laparoscopic nephrectomy with injury of the inferior vena cava
Authors: Yao Youxiu , Xu Mao
Published: March 2021

Rationale:

Carbon dioxide pneumoperitoneum in laparoscopic surgery can bring about occult perioperative cerebral infarction, advancing our understanding of the causes of severe postoperative delayed recovery.

Patient concerns:

Here, we report the case of a 35-year-old woman who underwent a right renal tumor resection in our institution, during which a raised pneumoperitoneum pressure (from 15 to 20 mm Hg) was adopted by the surgeon to prevent errhysis and to help stop the bleeding. Despite an accidental minor tearing of the inferior vena cava, vital signs remained stable throughout the procedure, and no obvious abnormality was observed in either end tidal carbon dioxide values or blood gas analysis. However, the patient unexpectedly suffered delayed recovery after the operation, presenting incomplete left hemiplegia and a positive Babinski sign.

Diagnoses:

Perioperative stroke was diagnosed by anesthesiologists, after excluding the effects of anesthesia. Cerebral hemorrhage was excluded, as no obvious abnormality was found in the density of brain parenchyma in the emergency computed tomography examination, and a digital subtraction angiography showed no abnormal thrombosis. Further magnetic resonance diagnosis led us to consider diffuse gas embolisms to be the cause of this acute stroke; a right echocardiography revealed that a patent foramen ovale (PFO) may account for the global cerebral gas embolisms.

Interventions:

The patient received neuroprotective drugs (Vinpocetine, Edaravone, and Xingnaojing, which are commonly used as a standard of care in China), antiplatelets and other symptomatic treatments, plus dexamethasone to relieve edema. A contrast-enhanced echocardiography of the right heart was performed, the results of which were consistent with the sonography of a PFO.

Outcomes:

The patient was hospitalized for 14 days and eventually discharged after recovery. At the latest follow-up in August 2019, the patient recovered without residual neurological sequelae.

Lessons:

Our results emphasize the need for vigilance regarding adverse cardiovascular and neurological events caused by carbon dioxide gas embolisms when encountering the inadvertent situation of vessels rupturing. Timely monitoring of paradoxical gas embolism by transoesophageal echocardiography is necessary and can avert the risk of severe complications. Urgent consideration should be given to stopping pneumoperitoneum and switching to laparotomy for hemostasis so that the patient can obtain the best benefit–risk ratio.
Use of venovenous extracorporeal membrane oxygenation for perioperative management of acute respiratory distress syndrome caused by fat embolism syndrome
Authors: Momii Kenta , Shono Yuji , Osaki Kanji , Nakanishi Yoshinori , Iyonaga Takeshi , Nishihara Masaaki , Akahoshi Tomohiko , Nakashima Yasuharu
Published: March 2021

Introduction:

Fat embolism syndrome (FES) is a known complication of long bone fracture and can affect multiple organs. The organ most commonly affected with FES is the lung. Severe cases of FES from long bone fracture can cause acute respiratory distress syndrome (ARDS). Although the treatment of ARDS remains challenging, it is reported that a lung protection strategy and prone positioning are effective. In addition, early fixation is reported to be beneficial in respiratory failure due to FES, though it may exacerbate respiratory failure during the perioperative period. We report the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the successful perioperative management of a patient diagnosed with ARDS due to FES.

Patient concerns:

A 24-year-old man injured in a traffic accident was brought to our emergency department due to shock and consciousness disorder.

Diagnosis:

After examining the patient, we noted bilateral pneumothorax, liver and spleen injuries, and multiple long bone fractures. Four days after admission, he was diagnosed with FES due to a prolonged consciousness disorder, progressive hypoxia with diffuse lung damage, and cutaneous and mucosal petechiae.

Intervention:

As respiratory failure progressed, VV-ECMO was initiated on the 6th day. To improve the respiratory failure caused by ARDS, prone position therapy was necessary. Thus, we performed osteosynthesis on the 9th day under ECMO. Prone position therapy was started after surgery.

Outcomes:

Subsequently, his respiratory condition and chest radiographs improved steadily. VV-ECMO was discontinued on the 17th day and the ventilator was removed on the 28th day. His consciousness levels improved without residual central nervous system complications.

Conclusion:

Our study reveals the successful improvement of FES-induced ARDS by osteosynthesis and prone positioning under VV-ECMO. This strategy prioritizes supportive treatment over pharmacologic interventions.
Influence of exercise test on platelet function in patients with coronary arterial disease
Authors: Mo Chunhua , Wang Yanhui , Yue Zong , Hu Dayi , Yin Chun
Published: March 2021

Background:

Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study is to investigate the platelet function and evaluate the risk of thrombotic events in CAD patients during ET.

Methods:

Pubmed, Embase, Cochrane Library, and Web of Science were searched for a systematic review from initiation to October 2019. The inclusion criteria were controlled clinical trails as study design; investigating platelet function in CAD patients during ET; with ET carried out by treadmill or bicycle ergometer; written in English. Included articles were screened based on title/abstract and full-text review by 2 independent reviewers. Platelet aggregation (PA), platelet surface expression of CD62p and PAC-1, plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (β-TG) were evaluated before and after ET.

Results:

Eighteen articles were included out of the 427 references initially identified. In most of the studies included ET was terminated because of limited symptoms. Prior to ET, no difference in platelet aggregation was observed in CAD patients compared with healthy controls in majority of the studies, with or without the treatment with Aspirin. Dual anti-platelet therapy suppressed adenosine diphosphate (ADP)-induced platelet aggregation at rest. After ET, platelet aggregation, the serum levels of β-thromboglobulin were found unchanged in majority of studies and platelet factor-4 were found unchanged in half of studies. The expression of platelet surface markers were elevated by ET in a few study.

Conclusion:

Symptom-limited exercise test did not affect platelet function in patients with coronary artery disease; however exercise to higher intensity may induce platelet activation.
Acupuncture and herbal medicine for postoperative care following anterior cruciate ligament reconstruction
Authors: Kim Hyungsuk , Chung Won-Seok
Published: March 2021

Background:

Anterior cruciate ligament reconstruction (ACLR) is the primary treatment for patients with anterior cruciate ligament (ACL) injury. Successful postoperative rehabilitation is imperative for their recovery. This protocol details the methods that will be used to systematically analyze the efficacy of acupuncture and herbal medicine for postoperative care following ACLR.

Methods and analysis:

Randomized controlled trials will be searched in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE/PubMed, Chinese National Knowledge Infrastructure, Japan Medical Abstracts Society, and 7 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean National Assembly Digital Library, Korean Association of Medical Journal Editors, Korean Studies Information Service System, Korean Traditional Knowledge Portal, National Digital Science Library, and Database Periodical Information Academic). The risk of bias will be assessed using the Cochrane assessment tool of risk of bias. The studies that are selected after checking for eligibility will be quantitatively analyzed as a meta-analysis. The primary outcome will be the scores of pain scales, and the secondary outcomes will be the range of motion of the knee, severity of the swelling, and parameters about the knee joint function.

Ethics and dissemination:

Ethical approval is not required for this protocol because it does not include patient data. The findings of this review will be disseminated through peer-reviewed publications or conference presentations.

Registration number:

DOI 10.17605/OSF.IO/ZY2W8 (https://osf.io/zy2w8).
The efficiency and safety of manual therapy for cervicogenic cephalic syndrome (CCS)
Authors: Jin Xin , Du Hong-Gen , Qiao Zu-Kang , Huang Qin , Chen Wen-Jun
Published: March 2021

Background:

Manual therapy is a common technique for the treatment of (CCS) cervicogenic cephalic syndrome, but the efficiency is various. The aim of the study is to evaluate the evidence pertaining to the efficiency and safety of using manual therapy to treat patients with CCS.

Methods:

We searched the electronic databases including PubMed, ScienceDirect, and the Cochrane Library. Only randomized controlled trials (RCTs) were enrolled in this systematic review and cumulative meta-analysis.

Results:

A total of 8 RCTs with 395 patients were included for meta-analysis. Patients who underwent manual therapy showed lower scores of visual analog scale (VAS) (weighted mean difference) WMD = 1.7, 95% confidence interval CI = 0.74–2.65, P = .0005); dizziness handicap inventory (DHI) (WMD = 0.66, 95%CI = 0.31–1, P = .0002); and neck disability index (NDI) (WMD = 0.59, 95%CI = 0.23–0.96, P = .002) and better rotation range of motion (ROM) of the cervical spine (WMD = −6.54, 95%CI = −7.60 to −5.48, P < .0001). However, these patients did not show much benefit from manual therapy with respect to the frequency of CCS episodes and head repositioning accuracy (HRA). No serious adverse effects were reported in our included studies lasting longer than 24 hours.

Conclusions:

Manual therapy offers an effective and safe approach to treat CCS with lower VAS, DHI, and NDI scores and better cervical spinal movement. Further high-quality RCTs are required to provide more conclusive evidence.

Systematic review registration number:

PROSPERO172740.
Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia
Authors: Xiao Bohan , Wang Peiguo , Zhao Yingru , Liu Ying , Ye Zhaoxiang
Published: March 2021

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).

Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.

The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).

ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.
Effectiveness of acupuncture for anxiety and depression in irritable bowel syndrome
Authors: Li Huaiyu , Chen Yun , Hu Ziyi , Jiang Jiawang , Ye Jing , Zhou Yuliang , Yu Zhiying , Tang Haiyi
Published: March 2021

Background:

Irritable bowel syndrome (IBS) is the most commonly gastrointestinal diseases. The Rome Foundation's global study on 33 countries shows the total prevalence of IBS under the Rome IV Diagnostic Criteria was 3.8%. It is well established that people with IBS have higher levels of anxiety and depression. The impact of the acupuncture associated with anxiety and depression has been widely studied in Western countries. Acupuncture may be a promising choice for the treatment of anxiety and depression in IBS.

Methods:

RCTs of acupuncture for depression and anxiety in IBS will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreement will be solved in consultation with a third reviewer.

Results:

Our study aims to explore the efficacy of acupuncture for depression and anxiety in IBS and to provide up-to-date evidence for clinical of IBS.

Conclusion:

This study will perform a comprehensive systematic review and meta-analysis on the efficacy of acupuncture for depression and anxiety in IBS, making up for the lack of relevant evidence of the clinical use of acupuncture.

INPLASY registration number:

INPLASY 202120014.
Using Dry-Erase Boards to Share Information in a Pediatric Emergency Department to Improve Family Experience of Care
Authors: Gould Lindsay M. , Byczkowski Terri L. , Bonsu Bema K. , Stoner Michael J. , Cohen Daniel M.
Published: March 2021

Objectives

To determine whether the use of dry-erase boards for communicating the plan of care of children evaluated in the pediatric emergency department (PED) improves the family experience of care.

Methods

Dry-erase boards were mounted at eye level in patient examination rooms. The study was conducted during a 4-week period during which physicians were instructed to use the boards on alternating weeks. During the 2 intervention weeks, they were instructed to write their name and plan of care in addition to their standard verbal communication. A questionnaire was administered to a convenience sample of caregivers that measured their perceptions of physician listening skills, time spent with the physician, their understanding of the care plan, their willingness to ask questions, likelihood to recommend the PED, and overall physician care. Differences between intervention and nonintervention weeks were analyzed using adjusted multivariable modeling taking into account clustered observations within physician.

Results

Surveys were completed by 672 caregivers. There were no significant differences in reported experience of care between the intervention and nonintervention weeks. During the intervention weeks, 59% of caregivers recalled use of the dry-erase boards, whereas 10% of caregivers recalled use during nonintervention weeks. Caregivers who recalled the use of dry-erase boards were more likely to report better physician listening skills, better understanding of the plan of care, and higher overall physician ratings.

Conclusions

Recommending use of dry-erase boards in pediatric emergency department rooms did not increase overall measures of experience of care, although patients who recalled dry-erase board use did report higher performance. Further study could explore how to effectively and efficiently use these boards.
Paenibacillus cymbidii sp. nov., isolated from Cymbidium goeringii roots
Authors: Sun Lei , Wang Panpan , Zhao Dongfang , Wang Jiashuo , Wu Qiji , Liu Lin , Lyu Zhitang
Published: March 2021

A Gram-stain-variable, aerobic, rod-shaped, endospore-forming strain R196T) was isolated from internal tissues of roots of Cymbidium goeringii. Cells were motile with peritrichous flagella. The colonies were light pink on tryptone soya agar medium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain R196T fell into a phylogenetic cluster belonging to the genus

Paenibacillus

. Strain R196T was closely related to

Paenibacillus cavernae

C4-5T and

Paenibacillus contaminans

CKOBP-6T with 93.6 and 93.3% sequence similarities, respectively. The major cellular polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids, two unidentified aminophospholipids and an unidentified aminolipid. The dominant respiratory quinone was MK-7. The main cellular fatty acids were anteiso-C15 : 0 (53.01%), C16 : 0 (13.04%) and iso-C16 : 0 (10.80%). The genome size of R196T was 9.45 Mb, containing 7617 predicted protein-coding genes, with a DNA G+C content of 57.7 mol%. Based on the results of phenotypic, chemotaxonomic and whole-genome analyses, strain R196T represents a novel species of the genus

Paenibacillus

, for which the name Paenibacillus cymbidii sp. nov. is proposed. The type strain is R196T (=ACCC 61713T=KCTC 33718T).
Modeling transmission dynamics and effectiveness of worker screening programs for SARS-CoV-2 in pork processing plants
Authors: VanderWaal Kimberly , Black Lora , Hodge Judy , Bedada Addisalem , Dee Scott
Published: March 2021

Pork processing plants were apparent hotspots for SARS-CoV2 in the spring of 2020. As a result, the swine industry was confronted with a major occupational health, financial, and animal welfare crisis. The objective of this work was to describe the epidemiological situation within processing plants, develop mathematical models to simulate transmission in these plants, and test the effectiveness of routine PCR screening at minimizing SARS-CoV2 circulation. Cumulative incidence of clinical (PCR-confirmed) disease plateaued at ∼2.5% to 25% across the three plants studied here. For larger outbreaks, antibody prevalence was approximately 30% to 40%. Secondly, we developed a mathematical model that accounts for asymptomatic, pre-symptomatic, and background “community” transmission. By calibrating this model to observed epidemiological data, we estimated the initial reproduction number (R) of the virus. Across plants,Rgenerally ranged between 2 and 4 during the initial phase, but subsequently declined to ∼1 after two to three weeks, most likely as a result of implementation/compliance with biosecurity measures in combination with population immunity. Using the calibrated model to simulate a range of possible scenarios, we show that the effectiveness of routine PCR-screening at minimizing disease spread was far more influenced by testing frequency than by delays in results,R, or background community transmission rates. Testing every three days generally averted about 25% to 40% of clinical cases across a range of assumptions, while testing every 14 days typically averted 7 to 13% of clinical cases. However, the absolute number of additional clinical cases expected and averted was influenced by whether there was residual immunity from a previous peak (i.e., routine testing is implemented after the workforce had experienced an initial outbreak). In contrast, when using PCR-screening to prevent outbreaks or in the early stages of an outbreak, even frequent testing may not prevent a large outbreak within the workforce. This research helps to identify protocols that minimize risk to occupational safety and health and support continuity of business for U.S. processing plants. While the model was calibrated to meat processing plants, the structure of the model and insights about testing are generalizable to other settings where large number of people work in close proximity.
Real World Performance of SARS-CoV-2 Antigen Rapid Diagnostic Tests in Various Clinical Settings
Authors: Regev-Yochay Gili , Kriger Or , Beni Sharon , Rubin Carmit , Mina Michael J. , Mechnik Bella , Hason Sabrina , Biber Elad , Nadaf Bian , Kreiss Yitshak , Amit Sharon
Published: March 2021

Background

Several uses of Antigen rapid diagnostic tests (Ag-RDT) have been suggested. Analytical studies reported high specificity yet with lower sensitivity for detecting SARS-CoV-2 compared to qRT-PCR. Here, we present the use of these tests as a decision support tool in several settings.

Methods

Samples were collected for both Ag-RDT and qRT-PCR in three different clinical settings; 1. Symptomatic patients presenting at the Emergency Departments 2. Asymptomatic patients screened upon hospitalization and 3. Health-care workers (HCW) following SARS-CoV-2 exposure. Positive percent agreement (PPA), negative percent agreement (NPA), positive predictive value (PPV) and negative predictive value (NPV) were calculated. To estimate the association between Ct value, Ag-RDT and the number of days since SARS-CoV-2 exposure or symptomatic COVID-19, a mixed model was applied.

Results

A total of 5172 samples were obtained from 4595 individuals, with Ag-RDT and qRT-PCR results. Of these, 485 samples were positive by qRT-PCR. The PPA of Ag-RDT was greater for lower Ct values, reaching 93% in cases where Ct value was lower than 25 and 85% where Ct value was lower than 30. PPA was similar between symptomatic and asymptomatic individuals. The NPV and PPV were 96.8% and 99.1%, respectively. We observed a significant correlation between Ct value and time from infection onset (p<0.001). Lower Ct values were significantly associated with a positive Ag-RDT (p=0.01).

Conclusions

Ag-RDT can be used as a decision support tool in various clinical settings and play a major role in early detection of SARS-CoV-2 infected individuals, highly specific and with high sensitivity to the infectious stage of disease, whether symptomatic or asymptomatic.
RT-RC-PCR: a novel and highly scalable next-generation sequencing method for simultaneous detection of SARS-COV-2 and typing variants of concern
Authors: Mattocks Christopher , Ward Daniel , Mackay Deborah
Published: March 2021

We describe a novel assay method: reverse-transcription reverse-complement polymerase chain reaction (RT-RC-PCR), which rationalises reverse transcription and NGS library preparation into a single closed tube reaction. By simplifying the analytical process and cross-contamination risks, RT-RC-PCR presents disruptive scalability and economy while using NGS and LIMS infrastructure widely available across health service, institutional and commercial laboratories.

We present a validation of RT-RC-PCR for the qualitative detection of SARS-CoV-2 RNA by NGS. The limit of detection is comparable to real-time RT-PCR, and no obvious difference in sensitivity was detected between extracted nasopharyngeal swab (NPS) RNA and native saliva samples.

The end point measurement of RT-RC-PCR is NGS of amplified sequences within the SARS-CoV-2 genome; we demonstrated its capacity to detect different variants using amplicons containing delH69-V70 and N501Y, both of which emerged in the UK Variant of Concern B.1.1.7 in 2020.

In summary, RT-RC-PCR has potential to facilitate accurate mass testing at disruptive scale and cost, with concurrent detection of variants of concern.
The Missing Link: A Closed Form Solution to the Kermack and Mckendrick Epidemic Model Equations
Authors: Duclos Ted , Reichert Tom
Published: March 2021

Susceptible–infectious–recovered (SIR) models are widely used for estimating the dynamics of epidemics. Such models project that containment measures “flatten the curve”, i.e., reduce but delay the peak in daily infections, cause a longer epidemic, and increase the death toll. These projections have entered common understanding; individuals and governments often advocate lifting containment measures such as social distancing to shift the peak forward, limit societal and economic disruption, and reduce mortality. It was, then, an extraordinary surprise to discover that COVID-19 pandemic data exhibit phenomenology opposite to the projections of SIR models. With the knowledge that the commonly used SIR equations only approximate the original equations developed to describe epidemics, we identified a closed form solution to the original epidemic equations. Unlike the commonly used approximations, the closed form solution replicates the observed phenomenology and quantitates pandemic dynamics with simple analytical tools for policy makers. The complete solution is validated using independently measured mobility data and accurately predicts COVID-19 case numbers in multiple countries.
A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy with Applications to the COVID-19 Outcome
Authors: Wang Anqi , Liu Zhonghua
Published: March 2021

Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and also have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy phenomenon. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalizedt-distribution (Arellano-Valle and Bolfarine, 1995) to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalizedt-distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the EM-type algorithms. We compute the standard errors by calibrating the evidence lower bound using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared to other competing methods. We also apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we find that coronary artery disease is associated with increased risk of critically ill coronavirus disease 2019 (COVID-19). We also develop a user-friendly R packageRBMR(https://github.com/AnqiWang2021/RBMR) for public use.
Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study.
Authors: Silva Marcelo , Espejo Andrés , L Pereyra María , Lynch Martín , Thompson Marcos , Taconelli Hernán , Baré Patricia , J Pereson Matías , Garbini Marcelo , Crucci Pablo , Enriquez Diego
Published: March 2021

The fast spread of COVID-19 has overcrowded Public Health Systems facilities in major countries due to the large number of seriously ill patients, particularly those requiring admission to intensive care units. Reducing viral load, along with other recommended epidemiological measures, such as social distancing and home confinement, can in time significantly help to reduce the infection R0 (Basic Reproductive Rate) and then mitigate disease burden. Early negativization or otherwise reduction of the viral load can potentially diminish disease severity, resulting in a better-controlled public health response, avoiding collapse of healthcare systems. Nitazoxanide, a widely used thiazolide approved by the FDA as an antiparasitic drug, also approved in Brazil for Norovirus and Rotavirus treatments, has an excellent safety record for a variety of indications. Nitazoxanide exhibits activity in vitro against MERS-CoV and other coronaviruses; and a specific antiviral effect (in micro molar doses) against SARS-CoV-2. The objective of this study was to evaluate the efficacy and safety of Nitazoxanide in reducing the SARS-COV 2 viral load within 7 days of treatment in respiratory samples from COVID-19-infected patients with mild to moderate disease, compared to placebo. An interim analysis showed that the ratio of patients with a viral load reduction ≥ 35% from baseline up to day 7 of treatment was significantly greater for Nitazoxanide compared to placebo (47.8% vs. 15.4%; Δ 34.6%; 95% CI: 64.7; 4.6: p = 0.037).

KEY POINTS

State of the Art

Different studies conclude that viral load (VL) would correlate with morbidity, mortality and contagiousness of COVID-19.

Early negativization or reduction of the viral load can potentially reduce the severity of this disease.

In vitro data demonstrated a specific antiviral effect of Nitazoxanide for SARS-CoV-2.

Article contribution

Nitazoxanide showed a statistically significant difference versus placebo in the number of patients who had their viral load reduced by at least 35% in mild to moderate COVID-19 disease.

The observed antiviral effect in vitro would seems to be verified in patients with mild to moderate COVID-19 infection, which should be confirmed by studies with a larger cohort of patients.
Quantification of seizure termination patterns reveals limited pathways to seizure end
Authors: Salami Pariya , Borzello Mia , Kramer Mark A. , Westover M. Brandon , Cash Sydney S.
Published: March 2021

Seizures result from a variety of pathologies and exhibit great diversity in their dynamics. Although many studies have examined the dynamics of seizure initiation, few have investigated the mechanisms leading to seizure termination. We examined intracranial recordings from patients with intractable focal epilepsy to differentiate seizure termination patterns and investigate whether these termination patterns are indicative of different underlying mechanisms.

Seizures (n=710) were recorded intracranially from 104 patients and visually classified as focal or secondarily generalized. Only two patterns emerged from this analysis: (a) those that end simultaneously across the brain (synchronous termination), and (b) those whose ictal activity terminates in some regions but continues in others (asynchronous termination). Finally, seizures ended with either an intermittent bursting pattern (burst suppression pattern), or continuous activity (continuous bursting). These findings allowed for a classification and quantification of the burst suppression ratio, absolute energy and network connectivity of all seizures and comparison across different seizure termination patterns.

We found that different termination patterns can manifest within a single patient, even in seizures originating from the same onset locations. Most seizures terminate with patterns of burst suppression regardless of generalization but that seizure that secondarily generalize show burst suppression patterns in 90% of cases, while only 60% of focal seizures exhibit burst suppression. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous bursting were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous bursting compared to seizures with burst suppression.

Our study demonstrates that there are a limited number of seizure termination patterns, suggesting that, unlike seizure initiation, the number of mechanisms underlying seizure termination is constrained. The study of termination patterns may provide useful clues about how these seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.
Economic Benefits of COVID-19 Screening Tests with a Vaccine Rollout
Authors: Atkeson Andrew , Droste Michael , Mina Michael J. , Stock James H.
Published: March 2021

This note estimates the costs and benefits of a nationwide COVID-19 screening testing program in the presence of vaccine distribution. Even for an optimistic vaccine rollout scenario, a well-designed federally-funded screening testing program, coupled with self-isolation of those who test positive, pays for itself in terms of increased GDP and is projected to save 20,000 or more lives. The sooner the testing program is put in place, the greater are its net economic benefits. This note updates the December 9, 2020 version to include updated deaths data, later dates for rolling out the screening testing program, and the spread of more contagious variants such as the B.1.1. 7 variant.
Saliva testing is accurate for early-stage and presymptomatic COVID-19
Authors: Johnson Abigail J. , Zhou Shannon , Hoops Suzie L. , Hillmann Benjamin , Schomaker Matthew , Kincaid Robyn , Daniel Jerry , Beckman Kenneth , Gohl Daryl M. , Yohe Sophia , Knights Dan , Nelson Andrew C.
Published: March 2021

Background

Although nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, making them amenable to population-scale screening.

Methods

To evaluate sampling alternatives for population screening, we collected NP, saliva, and nasal samples from two cohorts with varied levels and types of symptoms.

Results

In a mixed cohort of 60 symptomatic and asymptomatic participants, we found that saliva had 88% concordance with NP when tested in the same testing lab (n = 41), and 68% concordance when tested in different testing labs (n = 19). In a second cohort of 20 participants hospitalized for COVID-19, saliva had 74% concordance with NP tested in the same testing lab, but detected virus in two participants that tested negative with NP on the same day. Medical record review showed that the saliva-based testing sensitivity was related to the timing of symptom onset and disease stage.

Conclusions

We find that no sample site will be perfectly sensitive for COVID-19 testing in all situations, and the significance of negative results will always need to be determined in the context of clinical signs and symptoms. Saliva retained high clinical sensitivity while allowing easier collection, minimizing the exposure of healthcare workers and need for personal protective equipment, and making it a viable option for population-scale testing.
Integrating structured and unstructured citizen science data to improve wildlife population monitoring
Authors: Boersch-Supan Philipp H. , Robinson Robert A.
Published: March 2021

Accurate and robust population trend assessments are key to successful biodiversity conservation. Citizen science surveys have provided good evidence of biodiversity declines whilst engaging people with them. Citizen scientists are also collecting opportunistic biodiversity records at unprecedented scales, vastly outnumbering records gathered through structured surveys. Opportunistic records exhibit spatio-temporal biases and heterogeneity in observer effort and skill, but their quantity offers a rich source of information. Data integration, the combination of multiple information sources in a common analytical framework, can potentially improve inferences about populations compared to analysing either in isolation. We combine count data from a structured citizen science survey and detection-nondetection data from an opportunistic citizen science programme. Population trends were modelled using dynamic N-mixture models to integrate both data sources. We applied this approach to two different inferential challenges arising from sparse data: (i) the estimation of population trends for an area smaller than a structured survey stratum, and (ii) the estimation of national population trends for a rare but widespread species. In both cases, data integration yielded population trajectories similar to those estimated from structured survey data alone but had higher precision when the density of opportunistic records was high. In some cases this allowed inferences about population trends where indices derived from single data sources were too uncertain to assess change. However, there were differences in the trend magnitude between the integrated and the standard survey model.

We show that data integration of large-scale structured and unstructured data is feasible and offers potential to improve national and regional wildlife trend estimates, although a need to independently validate trends remains. Smaller gains are achieved in areas where uptake of opportunistic recording is low. The integration of opportunistic records from volunteer-selected locations alone may therefore not adequately address monitoring gaps for management and policy applications. To achieve the latter, scheme organisers should consider providing incentives for achieving representative coverage of target areas in both structured and unstructured recording schemes.
Targeting LDHC dysregulates the cell cycle and improves sensitivity to cisplatin and olaparib
Authors: Naik Adviti , Decock Julie
Published: March 2021

The cancer testis antigen (CTA) lactate dehydrogenase C (LDHC) is a promising anti-cancer target with tumor-specific expression, immunogenicity and a role in metabolic reprogramming. Interrogation of the TCGA breast cancer cohort demonstrates upregulation ofLDHCexpression, conferring unfavorable prognosis. Although the role of LDHC is well characterized in spermatocytes, its role in tumors remains largely unknown. We investigated whether LDHC is involved in regulating genomic stability and may be targeted to affect tumor cellular fitness. SilencingLDHCin four breast cancer cell lines significantly increased the presence of giant cells and nuclear aberrations, DNA damage and apoptosis.LDHCsilenced cells demonstrated aberrant cell cycle progression with differential expression of cell cycle checkpoint and DNA damage response regulators. In addition,LDHCsilencing induced microtubule destabilization, culminating in increased mitotic catastrophe and reduced long-term survival. Notably, cisplatin and olaparib treatment further reduced survival ofLDHCsilenced cells. This study supports the therapeutic potential of targeting LDHC to mitigate cancer cell survival, and improve sensitivity to DNA damaging and DNA damage repair inhibiting agents.
CaSR modulates sodium channel-mediated Ca2+-dependent excitability
Authors: Martiszus Briana J. , Tsintsadze Timur , Chang Wenhan , Smith Stephen M.
Published: March 2021

Increasing extracellular [Ca2+] ([Ca2+]o) strongly decreases intrinsic excitability in neurons but the mechanism is unclear. By one hypothesis, [Ca2+]oscreens surface charge reducing voltage-dependent sodium channel (VGSC) activation and by another [Ca2+]oactivates Calcium-sensing receptor (CaSR) closing the sodium-leak channel (NALCN). Here we report that action potential (AP) firing rates increased in wild-type (WT), but not CaSR null mutant (Casr-/-) neocortical neurons, following the switch from physiological to reduced Ca2+-containing Tyrode. However, after membrane potential correction, AP firing increased similarly in both genotypes inconsistent with CaSR regulation of NALCN. Activation of VGSCs was the dominant contributor to the increase in excitability after the [Ca2+]ochange. VGSC conductance-voltage relationships were hyperpolarized by decreasing [Ca2+]ofor Casr-/- neurons indicating CaSR contributes to [Ca2+]o-dependent excitability via VGSCs. Regulation of VGSC gating by [Ca2+]ois the key mechanism mediating [Ca2+]o-dependent changes in neocortical neuron excitability and CaSR influences neuronal excitability by its effects on VGSC gating.
Similarity Measure for Sparse Time Course Data Based on Gaussian Processes
Authors: Liu Zijing , Barahona Mauricio
Published: March 2021

We propose a similarity measure for sparsely sampled time course data in the form of a loglikelihood ratio of Gaussian processes (GP). The proposed GP similarity is similar to a Bayes factor and provides enhanced robustness to noise in sparse time series, such as those found in various biological settings, e.g., gene transcriptomics. We show that the GP measure is equivalent to the Euclidean distance when the noise variance in the GP is negligible compared to the noise variance of the signal. Our numerical experiments on both synthetic and real data show improved performance of the GP similarity when used in conjunction with two distance-based clustering methods.
A causal role for the right frontal eye fields in value comparison
Authors: Mitsumasu Andres , Krajbich Ian , Polania Rafael , Ruff Christian C. , Fehr Ernst
Published: March 2021

Recent studies have suggested close functional links between visual attention and decision making. This suggests that the corresponding mechanisms may interface in brain regions known to be crucial for guiding visual attention – such as the frontal eye field (FEF). Here, we combined brain stimulation, eye tracking and computational approaches to explore this possibility. We show that inhibitory transcranial magnetic stimulation (TMS) over the right FEF has a causal impact on decision-making, reducing the effect of gaze dwell time on choice while also increasing reaction times. We computationally characterize this putative mechanism by using the attentional drift diffusion model (aDDM), which reveals that FEF inhibition reduces the relative discounting of the non-fixated option in the comparison process. Our findings establish an important causal role of the right FEF in choice, elucidate the underlying mechanism, and provide support for one of the key causal hypotheses associated with the aDDM.