bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockin mouse model of the human CFL2 p.A35T mutation results in a unique splicing defect and severe myopathy phenotype
Authors: Rosen Samantha M , Joshi Mugdha , Hitt Talia , Beggs Alan H , Agrawal Pankaj B
Published: March 2020

Cofilin-2 is an actin-binding protein that is predominantly expressed in skeletal and cardiac muscles and belongs to the AC group of proteins, which includes cofilin-1 and destrin. In humans, cofilin-2 (CFL2) mutations have been associated with congenital myopathies that include nemaline and myofibrillar myopathy. To understand the pathogenicity of the human CFL2 mutation, p.A35T, that first linked cofilin-2 with the human disease, we created a knock-in mouse model. The Cfl2A35T/A35T (KI) mice were indistinguishable from their wild-type littermates at birth, but they rapidly worsened and died by postnatal day 9. The phenotypic, histopathologic and molecular findings mimicked the constitutive Cfl2-knockout (KO) mice described previously, including sarcomeric disruption and actin accumulations in skeletal muscles and negligible amounts of cofilin-2 protein. In addition, KI mice demonstrated a marked reduction in Cfl2 mRNA levels in various tissues including skeletal muscles. Further investigation revealed evidence of alternative splicing with the presence of two alternate transcripts of smaller size. These alternate transcripts were expressed at very low levels in the wild-type mice and were significantly upregulated in the mutant mice, indicating that pre-translational splicing defects may be a critical component of the disease mechanism associated with the mutation. Evidence of reduced expression of the full-length CFL2 transcript was also observed in the muscle biopsy sample of the patient with p.A35T mutation.
A critical review of symbiosis approaches in the context of Industry 4.0☆
Authors: Scafà Martina , Marconi Marco , Germani Michele
Published: March 2020

The implementation of symbiosis approaches is recognized as an effective industrial strategy towards the optimization of resource exploitation and the improvement of collaboration in the context of Industry 4.0. An industrial system can be considered as a complex environment in which material, energy, machine, and human resources should cooperate towards the improvement of efficiency and the creation of value. According to this vision, the paper presents a detailed literature review about the existing symbiosis approaches: (i) industrial symbiosis models, which mainly aim at the sharing of resources among different companies, and (ii) human symbiosis, which focuses on how to effectively strengthen the synergy among humans and machines. Strengths, weaknesses and correlations among the most common symbiosis approaches are analysed and classified. Finally, the existing symbiosis models are related with the pillars of the Industry 4.0 paradigm, in order to understand what should be the future directions of research in the context of collaborative manufacturing.
Datana drexelii (Lepidoptera: Notododontidae) Occurrence and Larval Survival on Highbush Blueberry Cultivars
Authors: Baranowski Alex K , Alm Steven R , Preisser Evan L
Published: March 2020

Plant genotype influences plant suitability to herbivores; domesticated plants selected for properties such as high fruit yield may be particularly vulnerable to herbivory. Cultivated strains of highbush blueberry, Vaccinium corymbosum L. can be high-quality hosts for larvae of the gregariously feeding notodontid Datana drexelii (Hy. Edwards). We conducted an experiment assessing D. drexelii larval survival and pupal weight when fed foliage from five blueberry cultivars: ‘Bluecrop’, ‘Bluetta’, ‘Blueray’, ‘Lateblue’, and ‘Jersey’. We complemented this experimental work with repeated bush-level surveys of a managed blueberry patch for naturally occurring D. drexelii larval clusters. Larval survival and pupal weight were significantly higher on ‘Lateblue’ foliage than from the ‘Bluecrop’, ‘Bluetta’, and ‘Jersey’ cultivars. The blueberry patch surveys found more D. drexelii larval clusters on ‘Bluehaven’, ‘Collins’, and ‘Darrow’ bushes than on the cultivars ‘Earliblue’ and ‘Jersey’. The low D. drexelii occurrence and performance on the ‘Jersey’ cultivar suggests that this variety may be appropriate for areas where this pest is common; conversely, their high occurrence on ‘Bluehaven’ ‘Collins’, and ‘Darrow’ suggests that these cultivars may be particularly vulnerable. Cultivar-level variation in herbivore vulnerability highlights how understanding plant–pest interactions can help manage agricultural species.
Outcome Assessment in Epidemiological Studies of Low-Dose Radiation Exposure and Cancer Risks: Sources, Level of Ascertainment, and Misclassification
Authors: Linet Martha S , Schubauer-Berigan Mary K , Berrington de González Amy
Published: March 2020

Background

Outcome assessment problems and errors that could lead to biased risk estimates in low-dose radiation epidemiological studies of cancer risks have not been systematically evaluated.

Methods

Incidence or mortality risks for all cancers or all solid cancers combined and for leukemia were examined in 26 studies published in 2006–2017 involving low-dose (mean dose ≤100 mGy) radiation from environmental, medical, or occupational sources. We evaluated the impact of loss to follow-up, under- or overascertainment, outcome misclassification, and changing classifications occurring similarly or differentially across radiation dose levels.

Results

Loss to follow-up was not reported in 62% of studies, but when reported it was generally small. Only one study critically evaluated the completeness of the sources of vital status. Underascertainment of cancers (“false negatives”) was a potential shortcoming for cohorts that could not be linked with high-quality population-based registries, particularly during early years of exposure in five studies, in two lacking complete residential history, and in one with substantial emigration. False positives may have occurred as a result of cancer ascertainment from self- or next-of-kin report in three studies or from enhanced medical surveillance of exposed patients that could lead to detection bias (eg, reporting precancer lesions as physician-diagnosed cancer) in one study. Most pediatric but few adult leukemia studies used expert hematopathology review or current classifications. Only a few studies recoded solid cancers to the latest International Classification of Diseases or International Classification of Diseases for Oncology codes. These outcome assessment shortcomings were generally nondifferential in relation to radiation exposure level except possibly in four studies.

Conclusion

The majority of studies lacked information to enable comprehensive evaluation of all major sources of outcome assessment errors, although reported data suggested that the outcome assessment limitations generally had little effect on risk or biased estimates towards the null except possibly in four studies.
Precedent in the WTO: Retrospective Reflections for a Prospective Dispute Settlement Mechanism
Authors: de Andrade Mariana Clara
Published: March 2020

Several factors triggered the legitimacy crisis which paralysed the WTO Appellate Body in December 2019. This article focuses on one of them: the criticism expressed by the United States that the ‘Appellate Body claims its reports are entitled to be treated as precedent’. This work describes the origins of the problem and examines the issue of the precedential value of adopted reports within the WTO dispute settlement. It argues that the problem cannot be addressed through textual attempts to better define the value of precedent, as some have suggested, but can be alleviated through the practice of adjudicators. Moreover, it argues that the criticisms regarding the precedential value of past reports is due to the inherent hierarchy ensuing from the existence of an appeals organ. Therefore, the demise of the Appellate Body may weaken the precedential value of past adopted reports.
White Devils, Satanic Jews: The Nation of Islam From Fard to Farrakhan
Authors: Norwood Stephen H , Pollack Eunice G
Published: March 2020

This article explores how the American white far right—including the Christian Front, Christian Mobilizers, and Gerald L. K. Smith—helped shape the Nation of Islam’s (NOI) antisemitism during the 1930s and 1940s. It also examines the strong influence of Harlem’s pro-Axis Black Fuehrers on the NOI during World War II. Nation of Islam and white far-right propaganda were remarkably similar. Both embraced the Protocols of the Learned Elders of Zion, denied or minimized the Holocaust, and were virulently anti-Zionist. After elaborating on the context within which the Nation of Islam created its ideology, the article explores how the NOI, which originally identified whites, Christians and Jews as devils, adopted an almost singular emphasis on Jews as agents of Satan, the Star of David replacing the cross as the symbol of iniquity. Jews were not victims, but Blacks’ major victimizers; never slaves, but dominant enslavers; not progressives, but those who impeded Blacks’ advance. Instead of giving the world Hebrew Scripture, they converted it into the “Poison Book,” from the beginning crafting a “dirty religion,” which blessed the subjugation of black people, and denied God’s promise to the “Real Children of Israel.” These “imposter Jews” concealed that the Hebrew Bible was a prophecy about “the so-called Negroes of America”—the true “Chosen of God”—who would be in bondage for 400 years, strangers in a strange land.
Collision between molecular clouds – I. The effect of the cloud virial ratio in head-on collisions
Authors: Tanvir Tabassum S , Dale James E
Published: March 2020

In a series of papers, we investigate the effect of collisions between turbulent molecular clouds on their structure, evolution, and star formation activity. In this paper, we look into the role of the clouds’ initial virial ratios. Three different scenarios were examined: both clouds initially bound, one cloud bound and one unbound, and both clouds initially unbound. Models in which one or both clouds are bound generate filamentary structures aligned along the collision axis and discernible in position–position and position–velocity space. If neither cloud is bound, no filaments result. Unlike in previous simulations of collisions between smooth clouds, owing to the substructure created in the clouds by turbulence before the collisions, dissipation of kinetic energy by the collision is very inefficient and in none of our simulations is sufficient bulk kinetic energy lost to render the clouds bound. Simulations where both clouds are bound created twice as much stellar mass than the bound–unbound model, and both these scenarios produced much more stellar mass than the simulation in which both clouds are unbound. Each simulation was also compared with a control run in which the clouds do not collide. We find the bound–bound collision increases the overall star formation efficiency by a factor of approximately two relative to the control, but that the bound–unbound collision produces a much smaller increase, and the collision has very little effect on the unbound–unbound cloud collision.
Urgent Treatment for Symptomatic Carotid Stenosis: The Pittsburgh Revascularization and Treatment Emergently After Stroke (PIRATES) Protocol
Authors: Jankowitz Brian T , Tonetti Daniel A , Kenmuir Cynthia , Rao Rahul , Ares William J , Zussman Benjamin , Brown Merritt W , Stone Jeremy G , Gardner Paul A , Friedlander Robert M , Gross Bradley A , Jadhav Ashutosh P , Jovin Tudor G
Published: March 2020

BACKGROUND

Patients with symptomatic carotid stenosis remain at high risk of early recurrent stroke without revascularization. This risk must be balanced against a higher rate of periprocedural complications associated with early revascularization.

OBJECTIVE

To analyze prospectively recorded data from an institutional protocol that standardized the urgent (<48 h) treatment of patients presenting with symptomatic carotid stenosis and underwent either carotid stenting (CAS) or carotid endarterectomy (CEA).

METHODS

All patients presenting over 28 mo to a comprehensive stroke center with symptomatic carotid stenosis within 48 h of index event were screened for inclusion. All patients were given dual-antiplatelet therapy. If there was clinical equipoise between CEA and CAS, patients underwent angiography and subsequently revascularization if digital subtraction angiography demonstrated ≥50% stenosis. The primary outcome was a composite of stroke or death within 30 d.

RESULTS

This study included 178 patients with a diagnosis of recently symptomatic carotid stenosis; 120 patients (67%) met the criteria. A total of 59 patients underwent CEA and 61 patients underwent CAS. There were not significant differences in the primary outcome; 3 patients (5.1%) in the CEA arm and 3 patients (4.9%) in the CAS arm met the primary outcome.

CONCLUSION

In this prospective analysis, urgent revascularization for symptomatic carotid stenosis can be done with equivalently low rates of stroke or death, regardless of revascularization strategy.
A Novel Foraminoplasty Technique for Posterolateral Percutaneous Transforaminal Endoscopic Lumbar Surgery
Authors: Liu Xinchun , Peng Yunfei
Published: March 2020

BACKGROUND

In posterolateral percutaneous transforaminal endoscopic lumbar surgery, foraminoplasty is currently performed by resecting part of the superior articular process together with surrounding soft tissues. This procedure remains technically demanding. An ideal foraminoplasty technique should be safe, easy, efficient, and controllable and should minimize X-ray exposure.

OBJECTIVE

To introduce a novel foraminoplasty technique that is designed in an attempt to obtain the ideal state.

METHODS

The technique is introduced step by step by case illustration. Briefly, the technique is based on the addition of a novel instrument, named a “Foraminoplasty Working Tube,” to the commercialized spinal endoscope system. Through the foraminoplasty working tube, the foraminoplasty procedure can be performed under either reduced X-ray guidance or direct endoscopic view.

RESULTS

The technique allows the surgeon to perform an accurate resection of the superior articular process by easily adjusting the foraminoplasty working tube to the target area. To a great extent, the volume of the bone resected is predictable and controllable and just meets the demands of the operation without excessive resection of the superior articular process.

CONCLUSION

The present technique would potentially be a safer, easier, and more efficient foraminoplasty technique.
Supraclinoid Internal Carotid Artery Aneurysm Clipping Complicated by Aneurysm Dome Origin of the Anterior Choroidal Artery: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: March 2020

Supraclinoid internal carotid artery (ICA) aneurysms most commonly arise at the origin of the posterior communicating or anterior choroidal artery. The unique angioarchitecture presented in this case involved the anterior choroidal artery (AChA) originating from the dome of a supraclinoid ICA aneurysm. Treatment is associated with high morbidity because of the eloquent parenchyma perfused by the AChA. Therefore, the preservation of flow within the AChA during clipping is paramount. Anterior choroidal syndrome, comprising hemiplegia, hemianesthesia, and hemianopsia, conveys a significant morbidity. This syndrome is observed in the setting of AChA sacrifice and can be observed in a delayed manner after clipping. Anterior choroidal syndrome is of uncertain etiology but is associated with AChA infarction. This patient presented with tinnitus and was found to have an incidental supraclinoid ICA aneurysm with AChA originating from the aneurysmal dome. A right orbitozygomatic craniotomy was performed for a transsylvian approach to the aneurysm. A fenestrated clip was applied to occlude the aneurysmal portion of the ICA up to the point of AChA origin. A curved clip was then used to occlude the AChA segment of the aneurysm, providing patency to the AChA takeoff along the ICA. Patency of the AChA and ICA was confirmed with intraoperative angiography, and the patient had a favorable clinical outcome. This case exemplified an excellent surgical clipping of a challenging supraclinoid ICA aneurysm involving the need to preserve a vessel off the aneurysm dome. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Large Cervical Ependymoma: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: March 2020

Spinal ependymomas compose approximately 60% of spinal gliomas, the predominance occurring within adults. These tumors are generally benign, and maximal surgical resection with neurological preservation is the surgical goal. This patient had a large upper cervical ependymoma, which was approached through a cervical laminotomy. The surgical resection of this lesion demonstrates the principles of pial venous plexus preservation during posterior midline raphe identification and dissection. Gross total surgical resection was achieved with the preservation of the patient's baseline neurological function. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Trajectory analysis combining pain and physical function in individuals with knee and hip osteoarthritis: results from the French KHOALA cohort
Authors: Wieczorek Maud , Rotonda Christine , Coste Joël , Pouchot Jacques , Saraux Alain , Guillemin Francis , Rat Anne-Christine
Published: March 2020

Objectives

The aims of this study were to identify homogeneous subgroups of knee and/or hip OA patients with distinct trajectories of the combination of pain and physical function (PF) over time and to determine the baseline factors associated with these trajectories.

Methods

We used data from the Knee and Hip Osteoarthritis Long-term Assessment (KHOALA) cohort, a French population-based cohort of 878 patients with symptomatic knee and/or hip OA. Pain and PF were measured annually over 5 years with the Medical Outcomes Study Short Form 36 questionnaire. First, trajectory models were estimated with varying numbers of groups for each of the outcomes separately then fitted into a multi-trajectory model. We used multinomial logistic regression to determine the baseline characteristics associated with each trajectory.

Results

Univariate four-class models were identified as most appropriate for pain and PF. Comparison of separate trajectories showed that 41% of patients included in the severe functional limitations trajectory did not belong to the more severe pain trajectory (Cramér’s V statistic = 0.45). Group-based multi-trajectory modelling revealed four distinct trajectories of pain and PF. On multivariate analyses, female sex, older age, high Kellgren grade, low physical activity intensity, low psychosocial distress score (high distress) and low vitality score were associated with the more severe symptoms trajectory.

Conclusion

Over 5 years, we identified four distinct trajectories combining pain and PF. Management of weight, fatigue and psychosocial distress and the practice of physical activity seem important to maintain function and limit pain in patients with lower-limb OA.
Universal Screening and Vaccination for Hepatitis B in Pregnancy
Authors: Prabhu Malavika , Riley Laura E.
Published: March 2020

Recommendations for screening for hepatitis B immunity in pregnancy and vaccinating susceptible women vary among professional societies. The American College of Obstetricians and Gynecologists recommends vaccinating high-risk women for hepatitis B. However, only one fourth of U.S. adults have received a complete hepatitis B vaccination series. Because two thirds of individuals with chronic hepatitis B are unaware of their diagnosis, risk-based screening for immunity followed by vaccination of susceptible women may not identify and protect all women at risk. Acquisition of hepatitis B poses short-term and long-term risks to maternal and fetal health, an outcome that can be prevented by vaccination. Hepatitis B vaccination in pregnancy is safe and efficacious and can be completed during the course of prenatal care. Universal screening for hepatitis B immunity and vaccination of susceptible women in pregnancy should be a priority during prenatal care. Cost-effectiveness studies are needed to validate this approach.
Inconsistent Mandated Access to Fertility Preservation
Authors: Sax Megan R. , Pavlovic Zoran , DeCherney Alan H.
Published: March 2020

With improvement in cancer therapies, there has been an increasing emphasis on survivorship, including options for fertility preservation. Fertility preservation is the process of either protecting or saving gametes or reproductive tissues for potential future procreation. Methods and outcomes of fertility preservation have similarly been rapidly advancing. Before initiation of gonadotoxic therapy, health care providers must consider future fertility of patients and provide options for fertility preservation. Nonetheless, the cost of fertility preservation can be prohibitory. Depending on a patient's state of residence, insurance may be mandated to cover, or offer to cover, the cost of fertility preservation. State legislation continues to change; however, legislation at the federal level has been proposed to make this coverage more cohesive. This commentary reviews current state legislation regarding mandates to cover the cost of fertility preservation for patients at risk for iatrogenic infertility and outlines the importance of developing federal legislation to improve patient access to care.
Peripherally acting opioid analgesics and peripherally-induced analgesia
Authors: Martínez Vicente , Abalo Raquel
Published: March 2020

The management of pain, particularly chronic pain, is still an area of medical need. In this context, opioids remain a gold standard for the treatment of pain. However, significant side effects, mainly of central origin, limit their clinical use. Here, we review recent progress to improve the therapeutic and safety profiles of opioids for pain management. Characterization of peripheral opioid-mediated pain mechanisms have been a key component of this process. Several studies identified peripheral µ, δ, and κ opioid receptors (MOR, DOR, and KOR, respectively) and nociceptin/orphanin FQ (NOP) receptors as significant players of opioid-mediated antinociception, able to achieve clinically significant effects independently of any central action. Following this, particularly from a medicinal chemistry point of view, main efforts have been directed towards the peripheralization of opioid receptor agonists with the objective of optimizing receptor activity and minimizing central exposure and the associated undesired effects. These activities have allowed the characterization of a great variety of compounds and investigational drugs that show low central nervous system (CNS) penetration (and therefore a reduced side effect profile) yet maintaining the desired opioid-related peripheral antinociceptive activity. These include highly hydrophilic/amphiphilic and massive molecules unable to easily cross lipid membranes, substrates of glycoprotein P (a extrusion pump that avoids CNS penetration), nanocarriers that release the analgesic agent at the site of inflammation and pain, and pH-sensitive opioid agonists that selectively activate at those sites (and represent a new pharmacodynamic paradigm). Hopefully, patients with pain will benefit soon from the incorporation of these new entities.
White blood cell subtypes as predictors of adverse cardiac events
Authors: Kristono Gisela A. , Holley Ana S. , Harding Scott A. , Larsen Peter D.
Published: March 2020

Background

White blood cell (WBC) subtypes have been associated with major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI). More recently, combining neutrophil and lymphocyte counts or lymphocyte and monocyte counts into a ratio has found to be promising for predicting MACE. This study aimed to confirm the association between MACE and the following WBC subtypes: neutrophils, lymphocytes, monocytes, neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR).

Methods

In a cohort of 860 AMI patients, we collected levels of WBC subtypes from the earliest blood tests recorded prior to angiography. Data on baseline demographics and one-year outcomes were also collected.

Results

At one year, 130 patients (15.1%) developed MACE. NLR and LMR were significantly associated with MACE on univariate analysis (P = 0.006 and 0.005, respectively). However, when combined into a multivariate model with age, hypertension, prior myocardial infarction and Type 2 diabetes, neither NLR nor LMR had significant associations (odds ratio = 1.058 and 0.966, P = 0.069 and 0.612, respectively).

Conclusion

As NLR and LMR were correlated with MACE only on univariate analysis, we do not believe that they are predictive enough to be used alone in a clinical setting. Further studies are required to assess the prognostic ability of these ratios in combination with other inflammatory markers.
Evolution of the gut microbiome in infancy within an ecological context
Authors: Donovan Sharon M.
Published: March 2020

Purpose of review

Humans and their commensal microbiota coexist in a complex ecosystem molded by evolutionary and ecological factors. Ecological opportunity is the prospective, lineage-specific characteristic of an environment that contains both niche availability leading to persistence coupled with niche discordance that drives selection within that lineage. The newborn gut ecosystem presents vast ecological opportunity. Herein, factors affecting perinatal infant microbiome composition are discussed.

Recent findings

Establishing a healthy microbiota in early life is required for immunological programming and prevention of both short-term and long-term health outcomes. The holobiont theory infers that host genetics contributes to microbiome composition. However, in most human studies, environmental factors are predominantly responsible for microbiome composition and function. Key perinatal elements are route of delivery, diet and the environment in which that infant resides. Vaginal delivery seeds an initial microbiome, and breastfeeding refines the community by providing additional microbes, human milk oligosaccharides and immunological proteins.

Early life represents an opportunity to implement clinical practices that promote the optimal seeding and feeding of the gut microbial ecosystem. These include reducing nonemergent cesarean deliveries, avoiding the use of antibiotics, and promoting exclusive breastfeeding.
Fusional Single Vision with Prism-induced Vergence Has More Influence than Diplopia on Postural Stability
Authors: Kim Sang-Yeob , Cho Hyun Gug , Moon Byeong-Yeon , Yu Dong-Sik
Published: March 2020

SIGNIFICANCE

Prism-induced convergence and vertical vergence for maintaining binocular fusion induced postural instability to a greater extent than diplopic conditions. This finding has important implication in relation to postural control of patients with large exophoria or vertical phoria in optometric clinic.

PURPOSE

The purpose of this study was to examine whether binocular single vision with prism-induced horizontal and vertical vergence and diplopia might affect the static postural stability.

METHODS

Forty-two subjects with a mean ± standard deviation age of 23.79 ± 2.81 years were enrolled in this study. To simulate convergence and divergence, base-in and base-out (BO) prisms of 4 and 8 Δ were added, respectively. To simulate vertical vergence, vertical prism of 2 Δ was added in a trial frame that corrected for the subject's refractive error during far distance (6 m) gaze. The prism power necessary to break fusion in each subject was detected and applied to induce diplopia in horizontal and vertical directions. Indices of general instability and sway power were measured under visual conditions using Tetrax and compared with normal viewing without the prism. Correlations between general instability indices and the ranges of break point in convergence and divergence were analyzed.

RESULTS

Postural instability was increased significantly when convergence induced by BO 4 and 8 Δ and vertical vergence induced by 2 Δ were stimulated. The correlation coefficient between ranges of BO break point and indices of general instability was −0.308 in the BO 4 Δ and −0.306 in the BO 8 Δ condition.

CONCLUSIONS

Although binocular input is recognized as an important factor in postural stability, binocular input with excessively stimulated convergence and vertical vergence during a far distance gaze is a latent factor affecting postural stability. On the other hand, diplopia did not influence postural stability.
A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital
Authors: Han Xiaoyu , Fan Yanqing , Wan Yung-Liang , Shi Heshui
Published: March 2020

Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks’ treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.
Caregiver Characteristics Associated With Quality of Cardiac Compressions on an Adult Mannequin With Real-Time Visual Feedback
Authors: Kessler David O. , Lemke Daniel S. , Jani Priti , Dewan Maya L. , Moore-Clingenpeel Melissa , Chang Todd P. , Pirie Jonathan , Lovett Marlina E. , Harwayne-Gidansky Ilana , Wolfe Heather A.
Published: March 2020

Introduction

Chest compression (CC) quality directly impacts cardiac arrest outcomes. Provider body type can influence the quality of cardiopulmonary resuscitation (CPR); however, the magnitude of this impact while using visual feedback is not well described. The aim of the study was to determine the association between provider anthropometric variables on fatigue and CC adherence to 2015 American Heart Association CPR while receiving visual feedback.

Methods

This was a planned secondary analysis of healthcare professionals from multiple hospitals performing continuous CC for 2 minutes on an adult CPR mannequin with dynamic visual feedback. Main outcome measures include compression data (depth, rate, and lean) evaluated in 30-second epochs to explore performance fatigue. Multivariable models examined the relationship of provider anthropometrics to CC quality. Binomial mixed effects models were used to characterize fatigue by examining performance for 4 epochs.

Results

Three hundred seventy-seven 2-minute CC episodes were analyzed. Extreme (low and high) BMI and weight are associated with poorer CC. Larger size (height, weight, and BMI) is associated with better depth but worse lean compliance. Performance fatigued for all providers for 2 minutes, but shorter, lighter weight, female participants had the greatest decline. On multivariable analysis, rate compliance did not deteriorate regardless of provider anthropometrics.

Conclusions

Anthropometrics impact provider CC quality. Despite visual feedback, variable effects are seen on compression depth, rate, recoil, and fatigue depending on the provider sex, weight, and BMI. The 2-minute interval for changing chest compressors should be reconsidered based on individual provider characteristics and risk of fatigue's impact on high-quality CPR.
Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review
Authors: Qiu Ruijin , Wei Xuxu , Zhao Mengzhu , Zhong Changming , Zhao Chen , Hu Jiayuan , Li Min , Huang Ya , Han Songjie , He Tianmai , Chen Jing , Shang Hongcai
Published: March 2020

Objectives

To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field.

Design

This study is a review.

Data sources

Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020.

Eligibility Criteria

Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered. Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19.

Data extraction and synthesis

The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis.

Results

19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame.

Conclusion

Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary.

Strengths and limitations of this study

1.

This review is the first to describe variation in outcomes, outcome measurement instruments and outcome measurement time reporting in clinical trials for Coronavirus Disease 2019 (COVID-19).

2.

All the database of ICMJE-accepted clinical trial registry platform were searched, and randomized controlled trials and observational studies were considered.

4.

The aim of this review was to provide a list of outcomes for clinical trials of COVID-19, both interventions of Traditional Chinese Medicine and western medicine were considered.

5.

When the searching was conducted, no clinical trials were registered by countries out of China, so all of included protocols were from China.
pyrpipe: a python package for RNA-Seq workflows
Authors: Singh Urminder , Li Jing , Seetharam Arun , Wurtele Eve Syrkin
Published: March 2020

The availability of terabytes of RNA-Seq data and continuous emergence of new analysis tools, enable unprecedented biological insight. However, implementing RNA-Seq analysis pipelines in a reproducible, flexible manner is challenging as data gets bigger and more complex. Thus, there is a pressing requirement for frameworks that allows for fast, efficient, easy-to-manage, and reproducibile analysis. Simple scripting has many challenges and drawbacks. We have developed a python package, python RNA-Seq Pipeliner (pyrpipe) that enables straightforward development of flexible, reproducible and easy-to-debug computational pipelines purely in python, in an object-oriented manner.pyrpipeprovides access to popular RNA-Seq tools, within python, via easy-to-use high level APIs. Pipelines can be customized by integrating new python code, third-party programs, or python libraries. Users can create checkpoints in the pipeline or integratepyrpipeinto a workflow management system, thus allowing execution on multiple computing environments.pyrpipeproduces detailed analysis, and benchmark reports which can be shared or included in publications.pyrpipeis implemented in python and is compatible with python versions 3.6 and higher. To illustrate the rich functionality ofpyrpipe, we provide case studies using RNA-Seq data from GTEx, SARS-CoV-2-infected human cells, and Zea mays. All source code is freely available athttps://github.com/urmi-21/pyrpipe; the package can be installed from the source or from PyPI (https://pypi.org/project/pyrpipe). Documentation is available at (http://pyrpipe.rtfd.io).
Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism
Authors: Othman Houcemeddine , Bouslama Zied , Brandenburg Jean-Tristan , Rocha Jorge da , Hamdi Yosr , Ghedira Kais , Srairi-Abid Najet , Hazelhurst Scott
Published: March 2020

The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.
Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins
Authors: Guan Hongxin , Wang Youwang , Saeed Abdullah F.U.H. , Li Jinyu , Jan Syed Sajid , Perčulija Vanja , Li Yu , Zhu Ping , Ouyang Songying
Published: March 2020

The current outbreak of Coronavirus Disease 2019 (COVID-19) by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has aroused great public health concern. Coronavirus has a history of causing epidemics in human and animals. In 2017 an outbreak in piglets by a novel coronavirus was emerged designated as swine acute diarrhea syndrome coronavirus (SADS-CoV) which is originated from the same genus of horseshoe bats (Rhinolophus) as Severe Acute Respiratory Syndrome CoV (SARS-CoV) having a broad species tropism. In addition to human cells, it can also infect cell lines from diverse species. Coronavirus host range is determined by its spike glycoprotein (S). Given the importance of S protein in viral entry to cells and host immune responses, here we report the cryo-EM structure of the SADS-CoV S in the prefusion conformation at a resolution of 3.55 Å. Our study reveals that SADS-CoV S structure takes an intra-subunit quaternary packing mode where the NTD and CTD from the same subunit pack together by facing each other. The comparison of NTD and CTD with that of the other four genera suggests the evolutionary process of the SADS-CoV S. Moreover, SADS-CoV S has several characteristic structural features, such as more compact architecture of S trimer, and masking of epitopes by glycan shielding, which may facilitate viral immune evasion. These data provide new insights into the evolutionary relationships of SADS-CoV S and would extend our understanding of structural and functional diversity, which will facilitate to vaccine development.
Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)
Authors: Fang Bin , Liu Linlin , Yu Xiao , Li Xiang , Ye Guojun , Xu Juan , Zhang Ling , Zhan Faxian , Liu Guiming , Pan Tao , Shu Yilin , Jiang Yongzhong
Published: March 2020

As the highly risk and infectious diseases, the outbreak of coronavirus disease 2019 (COVID-19) poses unprecedent challenges to global health. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread. Phylogenetic analysis showed that, compared with the coronavirus carried by pangolins (Pangolin-CoV), the virus carried by bats (bat-RaTG13-CoV) has a closer relationship with SARS-CoV-2. The network results showed that SARS-CoV-2 had diverse haplotypes around the world by February 11. Additionally, 16 genomes, collected from Huanan seafood market assigned to 10 haplotypes, indicated a circulating infection within the market in a short term. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019.
Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis Mechanisms of SARS-Related Coronaviruses
Authors: Tan Yongjun , Schneider Theresa , Leong Matthew , Aravind L , Zhang Dapeng
Published: March 2020

A novel coronavirus (SARS-CoV-2) is the causative agent of an emergent severe respiratory disease (COVID-19) in humans that is threatening to result in a global health crisis. By using genomic, sequence, structural and evolutionary analysis, we show that Alpha- and Beta-CoVs possess several novel families of immunoglobulin (Ig) domain proteins, including ORF8 and ORF7a from SARS-related coronaviruses and two protein groups from certain Alpha-CoVs. Among them, ORF8 is distinguished in being rapidly evolving, possessing a unique insert and a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover many Ig proteins from several metazoan viruses which are distinct in sequence and structure but share an architecture comparable to that of CoV Ig domain proteins. Hence, we propose that deployment of Ig domain proteins is a widely-used strategy by viruses, and SARS-CoV-2 ORF8 is a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts.
Appealing for Efficient, Well Organized Clinical Trials on COVID-19
Authors: Zhao Yang , Wei Yongyue , Shen Sipeng , Zhang Mingzhi , Chen Feng
Published: March 2020

ABSTRATC

The rapid emergence of clinical trials on COVID-19 stimulated a wave of discussion in scientific community. We reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and ClinicalTrials.gov. A total of 171 COVID-19-related interventional trials were identified on Feb 22nd, 2020. These trials are classified into 4 categories based on treatment modalities, including chemical drugs, biological therapies, traditional Chinese medicine treatments and other therapies. Our analysis focused on the issues of stage, design, randomization, blinding, primary endpoints definition and sample size of these trials. We found some studies with potential defects including unreasonable design, inappropriate primary endpoint definition, insufficient sample size and ethical issue. Clinical trials on COVID-19 should be designed based on scientific rules, ethics and benefits for patients.
Acute Myocardial Injury of Patients with Coronavirus Disease 2019
Authors: Xu Huayan , Hou Keke , Xu Hong , Li Zhenlin , Chen Huizhu , Zhang Na , Xu Rong , Fu Hang , Sun Ran , Wen Lingyi , Xie Linjun , Liu Hui , Zhang Kun , Selvanayagam Joseph B. , Fu Chuan , Zhao Shihua , Yang Zhigang , Yang Ming , Guo Yingkun
Published: March 2020

Background

Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them.

Methods

We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19–81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes.

Results

Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients.

Conclusions

Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.