bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral Gene Transfer Acts As an Evolutionary Shortcut to Efficient C4 Biochemistry
Authors: Phansopa Chatchawal , Dunning Luke T , Reid James D , Christin Pascal-Antoine
Published: June 2020

The adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase, an enzyme that catalyzes one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics, we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution.
Flow cytometry assay for the detection of single-copy DNA in human lymphocytes
Authors: Uno Naoki , Kaku Norihito , Morinaga Yoshitomo , Hasegawa Hiroo , Yanagihara Katsunori
Published: June 2020

Specific nucleic acid sequences can be detected in individual cells by in situ hybridization. However, when very few copies of a target sequence are present per cell, its signal is undetectable by flow cytometry. Although various approaches have been developed to increase fluorescence signals for in situ hybridization, flow cytometric detection of specific genomic DNA sequences has not been established. Here, we present a flow cytometry assay for detection of single-copy genomic sequences in human lymphocytes using in situ PCR with universal energy transfer-labelled primers.
Against the Public Goods Conception of Public Health
Authors: Bernstein Justin , Randall Pierce
Published: June 2020

Public health ethicists face two difficult questions. First, what makes something a matter of public health? While protecting citizens from outbreaks of communicable diseases is clearly a matter of public health, is the same true of policies that aim to reduce obesity, gun violence or political corruption? Second, what should the scope of the government’s authority be in promoting public health? May government enact public health policies some citizens reasonably object to or policies that are paternalistic? Recently, some theorists have attempted to address these questions by arguing that something is a matter of public health if and only if it involves a health-related public good, such as clean water or herd immunity. Relatedly, they have argued that appeals to the promotion of public health should only be used to justify the provision of health-related public goods. This public goods conception of public health (PGC) is meant to enjoy advantages over its rivals in three respects: it provides a better definition of public health than rival views, it respects moral disagreement, and it avoids licensing objectionably paternalistic public health policies. We argue, however, that the PGC does just as poorly, or worse, than its rivals in all three respects.
Emerging public health challenge in UK: perception and belief on increased COVID19 death among BAME healthcare workers
Authors: Moorthy Arumugam , Sankar Thangasamy K
Published: June 2020

Background

Coronavirus infection Disease 19 impacted every part of the world and routine life. Recent report from the Office of national statistics in UK reported disproportionate death among Black Asian and minority ethnic (BAME) population. NHS is heavily relied on the BAME work force both in front line and in the community. We attempted to explore the beliefs and perception about reported worrying issue among BAME health work force in a Diverse city of Leicester.

Methods

This is a cross-sectional survey using 20 questions in an electronic format. The target population was identified through Leicester Asian Doctors Society and Leicester Asian Nurses Society. The questionnaire was then distributed electronically to the members. Survey questionnaire was accessed by 372, incomplete response (172) were excluded and 200 completed responses were analysed.

Results

Majority of BAME workforce are routinely involved in front line duties. More than 70% were anxious about their role during this pandemic. The Personal Protective Equipment (PPE) supply was adequate, and the support received from the local healthcare providers was more than satisfactory. The work force perceived co-morbidity, lack of PPE and testing were one of the few reasons for increased death in BAME. BAME group felt adequate provision of PPE, increased testing and improving mental health well-being is required to alleviate concerns and improve BAME working life in NHS.

Conclusion

BAME workforce are routinely involved in front line work and current anxiety level is very high. Adequate provision of mental health support with clear risk stratification for return to work is required urgently.
Strategies and Tools to Enhance Team Performance
Authors: Sucato Daniel J.
Published: June 2020

Introduction:

The ability for teams to work together in a coordinated manner may be where the greatest improvements in health care occur in the next generation. To perform at the highest level there are several key principles that all teams must have no matter what playing field they are on, including health care.

Methods:

Several resources were used to identify the challenges we face in health care with respect to the delivery of quality care, improving outcomes and decreasing complications. A search of the lay press and scientific literature was evaluated to identify those key elements that lead to improvements in team performance. In addition, personal observations were accumulated with time and examples of strategies used at home institutions were identified.

Results:

The teams in our pediatric orthopaedic practices are many and include those in the clinic, the operating room, research, and our administrative office. The Institute of Medicine, in their influential article in 1999, defined the alarming rates of complications/harm occurring in the US health care system. In response, the Agency for Healthcare Research and Quality (AHRQ) and the Department of Defense (DOD) collaborated to create the Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) in 2006. This was implemented in military facilities and later civilian hospital settings with varied success in civilian hospital settings.

Discussion:

They defined key principles based around team structure, communication, leadership, situation monitoring, and mutual support. Other important foundational attributes of a successful team include identifying the vision of the team, hiring top-talent in the form of hard and soft skills, having open communication, being goal-focused, practicing accountability, and having an organized team. We can look to excellent examples in medicine, business, and sports to see where and how high-functioning teams have existed and to learn from them to implement similar successful teams.

Conclusions:

Team performance is a function of talented members who share a common vision, who have the opportunity to voice their thoughts/opinions, and have the ability to be accountable to each other. Surgeons need to lead by example, and provide each member of the team an opportunity to contribute in a meaningful way which ultimately will improve the lives of the patients we are honored to care for.
Building a Culture of Wellness in an Orthopaedic Group: Experiences at OrthoCarolina
Authors: Casey Virginia F. , Schenk Jennifer L.
Published: June 2020

Introduction:

Physician wellness is a much broader concept than physician satisfaction, although physician satisfaction tends to be the predominant form of measurement. The purpose of this paper is to offer some key strategies for building a culture of physician wellness in the unique setting of a large, private group of orthopaedic surgeons.

Methods:

Organizational culture was assessed formally through validated physician satisfaction surveys and data gathered through the Patient Advocacy Reporting System (PARS program, and informally through organic, organizational initiatives, and responses. In addition, the authors continuously reviewed literature related to physician engagement, satisfaction and wellness, and organizational interventions designed to promote the same.

Results:

From 2014 to 2018, overall physician engagement improved and remained above the 90th percentile as compared with the vendor’s database of over 95,000 physicians surveyed nationally. Physician resilience, a measure of the predictors of physician burnout, also improved from 2014 to 2018 and is now above the national physician average. During the same time period, significant improvement was noted as it relates to a physician’s ability to disconnect and “recharge” outside of work (an important element of overall wellness). From 2016 to 2018, PARS interventions aimed at increasing professionalism and identifying at-risk physicians decreased by 23%.

Discussion:

At OrthoCarolina, we believe that developing a nurturing environment with good interpersonal connections is foundational to our success. Physicians within the group also report that supportive avenues such as mentor programs and organized activities outside of the workplace amplified the sense of connection and community within the physician group.

Conclusions:

Organizational culture of a physician group is a key determinant of physician wellness. It is imperative to have the full support of the physicians within the organization and its leaders to promote and support a culture of wellness. Data-driven programs create awareness and foster curiosity, which in turn allows for the development of specific initiatives including informal, organic initiatives that build connection and community.
ABCA1 Polymorphism Is Associated With the Warfarin-Induced Aortic Stiffness After Coronary Artery Bypass Surgery in the Chinese Population
Authors: Liao Shutan , Zhou Qing , Zhang Yang
Published: June 2020

Warfarin is the most widely prescribed oral anticoagulant and is recommended for patients recovering from coronary artery bypass graft (CABG) with atrial fibrillation. Increasing evidence suggested that warfarin increased arterial stiffness in those patients. We aimed to examine the effect of warfarin therapy on aortic stiffness in patients who underwent CABG with or without postoperative warfarin treatment and explored the potential relationships of warfarin therapy with ABCA1 polymorphisms. This was a retrospect observational study of 24 patients who were continuously treated with warfarin were selected as the warfarin group and matched them by age (±3 years) and gender to 48 patients with nonuse of warfarin as the control group. The aortic stiffness, cholesterol efflux capacity, and plasma level of PIVKA-II were measured. Two ABCA1 polymorphisms were genotyped. Compared with baseline, treatment with warfarin for 1 year significantly increased the plasma level of PIVKA-II and aortic stiffness in pulse pressure and pulse wave velocity in patients after CABG. The increase of pulse wave velocity and plasma PIVKA-II level in the TT genotype was significantly greater than the CC genotype when comparing the −565C/T genotypes. The capacity of cholesterol efflux was significantly lower in the TT genotype at baseline and 1-year follow-up than the CC genotype. Postoperative treatment of warfarin for 1 year significantly increased aortic stiffness in patients who underwent CABG. ABCA1 −565C/T polymorphisms affected the cholesterol efflux capacity and were associated with the vitamin K status and the increased aortic stiffness after warfarin treatment in those patients.
Regenerative Peripheral Nerve Interfaces for the Management of Symptomatic Hand and Digital Neuromas
Authors: Hooper Rachel C. , Cederna Paul S. , Brown David L. , Haase Steven C. , Waljee Jennifer F. , Egeland Brent M. , Kelley Brian P. , Kung Theodore A.
Published: June 2020

Painful neuromas result from traumatic injuries of the hand and digits and cause substantial physical disability, psychological distress, and decreased quality of life among affected patients. The regenerative peripheral nerve interface (RPNI) is a novel surgical technique that involves implanting the divided end of a peripheral nerve into a free muscle graft for the purposes of mitigating neuroma formation and facilitating prosthetic limb control. The RPNI is effective in treating and preventing neuroma pain in major extremity amputations. The purpose of this study was to determine if RPNIs can be used to effectively treat neuroma pain following partial hand and digital amputations. We retrospectively reviewed the use of RPNI to treat symptomatic hand and digital neuromas at our institutions. Between November 2014 and July 2019, we performed 30 therapeutic RPNIs on 14 symptomatic neuroma patients. The average patient follow-up was 37 weeks (6–128 weeks); 85% of patients were pain-free or considerably improved at the last office visit. The RPNI can serve as a safe and effective surgical solution to treat symptomatic neuromas after hand trauma.
Corneal Blindness in Asia: A Systematic Review and Meta-Analysis to Identify Challenges and Opportunities
Authors: Tran Tu M. , Duong Huong , Bonnet Clemence , Kashanchi Ashkan , Buckshey Arjun , Aldave Anthony J.
Published: June 2020

Purpose:

To describe the causes and prevalence of moderate-to-severe visual impairment (MSVI) and blindness from corneal diseases, as well as corneal transplantation across Asia.

Methods:

A meta-analysis of the published literature to identify population-based surveys conducted from 2008 to 2019 in 22 Asian countries regarding the prevalence and causes of MSVI and blindness from corneal disease, and a review of national corneal transplant data and eye bank statistics.

Results:

A total of 5307 records were screened to identify 57 reports that were used to estimate a prevalence of MSVI and blindness caused by corneal diseases in Asia of 0.38% (95% confidence interval, 0.29%–0.48%). The most frequent corneal diseases were infectious keratitis, trauma, and pseudophakic bullous keratopathy. As expected, these represented the most common indications for corneal transplantation, although the percentages in each country differed based on the level of economic development, with pseudophakic bullous keratopathy being the most common indication in countries with higher gross national income per capita. Despite this, endothelial keratoplasty is not the most commonly performed form of corneal transplantation in any Asian country and represents only a small percentage of keratoplasty procedures performed in most countries.

Conclusions:

The prevalence of MSVI and blindness from corneal disease in Asia is approximately 0.4%, with a nearly 20-fold difference in the national prevalence across the region. The indications for keratoplasty, reflective of the causes of corneal dysfunction, also vary, more so according to the gross national income than to geographic location, and only a few Asian countries have rates of corneal transplantation above international means.
Transcriptome Analysis of Deafness: Intracellular Signal Transduction Signaling Pathways Regulate Neuroplastic Changes in the Auditory Cortex
Authors: Lee Sang-Yeon , Lee Ho Sun , Park Min-Hyun
Published: June 2020

Hypothesis and Background:

Hearing loss leads to synaptic changes in auditory neurons and their networks, and functions as a consequence of the interplay between genes and proteins. However, cellular and molecular mechanisms leading to deafness-induced plasticity in the auditory cortex (AC) remain unclear. Here, we examined the changes in gene expression and key signaling pathways that regulate differentially expressed genes (DEGs) in the AC following auditory deafferentation using RNA-sequencing (RNA-Seq) analysis.

Methods:

Cochlear ablation-induced bilaterally deafened Sprague-Dawley rats were maintained for 12 weeks and their ACs were harvested. RNA-seq analysis was performed on each sample to identify which genes were expressed. This information was then used for comparative analysis of DEGs between samples. The statistical significance of DEGs was determined by fold change (|FC| > 1.5) and independentttest (p < 0.05).

Results:

RNA-seq analysis identified 72 DEGs, of which 19 were upregulated and 53 were down-regulated after bilateral deafening in the ACs. Gene ontology (GO) analysis revealed the potential involvement of mitogen-activated protein kinase, tumor necrosis factor, and cyclic adenosine 3′,5′-monophosphate (e.g.,Bdnf,Gli1, andc-Fos) signaling pathways in regulating changes in the expression of the genes listed herein. The DEGs of interest—includingc-Fos,Arc,Ntf3, andGli1—from the RNA-seq analysis were consistent with result of quantitative reverse transcriptase polymerase chain reaction.

Conclusion:

RNA-seq analysis revealed that auditory deprivation in adult rats elicited changes in gene expression, transcription factor levels, and their complex interaction at specific gene promoters in the AC. Particularly, activation of intracellular signal transduction signaling pathways may be key to neuronal plasticity in deafness.
The Relationship Between Vestibular Migraine and Motion Sickness Susceptibility
Authors: Abouzari Mehdi , Cheung Dillon , Pham Tiffany , Goshtasbi Khodayar , Sarna Brooke , Tajran Sarah , Sahyouni Sammy , Lin Harrison W. , Djalilian Hamid R.
Published: June 2020

Objectives:

To determine the relationship between vestibular migraine (VM) and motion sickness (MoS) susceptibility and their comorbidity in a large student population, and to assess whether experiencing MoS is associated with higher susceptibility for VM.

Methods:

Surveys including Motion Sickness Susceptibility Questionnaire (MSSQ) and questions assessing migraine-related symptoms as well as family history of motion sickness and migraine headache were distributed to the university undergraduate students through Facebook and email. Diagnosis of definite VM (dVM) was based on the criteria of the International Classification of Headache Disorders.

Results:

Of 277 survey responders, 148 (53%) were found to be susceptible to MoS in which 74 (50%) met the criteria for dVM. Only childhood MSSQ score was significantly higher in participants with dVM compared with those without dVM (25.78 ± 15.89 versus 20.77 ± 14.28, p = 0.04); however, its significance faded out by regression analysis. Multivariate logistic regression showed having 1st degree relative with migraine headache (p = 0.02), neck stiffness (p = 0.001), and sinus pain, facial pressure, or headache with wind exposure (p = 0.02) to be independently associated with presence of dVM in MoS subjects.

Conclusions:

Though participants with MoS and dVM had significantly greater rates of migraine-related symptoms and family history of migraine headache compared with those with MoS only, childhood and adulthood MSSQ scores were similar. This and the high prevalence of dVM in our MoS cohort may suggest an existing association between MoS susceptibility and VM.
Kinetic patterns of liver enzyme elevation with COVID-19 in the USA
Authors: Da Ben L. , Mitchell Robert A. , Lee Brian T. , Perumalswami Ponni , Im Gene Y. , Agarwal Ritu , Schiano Thomas D. , Dieterich Douglas , Saberi Behnam
Published: June 2020

COVID-19 is a global pandemic that started in Wuhan, China. COVID-19 related liver enzyme elevations have been described however the clinical presentation, enzyme kinetics, and associated laboratory abnormalities of these patients have not been well described. Five cases of COVID-19 associated liver enzyme elevations are reported here. We found that COVID-19 related liver enzyme elevations occurred in a hepatocellular pattern and persisted throughout the initial hospitalization in all patients. Abnormalities in lactate dehydrogenase and ferritin levels were seen in all five cases. In conclusion, abnormalities in aminotransferase, lactate dehydrogenase, and ferritin levels are commonly seen in COVID-19 related liver injury. Elevated aminotransferase levels often persist throughout the entire hospitalization. However, the clinical course of COVID-19 related liver injury appears benign.
Incidence of and risk factors for tuberculosis among people with HIV on antiretroviral therapy in the United Kingdom
Authors: van Halsema Clare L. , Okhai Hajra , Hill Teresa , Sabin Caroline A.
Published: June 2020

Objective:

The United Kingdom has a low tuberculosis incidence and earlier combination antiretroviral therapy (cART) is expected to have reduced incidence among people with HIV. Epidemiological patterns and risk factors for active tuberculosis were analysed over a 20-year period among people accessing HIV care at sites participating in the UK CHIC observational study.

Design:

Cohort analysis.

Methods:

Data were included for individuals over 15 years old attending for HIV care between 1996 and 2017 inclusive, with at least 3 months follow-up recorded. Incidence rates of new tuberculosis events were calculated and stratified by ethnicity (white/Black/other) as a proxy for tuberculosis exposure. Poisson regression models were used to determine the associations of calendar year, ethnicity and other potential risk factors after cART initiation.

Results:

Fifty-eight thousand seven hundred and seventy-six participants (26.3% women; 54.5% white, 32.0% Black, 13.5% other/unknown ethnicity; median (interquartile range) age 34 (29–42) years) were followed for 546 617 person-years. Seven hundred and four were treated for active tuberculosis [rate 1.3; 95% confidence interval (CI) 1.2–1.4/1000 person-years). Tuberculosis incidence decreased from 1.3 (1.2–1.5) to 0.6 (0.4–0.9)/1000 person-years from pre-2004 to 2011–2017. The decline among people of Black ethnicity was less steep than among those of white/other ethnicities, with incidence remaining high among Black participants in the latest period [2.1 (1.4–3.1)/1000 person-years]. Two hundred and eighty-three participants [191 (67%) Black African] had tuberculosis with viral load less than 50 copies/ml.

Conclusion:

Despite the known protective effect of cART against tuberculosis, a continuing disproportionately high incidence is seen among Black African people. Results support further interventions to prevent tuberculosis in this group.
Pushing the Limits in Cheek Reconstruction: The Sub-Superficial Musculo-Aponeurotic System “Deep Plane” Cervicofacial Flap for Reconstruction of Large Eyelid-Cheek Junction Defects
Authors: Purnell Chad A. , Bricker Jonathan T. , Alghoul Mohammed S.
Published: June 2020

The cervicofacial flap is a workhorse flap for reconstruction of moderate to large sized defects of the cheek. Defects that involve the eyelid-cheek junction are often the most challenging of these. While the ideal plane of dissection has been debated, it is our belief that dissection in the sub-superficial musculo-aponeurotic system (SMAS) plane provides better aesthetic and functional outcomes due to enhanced vascularity, fascial support, and additional bulk of the flap itself. The authors present a series of 9 patients who presented with heterogeneous defects of the eyelid-cheek junction after cancer resection and underwent reconstruction using a sub-SMAS cervicofacial flap. At a mean follow-up time of 20 months, the cohort had 2 patients who developed lower lid retraction requiring revision and 2 other minor complications. This series lends support to the versatility and reliability of the sub-SMAS cervicofacial flap for large defects of the eyelid-cheek junction.
Managing Isolated Symphyseal and Parasymphyseal Fractures in Pediatric Patients
Authors: Yesantharao Pooja S. , Lopez Joseph , Reategui Alvaro , Najjar Omar , Redett Richard J. , Manson Paul N. , Dorafshar Amir
Published: June 2020

Background:

Isolated symphyseal or parasymphyseal mandibular fractures can confer significant morbidity in children. However, this mandibular injury pattern has not been well-characterized in children. This study investigated isolated symphyseal/parasymphyseal mandibular fractures in pediatric patients.

Methods:

This was a 29-year retrospective, longitudinal cohort study of pediatric patients who presented to a single institution with isolated symphyseal/parasymphyseal mandibular fractures. Patient data were abstracted from medical records and compared between patients of varying dentition stages.

Results:

Fourteen patients met inclusion criteria during the study period, of whom 2 (14.3%) had deciduous dentition, 7 (50.0%) had mixed dentition, and 5 (35.7%) had permanent dentition. Patients with deciduous dentition were significantly more likely to receive soft diet or closed treatment with mandibulomaxillary fixation than open reduction and internal fixation when compared to patients with mixed or permanent dentition (p = 0.04). The post-treatment complication rate was 40% among all patients treated with open reduction and internal fixation, 16.7% among patients who underwent closed treatment with mandibulomaxillary fixation, and 75% amongst patients treated with soft diet (though 2 patients who received soft diet had permanent dentition and thus were inappropriately managed). The most common complication overall was malocclusion (20%). A treatment algorithm was proposed based on study data; adherence to the algorithm significantly decreased odds of complications (odds ratio: 0.03, 95% confidence interval:0.001–0.6).

Conclusions:

The etiology, management, and outcomes of children with isolated symphyseal or parasymphyseal mandibular fractures at our institution varied by dentition stage. The authors proposed a treatment algorithm in order to optimize outcomes of symphyseal/parasymphyseal mandibular fractures in this patient population.
Impact of Physician Expertise on Probe Trajectory During Obstetric Ultrasound: A Quantitative Approach for Skill Assessment
Authors: Le Lous Maela , Despinoy Fabien , Klein Margaux , Fustec Elisa , Lavoue Vincent , Jannin Pierre
Published: June 2020

Introduction

The objective of the study was to identify objective metrics to evaluate the significance of a sonographer's expertise on trajectories of ultrasound probe during obstetric ultrasound training procedures.

Methods

This prospective observational study was conducted at Rennes University Hospital, Department of Obstetrics and Gynecology. We evaluated a panel of sonographers (expert, intermediate, and novice) in performing 3 tasks (brain, heart, and spine) with an obstetric ultrasound simulator (Scantrainer; Medaphor, Cardiff, UK). The trajectories of the probe were logged and recorded by a custom data acquisition software. We computed metrics on the trajectories (duration, path length, average velocity, average acceleration, jerk, working volume) to compare the 3 groups and identify discriminating metrics.

Results

A total of 33 participants were enrolled: 5 experts, 12 intermediates, and 16 novices. Discriminatory metrics were observed among the 3 levels of expertise for duration, velocity, acceleration, and jerk for brain and spine tasks. Working volume was discriminatory for the brain and the heart task. Path length was discriminatory for the brain task.

Conclusions

Our results suggest a relationship between the sonographer's level of expertise and probe trajectory metrics. Such measurements could be used as an indicator of sonographer proficiency and contribute to automatic analysis of probe trajectory to evaluate the quality of sonography and the sonographer.
Topiramate-Responsive Tremor in a Novel Pathogenic Variant of SPG15 Patient
Authors: Ersen Atilla , Gençpınar Pınar , Arıcan Pınar , Bozkaya Yılmaz Sema , Aliyeva Nargiz , Özdemir Taha Reşid , Öztekin Özgür , Olgaç Dündar Nihal
Published: June 2020

Hereditary spastic paraplegia (HSP) is group of a rare neurodegenerative disorder with both genetically and clinically diverse neurologic features. Indeed, disease progression is varying greatly within the different forms and current treatment modalities are exclusively symptomatic for HSP. Tremor in HSP patients is only mentioned with rare case reports, so treatment option is lack in clinical ground. We reported a case of a HSP-15 girl with a previously reported novel mutation of SPG15 complained of a life disturbing tremor and topiramate as a drug therapy for tremor in our HSP patient.
Campylobacter novaezeelandiae sp. nov., isolated from birds and water in New Zealand
Authors: Bloomfield Samuel , Wilkinson David , Rogers Lynn , Biggs Patrick , French Nigel , Mohan Vathsala , Savoian Matthew , Venter Pierre , Midwinter Anne
Published: June 2020

Six isolates of

Campylobacter

with similar non-standard colonial morphologies were identified during studies isolating

Campylobacter

from bird faeces and rivers in New Zealand. Genomic (16S rRNA gene sequencing and whole genome analysis) and phenotypic (MALDI-TOF analysis and conventional biochemical tests) showed that the isolates form a monophyletic clade with genetic relationships to

Campylobacter coli

/

Campylobacter jejuni

and

Campylobacter peloridis

/Campylobacter amoricus. They may be distinguished from other

Campylobacter

by their MALDI-TOF spectral pattern, their florid α-haemolysis, their ability to grow anaerobically at 37 °C, and on 2 % NaCl nutrient agar, and their lack of hippuricase. This study shows that these isolates represent a novel species within the genus

Campylobacter

for which the name Campylobacter novaezeelandiae sp. nov. is proposed. The presence of C. novaezeelandiae in water may be a confounder for freshwater microbial risk assessment as they may not be pathogenic for humans. The type strain is B423bT (=NZRM 4741T=ATCC TSD-167T).
Statistical Decision Properties of Imprecise Trials Assessing COVID-19 Drugs
Authors: Manski Charles F. , Tetenov Aleksey
Published: June 2020

As the COVID-19 pandemic progresses, researchers are reporting findings of randomized trials comparing standard care with care augmented by experimental drugs. The trials have small sample sizes, so estimates of treatment effects are imprecise. Seeing imprecision, clinicians reading research articles may find it difficult to decide when to treat patients with experimental drugs. Whatever decision criterion one uses, there is always some probability that random variation in trial outcomes will lead to prescribing sub-optimal treatments. A conventional practice when comparing standard care and an innovation is to choose the innovation only if the estimated treatment effect is positive and statistically significant. This practice defers to standard care as the status quo. To evaluate decision criteria, we use the concept of near optimality, which jointly considers the probability and magnitude of decision errors. An appealing decision criterion from this perspective is the empirical success rule, which chooses the treatment with the highest observed average patient outcome in the trial. Considering the design of recent and ongoing COVID-19 trials, we show that the empirical success rule yields treatment results that are much closer to optimal than those generated by prevailing decision criteria based on hypothesis tests.

We have benefitted from the comments of Michael Gmeiner, Valentyn Litvin, Francesca Molinari, and John Mullahy. Tetenov has received funding from the Swiss National Science Foundation through grant number 100018-192580.
Treatment with Arbidol and Moxifloxacin in Ordinary and Severe Adult Patients Infected with COVID-19
Authors: Xi Wen-Na , Jin Di , Sun Ke , Yu Rong-Yan , Yao Xue-Bing , Zou Biao-Shu , Song Zhi-Ying , Yang AO-Yu , Luo Rui-Xia , liu Yun , Li Yan-hua , Sun Shui-Lin , Yu Dong-Shan
Published: June 2020

Background

An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2.

Methods

We collected and analyzed data on 94 patients with COVID-19 including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes.

Results

In basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia (26% V.S 6%, p=0.03), and had more obvious dyspnea symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 decreased significantly in severe group (p=0.023).

Conclusion

In summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation during SARS-CoV2 infection, especially for negatively regulating fatal inflammation in severe COVID-19 patients. However, more evidence awaits further clinical verification.
Hospitalist perspectives of available tests to monitor volume status in patients with heart failure: a qualitative study
Authors: Maw Anna M , Ortiz-lopez Carolina , Morris Megan A , Jones Christine , Gee Elaine , Tchernodrinski Stephan , Kramer Henry , Galen Benjamin T , Dempsey Amanda F , Soni Nilam
Published: June 2020

Acute decompensated heart failure is the leading admitting diagnosis in patients 65 and older with more than 1 million hospitalizations per year in the US alone. Traditional tools to evaluate for and monitor volume status in patients with heart failure, including symptoms and physical exam findings, are known to have limited accuracy. In contrast, point of care lung ultrasound is a practical and evidenced-based tool for monitoring of volume status in patients with heart failure. However, few inpatient clinicians currently use this tool to monitor diuresis. We performed semi-structured interviews of 23 hospitalists practicing in 5 geographically diverse academic institutions in the US to better understand how hospitalists currently assess and monitor volume status in patients hospitalized with heart failure. We also explored their perceptions and attitudes toward adoption of lung ultrasound. Hospitalist participants reported poor reliability and confidence in the accuracy of traditional tools to monitor diuresis and expressed interest in learning or were already using lung ultrasound for this purpose. The time required for training and access to equipment that does not impede workflow were considered important barriers to its adoption by interviewees.
SARS-CoV2 Testing: The Limit of Detection Matters
Authors: Arnaout Ramy , Lee Rose A. , Lee Ghee Rye , Callahan Cody , Yen Christina F. , Smith Kenneth P. , Arora Rohit , Kirby James E.
Published: June 2020

Resolving the COVID-19 pandemic requires diagnostic testing to determine which individuals are infected and which are not. The current gold standard is to perform RT-PCR on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of ~100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss more infected patients, resulting in more false negatives. However, the false-negative rate for a given LoD remains unknown. Here we address this question using over 27,500 test results for patients from across our healthcare network tested using the Abbott RealTime SARS-CoV-2 EUA. These results suggest that each 10-fold increase in LoD is expected to increase the false negative rate by 13%, missing an additional one in eight infected patients. The highest LoDs on the market will miss a majority of infected patients, with false negative rates as high as 70%. These results suggest that choice of assay has meaningful clinical and epidemiological consequences. The limit of detection matters.
iSCAN: An RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2
Authors: Ali Zahir , Aman Rashid , Mahas Ahmed , Rao Gundra Sivakrishna , Tehseen Muhammad , Marsic Tin , Salunke Rahul , Subudhi Amit K. , Hala Sharif M. , Hamdan Samir M. , Pain Arnab , Hassan Norhan , Mahfouz Magdy M.
Published: June 2020

The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.
Adverse events associated with nifurtimox treatment for Chagas disease in children and adults
Authors: Berenstein A.J. , Falk N. , Moscatelli G. , Moroni S. , González N. , Garcia-Bournissen F. , Ballering G. , Freilij H. , Altcheh J.
Published: June 2020

BACKGROUND

Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, there is scarce data on NF safety, and many physicians defer or refuse NF treatment because of concerns about drug tolerance.

METHODS

Prospective cohort study with retrospective data collection of adverse drug reactions (ADRs) associated with NF treatment of ChD. Children received NF doses of 10-15 mg/kg/day for 60-90 days, and adults 8-10 mg/kg/day for 30 days.

RESULTS

215 children (median age: 2.6yrs, range 0-17) and 105 adults (median age: 34yrs, range 18-57) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 in adults, and 63/215 in children (OR = 3.7, 95%CI [2.2;6.3]). We observed 215 ADRs, 131 in adults (median: 2 events/patient (IQR25-75= 1-3) and 84 in children (median: 1 event/patient (IQR25-75= 1-1.5) (Wilcoxon-Test, PAdjusted < 8.10-5). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous and digestive systems were the most frequently affected, without differences between both groups.

Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95%CI = [1.5;24]).

CONCLUSIONS

Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence.
A Model for the Testing and Tracing Needed to Suppress COVID-19
Authors: Wang Victor
Published: June 2020

This paper presents the first analytical model for calculating how many tests and tracing needed to suppress COVID-19 transmission. The number of people needs to be tested daily is given by:

Where

N is the size of the population in consideration

Ar is the attack rate at any given time

Tp is the test-positive rate

ρ is the percentage of infectious people that have to be detected per day. To make the effective reproduction number Re below 1, ρ must satisfy the following equation:

Where

R0 is the basic reproduction number,

S/N is the percentage of the susceptible population over the entire population,

D is the length of the infectious period, and

η is the percentage of close contacts that have to be traced.

This model provides insights and guidance to deploy the testing and tracing resources optimally. An Excel model is attached to facilitate easy calculation of the number of tests and tracing needed. This model is also applicable to any infectious disease that can be suppressed by testing and tracing.
Estimating excess visual loss in people with neovascular age-related macular degeneration during the COVID-19 pandemic
Authors: Thomas Darren S. , Warwick Alasdair N , Olvera-Barrios Abraham , Egan Catherine , Schwartz Roy , Patra Sudeshna , Eleftheriadis Haralabos , Khawaja Anthony P. , Lotery Andrew , Müeller Philipp L. , Hamilton Robin , Preston Ella , Taylor Paul , Tufail Adnan ,   UK EMR Users Group
Published: June 2020

Objectives

To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at one year.

Design

Retrospective clinical audit and simulation model.

Setting

Multiple UK NHS ophthalmology centres.

Participants

Data on the reduction in new nAMD referrals was obtained from four NHS Trusts in England comparing April 2020 to April 2019. To estimate the potential impact on one-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20,825 nAMD eyes from 27 NHS Trusts.

Main outcome measures

Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at one year under four hypothetical scenarios: no treatment delay, 3, 6 and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at one year nationally.

Results

The number of nAMD referrals at four major eye treatment hospital groups based in England dropped on average by 72% (range 65 to 87%) in April 2020 compared to April 2019. Simulated one-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2 to 17.9) to 23.3% (20.7 to25.9), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1 to 38.1) to 26.4% (23.8 to29.2). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level at the national level for only one month, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at one-year with even a short treatment delay.

Conclusions

We report a large decrease in nAMD referrals during the first month of COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at one year.
VipariNama: RNA vectors to rapidly reprogram plant morphology and metabolism
Authors: Khakhar Arjun , Wang Cecily , Swanson Ryan , Stokke Sydney , Rizvi Furva , Sarup Surbhi , Hobbs John , Voytas Daniel F.
Published: June 2020

Synthetic transcription factors have great promise as tools to explore biological processes. By allowing precise alterations in gene expression, they can help elucidate relationships between gene expression and plant morphology or metabolism. However, the years-long timescales, high cost, and technical skill associated with plant transformation have dramatically slowed their use. In this work, we developed a new platform technology called VipariNama (ViN) in which RNA vectors are used to rapidly deploy synthetic transcription factors and reprogram gene expressionin planta. We demonstrate how ViN vectors can direct activation or repression of multiple genes, systemically and persistently over several weeks, and in multiple plant species. We also show how this transcriptional reprogramming can create predictable changes to metabolic and morphological phenotypes in the model plantsNicotiana benthamianaandArabidopsis thalianain a matter of weeks. Finally, we show how a model of gibberellin signaling can guide ViN vector-based reprogramming to rapidly engineer plant size in both model species as well as the cropSolanum lycopersicum(tomato). In summary, using VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.
In silico saturation mutagenesis of cancer genes
Authors: Muiños Ferran , Martinez-Jimenez Francisco , Pich Oriol , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: June 2020

Extensive bioinformatics analysis of datasets of tumor somatic mutations data have revealed the presence of some 500-600 cancer driver genes. The identification of all potential driver mutations affecting cancer genes is essential to implement precision cancer medicine and to understand the interplay of mutation probability and selection in tumor development. Here, we present an in silico saturation mutagenesis approach to identify all driver mutations in 568 cancer genes across 66 tumor types. For most cancer genes the mutation probability across tissues --underpinned by active mutational processes-- influences which driver variants have been observed, although this differs significantly between tumor suppressor and oncogenes. The role of selection is apparent in some of the latter, the observed and unobserved driver mutations of which are equally likely to occur. The number of potential driver mutations in a cancer gene roughly determines how many mutations are available for detection across newly sequenced tumors.