bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjustable Ptosis Correction via Posterior Levator Advancement With Minimal Superior Tarsectomy
Authors: Tran Ann Q. , DeMaria Lauren N. , Nair Archana A. , Tooley Andrea A. , Godfrey Kyle J. , Lisman Richard D.
Published: July 2020

Purpose:

To report the surgical technique and outcomes for adjustable ptosis correction using a posterior levator advancement with minimal superior tarsectomy.

Methods:

A retrospective single-center study was conducted on patients who underwent adjustable ptosis repair via posterior levator advancement with minimal superior tarsectomy by a single surgeon from 2002 to 2018. Patients with greater than 1 mm asymmetry between eyes or contour abnormalities underwent nonsurgical adjustment in the office within 6 days of surgery.

Results:

A total of 79 patients (146 eyelids) were included in this study. The patients were female (67%), underwent bilateral surgery (87%) with mean age of 63 years (range, 20–92). The mean improvement in marginal reflex distance 1 at postoperative month 1 was 2.56 ± 1.04 mm (p ≤ 0.0001). Postoperative symmetry of 1 mm or less between eyes was achieved in 96.6% of patients. Only 8 eyes (5.4%) underwent in-office adjustment postoperatively. No demographic or clinical differences were noted in eyes that required adjustments. Postoperative complications included dry eyes that resolved by 3 months (13.6%), suture cyst (1.4%), corneal abrasion (1.4%), and persistent eyelid edema (1.4%). Surgical revision was required in 2.8% of eyes.

Conclusions:

The adjustable posterior levator advancement with minimal superior tarsectomy is an effective surgical technique for ptosis repair with the added benefit of in-office adjustability to correct minor asymmetries.
Exercise, nutrition, and medication considerations in the light of the COVID pandemic, with specific focus on geriatric population: A literature review
Authors: Yang Yi-Chiang , Chou Cheng-Liang , Kao Chung-Lan
Published: July 2020

The pandemic of severe acute respiratory syndrome coronavirus 2 has spread across the world, causing causalities and inflicting chronic complications in those who survive the infection. Disruptions in the immune system and lowered physical levels caused by quarantine protocols are the major causes of chronic dysfunction and impaired life independency, especially in elderly patients. Multiple exercise suggestions and novel program delivery methods, including telerehabilitation/tele-exercise programs, home-gym strategies, and exergames, have emerged. Patients with underlying obesity, diabetes mellitus, malnutrition, or binge-eating problems are at a high risk of serious infection and sequela. Adequate education and coping strategies can lessen the potential infection complications and improve the quality of life. Acknowledging the possible benefits and risks of nonsteroidal anti-inflammatory drug usage in chronic pain patients, and the supplementation of vitamin D may also aid in treating post-infected patients.
Impedance Values Do Not Correlate With Speech Understanding in Cochlear Implant Recipients
Authors: Prenzler Nils K. , Weller Tobias , Steffens Melanie , Lesinski-Schiedat Anke , Büchner Andreas , Lenarz Thomas , Warnecke Athanasia
Published: July 2020

Objective:

To evaluate a possible correlation between impedance values and speech perception after cochlear implantation.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients and Intervention:

All patients implanted with a MedEl Flex28 device in our department with complete audiometric data (Freiburger monosyllabic testing at 65 dB, Hochmaier–Schulz–Moser testing in quiet and in 10 dB noise) and impedance measurements at the 1-year refitting appointment were enrolled in this study. Further inclusion criteria were age > 17 years, native speakers, and no use of electric-acoustic-stimulation.

Main Outcome Measures:

Mean values for impedances were calculated over all electrode contacts and separately for basal, medial, and apical regions. These data were correlated statistically (Pearson's correlation) with speech testing results. Furthermore, groups of patients with extreme values were built and compared against each other and against the rest of the collective.

Results:

Impedance values did not correlate significantly with speech performance in any of the audiometric tests neither for all electrode contacts nor for specific clusters of contacts. Patients with the lowest impedances did not perform statistically different than patients with the highest impedances in any condition.

Conclusion:

To our knowledge, this is the first data on a possible correlation between impedances and speech perception. The extent of the impedances as a benchmark for a good performance in speech discrimination tests could not be verified. Further prospective studies, possibly with more precise diagnostic tools, should be carried out to define the value of impedance measurements for cochlear implantation provision.
Accuracy of the WatchBP O3 device for ambulatory blood pressure monitoring according to the new criteria of the ISO81060-2 2018 protocol
Authors: Fania Claudio , Lazzaretto Ilaria , Fontana Umberto , Palatini Paolo
Published: July 2020

Objective

The aim of the study was to determine the accuracy of the Microlife WatchBP O3 monitor for ambulatory blood pressure (BP) measurement according to the new ISO81060-2 2018 protocol.

Methods

The WatchBP O3 was first tested in 97 subjects from the general population (mean age, 71.3 years; 48 men) using four cuffs of different sizes. In a second study, 36 subjects (mean age, 72.9 years; 18 men) underwent stress testing on a cycle ergometer in order to increase their heart rate by 15% or more.

Results

In the general population, the mean device–observer difference was 1.3 ± 3.2 mmHg for systolic BP and was 0.7 ± 3.2 mmHg for diastolic BP. These data were in agreement with criterion 1 of the protocol standard requirements (≤5 ± 8 mmHg). Also, criterion 2 was satisfied being the SDs of the 97 participants well below the maximum values required by the protocol (6.82 and 6.90 mmHg, respectively). During the ambulatory monitoring study, the average heart rate increase was 20.3% (range 15.4–28.9%). The mean device–observer difference was 1.5 ± 2.8 mmHg for systolic BP and was 1.7 ± 2.6 mmHg for diastolic BP. Also, these data were in agreement with criterion 1 of the protocol.

Conclusions

These data show that the Microlife WatchBP O3 monitor satisfied the ISO 81060-2:2018 standard requirements for a general population across a wide range of arm sizes and that also the protocol criteria for validation of devices intended for ambulatory BP monitoring were fulfilled.
Mental Health Factors Associated With Fatigue in Mexican Patients With Inflammatory Bowel Disease
Authors: Fresán Orellana Ana , Parra Holguín Norma N. , Yamamoto-Furusho Jesus K.
Published: July 2020

Goals:

The aim of this study was to describe mental health factors associated with the development of fatigue in inflammatory bowel disease (IBD) patients.

Background:

IBD includes ulcerative colitis and Crohn’s disease. Patients with chronic diseases can present fatigue differently and qualitatively more severely than those typically represented by healthy populations.

Study:

This was a cross-sectional study in which 200 Mexican patients were attending the Inflammatory Bowel Disease Clinic at the National Institute of Medical Sciences and Nutrition. All patients answered 3 instruments: the first IBD-fatigue, HADS (Hospital Anxiety and Depression Scale), and PSQI (Pittsburgh Sleep Quality Index). The statistical analysis was carried out in the statistical program SPSS v 24.

Results:

The percentage of fatigue in our patients was 55.5% (n=111) for mild-moderate fatigue, 31.5% (n=63) for severe fatigue, and only 13% (n=26) had no fatigue. Sleep disturbance and sleep latency were the most important predictors of fatigue in IBD patients.

Conclusions:

Sleep quality and depression have an impact on fatigue in Mexican patients with IBD. It is important for multidisciplinary management to reduce these symptoms and improve the quality of life of patients with IBD.
Low prevalence of upper endoscopic gastrointestinal findings despite high frequency of alarm symptoms at the time of diagnosis in adult coeliac disease
Authors: Maimaris Stiliano , Schiepatti Annalisa , Gabrielli Gian Marco , Costetti Martina , Costa Stefania , Sanders David S , Zingone Fabiana , Carroccio Antonio , Ciacci Carolina , Di Sabatino Antonio , Biagi Federico
Published: July 2020

Objectives

Exclusion of organic disorders involving the upper gastrointestinal (UGI) is a mandatory step before considering a biopsy-avoidance diagnostic strategy for adult coeliac disease. We aim to evaluate the prevalence of alarm symptoms and coincidental UGI endoscopic findings at the time of diagnosis of coeliac disease. To develop consensus criteria to identify patients with coeliac disease requiring a gastroscopy and to evaluate whether alarm symptoms prompting gastroscopy were predictive of endoscopic findings.

Methods

Presenting symptoms and UGI endoscopic findings at diagnosis of coeliac disease were collected retrospectively in 278 adult patients with coeliac disease diagnosed in Pavia between January 1999 and December 2017. A panel of experts developed criteria to evaluate which clinical scenarios warrant gastroscopy, which was then applied retrospectively to patients diagnosed in Pavia.

Results

At least one alarm symptom was present in 177/278 patients, 121/278 met our criteria for gastroscopy. Major UGI endoscopic findings included 3 cases of autoimmune atrophic gastritis, 19 oesophagitis and 20 Helicobacter pylori infections. No organic disorders were found. Prevalence of major endoscopic findings did not differ between patients who met our criteria and those who did not.

Conclusions

Despite the high prevalence of alarm symptoms at diagnosis, coincident major UGI endoscopic findings are rare in adult coeliac disease. These results may be relevant for future developments in coeliac disease diagnosis in adults.
Sim for Life: Foundations—A Simulation Educator Training Course to Improve Debriefing Quality in a Low Resource Setting
Authors: Robinson Traci , Santorino Data , Dube Mirette , Twine Margaret , Najjuma Josephine N. , Cherop Moses , Kyakwera Catherine , Brenner Jennifer , Singhal Nalini , Bajunirwe Francis , Wishart Ian , Lin Yiqun , Lorentzen Helge , Lutnæs Dag Erik , Cheng Adam
Published: July 2020

Introduction

Despite the importance of debriefing, little is known about the effectiveness of training programs designed to teach debriefing skills. In this study, we evaluated the effectiveness of a faculty development program for new simulation educators at Mbarara University of Science and Technology in Uganda, Africa.

Methods

Healthcare professionals were recruited to attend a 2-day simulation educator faculty development course (Sim for Life: Foundations), covering principles of scenario design, scenario execution, prebriefing, and debriefing. Debriefing strategies were contextualized to local culture and focused on debriefing structure, conversational strategies, and learner centeredness. A debriefing worksheet was used to support debriefing practice. Trained simulation educators taught simulation sessions for 12 months. Debriefings were videotaped before and after initial training and before and after 1-day refresher training at 12 months. The quality of debriefing was measured at each time point using the Objective Structured Assessment of Debriefing (OSAD) tool by trained, calibrated, and blinded raters.

Results

A total of 13 participants were recruited to the study. The mean (95% confidence interval) OSAD scores pretraining, posttraining, and at 12 months before and after refresher were 18.2 (14.3–22.1), 26.7 (22.8–30.6), 25.5 (21.2–29.9), and 27.0 (22.4–31.6), respectively. There was a significant improvement from pretraining to posttraining (P < 0.001), with no significant decay from posttraining to 12 months (P = 0.54). There was no significant difference in OSAD scores pre– versus post–refresher training at 12 months (P = 0.49).

Conclusions

The Sim for Life Foundations program significantly improves debriefing skills with retention of debriefing skills at 12 months.
Systematic identification of modifiable risk factors and drug repurposing options for Alzheimer’s disease: Mendelian randomization analyses
Authors: Wu Chong , Wu Lang , Wang Jingshen , Lin Lifeng , Li Yanming , Lu Qing , Deng Hong-wen
Published: July 2020

Introduction

Several Mendelian randomization studies have been conducted, which identified multiple risk factors for Alzheimer’s disease (AD). However, they typically focus on a few pre-selected risk factors.

Methods

Two-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1,054 risk factors/medical conditions and 28 drugs with the risk of late- onset AD. To correct for multiple comparisons, the false discovery rate was set at <0.05.

Results

There were strong evidence of a causal association between glioma risk, reduced trunk fat-free mass, lower education levels, lower intelligence and a higher risk of AD. For 28 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations.

Conclusion

MR found robust evidence of causal associations between glioma, trunk fat-free and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.
Cell-based culture of SARS-CoV-2 informs infectivity and safe de-isolation assessments during COVID-19
Authors: Basile K , McPhie K , Carter I , Alderson S , Rahman H , Donovan L , Kumar S , Tran T , Ko D , Sivaruban T , Ngo C , Toi C , O’Sullivan MV , Sintchenko V , Chen S C-A , Maddocks S , Dwyer DE , Kok J
Published: July 2020

Background

The detection of SARS-CoV-2 by real-time polymerase chain reaction (PCR) in respiratory samples collected from persons recovered from COVID-19 does not necessarily indicate shedding of infective virions. By contrast, the isolation of SARS-CoV-2 using cell-based culture likely indicates infectivity, but there are limited data on the correlation between SARS-CoV-2 culture and PCR. Here we review our experience using SARS-CoV-2 culture to determine infectivity and safe de-isolation of COVID-19 patients.

Methods

195 patients with diverse severity of COVID-19 were tested (outpatients [n=178]), inpatients [n=12] and ICU [n=5]). SARS-CoV-2 PCR positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was documented, PCR was performed on day four to confirm absence of virus replication. Cycle threshold (Ct) values of the day four PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined as a Ctsample - Ctculture value of ≥3.

Findings

Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was only successfully isolated from samples with Ctsample values <32, including in 28/181 (15%), 19/42 (45%) and 9/11 samples (82%) collected from outpatients, inpatients and ICU patients, respectively. The mean duration from symptom onset to culture positivity was 4.5 days (range 0-18 days). SARS-CoV-2 was significantly more likely to be isolated from samples collected from inpatients (p<0.001) and ICU patients (p<0.0001) compared with outpatients, and in samples with lower Ctsample values.

Conclusion

SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.
Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations
Authors: Sarkar Rakesh , Mitra Suvrotoa , Chandra Pritam , Saha Priyanka , Banerjee Anindita , Dutta Shanta , Chawla-Sarkar Mamta
Published: July 2020

Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Comprehensive analysis of whole genome sequences of 441 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 21 being distinctive to India. Emergence of novel mutations were observed in S glycoprotein (7/33), NSP3 (6/33), RdRp/NSP12 (4/33), NSP2 (2/33) and N (2/33). Non-synonymous mutations were found to be 3.4 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on the co-existing mutations. Phylogenetic analyses revealed that representative strain of each group divided themselves into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. India was dominated by A2a clade (55.60%) followed by A3 (37.38%) and B (7%), but exhibited heterogeneous distribution among various geographical regions. The A2a clade mostly predominated in East India, Western India and Central India, whereas A3 clade prevailed in South and North India. In conclusion, this study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations would pave ways for vaccine formulation and designing of antiviral drugs.
Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide
Authors: Yin Rui , Luo Zihan , Kwoh Chee Keong
Published: July 2020

A newly emerging novel coronavirus appeared and rapidly spread worldwide and World Health Organization declared a pandemic on March 11, 2020. The roles and characteristics of coronavirus have captured much attention due to its power of causing a wide variety of infectious diseases, from mild to severe on humans. The detection of the lethality of human coronavirus is key to estimate the viral toxicity and provide perspective for treatment. We developed alignment-free machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of potential human-adapted coronavirus using genomic nucleotide. We performed extensive experiments through six different feature transformation and machine learning algorithms in combination with digital signal processing to infer the lethality of possible future novel coronaviruses using previous existing strains. The results tested on SARS-CoV, MERS-Cov and SARS-CoV-2 datasets show an average 96.7% prediction accuracy. We also provide preliminary analysis validating the effectiveness of our models through other human coronaviruses. Our study achieves high levels of prediction performance based on raw RNA sequences alone without genome annotations and specialized biological knowledge. The results demonstrate that, for any novel human coronavirus strains, this alignment-free machine learning-based approach can offer a reliable real-time estimation for its viral lethality.
Towards genetic modification of plant-parasitic nematodes: delivery of macromolecules to adults and expression of exogenous mRNA in second stage juveniles
Authors: Kranse Olaf , Beasley Helen , Adams Sally , da Silva Andre Pires , Bell Chris , Lilley Catherine , Urwin Peter , Bird David , Miska Eric , Smant Geert , Gheysen Godelieve , Jones John , Viney Mark , Abad Pierre , Maier Thomas R. , Baum Thomas J. , Siddique Shahid , Williamson Valerie , Akay Alper , den Akker Sebastian Eves-van
Published: July 2020

Plant-parasitic nematodes are a continuing threat to food security, causing an estimated 100 billion USD in crop losses each year. The most problematic are the obligate sedentary endoparasites (primarily root knot nematodes and cyst nematodes). Progress in understanding their biology is held back by a lack of tools for functional genetics: forward genetics is largely restricted to studies of natural variation in populations, and reverse genetics is entirely reliant on RNA interference. There is an expectation that the development of functional genetic tools would accelerate the progress of research on plant-parasitic nematodes, and hence the development of novel control solutions. Here, we develop some of the foundational biology required to deliver a functional genetic tool kit in plant-parasitic nematodes. We characterise the gonads of maleHeterodera schachtiiandMeloidogyne haplain the context of spermatogenesis. We test and optimise various methods for the delivery, expression, and/or detection of exogenous nucleic acids in plant-parasitic nematodes. We demonstrate that delivery of macromolecules to cyst and root knot nematode male germlines is difficult, but possible. Similarly, we demonstrate the delivery of oligonucleotides to root knot nematode gametes. Finally, we develop a transient expression system in plant-parasitic nematodes by demonstrating the delivery and expression of exogenous mRNA encoding various reporter genes throughout the body ofH. schachtiijuveniles using lipofectamine-based transfection. We anticipate these developments to be independently useful, will expedite the development of genetic modification tools for plant-parasitic nematodes, and ultimately catalyze research on a group of nematodes that threaten global food security.
Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition
Authors: Siddiqui Shoib S. , Dhar Chirag , Sundaramurthy Venkatasubramaniam , Sasmal Aniruddha , Yu Hai , Bandala-Sanchez Esther , Li Miaomiao , Zhang Xiaoxiao , Chen Xi , Harrison Leonard C. , Xu Ding , Varki Ajit
Published: July 2020

Blood pH is tightly regulated between 7.35-7.45, with values below 7.3 during sepsis being associated with lactic acidosis, low serum zinc, and release of proinflammatory HMGB1 from activated and/or necrotic cells. Using anex vivowhole blood system to model lactic acidosis, we show that while HMGB1 does not engage leukocyte receptors at physiological pH, lowering pH with lactic acid facilitates binding. At normal pH, micromolar zinc supports plasma sialoglycoprotein binding by HMGB1, which is markedly reduced when pH is adjusted with lactic acid to sepsis levels. Glycan array studies confirmed zinc and pH-dependent HMGB1 binding to sialoglycans typical of plasma glycoproteins. Thus, proinflammatory effects of HMGB1 are suppressed via plasma sialoglycoproteins until drops in pH and zinc release HMGB1 to trigger downstream immune activation.

Significance Statement

HMGB1 sequestered by plasma sialoglycoproteins at physiological pH is released when pH and zinc concentrations fall in sepsis.
A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death
Authors: Scott Duncan E. , Francis-Newton Nicola J. , Marsh May E. , Coyne Anthony G. , Fischer Gerhard , Moschetti Tommaso , Bayly Andrew R. , Sharpe Timothy D. , Haas Kalina T. , Barber Lorraine , Valenzano Chiara R. , Srinivasan Rajavel , Huggins David J. , Ehebauer Matthias , Esposito Alessandro , Pellegrini Luca , Perrior Trevor , McKenzie Grahame , Blundell Tom L. , Hyvönen Marko , Skidmore John , Venkitaraman Ashok R. , Abell Chris
Published: July 2020

BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily-conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51:BRC with a Kdof 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted α-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionising radiation, augmenting4Ncell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.
Early Improvement of Acute Respiratory Distress Syndrome in Patients with COVID-19: Insights from the Data of ICU Patients in Chongqing, China
Authors: Zhan Zhu , Yang Xin , Du Hu , Zhang Chuanlai , Song Yuyan , Ran Xiaoyun , Zhang An , Yang Mei
Published: July 2020

Acute respiratory distress syndrome (ARDS) may be the main cause of death in patients with coronavirus disease 2019 (COVID-19). Herein, we retrospect clinical features, outcomes and ARDS characteristics of 75 intensive care unit (ICU) patients with COVID-19 in Chongqing, China. We found a 5.3% case fatality rate of the ICU patients in Chongqing. 93% patients developed ARDS during the intensive care, and more than half were moderate. However, most of the patients (55%) supported with high flow nasal cannula (HFNC) oxygen therapy, but not mechanical ventilation. Nearly one third of patients with ARDS got an early improvement (eiARDS), and the rate is much higher than the other causes of ARDS in a previous study. Patients with eiARDS had a higher survival rate and lower length of ICU stay. The age (< 55 years) is an independent predictor for the eiARDS, and stratification of COVID-19 patients by age is recommended.
The amplified second outbreaks of global COVID-19 pandemic
Authors: Huang Jianping , Liu Xiaoyue , Zhang Li , Yang Kehu , Chen Yaolong , Huang Zhongwei , Liu Chuwei , Lian Xinbo , Wang Danfeng
Published: July 2020

COVID-19 is now in an epidemic phase, with a second outbreak likely to appear at any time. The intensity and timing of a second outbreak is a common concern worldwide. In this study, we made scenario projections of the potential second outbreak of COVID-19 using a statistical-epidemiology model, which considers both the impact of seasonal changes in meteorological elements and human social behaviors such as protests and city unblocking. Recent street protests in the United States and other countries are identified as a hidden trigger and amplifier of the second outbreak. The scale and intensity of subsequent COVID-19 outbreaks in the U.S. cities where the epidemic is under initial control are projected to be much greater than those of the first outbreak. For countries without reported protests, lifting the COVID-19 related restrictions prematurely would accelerate the spread of the disease and place mounting pressure on the local medical system that is already overloaded. We anticipate these projections will support public health planning and policymaking by governments and international organizations.
The impact of host resistance on cumulative mortality and the threshold of herd immunity for SARS-CoV-2
Authors: Lourenço José , Pinotti Francesco , Thompson Craig , Gupta Sunetra
Published: July 2020

It is widely believed that the herd immunity threshold (HIT) required to prevent a resurgence of SARS-CoV-2 is in excess of 50% for any epidemiological setting. Here, we demonstrate that HIT may be greatly reduced if a fraction of the population is unable to transmit the virus due to innate resistance or cross-protection from exposure to seasonal coronaviruses. The drop in HIT is proportional to the fraction of the population resistant only when that fraction is effectively segregated from the general population; however, when mixing is random, the drop in HIT is more precipitous. Significant reductions in expected mortality can also be observed in settings where a fraction of the population is resistant to infection. These results help to explain the large degree of regional variation observed in seroprevalence and cumulative deaths and suggest that sufficient herd-immunity may already be in place to substantially mitigate a potential second wave.
Moderate to vigorous physical activity and sedentary behavior change in self-isolating adults during the COVID-19 pandemic in Brazil: A cross-sectional survey exploring correlates
Authors: Schuch Felipe B. , Bulzing Rugero A. , Meyer Jacob , López-Sánchez Guillermo F. , Grabovac Igor , Willeit Peter , Vancampfort Davy , Caperchione Cristina M. , Sadarangani Kabir P. , Werneck André O. , Ward Philip B. , Tully Mark , Smith Lee
Published: July 2020

Background

Self-distancing measures imposed major changes in daily life. This study aimed to (i) evaluate the changes (pre-versus during pandemic) in time spent in moderate to vigorous physical activity (MVPA) and sedentary behavior (SB) in self-isolating Brazilians during the COVID-19 pandemic, and (ii) to explore correlates of MVPA and SB.

Methods

A cross-sectional self-report online survey, evaluating the time spent in MVPA and SB pre and during the COVID-19 pandemic. Sociodemographic, behavioral, clinical, variables, and time in self-isolation were also obtained. Changes in MVPA and SB and their correlates were explored using generalized estimating equations (GEE).

Results

A total of 877 participants (72.7% women, 53.7% young adults [18-34 years]) were included. Overall, participants reported a 59.7% reduction (95%CI:35.6 to 82.2) in time spent on MVPA during the pandemic. Time spent in SB increased 42.0% (95%CI:31.7 to 52.5). Greater reductions in MVPA and/or increases in SB were seen in younger adults, those not married, those employed and those with a self-reported previous diagnosis of a mental disorder.

Conclusions

People in self-isolation significantly reduced MVPA levels and increased SB. Public health strategies should be implemented during epidemic times to mitigate the impact of self-isolation on MVPA and SB, particularly in vulnerable groups.
Controlling COVID-19 via test-trace-quarantine
Authors: Kerr Cliff C. , Mistry Dina , Stuart Robyn M. , Rosenfeld Katherine , Hart Gregory R. , Núñez Rafael C. , Cohen Jamie A. , Selvaraj Prashanth , Abeysuriya Romesh G. , Jastrzębski Michał , George Lauren , Hagedorn Brittany , Panovska-Griffiths Jasmina , Fagalde Meaghan , Duchin Jeffrey , Famulare Michael , Klein Daniel J.
Published: July 2020

Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine. We performed this analysis using Covasim, an open-source agent-based model, which was calibrated to detailed demographic, mobility, and epidemiological data for the Seattle region from January through June 2020. With current levels of mask use and schools remaining closed, we found that high but achievable levels of testing and tracing are sufficient to maintain epidemic control even under a return to full workplace and community mobility and with low vaccine coverage. The easing of mobility restrictions in June 2020 and subsequent scale-up of testing and tracing programs through September provided real-world validation of our predictions. Although we show that test-trace-quarantine can control the epidemic in both theory and practice, its success is contingent on high testing and tracing rates, high quarantine compliance, relatively short testing and tracing delays, and moderate to high mask use. Thus, in order for test-trace-quarantine to control transmission with a return to high mobility, strong performance in all aspects of the program is required.
Transcriptional response of the calcification and stress response toolkits in an octocoral under heat and pH stress
Authors: Vargas Sergio , Zimmer Thorsten , Conci Nicola , Lehmann Martin , Wörheide Gert
Published: July 2020

Up to one-third of all described marine species inhabit coral reefs, but the future of these hyperdiverse ecosystems is insecure due to local and global threats, such as overfishing, eutrophication, ocean warming, and acidification. Although these impacts are expected to have a net detrimental effect on reefs, it has been shown that some organisms like octocorals may remain unaffected, or benefit from, anthropogenically induced environmental change, and may replace stony corals in future reefs. Despite their potential importance in future shallow-water coastal environments, the molecular mechanisms leading to the resilience to anthropogenic-induced stress observed in octocorals remain unknown. Here, we use manipulative experiments, proteomics, and transcriptomics to show that the molecular toolkit used by Pinnigorgia flava, a common Indo-Pacific gorgonian octocoral, to deposit its calcium-carbonate skeleton is resilient to heat and seawater acidification stress. Sublethal heat stress triggered a stress response in P. flava but did not affect the expression of 27 transcripts encoding Skeletal Organic Matrix (SOM) proteins. Exposure to seawater acidification did not cause a stress response but triggered the downregulation of many transcripts, including an osteonidogen homolog present in the SOM. The observed transcriptional decoupling of the skeletogenic and stress-response toolkits provides insights into the mechanisms of resilience to anthropogenically-driven environmental change observed in octocorals.
Definition and Signatures of Lung Fibroblast Populations in Development and Fibrosis in Mice and Men
Authors: Liu Xue , Rowan Simon C. , Liang Jiurong , Yao Changfu , Huang Guanling , Deng Nan , Xie Ting , Wu Di , Wang Yizhou , Burman Ankita , Parimon Tanyalak , Borok Zea , Chen Peter , Parks William C. , Hogaboam Cory M. , Weigt S. Samuel , Belperio John , Stripp Barry R. , Noble Paul W. , Jiang Dianhua
Published: July 2020

The heterogeneity of fibroblasts in the murine and human lung during homeostasis and disease is increasingly recognized. It remains unclear if the different phenotypes identified to date are characteristic of unique subpopulations with unique progenitors or whether they arise by a process of differentiation from common precursors. Our understanding of this ubiquitous cell type is limited by an absence of well validated, specific, markers with which to identify each cell type and a clear consensus on the distinct populations present in the lung. Here we describe single cell RNA sequencing (scRNA-seq) analysis on mesenchymal cells from the murine lung throughout embryonic (E) development (E9.5 – 17.5), at post-natal day (P1 – 15), as well as in the adult and the aged murine lungs before and after bleomycin-induced fibrosis. We carried out complementary scRNA-seq on human lung tissue from a P1 lung, a month 21 lung and lung tissue from healthy donors and patients with idiopathic pulmonary fibrosis (IPF). The murine and human data were supplemented with publicly available scRNA-seq datasets. We consistently identified lipofibroblasts, myofibroblasts, pericytes, mesothelial cells and smooth muscle cells. In addition, we identified a novel population delineated by Ebf1 (early B-cell factor 1) expression and an intermediate subtype. Comparative analysis with human mesenchymal cells revealed homologous mesenchymal subpopulations with remarkably conserved transcriptomic signatures. Comparative analysis of changes in gene expression in the fibroblast subpopulations from age matched non-fibrotic and fibrotic lungs in the mouse and human demonstrates that many of these subsets contribute to matrix gene expression in fibrotic conditions. Subtype selective transcription factors were identified and putative divergence of the clusters during development were delineated. Prospective isolation of these fibroblast subpopulations, localization of signature gene markers, and lineage-tracing each cluster are under way in the laboratory. This analysis will enhance our understanding of fibroblast heterogeneity in homeostasis and fibrotic disease conditions.
Identifying differences in gait adaptability across various speeds using movement synergy analysis
Authors: Ó’Reilly David , Federolf Peter
Published: July 2020

Introduction

The aim of this study was to identify movement synergies during normal-walking that can differentiate healthy adults in terms of gait adaptability at various speeds. To this end, the association between movement synergies and lower-limb coordination variability or Deviation Phase (DP) was investigated. A secondary aim of this study included an investigation into the moderating effect of these movement synergies on the relationship between DP and the smoothness of arm-swing motion quantified as the normalised jerk index (NJI).

Method

A principal component analysis of whole-body marker trajectories from normal-walking treadmill trials at 0.8m/s, 1.2m/s and 1.6m/s was undertaken. Both DP and NJI were derived from approx. 8 minutes of perturbed-walking treadmill trials. Principal movement components, PMk, were derived and the RMS of the 2nd-order differentiation of these PMk(PAkRMS) were included as independent variables representing the magnitude of neuromuscular control in each PMk. The PAkRMS were input into separate maximal linear mixed-effects regression models to explain the variance in DP and (DP × NJI). A stepwise elimination of terms and comparison of models using Anova identified optimal models for both aims.

Results

Among the first 7 validated PMk, PA4RMS (double-support phase) was identified as an optimal model and demonstrated a significant negative effect on DP however this effect may differ considerably across walking-speeds. An optimal model for describing the variance in (DP × NJI) included a fixed-effect of PA6RMS (Left – Right side weight transfer). Within-participant clustering was prevalent within both optimal models.

Interpretation

The hypotheses that individuals who exhibited greater control on specific kinematic synergies would exhibit variations during perturbed walking was substantiated. Supporting evidence for the role of movement synergies during the double-support phase of gait in proactively correcting balance was presented. The potential influence of leg dominance on gait adaptability was also discussed. Future studies should investigate further the role of walking-speed and leg dominance on movement synergies and look to generalize these findings to patient populations.

Highlights

Baseline movement synergies representing terminal-swing and double-support phases of gait were found to have significant negative effects on lower-limb coordination variability during perturbed-walking trials at various speeds.

Movement synergies related to the double-support phase and weight transfer events of gait were determined to have a negative moderating effect on the translation of lower-limb coordination variability into upper-limb postural corrections.

Evidence was presented for the important role of the double-stance phase of gait in gait adaptability while leg dominance was shown to play a potential role in differentiating healthy adults in this study.
Actin and an unconventional myosin motor, TgMyoF control the organization and dynamics of the endomembrane network inToxoplasma gondii
Authors: Carmeille Romain , Heaslip Aoife T.
Published: July 2020

Toxoplasma gondiiis an obligate intracellular parasite that relies on three distinct secretory organelles, the micronemes, rhoptries and dense granules, for parasite survival and disease pathogenesis. Secretory proteins destined for these organelles are synthesized in the endoplasmic reticulum (ER) and sequentially trafficked through a highly polarized endomembrane network that consists of the Golgi and multiple post-Golgi compartments. Currently, little is known about how the parasite cytoskeleton controls the positioning of the organelles in this pathway, or how vesicular cargo is trafficked between organelles. Here we show that F-actin and an unconventional myosin motor, TgMyoF, control the dynamics and organization of the organelles in the secretory pathway, specifically ER tubule movement, apical positioning of the Golgi and post-Golgi compartments, apical positioning of the rhoptries and finally, the directed transport of Rab6-positive and Rop1-positive vesicles. Thus, this study identifies TgMyoF and actin as the key cytoskeletal components that organize the endomembrane system inT. gondii.

Author Summary

Endomembrane trafficking is a vital cellular process in all eukaryotic cells. In most cases the molecular motors myosin, kinesin and dynein transport cargo including vesicles, organelles and transcripts along actin and microtubule filaments in a manner analogous to a train moving on its tracks. For the unicellular eukaryoteToxoplasma gondii, the accurate trafficking of proteins through the endomembrane system is vital for parasite survival and pathogenicity. However, the mechanisms of cargo transport in this parasite are poorly understood. In this study, we fluorescently labeled multiple endomembrane organelles and imaged their movements using live cell microscopy. We demonstrate that filamentous actin and an unconventional myosin motor named TgMyoF control both the positioning of organelles in this pathway and the movement of transport vesicles throughout the parasite cytosol. This data provides new insight into the mechanisms of cargo transport in this important pathogen and expands are understanding of the biological roles of actin in the intracellular phase of the parasite’s growth cycle.
Sites of Vulnerability on Ricin B Chain Revealed through Epitope Mapping of Toxin-Neutralizing Monoclonal Antibodies
Authors: Vance David J. , Poon Amanda Y. , Mantis Nicholas J.
Published: July 2020

Ricin toxin’s B subunit (RTB) is a multifunctional galactose (Gal)-/N-acetylgalactosamine (GalNac)-specific lectin that promotes efficient uptake and intracellular trafficking of ricin’s ribosome-inactivating subunit (RTA) into mammalian cells. Structurally, RTB consists of two globular domains (RTB-D1, RTB-D2), each divided into three homologous sub-domains (α, β, γ). The two carbohydrate recognition domains (CRDs) are situated on opposite sides of RTB (sub-domains 1α and 2γ) and function non-cooperatively. Previous studies have revealed two distinct classes of toxin-neutralizing, anti-RTB monoclonal antibodies (mAbs). Type I mAbs, exemplified by SylH3, inhibit (∼90%) toxin attachment to cell surfaces, while type II mAbs, epitomized by 24B11, interfere with intracellular toxin transport between the plasma membrane and the trans-Golgi network (TGN). Localizing the epitopes recognized by these two classes of mAbs has proven difficult, in part because of RTB’s duplicative structure. To circumvent this problem, full-length RTB or the two individual domains, RTB-D1 and RTB-D2, were expressed as pIII fusion proteins on the surface of filamentous phage M13 and subsequently used as “bait” in mAb capture assays. The results indicated that SylH3 captured RTB-D1, while 24B11 captured RTB-D2. Analysis of additional toxin-neutralizing and non-neutralizing mAbs along with single chain antibodies (VHHs) known to compete with SylH3 or 24B11 confirmed these domain assignments. These results not only indicate that so-called type I and type II mAbs segregate on the basis of domain specificity, but suggest that RTB’s two domains may contribute to distinct steps in the intoxication pathway.
Deconstructing biodiversity-ecosystem function relationships: Filtering of macroinvertebrate traits in a large river floodplain
Authors: Rideout Natalie K. , Compson Zacchaeus G. , Monk Wendy A. , Bruce Meghann R. , Hajibabaei Mehrdad , Porter Teresita M. , Wright Michael T.G. , Baird Donald J.
Published: July 2020

The Biodiversity-Ecosystem Function hypothesis postulates that higher biodiversity is correlated with ecosystem function by providing a high number of filled niches through species response types and resource use patterns. Through their high spatio-temporal habitat diversity, floodplains are highly productive ecosystems, supporting communities that are naturally resilient and highly diverse. We examined linkages among floodplain wetland habitats, invertebrate communities and their associated traits, and ecosystem function across 60 sites within the floodplain wetlands of the lower Wolastoq | Saint John River, New Brunswick, using structural equation modelling and Threshold Indicator Taxa ANalysis (TITAN2). We identified key environmental filters of invertebrate communities, namely linking increased niche differentiation through historical change, flood pulse dynamics, and macrophyte bed complexity with increased taxa and functional diversity. Examination of traits linked to ecosystem functions revealed that healthy wetlands with higher primary productivity were associated with greater functional evenness and richness, while habitat patches with increased decomposition rates had low functional richness, reflecting highly disturbed habitat. Our results highlight key differences between wetland and riverine ecosystems, relating to how critical functions support healthy wetland habitats by providing increased resilience to disturbance, here associated with differing levels of conservation protection.
Enrichment-Free Identification of Native Definitive (EnFIND) O-glycoproteome of antibodies in autoimmune diseases
Authors: Sun Xue , Cheng Jianhui , Tian Wenmin , Gao Shuaixin , Guo Jiangtao , Hu Fanlei , Zhang Hong , Huang Xiaojun , Chen Da Yong , Chen Yang , Wong Catherine CL
Published: July 2020

The detection of O-glycosylation at the proteome level has long been a challenging task and a roadblock for O-linked protein glycosylation research. We report an Enrichment-Free Identification of Native Definitive (EnFIND) O-glycoproteome using Trapped Ion Mobility Spectrometry coupled to TOF Mass Spectrometry (TIMS-TOF MS) for direct analysis of protein O-glycosylation in native samples with minimum sample requirement. This approach enabled separation of O-glycopeptide isomers, resolution of O-glycosites and O-glycoform, reduction of sample complexity, and increased sensitivity, thus greatly enhancing analysis of the O-glycoproteome of cell lysates, human serum and exosomes. In addition, we found that antibodies in human serum are highly O-glycosylated on variable, especially hypervariable regions and constant regions, which significantly increases antibody diversity. This method was used to successfully identify characteristic O-glycosylation features of autoimmune diseases.
Contextual dependencies expand the re-usability of genetic inverters
Authors: Tas Huseyin , Grozinger Lewis , Stoof Ruud , de Lorenzo Victor , Goñi-Moreno Angel
Published: July 2020

The design and implementation of Boolean logic functions in living cells has become a very active field within synthetic biology. By controlling networks of regulatory proteins, novel genetic circuits are engineered to generate predefined output responses. Although many current implementations focus solely on the genetic components of the circuit, the host context in which the circuit performs is crucial for its outcome. Here, we characterise 20 genetic NOT logic gates (inverters) in up to 7 bacterial-based contexts each, to finally generate 135 different functions. The contexts we focus on are particular combinations of four plasmid backbones and three hosts, twoEscherichia coliand onePseudomonas putidastrains. Each NOT logic gate shows seven different logic behaviours, depending on the context. That is, gates can be reconfigured to fit response requirements by changing only contextual parameters. Computational analysis shows that this range of behaviours improves the compatibility between gates, because there are considerably more possibilities for combination than when considering a unique function per genetic construct. Finally, we address the issue of interoperability and portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expand the scope of the functions that can be engineered in complex cellular environments, and advocate for considering context as a fundamental design parameter for synthetic biology.