bluuebunny/crossref_metadata_2025 huggingface dataset:
Ozone Therapy on Reduction of Bacterial Colonies and Acceleration of Diabetic Foot Ulcer Healing
Authors: Kadir Kasmawati , Syam Yuliana , Yusuf Saldy , Zainuddin Masriani
Published: July 2020

Diabetic foot ulcers (DFUs) are highly vulnerable to infection and pose risk for limb amputations. Studies have shown that ozone therapy reduces wound size and improves wound healing time better than standard treatments. We examined the effectiveness of combining standard wound care with ozone therapy to reduce bacterial colonization and accelerate healing of DFUs in the home care setting. The control group (n = 12) received standard wound care with antimicrobial dressings every 3 days for 21 days, and the intervention group (n = 15) received the same as control group plus ozone bagging therapy at 70 μg/mL for 10 minutes every 3 days for 21 days. Combining standard wound care with ozone therapy significantly decreased the number of bacterial colonies (p = 0.001). However, no significant difference in DFU assessment score was found between the intervention and control groups (p > 0.05). Combining standard wound care with ozone therapy reduced the number of bacteria in the DFUs but exerted no significant effect on wound healing. Future studies should examine the administration of ozone therapy with different concentrations and times of exposure to explore the right dose for healing DFUs.
Reversible Cerebral Vasoconstriction Syndrome Following Carotid Endarterectomy
Authors: Judge Casey , Yacoub Hussam , Chu Chun , Nizam Ahmad , Sivakumar Keithan , Mehta Dev
Published: July 2020

Introduction:

Reversible cerebral vasoconstriction syndrome (RCVS) is a cerebrovascular disorder associated with multifocal intracranial arterial constriction and dilation that occurs spontaneously or as a result of a stimulant. The authors present a case of RCVS in a patient who presented with a new-onset thunderclap headache a day after carotid endarterectomy (CEA). RCVS has been rarely reported after CEA.

Case Report:

A 65-year-old woman was evaluated for a new-onset thunderclap headache a day after left-sided CEA. Computed tomography (CT) of the head revealed left frontal and parietal subarachnoid hemorrhage (SAH). CT angiography did not show any saccular aneurysms or vessel stenosis. The initial impression was SAH related to reperfusion injury after carotid revascularization. Seven days postoperatively, the patient returned to the hospital with a persistent headache. CT revealed SAH in the vertex of the frontal region bilaterally. Magnetic resonance angiogram (MRA) of the head revealed multifocal stenosis of the intracranial circulation bilaterally. A follow-up MRA 9 weeks postoperatively showed interval improvement of the caliber of the circle of Willis branches and significant improvement of the multifocal stenosis. The patient was diagnosed with RCVS as a result of CEA.

Conclusion:

The authors advise clinicians to consider RCVS as a cause of thunderclap headache or recurrence of a severe headache shortly after CEA—particularly with the presence of a nonaneurysmal convexity SAH.
Treatment of Status Epilepticus
Authors: Parsons Angela M. , Patel Akta A. , Crepeau Amy Z.
Published: July 2020

Objectives:

Status epilepticus (SE) is associated with high morbidity and mortality. The American Epilepsy Society (AES) has established guidelines regarding proper dosing of antiepileptic drugs (AEDs). There are also recommendations for appropriate weaning off anesthetic agents in SE. Our aim was to determine the frequency with which guidelines were being followed during routine clinical care.

Methods:

A retrospective chart review was completed for patients with a diagnosis of SE within the last 10 years. All patients with SE on anesthetic agents were included when analyzing AED dosing. Patients with anoxic brain injury were excluded when reviewing anesthetic wean times.

Results:

Seventy-six patients were identified on anesthetic agents. Five patients had anoxic brain injury and were excluded from the anesthetic weaning analysis. Medications were under dosed as follows: lorazepam 0.05 mg/kg (N=51), midazolam 0.07 mg/kg (N=14), fosphenytoin 17.9 mg/kg (N=47), levetiracetam 21.7 mg/kg (N=42), valproate sodium 16.7 mg/kg (N=12), phenobarbital 4.1 mg/kg (N=4), lacosamide 215 mg (N=13), and topiramate 333 mg (N=3). Anesthetic agents were weaned as follows: <24 hours 32/71 (45%), 24 to 48 hours 11/71 (15%), 48 to 72 hours 12/71 (17%), and >72 hours 11/71 (15%). Seizure recurrence rates were: 8/32 (25%) <24 hours, 2/11 (18%) 24 to 48 hours, 1/12 (8.3%) 48 to 72 hours, and 1/11 (9%) at >72 hours.

Conclusions:

This retrospective review demonstrates how guidelines and recommendations for SE are not consistently followed. Under dosing of AEDs and aggressive weaning of anesthetic agents may result in higher morbidity and mortality.
Reducing Opioid Exposure in a Level IV Neonatal Intensive Care Unit
Authors: Stetson Raymond C. , Smith Brandi N. , Sanders Nicole L. , Misgen Megan A. , Ferrie LaRae J. , Schuning Virginia S. , Schuh Allison R. , Fang Jennifer L. , Brumbaugh Jane E.
Published: July 2020

Introduction:

Infants in neonatal intensive care units require painful and noxious stimuli as part of their care. Judicious use of analgesic medications, including opioids, is necessary. However, these medications have long- and short-term side effects, including potential neurotoxicity. This quality improvement project’s primary aim was to decrease opioid exposure by 33% in the first 14 days of life for infants less than 1,250 g at birth within 12 months.

Methods:

A multidisciplinary care team used Define, Measure, Analyze, Improve, Control methodology to identify root causes of the quality gap including: (1) inconsistent reporting of objective pain scales; (2) variable provider prescribing patterns; and (3) variable provider bedside assessment of pain. These root causes were addressed by two interventions: (1) standardized reporting of the premature infant pain profile scores and (2) implementation of an analgesia management pathway.

Results:

Mean opioid exposure, measured in morphine equivalents, in infants less than 1,250 g at birth during their first 14 days of life decreased from 0.64 mg/kg/d (95% confidence interval 0.41–0.87) at baseline to 0.08 mg/kg/d (95% confidence interval 0.03–0.13) during the postintervention period (P < 0.001). There was no statistical difference in rates of days to full feedings, unintentional extubations, or central line removals between epochs.

Conclusions:

Following the implementation of consistent pain score reporting and an analgesia management pathway, opioid exposure in the first 14 days of life for infants less than 1,250 g was significantly reduced by 88%, exceeding the project aim.
Reducing Antibiotic Prescription Errors in the Emergency Department: A Quality Improvement Initiative
Authors: Kasmire Kathryn E. , Cerrone Crista , Hoppa Eric C.
Published: July 2020

Introduction:

Discharge prescription errors from the pediatric emergency department (ED) are common. Despite the implementation of clinical pathways for common infections recommending specific antibiotic therapy and aids built into the electronic health record, errors in antibiotic prescriptions for patients discharged home from the ED persist.

Methods:

We developed and implemented ED antibiotic discharge order panels for urinary tract infection (UTI) and skin and soft tissue infections (SSTI) that modeled antibiotic therapy from our institutional clinical pathways. We aimed to reduce antibiotic prescription errors by 50% within 6 months of implementation.

Results:

With the implementation of the ED discharge order panels, the overall error rate for prescriptions for UTI and SSTI improved from a baseline rate of 29.3% to 12.6% (P < 0.001). Individually, the baseline number of prescriptions with errors for UTI and SSTI improved from 26.1% and 32.8%, respectively, to 13.8% and 12.5% within 6 months. Sustained improvement continued for 17 months after the implementation of the order panels.

Conclusions:

Development and implementation of ED antibiotic discharge order panels decrease antibiotic prescription errors for UTI and SSTI by improving compliance with institutional clinical pathways. Additional order panels should be developed and implemented for other conditions to help reduce discharge prescription errors.
Sibling rivalry versus mother's curse: can kin competition facilitate a response to selection on male mitochondria?
Authors: Keaney Thomas A. , Wong Heidi W. S. , Dowling Damian K. , Jones Therésa M. , Holman Luke
Published: July 2020

Assuming that fathers never transmit mitochondrial DNA (mtDNA) to their offspring, mitochondrial mutations that affect male fitness are invisible to direct selection on males, leading to an accumulation of male-harming alleles in the mitochondrial genome (mother's curse). However, male phenotypes encoded by mtDNA can still undergo adaptation via kin selection provided that males interact with females carrying related mtDNA, such as their sisters. Here, using experiments withDrosophila melanogastercarrying standardized nuclear DNA but distinct mitochondrial DNA, we test whether the mitochondrial haplotype carried by interacting pairs of larvae affects survival to adulthood, as well as the fitness of the adults. Although mtDNA had no detectable direct or indirect genetic effect on larva-to-adult survival, the fitness of male and female adults was significantly affected by their own mtDNA and the mtDNA carried by their social partner in the larval stage. Thus, mtDNA mutations that alter the effect of male larvae on nearby female larvae (which often carry the same mutation, due to kinship) could theoretically respond to kin selection. We discuss the implications of our findings for the evolution of mitochondria and other maternally inherited endosymbionts.
Phylogenetic and functional distinctiveness explain alien plant population responses to competition
Authors: Levin Sam C. , Crandall Raelene M. , Pokoski Tyler , Stein Claudia , Knight Tiffany M.
Published: July 2020

Several invasion hypotheses predict a positive association between phylogenetic and functional distinctiveness of aliens and their performance, leading to the idea that distinct aliens compete less with their resident communities. However, synthetic pattern relationships between distinctiveness and alien performance and direct tests of competition as the driving mechanism have not been forthcoming. This is likely because different patterns are observed at different spatial grains, because functional trait and phylogenetic information are often incomplete, and because of the need for competition experiments that measure demographic responses across a variety of alien species that vary in their distinctiveness. We conduct a competitor removal experiment and parameterize matrix population and integral projection models for 14 alien plant species. More novel aliens compete less strongly with co-occurring species in their community, but these results dissipate at a larger spatial grain of investigation. Further, we find that functional traits used in conjunction with phylogeny improve our ability to explain competitive responses. Our investigation shows that competition is an important mechanism underlying the differential success of alien species.
Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent
Authors: Hahn Georg , Cho Michael H. , Weiss Scott T. , Silverman Edwin K. , Lange Christoph
Published: July 2020

Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.
When the best pandemic models are the simplest
Authors: Jahedi Sana , Yorke James A.
Published: July 2020

As a pandemic of coronavirus spreads across the globe, people debate policies to mitigate its severity. Many complex, highly detailed models have been developed to help policy setters make better decisions. However, the basis of these models is unlikely to be understood by non-experts.

We describe the advantages of simple models for covid-19. We say a model is “simple”if its only parameter is the rate of contact between people in the population. This contact rate can vary over time, depending on choices by policy setters. Such models can be understood by a broad audience, and thus can be helpful in explaining the policy decisions to the public. They can be used to evaluate outcomes of different policy strategies. However, simple models have a disadvantage when dealing with inhomogeneous populations.

To augment the power of a simple model to evaluate complicated situations, we add what we call“satellite”equations that do not change the original model. For example, with the help of a satellite equation, one could know what his/her chance is of remaining uninfected through the end of epidemic. Satellite equations can model the effect of the epidemic on high-risk individuals, or death rates, or on nursing homes, and other isolated populations.

To compare simple models with complex models, we introduce our“slightly complex” Model J. We find the conclusions of simple and complex models can be quite similar. But, for each added complexity, a modeler may have to choose additional parameter values describing who will infect whom under what conditions, choices for which there is often little rationale but that can have a big impact on predictions. Our simulations suggest that the added complexity offers little predictive advantage.

Author Summary

There is a large variety of available data about the coronavirus pandemic, but we still lack data about some important factors. Who is likely to infect whom and under what conditions and how long after becoming infected? These factors are the essence of transmission dynamics. Two groups using identical complex models can be expected to make different predictions simply because they make different choices for such transmission parameters in the model. The audience has no way to choose between their predictions. We explain how simple models can be used to answer complex questions by adding what we call satellite equations, addressing questions involving age groups, death rates, and likelihood of transmission to nursing homes and to uninfected, isolated populations. Simple models are ideal for seeing what kinds of interventions are needed to achieve goals of policy setters.
A highly contiguous genome assembly ofBrassica nigra(BB) and revised nomenclature for the pseudochromosomes
Authors: Paritosh Kumar , Pradhan Akshay Kumar , Pental Deepak
Published: July 2020

Brassica nigra(BB), also called black mustard, is grown as a condiment crop in India.B. nigrarepresents the B genome of U’s triangle and is one of the progenitor species ofB. juncea(AABB), an important oilseed crop of the Indian subcontinent. We report here a highly contiguous genome assembly ofB. nigravariety Sangam. The genome assembly has been carried out using Oxford Nanopore long-read sequencing and optical mapping. The resulting chromosome-scale assembly is a significant improvement over the previous draft assemblies ofB. nigra; five out of the eight pseudochromosomes were represented by one scaffold each. The assembled genome was annotated for the transposons, centromeric repeats, and genes. TheB. nigragenome was compared with the recently available contiguous genome assemblies ofB. rapa(AA),B. oleracea(CC), andB. juncea(AABB). Based on the maximum homology among the three diploid genomes of U’s triangle, we propose a new nomenclature forB. nigrapseudochromosomes, taking theB. rapapseudochromosome nomenclature as the reference.
Dynamic community detection reveals transient reorganization of functional brain networks across a female menstrual cycle
Authors: Mueller Joshua M. , Pritschet Laura , Santander Tyler , Taylor Caitlin M. , Grafton Scott T. , Jacobs Emily Goard , Carlson Jean M.
Published: July 2020

Sex steroid hormones have been shown to alter regional brain activity, but the extent to which they modulate connectivity within and between large-scale functional brain networks over time has yet to be characterized. Here, we applied dynamic community detection techniques to data from a highly sampled female with 30 consecutive days of brain imaging and venipuncture measurements to characterize changes in resting-state community structure across the menstrual cycle. Four stable functional communities were identified consisting of nodes from visual, default mode, frontal control, and somatomotor networks. Limbic, subcortical, and attention networks exhibited higher than expected levels of nodal flexibility, a hallmark of between-network integration and transient functional reorganization. The most striking reorganization occurred in a default mode subnetwork localized to regions of the prefrontal cortex, coincident with peaks in serum levels of estradiol, luteinizing hormone, and follicle stimulating hormone. Nodes from these regions exhibited strong intra-network increases in functional connectivity, leading to a split in the stable default mode core community and the transient formation of a new functional community. Probing the spatiotemporal basis of human brain–hormone interactions with dynamic community detection suggests that ovulation results in a temporary, localized patterns of brain network reorganization.

Author Summary

Sex steroid hormones influence the central nervous system across multiple spatiotemporal scales. Estrogen and progesterone concentrations rise and fall throughout the menstrual cycle, but it remains poorly understood how day-to-day fluctuations in hormones shape human brain dynamics. Here, we assessed the structure and stability of resting-state brain network activity in concordance with serum hormone levels from a female who underwent fMRI and venipuncture for 30 consecutive days. Our results reveal that while network structure is largely stable over the menstrual cycle, there is temporary reorganization of several largescale functional brain networks during the ovulatory window. In particular, a default mode subnetwork exhibits increased connectivity with itself and with regions from temporoparietal and limbic networks, providing novel perspective into brain-hormone interactions.
Insights into the secondary structural ensembles of the full SARS-CoV-2 RNA genome in infected cells
Authors: Lan Tammy C. T. , Allan Matthew F. , Malsick Lauren E. , Khandwala Stuti , Nyeo Sherry S. Y. , Sun Yu , Guo Junjie U. , Bathe Mark , Griffiths Anthony , Rouskin Silvi
Published: July 2020

SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on native RNA structures in SARS-CoV-2 and most putative regulatory sequences are functionally uncharacterized. Here we report secondary structure ensembles of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and the algorithm ‘detection of RNA folding ensembles using expectation–maximization’ clustering (DREEM). Our results reveal previously undescribed alternative RNA conformations across the genome, including structures of the frameshift stimulating element (FSE), a major drug target, that are drastically different from prevailingin vitropopulation average models. Importantly, we find that this structural ensemble promotes frameshifting rates (~40%) similar toin vivoribosome profiling studies and much higher than the canonical minimal FSE (~20%). Overall, our result highlight the value of studying RNA folding in its native, dynamic and cellular context. The genomic structures detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.
Integrated glycoproteomics identifies a role ofN-glycosylation and galectin-1 on myogenesis and muscle development
Authors: Blazev Ronnie , Ashwood Christopher , Abrahams Jodie L. , Chung Long H. , Francis Deanne , Yang Pengyi , Watt Kevin I. , Qian Hongwei , Quaife-Ryan Gregory A. , Hudson James E. , Gregorevic Paul , Thaysen-Andersen Morten , Parker Benjamin L.
Published: July 2020

Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of releasedN-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown di-galactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labelling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins most notably the up-regulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion ofLgals1inhibited differentiation and myotube formation suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes inN-glycosylation and the up-regulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.
Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro
Authors: Bobrowski Tesia , Chen Lu , Eastman Richard T. , Itkin Zina , Shinn Paul , Chen Catherine , Guo Hui , Zheng Wei , Michael Sam , Simeonov Anton , Hall Matthew D. , Zakharov Alexey V. , Muratov Eugene N.
Published: July 2020

COVID-19 is undoubtedly the most impactful viral disease of the current century, afflicting millions worldwide. As yet, there is not an approved vaccine, as well as limited options from existing drugs for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2. Usingin silicoapproaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested themin vitro. Overall, we identified 16 synergistic and 8 antagonistic combinations, 4 of which were both synergistic and antagonistic in a dose-dependent manner. Among the 16 synergistic cases, combinations of nitazoxanide with three other compounds (remdesivir, amodiaquine and umifenovir) were the most notable, all exhibiting significant synergy against SARS-CoV-2. The combination of nitazoxanide, an FDA-approved drug, and remdesivir, FDA emergency use authorization for the treatment of COVID-19, demonstrate a strong synergistic interaction. Notably, the combination of remdesivir and hydroxychloroquine demonstrated strong antagonism. Overall, our results emphasize the importance of both drug repurposing and preclinical testing of drug combinations for potential therapeutic use against SARS-CoV-2 infections.
Membrane pore energetics and the pathways to membrane rupture
Authors: An Dong , Thiyagarajan Sathish , Antipov Egor , Alcott Brett , O’Shaughnessy Ben
Published: July 2020

Biological membranes owe their strength and low permeability to the phospholipid bilayers at their core. Membrane strength is determined by the energetics and dynamics of membrane pores, whose tension-dependent nucleation and growth leads to rupture. Creation of nanoscale membrane pores is central to exocytosis, trafficking and other processes fundamental to life that require breaching of secure plasma or organelle membranes, and is the basis for biotechnologies using drug delivery, delivery of genetic material for gene editing and antimicrobial peptides. A prevailing view from seminal electroporation and membrane rupture studies is that pore growth and bilayer rupture are controlled by macroscopically long-lived metastable defect states that precede fully developed pores. It was argued that defect nucleation becomes rate-limiting at high tensions, explaining the exponential tension-dependence of rupture times [E. Evans et al.,Biophys. J.85, 2342-2350 (2003)]. Here we measured membrane pore free energies and bilayer rupture using highly coarse-grained simulations that probe very long time scales. We find no evidence of metastable pore states. At lower tensions, small hydrophobic pores mature into large hydrophilic pores on the pathway to rupture, with classical tension dependence of rupture times. Above a critical tension membranes rupture directly from a small hydrophobic pore, and rupture times depend exponentially on tension. Thus, we recover the experimentally reported regimes, but the origin of the high tension exponential regime is unrelated to macroscopically long-lived pre-pore defects. It arises because hydrophilic pores cannot exist above a critical tension, leading to radically altered pore dynamics and rupture kinetics.
A simple, safe and sensitive method for SARS-CoV-2 inactivation and RNA extraction for RT-qPCR
Authors: Kalnina Lelde , Mateu-Regué Àngels , Oerum Stephanie , Hald Annemette , Gerstoft Jan , Oerum Henrik , Nielsen Finn Cilius , Iversen Astrid K.N.
Published: July 2020

The SARS-CoV-2 pandemic has created an urgent need for large amounts of diagnostic tests to detect viral RNA, which commercial suppliers are increasingly unable to deliver. In addition to the lack of availability, the current methods do not always fully inactivate the virus. Together, this calls for the development of safer methods for extraction and detection of viral RNA from patient samples that utilise readily available reagents and equipment present in most standard laboratories. We present a rapid and straightforward RNA extraction protocol for inactivating the SARS-CoV-2 virus that uses standard lab reagents. This protocol expands analysis capacity as the inactivated samples can be used in RT-qPCR detection tests at laboratories not otherwise classified for viral work. The method circumvents the need for commercial RNA purification kits, takes about 30 minutes from swab to PCR-ready viral RNA, and enables downstream detection of SARS-CoV-2 by RT-qPCR with very high sensitivity (~4 viral RNA copies per RT-qPCR). In summary, we present a rapid, safe and sensitive method for high-throughput detection of SARS-CoV-2, that can be conducted in any laboratory equipped with a qPCR machine.
Pseudo-Likelihood Based Logistic Regression for Estimating COVID-19 Infection and Case Fatality Rates by Gender, Race, and Age in California
Authors: Xiong Di , Zhang Lu , Watson Gregory L. , Sundin Phillip , Bufford Teresa , Zoller Joseph A. , Shamshoian John , Suchard Marc A. , Ramirez Christina M.
Published: July 2020

In emerging epidemics, early estimates of key epidemiological characteristics of the disease are critical for guiding public policy. In particular, identifying high risk population subgroups aids policymakers and health officials in combatting the epidemic. This has been challenging during the coronavirus disease 2019 (COVID-19) pandemic, because governmental agencies typically release aggregate COVID-19 data as marginal summary statistics of patient demographics. These data may identify disparities in COVID-19 outcomes between broad population subgroups, but do not provide comparisons between more granular population subgroups defined by combinations of multiple demographics.

We introduce a method that overcomes the limitations of aggregated summary statistics and yields estimates of COVID-19 infection and case fatality rates — key quantities for guiding public policy related to the control and prevention of COVID-19 — for population subgroups across combinations of demographic characteristics. Our approach uses pseudo-likelihood based logistic regression to combine aggregate COVID-19 case and fatality data with population-level demographic survey data to estimate infection and case fatality rates for population subgroups across combinations of demographic characteristics.

We illustrate our method on California COVID-19 data to estimate test-based infection and case fatality rates for population subgroups defined by gender, age, and race and ethnicity. Our analysis indicates that in California, males have higher test-based infection rates and test-based case fatality rates across age and race/ethnicity groups, with the gender gap widening with increasing age. Although elderly infected with COVID-19 are at an elevated risk of mortality, the test-based infection rates do not increase monotonically with age. LatinX and African Americans have higher test-based infection rates than other race/ethnicity groups. The subgroups with the highest 5 test-based case fatality rates are African American male, Multi-race male, Asian male, African American female, and American Indian or Alaska Native male, indicating that African Americans are an especially vulnerable California subpopulation.
Multimodal imaging improves brain age prediction and reveals distinct abnormalities in patients with psychiatric and neurological disorders
Authors: Rokicki Jaroslav , Wolfers Thomas , Nordhøy Wibeke , Tesli Natalia , Quintana Daniel S. , Alnæs Dag , Richard Genevieve , de Lange Ann-Marie G. , Lund Martina J. , Norbom Linn , Agartz Ingrid , Melle Ingrid , Nærland Terje , Selbæk Geir , Persson Karin , Nordvik Jan Egil , Schwarz Emanuel , Andreassen Ole A. , Kaufmann Tobias , Westlye Lars T.
Published: July 2020

Background

The deviation between chronological age and age predicted using brain MRI is a putative marker of brain health and disease-related deterioration. Age prediction based on structural MRI data shows high accuracy and sensitivity to common brain disorders. However, brain aging is complex and heterogenous, both in terms of individual differences and the biological processes involved. Here, we implemented a multimodal age prediction approach and tested the predictive value across patients with a range of disorders with distinct etiologies and clinical features.

Methods

We implemented a multimodal model to estimate brain age using different combinations of cortical area, thickness and sub-cortical volumes, cortical and subcortical T1/T2-weighted ratios, and cerebral blood flow (CBF) calculated from functional arterial spin labeling (ASL) data. For each of the 11 models we assessed the age prediction accuracy in HC n=761 and compared the resulting brain age gaps (BAGs) between each clinical group and age-matched subsets of HC in patients with Alzheimer’s disease (AD, n=54), mild cognitive impairment (MCI, n=88), subjective cognitive impairment (SCI, n=55), schizophrenia (SZ, n=156), bipolar disorder (BD, n=136), autism spectrum disorder (ASD, n=28).

Results

Among the 11 models, we found highest age prediction accuracy in HC when integrating all modalities (mean absolute error=6.5 years). Beyond this global BAG, the area under the curve for the receiver-operating characteristics based on two-group case-control classifications showed strongest effects for AD and ASD in global T1-weighted BAG (T1w-BAG), while MCI, SCI, BD and SZ showed strongest effects in CBF-based BAGs.

Conclusions

Combining multiple MRI modalities improves brain age prediction and reveals distinct deviations in patients with psychiatric and neurological disorders. The multimodal BAG was most accurate in predicting age in HC, while group differences between patients and controls were often larger for BAGs based on single modalities. These findings demonstrate that multidimensional phenotyping provides a mapping of overlapping and distinct pathophysiology in common disorders of the brain, and specifically suggest metabolic and neurovascular aberrations in SZ and at-risk and early stage dementia.
Droughts, cyclones, and intimate partner violence: A disastrous mix for Indian women
Authors: Rai Ayushi , Sharma Anupam Joya , Subramanyam Malavika A.
Published: July 2020

India has reported a high prevalence of Intimate Partner Violence (IPV) against women over the years. Previous Western research have found an increased IPV risk among women in the aftermath of natural disasters, underscoring the need for such studies in India. We could not locate any study focusing on the impact of slow-onset versus rapid-onset disasters, which might have differing impacts on the vulnerable, especially on the incidence of IPV in India. Using data on ever-married women from the National Family Health Survey-4, we investigated the association of residing in districts exposed to a drought (N=31,045), and separately, to two cyclones (N=8469), with three forms of self-reported IPV against women (emotional, physical, and sexual). Survey-adjusted logistic regression models showed that exposure to cyclone was positively associated with emotional IPV (AOR: 1.59, CI: 1.20, 2.10) after adjusting for sociodemographic covariates. Although not statistically significant, exposure to cyclone was also positively associated with physical and sexual IPV, and drought with physical IPV. However, we did not find an association of drought with emotional and sexual violence. Notably, we corroborated previous findings that women from wealthier households, educated, and whose husbands had no history of alcohol consumption, were less likely to experience any form of IPV independent of the influence of other factors. These results highlight the potential increased risk of IPV following natural disasters. In a patriarchal society such as India vulnerable to climate-change, these sobering results highlight the need to prepare for the social disasters that might accompany natural disasters.
Social Distancing Causally Impacts the Spread of SARS-CoV-2: A U.S. Nationwide Event Study
Authors: Gagnon Louis , Gagnon Stephanie , Lloyd Jessica
Published: July 2020

Objectives

To assess the causal impact of a spontaneous relaxation of social distancing on the spread of SARS-CoV-2 in the United States (U.S.), while controlling for social mobility and state-imposed social distancing restrictions.

Design

Event study.

Setting

Quasi-experimental setting created by the U.S. nationwide protests precipitated by George Floyd’s tragic death on May 25, 2020.

Population

Individuals in 3,142 U.S. counties from all 50 states and the District of Columbia.

Main Outcome Measures

The number of daily confirmed COVID-19 cases in all U.S. counties between the period of January 22, 2020, and June 20, 2020, and the cumulative change in COVID-19 cases in protest counties relative to non-protest counties following the onset of the protests.

Results

We document a country-wide increase of over 3·06 cases per day, per 100,000 population, following the onset of the protests (95%CI: 2·47–3·65), and a further increase of 1·73 cases per day, per 100,000 population, in the counties in which the protests took place (95%CI: 0·59–2·87). Relative to the week preceding the onset of the protests, this represents a 61·2% country-wide increase in COVID-19 cases, and a further 34·6% increase in the protest counties.

Conclusions

Our study documents a significant increase in COVID-19 case counts in counties that experienced a protest, and we conclude that social distancing practices causally impact the spread of SARS-CoV-2. The observed effect cannot be explained by changes in social distancing restrictions and social mobility, and placebo tests rule out the possibility that this finding is attributable to chance. Our research informs policy makers and provides insights regarding the usefulness of social distancing as an intervention to minimize the spread of SARS-CoV-2.
Lungs contribute to solving the frog’s cocktail party problem by enhancing the spectral contrast of conspecific vocal signals
Authors: Lee N. , Christensen-Dalsgaard J. , White L. A. , Schrode K. M. , Bee M. A.
Published: July 2020

Noise impairs signal perception and is a major source of selection on animal communication. Identifying adaptations that enable receivers to cope with noise is critical to discovering how animal sensory and communication systems evolve. We integrated biophysical and bioacoustic measurements with physiological modeling to demonstrate that the lungs of frogs serve a heretofore unknown noise-control function in vocal communication. Lung resonance enhances the signal-to-noise ratio for communication by selectively reducing the tympanum’s sensitivity at critical frequencies where the tuning of two inner ear organs overlaps. Social network analysis of citizen-science data on frog calling behavior indicates the calls of other frog species in multi-species choruses are a prominent source of environmental noise attenuated by the lungs. These data reveal that an ancient adaptation for detecting sound via the lungs has been evolutionarily co-opted to create spectral contrast enhancement that contributes to solving a multi-species cocktail party problem.
Development of RNA-based assay for rapid detection of SARS-CoV-2 in clinical samples
Authors: Kumar Vinod , Mishra Suman , Sharma Rajni , Agarwal Jyotsana , Ghoshal Ujjala , Khanna Tripti , Sharma Lokendra K. , Verma Santosh Kumar , Mishra Prabhakar , Tiwari Swasti
Published: July 2020

The ongoing spread of pandemic coronavirus disease (COVID-19) is caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). In the lack of specific drugs or vaccines for SARS-CoV-2, demands rapid diagnosis and management are crucial for controlling the outbreak in the community. Here we report the development of the first rapid-colorimetric assay capable of detecting SARS-CoV-2 in the human nasopharyngeal RNA sample in less than 30 minutes. We utilized a nanomaterial-based optical sensing platform to detect RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2, where the formation of oligo probe-target hybrid led to salt-induced aggregation and changes in gold-colloid color from pink to blue in visible range. Accordingly, we found a change in colloid color from pink to blue in assay containing nasopharyngeal RNA sample from the subject with clinically diagnosed COVID-19. The colloid retained pink color when the test includes samples from COVID-19 negative subjects or human papillomavirus (HPV) infected women. The results were validated using nasopharangeal RNA samples from suspected COVID-19 subjects (n=136). Using RT-PCR as gold standard, the assay was found to have 85.29% sensitivity and 94.12% specificity. The optimized method has detection limit as little as 0.5 ng of SARS-CoV-2 RNA. Overall, the developed assay rapidly detects SARS-CoV-2 RNA in clinical samples in a cost-effective manner and would be useful in pandemic management by facilitating mass screening.
Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice
Authors: Goldblum Rebecca R. , McClellan Mark , Hou Cody , Thompson Brian R. , White Kyle , Vang Hluechy X. , Cohen Houda , Metzger Joseph M. , Gardner Melissa K.
Published: July 2020

In the failing heart, the cardiac myocyte microtubule network is remodeled, which increases cellular stiffness and disrupts contractility, contributing to heart failure and death. However, the origins of this deleterious cytoskeletal reorganization are unknown. We now find that oxidative stress, a condition characteristic of failing heart cells, leads to cysteine oxidation of microtubules. Further, our electron and fluorescence microscopy experiments revealed regions of structural damage within the oxidized microtubule lattice. These damaged regions led to the lengthening, realignment, and acetylation of dynamic microtubules within cardiac myocytes. Thus, we found that oxidative stress acts inside of cardiac myocytes to facilitate a dramatic, pathogenic shift from a dynamic, multifaceted microtubule network into a highly acetylated, longitudinally aligned, and static microtubule network. Our results demonstrate how a disease condition characterized by oxidative stress can trigger a molecular oxidation event, which propagates a toxic cellular-scale transformation of the cardiac myocyte microtubule network.
Solution structure ofGaussiaLuciferase with five disulfide bonds and identification of a putative coelenterazine binding cavity by heteronuclear NMR
Authors: Wu Nan , Kobayashi Naohiro , Tsuda Kengo , Unzai Satoru , Saotome Tomonori , Kuroda Yutaka , Yamazaki Toshio
Published: July 2020

Gaussialuciferase (GLuc) is the smallest luciferase (18.2kDa; 168 residues) reported so far and is thus attracting much attention as a reporter protein, but the lack of structural information is hampering further application. Here, we report the first solution structure of a fully active, recombinant GLuc determined by heteronuclear multidimensional NMR. We obtained a natively folded GLuc by bacterial expression and efficient refolding using a solubility tag. Almost perfect assignments of GLuc’s1H,13C and15N backbone signals were obtained. GLuc structure was determined using CYANA, which automatically identified over 2500 NOEs of which > 570 were long-range. GLuc is an all-alpha-helix protein made of nine helices. The region spanning residues 10–18, 36-81, 96-145 and containing eight out of the nine helices was determined with a Cα-atom RMSD of 1.39 Å± 0.39 Å. The structure of GLuc is novel and unique. Two homologous sequential repeats form two anti-parallel bundles made by 4 helices and tied together by three disulfide bonds. The N-terminal helix 1 is grabbed by these 4 helices. Further, we found a hydrophobic cavity where several residues responsible for bioluminescence were identified in previous mutational studies, and we thus hypothesize that this is a catalytic cavity, where the hydrophobic coelenterazine binds and the bioluminescence reaction takes place.
Characterisation of Geometric Variance in the Epithelial Nerve Net of the CtenophorePleurobrachia pileus
Authors: Courtney Amy , Liegey Jérémy , Burke Niamh , Lowey Madeleine , Pickering Mark
Published: July 2020

Neuroscience currently lacks a diverse repertoire of model organisms, resulting in an incomplete understanding of what principles of neural function generalise and what are species-specific. Ctenophores display many neurobiological and experimental features which make them a promising candidate to fill this gap. They possess a nerve net distributed across their outer body surface, just beneath the epithelial layer. There is a long-held assumption that nerve nets are ‘simple’ and random while lacking distinct organisational principles. We want to challenge this assumption and determine how stereotyped the structure of this network really is. We validated an approach to estimate body surface area inPleurobrachia pileususing custom Optical Projection Tomography and Light Sheet Morphometry imaging systems. We used an antibody against tyrosylatedα-tubulin to visualise the nerve net in situ. We used an automated segmentation approach to extract the morphological features of the nerve net. We characterised organisational rules of the epithelial nerve net inP. pileusin animals of different sizes and at different regions of the body. We found that specific morphological features within the nerve net are largely un-changed during growth. These properties must be essential to the functionality of the nervous system and therefore are maintained during a change in body size. We have also established the principles of organisation of the network and showed that some of the geometric properties are variable across different parts of the body. This suggests that there may be different functions occurring in regions with different structural characteristics. This is the most comprehensive structural description of a nerve net to date. This study also demonstrates the amenability of the ctenophoreP. pileusfor whole organism network analysis and shows their promise as a model organism for neuroscience, which may provide insights into the foundational principles of nervous systems.
A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies
Authors: Acharya Priyamvada , Williams Wilton , Henderson Rory , Janowska Katarzyna , Manne Kartik , Parks Robert , Deyton Margaret , Sprenz Jordan , Stalls Victoria , Kopp Megan , Mansouri Katayoun , Edwards Robert J , Meyerhoff R. Ryan , Oguin Thomas , Sempowski Gregory , Saunders Kevin , Haynes Barton F.
Published: July 2020

The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 Å resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design.

Highlights

Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike.

3.1 Å resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12.

2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike.

Our studies suggest a common epitope for FDG antibodies centered around glycan 709.