bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality in Norway and Sweden before and after the Covid-19 outbreak: a cohort study
Authors: Juul Frederik E , Jodal Henriette C , Barua Ishita , Refsum Erle , Olsvik Ørjan , Helsingen Lise M , Løberg Magnus , Bretthauer Michael , Kalager Mette , Emilsson Louise
Published: November 2020

Objectives

Norway and Sweden are similar countries regarding ethnicity, socioeconomics and health care. To combat Covid-19, Norway implemented extensive measures such as school closures and lock-downs, while Sweden has been criticised for relaxed measures against Covid-19. We compared the effect of the different national strategies on all-cause and Covid-19 associated mortality.

Design

Retrospective cohort.

Setting

The countries Norway and Sweden.

Participants

All inhabitants.

Main outcome measures

We calculated weekly mortality rates (MR) with 95% confidence intervals (CI) per 100,000 individuals as well as mortality rate ratios (MRR) comparing the epidemic year (29th July, 2019 to 26th July, 2020) to the four preceding years (July 2015 to July 2019). We also compared Covid-19 associated deaths and mortality rates for the weeks of the epidemic in Norway and Sweden (16th March to 26th July, 2020).

Results

In Norway, mortality rates were stable during the first three 12-month periods of 2015/16; 2016/17 and 2017/18 (MR 14.8 to 15.1 per 100,000), and slightly lower in the two most recent periods including during epidemic period (2018/19 and 2019/20; 14.5 per 100,000). In Sweden, all-cause mortality was stable during the first three 12-month periods of 2015/16; 2016/17 and 2017/18 (MR 17.2 to 17.5 per 100,000), but lower in the year 2018/19 immediately preceding the epidemic (16.2 per 100,000). Covid-19 associated mortality rates were 0.2 per 100,000 (95%CI 0.1 to 0.4) in Norway and 2.9 (95%CI 1.9 to 3.9) in Sweden. The increase in mortality was confined to individuals in 70 years or older.

Conclusions

All-cause mortality remained unaltered in Norway. In Sweden, the observed increase in all-cause mortality during Covid-19 was partly due to a lower than expected mortality preceding the epidemic and the observed excess mortality, was followed by a lower than expected mortality after the first Covid-19 wave. This may suggest mortality displacement.

Strengths and limitations of this study

Compares two similar contries in all aspects but the handling of the Covid-19 epidemic

Evaluates the mortality for several years before and during the epidemic

Provides a possible explanation of the observed mortality changes

Discusses the socioeconomic effects of the different strategies in the two countries

Does not evaluate cause-specific mortality
Impact of COVID-19 on the outreach strategy of cancer social service agencies in Singapore: A pre-post analysis with Facebook data
Authors: Tan Kieran Ethan , Raamkumar Aravind Sesagiri , Wee Hwee Lin
Published: November 2020

The Singapore government implemented multiple restrictive measures as the novel coronavirus infection (COVID-19) spread through the community, thereby affecting the support service of cancer-related social service agencies (cancer-SSAs). We are interested to understand how Singapore’s cancer-SSAs utilized the social media platform Facebook to overcome the restrictions which were introduced due to COVID-19. Facebook posts from cancer-SSAs 365 Cancer Prevention Society (365CPS) and Singapore Cancer Society (SCS) between comparable periods in 2019 and 2020 were extracted. These posts were categorized using a classification scheme specifically developed for this study. Statistical analyses were performed to determine if there was a significant difference in the frequency of posts between 2019 and 2020, and across three specific periods in 2020. Results indicate that 365CPS appears to have adapted to the pandemic by increasing their posting frequency on Facebook in 2020, but the same was not evident for SCS. However, both SSAs tweaked their social media outreach strategy in line with social distancing measures, publishing posts detailing activities that beneficiaries can participate from home such as healthy recipes and virtual events. SSAs can scale up their efforts to achieve a higher level of health promotion and support for their beneficiaries.
Excess mortality for care home residents during the first 23 weeks of the COVID-19 pandemic in England: a national cohort study
Authors: Morciano Marcello , Stokes Jonathan M , Kontopantelis Evangelos , Hall Ian , Turner Alexander J
Published: November 2020

Background: To estimate excess mortality for care home residents during the COVID-19 pandemic in England, exploring associations with care home characteristics.

Methods: Daily number of deaths in all residential and nursing homes in England notified to the Care Quality Commission (CQC) from 1st January 2017 to 7th August 2020. Care home level data linked with CQC care home register to identify homes characteristics: client type (over 65s/children and adults), ownership status (for-profit/not-for-profit; branded/independent), and size (small/medium/large).

Excess deaths computed as the difference between observed and predicted deaths using local authority fixed-effect Poisson regressions on pre-pandemic data. Fixed-effect logistic regressions were used to model odds of experiencing COVID-19 suspected/confirmed deaths.

Findings: Up to 7th August 2020 there were 29,542 (95%CI: 25,176 to 33,908) excess deaths in all care homes. Excess deaths represented 6.5% (95%CI: 5.5% to 7.4%) of all care home beds, higher in nursing (8.4%) than residential (4.6%) homes. 64.7% (95%CI: 56.4% to 76.0%) of the excess deaths were confirmed/suspected COVID-19. Almost all excess deaths were recorded in the quarter (27.4%) of homes with any COVID-19 fatalities.

The odds of experiencing COVID-19 attributable deaths were higher in homes providing nursing services (OR: 1.8, 95%CI: 1.6 to 2.0); to older people and/or with dementia (OR: 5.5, 95%CI: 4.4 to 6.8); among larger (vs. small) homes (OR: 13.3, 95%CI: 11.5 to 15.4); belonging to a large provider/brand (OR: 1.2, 95%CI: 1.1 to 1.3). There was no significant association with for-profit status of providers.

Interpretation: To limit excess mortality, policy should be targeted at care homes to minimise the risk of ingress of disease and limit subsequent transmission. Our findings provide specific characteristic targets for further research on mechanisms and policy priority.
COVID-PCD – a participatory research study on the impact of COVID-19 in people with Primary Ciliary Dyskinesia
Authors: Pedersen Eva SL , Collaud Eugénie NR , Mozun Rebeca , Ardura-Garcia Cristina , Lam Yin Ting , Harris Amanda , Lucas Jane S , Copeland Fiona , Manion Michele , Rindlishbacher Bernhard , Silberschmidt Hansruedi ,   COVID-PCD patient advisory group, Goutaki Myrofora , Kuehni Claudia E
Published: November 2020

Introduction

COVID-PCD is a participatory study initiated by people with PCD who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real time from people with PCD throughout the pandemic to describe incidence of COVID-19, symptoms, and course of disease; identify risk factors for prognosis; and assess experiences, wishes, and needs.

Methods

The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms, and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident SARS-CoV-2 infections, current symptoms, social contact behaviour, and physical activity. Occasional thematic questionnaires are sent out focusing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online.

Conclusion

The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians, and researchers.
Determinants of Persistent Post COVID-19 symptoms: Value of a Novel COVID-19 symptoms score
Authors: Galal Islam , Hussein Aliae AR Mohamed , Amin Mariam T , Saad Mahmoud M , Zayan Hossam Eldeen E , Abdelsayed Mustafa Z , Moustafa Mohamed M , Ezzat Abdel Rahman , Helmy Radwa ED , Abd- Elaal Howaida K , Massry Nasrallah A Al , Soliman Mohamed A. , Ismail Asmaa M , Kholief Karima MS , Fathy Enas , Hashem Maiada K
Published: November 2020

Background

Being a newly emerging disease little is known about its long-lasting post COVID-19 consequences. Aim of this work is to assess the frequency, patterns and determinants of persistent post COVID-19 symptoms and to evaluate the value of a proposed Novel COVID-19 symptoms score. Patients with confirmed COVID-19 in the registry were included in a cross sectional study. The patient demographics, comorbid disorders, the mean duration since the onset of the symptoms, history of hospital or ICU admittance, and treatment taken during acute state, as well as symptoms score before and after convalescence were recorded.

Results

The most frequent constitutional and neurological symptoms were myalgia (60.0%), arthralgia (57.2%), restriction of daily activities (57.0%), sleeping troubles (50.9%), followed by anorexia (42.6%), chest pain (32.6%), gastritis (32.3%), cough (29.3%) and dyspnea (29.1%). The mean total score of acute stage symptoms was 31.0 ± 16.3 while post COVID 19 symptoms score was 13.1±12.6 (P<0.001). The main determinants of the persistent post COVID-19 symptoms were the need for oxygen therapy (P<0.001), pre-existing hypertension (P=0.039), chronic pulmonary disorders (P=0.012), and any chronic comorbidity (P=0.004). There was a correlation between the symptom score during the acute attack and post COVID-19 stage (P<0.001, r=0.67). The acute phase score had 83.5% sensitivity and 73.3% specificity for the cutoff point > 18 to predict occurrence of Post-COVID-19 symptoms.

Conclusions

COVID-19 can present with a diverse spectrum of long-term post COVID-19 symptoms. Increased acute phase symptom severity and COVID-19 symptom score > 18 together with the presence of any comorbid diseases increase the risk for persistent post COVID-19 manifestations and severity.
Inferring temporal organization of postembryonic development from high-content behavioral tracking
Authors: Faerberg Denis F. , Gurarie Victor , Ruvinsky Ilya
Published: November 2020

Abstract

Understanding temporal regulation of development remains an important challenge. Whereas average, species-typical timing of many developmental processes has been established, less is known about inter-individual variability and correlations in timing of specific events. We addressed these questions in the context of postembryonic development inCaenorhabditis elegans. Based on patterns of locomotor activity of freely moving animals, we inferred durations of four larval stages (L1-L4) in over 100 individuals. Analysis of these data supports several notable conclusions. Individuals have consistently faster or slower rates of development because durations of L1 through L3 stages are positively correlated. The last larval stage, the L4, is less variable than earlier stages and its duration is largely independent of the rate of early larval development, implying existence of two distinct larval epochs. We argue that characteristic patterns of variation and correlation arise because duration of each stage tends to scale relative to total developmental time. This scaling relationship suggests that each larval stage is not limited by an absolute duration, but is instead terminated when a subset of events that must occur prior to adulthood have been completed. The approach described here offers a scalable platform that will facilitate the study of temporal regulation of postembryonic development.
EARLY FLOWERING 3controls temperature responsiveness of the circadian clock
Authors: Zhu Zihao , Quint Marcel , Anwer Muhammad Usman
Published: November 2020

Predictable changes in light and temperature during a diurnal cycle are major entrainment cues that enable the circadian clock to generate internal biological rhythms that are synchronized with the external environment. With the average global temperature predicted to keep increasing, the intricate light-temperature coordination that is necessary for clock functionality is expected to be seriously affected. Hence, understanding how temperature signals are perceived by the circadian clock has become an important issue, especially in light of climate change scenarios. InArabidopsis, the clock componentEARLY FLOWERING 3(ELF3) not only serves as an essential lightZeitnehmer, but also functions as a thermosensor participating in thermomorphogenesis. However, the role ofELF3in temperature entrainment of the circadian clock is not fully understood. Here, we report thatELF3is essential for delivering temperature input to the clock. We demonstrate that in the absence ofELF3, the oscillator was unable to properly respond to temperature changes, resulting in an impaired gating of thermoresponses. Consequently, clock-controlled physiological processes such as rhythmic growth and cotyledon movement were disturbed. Together, our results reveal thatELF3is an essentialZeitnehmerfor temperature sensing of the oscillator, and thereby for coordinating the rhythmic control of thermoresponsive physiological outputs.
Bedshift: perturbation of genomic interval sets
Authors: Gu Aaron , Cho Hyun Jae , Sheffield Nathan C.
Published: November 2020

Functional genomics experiments, like ChIP-Seq or ATAC-Seq, produce results that are summarized as a region set. Many tools have been developed to analyze region sets, including computing similarity metrics to compare them. However, there is no way to objectively evaluate the effectiveness of region set similarity metrics. In this paper we presentBedshift, a command-line tool and Python API to generate new BED files by making random perturbations to an original BED file. Perturbed files have known similarity to the original file and are therefore useful to benchmark similarity metrics. To demonstrate, we used Bedshift to create an evaluation dataset of hundreds of perturbed files generated by shifting, adding, and dropping regions from a reference BED file. Then, we compared four similarity metrics: Jaccard score, coverage score, Euclidean distance, and cosine similarity. Our results highlight differences in behavior among these metrics, such as that Jaccard score is most sensitive to added or dropped regions, while coverage score is most sensitive to shifted regions. Together, we show that Bedshift is a useful tool for creating randomized region sets for a variety of uses.

Availability

BSD2-licensed source code and documentation can be found athttps://bedshift.databio.org.
Repression precedes the stepwise evolution of a highly specific gene expression pattern
Authors: Pu Jian , Wang Zinan , Cong Haosu , Chin Jacqueline S.R. , Justen Jessa , Yew Joanne Y. , Chung Henry
Published: November 2020

Well-controlled gene expression is critical for the proper development and function of many traits. Highly-specific temporal and spatial expression patterns are often due to the overlapping activities of activator and repressor sequences that formcis-regulatory elements called enhancers. While many studies have shown that evolutionary changes in enhancers can result in novel traits, few studies illuminate how enhancers originate, how activator and repressor sequences interact during enhancer evolution, and the order in which they evolve. Here, we traced the evolutionary origin of a recently evolved enhancer that drives the expression of the fatty acyl-CoA elongase,bond, specifically in the semicircular wall epithelium (swe) of theDrosophilamale ejaculatory bulb (EB). We show that this enhancer consists of two activator regions that drivebondexpression in the entire EB and a repressor region that restricts expression specifically to the EB swe. Interestingly, the repressor region preceded the evolution of the two activator regions. The evolution of the first activator region, consisting of two putativeAbdominal-Bsites, did not drive expression in the EB due to the action of the repressor region. Expression ofbondin the EB swe requires the evolution of the second activator region, which does not drive expression on its own, but synergizes with the first activator region and the repressor region to produce a highly-specific spatial expression pattern. Our results show that the origin and evolution of a novel enhancer require multiple steps and the evolution of repressor sequences can precede the evolution of activator sequences.
Dynamic Domain Specificity In Human Ventral Temporal Cortex
Authors: Bankson Brett B. , Boring Matthew J. , Richardson R. Mark , Ghuman Avniel Singh
Published: November 2020

An enduring neuroscientific debate concerns the extent to which neural representation is restricted to neural populations specialized for particular domains of perceptual input, or distributed outside of highly selective populations as well. A critical level for this debate is the neural representation of the identity of individual images, such as individual-level face or written word recognition. Here, intracranial recordings throughout ventral temporal cortex across 17 human subjects were used to assess the spatiotemporal dynamics of individual word and face processing within and outside regions strongly selective for these categories of visual information. Individual faces and words were first discriminable primarily only in strongly selective areas, beginning at about 150 milliseconds after word or face onset, and then discriminable both within and outside strongly selective areas approximately 170 milliseconds later. Regions of ventral temporal cortex that were and were not strongly selective both contributed non-redundant information to the discrimination of individual images. These results can reconcile previous results endorsing disparate poles of the domain specificity debate by highlighting the temporally segregated contributions of different functionally defined cortical areas to individual level representations. This work supports a dynamic model of neural representation characterized by successive domain-specific and distributed processing stages.
Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior
Authors: Raiders Stephan , Black Erik Calvin , Bae Andrea , MacFarlane Stephen , Shaham Shai , Singhvi Aakanksha
Published: November 2020

Glia in the central nervous system engulf neuron fragments during synapse remodeling and recycling of photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively remove neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report that adultC. elegansAMsh glia engulf sensory endings of the AFD thermosensory neuron. Engulfment is regulated by temperature, AFD’s sensory input, and tracks AFD activity. Phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. Glial CED-10/Rac1 GTPase, acting through a conserved GEF complex, executes phagocytosis using the actin-remodeler WSP-1/nWASp and the membrane-sealing factor EFF-1 fusogen. CED-10 levels determine engulfment rates, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underpinning glia-dependent phagocytosis in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal behavior.
Neural support for contributions of utility and narrative processing of evidence in juror decision making
Authors: Castrellon Jaime J. , Hakimi Shabnam , Parelman Jacob M. , Yin Lun , Law Jonathan R. , Skene Jesse A.G. , Ball David A. , Malekpour Artemis , Beskind Donald H. , Vidmar Neil , Pearson John M. , Carter R. McKell , Pate Skene J. H.
Published: November 2020

Efforts to explain complex human decisions have focused on competing theories emphasizing utility and narrative mechanisms. These are difficult to distinguish using behavior alone. Both narrative and utility theories have been proposed to explain juror decisions, which are among the most consequential complex decisions made in a modern society. Here, we asked jury-eligible male and female subjects to rate the strength of a series of criminal cases while recording the resulting patterns of brain activation. We compared patterns of brain activation associated with evidence accumulation to patterns of brain activation derived from a large neuroimaging database to look for signatures of the cognitive processes associated with different models of juror decision making. Evidence accumulation correlated with multiple narrative processes, including reading and recall. Of the cognitive processes traditionally viewed as components of utility, activation patterns associated with uncertainty, but not value, were more active with stronger evidence. Independent of utility and narrative, activations linked to reasoning and relational logic also correlated with increasing evidence. Hierarchical modeling of cognitive processes associated with evidence accumulation supported a more prominent role for narrative in weighing evidence in complex decisions. However, utility processes were also associated with evidence accumulation. These complementary findings support an emerging view that integrates utility and narrative processes in complex decisions.

Significance Statement

The last decade has seen a sharply increased interest in narrative as a central cognitive process in human decision making and as an important factor in the evolution of human societies. However, the roles of narrative versus utility models of decision making remain hotly debated. While available models frequently produce similar behavioral predictions, they rely on different cognitive processes and so their roles can be separated using the right neural tests. Here, we use brain imaging during mock juror decisions to show that cognitive processes associated with narrative, and to a lesser extent utility, were engaged while subjects evaluated evidence. These results are consistent with interactions between narrative and utility processes during complex decision making.
A Markov Random Field Model for Network-based Differential Expression Analysis of Single-cell RNA-seq Data
Authors: Li Hongyu , Zhu Biqing , Xu Zhichao , Adams Taylor , Kaminski Naftali , Zhao Hongyu
Published: November 2020

Background

Recent development of single cell sequencing technologies has made it possible to identify genes with different expression (DE) levels at the cell type level between different groups of samples. In this article, we propose to borrow information through known biological networks to increase statistical power to identify differentially expressed genes (DEGs).

Results

We develop MRFscRNAseq, which is based on a Markov Random Field (MRF) model to appropriately accommodate gene network information as well as dependencies among cell types to identify cell-type specific DEGs. We implement an Expectation-Maximization (EM) algorithm with mean field-like approximation to estimate model parameters and a Gibbs sampler to infer DE status. Simulation study shows that our method has better power to detect cell-type specific DEGs than conventional methods while appropriately controlling type I error rate. The usefulness of our method is demonstrated through its application to study the pathogenesis and biological processes of idiopathic pulmonary fibrosis (IPF) using a single-cell RNA-sequencing (scRNA-seq) data set, which contains 18,150 protein-coding genes across 38 cell types on lung tissues from 32 IPF patients and 28 normal controls.

Conclusions

The proposed MRF model is implemented in the R package MRFscRNAseq available on GitHub. By utilizing gene-gene and cell-cell networks, our method increases statistical power to detect differentially expressed genes from scRNA-seq data.
The effect of soil potassium and carbohydrates on xylem conductivity and embolism in an evergreen angiosperm tree and a gymnosperm tree before and after drought
Authors: Wagner Yael , Brumfeld Vlad , Grünzweig José M. , Klein Tamir
Published: November 2020

Xylem embolism is a major threat to tree function and survival under drought, in natural and agricultural settings alike, with its impact increasing in light of global climate change. Conversely, potassium (K+) has been shown to increase xylem conductivity (Ks) in trees, and carbohydrates were reported to impact leaf gas exchange.

In this study we examined the effects of K+and carbohydrates on Ksin two divergent evergreen tree species that are regularly exposed to drought: pine (Pinus brutia) and lemon (Citrus × limon). Five-year-old trees were pretreated with zero, moderate, and high K+, and with ambient or elevated CO2, to experimentally increase their xylem K+or carbohydrates levels, respectively. Trees were then monitored for Ksand embolism (using a microCT), along with leaf gas exchange and water potential, before and after a 1.5-2.5 month drought period.

Potassium fertigation had a positive effect on Ks, in both species when irrigated, which was eliminated following drought. Drought decreased Ksabout 10-fold in lemon, with little effect in pine. CO2-treated trees had the same Ksas control trees before and after drought.

Our results indicate a positive effect of K+on tree hydraulics, which was more pronounced in lemon than in pine, supporting the hypothesis of interaction with the angiosperm pit membrane, and not with the gymnosperm bordered pit. Yet, the elimination of this benefit following drought, and the lack of benefit from elevated carbohydrates following a short-term CO2treatment, question the relevance of these components to tree drought resistance mechanisms.

Key massage

Potassium fertigation increases hydraulic conductivity and reduces xylem embolism in the gymnosperm pine, and more so in the angiosperm lemon tree, benefits which were eliminated following drought.
Critical care workers have lower seroprevalence of SARS-CoV-2 IgG compared with non-patient facing staff in first wave of COVID19
Authors: Baxendale H.E. , Wells D. , Gronlund J. , Nadesalingam A. , Paloniemi M. , Carnell G. , Tonks P. , Ceron-Gutierrez L. , Ebrahimi S. , Sayer A. , Briggs J.A.G. , Xiong X. , Nathan J.A. , Grice G.L. , James L.C. , Luptak J. , Pai S. , Heeney J.L. , Doffinger R.
Published: November 2020

With the first 2020 surge of the COVID-19 pandemic, many health care workers (HCW) were re-deployed to critical care environments to support intensive care teams to look after high numbers of patients with severe COVID-19. There was considerable anxiety of increased risk of COVID19 for staff working in these environments.

Using a multiplex platform to assess serum IgG responses to SARS-CoV-2 N, S and RBD proteins, and detailed symptom reporting, we screened over 500 HCW (25% of the total workforce) in a quaternary level hospital to explore the relationship between workplace and evidence of exposure to SARS-CoV-2.

Whilst 45% of the cohort reported symptoms that they consider may have represented COVID-19, overall seroprevalence was 14% with anosmia and fever being the most discriminating symptoms for seropositive status. There was a significant difference in seropositive status between staff working in clinical and non-clinical roles (9% patient facing critical care, 15% patient facing non-critical care, 22% nonpatient facing). In the seropositive cohort, symptom severity increased with age for men and not for women. In contrast, there was no relationship between symptom severity and age or sex in the seronegative cohort reporting possible COVID-19 symptoms. Of the 12 staff screened PCR positive (10 symptomatic), 3 showed no evidence of seroconversion in convalescence.

Conclusion

The current approach to Personal Protective Equipment (PPE) appears highly effective in protecting staff from patient acquired infection in the critical care environment including protecting staff managing interhospital transfers of COVID-19 patients. The relationship between seroconversion and disease severity in different demographics warrants further investigation. Longitudinally paired virological and serological surveillance, with symptom reporting are urgently required to better understand the role of antibody in the outcome of HCW exposure during subsequent waves of COVID-19 in health care environments.
Upper Limb Motor Improvement after TBI: Systematic Review of Interventions
Authors: Subramanian Sandeep K. , Fountain Melinda A. , Hood Ashley F. , Verduzco-Gutierrez Monica
Published: November 2020

Background

Traumatic Brain Injury (TBI) is a leading cause of adult morbidity and mortality. Individuals with TBI have impairments in both cognitive and motor domains. Motor improvements post-TBI are attributable to adaptive neuroplasticity and motor learning. Majority of the studies focus on remediation of balance and mobility issues. There is limited understanding on the use of interventions for upper limb (UL) motor improvements in this population.

Objective

We examined the evidence regarding the effectiveness of different interventions to augment UL motor improvement after a TBI.

Methods

We systematically examined the evidence published in English from 1990-2020. The modified Downs and Black checklist helped assess study quality (total score:28). Studies were classified as excellent:24-28, good:19-23, fair:14-18 and poor:≤13 in quality. Effect sizes helped quantify intervention effectiveness.

Results

Twenty-three studies were retrieved. Study quality was excellent(n=1), good(n=5) or fair(n=17). Interventions used included strategies to decrease muscle tone (n=6), constraint induced movement therapy (n=4), virtual reality gaming (n=5), noninvasive stimulation (n=3), arm motor ability training (n=1), stem-cell transplant (n=1); task-oriented training (n=2) and feedback provision (n=1). Motor impairment outcomes included Fugl-Meyer Assessment, Modified Ashworth Scale, and kinematic outcomes (error and movement straightness). Activity limitation outcomes included Wolf Motor Function Test and Motor Activity Log. Effect sizes for majority of the interventions ranged from medium(0.5-0.79) to large(≥0.8). Only ten studies included retention testing.

Conclusion

There is preliminary evidence that using some interventions may enhance UL motor improvement after a TBI. Answers to emergent questions can help select the most appropriate interventions in this population.
A nanobody-functionalized organic electrochemical transistor for the rapid detection of SARS-CoV-2 and MERS antigens at the physical limit
Authors: Guo Keying , Wustoni Shofarul , Koklu Anil , Díaz-Galicia Escarlet , Moser Maximilian , Hama Adel , Alqahtani Ahmed A. , Ahmad Adeel Nazir , Alhamlan Fatimah Saeed , McCulloch Iain , Arold Stefan T. , Grünberg Raik , Inal Sahika
Published: November 2020

The COVID-19 pandemic highlights the need for rapid protein detection and quantification at the single-molecule level in a format that is simple and robust enough for widespread point-of-care applications. We here introduce a modular nanobody-organic electrochemical transistor architecture that enables the fast and specific detection and quantification of single-molecule to nanomolar protein antigen concentrations in complex bodily fluids. The sensor combines a new solution-processable organic semiconductor material in the transistor channel with the high-density and orientation-controlled bioconjugation of nanobody fusion proteins on disposable gate electrodes. It provides results after a 10 minutes exposure to 5 µL of unprocessed samples, maintains high specificity and single-molecule sensitivity in human saliva or serum, and is rapidly reprogrammed towards any protein target for which nanobodies exist. We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.
Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: A Systematic Review and Meta-analysis
Authors: Lee Rose A. , Herigon Joshua C. , Benedetti Andrea , Pollock Nira R. , Denkinger Claudia M.
Published: November 2020

Background

Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs.

Methods

We systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval October 1st, 2020) for comparative studies of alternative specimen types [saliva, oropharyngeal (OP), and nasal (NS) swabs] versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in sub-groups. The QUADAS 2 tool was used to assess bias.

Results

From 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives [NS (0.82, 95% CI: 0.73-0.90), OP (0.84, 95% CI: 0.57-1.0), saliva (0.88, 95% CI: 0.81 – 0.93)] than NP swabs, while combined OP/NS matched NP performance (0.97, 95% CI: 0.90-1.0). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield.

Conclusions

NP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric vs. adult, late vs. early in disease course) and head-to head studies of sampling strategies are urgently needed.
Inhibition of SARS-CoV-2 main protease by allosteric drug-binding
Authors: Günther Sebastian , Reinke Patrick Y. A. , Fernández-García Yaiza , Lieske Julia , Lane Thomas J. , Ginn Helen M. , Koua Faisal H. M. , Ehrt Christiane , Ewert Wiebke , Oberthuer Dominik , Yefanov Oleksandr , Meier Susanne , Lorenzen Kristina , Krichel Boris , Kopicki Janine-Denise , Gelisio Luca , Brehm Wolfgang , Dunkel Ilona , Seychell Brandon , Gieseler Henry , Norton-Baker Brenna , Escudero-Pérez Beatriz , Domaracky Martin , Saouane Sofiane , Tolstikova Alexandra , White Thomas A. , Hänle Anna , Groessler Michael , Fleckenstein Holger , Trost Fabian , Galchenkova Marina , Gevorkov Yaroslav , Li Chufeng , Awel Salah , Peck Ariana , Barthelmess Miriam , Schlünzen Frank , Xavier P. Lourdu , Werner Nadine , Andaleeb Hina , Ullah Najeeb , Falke Sven , Srinivasan Vasundara , Franca Bruno Alves , Schwinzer Martin , Brognaro Hévila , Rogers Cromarte , Melo Diogo , Zaitseva-Kinneberg Joanna I. , Knoska Juraj , Peña Murillo Gisel E. , Mashhour Aida Rahmani , Guicking Filip , Hennicke Vincent , Fischer Pontus , Hakanpää Johanna , Meyer Jan , Gribbon Phil , Ellinger Bernhard , Kuzikov Maria , Wolf Markus , Beccari Andrea R. , Bourenkov Gleb , Stetten David von , Pompidor Guillaume , Bento Isabel , Panneerselvam Saravanan , Karpics Ivars , Schneider Thomas R. , Garcia Alai Maria Marta , Niebling Stephan , Günther Christian , Schmidt Christina , Schubert Robin , Han Huijong , Boger Juliane , Monteiro Diana C. F. , Zhang Linlin , Sun Xinyuanyuan , Pletzer-Zelgert Jonathan , Wollenhaupt Jan , Feiler Christian G. , Weiss Manfred S. , Schulz Eike-Christian , Mehrabi Pedram , Karničar Katarina , Usenik Aleksandra , Loboda Jure , Tidow Henning , Chari Ashwin , Hilgenfeld Rolf , Uetrecht Charlotte , Cox Russell , Zaliani Andrea , Beck Tobias , Rarey Matthias , Günther Stephan , Turk Dusan , Hinrichs Winfried , Chapman Henry N. , Pearson Arwen R. , Betzel Christian , Meents Alke
Published: November 2020

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for the virus replication and, thus, a potent drug target. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.
Western KenyanAnopheles gambiae s.s.showing intense permethrin resistance harbor distinct microbiota
Authors: Omoke Diana , Kipsum Mathew , Otieno Samson , Esalimba Edward , Sheth Mili , Lenhart Audrey , Njeru Ezekiel Mugendi , Ochomo Eric , Dada Nsa
Published: November 2020

Background

Insecticide resistance poses a growing challenge to malaria vector control in Kenya and around the world. Following evidence of associations between the mosquito microbiota and insecticide resistance, we comparatively characterized the microbiota ofAn. gambiae s.s. from Tulukuyi village, Bungoma, Kenya, with differing permethrin resistance profiles.

Methods

Using the CDC bottle bioassay, 133 2-3 day-old, virgin, non-blood fed female F1progeny of field-caughtAn. gambiae s.s. were exposed to five times (107.5μg/ml) the discriminating dose of permethrin. Post bioassay, 50 resistant and 50 susceptible mosquitoes were subsequently screened forkdrEast and West mutations, and individually processed for microbial analysis using high throughput sequencing targeting the universal bacterial and archaeal 16S rRNA gene.

Results

47% of the samples tested (n=133) were resistant, and of the 100 selected for further processing, 99% were positive forkdrEast and 1% forkdrWest. Overall, 84 bacterial taxa were detected across all mosquito samples, with 36 of these shared between resistant and susceptible mosquitoes. A total of 20 were unique to the resistant mosquitoes and 28 were unique to the susceptible mosquitoes. There were significant differences in bacterial composition between resistant and susceptible individuals (F=2.33, P=0.001), with presence ofSphingobacterium, LysinibacillusandStreptococcus(all known pyrethroid-degrading taxa), and the radiotolerantRubrobacter, being significantly associated with resistant mosquitoes. On the other hand, the presence ofMyxococcus, was significantly associated with susceptible mosquitoes.

Conclusion

This is the first report of distinct microbiota inAn. gambiae s.s. associated with intense pyrethroid resistance. The findings highlight differentially abundant bacterial taxa between resistant and susceptible mosquitoes, and further suggest a microbe-mediated mechanism of insecticide resistance in mosquitoes. Our results also indicate fixation of thekdrEast mutation in this mosquito population, precluding further analysis of its associations with the mosquito microbiota, but presenting the hypothesis that any microbe-mediated mechanism of insecticide resistance would be likely of a metabolic nature. Overall, this study lays initial groundwork for understanding microbe-mediated mechanisms of insecticide resistance in African malaria vectors, and potentially identifying novel microbial markers of insecticide resistance that could supplement existing vector surveillance tools.
Molecular characterisation of, and antimicrobial resistance in,Clostridioides difficilefrom Thailand, 2017-2018
Authors: Imwattana Korakrit , Putsathit Papanin , Knight Daniel R , Kiratisin Pattarachai , Riley Thomas V
Published: November 2020

Background

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread ofClostridioides difficileinfection (CDI). Many antimicrobials, such as fluoroquinolones, have been associated with outbreaks of CDI globally.

Objectives

This study aimed to characterise AMR among clinicalC. difficilestrains in Thailand, a country where the use of antimicrobials remains inadequately regulated.

Methods

Stool samples were screened fortcdBand positives were cultured.C. difficileisolates were characterised by toxin profiling and PCR ribotyping. Antimicrobial susceptibility testing was performed using an agar incorporation method, and whole-genome sequencing and AMR genotyping performed on a subset of strains.

Results

There were 321C. difficilestrains isolated from 326 stool samples. The most common toxigenic ribotype (RT) was RT 017 (18%), followed by RTs 014 (12%) and 020 (7%). There was a high resistance prevalence (≥ 10%) to clindamycin, erythromycin, moxifloxacin and rifaximin, and resistance prevalence was greatest among RT 017 strains. AMR genotyping revealed a strong correlation between resistance genotype and phenotype for moxifloxacin and rifampicin. The presence oferm-class genes was associated with high-level clindamycin and erythromycin resistance. Point substitutions on the penicillin-binding proteins (PBP1 and PBP3) were not sufficient to confer meropenem resistance, however, a Y721S substitution in PBP3 was associated with a slight increase in meropenem MIC. No resistance to metronidazole, vancomycin or fidaxomicin was observed.

Conclusion

There was a large proportion ofC. difficileRT 017 in Thailand and a high AMR prevalence among these strains. The concordance between AMR phenotype and genotype was strong.
Costs of choosiness can promote reproductive isolation in parapatry
Authors: Aubier Thomas G. , Joron Mathieu
Published: November 2020

Species often replace each other spatially along contact zones, giving scope for parapatric speciation. In models of parapatric speciation driven by assortative mating, costs of female choosiness have so far be ignored. Yet, if females encounter only a limited number of males, those that are too choosy may remain unmated, and this should create direct sexual selection against choosiness. In our individual-based model of parapatric ecological speciation, disruptive viability selection leads to divergence of an ecological trait. Additionally, female choosiness (following a ‘matching mating rule’ based on the same ecological trait) can evolve at the risk of remaining unmated, and can limit gene flow between diverging populations. In line with previous litterature, out of the contact zone, the evolution of cost-free choosiness stops at intermediate values due to indirect selection against strong choosiness. Here we show that a weak cost of choosiness, by modifying genotypic frequencies on which viability selection acts, reduces this selection pressure, thus permitting the evolution of stronger choosiness than in the absence of costs. In strong contrast to sympatric models, costs of choosiness can therefore promote reproductive isolation in parapatry.
Unraveling Molecular Mechanisms of Low-Salinity Adaptation inFenneropenaeus chinensis: Insights from Gill Tissue Transcriptomics
Authors: Liu Jun , Liu Rongchen , Jiang Hui , Zhang Hai , Zheng Dianyuan , Zhang Daizhen
Published: November 2020

This study investigates the molecular responses of Chinese shrimp (Fenneropenaeus chinensis) to low salinity stress, employing RNA-seq and functional enrichment analyses. A total of 12,332 expressed genes were identified, with 227 differentially expressed genes (DEGs) detected, revealing intricate adaptive responses in gill tissues. Functional enrichment analysis highlighted DEGs associated with ion-transport regulation, bio-metabolism and detoxification (based on GO terms). The upregulation ofATP1A1,SLC26A2, andSTK39suggested a pivotal role of ion-transport regulation, emphasizing the importance of maintaining osmotic balance. In terms of bio-metabolism,ENPP6,GLS, andDMGDHexhibited significant upregulation, indicating adjustments in energy metabolism for low-salinity adaptation. Notably, the downregulation ofGSTO1andCTHraised questions about detoxification pathways, potentially reflecting adaptations or compromises in response to low salinity. Further correlation network analysis highlighted key genes likeGLS,STK39,SESN1, andSARDH, revealing intricate relationships among DEGs. RT-qPCR validation confirmed the consistency of gene expression patterns with RNA-seq results. In conclusion, this study provides a comprehensive understanding of the molecular mechanisms underlying Chinese shrimp responses to low salinity stress. The identified genes lay the groundwork for targeted interventions and strategies to enhance shrimp aquaculture system resilience amid changing salinity levels.
In vitroselection of a microbial consortium predictive of synergistic functioning along multiple ecosystem scales
Authors: Baas Peter , Bell Colin , Mancini Lauren , Lee Melanie , Wallenstein Matthew D. , Conant Richard T.
Published: November 2020

Soil microbes form complex interactive networks throughout the soil and plant rhizosphere. These interactions can result in emergent properties for consortia that are not predictable from the phenotypes of constituents in isolation. We used a four-species consortium to assess the capacity of individual microbial species versus different consortia permutations of the four species to contribute to increased P-solubilization using soil incubations and plant growth experiments. We found that as different combinations of bacterial species were assembled into differing consortia, they demonstrated differing abilities to stimulate soil P cycling and plant growth. The combination of all four microbes in the consortia were much more effective at solubilizing P and stimulating plant growth than any of the individual bacterial species alone. This suggests thatin vivofunctionally synergistic soil microbial consortia can be adept at performing specific ecosystem functionsin situ. Improving our understanding of the mechanisms that facilitate synergistic functioning examined in this study is important for maximizing future food production and agroecosystem sustainability.