bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users
Authors: Charre Caroline , Icard Vinca , Pradat Pierre , Brochier Corinne , Lina Bruno , Chidiac Christian , Cotte Laurent
Published: July 2020

Objective:

A new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in China during late 2019 and resulted in the coronavirus disease 2019 (COVID-19) pandemic which peaked in France in March–April 2020. Immunodeficiency, precariousness and promiscuity could increase the risk of COVID-19 in HIV-infected patients and in preexposure prophylaxis (PrEP) users. No epidemiological data are available in these two populations. We report COVID-19 attack rate in HIV-infected patients and in PrEP users in the Rhône department, France, and compared it with the general population.

Design:

Retrospective analysis of a laboratory database.

Methods:

COVID-19 testing strategy in France was centered on symptomatic infections, hospitalized patients and symptomatic healthcare workers while most asymptomatic cases were not confirmed. SARS-CoV-2 positivity rate on PCR assays and COVID-19 attack rate were determined in HIV-infected patients and in PrEP users. COVID-19 attack rate in the general population was estimated from health authorities’ database and demographic data. A corrected attack rate taking into account the laboratory representativeness was calculated.

Results:

From March to April 2020, 24 860 samples from 19 113 patients (HIV-infected 77, PrEP users 27, others 19 009) were assessed for SARS-CoV-2 PCR assay. The positivity rate appeared similar in HIV-infected patients (15.6%), in PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in HIV-infected patients (0.31/0.38%) and in PrEP users (0.38/0.42%), and of the same order as the estimated attack rate in the general population (0.24%).

Conclusion:

The risk of symptomatic COVID-19 in France appeared similar in HIV-infected patients and in PrEP users compared with the general population.
Reducing the Discussion Divide by Digital Questionnaires in Health Care Settings: Disruptive Innovation for HIV Testing and PrEP Screening
Authors: John Steven A. , Petroll Andrew E. , Walsh Jennifer L. , Quinn Katherine G. , Patel Viraj V. , Grov Christian
Published: July 2020

Background:

Health care provider assessment of patient sexual behavior and substance use is essential for determining appropriate prevention interventions—including HIV pre-exposure prophylaxis (PrEP)—for sexual minority men (SMM). We sought to explore acceptability and utility of using electronic surveys to conduct health behavior assessments in clinical settings among SMM.

Methods:

Among a US nationwide sample of SMM (n = 4187; mean age = 38.3 years; 60% white; 82% HIV-negative), we examined associations of demographics, recruitment venue, sexual behavior characteristics, and recent substance use with participants' comfort communicating verbally and through electronic survey with a health care provider about sexual and substance use behavior.

Results:

On average, SMM had greater comfort communicating through electronic survey vs. verbally. In our fully adjusted analysis, preference favoring electronic surveys more strongly than verbal communication differed by age (β = −0.07, P ≤ 0.001). SMM with a bachelor's degree or more (β = 0.04, P < 0.05), those recruited from nonclinical settings (β = 0.06, P ≤ 0.001), and those without primary care providers (β = 0.04, P < 0.05) favored electronic surveys more strongly in the fully adjusted multivariable model. SMM who reported any recent casual sex partners (β = 0.05, P < 0.01), those never tested for HIV (β = 0.03, P < 0.05), and HIV-negative/unknown men not on PrEP (compared with PrEP users; β = 0.09, P ≤ 0.001) also favored electronic surveys in the fully adjusted model.

Conclusions:

Reducing communication barriers by incorporating electronic surveys into patient assessments could help identify HIV testing and PrEP needs for SMM most susceptible to HIV acquisition. Nonetheless, no one screening strategy is likely to work for most SMM, and multiple approaches are needed.
Supportive and palliative care of adults with respiratory problems experiencing structural vulnerability from homelessness, prison or other criminal justice system involvement
Authors: Gardener Carole , Kuhn Isla , Micklewright Kerry , Farquhar Morag
Published: July 2020

Purpose of review

This review seeks to identify the current prevalence of potentially life-limiting respiratory conditions among those who have experienced homelessness, incarceration or had criminal justice involvement, and current developments in, and barriers to, delivery of supportive and palliative respiratory care to these populations. These structurally vulnerable populations are known to be growing, their health behaviours more risky, and their morbidity and mortality higher, with evidence of accelerated ageing.

Recent findings

Most studies identified investigated prevalence of respiratory conditions, which were found to be high. In contrast, only one study directly explored supportive and palliative care (in a prison population) and none considered or addressed palliative and end-of-life needs of these populations, or mechanisms to address them. There was an absence of qualitative work and studies of the impact on, or role of, family, friends or informal networks.

There is a need for evidence-based interventions to reduce the risk of communicable respiratory conditions and a greater understanding of disease trajectories and management for these vulnerable populations, including provision of accessible appropriate supportive, palliative and end-of-life care.
Effects of Lightweight Wearable Ankle Exoskeleton in an Individual With Parkinson Disease
Authors: Jain Tarang K. , Carter Valerie , Lerner Zachary F.
Published: July 2020

Background:

This is a feasibility study aimed to investigate the effects of a novel lightweight ankle exoskeleton on gait and balance in an individual with Parkinson disease (PD).

Case Description:

An 85-year old woman with a 5-year history of PD (Hoehn and Yahr stage 2.5) participated in the study. The participant received 4 visits over 4 weeks including 1 evaluation and three 30-minute training sessions wearing the ankle exoskeleton.

Results:

The participant demonstrated a 26% reduction in metabolic cost during walking and nearly 10% improvement in peak anterior-posterior center-of-pressure displacement during balance testing with untethered exoskeleton assistance compared with baseline.

Conclusion:

Participant-specific ankle exoskeleton is a feasible and safe intervention that can improve walking economy as well as balance in individuals with PD.
Boxing to Improve Sleep Quality and Daytime Sleepiness in Individuals With Parkinson Disease
Authors: Urrutia Macy , Ivy Cynthia , Pohl Patricia S. , Denney Linda
Published: July 2020

The purpose of this study was to determine whether high-intensity exercise boxing has an effect on sleep quality and daytime sleepiness in individuals with Parkinson disease (PD). Fifteen (male: n = 10; female: n = 5) participants with PD completed biweekly high-intensity boxing sessions for 6 weeks. Outcome measures for sleep quality, daytime sleepiness, and depression were taken at baseline, posttraining (7 weeks), and 12 weeks. A repeated-measures multivariate analysis of variance was used to examine changes in sleep and depression. Participation in a 6-week high-intensity boxing program significantly decreased depression, as well as showed trends of improved sleep quality and decreased daytime sleepiness.
Duganella lactea sp. nov., Duganella guangzhouensis sp. nov., Duganella flavida sp. nov. and Massilia rivuli sp. nov., isolated from a subtropical stream in PR China and proposal to reclassify Duganella ginsengisoli as Massilia ginsengisoli comb. nov.
Authors: Lu Huibin , Deng Tongchu , Liu Feifei , Wang Yonghong , Yang Xunan , Xu Meiying
Published: July 2020

Five Gram-stain-negative, catalase- and oxidase-positive, rod-shaped and motile strains (FT50WT, FT80WT, FT92WT, FT94W and FT135WT) were isolated from a subtropical stream in PR China. Comparisons based on 16S rRNA gene sequences showed that strains FT50WT, FT94W and FT135WT take strain

Duganella sacchari

Sac-22T, and strains FT80WT and FT92WT take strain

Duganella ginsengisoli

DCY83T as their closest neighbour in the phylogenetic trees, respectively. The G+C contents of strains FT50WT, FT80WT, FT92WT, FT94W and FT135WT were 63.3, 62.4, 62.8, 63.8 and 60.8 %, respectively. The reconstructed phylogenomic tree based on concatenated 92 core genes showed that strains FT50WT, FT80WT, FT94W and FT135WT clustered together with species of the genus

Duganella

, but strains FT92WT and

D. ginsengisoli

KCTC 42409T were located in the clades of the genus

Massilia

. The calculated pairwise average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values among strains FT50WT, FT80WT, FT92WT, FT94W, FT135WT and related strains were in the ranges of 75.6–87.8% and 20.3–33.8% except that the values between strains FT50WT and FT94W were 98.7 and 89.2%, respectively. The respiratory quinone of these five strains was Q-8. The major fatty acids were C16 : 1
 ω7c, C16 : 0, C18 : 1
 ω7c and C12 : 0. The polar lipids included phosphatidylethanolamine, phosphatidylglycerol and one unidentified phospholipid. Considering the distinct phylogenetic relationships of

D. ginsengisoli

with species of the genus

Massilia

in the phylogenomic tree, it was reasonable to transfer

D. ginsengisoli

to the genus

Massilia

as Massilia ginsengisoli comb. nov. Combining the results of phylogenomic analysis, ANI and dDDH data, and a range of physiological and biochemical characteristics together, strains FT50WT and FT94W should belong to the same species and be assigned to genus

Duganella

with strains FT80WT and FT135WT together, and strain FT92WT should be assigned to the genus

Massilia

, for which the names Duganella lactea sp. nov. (type strain FT50WT=GDMCC 1.1674T=KACC 21466T), Duganella guangzhouensis sp. nov. (FT80WT=GDMCC 1.1678T=KACC 21470T), Duganella flavida sp. nov. (FT135WT=GDMCC 1.1745T=KACC 21659T) and Massilia rivuli sp. nov. (FT92WT=GDMCC 1.1682T=KACC 21474T) are proposed.
Metagenomic approaches in microbial ecology: an update on whole-genome and marker gene sequencing analyses
Authors: Pérez-Cobas Ana Elena , Gomez-Valero Laura , Buchrieser Carmen
Published: July 2020

Metagenomics and marker gene approaches, coupled with high-throughput sequencing technologies, have revolutionized the field of microbial ecology. Metagenomics is a culture-independent method that allows the identification and characterization of organisms from all kinds of samples. Whole-genome shotgun sequencing analyses the total DNA of a chosen sample to determine the presence of micro-organisms from all domains of life and their genomic content. Importantly, the whole-genome shotgun sequencing approach reveals the genomic diversity present, but can also give insights into the functional potential of the micro-organisms identified. The marker gene approach is based on the sequencing of a specific gene region. It allows one to describe the microbial composition based on the taxonomic groups present in the sample. It is frequently used to analyse the biodiversity of microbial ecosystems. Despite its importance, the analysis of metagenomic sequencing and marker gene data is quite a challenge. Here we review the primary workflows and software used for both approaches and discuss the current challenges in the field.
On the effect of age on the transmission of SARS-CoV-2 in households, schools and the community
Authors: Goldstein E , Lipsitch M , Cevik M
Published: July 2020

Background

There is limited information on the effect of age on the transmission of SARS-CoV-2 infection in different settings, including primary, secondary and high schools, households, and the whole community. We undertook a literature review of published studies/data on detection of SARS-CoV-2 infection in contacts of COVID-19 cases, as well as serological studies, and studies of infections in the school setting to examine those issues.

Results

Our literature review presents evidence for significantly lower susceptibility to infection for children aged under 10 years compared to adults given the same exposure, for elevated susceptibility to infection in adults aged over 60y compared to younger/middle aged adults, and for the risk of SARS-CoV-2 infection associated with sleeping close to an infected individual. Published serological studies also suggest that younger adults (particularly those aged under 35y) often have high cumulative rates of SARS-CoV-2 infection in the community. Additionally, there is some evidence of robust spread of SARS-CoV-2 in secondary/high schools, and there appears to be more limited spread in primary schools. Some countries with relatively large class sizes in primary schools (e.g.Chile and Israel) reported sizeable outbreaks in some of those schools, though routes of transmission of infection to both students and staff are not clear from current reports.

Conclusions

Opening secondary/high schools is likely to contribute to the spread of SARS-CoV-2, and, if implemented, it should require both lower levels of community transmission and greater safeguards to reduce transmission. Compared to secondary/high schools, opening primary schools and daycare facilities may have a more limited effect on the spread of SARS-CoV-2 in the community, particularly under smaller class sizes and in the presence of mitigation measures. Efforts to avoid crowding in the classroom and other mitigation measures should be implemented, to the extent possible, when opening primary schools. Efforts should be undertaken to diminish the mixing in younger adults to mitigate the spread of the epidemic in the whole community.
Fluorescent protein-based reporters reveal stress response of intracellularSalmonella entericaon single cell level
Authors: Schulte Marc , Olschewski Katharina , Hensel Michael
Published: July 2020

Intracellular bacteria such asSalmonella entericaare confronted with a broad array of defense mechanisms of their mammalian host cells. The ability to sense host cell-imposed damages, and to mount efficient stress responses are crucial for survival and proliferation of intracellular pathogens. The various combinations of host defense mechanisms acting on intracellular bacteria and their individual response also explain the occurrence of distinct subpopulations of intracellularS. entericasuch as dormant or persisting, slowly or rapidly replicating cells. Here we describe a set of fluorescence protein (FP)-based reporter strains that were used to monitor the expression of cytoplasmic or periplasmic stress response systems on a single cell level. This is mediated by a fast maturing FP as reporter for induction of stress response genes. We evaluated slower maturing FPs for a second function, i.e. the analyses of the status of intracellular proliferation of pathogens. The combination of two FPs allows, on a single cell level, the interrogation of stress response and intracellular proliferation. Application of these reporters toS. entericaallowed us to detect and quantify distinct intracellular subpopulations with different levels of stress response and proliferation.

Importance

Sensing of, and responding to host-mediated damages are important defensive virulence traits of bacterial pathogens. Intracellular pathogens such asSalmonella entericaare exposed to various types of antimicrobial host cell defenses that impose, among other, periplasmic and cytosolic stresses. IntracellularS. entericaform distinct subpopulations that differ in proliferation rate, metabolic activity and persister formation. Here we deploy fluorescence protein-based reporter strains to monitor, on a single cell level, the response of intracellularS. entericato periplasmic or cytoplasmic stress. A second fluorescent protein reports the biosynthetic capacity of individual intracellularS. enterica. The dual fluorescence reporters can be deployed to characterize by flow cytometry phenotypically diverse subpopulations and stress responses in intracellular bacteria.
Plasma amyloid, phosphorylated tau, and neurofilament light for individualized risk prediction in mild cognitive impairment
Authors: Cullen Nicholas C. , Leuzy Antoine , Palmqvist Sebastian , Janelidze Shorena , Stomrud Erik , Pesini Pedro , Sarasa Leticia , Allué José Antonio , Proctor Nicholas K. , Zetterberg Henrik , Dage Jeffrey L. , Blennow Kaj , Mattsson-Carlgren Niklas , Hansson Oskar
Published: July 2020

We developed models for individualized risk prediction of cognitive decline in mild cognitive impairment (MCI), using plasma biomarkers of β-amyloid (Aβ), tau, and neurodegeneration. We included MCI patients from the Swedish BioFINDER study (n=148) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n=86 for model selection; n=425 for prognostic validation). The primary outcomes were longitudinal cognition and conversion to AD dementia, predicted by plasma Aβ42/Aβ40, P-tau181, and neurofilament light (NfL). A model which included P-tau181 and NfL, but not Aβ42/Aβ40, had the best performance (AUC=0.88 for four-year conversion to AD in BioFINDER, validated in ADNI). The prognostic ability of plasma biomarkers was stronger than a basic model of age, sex, education, and baseline cognition and similar to cerebrospinal fluid biomarkers. Plasma biomarkers, in particular P-tau181 and NfL, may be of high value to identify MCI individuals who will progress to AD dementia in clinical trials and in clinical practice.
SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19
Authors: Wu Jun , Liang Boyun , Chen Cunrong , Wang Hua , Fang Yaohui , Shen Shu , Yang Xiaoli , Wang Baoju , Chen Liangkai , Chen Qi , Wu Yang , Liu Jia , Yang Xuecheng , Li Wei , Zhu Bin , Zhou Wenqing , Wang Huan , Li Shumeng , Lu Sihong , Liu Di , Li Huadong , Krawczyk Adalbert , Lu Mengji , Yang Dongliang , Deng Fei , Dittmer Ulf , Trilling Mirko , Zheng Xin
Published: July 2020

Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected. The positivity rate and magnitude of IgM-S and IgG-N responses increased rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset were associated with virus control and IgG-S titers correlated closely with the capacity to neutralize SARS-CoV-2. While specific IgM-S/N became undetectable 12 weeks after disease onset in most patients, IgG-S/N titers showed an intermediate contraction phase, but stabilized at relatively high levels over the six months observation period. At late time points the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies was still over 70%. Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity.
“We are at risk too”: The disparate impacts of the pandemic on younger generations
Authors: El-Gabalawy Renée , Sommer Jordana L.
Published: July 2020

Background

The COVID-19 pandemic has resulted in profound global impact with high rates of morbidity and mortality. It is essential to understand the psychosocial impacts of the pandemic to identify appropriate prevention and intervention targets. Across generational groups, this study examined: (1) rates of precautions and adaptive and maladaptive health behaviours, (2) differences in levels of anxiety, and (3) rates of and changes in COVID-related concerns over time during the early outbreak of COVID-19 in Canada.

Methods

We analyzed data from two Canadian population-based datasets: the Canadian Perspective Survey Series: Impact of COVID-19 survey (N=4,627; March 29-April 3, 2020), and Crowdsourcing: Impacts of COVID-19 on Canadians – Your Mental Health (N=45,989; April 24-May 11, 2020). We categorized generational age group, participants self-reported changes in behaviours and COVID-related concerns, and a validated measure assessed anxiety symptoms.

Results

There are age differences in behavioural responses to the pandemic; adaptive health habits (e.g., exercise) were stable across groups, while maladaptive health habits (e.g., substance use) were highest among younger groups. COVID-related precautions were also highest among the younger generations, with Generation X exhibiting the highest rate of precautionary behaviour. Results also revealed that anxiety and worry are prevalent in response to the pandemic across all generations, with the highest rate of clinically significant anxiety among Millennials (36.0%). Finally, COVID-related concerns are greatest for younger generations and appear to be decreasing with time.

Conclusion

These early data are essential in understanding at-risk groups given the unpredictable nature of the pandemic and its potential long-term implications.
Phenotypic signatures in clinical data enable systematic identification of patients for genetic testing
Authors: Morley Theodore J. , Han Lide , Morra Jonathan , Cox Nancy J. , Bastarache Lisa , Ruderfer Douglas M.
Published: July 2020

Around five percent of the population is affected by a rare disease, most often due to genetic variation. A genetic test is the quickest path to a diagnosis, yet most suffer through years of diagnostic odyssey before getting a test, if they receive one at all. Identifying patients that are likely to have a genetic disease and therefore need genetic testing is paramount to improving diagnosis and treatment. While there are thousands of previously described genetic diseases with specific phenotypic presentations, a common feature among them is the presence of multiple rare phenotypes which often span organ systems. Here, we hypothesize that these patients can be identified from longitudinal clinical data in the electronic health record (EHR). We used diagnostic information from the EHRs of 2,286 patients that received a chromosomal microarray and 9,144 matched controls to train and test a prediction model. We identified high prediction accuracy (AUROC = 0.97, AUPR = 0.92) in a held-out test sample and in 172,265 hospital patients where cases were defined broadly as interacting with a genetics provider (AUROC = 0.9, AUPR = 0.63). High probabilities (median = 0.97) were associated with 46 patients carrying a known pathogenic copy number variant (CNV) among a subset of 6,445 genotyped patients. Our model identified many more patients needing a genetic test while increasing the proportion having a putative genetic disease compared to the current nonsytematic approach. Taken together, we demonstrate that phenotypic patterns representative of a genetic disease can be captured from EHR data and provide an opportunity to systematize decision making on genetic testing to speed up diagnosis, improve care, and reduce costs.
Paso doble: A two-step Late Pleistocene range expansion in the Tyrrhenian tree frogHyla sarda
Authors: Spadavecchia Giada , Chiocchio Andrea , Bisconti Roberta , Canestrelli Daniele
Published: July 2020

The Tyrrhenian tree frog,Hyla sarda, is an amphibian endemic to the Tyrrhenian islands (Western Mediterranean). Previous investigations of its Pleistocene evolutionary history suggested that it colonised the northern portion of its current range, through a spatial diffusion process from the Sardinia island, during the last glaciation. However, southern and northern portions of the species’ range experienced markedly different climatic conditions during the Late Pleistocene, suggesting the possibility of an unusual two-step process of demographic expansion. Here, we use Bayesian phylogeographic approaches to locate the ancestral area in Sardinia and to characterise better the demographic component of this expansion event. These analyses located the ancestral area forH. sardapopulations along the central-eastern coast of the Sardinia island, within an area previously shown to host suitable bioclimatic conditions forH. sardapopulations throughout the Late Pleistocene. Historical demographic reconstructions clearly showed that a two-step process of demographic growth fits well the data, with northern populations expanding later than Sardinia populations. The harsher climatic conditions occurred in northern islands during the glacial epoch, as compared to Sardinia, likely delayed tree frog colonisation of northern territories, and the associated demographic growth.
Sensitivity to perturbations of a cell migration under temporal regulation
Authors: Dubois Clément , Gupta Shivam , Mugler Andrew , Félix Marie-Anne
Published: July 2020

Few studies have measured the robustness to perturbations of the final position of a long-range migrating cell. In the nematodeCaenorhabditis elegans, the QR neuroblast migrates anteriorly in the young larva, while undergoing three rounds of division. The daughters of QR.pa stop their migration at an anterior body position and acquire a neuronal fate. Previous studies showed that the migration stops upon expression of the Wnt receptor MIG-1, which surprisingly is not induced by positional cues but by a timing mechanism (Mentink et al. 2014). Given this temporal regulation, we wondered 1) how precise QR.pax positioning is when confronted with various challenges, such as stochastic noise, environment or body size variation and 2) whether QR.pax position varies amongC. eleganswild isolates. We find that the variance of QR.pax final position is similar to that of other long-range migrating neurons. Its mean position undergoes a slight posterior shift at higher temperature, while its variance is greatly increased following sustained starvation at hatching. We manipulated body size using mutants and tetraploid animals. As expected from the temporal mechanism, smaller mutants display anteriorly shifted QR.pax cells, while longer mutants and tetraploids display posteriorly shifted QR.pax cells. Using a mathematical model, we show however that body size variation is partially compensated. We find that cell speed is indeed altered in body size mutants. Finally, we could detect highly significant variation amongC. eleganswild isolates. Overall, this study reveals that the final cell position of QR.pax shows some degree of sensitivity to external perturbations and natural genetic variation.
Translating the Human CANTAB Touchscreen Based Tasks to Evaluate Learning and Memory in Mouse Models of Down Syndrome
Authors: Siegel Ashley , Bianchi Diana W , Guedj Faycal
Published: July 2020

Humans with Down syndrome (DS) exhibit hippocampal learning deficits in the Cambridge Neuropsychological Test Automated Battery (CANTAB). Here we translated the CANTAB Visual Discrimination (VD) and Extinction tasks to investigate hippocampal learning and cortical inhibitory control in the Dp(16)1/Yey, Ts65Dn and Ts1Cje mouse models of DS. No food or water restriction was used prior to testing. The number of days to reach 70% correct answers and percent of correct responses were analyzed. All Dp(16)1/Yey, Ts1Cje and WT mice reached Stage 5 of pre-training. No differences between genotypes were found in percent of correct responses. Five Ts65Dn and one WT animals reached Stage 5 and only one Ts65Dn mouse reached VD. Ts1Cje mice took longer (17.86±3.19 days) to move to VD vs. WT (11.44±1.96 days,P=0.09). There were no differences between Dp(16)1/Yey and WT mice. At VD, the average percent of correct answers was significantly lower in Dp(16)1/Yey (22.70±1.93%) and Ts1Cje (34.39±1.98%) compared to WT littermates (32.18±1.49% and 41.11±1.45%, respectively,P<0.05). In another set of experiments, we demonstrated that mild food restriction significantly reduced the time needed to complete pre-training in C57BL/6J mice compared to C67BL/6J mice that hadad libitumaccess to food and water. In conclusion, we were able to apply human cognitive tests to evaluate hippocampal learning and cortical inhibitory control in three mouse models of DS. These studies demonstrate significant cognitive differences between strains. Future experiments will evaluate whether food restriction and/or pre- and postnatal therapy decreases the time intervals to achieve training mile.
Malaria Outbreak Detection with Machine Learning Methods
Authors: Comert Gurcan , Begashaw Negash , Turhan-Comert Ayse
Published: July 2020

Abstract

In this paper, we utilized and compared selected machine learning techniques to detect malaria out-break using observed variables of maximum temperature, minimum temperature, humidity, rainfall amount, positive case, and Plasmodium Falciparum rate. Random decision tree, logistic regression, and Gaussian processes are specially analyzed and adopted to be applied for malaria outbreak detection. The problem is a binary classification with outcomes of outbreak or no outbreak. Sample data provided in the literature from Maharashtra, India is used. Performance of the models are compared with the results from similar studies. Based on the sample data used, we were able to detect the malaria outbreak without any false positive or false negative errors in the testing dataset.
Cyclin G2 inhibits oral squamous cell carcinoma growth and metastasis by binding to insulin-like growth factor binding protein 3 and regulating the FAK-SRC-STAT signaling pathway
Authors: Wang Danning , Gao Jinlan , Zhao Chenyang , Li Sen , Zhang Di , Hou Xiaoyu , Zhuang Xinbin , Liu Qi , Luo Yang
Published: July 2020

The cell cycle protein cyclin G2 is considered a tumor suppressor. However, its regulatory effects and potential mechanisms in oral cancers are not well understood. This study aimed to investigate the effect of cyclin G2 on oral squamous cell carcinoma (OSCC). The data from 80 patients with OSCC were utilized to predict the abnormal expression of cyclin G2. The proliferation and metastasis were determined by a cell counting Kit-8 assay, flow cytometry, a wound-healing assay and a cell invasion assay. The expression of key proteins and genes associated with the cyclin G2 signaling pathways was determined by western blotting and real-time PCR, respectively. The orthotopic nude mice model was established by a mouth injection of SCC9 cells overexpressing cyclin G2. We showed that the low level of cyclin G2 in OSCC, which is negatively correlated with clinical staging, was a negative prognostic factor for the disease. We also found that cyclin G2 inhibited the proliferation, metastasis and blocked the cell cycle at G1/S of OSCC cells, suggesting that cyclin G2 has an inhibitory effect in OSCC. Mechanistically, cyclin G2 inhibited the growth and metastasis of OSCC by binding to insulin-like growth factor binding protein 3 (IGFBP3) and regulating the focal adhesion kinase (FAK) -SRC-STAT signal transduction pathway. Cyclin G2 competed with integrin to bind to IGFBP3; the binding between integrin and IGFBP3 was reduced after cyclin G2 overexpression, thereby inhibiting the phosphorylation of FAK and SRC. These results showed that cyclin G2 inhibited the progression of OSCC by interacting with IGFBP3 and that it may be a new target for OSCC treatment.
Chronic Hemodialysis Patients have better outcomes with COVID-19 - a retrospective cohort study
Authors: Naaraayan Ashutossh , Nimkar Abhishek , Hasan Amrah , Pant Sushil , Durdevic Momcilo , Elenius Henrik , Suarez Corina Nava , Basak Prasanta , Lakshmi Kameswari , Mandel Michael , Jesmajian Stephen
Published: July 2020

Introduction

Several comorbid conditions, have been identified as risk factors in patients with COVID-19. However, there is a dearth of data describing the impact of COVID-19 infection in patients with end-stage renal disease on hemodialysis (ESRD-HD).

Methods

This retrospective case series analyzed 362 adult patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020 and May 13, 2020, at a teaching hospital in the New York City metropolitan area. Primary outcome was severe pneumonia as defined by the World Health Organization. Secondary outcomes were: 1) the Combined Outcome of Acute respiratory distress syndrome or in-hospital Death (COAD), and 2) the need for High-levels of Oxygen supplementation (HiO2).

Results

Patients with ESRD-HD had lower odds for poor outcomes including severe pneumonia [Odds Ratio (OR) 0.4, Confidence Interval (CI) (0.2–0.9) p=.04], HiO2 [OR 0.3, CI (0.1– 0.8) p=.02] and COAD [OR 0.4, CI (0.2–1.05) p=.06], when compared to patients without ESRD. In contrast, higher odds for severe pneumonia, COAD and HiO2 were seen with advancing age. African-Americans were over-represented in the hospitalized patient cohort, when compared to their representation in the community (35% vs 18%). Hispanics had higher odds for severe-illness and HiO2 when compared to Caucasians.

Conclusions

Patients with ESRD-HD had a milder course of illness with a lower likelihood of severe pneumonia and a lesser need for aggressive oxygen supplementation when compared to patients not on chronic dialysis. This “protective effect” might have a pathophysiologic basis and needs to be further explored.
Use of finger length ratio as a marker for knee osteoarthritis: A case-control study of 2,456 patients
Authors: Magu Dukhum , Aggarwal Aditya , Behera Prateek , Khurana Ankit
Published: July 2020

Background

In the human hand, the index and ring finger present a considerable variation in their relative lengths and the ratio of their lengths (2D:4D ratio). This ratio is associated with a variety of behavioral and physiological traits possibly linked to variation in sex hormones levels. Previous studies have revealed inconsistent results while assessing the association of 2D:4D ratio as a risk factor for occurrence of knee osteoarthritis (KOA). This study was designed as a prospective observational study to analyze this association using a better methodology.

Methods

Patients were enrolled into KOA group (1396 patients) and non-KOA group (1060 patients) based on ACR criteria for OA knee. Knee and hand radiographs of all patients enrolled were assessed. The 2D:4D length ratio was calculated for phalanges, metacarpal bones and for the combined (metacarpal & phalanx) finger lengths on radiographs and visual finger lengths. The finger patterns were classified and assessment was done between these ratios and finger pattern types for occurrence and severity of KOA.

Results

A lower 2D:4D ratio in an individual was associated with an increased chance of KOA and a dose response relationship was found between radiographic grading of KOA and 2D:4D ratio.

Conclusion

Based on the findings of this study one can predict the risk of developing KOA using this simple technique which can be used as a screening tool whereby preventive intervention can be started if someone presents early with a low 2D:4D finger length ratio.

KEY MESSAGES

Evaluation of finger patterns reveals an association with osteoartritis knee (KOA)

Low 2D:4D ratio and Type 3 finger pattern is associated with increased KOA risk

Low 2D:4D ratio has as positive correlation to radiographic severity of KOA

Preventive interventons can be initiated for those with at risk finger pattern
Excess deaths in Spain during the first year of the COVID–19 pandemic outbreak from age/sex–adjusted death rates
Authors: Martín-Olalla José María
Published: July 2020

Objectives

Assess the impact of the illness designated COVID–19 during the first year of pandemic outbreak in Spain through age/sex–specific death rates.

Study design

Age/sex–specific weeekly deaths in Spain were retrieved from Eurostat. Spanish resident population was obtained from the National Statistics Office.

Methods

Generalized linear Poisson regressions were used to compute the contrafactual expected rates after one year (52 weeks or 364 days) of the pandemic onset. From this one–year age/sex–specific and age/sex–adjusted mortality excess rates were deduced.

Results

For the past continued 13 years one–year age/sex–adjusted death rates had not been as high as the rate observed on February 28th, 2021.

The excess death rate was estimated as 1.790×10−3 (95 % confidence interval, 1.773×10−3 to 1.808×10−3; P−score = 20.2 % and z−score = 11.4) with an unbiased standard deviation of the residuals equal to 157×10−6. This made 84 849 excess deaths (84 008 to 85 690). Sex disaggregation resulted in 44 887 (44 470 to 45 303) male excess deaths and 39 947 (39 524 to 40 371) female excess deaths.

Conclusion

With 73 571 COVID–19 deaths and 9772 COVID–19 suspected deaths that occurred in nursing homes during the spring of 2020 it is only 1496 excess deaths (1.8 %, a z−score of 0.2) that remains unattributed.

The infection rate during the first year of the pandemic is estimated in 16 % of population after comparing the ENE–COVID seroprevalence, the excess deaths at the end of the spring 2020 and the excess deaths at the end of the first year of the pandemic.
The biphasic and age-dependent impact of Klotho on hallmarks of aging and skeletal muscle function
Authors: Pius Abish , Clemens Zachary , Sivakumar Sruthi , Sahu Amrita , Shinde Sunita , Mamiya Hikaru , Luketich Nathaniel , Cui Jian , Hoeck Joerg D. , Kreuz Sebastian , Franti Michael , Barchowsky Aaron , Ambrosio Fabrisia
Published: July 2020

Aging is accompanied by a disrupted information flow, which results from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders such as skeletal muscle wasting, or sarcopenia. To estimate the growing “disorderliness” of the aging muscle system, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Although the most prominent structural and functional alterations were observed in the oldest old mice (27-29 months), we found that the escalating network entropy reached an inflection point at old age (22-24 months). To probe the potential for restoration of molecular “order” and reversal of the sarcopenic phenotype, we overexpressed the longevity protein, α-Klotho. Klotho overexpression modulated genes representing all hallmarks of aging in both old and oldest-old mice. However, whereas Klotho improved strength in old mice, intervention failed to induce a benefit beyond the entropic tipping point.
Soil N2O emission potential falls along a denitrification phenotype gradient linked to differences in microbiome, rainfall and carbon availability
Authors: Highton Matthew P. , Bakken Lars R. , Dörsch Peter , Wakelin Steve , de Klein Cecile A. M. , Molstad Lars , Morales Sergio E.
Published: July 2020

Soil denitrification produces the potent greenhouse gas nitrous oxide (N2O) and by further reduction of N2O, the harmless inert gas N2. N2O emission is determined by rate and timing of the N2O producing and reducing steps which are sensitive to a series of proximal and distal regulators such as pH and microbial community composition. Microbial community associations to N2O emission potential (N2O/(N2O+N2)) are commonly entangled with pH leaving the true role of community composition unclear. Here, we leverage a set of soil microbiomes strongly linked to rainfall above pH to test the hypothesis that microbiome vs. N2O emission potential (N2O/(N2O+N2)) correlations will be maintained across alternative distal drivers. N2O emission potential (N2O/(N2O+N2)) and denitrification gas (NO, N2O, N2) kinetics were assessed by automated gas chromatography while community composition was assessed by 16S rRNA gene sequencing and qPCR ofnosZIandIIgenes. Analyses revealed a sustained correlation between microbiome and N2O emission potential (N2O/(N2O+N2)) in the absence of a pH effect. Further, a continuum of gas accumulation phenotypes linked to NO accumulation and sensitive to carbon addition are identified. Separate phenotypes carried out N2O production and reduction steps more concurrently or sequentially and thus determined N2O accumulation and emission potential (N2O/(N2O+N2)). Concurrent N2O producing/reducing soils typically contained NO accumulation to a low steady state, while carbon addition manipulations which increased NO accumulation also increased sequentiality of N2O production/reduction and thus emission potential (N2O/(N2O+N2)). These features may indicate a conserved NO inhibitory mechanism across multiple effectors (rainfall, community composition, carbon availability).

Highlights

N2O emission potential is linked to microbiome changes associated with rainfall, but not to pH.

Sequential vs. concurrent denitrification phenotypes differing in NO and N2O accumulation are identified.

High N2O accumulation is associated with increased NO accumulation.

Sequentiality of N2O production/reduction determines soil N2O emission potential.

Sequentiality of N2O reduction was susceptible to manipulation via carbon addition.
De novo protein design by deep network hallucination
Authors: Anishchenko Ivan , Chidyausiku Tamuka M. , Ovchinnikov Sergey , Pellock Samuel J. , Baker David
Published: July 2020

There has been considerable recent progress in protein structure prediction using deep neural networks to infer distance constraints from amino acid residue co-evolution1–3. We investigated whether the information captured by such networks is sufficiently rich to generate new folded proteins with sequences unrelated to those of the naturally occuring proteins used in training the models. We generated random amino acid sequences, and input them into the trRosetta structure prediction network to predict starting distance maps, which as expected are quite featureless. We then carried out Monte Carlo sampling in amino acid sequence space, optimizing the contrast (KL-divergence) between the distance distributions predicted by the network and the background distribution. Optimization from different random starting points resulted in a wide range of proteins with diverse sequences and all alpha, all beta sheet, and mixed alpha-beta structures. We obtained synthetic genes encoding 129 of these network hallucinated sequences, expressed and purified the proteins in E coli, and found that 27 folded to monomeric stable structures with circular dichroism spectra consistent with the hallucinated structures. Thus deep networks trained to predict native protein structures from their sequences can be inverted to design new proteins, and such networks and methods should contribute, alongside traditional physically based models, to the de novo design of proteins with new functions.
Ecological aspects of sandfly fauna (Diptera: Psychodidae, Phlebotominae) of Sumidouro District, State of Rio de Janeiro, Brazil
Authors: Alves João Ricardo Carreira , Carmo Cleber Nascimento do , Menezes Rodrigo Caldas , Luís Vilela Mauricio , dos Santos-Mallet Jacenir Reis
Published: July 2020

Aiming to compare and update the sand fly fauna of Portão de Pedra site, Sumidouro District, Rio de Janeiro State, Brazil, and considering the environmental changes occurred, the biology and ecology of the local sandfly species were examined five years later as a complementary study carried. Captures were made in the cave, surroundings of cave and forest of the region, from 6 p.m. to 6 a.m. 2 3 2 3 sandflies of eigth species of theLutzomyiawere captured:L. gasparviannai, L. edwardsi, L. tupynambai, L. hirsuta, L. whitmani, L. migonei, L. intermedia, Lutzomyia. sp and one species of theBrumptomyiaKind:B. brumpti. In 2009 and 2010 were collected 1756 samples from ten species of the former genus and two of the second.L. gasparviannaiwas predominant, in the three collection sites, in both periods. Five species implicated as vector ofLeishmania:L. intermedia, L. whitmani, L. migonei, L. hirsutaandL. davisihave been collected in the area. Poisson regression and ANOVA were used to perform statistical analysis of species most relevant. The record ofL. intermediaand a case of American tegumentary leishmaniasis are relevant to public health of municipality and of state of Rio de Janeiro.
Physical modeling of a sliding clamp mechanism for the spreading of ParB at short genomic distance from bacterial centromere sites
Authors: Walter Jean-Charles , Rech Jérôme , Walliser Nils-Ole , Dorignac Jérôme , Geniet Frédéric , Palmeri John , Parmeggiani Andrea , Bouet Jean-Yves
Published: July 2020

Bacterial ParB partitioning proteins involved in chromosomes and low-copy-number plasmid segregation have recently been shown to belong to a new class of CTP-dependent molecular switches. Strikingly, CTP binding and hydrolysis was shown to induce a conformational change enabling ParB dimers to switch between an open and a closed conformation. This latter conformation clamps ParB dimers on DNA molecules, allowing their diffusion in one dimension along the DNA. It has been proposed that this novel sliding property may explain the spreading capability of ParB over more than 10-Kb fromparScentromere sites where ParB is specifically loaded. Here, we modeled such a mechanism as a typical reaction-diffusion system and compared this ‘Clamping & sliding’ model to the ParB DNA binding pattern from high-resolution ChIP-sequencing data. We found that this mechanism cannot account for all thein vivocharacteristics, especially the long range of ParB binding to DNA. In particular, it predicts a strong effect from the presence of a roadblock on the ParB binding pattern that is not observed in ChIP-seq. Moreover, the rapid assembly kinetics observedin vivoafter the duplication ofparSsites is not easily explained by this mechanism. We propose that ‘Clamping & sliding’ might explain the ParB spreading pattern at short distances fromparSbut that another mechanism must apply for ParB recruitment at larger genomic distances.
Nasal respiration is necessary for the emergence of ketamine-induced high frequency network oscillations and behavioral hyperactivity in freely moving rats
Authors: Wróbel Jacek , Średniawa Władysław , Bernatowicz Gabriela , Zygierewicz Jaroslaw , Wójcik Daniel K , Whittington Miles Adrian , Hunt Mark Jeremy
Published: July 2020

Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130-180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked “fast” theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to “fast” theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were in phase with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. In conclusion, nasal entrainment of ketamine-dependent HFO across cortical and subcortical regions at theta frequencies represents a mechanism of orchestrated neural activity across distinct brain regions. The dense divergent connectivity of the olfactory system serves to broadcast this HFO to limbic areas.