bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of reduced graphene oxide on stem cells: a perspective in peripheral nerve regeneration
Authors: Yao Xiangyun , Yan Zhiwen , Wang Xu , Jiang Huiquan , Qian Yun , Fan Cunyi
Published: June 2021

Graphene and its derivatives are fascinating materials for their extraordinary electrochemical and mechanical properties. In recent decades, many researchers explored their applications in tissue engineering and regenerative medicine. Reduced graphene oxide (rGO) possesses remarkable structural and functional resemblance to graphene, although some residual oxygen-containing groups and defects exist in the structure. Such structure holds great potential since the remnant-oxygenated groups can further be functionalized or modified. Moreover, oxygen-containing groups can improve the dispersion of rGO in organic or aqueous media. Therefore, it is preferable to utilize rGO in the production of composite materials. The rGO composite scaffolds provide favorable extracellular microenvironment and affect the cellular behavior of cultured cells in the peripheral nerve regeneration. On the one hand, rGO impacts on Schwann cells and neurons which are major components of peripheral nerves. On the other hand, rGO-incorporated composite scaffolds promote the neurogenic differentiation of several stem cells, including embryonic stem cells, mesenchymal stem cells, adipose-derived stem cells and neural stem cells. This review will briefly introduce the production and major properties of rGO, and its potential in modulating the cellular behaviors of specific stem cells. Finally, we present its emerging roles in the production of composite scaffolds for nerve tissue engineering.
The Application of Machine Learning Approaches on Real-Time Apartment Prices in the Tokyo Metropolitan Area
Authors: Peng Ti-Ching , Wang Chun-Chieh
Published: June 2021

The widely applied hedonic regression approach for the relationship between property prices and housing attributes is subject to assumptions and specifications of models as well as the availability and content of second-hand official data. In a cross-disciplinary spirit, this study employs machine learning techniques to examine hedonic apartment prices in the Tokyo Metropolitan Area of Japan based on online sales data extracted by web-parsing technology. With 14,579 apartment observations, two machine learning regressions—decision tree (DT) and random forest (RF)—are compared to conventional ordinary least squares regression (OLS) for hedonic modelling. Empirical results demonstrated that RF regressions led to the highest accuracy in model prediction performance, followed by DT and OLS. The comparison with results across models revealed that the housing features that have consistent influences on apartment prices tend to be those associated with living quality (including management funds, repair fund fees, floor size, located floor, total floor of the building, and location in Tokyo). Other commonly appreciated features, such as southward orientation or corner-lot location, did not demonstrate importance, possibly due to changes in residents’ preferences. In this big-data era, the adaptation of real-time data and machine learning approaches should add value to the variable selection process and model performance.
Taxonomy in the phylogenomic era: species boundaries and phylogenetic relationships among North American ants of theCrematogaster scutellarisgroup (Formicidae: Hymenoptera)
Authors: Ward Philip S , Blaimer Bonnie B
Published: June 2021

We investigate the species-level taxonomy and evolutionary history of Nearctic ants in the Crematogaster scutellaris group (Hymenoptera: Formicidae), drawing on evidence from morphology and UCE (ultraconserved element) phylogenomics. The New World species in this group form a well-supported clade that originated in the Late Miocene (~7.3 Mya) and subsequently diverged into three major lineages: the C. coarctata clade (south-western Nearctic), the C. opaca clade (south-western Nearctic and northern Neotropics) and the C. lineolata clade (eastern Nearctic and Caribbean, with four isolated south-west endemics). We hypothesize trans-Beringian dispersal into the New World, west-to-east movement within North America and restriction of mesophilic species to the east with increasing aridification of the west. The ancestral nesting behaviour of these ants is inferred to be ground-dwelling, and this is still the predominant condition in the arid west, whereas most species in the eastern United States are arboreal. We resurrect from synonymy nine species and describe three new species: C. detecta sp. nov. (from Nevada), C. parapilosa sp. nov. (Florida) and C. vetusta sp. nov. (Arizona). We provide a worker-based key to the 34 species of Crematogaster occurring in America north of Mexico, but emphasize that there are still ongoing taxonomic issues that need to be resolved.
Incorporating Early Palliative Medicine Consultation Into Daily Morning Huddle in the ICU
Authors: Babar Arslan , Eilenfeld Katherine , Alqaisi Sura , MohamedElfadil Mahmoud , Al-Jaghbeer Mohammed J.
Published: June 2021

OBJECTIVES:

Early palliative medicine consult in the ICU can significantly improve outcomes in high-risk patients. We describe a pilot study of including a recommendation for palliative medicine consult in the ICU morning huddle.

DESIGN:

A prospective, observational, quality improvement study.

PATIENTS AND SETTING:

Adult patients (age above 18 yr) admitted with cardiac arrest, stage IV cancer, admission from a long-term acute care facility, and circulatory shock on mechanical ventilation to the medical ICU.

INTERVENTIONS:

We aim to assess the effect of an early palliative medicine consultation in selected high-risk patients on change in code status, referral to hospice, tracheostomy, and or percutaneous gastrostomy tube placement.

MEASUREMENTS AND MAIN RESULTS:

There were 83 patients who triggered an early palliative medicine consult. Palliative medicine consultation occurred in 44 patients (53%); 23 patients (28%) had a palliative medicine consult within the first 48 hours, 21 (25%) had a palliative medicine consult afterwards. There was a significantly higher number of patients who de-escalated their code status in the palliative medicine consult group compared with the no palliative medicine consult group (63.6% vs 7.7%); however, the number was higher in the late palliative medicine consult group (71.4% vs 56.5%). There were more patients referred to hospice in the palliative medicine consult group. No difference in length of stay was observed.

CONCLUSIONS:

Early palliative medicine consultation in the daily ICU morning huddle is achievable, can produce a palliative medicine consultation in most cases, and results in a significant change in code status toward less aggressive measures.
Psychological Symptoms in Relatives of Critically Ill Patients: A Longitudinal Cohort Study
Authors: de Ridder Carin , Zegers Marieke , Jagernath Danny , Brunnekreef Gert , van den Boogaard Mark
Published: June 2021

OBJECTIVES:

To explore the psychologic impact of an ICU stay on relatives and to determine patient and relative factors, including their pre-ICU mental health status, associated with psychologic symptoms 3 months after ICU admission.

DESIGN:

A prospective, exploratory, longitudinal cohort study.

SETTING:

A 12-bed ICU in a Dutch tertiary teaching hospital.

PATIENTS:

The relatives of ICU patients admitted between March 2018 and December 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Relatives completed the Hospital Anxiety and Depression Scale shortly after patients’ ICU admission referring to the week before ICU admission and 3 months later, together with the Impact of Event Scale-Revised, assessing posttraumatic stress. A total of 387 were eligible of which 78 (20%) responded. Almost a quarter reported an increase of anxiety (23.1%) and depression (24.4%) between baseline and 3 months follow-up. One in six (17.9%) reported posttraumatic stress. Anxiety, depression, and posttraumatic stress at 3 months follow-up were significantly associated with preexisting anxiety and depression. Patients’ factor associated with depression 3 months follow-up in relatives was length of ICU stay (odds ratio, 1.09; 95% CI, 1.02–1.16).

CONCLUSIONS:

Relatives with preexisting psychologic symptoms before ICU admission are at risk to develop anxiety, depression, or posttraumatic stress shortly after ICU discharge of the patient. Screening and identification in an early stage enables early interventions to prevent relatives from worsening mental health during and after ICU admission.
Lead Toxicity From a Swallowed Fishing Sinker: A Case Report
Authors: Gupta Shivani R. , Mezoff Ethan , Dienhart Molly
Published: June 2021

Lead toxicity is relatively common despite increased public awareness, with lifelong neurologic sequelae. Common sources of exposure include lead paint, contaminated water, curtain weights, and bullets. However, few reports consider management of lead fishing equipment ingestions, such as weights or sinkers. We present a 5-year-old male who swallowed a lead fishing weight and had a high serum lead level despite urgent removal. When managing ingestion of a lead foreign body, if accessible by upper endoscopy, we recommend urgent removal with subsequent monitoring of serum lead levels.
Native Spleen Preservation During Visceral Transplantation Inhibits Graft-Versus-Host-Disease Development
Authors: Stringa Pablo , Papa-Gobbi Rodrigo , Vela María , Gentilini María Virginia , Machuca Mariana , Klin Pablo , Arreola Nidia M. , Serradilla Javier , Bueno Alba , Andrés Ane M. , Ramos Esther , Alcolea Alida , Pérez-Martínez Antonio , Prieto Gerardo , López-Santamaría Manuel , Gondolesi Gabriel , Rumbo Martín , Hernández Francisco
Published: June 2021

Objective:

We aimed to assess whether native spleen preservation during visceral transplantation (VT) affects graft-versus-host-disease (GVHD) incidence.

Summary Background Data:

GVHD is one of the most severe and frequently lethal hematological complications after VT procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation.

Methods:

Our study included both clinical and experimental data. A total of 108 patients were divided into 3 groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into 2 groups: a native spleen preservation (+SP) group and a native spleen removal (−S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed.

Results:

The patients with native spleen preservation showed a lower rate of GVHD (P<.001) and better survival (P<.05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group (P<.05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved (P<.01 and P<.0001, respectively).

Conclusions:

The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.
Integrating PCR-free amplification and synergistic sensing for ultrasensitive and rapid CRISPR/Cas12a-based SARS-CoV-2 antigen detection
Authors: Zhao Xiangxiang , Wang Zhengduo , Yang Bowen , Li Zilong , Tong Yaojun , Bi Yuhai , Li Zhenghong , Xia Xuekui , Chen Xiangyin , Wang Weishan , Tan Gao-Yi , Zhang Lixin
Published: June 2021

Antigen detection provides particularly valuable information for medical diagnoses; however, the current detection methods are less sensitive and accurate than nucleic acid analysis. The combination of CRISPR/Cas12a and aptamers provides a new detection paradigm, but sensitive sensing and stable amplification in antigen detection remain challenging. Here, we present a PCR-free multiple trigger dsDNA tandem-based signal amplification strategy and a de novo designed dual aptamer synergistic sensing strategy. Integration of these two strategies endowed the CRISPR/Cas12a and aptamer-based method with ultra-sensitive, fast, and stable antigen detection. In a demonstration of this method, the limit of detection was at the single virus level (0.17 fM, approximately two copies/μL) in SARS-CoV-2 antigen nucleocapsid protein analysis of saliva or serum samples. The entire procedure required only 20 minutes. Given our system’s simplicity and modular setup, we believe that it could be adapted reasonably easily for general applications in CRISPR/Cas12a-aptamer-based detection.
The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan
Authors: Kaneko Yudai , Sugiyama Akira , Tanaka Toshiya , Fukui Kazushige , Taguchi Akashi , Nakayama Aya , Koga Kazumasa , Kishi Yoshiro , Daming Wang , Qian Chungen , Xia Fuzhen , He Fan , Zheng Liang , Yu Yi , Wada Youichiro , Wada Yoshiaki , Kodama Tatsuhiko , Kawamura Takeshi
Published: June 2021

Objectives

To compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19.

Methods

A total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2.

Results

The levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didn’t exceed 10 AU/mL.

Conclusions

Our findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients’ immune mechanisms.
Socioeconomic position and SARS-CoV-2 infections: seroepidemiological findings from a German nationwide dynamic cohort
Authors: Hoebel Jens , Grabka Markus M. , Schröder Carsten , Haller Sebastian , Neuhauser Hannelore , Wachtler Benjamin , Schaade Lars , Liebig Stefan , Hövener Claudia , Zinn Sabine
Published: June 2021

Background

Evidence on the relationship between socioeconomic position (SEP) and infections with the SARS-CoV-2 coronavirus is still limited as most of the available studies are ecological in nature. This is the first German nationwide study to examine differences in the risk of SARS-CoV-2 infections according to SEP at the individual level.

Methods

The ‘CORONA-MONITORING bundesweit’ (RKI-SOEP) study is a seroepidemiological survey among a dynamic cohort of the German adult population (n=15,122; October 2020 – February 2021). Dried blood samples were tested for SARS-CoV-2 antibodies and oral-nasal swabs for viral RNA. SEP was measured by education and income. Robust logistic regression was used to examine adjusted associations of SARS-CoV-2 infections with SEP.

Results

288 participants were seropositive, PCR-positive, or self-reported a previous laboratory-confirmed SARS-CoV-2 infection. The adjusted odds of SARS-CoV-2 infection were 1.87-fold (95% confidence interval [CI]=1.06-3.29) higher among low-educated than highly educated adults. Evidence was weaker for income differences in infections (odds ratio=1.65; 95% CI=0.89-3.05). Highly educated adults had lower odds of undetected infection.

Conclusion

The results indicate an increased risk of SARS-CoV-2 infection in low-educated groups. To promote health equity in the pandemic and beyond, social determinants should be addressed more in infection protection and pandemic planning.
Meta-Analytic Evidence of Depression and Anxiety in Eastern Europe during the COVID-19 Pandemic
Authors: Zhang Stephen X. , Miller Saylor O. , Xu Wen , Yin Allen , Chen Bryan Z. , Delios Andrew , Dong Rebecca Kechen , Chen Richard Z. , McIntyre Roger S. , Wan Xue , Wang Senhu , Chen Jiyao
Published: June 2021

Objective

To perform a systematic and meta-analysis on the prevalence rates of mental health symptoms including anxiety and depression during the COVID-19 pandemic in the general population in Eastern Europe, as well as three select sub-populations: students, general healthcare workers, and frontline healthcare workers.

Data sources

Studies in PubMed, Embase, Web of Science, Psycinfo, and medRxiv up to February 6, 2021.

Eligibility criteria and data analysis

Prevalence rates of mental health symptoms in the general population and key sub-populations during the COVID-19 pandemic in Eastern Europe. Data were pooled using a random-effects meta-analysis to estimate the prevalence rates of anxiety and depression.

Results

The meta-analysis identifies and includes 21 studies and 26 independent samples in Eastern Europe. Poland (n=4), Serbia (n=4), Russia (n=3), and Croatia (n=3) had the greatest number of studies. To our knowledge, no studies have been conducted in eleven Eastern European countries including Hungary, Slovakia, and Slovenia. The pooled prevalence of anxiety in 18 studies with 22 samples was 30% (95% CI: 24% – 37%) and pooled prevalence of depression in 18 studies with 23 samples was 27% (95% CI: 21% – 34%).

Implications

The cumulative evidence from the meta-analysis reveals high prevalence rates of clinically significant symptoms during the COVID-19 pandemic in Eastern Europe. The findings suggest evidence of a potential mental health crisis in Eastern Europe during the ongoing COVID-19 pandemic. Our synthesis also reveals a relative lack of studies in certain Eastern European countries as well as high heterogeneities among the existing studies, calling for more effort to achieve evidence-based mental healthcare in Eastern Europe.

Highlights

The pooled prevalence of anxiety and depression were 30% and 27% in Eastern Europe, respectively.

Trial registration

CRD42020224458
Interpretable gender classification from retinal fundus images using BagNets
Authors: Ilanchezian Indu , Kobak Dmitry , Faber Hanna , Ziemssen Focke , Berens Philipp , Ayhan Murat Seçkin
Published: June 2021

Deep neural networks (DNNs) are able to predict a person’s gender from retinal fundus images with high accuracy, even though this task is usually considered hardly possible by ophthalmologists. Therefore, it has been an open question which features allow reliable discrimination between male and female fundus images. To study this question, we used a particular DNN architecture called BagNet, which extracts local features from small image patches and then averages the class evidence across all patches. The BagNet performed on par with the more sophisticated Inception-v3 model, showing that the gender information can be read out from local features alone. BagNets also naturally provide saliency maps, which we used to highlight the most informative patches in fundus images. We found that most evidence was provided by patches from the optic disc and the macula, with patches from the optic disc providing mostly male and patches from the macula providing mostly female evidence. Although further research is needed to clarify the exact nature of this evidence, our results suggest that there are localized structural differences in fundus images between genders. Overall, we believe that BagNets may provide a compelling alternative to the standard DNN architectures also in other medical image analysis tasks, as they do not require post-hoc explainability methods.
The tumor suppressor Adenomatous polyposis coli regulates T lymphocyte migration. Insights from familial polyposis patients
Authors: Mastrogiovanni Marta , Vargas Pablo , Rose Thierry , Cuche Céline , Juzans Marie , Esposito Elric , Laude Hélène , Renaudat Charlotte , Ungeheuer Marie-Noëlle , Delon Jérôme , Alcover Andrés , Di Bartolo Vincenzo
Published: June 2021

Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance for anti-tumor immunity is ill defined. APC regulates cytoskeleton organization, cell polarity and migration in various cells types. Here we address whether APC plays a role in T lymphocyte migration, a key step of anti-tumor immune responses.

Using a series of cell biology tools, we demonstrated that T cells from FAP patients carrying APC mutations display adhesion and migration defects. Concomitantly, they presented lower expression of the integrin VLA-4. To further dissect the cellular mechanisms underpinning these defects, we depleted APC in the CEM T cell line. We found that APC is critical not only for VLA-4-dependent adhesion but also for actomyosin and microtubule organization in migrating T cells. Finally, APC-silenced CEM cells preferentially adopt an ameboid-like migration featuring unstructured pseudopodia and blebbing.

These findings underscore a role of APC in T cell migration via modulation of integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms, but also impair T cell migration, potentially leading to inefficient T cell-mediated anti-tumor immunity.
Using deep learning to predict brain age from brain magnetic resonance images and cognitive tests reveals that anatomical and functional brain aging are phenotypically and genetically distinct
Authors: Goallec Alan Le , Diai Samuel , Collin Sasha , Vincent Théo , Patel Chirag J.
Published: June 2021

With the world population aging, the prevalence of age-related brain diseases such as Alzheimer’s, Parkinson’s, Lou Gehrig’s, and cerebrovascular diseases. In the following, we built brain age predictors by leveraging 46,000 brain magnetic resonance images [MRIs] and cognitive tests from UK Biobank participants. We predicted age with a R-Squared [R2] of 76.4±1.0% and a root mean squared error of 3.58±0.05 years and identified the features driving the prediction using attention maps. We defined accelerated brain aging as the difference between brain age (predicted age) and age. Accelerated brain aging is partially heritable (h_g2=35.9±2.6%), and is associated with 219 single nucleotide polymorphisms [SNPs] in 25 genes (e.g CRHR1, involved in the hypothalamic-pituitary-adrenal pathway). Similarly, it is associated with biomarkers (e.g blood pressure), clinical phenotypes (e.g general health), diseases (e.g diabetes), environmental (e.g smoking) and socioeconomic variables (e.g income and education). We performed the same analysis, this time distinguishing between anatomical (MRI-based) and functional (cognitive tests-based) brain aging. We found the two accelerated aging phenotypes to be phenotypically .112±.006 correlated and genetically uncorrelated, with distinct SNPs and non-genetic factors associated with each. In conclusion, anatomical and functional brain aging are two distinct, complex phenotypes, which also differ in their genetic and non-genetic factors. Our brain predictors could be used to monitor the effects of emerging rejuvenating therapies on the brain.
A tool to distinguish viral from bacterial pneumonia
Authors: Tagarro Alfredo , Moraleda Cinta , Domínguez-Rodríguez Sara , Rodríguez Mario , Dolores Martín María , Luisa Herreros María , Folgueira María Dolores , Pérez-Rivilla Alfredo , Jensen Julia , López Agustín , Berzosa Arantxa , de Santaeufemia Francisco José Sanz , Jiménez Ana Belén , Sainz Talía , Llorente Marta , Garrote Elisa , Muñoz Cristina , Sánchez Paula , Santos Mar , Illán Marta , Barrios Ana , Pacheco Mónica , Corral Raquel Ramos , Arquero Carmen , Bernardino María , Prieto Luis , Gutiérrez Lourdes , Epalza Cristina , Rojo Pablo , Oviedo Lidia , Serna-Pascual Miquel , Soto Beatriz , Guillén Sara , Molina David , Martín Elvira , Vázquez Carmen , Gerig Natalia , Calvo Cristina , Pilar Romero María , Imaz Manuel , Cañete Alfonso , Ramos José-Tomás , Galán Juan Carlos , Otheo Enrique
Published: June 2021

Background and Objectives

Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most children receive antibiotics that do not need.

This study aims to build and validate a diagnostic tool combining clinical, analytical and radiographical features to sequentially differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria, to improve choice of treatment.

Methods

Consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. An extensive microbiological workup was performed. A score was built with a training set of 70% patients, to first differentiate between viral and bacterial CAP and secondly, typical from atypical bacterial CAP. To select variables, a Ridge model was used. Optimal cut-off points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. The score was validated with the rest of the participants.

Results

In total, 262 (53%) children (median age, 2 years, 52.3% male) had an etiological diagnosis.

The step 1 discriminates viral from bacterial CAP. Bacterial CAPs were classified with a sensitivity=97%, a specificity=48%, and a ROC’s area under the curve (AUC)=0.81. If a CAP was classificated as bacterial, it was assessed with step 2. The step 2 differentiates typical vs. atypical bacterial CAP. Typical bacteria were classified with a sensitivity=100%, a specificity=64%, and AUC=0.90.

Conclusion

This two-steps tool can facilitate the physician’s decision to prescribe antibiotics without compromising patient safety.

Article summary

We validated a clinical tool to predict the aetiology of CAP in children safely. This tool differentiates CAP into viral, atypical bacteria and typical bacteria.

“What’s Known on This Subject”

Establishing the aetiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most admitted children with CAP receive antibiotics.

“What This Study Adds”

We validated a clinical tool to predict the aetiology of pneumonia in children safely, differentiating among viral, atypical bacteria and typical bacteria.
Ongoing HIV transmission following a large outbreak among people who inject drugs in Athens, Greece (2014-2020)
Authors: Roussos Sotirios , Paraskevis Dimitrios , Psichogiou Mina , Kostaki Evangelia Georgia , Flountzi Eleni , Angelopoulos Theodoros , Chaikalis Savvas , Papadopoulou Martha , Pavlopoulou Ioanna D , Malliori Meni , Hatzitheodorou Eleni , Pylli Magdalini , Tsiara Chrissa , Paraskeva Dimitra , Beloukas Apostolos , Kalamitsis George , Hatzakis Angelos , Sypsa Vana
Published: June 2021

Background and Aims

The HIV outbreak among People Who Inject Drugs (PWID) in Athens, Greece in 2011-2013 was the largest recent epidemic in Europe and North America. We aim to assess trends in HIV prevalence, drug use and access to prevention among PWID in Athens, to estimate HIV incidence and identify risk factors and to explore HIV-1 dispersal using molecular methods during 2014-2020.

Methods

Two community-based HIV/hepatitis C programs on PWID were implemented in 2012-2013 (N=3,320) and 2018-2020 (N=1,635) through consecutive Respondent-Driven Sampling (RDS) rounds. PWID were uniquely identified across rounds/programs. We obtained RDS-weighted HIV prevalence estimates per round for 2018-2020 and compared them to 2012-2013. We assessed changes in HIV status, behaviours, and access to prevention in PWID participating in both periods. We estimated HIV incidence in a cohort of seronegative PWID as the number of HIV seroconversions/100 persons-years during 2014-2020 and used Cox regression to identify associated risk factors. Molecular sequencing and phylogenetic analysis were performed in HIV seroconverters.

Results

HIV prevalence per round ranged between 12.0%-16.2% in 2012-2013 and 10.7%-11.3% in 2018-2020 with overlapping 95% Confidence Intervals (95% CI). Among PWID participating in both programs, HIV prevalence[95% CI] increased from 14.2%[11.7%-17.1%] in 2012-2013 to 22.0%[19.0%-25.3%] in 2018-2020 (p<0.001). There was a deterioration of socioeconomic characteristics such as homelessness (from 16.2%[95% CI: 13.5%-19.2%] to 25.6%[22.3%-29.0%]), a shift in cocaine use (16.6%[13.9%-19.6%] vs. 28.1%[24.7%-31.7%], reduced access to free syringes (51.8%[48.0%-55.7%] vs. 44.5%[40.7%-48.3%]) and a decrease in daily injecting (36.2%[32.6%-39.9%] vs. 28.5%[25.2%-32.1%]). HIV incidence (95% CI) in 2014-2020 was 1.94 (1.50-2.52) new cases/100 person-years and younger age, lower educational level, larger injection network and daily injecting were risk factors. Almost 9% of HIV seroconversions occurred within a newly expanding phylogenetic cluster.

Conclusions

The ongoing HIV transmission among PWID in Athens provides empirical evidence that the current levels of prevention and treatment are inadequate to control the epidemic. Re-evaluation of prevention programs is urgently needed.
Using mobile health technology to assess childhood autism in low-resource community settings in India : an innovation to address the detection gap
Authors: Dubey Indu , Bishain Rahul , Dasgupta Jayashree , Bhavnani Supriya , Belmonte Matthew K. , Gliga Teodora , Mukherjee Debarati , Estrin Georgia Lockwood , Johnson Mark H. , Chandran Sharat , Patel Vikram , Gulati Sheffali , Divan Gauri , Chakrabarti Bhismadev
Published: June 2021

Autism Spectrum Disorders, hereafter referred to as autism, emerge early and persist throughout life, contributing significantly to global years lived with disability. Typically, an autism diagnosis depends on clinical assessments by highly trained professionals. This high resource demand poses a challenge in resource-limited areas where skilled personnel are scarce and awareness of neurodevelopmental disorder symptoms is low. We have developed and tested a novel app, START, that can be administered by non-specialists to assess several domains of the autistic phenotype (social, sensory, motor functioning) through direct observation and parent report. N=131 children (2-7 years old; 48 autistic, 43 intellectually disabled, and 40 typically developing) from low-resource settings in the Delhi-NCR region, India were assessed using START in home settings by non-specialist health workers. We observed a consistent pattern of differences between typically and atypically developing children in all three domains assessed. The two groups of children with neurodevelopmental disorders manifested lower social preference, higher sensory sensitivity, and lower fine-motor accuracy compared to their typically developing counterparts. Parent-report further distinguished autistic from non-autistic children. Machine-learning analysis combining all START-derived measures demonstrated 78% classification accuracy for the three groups (ASD, ID, TD). Qualitative analysis of the interviews with health workers and families (N= 15) of the participants suggest high acceptability and feasibility of the app. These results provide proof of principle for START, and demonstrate the potential of a scalable, mobile tool for assessing neurodevelopmental disorders in low-resource settings.
Differential pre-pandemic IgA reactivity against SARS-CoV-2 and circulating human coronaviruses measured in milk collected in Uganda and the USA
Authors: Egwang Thomas G. , Owalla Tonny Jimmy , Okurut Emmanuel , Apungia Gonzaga , Fox Alisa , DeCarlo Claire , Powell Rebecca L.
Published: June 2021

Objective

Uganda, like other African countries, has registered fewer COVID-19 cases and deaths per capita than non-African countries. The lower numbers of cases and deaths in Uganda might be due to pre-existing cross-immunity induced by zoonotic coronaviruses or circulating common cold human coronaviruses (HCoVs) before the COVID-19 pandemic. In order to test this premise, we compared IgA reactivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HCoVs in breast milk of US and rural Ugandan mothers collected in 2018 before the COVID-19 epidemic. Ugandan and US pre-pandemic breast milk samples were run in duplicate on enzyme-linked immunoadsorbent assay (ELISA) to measure specific IgA antibody reactivity to the spike proteins of SARS-CoV-2, human coronaviruses (HCoV) NL63, OC43, HKU1, and 229E. Pooled plasma from US COVID-19 positive and negative cases were employed as positive and negative controls, respectively. One Ugandan pre-pandemic milk sample had remarkably high reactivity against all HCoVs and SARS-CoV-2 spike proteins. There was higher IgA reactivity against the betacoronavirus HCoV-OC43 in Ugandan pre-pandemic milk samples by comparison with US pre-pandemic milk samples (p = 0.018). By contrast, there was significantly higher IgA reactivity against the alphacoronaviruses HCoV-229E and HCoV-NL63 in US pre-pandemic milk samples by comparison with Ugandan pre-pandemic milk samples (p < 0.0001 and 0.035, respectively).

Conclusion

Some Ugandan mothers may have robust pre-existing immunity against SARS-CoV-2 due to cross-immunity induced by HCoVs which may be passed on to their infants via breastfeeding. The differential pre-pandemic reactivity of US mothers to HCoV 229E and HCoV NL63 may have contributed to suboptimal antibody responses to SARS-CoV-2.
Communication of pain intensity and unpleasantness through magnitude ratings: Influence of scale type, but not sex of the participant
Authors: Nahman-Averbuch Hadas , Hughes Cassidy , Hoeppli Marie-Eve , White Kristina , Peugh James , Leon Eric , King Christopher D. , Coghill Robert C.
Published: June 2021

A critical aspect for much human pain research is the ability of participants to communicate their first person, experiential perspective to a third person observer. This communication is frequently accomplished via pain ratings. The type of scale and how participants/patients may differentially use the scale has a major influence on the communication of pain experiences. The present study examined the role of sex on the pain rating process using both noxious and innocuous stimuli and two different types of rating scales. Participants underwent noxious heat, auditory and visual stimulation paradigms. Pain intensity and unpleasantness ratings were collected using the visual analog scale (VAS) and numerical rating scale (NRS) in a random order. For noxious heat stimuli, low (44-45°C) and high (47-48°C) intensity stimuli were delivered. To identify if one rating scale allows better discrimination between different stimulus intensities and if this is dependent on sex, discrimination thresholds were calculated. Significant effect for rating scale and intensity level of stimuli were found for all stimulus modalities (noxious heat, auditory and visual) indicating that higher intensity and unpleasantness ratings were found using the NRS compared to the VAS. No effect of sex or interaction with sex was found. No differences in rating scale and sex were found for the discrimination thresholds. Biases in rating scales usage exist with NRS yielding higher ratings to the same stimuli. However, this bias does not appear to contribute significantly to sex differences in pain.
Landscape of human gut antibiotic resistome and progression of diabetes
Authors: Shuai Menglei , Zhang Guoqing , Zeng Fang-fang , Fu Yuanqing , Liang Xinxiu , Yuan Ling , Xu Fengzhe , Gou Wanglong , Miao Zelei , Jiang Zengliang , Wang Jia-ting , Zhuo Lai-bao , Chen Yu-ming , Ju Feng , Zheng Ju-Sheng
Published: June 2021

Objective: To investigate the association between human gut antibiotic resistome and the progression of type 2 diabetes (T2D) in a large cohort study.
Design: The present study included 1210 participants from the Guangzhou Nutrition and Health Study. We depicted the landscape of human gut antibiotic resistome with shotgun metagenomic data and examined its association with T2D and cardiometabolic traits. The co-occurrence network analysis was used to explore the associations between T2D-related ARGs and gut microbial species. We also examined the associations between gut antibiotic resistome features and fecal metabolome.
Results: There was a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes and T2D groups (p = 0.004). We found that larger ARG diversity was associated with a higher risk of T2D (all p < 0.05). Based on the association found between resistomes and T2D, we developed diabetes ARG score and demonstrated its creative use as a new predictor for T2D progression manifested by the change of insulin resistance. Further network analysis showed the co-occurrence association between T2D-related ARGs and gut microbial species, which indicated the potential bacterial hosts of these ARG biomarkers. Resistome-metabolome co-analysis suggests a potential link of ARGs with fecal metabolites, which may reflect the host-microbial metabolic adaptation.
Conclusion: Our data depict the landscape of gut antibiotic resistome diversity and composition and uncover a close relationship between human gut antibiotic resistome and T2D progression.
Transposable elements in the genome of the lichen-forming fungus Umbilicaria pustulata, and their distribution in different climate zones along elevation
Authors: Dal Grande Francesco , Jamilloux Veronique , Choisne Nathalie , Calchera Anjuli , Petersen Malte , Schulz Meike , Nilsson Maria A. , Schmitt Imke
Published: June 2021

Background

Transposable elements (TEs) are an important source of genome plasticity across the tree of life. Accumulating evidence suggests that TEs may not be randomly distributed in the genome. Drift and natural selection are important forces shaping TE distribution and accumulation, acting directly on the TE element or indirectly on the host species. Fungi, with their multifaceted phenotypic diversity and relatively small genome size, are ideal models to study the role of TEs in genome evolution and their impact on the host’s ecological and life history traits. Here we present an account of all TEs found in a high-quality reference genome of the lichen-forming fungus Umbilicaria pustulata, a macrolichen species comprising two climatic ecotypes: Mediterranean and cold-temperate. We trace the occurrence of the newly identified TEs in populations along three replicated elevation gradients using a Pool-Seq approach, to identify TE insertions of potential adaptive significance.

Results

We found that TEs cover 21.26 % of the 32.9 Mbp genome, with LTR Gypsy and Copia clades being the most common TEs. Out of a total of 182 TE copies we identified 28 insertions displaying consistent insertion frequency differences between the two host ecotypes across the elevation gradients. Most of the highly differentiated insertions were located near genes, indicating a putative function.

Conclusions

This pioneering study into the content and climate niche-specific distribution of TEs in a lichen-forming fungus contributes to understanding the roles of TEs in fungal evolution. Particularly, it may serve as a foundation for assessing the impact of TE dynamics on fungal adaptation to the abiotic environment, and the impact of TE activity on the evolution and maintenance of a symbiotic lifestyle.
A novel flight style allowing the smallest featherwing beetles to excel
Authors: Farisenkov Sergey E. , Kolomenskiy Dmitry , Petrov Pyotr N. , Lapina Nadejda A. , Engels Thomas , Lehmann Fritz-Olaf , Onishi Ryo , Liu Hao , Polilov Alexey A.
Published: June 2021

Flight speed generally correlates positively with animal body size1. Surprisingly, miniature featherwing beetles can fly at speeds and accelerations of insects three times as large2. We show here that this performance results from a previously unknown type of wing motion. Our experiment combines three-dimensional reconstructions of morphology and kinematics in one of the smallest insects, Paratuposa placentis (body length 395 μm). The flapping bristled wing follows a pronounced figure-eight loop that consists of subperpendicular up and down strokes followed by claps at stroke reversals, above and below the body. Computational analyses suggest a functional decomposition of the flapping cycle in two power half strokes producing a large upward force and two down-dragging recovery half strokes. In contrast to heavier membranous wings, the motion of bristled wings of the same size requires little inertial power. Muscle mechanical power requirements thus remain positive throughout the wing beat cycle, making elastic energy storage obsolete. This novel flight style evolved during miniaturization may compensate for costs associated with air viscosity and helps explain how extremely small insects preserved superb aerial performance during miniaturization. Incorporating this flight style in artificial flappers is a challenge for designers of micro aerial vehicles.
The cerebellum encodes and influences the initiation and termination of discontinuous movements
Authors: Gaffield Michael A. , Christie Jason M.
Published: June 2021

The cerebellum is hypothesized to represent timing information important for organizing salient motor events during periodically performed discontinuous movements. To provide functional evidence validating this idea, we measured and manipulated Purkinje cell (PC) activity in the lateral cerebellum of mice trained to volitionally elicit periodic bouts of stereotyped licking for regularly allocated water rewards. Overall, PC simple spiking modulated during task performance, ramping prior to both lick-bout initiation and termination, two important motor events delimiting movement cycles. The ramping onset occurred earlier for the initiation of un-cued exploratory licking that anticipated water availability relative to licking that was reactive to water allocation, suggesting that the cerebellum is engaged differently depending on the movement context. In a subpopulation of PCs, climbing-fiber-evoked responses also increased during lick-bout initiation, but not termination, highlighting differences in how cerebellar input pathways represent task-related information. Optogenetic perturbation of PC activity disrupted the behavior in both initiating and terminating licking bouts and reduced the ability of animals to finely time predictive action around reward delivery, confirming a causative role in movement organization. Together, these results substantiate that the cerebellum contributes to the control of explicitly timed repeated motor actions.
MVPAlab: A Machine Learning decoding toolbox for multidimensional electroencephalography data
Authors: López-García David , Peñalver Jose M.G. , Górriz Juan M. , Ruz María
Published: June 2021

Background and Objective

The study of brain function has recently expanded from classical univariate to multivariate analyses. These multivariate, machine learning-based algorithms afford neuroscientists extracting more detailed and richer information from the data. However, the implementation of these procedures is usually challenging, especially for researchers with no coding experience. To address this problem, we have developed MVPAlab, a MATLAB-based, flexible decoding toolbox for multidimensional electroencephalography and magnetoencephalography data.

Methods

The MVPAlab Toolbox implements several machine learning algorithms to compute multivariate pattern analyses, cross-classification, temporal generalization matrices and feature and frequency contribution analyses. It also provides access to an extensive set of preprocessing routines for, among others, data normalization, data smoothing, dimensionality reduction and supertrial generation. To draw statistical inferences at the group level, MVPAlab includes a non-parametric cluster-based permutation approach.

Results

A sample electroencephalography dataset was compiled to test all the MVPAlab main functionalities. Significant clusters (p<0.01) were found for the proposed decoding analyses and different configurations, proving the software capability for discriminating between different experimental conditions.

Conclusions

This toolbox has been designed to include an easy-to-use and intuitive graphic user interface and data representation software, which makes MVPAlab a very convenient tool for users with few or no previous coding experience. In addition, MVPAlab is not for beginners only, as it implements several high and low-level routines allowing more experienced users to design their own projects in a highly flexible manner.
GraphOmics: An Interactive Platform To Explore And Integrate Multi-Omics Data
Authors: Wandy Joe , Daly Ronan
Published: June 2021

Abstract

Background

An increasing number of studies now produce multiple omics measurements that require using sophisticated computational methods for analysis. While each omics data can be examined separately, jointly integrating multiple omics data allows for a deeper understanding and insights to be gained from the study. In particular data integration can be performed horizontally, where biological entities from multiple omics measurements are mapped to common reactions and pathways. However, data integration remains a challenge due to the complexity of the data and the difficulty in interpreting analysis results.

Results

Here we present GraphOmics, a user-friendly platform to explore, integrate multiple omics datasets and support hypothesis generations. Users can upload transcriptomics, proteomics and metabolomics data to GraphOmics. Relevant entities are connected based on their biochemical relationships, and mapped to reactions and pathways from Reactome. From the Data Browser in GraphOmics, mapped entities and pathways can be ranked, sorted and filtered according to their statistical significance (p-values) and fold changes. Context-sensitive panels provide information on the currently selected entities, while interactive heatmaps and clustering functionalities are also available. As a case study, we demonstrated how GraphOmics was used to interactively explore multi-omics data and support hypothesis generations using two complex datasets from existing Zebrafish regeneration and Covid-19 human studies.

Conclusions

GraphOmics is fully open-sourced and freely accessible from https://graphomics.glasgowcompbio.org/. It can be used to integrate multiple omics data horizontally by mapping entities across omics to reactions and pathways. Our demonstration showed that using interactive explorations from GraphOmics, interesting insights and biological hypotheses could be rapidly revealed.