bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Hand Function and Its Association With Self-Perceived Hand Functional Ability and Quality of Life in Parkinson Disease
Authors: Wong-Yu Irene S.K. , Ren Longjun , Mak Margaret K.Y.
Published: November 2021

Objective

Comprehensive hand function in people with Parkinson disease (PD) has been underevaluated. The objectives were to compare self-perceived and objective hand functions of PD and controls, compare outcomes between more and less affected hand subgroups, and evaluate relationship between self-perceived and objective outcomes in subgroups.

Design

A total of 165 PD and 82 healthy participants completed the Jebsen-Taylor Hand Function Test, Purdue Pegboard Test, grip strength test, and Manual Ability Measure-16 in a cross-sectional study. PD participants completed the Parkinson Disease Questionnaire-39. Associations between objective and self-perceived/quality of life outcomes in PD groups were analyzed, and nondominant and dominant more affected subgroups performance was compared.

Results

PD participants had significantly worse performance in most Jebsen-Taylor Hand Function Test and all Purdue Pegboard Test items, lower Manual Ability Measure-16 scores, and poorer handgrip strength. Weak associations were found between dexterity, but not grip strength, and self-perceived functional hand ability and Parkinson Disease Questionnaire-39 scores in PD subgroups. For nondominant more affected subgroup, poorer dexterity was associated with better Parkinson Disease Questionnaire-39 Activity of Daily Living domain scores.

Conclusion

People with mild to moderate PD were shown to have poorer manual dexterity, reduced grip strength, and lower self-perceived functional hand ability than controls. Associations between dexterity and self-perceived outcomes highlight the importance of unimanual and bimanual training.
Development and Implementation of an International Virtual Didactic Series for Physical Medicine and Rehabilitation Graduate Medical Education During COVID-19
Authors: Haring R. Sterling , Rydberg Leslie K. , Mallow Michael K. , Kortebein Patrick , Verduzco-Gutierrez Monica
Published: November 2021

Coronavirus disease of 2019 presented significant challenges to residency and fellowship programs. Didactic lectures were particularly affected as redeployment of faculty and trainees, limitations on in-person gathering, and other barriers limited opportunities for educational engagement. We sought to develop an online didactic series to address this gap in graduate medical education.

Lecturers were recruited via convenience sample and from previous Association of Academic Physiatrists presenters from across the United States and Canada; these presented via Zoom during April and May 2020. Lecturers and content reflected the diverse nature of the specialty. Learning objectives were adapted from the list of board examination topics provided by the American Board of Physical Medicine and Rehabilitation.

Fifty-nine lectures were presented. Maximum concurrent live viewership totaled 4272 and recorded lecture viewership accounted for an additional 6849 views, for a total of at least 11,208 views between the date of the first lecture (April 9, 2020) and May 1, 2021. Live viewers of one of the lectures reported participating from several states and 16 countries.

The Association of Academic Physiatrists–led virtual didactics augmented graduate medical education during the coronavirus disease of 2019 pandemic, and data confirm that the lectures have continued to enjoy a high level of viewership after the cessation of live lectures.
Twelve-Week Daily Gluteal and Hamstring Electrical Stimulation Improves Vascular Structure and Function, Limb Volume, and Sitting Pressure in Spinal Cord Injury
Authors: Barton Thomas , Low David A. , Thijssen Dick H.J. , Romviel Suzanne , Sloots Maurits , Smit Christof A.J. , Janssen Thomas W.J.
Published: November 2021

Objective

We examined the long-term effects of low-intensity electrical stimulation on (micro)vasculature and sitting pressure of a home-based, wearable electrical stimulation device in a pilot feasibility study.

Design

In a cohort observation before-after trial, nine middle-aged male (n = 8) and female (n = 1) individuals (48 ± 15 yrs) with American Spinal Injury Association A–C classified chronic (1–24 yrs) spinal cord injury underwent 12 wks of self-administered daily, low-intensity gluteal and hamstring electrical stimulation (50 Hz, 6 hrs [30-min electrical stimulation, 15-min rest]). Common femoral artery diameter and blood blow were determined with ultrasound, skin vascular function during local heating was assessed using Laser-Doppler flowmetry, thigh volume was estimated using leg circumferences and skinfolds, and interface sitting pressure was measured using pressure mapping.

Results

Resting common femoral artery diameter increased (0.73 ± 0.20 to 0.79 ± 0.22 cm, P < 0.001) and baseline common femoral artery blood flow increased (0.28 ± 0.12 to 0.40 ± 0.15 l/min, P < 0.002). Gluteal cutaneous vascular conductance showed a time*temperature interaction (P = 0.01) with higher conductance at 42°C after 12 wks. Ischial peak pressure decreased (P = 0.003) by 32 ± 23 mm Hg and pressure gradient decreased (23 ± 7 to 16 ± 6 mm Hg, P = 0.007). Thigh volume increased (+19%, P = 0.01).

Conclusions

Twelve-week daily home-based gluteal and hamstring electrical stimulation is feasible and effective to improve (micro)vasculature and sitting pressure, and electrical stimulation may have clinical implications for ameliorating pressure ulcers and (micro)vascular complications in spinal cord injury.
Compliance to antenatal psychosocial assessment practice among midwives: a best practice implementation project
Authors: Tessema Marta , Birhanu Dagmawit , Mizana Biru Abdissa , Belay Admasu , Tura Gurmesa , Abera Muluemebet , Birhanu Zewdie , Feyissa Garumma Tolu
Published: November 2021

Introduction and aims:

As directed by the WHO, antenatal care providers have good opportunities to identify and refer mothers who are struggling with psychosocial problems. In Ethiopia, the pooled prevalence of perinatal depression is 25.8%, which is almost two-fold of the pooled global prevalence. Though this is an indication of the need for prompt interventions, there is no assessment targeted to this population. Therefore, the aim of this project was to promote an antenatal psychosocial assessment practice among midwives.

Methods:

Using the Joanna Briggs Institute Practical Application of Evidence System, 66 first visit antenatal care assessment opportunities were observed in both baseline and follow-up audit using three audit criteria. Fourteen midwives were interviewed for the first criterion. On the basis of the results, the gaps and barriers were analyzed using Getting Research into Practice strategies.

Result:

The baseline audit result revealed a 0% compliance rate for all evidence-based antenatal psychosocial assessment audit criteria. This scenario disclosed that there had not been psychosocial problem assessment practice at antenatal clinic. However, the postimplementation result showed that an average 91.5% practice of evidence-based antenatal psychosocial assessment was applied as per standards.

Conclusion:

Carrying out discussions on evidence summary with providers, on-the-job training, using local leaders’ opinions, and involving relevant stakeholders appeared to be the key methods in improving compliance to best available evidence in antenatal psychosocial assessment.
A SARS-CoV-2 Delta Variant Containing Mutation in the Probe Binding Region Used for qRT-PCR Test in Japan Exhibited Atypical PCR Amplification and Might Induce False Negative Result
Authors: Rajib Samiul Alam , Ogi Yasuhiro , Hossain Md. Belal , Ikeda Terumasa , Tanaka Eiichi , Kawaguchi Tatsuya , Satou Yorifumi
Published: November 2021

A recent pandemic of SARS-CoV-2 infection has caused severe health problems and substantially restricted social and economic activities. To cope with such an outbreak, the identification of infected individuals with high accuracy is vital. qRT-PCR plays a key role in the diagnosis of SARS-CoV-2 infection. The N protein-coding region is widely analyzed in qRT-PCR for the diagnosis of SARS-CoV-2 infection in Japan. We recently encountered two cases of SARS-CoV-2-positive specimens showing atypical amplification curves in the qRT-PCR. We performed whole-genome sequencing and found that the virus was a Delta-type variant of SARS-CoV-2 with a single nucleotide mutation in the probe-binding site. To evaluate the extent of spread of the variant in the area, we performed whole viral genome sequencing of samples collected from 61 patients infected with SARS-CoV-2 during the same time and in the same area. There were no other cases with the same mutation, indicating that the variant had not spread in the area. Furthermore, we performed phylogenetic analysis with various SARS-CoV-2 sequences deposited in the public database. Hundreds of variants were reported globally, and one in Japan were found to contain the same mutation. Phylogenetic analysis showed that the variant was very close to other Delta variants endemic in Japan but quite far from the variants containing the same mutation reported from outside Japan, suggesting that the variant would have been sporadically generated in some domestic areas. These findings propose two key points: i) mutations in the region used for SARS-CoV-2 qRT-PCR can cause abnormal amplification curves; therefore, the qRT-PCR result should not just be judged in an automated manner, but also manually checked by the examiner to prevent false-negative results, and ii) various mutations can be generated sporadically and unpredictably; therefore, efficient and robust screening systems are needed to promptly monitor the emergence of de novo variants.
Strategy for a rapid screening and surveillance of SARS-CoV-2 variants by real time RT-PCR: a key tool that allowed control and delay in Delta spread in Cordoba, Argentina
Authors: Castro Gonzalo M. , Sicilia Paola , Bolzon María Laura , López Laura , Barbás María Gabriela , Pisano María Belén , Ré Viviana E.
Published: November 2021

Background

SARS-CoV-2 variants of concern (VOC) and interest (VOI) present mutations in reference to the original virus, being more transmissible. We implemented a rapid strategy for the screening of SARS-CoV-2 VOC/VOIs using real time RT-PCR and performed monitoring and surveillance of the variants in our region.

Methods

consecutive real-time RT-PCRs for detection of the relevant mutations/deletions present in the Spike protein in VOC/VOIs (TaqMan™ SARS-CoV-2 Mutation Panel, Applied Biosystems) were implemented. An algorithm was established and 3941 SARS-CoV-2 RNA samples (Cts<30) obtained from oropharyngeal swabs from infected individuals in Córdoba, Argentina, between January and October 2021, were analyzed.

Results

the strategy of choice included a first screening of 3 mutations (N501Y, E484K, L452R) followed by the detection of other mutations/deletions based on the results. The analyses of the samples showed introductions of VOCs Alpha and Gamma in February and March 2021, respectively. Since then, Alpha presented a low to moderate circulation (1.7% of the SARS-CoV-2 currently detected). Gamma showed an exponential increase, with a peak of detection in July (72%), until reaching a current frequency of 41.1%. VOC Delta was first detected in July in travellers and currently represents 35% of detections in the community. VOI Lambda presented a gradual increase, showing a current frequency of 29%.

Conclusions

we report a useful tool for VOC/VOI detection, innovative for Argentina, capable to quickly and cost-effectively monitor currently recognized variants. It was key in the early detection of Delta, being able to implement measures to delay its dissemination.
Mutant IDH Inhibitors Induce Lineage Differentiation in IDH-mutant Oligodendroglioma
Authors: Spitzer Avishay , Gritsch Simon , Weisman Hannah R. , Gonzalez Castro L. Nicolas , Nomura Masashi , Druck Nicholas , Chanoch-Myers Rony , Lee Christine K. , Nagashima Hiroaki , Miller Julie J. , Arrillaga-Romany Isabel , Louis David N. , Wakimoto Hiroaki , Pisano Will , Wen Patrick Y. , Ligon Keith L. , Cahill Daniel P. , Suvà Mario L. , Tirosh Itay
Published: November 2021

Recent data showed promising signs of objective tumor responses in subsets of patients with low grade glioma treated with inhibitors of mutant IDH (IDHi) (1). However, the molecular and cellular underpinnings of such responses are not known. Here, we profiled 6,039 transcriptomes by single-cell or single-nucleus RNA-sequencing isolated from three IDH-mutant oligodendroglioma patients with clinical response to IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation and our dataset includes a matched pre- and on-treatment sample pair. We integrate our findings with analysis of 8,241 transcriptomes from seven untreated samples, 134 bulk samples from the TCGA and experimental models.(2,3) We find that IDHi treatment induces a robust differentiation towards glial lineages, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Our study provides the first evidence in patients of the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas.
HLA-A*03:01 is associated with increased risk of fever, chills, and more severe reaction to Pfizer-BioNTech COVID-19 vaccination
Authors: Bolze Alexandre , Neveux Iva , Barrett Kelly M. Schiabor , White Simon , Isaksson Magnus , Dabe Shaun , Lee William , Grzymski Joseph J. , Washington Nicole L. , Cirulli Elizabeth T.
Published: November 2021

COVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the US have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination. Our GWAS identifies an association between severe difficulties with daily routine after vaccination and HLA-A*03:01. This association was statistically significant only for those who received the Pfizer-BioNTech vaccine (BNT162b2; p=4.70E-11), but showed a trending association in those who received the Moderna vaccine (mRNA-1273; p=0.005) despite similar sample sizes for study. In Pfizer-BioNTech recipients, HLA-A*03:01 was associated with a two-fold increase in risk of severe vaccine reactions. The effect was consistent across ages, sexes, and whether the person had previously had a COVID-19 infection. The reactions experienced by HLA-A*03:01 carriers were driven by associations with chills, fever, fatigue, and in general feeling unwell.
Association between Fat-Infiltrated Axillary Lymph Nodes on Screening Mammography and Cardiometabolic Disease
Authors: Song Qingyuan , diFlorio-Alexander Roberta M. , Patel Sohum D. , Sieberg Ryan T. , Margron Michael J. , Ansari Saif M. , Karagas Margaret R. , Mackenzie Todd A. , Hassanpour Saeed
Published: November 2021

Objective

Ectopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index. Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms.

Methods

A cross-sectional study was conducted on 834 women presenting for full-field digital screening mammography. The status of fat-infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease.

Results

Fat-infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve).

Conclusion

Fat-infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat-infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.
Trajectory of rich club properties in structural brain networks
Authors: Riedel Levin , van den Heuvel Martijn P. , Markett Sebastian
Published: November 2021

Many organizational principles of structural brain networks are established before birth and undergo considerable developmental changes afterwards. These include the topologically central hub regions and a densely connected rich club. While several studies have mapped developmental trajectories of brain connectivity and brain network organization across childhood and adolescence, comparatively little is known about subsequent development over the course of the lifespan. Here, we present a cross-sectional analysis of structural brain network development in N = 8,066 participants aged 5 to 80 years. Across all brain regions, structural connectivity strength followed an ‘inverted-U’-shaped trajectory with vertex in the early 30s. Connectivity strength of hub regions showed a similar trajectory and the identity of hub regions remained stable across all age groups. While connectivity strength declined with advancing age, the organization of hub regions into a rich club did not only remain intact but became more pronounced, presumingly through a selected sparing of relevant connections from age-related connectivity loss. The stability of rich club organization in the face of overall age-related decline is consistent with a “first come, last served” model of neurodevelopment, where the first principles to develop are the last to decline with age. Rich club organization has been shown to be highly beneficial for communicability and higher cognition. A resilient rich club might thus be protective of a functional loss in late adulthood and represent a neural reserve to sustain cognitive functioning in the aging brain.
The evidence for anthocyanins in the betalain-pigmented genus Hylocereus is weak
Authors: Pucker Boas , Brockington Samuel F.
Published: November 2021

Here we respond to Zhou et al., 2020 “Combined Transcriptome and Metabolome analysis of Pitaya fruit unveiled the mechanisms underlying Peel and pulp color formation” published in BMC Genomics. Given the evolutionary conserved anthocyanin biosynthesis pathway in betalain-pigmented species, we are open to the idea that species with both anthocyanins and betalains might exist. However, in absence of LC-MS/MS spectra, apparent lack of biological replicates, and no comparison to authentic standards, the findings of Zhou et al., 2020 are not a strong basis to propose the presence of anthocyanins in betalain-pigmented pitaya. In addition, our re-analysis of the datasets indicates the misidentification of important genes and the omission of key anthocyanin synthesis genes ANS and DFR. Finally, our re-analysis of the RNA-Seq dataset reveals no correlation between anthocyanin biosynthesis gene expression and pigment status.
VIVID: a web application for variant interpretation and visualisation in multidimensional analyses
Authors: Tichkule Swapnil , Myung Yoochan , Naung Myo T. , Ansell Brendan R. E. , Guy Andrew J. , Srivastava Namrata , Mehra Somya , Caccio Simone M. , Mueller Ivo , Barry Alyssa E. , van Oosterhout Cock , Pope Bernard , Ascher David B. , Jex Aaron R.
Published: November 2021

Large-scale comparative genomics- and population genetic studies generate enormous amounts of polymorphism data in the form of DNA variants. Ultimately, the goal of many of these studies is to associate genetic variants to phenotypes or fitness. We introduce VIVID, an interactive, user-friendly web application that integrates a wide range of approaches for encoding genotypic to phenotypic information in any organism or disease, from an individual or population, in three-dimensional (3D) space. It allows mutation mapping and annotation, calculation of interactions and conservation scores, prediction of harmful effects, analysis of diversity and selection, and 3-dimensional (3D) visualisation of genotypic information encoded in Variant Call Format (VCF) on AlphaFold2 protein models. VIVID enables the rapid assessment of genes of interest in the study of adaptive evolution and the genetic load, and it helps prioritising targets for experimental validation. We demonstrate the utility of VIVID by exploring the evolutionary genetics of the parasitic protistPlasmodium falciparum, revealing geographic variation in the signature of balancing selection in potential targets of functional antibodies.
Proteomic analysis of liver tissue revealsAeromonas hydrophilainfection mediated modulation of host metabolic pathways inLabeo rohita
Authors: Nissa Mehar Un , Pinto Nevil , Ghosh Biplab , Singh Urvi , Goswami Mukunda , Srivastava Sanjeeva
Published: November 2021

Aeromonas hydrophila (Ah)is an opportunistic Gram-negative bacterium and a serious global pathogen causing Motile Aeromonas Septicaemia (MAS) in fish and many other vertebrates. The pathogenesis of aeromonas septicaemia is complex and involves multiple perturbed pathways. Molecular analysis of host tissues could be a powerful approach to identify mechanistic and diagnostic immune signatures of disease. We performed a deep proteomic analysis ofLabeo rohitaliver tissue to examine changes in the host proteome duringAhinfection. A total of 2525 proteins were identified of which 158 were found differentially expressed duringAhinfection. Functional analysis of significant proteins identified the dysregulation of several metabolic enzymes, antioxidative proteins, cytoskeletal proteins and immune related proteins. Proteomic analysis revealed the alterations in the cellular defence mechanisms including phagolysosomal killing and apoptosis duringAhinfection. Our systemic approach revealed the protein dynamics in the host cells to explore the putative biological processes underlying the metabolic reprogramming of the host cells duringAhinfection. Our findings paved the way for future research into the role of Toll-like receptors (Tlr3), C-type lectins (Clec4e) and metabolic enzymes inAhpathogenesis leading towards host directed immunotherapies to tackle theAhinfection in fish.

IMPORTANCE

Bacterial disease is one of the most serious problems in aquaculture industry.Aeromonas hydrophila(Ah), a Gram-negative bacterium causes motile aeromonas septicaemia (MAS) in fish. Small molecules that target the metabolism of the host have recently emerged as potential treatment possibilities in infectious diseases. However, the ability to develop new therapies is hampered due to lack of knowledge about pathogenesis mechanisms and host-pathogen interactions. Molecular level analysis of host tissues could be helpful in finding mechanistic immunological markers of diseases. We examined alterations in the host proteome duringAhinfection inLabeo rohitaliver tissue to find cellular proteins and processes affected byAhinfection. Our systemic approach revealed protein dynamics underlying the host cells’ metabolic reprogramming duringAhinfection. Our work is an important step towards leveraging host metabolism in targeting the disease by providing a bigger picture on proteome pathology correlation duringAhinfection.
Anti-SARS-CoV-2 antibodies seroprevalence among patients submitted to treatment for tuberculosis in Rio de Janeiro, Brazil: a cross-sectional study
Authors: Gomes Karen Machado , Leite Suzanne Pereira , Moutinho Maria Helena Vieira , de Souza Thatiana Alfena , de Cássia Batista Rita , de Oliveira Luiz Claudio Motta , Redner Paulo , Ramos Jesus Pais , da Rocha Fatima Maria Gomes , de Oliveira Gisele Pinto , Teva Antônio , do Couto Motta Fernando , de Siqueira Marilda Agudo Mendonça Teixeira , Duarte Rafael Silva , Bastos Francisco Inácio Pinkusfeld Monteir , de Sousa Viana Paulo Victor
Published: November 2021

Due to tuberculosis (TB) patients’ pulmonary damages, some authors believe that a SARS-CoV-2 coinfection may result in unfavorable outcomes. A cross-sectional anti-SARS-CoV-2 antibodies seroprevalence study was conducted at a TB treatment tertiary referral unit in Rio de Janeiro, Brazil, to estimate the proportion (in %) of TB patients exposed to the new coronavirus and their main outcomes. Of 83 patients undergoing TB treatment, 26.5% have already been infected by the new coronavirus. Most patients were asymptomatic (69%) or had mild COVID-19 cases (31%). Only one patient required hospitalization. Among the symptoms and signs presented, the most frequently reported were: fever, headache, and myalgia. People with less education and less purchasing power seemed to had been more exposed to SARS-CoV-2.
A territory-wide study of arrhythmogenic right ventricular cardiomyopathy patients from Hong Kong
Authors: Lakhani Ishan , Zhou Jiandong , Lee Sharen , Christien Li Ka Hou , Kit Leung Keith Sai , Li Guoliang , Liu Tong , Wong Wing Tak , Kei Wong Ian Chi , Mok Ngai Shing , Mak Chloe , Zhang Qingpeng , Tse Gary
Published: November 2021

Background

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterized by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). The present study aims to investigate the risk of detrimental cardiovascular events in an Asian population of ARVC/D patients, including the incidence of malignant ventricular arrhythmias, new-onset heart failure with reduced ejection fraction (HFrEF), as well as long-term mortality.

Methods and Results

This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019 in Hong Kong. This study consisted of 109 ARVC/D patients (median age: 61 [46-71] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariable Cox regression identified prolonged QRS duration as a predictor of VT/VF (p < 0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (P < 0.05. The presence of epsilon waves, in addition to the parameters of prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p<0.05). Clinical scores were developed to predict incident VT/VF, new-onset HFrEF and all-cause mortality, and all were significantly improved by machine learning techniques.

Conclusion

Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients and should in turn be used in tandem to aid risk stratification in the hospital setting.
Impact of dexamethasone on persistent symptoms of COVID-19: an observational study
Authors: Milne A , Maskell S , Sharp C , Hamilton FW , Arnold DT
Published: November 2021

Introduction

Dexamethasone has been shown to reduce mortality for patients hospitalised with acute COVID-19 pneumonia. However, a significant proportion of patients suffer persistent symptoms following COVID-19 and little is known about the longer-term impact of this intervention on symptom burden.

Methods

Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study (April-August 2020) with follow-up at 8 months (Dec 2020-April 2021) post-admission. A review of ongoing symptoms using a standardised systems-based proforma was performed alongside health-related quality of life assessment. In the UK, patients with COVID-19 (requiring oxygen) only received dexamethasone following the pre-print of the RECOVERY trial (June 2020), or as part of randomisation to that trial, allowing for a comparison between patients treated and not treated with dexamethasone.

Results

Between April to August 2020, 198 patients were recruited to this observational study. 87 required oxygen and were followed up at 8-months, so were eligible for this analysis. Of these 39 received an inpatient course of dexamethasone (cases) and 48 did not (controls). The groups were well matched at baseline in terms of age, comorbidity and frailty score. Over two-thirds of patients reported at least 1 ongoing symptom at 8-month follow-up. Patients in the dexamethasone group reported fewer symptoms (n=73, 1.9 per patient) than the non-dexamethasone group (n=152, 3.2 per patient) (p = 0.01).

Conclusions

In conclusion, in this case-control observational study, patients who received oral dexamethasone for hospitalised COVID-19 were less likely to experience persistent symptoms at 8-month follow-up. These are reassuring results for physicians administering dexamethasone to this patient group.
Kilohertz Transcranial Magnetic Perturbation (kTMP): A New Non-invasive Method to Modulate Cortical Excitability
Authors: Labruna Ludovica , Merrick Christina , Peterchev Angel V , Inglis Ben , Ivry Richard B , Sheltraw Daniel
Published: November 2021

Non-invasive brain stimulation (NIBS) provides a method for safely perturbing brain activity, and has been employed in basic research to test hypotheses concerning brainbehavior relationships with increasing translational applications. We introduce and evaluate a novel subthreshold NIBS method: kilohertz transcranial magnetic perturbation (kTMP). kTMP is a magnetic induction method that delivers continuous kHz-frequency cortical electric fields (E-fields) which may be amplitude-modulated to potentially mimic electrical activity at endogenous frequencies. We used TMS to compare the amplitude of motor-evoked potentials (MEPs) in a hand muscle before and after kTMP. In Experiment 1, we applied kTMP for 10 min over motor cortex to induce an E-field amplitude of approximately 2.0 V/m, comparing the effects of waveforms at frequencies of 2.0, 3.5, or 5.0 kHz. In Experiments 2 and 3 we used two forms of amplitude-modulated kTMP with a carrier frequency at 3.5 kHz and modulation frequencies of either 20 or 140 Hz. The only percept associated with kTMP was an auditory tone, making kTMP amenable for doubleblind experimentation. Relative to sham stimulation, non-modulated kTMP at 2.0 and 3.5 kHz resulted in an increase in cortical excitability, with Experiments 2 and 3 providing a replication of this effect for the 3.5 kHz condition. Although amplitude-modulated kTMP increased MEP amplitude compared to sham, no enhancement was found compared to non-modulated kTMP. kTMP opens a new experimental NIBS space inducing relatively large amplitude subthreshold E-fields able to increase cortical excitability with minimal sensation.
Towards a catalog of pome tree architecture genes: the draft ‘d’Anjou’ genome (Pyrus communis L.)
Authors: Zhang Huiting , Wafula Eric K. , Eilers Jon , Harkess Alex E. , Ralph Paula E. , Timilsena Prakash Raj , dePamphilis Claude W. , Waite Jessica M. , Honaas Loren A.
Published: November 2021

The rapid development of sequencing technologies has led to a deeper understanding of horticultural plant genomes. However, experimental evidence connecting genes to important agronomic traits is still lacking in most non-model organisms. For instance, the genetic mechanisms underlying plant architecture are poorly understood in pome fruit trees, creating a major hurdle in developing new cultivars with desirable architecture, such as dwarfing rootstocks in European pear (Pyrus communis). Further, the quality and content of genomes vary widely. Therefore, it can be challenging to curate a list of genes with high-confidence gene models across reference genomes. This is often an important first step towards identifying key genetic factors for important traits. Here we present a draft genome of P. communis ‘d’Anjou’ and an improved assembly of the latest P. communis ‘Bartlett’ genome. To study gene families involved in tree architecture in European pear and other rosaceous species, we developed a workflow using a collection of bioinformatic tools towards curation of gene families of interest across genomes. This lays the groundwork for future functional studies in pear tree architecture. Importantly, our workflow can be easily adopted for other plant genomes and gene families of interest.
Evaluating the contribution of aestivation to the persistence of malaria mosquitoes through the Sahelian dry season using stable isotopes
Authors: Faiman Roy , Yaro Alpha S. , Dao Adama , Sanogo Zana L. , Diallo Moussa , Samake Djibril , Yossi Ousmane , Veru Laura R. , Graber Leland C. , Conte Abigail R. , Kouam Cedric , Krajacich Benjamin J. , Lehmann Tovi
Published: November 2021

Data suggests the malaria vector Anopheles coluzzii persists in the Sahel by dry-season aestivation though evidence is scant. We have marked Anopheles mosquitoes using deuterium (2H) to assess the contribution of aestivation to persistence of mosquitoes through the seven-month dry season. If local aestivation is the only way A. coluzzii persists, the frequency of marked mosquitoes should remain stable throughout, whereas finding no marked mosquitoes would be evidence against aestivation. Larval sites were spiked with 2H at the end of the 2017 wet season in two Sahelian villages in Mali. We monitored 2H-enriched populations until the onset of rains. By the end of the enrichment period, 33% of A. coluzzii mosquitoes were clearly marked. Expectedly, 2H levels in marked mosquitoes degraded over time, resulting in a partial overlap of the marked and non-marked 2H distributions. We utilized three methods to estimate the fraction of marked mosquitoes in the population. Seven months after enrichment, 7% of the population had 2H values above the highest pre-enrichment value. An excess of 21% exceeded the 3rd quartile of the pre-enrichment population. A finite mixed population model showed 2.5% represented a subpopulation of marked mosquitoes with elevated 2H, compatible with our predictions. We provide evidence that aestivation is a major persistence mechanism of A. coluzzii in the Sahel, contributing at least 20% of the adults at the onset of rains, suggesting A. coluzzii utilizes multiple persistence strategies enabling its populations rapid buildup, facilitating subsequent malaria resurgence. These may complicate vector control and malaria elimination campaigns.

Significance statement

Here we estimated the contribution of aestivation to the persistence of mosquitoes through the seven-month long dry season, by marking a known fraction of the adult population through larval site 2H-spiking by the end of the wet season and assessing the change in this fraction through the dry season, until after the onset of the first rain of the subsequent wet season. In a mark-release-recapture study using stable isotopes, we provide compelling evidence that the primary Sahelian malaria vector Anopheles coluzzii aestivates on a population-scale, contributing at least 20% of the adults which reestablish the population of the subsequent wet season. The capacity to use multiple strategies of persistence in time and space might complicate vector control and elimination campaigns.
Self-organization of in vitro neuronal assemblies drives to complex network topology
Authors: Antonello Priscila C. , Varley Thomas F. , Beggs John , Porcionatto Marimelia , Sporns Olaf , Faber Jean
Published: November 2021

Activity-dependent self-organization plays an important role in the formation of specific and stereotyped connectivity patterns in neural circuits. By combining neuronal cultures, tools with approaches from network neuroscience and information theory, we can study how complex network topology emerges from local neuronal interactions. We constructed effective connectivity networks using a transfer entropy analysis of electrophysiological signals recorded from rat embryo dissociated hippocampal neuron cultures between 6 and 35 days in vitro to investigate how the neuronal network topology evolves during maturation. The methodology for constructing the networks considered the synapse delay and addressed the influence of firing rate and population bursts as well as spurious effects on the inference of connections. We found that the number of links in the networks grew over the course of development, shifting from a segregated to a more integrated architecture. As part of this progression, three significant aspects of complex network topology emerged. In agreement with previous in silico and in vitro studies, a small-world architecture was detected, largely due to strong clustering among neurons. Additionally, the networks developed in a modular community topology, with most modules comprising nearby neurons. Finally, highly active neurons acquired topological characteristics that made them important nodes to the network and integrators of communities. These findings leverage new insights into how neuronal effective network topology relates to neuronal assembly self-organization mechanisms.
Modeling naturalistic face processing in humans with deep convolutional neural networks
Authors: Jiahui Guo , Feilong Ma , Visconti di Oleggio Castello Matteo , Nastase Samuel A. , Haxby James V. , Gobbini M. Ida
Published: November 2021

Deep convolutional neural networks (DCNNs) trained for face identification can rival and even exceed human-level performance. The ways in which the internal face representations in DCNNs relate to human cognitive representations and brain activity are not well understood. Nearly all previous studies focused on static face image processing with rapid display times and ignored the processing of naturalistic, dynamic information. To address this gap, we developed the largest naturalistic dynamic face stimulus set in human neuroimaging research (700+ naturalistic video clips of unfamiliar faces). We used this novel naturalistic dataset to compare representational geometries estimated from DCNNs, behavioral responses, and brain responses. We found that DCNN representational geometries were consistent across architectures, cognitive representational geometries were consistent across raters in a behavioral arrangement task, and neural representational geometries in face areas were consistent across brains. Representational geometries in late, fully-connected DCNN layers, which are optimized for individuation, were much more weakly correlated with cognitive and neural geometries than were geometries in late-intermediate layers. The late-intermediate face-DCNN layers successfully matched cognitive representational geometries, as measured with a behavioral arrangement task that primarily reflected categorical attributes, and correlated with neural representational geometries in known face-selective topographies. Our study suggests that current DCNNs successfully capture neural cognitive processes for categorical attributes of faces, but less accurately capture individuation and dynamic features.
Analysis of the computational strategy of a detailed laminar cortical microcircuit model for solving the image-change-detection task
Authors: Scherr Franz , Maass Wolfgang
Published: November 2021

The neocortex can be viewed as a tapestry consisting of variations of rather stereotypical local cortical microcircuits. Hence understanding how these microcircuits compute holds the key to understanding brain function. Intense research efforts over several decades have culminated in a detailed model of a generic cortical microcircuit in the primary visual cortex from the Allen Institute. We are presenting here methods and first results for understanding computational properties of this largescale data-based model. We show that it can solve a standard image-change-detection task almost as well as the living brain. Furthermore, we unravel the computational strategy of the model and elucidate the computational role of diverse subtypes of neurons. Altogether this work demonstrates the feasibility and scientific potential of a methodology based on close interaction of detailed data and large-scale computer modelling for understanding brain function.
Awake ripples enhance emotional memory encoding in the human brain
Authors: Zhang Haoxin , Skelin Ivan , Ma Shiting , Paff Michelle , Yassa Michael A. , Knight Robert T. , Lin Jack J.
Published: November 2021

Intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task reveal increased awake sharp-wave/ripples (aSWR) after encoding of emotional compared to neutral stimuli. Further, post-encoding aSWR-locked memory reinstatement in the amygdala and the hippocampus was predictive of later memory discrimination. These findings provide electrophysiological evidence that post-encoding aSWRs enhance memory for emotional events.
In silicodrug discovery strategies identified ADMET properties of decoquinate RMB041 and its potential drug targets againstMycobacterium Tuberculosis
Authors: Knoll Kirsten E. , van der Walta Mietha M. , Loots Du Toit
Published: November 2021

The highly adaptive cellular response ofMycobacterium tuberculosisto various antibiotics and the high costs for clinical trials, hampers the development of novel antimicrobial agents with improved efficacy and safety. Subsequently,in silicodrug screening methods are more commonly being used for the discovery and development of drugs, and have been proven useful for predicting the pharmacokinetics, toxicities, and targets, of prospective new antimicrobial agents. In this investigation we used a reversed target fishing approach to determine potential hit targets and their possible interactions betweenM. tuberculosisand decoquinate RMB041, a propitious new antituberculosis compound. Two of the thirteen identified targets, Cyp130 and BlaI, were strongly proposed as optimal drug-targets for dormantM. tuberculosis, of which the first showed the highest comparative binding affinity to decoquinate RMB041. The metabolic pathways associated to the selected target proteins were compared to previously published molecular mechanisms of decoquinate RMB041 againstM. tuberculosis, whereby we confirmed disrupted metabolism of proteins, cell wall components, and DNA. We also described the steps within these pathways that are inhibited and elaborated on decoquinate RMB041’s activity against dormantM. tuberculosis. This compound has previously showed promisingin vitrosafety and good oral bioavailability, which were both supported by thisin silicostudy. The pharmacokinetic properties and toxicity of this compound were predicted and investigated using the online tools pkCSM and SwissADME, and Discovery Studio software, which furthermore supports previous safety and bioavailability characteristics of decoquinate RMB041 for use as an antimycobacterial medication.
Trajectories: a framework for detecting temporal clinical event sequences from health data standardized to the OMOP Common Data Model
Authors: Künnapuu Kadri , Ioannou Solomon , Ligi Kadri , Kolde Raivo , Laur Sven , Vilo Jaak , Rijnbeek Peter R. , Reisberg Sulev
Published: November 2021

Objective

To develop a framework for identifying prominent clinical event trajectories from OMOP-formatted observational healthcare data.

Methods

A four-step framework based on significant temporal event pair detection is described and implemented as an open-source R package. It is used on a population-based Estonian dataset to first replicate a large Danish population-based study and second, to conduct a disease trajectory detection study for Type 2 Diabetes patients in the Estonian and Dutch databases as an example.

Results

As a proof of concept, we apply the methods in the Estonian database and provide a detailed breakdown of our findings. All Estonian population-based event pairs are shown. We compare the event pairs identified from Estonia to Danish and Dutch data and discuss the causes of the differences.

Conclusions

For the first time, there is a complete software package for detecting disease trajectories in health data.
Semi-supervised single-cell cross-modality translation using Polarbear
Authors: Zhang Ran , Meng-Papaxanthos Laetitia , Vert Jean-Philippe , Noble William Stafford
Published: November 2021

The emergence of single-cell co-assays enables us to learn to translate between single-cell modalities, potentially offering valuable insights from datasets where only one modality is available. However, the sparsity of single-cell measurements and the limited number of cells measured in typical co-assay datasets impedes the power of cross-modality translation. Here, we propose Polarbear, a semi-supervised translation framework to predict cross-modality profiles that is trained using a combination of co-assay data and traditional “single-assay” data. Polarbear uses single-assay and co-assay data to train an autoencoder for each modality and then uses just the co-assay data to train a translator between the embedded representations learned by the autoencoders. With this approach, Polarbear is able to translate between modalities with improved accuracy relative to state-of-the-art translation techniques. As an added benefit of the training procedure, we show that Polarbear also produces a matching of cells across modalities.
Slow fluctuations in ongoing brain activity decrease in amplitude with ageing yet their impact on task-related evoked responses is dissociable from behaviour
Authors: Ribeiro Maria J. , Castelo-Branco Miguel
Published: November 2021

In humans, ageing is characterized by decreased brain signal variability and increased behavioural variability. To understand how reduced brain variability segregates with increased behavioural variability, we investigated the association between reaction time variability, evoked brain responses and ongoing brain signal dynamics, in young (N = 36) and older adults (N = 39). We studied the electroencephalogram (EEG) and pupil size fluctuations to characterize the cortical and arousal responses elicited by a cued go/no-go task. Evoked responses were strongly modulated by slow (< 2 Hz) fluctuations of the ongoing signals, which presented reduced power in the older participants. Although variability of the evoked responses was lower in the older participants, once we adjusted for the effect of the ongoing signal fluctuations, evoked responses were equally variable in both groups. Moreover, the modulation of the evoked responses caused by the ongoing signal fluctuations had no impact on reaction time, thereby explaining why although ongoing brain signal variability is decreased in older individuals, behavioural variability is not. Finally, we showed that adjusting for the effect of the ongoing signal was critical to unmask the link between neural responses and behaviour.