bluuebunny/crossref_metadata_2025 huggingface dataset:
Corchorus hirtus (Orinoco jute).
Authors: Dube Shruti
Published: May 2021

Genetics: Most Corchorus species are diploids with 2n = 14, while wild species like, C. cunninghamii, C. hirtus, C. junodii, and C. siliquosus are similar in chromosome structure and are tetraploids (Belay, 2011). C. hirtus has a chromosome number 2n=4x=28 (Sinha et al., 2011; Flora of North American Editorial Committee, 2016). Physiology and Phenology: C. hirtus flowers and fruits all year (Axelrod, 2011). The flowers are bright yellow and 1.5 cm wide, and open in the afternoon (Missouri Botanical Garden, 2016). Reproductive Biology: Most Corchorus species can be identified during the reproductive stage using capsule and seed morphology (Belay, 2011). Seed is the main medium of reproduction (Mascarenhas et al., 1995). Ideal germination conditions in the laboratory have been found to be 31°C, 12/12 meaning seeds were incubated at 31°C during 12 light hours (Royal Botanical Gardens Kew, 2008). Environmental Requirements: C. hirtus needs a tropical climate to grow but it is also present in some southern states of the USA including Arizona, Alabama and Florida. It is usually found in deciduous tropical forests, semi-deciduous and evergreen tropical forests. It prefers soils that are well drained and mostly calcareous (Mas and Lugo-Torres, 2013).
Reflexing Suspicious β-Region Findings on Capillary Serum Protein Electrophoresis to Immunofixation or Immunosubtraction for Detecting Monoclonal Proteins
Authors: Kitson Amanda L , Taylor Alexander S , Giacherio Donald A , Keren David F
Published: May 2021

Objectives

Monoclonal immunoglobulins (M-proteins) that migrate in the β region on serum protein electrophoresis (SPEP) are often cloaked by this region’s normal constituents. The present study interrogates the utility of using both quantitative and qualitative alterations in β-region bands for detection of β-migrating M-proteins.

Methods

Consecutive SPEP cases analyzed by capillary electrophoresis were searched to identify the initial workup on 1,841 patients with increased total β regions, suspicious β-region findings resulting in reflex immunofixation (IFE), or immunosubtraction (ISUB). To augment quantitative information, separate β1 and β2 measurements were established and retrospectively used to evaluate their sensitivity for M-protein detection.

Results

We identified M-proteins in 205 (11.1%) cases, including immunoglobulin A (IgA) (54%), IgG (24%), IgM (13%), and free light chain (9%) isotypes. Of the 15 cases flagged by separate β1 and β2 measurements that were not identified by total β-region measurement, 1 progressed to myeloma. Of the 56 β-migrating M-proteins identified by qualitative features but without increase in any of the β-region measurements, 1 progressed to myeloma.

Conclusions

A combination of separate measurements for β1 and β2 regions together with detection of β-region distortions increase sensitivity for identifying β-migrating M-proteins via reflex IFE or ISUB.
Impact of clinical decision support therapeutic interchanges on hospital discharge medication omissions and duplications
Authors: Maxwell Erin , Amerine James , Carlton Glenda , Cruz Jennifer L , Pappas Ashley L , Heindel Gregory A
Published: May 2021

Purpose

Automatic therapeutic substitution (ATS) protocols are formulary tools that allow for provider-selected interchange from a nonformulary preadmission medication to a formulary equivalent. Previous studies have demonstrated that the application of clinical decision support (CDS) tools to ATS can decrease ATS errors at admission, but there are limited data describing the impact of CDS on discharge errors. The objective of this study was to describe the impact of CDS-supported interchanges on discharge prescription duplications or omissions.

Methods

This was a single-center, retrospective cohort study conducted at an academic medical center. Patients admitted between June 2017 and August 2019 were included if they were 18 years or older at admission, underwent an ATS protocol–approved interchange for 1 of the 9 included medication classes, and had a completed discharge medication reconciliation. The primary outcome was difference in incidence of therapeutic duplication or omission at discharge between the periods before and after CDS implementation.

Results

A total of 737 preimplementation encounters and 733 postimplementation encounters were included. CDS did not significantly decrease the incidence of discharge duplications or omissions (12.1% vs 11.2%; 95% confidence interval [CI], –2.3% to 4.2%) nor the incidence of admission duplication or inappropriate reconciliation (21.4% vs 20.7%; 95% CI, –3.4% to 4.8%) when comparing the pre- and postimplementation periods. Inappropriate reconciliation was the primary cause of discharge medication errors for both groups.

Conclusion

CDS implementation was not associated with a decrease in discharge omissions, duplications, or inappropriate reconciliation. Findings highlight the need for thoughtful medication reconciliation at the point of discharge.
Enhanced stress-resilience training for surgical trainees
Authors: Luton O W , James O P , Mellor K , Eley C , Hopkins L , Robinson D B T , Lebares C C , Powell A G M T , Lewis W G , Egan R J
Published: May 2021

Introduction

Core surgical training programmes are associated with a high risk of burnout. This study aimed to assess the influence of a novel enhanced stress-resilience training (ESRT) course delivered at the start of core surgical training in a single UK statutory education body.

Method

All newly appointed core surgical trainees (CSTs) were invited to participate in a 5-week ESRT course teaching mindfulness-based exercises to develop tools to deal with stress at work and burnout. The primary aim was to assess the feasibility of this course; secondary outcomes were to assess degree of burnout measured using Maslach Burnout Inventory (MBI) scoring.

Results

Of 43 boot camp attendees, 38 trainees completed questionnaires, with 24 choosing to participate in ESRT (63.2 per cent; male 13, female 11, median age 28 years). Qualitative data reflected challenges delivering ESRT because of arduous and inflexible clinical on-call rotas, time pressures related to academic curriculum demands and the concurrent COVID-19 pandemic (10 of 24 drop-out). Despite these challenges, 22 (91.7 per cent) considered the course valuable and there was unanimous support for programme development. Of the 14 trainees who completed the ESRT course, nine (64.3 per cent) continued to use the techniques in daily clinical work. Burnout was identified in 23 trainees (60.5 per cent) with no evident difference in baseline MBI scores between participants (median 4 (range 0–11) versus 5 (1–11), P = 0.770). High stress states were significantly less likely, and mindfulness significantly higher in the intervention group (P < 0.010); MBI scores were comparable before and after ESRT in the intervention cohort (P = 0.630, median 4 (range 0–11) versus 4 (1–10)).

Discussion

Despite arduous emergency COVID rotas ESRT was feasible and, combined with protected time for trainees to engage, deserves further research to determine medium-term efficacy.
The Significance of Space: Experiences of Arab Social Work Professionals with EAGALA Equine-Assisted Learning
Authors: Moshe-Grodofsky Merav , Allassad Alhuzail Nuzha
Published: May 2021

The value of equine-assisted interventions that promote growth and learning is increasingly recognised in professional practice. The aim of this study was to examine how equine-assisted intervention enhanced personal and professional growth for social work professionals. Arab social workers from the social service department in the Bedouin city Hura, Israel participated in three workshops based on the Equine Assisted Growth and Learning Association (EAGALA) model. Observations conducted through the workshops, debriefing sessions with participants and fourteen in-depth semi-structured interviews were analysed. Analysis exposed the importance of space in promoting development. Specifically, participants described the value of space for self-reflection, the importance of the space within and between relationships and space as a site for team building. Changes amongst the participants from dependence on external instruction to autonomous decision making, enhanced spontaneous activity with the horses and mutual assistance were identified. This is the first equine-assisted learning workshop and research conducted with social workers in Israel. The results highlight the value of equine-assisted learning as a new avenue to help grow social work professionals as they continue to work with their clientele. Results suggest that there is potential for equine-assisted interventions to support social workers internationally.
Substantial decline in hospital admissions for heart failure accompanied by increased community mortality during COVID-19 pandemic
Authors: Shoaib Ahmad , Van Spall Harriette G C , Wu Jianhua , Cleland John G F , McDonagh Theresa A , Rashid Muhammad , Mohamed Mohamed O , Ahmed Fozia Z , Deanfield John , de Belder Mark , Gale Chris P , Mamas Mamas A
Published: May 2021

Aims

We hypothesized that a decline in admissions with heart failure during COVID-19 pandemic would lead to a reciprocal rise in mortality for patients with heart failure in the community.

Methods and results

We used National Heart Failure Audit data to identify 36 974 adults who had a hospital admission with a primary diagnosis of heart failure between February and May in either 2018, 2019, or 2020. Hospital admissions for heart failure in 2018/19 averaged 160/day but were much lower in 2020, reaching a nadir of 64/day on 27 March 2020 [incidence rate ratio (IRR): 0.40, 95% confidence interval (CI): 0.38–0.42]. The proportion discharged on guideline-recommended pharmacotherapies was similar in 2018/19 compared to the same period in 2020. Between 1 February–2020 and 31 May 2020, there was a 29% decrease in hospital deaths related to heart failure (IRR: 0.71, 95% CI: 0.67–0.75; estimated decline of 448 deaths), a 31% increase in heart failure deaths at home (IRR: 1.31, 95% CI: 1.24–1.39; estimated excess 539), and a 28% increase in heart failure deaths in care homes and hospices (IRR: 1.28, 95% CI: 1.18–1.40; estimated excess 189). All-cause, inpatient death was similar in the COVID-19 and pre-COVID-19 periods [odds ratio (OR): 1.02, 95% CI: 0.94–1.10]. After hospital discharge, 30-day mortality was higher in 2020 compared to 2018/19 (OR: 1.57, 95% CI: 1.38–1.78).

Conclusion

Compared with the rolling daily average in 2018/19, there was a substantial decline in admissions for heart failure but an increase in deaths from heart failure in the community. Despite similar rates of prescription of guideline-recommended therapy, mortality 30 days from discharge was higher during the COVID-19 pandemic period.
Successful uterine-sparing surgical management in a patient with a large multi-fibroid uterus
Authors: Holden Lucy M
Published: May 2021

Uterine fibroids are a common gynaecological condition. A key factor when deciding on surgical approach for fibroid management is a patient’s age and desire for fertility with uterine-sparing treatment generally recommended in women who are aiming for future pregnancies. This case report discusses a woman who presented with a very large multi-fibroid uterus. In this case, a hysterectomy was recommended due to safety concerns however, this advice was declined as the patient desired uterine preservation. Fertility testing showed that the patient was not peri-menopausal and abdominal myomectomy was safely performed to good effect. This case report outlines the surgical approach undertaken, in addition to considerations for fertility and pregnancy management.
Nephrotoxicity of immune checkpoint inhibitor therapy: a pharmacovigilance study
Authors: Haeuser Lorine , Marchese Maya , Cone Eugene B , Noldus Joachim , Bayliss George , Kilbridge Kerry Laing , Trinh Quoc-Dien
Published: May 2021

Background

Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADRs) occur in every organ system, often due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes would be reported more frequently in association with ICIs.

Methods

We analyzed VigiBase, the World Health Organization pharmacovigilance database, to identify renal ADRs (rADRs), such as nephritis, nephropathy and vascular disorders, reported in association with ICI therapy. We performed a disproportionality analysis to explore if rADRs were reported at a different rate with one of the ICI drugs compared with rADRs in the entire database, using an empirical Bayes estimator as a significance screen and defining the effect size with a reporting odds ratio (ROR).

Results

We found 2341 rADR for all examined ICI drugs, with a disproportionality signal solely for nephritis [ROR = 3.67, 95% confidence interval (CI) 3.34–4.04]. Examining the different drugs separately, pembrolizumab, nivolumab and ipilimumab + nivolumab combination therapy had significantly higher reporting odds of nephritis than the other ICI drugs (ROR = 4.54, 95% CI 3.81–5.4; ROR = 3.94, 95% CI 3.40–4.56; ROR 3.59, 95% CI 2.71–4.76, respectively).

Conclusions

Using a pharmacovigilance method, we found increased odds of nephritis when examining rADRs associated with ICI therapy. Pembrolizumab, nivolumab and a combination of ipilimumab + nivolumab showed the highest odds. Clinicians should consider these findings and be aware of the increased risk of nephritis, especially in patients treated with pembrolizumab, when administering ICI therapy.
Standardized Treatment and Assessment Pathway Improves Mortality in Adults With Methicillin-resistant Staphylococcus aureus Bacteremia: STAPH Study
Authors: Alosaimy Sara , Lagnf Abdalhamid M , Morrisette Taylor , Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Scipione Marco R , Zhao Jing J , Mynatt Ryan , Herbin Shelbye , Dhar Sorabh , Chopra Teena , Janisse James , Rebold Nicholas , Pogue Jason M , Rybak Michael J
Published: May 2021

Background

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN) and daptomycin (DAP) are combined with beta-lactams (BLs), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality.

Methods

The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard of care (VAN or DAP) and a mandatory Infectious Diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013 and 2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables.

Results

Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared with prepathway (PRE) patients (n = 379), those treated postpathway (POST; n = 434) had a significant reduction in 30-day and 90-day mortality: 9.7% in POST vs 15.6% in PRE (P = .011) and 12.2% in POST vs 19.0% in PRE (P = .007), respectively.

The incidence of acute kidney injury (AKI) was higher in the PRE compared with the POST group: 9.6% vs 7.2% (P = .282), respectively. After adjusting for confounding variables including Infectious Diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% CI, 0.375–0.986).

Conclusions

Implementation of an MRSA BSI treatment pathway with early use of BL reduced mortality with no increased rate of AKI. Further prospective evaluation of this pathway approach is warranted.
Modeling Poliovirus Surveillance and Immunization Campaign Quality Monitoring Costs for Pakistan and Afghanistan for 2019–2023
Authors: Kalkowska Dominika A , Pallansch Mark A , Cochi Stephen L , Thompson Kimberly M
Published: May 2021

Background

The Global Polio Eradication Initiative (GPEI) Strategic Plan for 2019–2023 includes commitments to monitor the quality of immunization campaigns using lot quality assurance sampling surveys (LQAS) and to support poliovirus surveillance in Pakistan and Afghanistan.

Methods

We analyzed LQAS and poliovirus surveillance data between 2016 and 2020, which included both acute flaccid paralysis (AFP) case-based detection and the continued expansion of environmental surveillance (ES). Using updated estimates for unit costs, we explore the costs of different options for future poliovirus monitoring and surveillance for Pakistan and Afghanistan.

Results

The relative value of the information provided by campaign quality monitoring and surveillance remains uncertain and depends on the design, implementation, and performance of the systems. Prospective immunization campaign quality monitoring (through LQAS) and poliovirus surveillance will require tens of millions of dollars each year for the foreseeable future for Pakistan and Afghanistan.

Conclusions

LQAS campaign monitoring as currently implemented in Pakistan and Afghanistan provides limited and potentially misleading information about immunization quality. AFP surveillance in Pakistan and Afghanistan provides the most reliable evidence of transmission, whereas ES provides valuable supplementary information about the extent of transmission in the catchment areas represented at the time of sample collection.
Monoclonal Antibodies for Early Treatment of COVID-19 in a World of Evolving SARS-CoV-2 Mutations and Variants
Authors: Pogue Jason M , Lauring Adam S , Gandhi Tejal N , Marshall Vincent D , Eschenauer Gregory A , Nagel Jerod L , Baang Ji Hoon , Zhou Shiwei , Valesano Andrew L , Petty Lindsay A
Published: May 2021

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.
tDCS effect on prosocial behavior: a meta-analytic review
Authors: Yuan Bo , Tolomeo Serenella , Yang Chunliang , Wang Ying , Yu Rongjun
Published: May 2021

Previous studies have shown that transcranial direct current stimulation (tDCS) could potentially promote prosocial behaviors. However, results from randomized controlled trials are inconsistent. The current meta-analysis aimed to assess the effects of anodal and cathodal tDCS using single-session protocols on prosocial behaviors in healthy young adults and explore potential moderators of these effects. The results showed that compared with sham stimulation, anodal (excitatory) stimulation significantly increased (g = 0.27, 95% CI [0.11, 0.43], Z = 3.30, P = 0.001) and cathodal (inhibitory) stimulation significantly decreased prosocial behaviors (g = −0.19, 95% CI [−0.39, −0.01], Z = −1.95, P = 0.051) using a multilevel meta-analytic model. These effects were not significantly modulated by stimulation parameters (e.g. duration, intensity and site) and types of prosocial behavior. The risk of publication bias for the included effects was minimal, and no selective reporting (e.g. P-hacking) was found in the P-curve analysis. This meta-analysis showed that both anodal and cathodal tDCS have small but significant effects on prosocial behaviors. The current study provides evidence that prosocial behaviors are linked to the activity of the ‘social brain’. Future studies are encouraged to further explore whether tDCS could effectively treat social dysfunctions in psychiatry disorders.
Changes of renal transporters in the kinetic process of VCM-induced nephrotoxicity in mice
Authors: Li Hongjing , Yang Qiaoling , Gui Mingzhu , Ding Lili , Yang Li , Sun Huajun , Li Zhiling
Published: May 2021

Renal transporters involved in tubular excretion pathway are considered to be the key concern in drug evaluations in nephrotoxicity. However, the relationship between the alternation of renal transporters and the kinetic process of vancomycin (VCM)-induced nephrotoxicity has not been fully elucidated. The present study investigated the alteration of renal transporters expression in the kinetic process of VCM-induced nephrotoxicity in mice. C57BL/6 mice were administrated with normal saline or VCM for 7 days. Biochemical and pathological analyses were conducted to investigate the nephrotoxicity induced by VCM administration. Renal oxidative status, plasma, and kidney content of VCM were monitored. Quantitative real-time polymerase chain reaction and immunohistochemistry analyses were performed to analyze the expression of renal transporters. Finally, our data showed that the exposure of VCM (400 mg/kg) caused a slight nephrotoxicity in mice, whereas exposure of VCM (600 mg/kg) resulted in the severe nephrotoxicity in mice as evidenced by biochemical parameters and renal morphological changes. In addition, the accumulation of VCM in kidney is higher than plasma. Interestingly, VCM (600 mg/kg, body weight) resulted in the induction of Oct2–Mate1 and Oat1/3–Mrp2/Mrp4/Bcrp pathways. However, VCM (400 mg/kg, body weight) caused the induction of Oct2–Mate1/Mate2 and Oat1/3–Mrp4/Bcrp pathways. The changes of renal transporters in association with the kinetic process of VCM-induced nephrotoxicity may exert important practical implications for its optimal use in clinic.
Predictors of SARS CoV-2 Infection Among Healthcare Workers: The Impact of Community-Hospital Gradient
Authors: Pınarlık Fatihan , Genç Zeliha , Tekin Süda , Kapmaz Mahir , Ergönül Önder
Published: May 2021

Aim

We aimed to detect the risk factors for SARS-CoV-2 infection among healthcare workers (HCWs) in 2020, before vaccination era.

Methods

We surveyed the SARS-CoV-2 infection among the HCWs in a hospital by screening of antibody levels and detection of viral RNA by reverse transcription polymerase chain reaction (RT-PCR) between May 2020 to December 2020. Occupational and non-occupational potential predictors of disease were surveyed for the HCWs included in this study.

Results

Among 1925 personnel in the hospital, 1732 were included to the study with the response rate of 90%. Overall seroprevalence was 15% at the end of 2020, before vaccinations started. In multivariate analysis, being janitorial staff (OR:2.24, CI:1.21-4.14, p=0.011), being medical secretary (OR: 4.17, CI: 2.12-8.18, p<0.001), having at least one household member with COVID-19 diagnosis (OR:8.98, CI: 6.64-12.15, p<0.001) and number of household members >3 (OR:1.67, CI:1.26-2.22, p<0.001) were found to be significantly associated with SARS-CoV-2 infection.

Conclusion

By the end of 2020, just before the era of vaccination and variants, seroprevalence was 15% among HCWs. Medical secretary and janitorial staff were under increased risk of SARS-CoV-2 infection. Community-hospital gradient can explain the mode of transmission for infection among HCWs. In the setting of this study, community measures were less strict, whereas hospital infection control was adequate and provided necessary personal protective equipment. Increasing risk in larger households and households with diagnosed COVID-19 patient indicates community acquired transmission of the infection.
Diagnostic Accuracy in Bronchial Carcinoid tumors is Dependent of Biopsy Size
Authors: Reuling E.M.B.P. , Naves D.D. , Daniels J.M.A. , Dickhoff C. , Kortman P.C. , Broeckaert M.A.M.B. , Plaisier P.W. , Thunnissen Erik , Radonic T.
Published: May 2021

Objective

Recently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid.

Methods

Biopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists.

Results

After screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring <2 mm2, 79% were classified as discordant and 52% of the discordant biopsies measured <4 mm2.

Conclusion

Histological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies <4 mm2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.
Towards Internationally standardised humoral Immune Correlates of Protection from SARS-CoV-2 infection and COVID-19 disease
Authors: Castillo-Olivares Javier , Wells David A. , Ferrari Matteo , Chan Andrew , Smith Peter , Nadesalingam Angalee , Paloniemi Minna , Carnell George , Ohlendorf Luis , Cantoni Diego , Mayora-Neto Martin , Palmer Phil , Tonks Paul , Temperton Nigel , Wagner Ralf , Neckermann Patrick , Peterhoff David , Doffinger Rainer , Kempster Sarah , Otter Ashley , Semper Amanda , Brooks Tim , Page Mark , Albecka Anna , James Leo C. , Briggs John , Schwaeble Wilhelm , Baxendale Helen , Heeney Jonathan
Published: May 2021

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD, and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study, was to identify biomarkers of humoral immunity that could be used as candidate CoP in internationally accepted unitage. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (INU) for virus neutralisation assays or International Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG / IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD / S binding assays. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.
Synergistic epistasis of the deleterious effects of transposable elements
Authors: Lee Yuh Chwen G.
Published: May 2021

The replicative nature and generally deleterious effects of transposable elements (TEs) give rise to an outstanding question about how TE copy number is stably contained in host populations. Classic theoretical analyses predict that, when the decline in fitness due to each additional TE insertion is greater than linear, or when there is synergistic epistasis, selection against TEs can result in a stable equilibrium of TE copy number. While several mechanisms are predicted to yield synergistic deleterious effects of TEs, we lack empirical investigations of the presence of such epistatic interactions. Purifying selection with synergistic epistasis generates repulsion linkage between deleterious alleles and, accordingly, an underdispersed distribution for the number of deleterious mutations among individuals. We investigated this population genetic signal in an African Drosophila melanogaster population and found evidence for synergistic epistasis among TE insertions, especially those expected to have large fitness impacts. Curiously, even though ectopic recombination has long been predicted to generate nonlinear fitness decline with increased TE copy number, TEs predicted to suffer higher rates of ectopic recombination are not more likely to be underdispersed. On the other hand, underdispersed TE families are more likely to show signatures of deleterious epigenetic effects and stronger ping-pong signals of piRNA amplification, a hypothesized source from which synergism of TE-mediated epigenetic effects arises. Our findings set the stage for investigating the importance of epistatic interactions in the evolutionary dynamics of TEs.
Bimanual digit training improves right-hand dexterity in older adults by reactivating declined ipsilateral motor-cortical inhibition
Authors: Naito Eiichi , Morita Tomoyo , Hirose Satoshi , Kimura Nodoka , Okamoto Hideya , Kamimukai Chikako , Asada Minoru
Published: May 2021

Improving deteriorated sensorimotor functions in older individuals is a social necessity in a super-aging society. Previous studies suggested that the declined interhemispheric sensorimotor inhibition observed in older adults is associated with their deteriorated hand/finger dexterity. Here, we examined whether bimanual digit exercises, which can train the interhemispheric inhibitory system, improve deteriorated hand/finger dexterity in older adults. Forty-eight healthy, right-handed, older adults (65-78 years old) were divided into two groups, i.e., the bimanual (BM) digit training and right-hand (RH) training groups, and intensive daily training was performed for 2 months. Before and after the training, we evaluated individual right hand/finger dexterity using a peg task, and the individual state of interhemispheric sensorimotor inhibition by analyzing ipsilateral sensorimotor deactivation via functional magnetic resonance imaging when participants experienced a kinesthetic illusory movement of the right-hand without performing any motor tasks. Before training, the degree of reduction/loss of ipsilateral motor-cortical deactivation was associated with dexterity deterioration. After training, the dexterity improved only in the BM group, and the dexterity improvement was correlated with reduction in ipsilateral motor-cortical activity. The capability of the brain to inhibit ipsilateral motor-cortical activity during a simple right-hand sensory-motor task is tightly related to right-hand dexterity in older adults.
The Neural Correlates of Working Memory Training in Typically Developing Children – Working Paper
Authors: Jones J. S. , Adlam A-L. R. , Benatayallah A. , Milton F.
Published: May 2021

Working memory training improves children’s cognitive performance on untrained tasks; however, little is known about the underlying neural mechanisms. We investigated this in 32 typically developing children aged 10-14 years (19 girls and 13 boys; Devon, UK) using a randomized controlled design and multi-modal MRI. Training improved working memory performance and increased intrinsic functional connectivity between the bilateral intraparietal sulci. Furthermore, improvements in working memory were associated with greater recruitment of the left middle frontal gyrus on a complex span task. The repeated engagement of fronto-parietal regions during training may increase their activity and functional connectivity over time, affording greater working memory performance. We discuss the plausibility of generalizable cognitive benefits from a neurobiological perspective and implications for neurodevelopmental theory. This is not the version of record.
Schmidtea sp., from the S-W Romania (Platyhelminthes, Tricladida, Dugesiidae)
Authors: Felicia Babalean Anda
Published: May 2021

The morphology and the anatomy of the copulatory apparatus in a Dugesiidae population from the SW Romania are presented. The copulatory apparatus is characterized by intermingled bursal canal musculature and two distinct penis bulbs with two large seminal vesicles. Based on these morphological characters, the population is assigned to the “lugubris-polychroa” group of species, now belonging to the genusSchmidtea(de Vries & Sluys 1991). The copulatory apparatus is also characterised by the presence of an atrial fold, characteristic ofS. mediterranea. The assign of the morphotype here presented to the species level is delayed until integrative molecular analysis.
No one tool to rule them all: Prokaryotic gene prediction tool performance is highly dependent on the organism of study
Authors: Dimonaco Nicholas J. , Aubrey Wayne , Kenobi Kim , Clare Amanda , Creevey Christopher J.
Published: May 2021

Motivation

The biases in Open Reading Frame (ORF) prediction tools, which have been based on historic genomic annotations from model organisms, impact our understanding of novel genomes and metagenomes. This hinders the discovery of new genomic information as it results in predictions being biased towards existing knowledge. To date users have lacked a systematic and replicable approach to identify the strengths and weaknesses of any ORF prediction tool and allow them to choose the right tool for their analysis.

Results

We present an evaluation framework (ORForise) based on a comprehensive set of 12 primary and 60 secondary metrics that facilitate the assessment of the performance of ORF prediction tools. This makes it possible to identify which performs better for specific use-cases. We use this to assess 15 ab initio and model-based tools representing those most widely used (historically and currently) to generate the knowledge in genomic databases. We find that the performance of any tool is dependent on the genome being analysed, and no individual tool ranked as the most accurate across all genomes or metrics analysed. Even the top-ranked tools produced conflicting gene collections which could not be resolved by aggregation. The ORForise evaluation framework provides users with a replicable, data-led approach to make informed tool choices for novel genome annotations and for refining historical annotations.

Availability

https://github.com/NickJD/ORForise

Contact

nicholas@dimonaco.co.uk

Supplementary information

Supplementary data are available at bioRxiv online.
Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data
Authors: Dimitrov Daniel , Türei Dénes , Boys Charlotte , Nagai James S. , Ramirez Flores Ricardo O. , Kim Hyojin , Szalai Bence , Costa Ivan G. , Dugourd Aurélien , Valdeolivas Alberto , Saez-Rodriguez Julio
Published: May 2021

The growing availability of single-cell data has sparked an increased interest in the inference of cell-cell communication from this data. Many tools have been developed for this purpose. Each of them consists of a resource of intercellular interactions prior knowledge and a method to predict potential cell-cell communication events. Yet the impact of the choice of resource and method on the resulting predictions is largely unknown. To shed light on this, we created a framework, available athttps://github.com/saezlab/ligrec_decoupler, to facilitate a comparative assessment of methods for inferring cell-cell communication from single cell transcriptomics data and then compared 15 resources and 6 methods. We found few unique interactions and a varying degree of overlap among the resources, and observed uneven coverage in terms of pathways and biological categories. We analysed a colorectal cancer single cell RNA-Seq dataset using all possible combinations of methods and resources. We found major differences among the highest ranked intercellular interactions inferred by each method even when using the same resources. The varying predictions lead to fundamentally different biological interpretations, highlighting the need to benchmark resources and methods.

Findings

Built a framework to systematically combine 15 resources and 6 methods to estimate cell-cell communication from single-cell RNA data

Cell-cell communication resources are often built from the same original databases and very few interactions are unique to a single resource. Yet overlap varies among resources and certain biological terms are unevenly represented

Different methods and resources provided notably different results

The observed disagreement among the methods could have a considerable impact on the interpretation of results
Mast cell-specific receptor/corticotropin-releasing factor axis regulates alcohol withdrawal-associated headache
Authors: Son Hyeonwi , Zhang Yan , Shannonhouse John , Ishida Hirotake , Gomez Ruben , Akopian Armen , Kim Yu Shin
Published: May 2021

Rehabilitation from alcohol addiction or abuse is challenging due to alcohol withdrawal symptoms. Headache is a severe alcohol withdrawal symptom that frequently contributes to rehabilitation failure. Despite the need for treating alcohol withdrawal-induced headache, there is no appropriate therapeutic option available. Development of improved therapeutics will depend on obtaining a clearer understanding of alcohol withdrawal-induced headache pain mechanisms. Here, we show that the mast cell-specific receptor MrgprB2 controls development of alcohol withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces strong headache behaviors, including facial allodynia, facial pain expressions, and reduced walking movement, symptoms often observed in humans suffering from headache. Observed pain behaviors were abolished in MrgprB2-deficient mice. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia neurons in alcohol withdrawal mice, but not in MrgprB2-deficient mice. Corticotropin-releasing factor (CRF) was increased in dura mater after alcohol withdrawal. Injection of CRF into dura mater resulted in activation of trigeminal ganglia neurons and vasodilation, which was accompanied by headache behavior. In cells, CRF evoked Ca2+ transients via MrgprB2 or human MrgprX2. The results indicate that alcohol withdrawal causes headache via mast cell degranulation in dura mater. The process is under control of MrgprB2/MrgprX2, which would appear to represent a potential target for treating alcohol withdrawal-related headache.
Met is required for oligodendrocyte progenitor cell migration in Danio rerio
Authors: Ali Maria F. , Latimer Andrew J. , Wang Yinxue , Hogenmiller Leah , Fontenas Laura , Isabella Adam J. , Moens Cecilia B. , Yu Guoqiang , Kucenas Sarah
Published: May 2021

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.
Cell type-specific signal analysis in EWAS
Authors: Breeze Charles E.
Published: May 2021

Hundreds of epigenome-wide association studies (EWAS) have been performed, successfully identifying replicated epigenomic signals in processes such as ageing and smoking. Despite this progress, it remains a major challenge in EWAS to detect both cell type-specific and cell type confounding effects impacting study results. One way to identify these effects is through eFORGE (experimentally derived Functional element Overlap analysis of ReGions from EWAS), a published tool that uses 815 datasets from large-scale mapping studies to detect enriched tissues, cell types and genomic regions. Here, I show that eFORGE analysis can be extended to EWAS differentially variable positions (DVPs), identifying target cell types and tissues. In addition, I also show that eFORGE tissue-specific enrichment can be detected for sites below EWAS significance threshold. I develop on these and other analysis examples, extending our knowledge of eFORGE cell type- and tissue-specific enrichment results for different EWAS.
Istradefylline, an adenosine A2a receptor antagonist, ameliorates neutrophilic airway inflammation and psoriasis in mice
Authors: Tokano Mieko , Kawano Masaaki , Takagi Rie , Matsushita Sho
Published: May 2021

Objective

Extracellular adenosine is produced from secreted ATP by cluster of differentiation (CD)39 and CD73. Both are critical nucleotide metabolizing enzymes of the adenosine generating pathway and are secreted by neuronal or immune cells. Adenosine plays a role in energy processes, neurotransmission, and endogenous regulation of inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson’s disease. We have reported that adenosine primes hypersecretion of interleukin (IL)-17A via A2aR. Istradefylline, as well as an inhibitor of CD39 (ARL67156) and an inhibitor of CD73 (AMP-CP), suppressed IL-17A production, and the administration of istradefylline to mice with experimental autoimmune encephalomyelitis (EAE) led to the marked amelioration of the disease. These previous results suggest that adenosine is an endogenous modulator of neutrophilic inflammation. We investigated the effect of istradefylline, ARL67156 and AMP-CP on other mouse models of neutrophilic inflammation.

Methods

We tested the effect of istradefylline, ARL67156 and AMP-CP on OVA-induced neutrophilic airway inflammation or imiquimod (IMQ)-induced psoriasis in mice. These two model mice received these drugs orally or percutaneously, respectively. The production of IL-17A in the lung and ear thickness were used as an index of the effects.

Results

We show that istradefylline, ARL67156 and AMP-CP suppressed the OVA-induced IL-17A production in the lung and IMQ-induced psoriasis.

Conclusion

These results indicate that adenosine-mediated IL-17A production plays a role in neutrophilic inflammation models, and moreover, istradefylline, ARL67156, and AMP-CP are effective in animal models of neutrophilic inflammation. Some clinical relevancies in COVID-19 are discussed.
Evidence for Normalization as a Fundamental Operation Across the Human Visual Cortex
Authors: Doostani Narges , Hossein-Zadeh Gholam-Ali , Vaziri-Pashkam Maryam
Published: May 2021

Divisive normalization of the neural responses by the activity of the neighboring neurons has been proposed as a fundamental operation in the nervous system based on its success in predicting neural responses recorded in primate electrophysiology studies. Nevertheless, experimental evidence for the existence of this operation in the human brain is still scant. Here, using functional MRI, we explored the role of normalization across the visual hierarchy in the human visual cortex. Using stimuli form the two categories of human bodies and houses, we presented objects in isolation or in clutter and asked participants to attend or ignore the stimuli.Focusing on the primary visual area V1, the object-selective regions LO and pFs, and the category-selective regions EBA and PPA, we first modeled single-voxel responses using a weighted sum, a weighted average, and a normalization model and demonstrated that the response to multiple stimuli could best be described by a model that takes normalization into account. We then explored the observed effects of attention on cortical responses and demonstrated that these effects were predicted by the normalization model, but not by the weighted sum or the weighted average models. Our results thus provide compelling evidence for normalization as a canonical computation operating in the human brain.
Mitigating antimicrobial resistance with aspirin (acetylsalicylic acid) and paracetamol (acetaminophen): Conversion of doxycycline and minocycline resistant bacteria into sensitive in presence of aspirin and paracetamol
Authors: Singh Bhoj Raj
Published: May 2021

The emergence of antimicrobial resistance (AMR) stimulated research for alternatives antimicrobials, repurposing of other drugs, antibiotic adjuvants and alternative therapies for infections. Antimicrobial activity of NSAIDs is often reported and this study evaluated the antimicrobial potential of the two most common NSAIDs, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), against 293 clinical strains of bacteria. The ability of aspirin and paracetamol to convert minocycline and doxycyclin-resistant bacteria into sensitivity was also tested using micro-broth dilution assays used for determining minimum inhibitory concentration (MIC). Aspirin inhibited all 293 bacterial strains at ≤10.24 mg/ mL concentration. Except for one strain each of Serratia grimaceae and S, aureus paracetamol inhibited none of the 293 strains at 10.24 mg/ mL. Of the 293 strains 116 (39.59%) were sensitive (MIC ≤4 μg/mL) to doxycycline and 127 (43.34%) to minocycline. Of the selected 57 minocycline-resistant (MIC >4 μg/mL) strains aspirin converted 32 (56.14%) to minocycline-sensitive. Of the 49 doxycycline-resistant (MIC >4 μg/mL) strains tested in presence of aspirin 30 (61.22%) turned sensitive. Of the 34 doxycycline-resistant strains tested in presence of paracetamol 11 (32.35%) become sensitive. The study concluded that most of the bacterial strains were not susceptible to aspirin and paracetamol at their concentrations often available in plasma at maximum therapeutic dose levels and had no significant change in their susceptibility to doxycycline and minocycline. The study indicated the potential of aspirin and its combination with antibiotics in the development of therapeutically useful topical antimicrobial formulations.