bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dual-Platform Point-of-Care Test for Neurosyphilis Diagnosis
Authors: Gonzalez Hemil , Koralnik Igor Jerome , Huhn Gregory D. , Tantalo Lauren C. , Ritz Ethan M. , Orban Zachary , Marra Christina M.
Published: April 2021

Background

The diagnosis of neurosyphilis relies on cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein) and CSF–Venereal Disease Research Laboratory (VDRL) test. In resource-limited settings, the CSF-VDRL test may not be widely available.

Methods

We optimized a commercial immunochromatographic strip test, the DPP Chembio syphilis assay, for performance with CSF and tested centrifuged CSF samples of 71 patients with syphilis (35 with neurosyphilis and 36 without neurosyphilis). A CSF dilution of 1:4 was chosen based on agreement with CSF pools with documented results from the CSF-VDRL test and fluorescent treponemal antibody absorption test on CSF. Using an electronic reader, we obtained unit values of treponemal and nontreponemal antibodies for all study samples and generated a receiver operating characteristic curve; using the Youden index, we established diagnostic cutoffs with optimal sensitivity and specificity.

Results

Diagnostic sensitivity of the nontreponemal test was 80% (95% confidence interval, 63%–92%) and specificity was 97% (95% confidence interval, 85%–100%) for neurosyphilis diagnosis using a reactive CSF-VDRL that improved after neurosyphilis therapy as a criterion standard.

Conclusions

In this small study, the DPP Chembio test showed promising results for neurosyphilis diagnosis. Further studies are needed to assess its performance in resource-limited settings.
Disseminated and Central Nervous System Vaccine-Strain Herpes Zoster Infection in a Teenager With Crohn’s Disease on Maintenance Adalimumab Therapy
Authors: D’Arienzo David , Rumjahn Gryte Kailas , Noya Francisco , Morinville Veronique D.
Published: April 2021

Patients on immunosuppression, including inflammatory bowel disease patients on anti-tumor necrosis factor therapies, are at increased risk of severe varicella and herpes zoster infections. Although varicella vaccine-related herpes zoster reactivation is a rare complication, physicians must remain vigilant about this diagnosis, particularly in those on immunosuppressive medications. Here, we report a case of a patient with Crohn disease, on only adalimumab immunosuppression, who developed varicella vaccine-related disseminated herpes zoster with meningitis, over 15 years after immunization.
A scoping review of chronic pain in emerging adults
Authors: Brown Donnamay , Schenk Sabrina , Genent Dunja , Zernikow Boris , Wager Julia
Published: April 2021

Much of the adult chronic pain literature addresses pain in typical pain cohorts of middle-aged to older individuals. To date, little research has focused on chronic pain in younger adults, who likely have a completely different pain experience. This scoping review aimed to address this gap by describing the emerging adult (18–29 years) chronic pain experience regarding prevalence, associated factors, outcomes, and pain management. Searches of primary electronic databases including PubMed, Embase, PsycINFO, and CINAHL were performed on February 26, 2020, restricting the publication date from database inception to December 31, 2019. The search strategy, conducted in English, covered search term combinations of “chronic pain” and “young adults.” A total of 6,612 records were considered—3,141 after removing duplicates. These records were screened by title and abstract; 871 through full-text screening. Of these, 78 articles covered the topic of emerging adults with chronic pain. Collectively, results indicated that between 5% and 30% of emerging adults experience chronic pain, depending on the sample and exact chronic pain definition. The most consistent associated factors were female sex, familial chronic pain, and previous experiences of chronic pain in childhood. Anxiety, depression, and sleep issues appeared associated both before and after the onset of chronic pain. Outcomes of pain included interruptions to study and work, poorer physical functioning, and pain-related interference to socializing. We observed that few pain treatments have been tested specifically in this cohort. A greater ongoing focus on chronic pain in emerging adults is required to improve long-lasting outcomes.
Microaggressions and Implicit Bias in Surgical Training: An Undocumented but Pervasive Phenomenon
Authors: Alimi Yewande , Bevilacqua Lisa A. , Snyder Rebecca A. , Walsh Danielle , Jackson Patrick G. , DeMaria Eric J. , Tuttle Janet E. , Altieri Maria S.
Published: April 2021

Objective:

To examine the prevalence, nature, and source of microaggressions experienced by surgical residents during training.

Summary and Background Data:

The role of microaggressions in contributing to workplace culture, individual performance, and professional satisfaction has become an increasingly studied topic across various fields. Little is known about the prevalence and impact of microaggressions during surgical training.

Methods:

A 46-item survey distributed to current surgical residents in training programs across the United States via the Association of Program Directors in Surgery listserv and social media platforms between January and May 2020. Survey questions explored the frequency and extent of events of experiencing, witnessing, and responding to microaggressions in the workplace. The primary outcome was the occurrence of microaggressions experienced by surgical residents. Secondary outcomes included the nature, impact, and responses to these events.

Results:

A total of 1624 responses were collected, with an equal distribution by self-identified gender (female, n = 815; male, n = 809). The majority of trainees considered themselves heterosexual (n = 1490, 91.7%) and White (n = 1131, 69.6%). A majority (72.2%, n = 1173) of respondents reported experiencing microaggressions, most commonly from patients (64.1%), followed by staff (57.5%), faculty (45.3%), and co-residents (38.8%). Only a small proportion (n = 109, 7.0%) of residents reported these events to graduate medical education office/program director. Nearly one third (30.8%) of residents said they experienced retaliation due to reporting of micro-aggressions.

Conclusions:

Based on this large, national survey of general surgery and surgical subspecialty trainees, microaggressions appear to be pervasive in surgical training. Microaggressions are rarely reported to program leadership, and when reported, can result in retaliation.
Comamonas suwonensis sp. nov., isolated from stream water in the Republic of Korea
Authors: Park Kyu-Hyun , Yu Zhi , Dong Ke , Lee Sang-Seob
Published: April 2021

A novel bacterial strain, EJ-4T, isolated from stream water collected at Seo-ho in Suwon, Republic of Korea, was characterized based on a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EJ-4T belonged to the genus

Comamonas

. The isolate is Gram-stain-negative, non-motile, aerobic, rod-shaped and forms pale yellow colonies on trypticase soy agar. The optimal growth of this strain was observed aerobically at 30 °C, pH 7 and 0.5 % NaCl. The major fatty acids were summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c; 39.7 %) and C16 : 0 (32.0 %). The G+C content of strain EJ-4T was 58.4mol %. The average nucleotide identity and digital DNA–DNA hybridization values between strain EJ-4T and Comamoas testosteroni were 91.8 and 31.2 %, respectively. The major polar lipids detected in the isolate were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant isoprenoid quinone was ubiquinone-8. Based on the results of polyphasic taxonomic analysis of strain EJ-4T, we describe a novel species of the genus

Comamonas

, for which the name Comamonas suwonensis sp. nov. has been proposed, with EJ-4T (=KCTC 82074T=JCM 34179T=KEMB 1602-279T) as the type strain.
Assessment of the COVID-19 Vaccine Program: Impact of the No Mask Mandate Executive Order in the State of Texas
Authors: Richardson Ariana , Ruffin Rachel , Iboi Enahoro A.
Published: April 2021

On March 10, 2021, a new executive order to lift the mask mandate and allow businesses to open at 100 percent capacity, went into effect in the U.S. state of Texas. This was due to the decrease in the daily number of COVID-19 cases and deaths as the state continues to vaccinate the population. A simple compartmental model was used to assess the implications of the executive order on the ongoing vaccination program. Our simulation shows that approximately 51% of the entire population needs to be fully vaccinated to bring the control reproduction number to a value less than one (threshold condition needed for disease elimination) as compared to the 14.32% that has been fully vaccinated as of March 31, 2021. Hence, the need for an aggressive vaccination program if the state is to open businesses to full capacity and do not require the use of a face mask by the general public.
Compliance with Covid-19 measures: evidence from New Zealand
Authors: Kaine Geoff , Greenhalgh Suzie , Wright Vic
Published: April 2021

Governments around the world are seeking to slow the spread of Covid-19 by implementing measures that encourage, or mandate, changes in people’s behaviour. These changes include the wearing of face masks, social distancing, and testing and self-isolating when unwell. The success of these measures depends on the commitment of individuals to change their behaviour accordingly. Understanding and predicting the motivation of individuals to change their behaviour is therefore critical in assessing the likely effectiveness of these measures in slowing the spread of the virus.

In this paper we draw on a novel framework, the I3Compliance Response Framework, to understand and predict the motivation of residents in Auckland, New Zealand, to comply with measures to prevent the spread of Covid-19. The Framework is based on two concepts. The first uses the involvement construct to predict the motivation of individuals to comply. The second separates the influence of the policy measure from the influence of the policy outcome on the motivation of individuals to comply.

In short, the Framework differentiates between the strength of individuals’ motivation and their beliefs about the advantages and disadvantages of policy outcomes and policy measures. We found this differentiation was useful in predicting an individual’s possible behavioural responses to a measure and discuss how it could assist government agencies to develop strategies to enhance compliance.
Cone Rescue with Laser Photobiomodulation in Murine and Human Retinal Dystrophy
Authors: Casson Robert J. , Wood John P.M. , Ao Jack , Gilhotra Jagjit S. , Durkin Shane R. , Chan WengOnn , Chidlow Glyn
Published: April 2021

Retinitis pigmentosa (RP) encompasses a genetically diverse group of blinding inherited retinal diseases. In most subtypes the gene defect is expressed in the rod photoreceptors, yet in many affected individuals the cone photoreceptors undergo secondary degeneration, leading to loss of the remaining central vision. There is evidence that bioenergetic and oxidative stress are involved in this secondary cone loss. Photobiomodulation (PBM) uses low energy light in the far red or near-infrared spectrum to manipulate cellular activity. We have used a novel slit lamp-mounted retinal PBM laser to deliver precise energy levels to targeted retina. We showed that PBM laser attenuates oxidative and bioenergetic stress-induced photoreceptor loss in vitro and rescues cones in the rd1 murine model of RP. In a phase I trial (ACTRN12618000651280), foveal laser treatment was safe in humans with RP and temporarily recovered, on average, 5 letters of visual acuity.
Informed decision making on the uptake of evidence-based smoking cessation assistance: A needs assessment among end users and experts to inform decision aid development
Authors: Gültzow Thomas , Smit Eline Suzanne , Hudales Raesita , Dirksen Carmen D. , Hoving Ciska
Published: April 2021

Introduction

Evidence-based cessation assistance is known to increase cessation rates. Activating personal preferences as part of the decision for smoking cessation assistance tools could further improve tools’ effectiveness. Decision aids (DAs) help individuals to choose amongst the various options by taking these preferences into account and, therefore, could have a positive effect on cessation rates. To develop attractive and effective DAs, potential end users’ needs, and experts’ viewpoints should be considered during development processes. Therefore, the aim of this study was: (1) To explore smokers’ needs and viewpoints regarding a smoking cessation assistance DA, and (2) to obtain consensus among smoking cessation counsellors and scientific experts about the content and format of such a DA.

Materials and methods

Data was gathered via two approaches applied across three studies: (1) 20 semi-structured interviews with potential end users, (2) two three-round Delphi studies with 61 smoking cessation counsellors and 44 scientific experts. Data from the interviews and the first round of the Delphi studies were analysed qualitatively using the Framework method, while data from the second and third round of the Delphi studies were analysed quantitatively using medians and interquartile ranges.

Results

Potential end users reported to acquire information in different ways: Via own experiences, their social environment, and the media. Important characteristics to decide between tools also varied, however effectiveness and costs were commonly reported as the most important characteristics. The experts reached consensus on 38 (smoking cessation counsellors) and 40 (scientific experts) statements regarding important cessation assistance tools’ characteristics and their viewpoints on a smoking cessation assistance DA, e.g., that a tool should be appropriate for users’ level of addiction.

Discussion and conclusion

Some clear trends emerged among the potential end users (especially regarding important characteristics). Experts also reached consensus among a number of statements. However, there was some variation in the needs and wishes among the (different) stakeholders. The combination of these studies highlights that a ‘one size fits all’ approach is not desirable. In the development of DAs, this heterogeneity should be taken into account, e.g., by enabling users to customize a DA based on their personal preferences while safeguarding essential elements.

Highlights

Potential end users’ needs for a smoking cessation DA vary greatly

However, tools’ effectiveness and costs were commonly named as important

Customizable elements within a DA could be used to deal with this heterogeneity

Conceptualizations (e.g., of effectiveness) may vary between stakeholders

Information should be provided to end users in an easily understandable manner
SARS-CoV-2 UK, South African and Brazilian Variants in Karachi- Pakistan
Authors: Khan Adnan , Hanif Muhammad , Syed Sarosh , Ahmed Akhtar , Ghazali Saqib , Khanani Rafiq
Published: April 2021

COVID-19 pandemic has been evolving in Pakistan since the UK, South African and Brazilian variants have started surfacing which are known for increase transmissibility and can also be responsible for escape from immune responses. The gold standard to detect these variants of concern is sequencing, however routine genomic surveillance in resource limited countries like Pakistan is not always readily available. With the emergence of variants of concern and a dearth of facilities for genomic scrutiny leaves policy makers and health authorities an inconsistent and twisted image to make decisions. The inadvertent detection of B.1.1.7 by target failure because of a key deletion in spike Δ69-70 in the UK by commercially available COVID-19 PCR assay helps to understand target failures as an alternative approach to detect variants. It was ascertained further that a deletion in the ORF1a gene (ORF1a Δ3675-3677) found common in B.1.1.7, B.135 and P.1 variants of concern. The Real Time Quantitative PCR (RT-qPCR) assay for detection of emergence and spread of SARS-CoV-2 variants, by these target failures is used here. The positive samples archived in respective labs were divided in two groups used in the present study. Group I constitutes 261 positive samples out of 16964 (1.53%) collected from August till September 2020. Group II include 3501 positive samples out of 46041 (7.60%) from November 2020 till January 2021. In positive samples of group I, no variant of concern was found. A staggering difference in results was noted in group II where positivity ratio increased exponentially and the variants of concern started appearing in significant numbers (53.64% overall). This is indicative that the third wave in Pakistan is due to the importation of SARS-CoV-2 variants. This calls for measures to increase surveillance by RT-qPCR which would help authorities in decision making.
End-to-End Deep Learning for Detecting Metastatic Breast Cancer in Axillary Lymph Node from Digital Pathology Images
Authors: Turki Turki , Al-Sharif Anmar , Taguchi Y-h.
Published: April 2021

Metastatic breast cancer is one of the attributed leading causes of women deaths worldwide. Accurate diagnosis to the spread of breast cancer to axillary lymph nodes (ALNs) is done by breast pathologist, utilizing the microscope to inspect and then providing the biopsy report. Because such a diagnosis process requires special expertise, there is a need for artificial intelligence-based tools to assist breast pathologists to automatically detect breast cancer metastases. This study aims to detect breast cancer metastasized to ALN with end-to-end deep learning (DL). Also, we utilize several DL architectures, including DenseNet121, ResNet50, VGG16, Xception as well as a customized lightweight convolutional neural network. We evaluate the DL models on NVIDIA GeForce RTX 2080Ti GPU using 114 processed microscopic images pertaining to ALN metastases in breast cancer patients. Compared to all DL models employed in this study, experimental results show that DenseNet121 generates the highest performance results (64– 68%) based on AUC and accuracy.
Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus
Authors: Kasela Silva , Daniloski Zharko , Jordan Tristan X. , tenOever Benjamin R. , Sanjana Neville E. , Lappalainen Tuuli
Published: April 2021

To date the locus with the most robust human genetic association to COVID-19 susceptibility is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that mediate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.
The Importance of Automation in Genetic Diagnosis: Lessons from Analyzing an Inherited Retinal Degeneration Cohort with the Mendelian Analysis Toolkit (MATK)
Authors: Zampaglione Erin , Maher Matthew , Place Emily M. , Wagner Naomi E. , DiTroia Stephanie , Chao Katherine R. , England Eleina ,   Broad CMG, Catomeris Andrew , Nassiri Sherwin , Himes Seraphim , Pagliarulo Joey , Ferguson Charles , Galdikaité-Braziené Eglé , Cole Brian , Pierce Eric A. , Bujakowska Kinga M.
Published: April 2021

Purpose

In Mendelian disease diagnosis, variant analysis is a repetitive, error-prone, and time-consuming process. To address this, we have developed the Mendelian Analysis Toolkit (MATK), a configurable automated variant ranking program.

Methods

MATK aggregates variant information from multiple annotation sources and uses expert-designed rules with parameterized weights to produce a ranked list of potentially causal solutions. MATK performance was measured by a comparison of MATK-aided versus human domain-expert analyses of 1060 inherited retinal degeneration (IRD) families investigated with an IRD-specific gene panel (589 individuals) and exome sequencing (471 families).

Results

When comparing MATK-assisted analysis to expert curation in both IRD-specific and exome sequencing (1060 subjects), 97.3% of potential solutions found by experts were also identified by the MATK-assisted analysis (541 solutions identified with MATK of 556 solutions found by conventional analysis). Furthermore, MATK-assisted analysis identified 114 additional potential solutions from the 504 cases unsolved by the conventional analysis.

Conclusion

MATK expedites the process of identifying likely solving variants in Mendelian traits and reduces variability coming from human error and researcher bias. MATK facilitates data re-analysis to keep up with the constantly improving annotation sources and NGS processing pipelines. The software is open source, available at https://gitlab.com/matthew_maher/mendelanalysis
Antibody and T cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naïve health care workers in Sri Lanka
Authors: Jeewandara Chandima , Kamaladasa Achala , Pushpakumara Pradeep Darshana , Jayathilaka Deshni , Abayrathna Inoka Sepali , Danasekara Saubhagya , Guruge Dinuka , Ranasinghe Thushali , Dayarathne Shashika , Pathmanathan Thilagaraj , Somathilaka Gayasha , Madhusanka Deshan , Tanussiya Shyrar , TPJ Tibutius , Kuruppu Heshan , Wijesinghe Ayesha , Thashmi Nimasha , Milroy Dushantha , Nandasena Achini , Sanjeewani Nilanka , Wijayamuni Ruwan , Samaraweera Sudath , Schimanski Lisa , Tan T.K. , Dong Tao , Ogg Graham S. , Townsend Alain , Malavige Gathsaurie Neelika
Published: April 2021

Background

In order to determine the immunogenicity of a single dose of the AZD1222/Covishield vaccine in a real-world situation, we assessed the immunogenicity, in a large cohort of health care workers in Sri Lanka.

Methods

SARS-CoV-2 antibodies was carried out in 607 naïve and 26 previously infected health care workers (HCWs) 28 to 32 days following a single dose of the vaccine. Haemagglutination test (HAT) for antibodies to the receptor binding domain (RBD) of the wild type virus, B.1.1.7, B.1.351 and the surrogate neutralization assay (sVNT) was carried out in 69 naïve and 26 previously infected individuals. Spike protein (pools S1 and S2) specific T cell responses were measured by ex vivo ELISpot IFNγ assays in 76 individuals.

Results

92.9% of previously naive HCWs seroconverted to a single dose of the vaccine, irrespective of age and gender; and ACE2 blocking antibodies were detected in 67/69 (97.1%) previously naïve vaccine recipients. Although high levels of antibodies were found to the RBD of the wild type virus, the titres for B.1.1.7 and B.1.351 were lower in previously naïve HCWs. Ex vivo T cell responses were observed to S1 in 63.9% HCWs and S2 in 31.9%. The ACE2 blocking titres measured by the sVNT significantly increased (p<0.0001) from a median of 54.1 to 97.9 % of inhibition, in previously infected HCWs and antibodies to the RBD for the variants B.1.1.7 and B.1.351 also significantly increased.

Discussion

a single dose of the AZD1222/Covishield vaccine was shown to be highly immunogenic in previously naïve individuals inducing antibody levels greater than following natural infection. In infected individuals, a single dose induced very high levels of ACE2 blocking antibodies and antibodies to RBDs of SARS-CoV-2 variants of concern.

Funding

We are grateful to the World Health Organization, UK Medical Research Council and the Foreign and Commonwealth Office.
Ovarian follicular function is not altered by SARS-Cov-2 infection or BNT162b2 mRNA Covid-19 vaccination
Authors: Bentov Yaakov , Beharier Ofer , Moav-Zafrir Arbel , Kabessa Maor , Godin Miri , Greenfield Caryn S. , Ketzinel-Gilad Mali , Broder Efrat Esh , Holzer Hananel E. G. , Wolf Dana , Oiknine-Djian Esther , Barghouti Iyad , Goldman-Wohl Debra , Yagel Simcha , Walfisch Asnat , Klement Anat Hersko
Published: April 2021

Importance

This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function.

Objective

To characterize anti-COVID-19 antibodies in follicular fluid and compare ovarian follicle function in women following confirmed SARS-CoV-2 infection, COVID-19 vaccination, and non-infected, unvaccinated controls.

Design

This is a cohort study conducted between February 1 and March 10, 2021.

Setting

A single university hospital-based IVF clinic.

Participants

Consecutive sample of female patients undergoing oocyte retrieval.

Interventions

Consenting patients were recruited and assigned to one of three study groups: recovering from confirmed COVID 19 (n=9); vaccinated (n=9); and uninfected, non-vaccinated controls (n=14). Serum and follicular fluid samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and HSPG2 concentration, as well as the number and maturity of aspirated oocytes and previous estrogen and progesterone measurements.

Main outcome measures

Follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.

Results

Both natural and vaccine elicited anti-COVID IgG antibodies were detected in the follicular fluid in levels proportional to the IgG serum concentration. No differences were detected in any of the surrogate ovarian follicle quality reporting parameters.

Conclusions and relevance

Both SARS-COV-2 infection and vaccination with the BNT162b2 mRNA vaccine mediate IgG immunity that crosses into the follicular fluid. No detrimental effect on follicular function was detected.

Trial Registration

CinicalTrials.gov registry number NCT04822012

Key Point

COVID 19 disease and BNT162b2 mRNA vaccine induce anti-COVID IgG in follicular fluid; neither recent infection nor vaccination appear to negatively effect follicular function.
Prefrontal glutamate neurotransmission in PTSD: A novel approach to estimate synaptic strength in vivo in humans
Authors: Averill Lynnette A. , Jiang Lihong , Purohit Prerana , Coppoli Anastasia , Averill Christopher L. , Roscoe Jeremy , Kelmendi Benjamin , De Feyter Henk M. , de Graaf Robin A , Gueorguieva Ralitza , Sanacora Gerard , Krystal John H. , Rothman Douglas L. , Mason Graeme F. , Abdallah Chadi G.
Published: April 2021

Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma psychopathology. Healthy control (n=18) and patients with posttraumatic stress (PTSD; n=16) completed 13C-acetate magnetic resonance spectroscopy scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (VTCA/VCycle). Patients with PTSD were found to have 28% reduction in prefrontal EPC (t=3.0; df=32, p=0.005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups (r=–0.46, n=34, p=0.006). Controlling for age did not affect the study results. The feasibility and utility of EPC were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments.

Highlights

Glutamatergic synaptic strength is critical for brain function in health and disease.

In vivo in human methods to estimate glutamatergic synaptic strength are limited.

We here propose a new approach to estimate glutamatergic synaptic strength.

The new method employs carbon-13 magnetic resonance spectroscopy (13C MRS).

The utility of the new approach was demonstrated in posttraumatic stress disorder (PTSD).
Early Experience With Neutralizing Monoclonal Antibody Therapy For COVID-19
Authors: Jarrett Mark , Licht Warren B. , Bock Kevin , Brown Zenobia , Hirsch Jamie S. , Coppa Kevin , Brar Rajdeep , Bello Steven , Nash Ira S.
Published: April 2021

Importance

Neutralizing monoclonal antibody (MAB) therapies may benefit patients with mild to moderate COVID-19 at high risk for progressing to severe COVID-19 and/or hospitalization. Studies documenting approaches to deliver MAB infusions as well as demonstrating their efficacy are lacking.

Objective

We describe our experience and patient outcomes of almost 3,000 patients who received MAB infusion therapy at Northwell Health, a large integrated health care system in New York.

Design, Setting, and Participants

This is a descriptive study of adult patients who received MAB therapy between November 20, 2020, to January 31, 2021, and a retrospective cohort survival analysis comparing patients who received MAB therapy prior to admission versus those who did not. A multivariable Cox model with inverse probability weighting according to the propensity score including covariates (sociodemographic, comorbidities, and presenting vital signs) was used.

Main outcomes and measures

The primary outcome was in-hospital mortality; additional evaluations included ED utilization and hospitalization within 28 days of a positive COVID-19 test for patients who received MAB therapy.

Results

During the study period, 2818 adult patients received MAB infusion. Following therapy and within 28 days of COVID-19 test, 123 patients (4.4%) presented to the ED and were released and 145 patients (5.1%) were hospitalized. These 145 patients were compared with 200 controls who were eligible for but did not receive MAB therapy, and were hospitalized. In the MAB group, 16 (11%) patients met the primary outcome of in-hospital mortality, versus 21 (10.5%) in the control group. In an unadjusted Cox model, the hazard ratio (HR) for time to in-hospital mortality for the MAB group was 1.38 (95% confidence interval [95% CI] 0.696-2.719). Models adjusting for demographics (HR 1.1, 95% CI 0.53-2.23), demographics and Charlson Comorbidity Index (CCI) (HR 1.22, 95% CI 0.573-2.59), and with inverse probability weighting according to propensity scores (HR 1.19, 95% CI 0.619-2.29) did not demonstrate significance. The hospitalization rate was 4.4% for patients who received MAB therapy within 0-4 days, 5% within 5-7 days, and 6.1% within ≥8 days of symptom onset (p-value = 0.15).

Conclusions and relevance

Establishing the capability to provide neutralizing MAB infusion therapy requires significant planning and coordination. While this therapy may be an important treatment option for early mild to moderate COVID-19 in high-risk patients, further investigations are needed to define the optimal timing of MAB treatment in order to reduce hospitalization and mortality.
Impact of COVID -19 on Depression and Anxiety among Healthcare Professionals in Abu Dhabi
Authors: Zarooni Amal Abdul Rahim Al , Alghfeli Aljazia Khalfan , Alremeithi Hamda Musabbah , Almadhaani Roqayah Abdulla , Alketbi Latifa Baynouna
Published: April 2021

COVID-19 have affected Healthcare workers is many ways. One of the important areas is the psychological impact. The aim of this study is to examine the effects of the COVID-19 outbreak on the mental health of healthcare Professionals (HCP). A cross-sectional study was conducted between April 11th, and July 23rd, 2020, to assess depression and anxiety of healthcare workers, during the COVID-19 pandemic. An online, self-administered, anonymous questionnaire evaluated 1,268 HCP. More than half of the participants reported symptoms of anxiety (51.5%). Mild anxiety was reported in 28.8% of participating HCP, and 12.68 % of the participants registered moderate anxiety scores, while 9.95 % reported severe anxiety. Depression symptoms were revealed in 38.3 % of participating providers. Among all participates, 4.3 % and 2.7 % reported moderately severe and severe depression, accordingly, while 22.5%, and 8.8 % of the participating health care providers documented mild and moderate depression. The high prevalence of anxiety and depression recorded among HCP during the pandemic suggests that mental health intervention and support are necessary to ensure the psychological well-being of HCP.
Contrasting patterns and co-occurrence network of soil bacterial and fungal community along depth profiles in cold temperate montane forests of China
Authors: Ji Li , Shen Fangyuan , Liu Yue , Yang Yuchun , Wang Jun , Yang Lixue
Published: April 2021

Soil bacterial and fungal communities with different key ecological functions play an important role in the boreal forest ecosystem. Despite several studies have reported the microbial altitudinal distribution patterns, our understanding about the characteristics of the microbial community and the core composition of the microbiome in cold-temperate mountain forests is still limited. In this study, Illumina MiSeq sequencing was used to investigate the changes in soil bacterial and fungal communities in surface and subsurface soils along at an altitudinal gradient (from 830 m to 1300 m) on Oakley Mountain in the northern Greater Khingan Mountains. Altitude and soil depth had significant impacts on the relative abundance of Proteobacteria, Acidobacteria and Actinobacteria (dominant phylum for bacteria), and altitude had significant impacts on the Ascomycota, Basidiomycota and Mucoromycota (dominant phylum for fungi). The diversity of bacterial and fungal communities showed a monotonous decrease and increase with altitude. The influence of altitude on bacterial and fungal community composition was greater than that of soil depth. The variation of pH and dissolved organic nitrogen (DON) content in different altitudes were the main factors driving the bacterial and fungal community structure, respectively. There is no obvious difference between the network structure of surface and subsurface soil fungal communities, while the network of subsurface soil bacterial communities was more complex and compact than the surface layer. The network nodes mainly belonging to Proteobacteria and Actinobacteria are the key species in the two soil layers. Our results demonstrated that the altitude had a stronger influence on soil bacterial and fungal communities than soil depth, and bacterial and fungal communities showed divergent patterns along the altitudes and soil profiles.
Cardiorespiratory fitness predicts cortical thickness of medial temporal brain areas associated with spatial cognition in young but not older adults
Authors: Rosario Michael A. , Kern Kathryn L. , Mumtaz Shiraz , Storer Thomas W. , Schon Karin
Published: April 2021

Cardiorespiratory fitness (CRF) has been shown to have a potent effect on neurocognitive health. However, less is known about the impact of CRF on extrahippocampal neocortical regions in the medial temporal lobes (MTL). Specifically, it is unclear whether CRF modulates these MTL regions in young adulthood and if these brain areas are differentially related to CRF in young vs. older adults. The primary goal of the current study was to investigate if CRF predicted cortical thickness of MTL neocortical regions that, along with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of the MTL cortices in spatial navigation, we sought to determine if CRF and MTL cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross-sectional data from 56 young adults (20-35 years) and 44 older adults (55-85 years) were included. Using hierarchical multiple regression analyses, we confirmed significant positive relationships between greater CRF and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal thickness interacted with age group to differentially predict sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, relationship between left parahippocampal thickness and sense of direction. Our findings extend previous work on the association between CRF and hippocampal subfield structure in young adulthood to left MTL neocortical regions.

Highlights

Cardiorespiratory fitness assessed in young and older adults using a submaximal treadmill test.

Surface-based structural analysis of cortical thickness of medial temporal regions.

Cardiorespiratory fitness predicted left medial temporal cortical thickness in young but not older adults.

Left parahippocampal thickness differentially predicted sense of direction in young and older adults.
Survey of Behaviour Attitudes Towards Preventive Measures Following COVID-19 Vaccination
Authors: Rahamim-Cohen Daniella , Gazit Sivan , Perez Galit , Nada Barak , Moshe Shay Ben , Mizrahi-Reuveni Miri , Azuri Joseph , Patalon Tal
Published: April 2021

Following the widespread vaccination program for COVID-19 carried out in Israel, a survey was conducted to preliminarily assess behavior changes in the vaccinated population, prior to the expected upcoming policy change as to mask wearing and social distancing regulation in Israel. 200 people answered at least one question pertaining to preventive behaviour. Among the respondents, 21.1% reported a decrease in mask wearing compared to 47.3% who reported a decrease in social distancing. There was no difference in these measures between the sexes. However, people under the age of 50 were more likely to decrease mask wearing (28.1%) and decrease social distancing (56.1%), as compared with people over the age of 50 (17.2% and 41.8%, respectively). Among health care workers, there was a minimal decrease in mask wearing (1/23 people) compared to a more widespread decrease in social distancing (10/23). These data suggest that preventive attitudes change following COVID-19 vaccination, with less adherence to social distancing as compared to mask wearing, and should be taken into account when planning public policy in the future.
Long COVID In Adults at 12 Months After Mild-to-Moderate SARS-CoV-2 Infection
Authors: Boscolo-Rizzo Paolo , Guida Francesco , Polesel Jerry , Marcuzzo Alberto Vito , Capriotti Vincenzo , D’Alessandro Andrea , Zanelli Enrico , Marzolino Riccardo , Lazzarin Chiara , Antonucci Paolo , Sacchet Erica , Tofanelli Margherita , Borsetto Daniele , Gardenal Nicoletta , Pengo Martino , Tirelli Giancarlo
Published: April 2021

Background

In a proportion of patients recovered from the acute COVID-19 phase, a variable range of symptoms has been observed to persist for at least 6-months.

Objectives

The main aim of this study was to evaluate the prevalence of COVID-related symptoms 12-months after the onset of mild-to-moderate disease.

Methods

Prospective study based on structured questionnaires and additional outcomes.

Results

304/354 patients completing the survey at baseline also completed the follow-up interview (85.9%; median [range] age, 47 [18-76] years; 185 [60.9%] women). Persistence of at least one symptom at 12-months follow-up was reported by 161 patients (53.0%). The most commonly reported symptom of long COVID was felt tired (n=83, 27.3%), followed by smell or taste impairment (n=67, 22.0%), shortness of breath (n=39, 12.8%) and muscle pain (n=28, 9.2%). Being females (OR=1.64; 95% CI: 1.00-2.70), aged between 40-54 (OR=1.92; 95% CI: 1.07-3.44), having a BMI ≥25 (OR=1.67; 95% CI: 1.00-2.78), and experiencing more symptoms during the acute phase of the disease (OR=8.71 for ≥8 symptoms; 95% CI: 2.73-27.76) were associated with long COVID. Persistence of symptoms showed a significant impact on quality of life (p<0.0001) and depression scale scores (p=0.0102).

Conclusion

More than half of patients with previous mild-to-moderate symptomatic COVID-19 complained the persistence of at least one symptom 12-months after the onset of the illness.
Genome-wide chromosomal association of Upf1 is linked to Pol II transcription inSchizosaccharomyces pombe
Authors: De Sandip , Dwivedi Vibha , Wang Jianming , Edwards David M. , Varsally Wazeer , Singh Anand K. , Dixon Hannah L. , Wojewodzic Marcin W. , Falciani Francesco , Hodges Nikolas J. , Saponaro Marco , Tanaka Kayoko , Azzalin Claus M. , Baumann Peter , Hebenstreit Daniel , Brogna Saverio
Published: April 2021

Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes inSchizosaccharomyces pombe. This association is RNase sensitive and it correlates with Pol II transcription and mRNA expression levels. While changes in Pol II occupancy were detected at only some genes in a Upf1-deficient (upf1Δ) strain, there is an increased Ser2 Pol II signal at all highly transcribed genes examined by ChIP-qPCR. Furthermore,upf1Δcells are hypersensitive to the transcription elongation inhibitor 6-azauracil and display Pol II abnormalities suggestive of Pol II hyperphosphorylation. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated inupf1Δ.These data envisage that by operating on the nascent transcript Upf1 might influence Pol II phosphorylation and transcription.
LRR protein RNH1 dampens the inflammasome activation and is associated with adverse clinical outcomes in COVID-19 patients
Authors: Bombaci Giuseppe , Sarangdhar Mayuresh Anant , Andina Nicola , Tardivel Aubry , Yu Eric Chi-Wang , Mackie Gillian M. , Pugh Matthew , Ozan Vedat Burak , Banz Yara , Spinetti Thibaud , Hirzel Cedric , Youd Esther , Schefold Joerg C. , Taylor Graham , Gazdhar Amiq , Bonadies Nicolas , Angelillo-Scherrer Anne , Schneider Pascal , Maslowski Kendle M. , Allam Ramanjaneyulu
Published: April 2021

Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1 mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in COVID-19. However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine rich repeat (LRR) protein Ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases IL-1β production and caspase-1 activation for inflammasome stimuli. Mechanistically, RNH1 decreases pro-IL-1β expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and LPS-induced endotoxemia, which are dependent on caspase-1, respectively show increased neutrophil infiltration and lethality inRnh1-/-mice compared to WT mice. Furthermore, RNH1 protein levels are negatively correlated with inflammation and disease severity in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.
ReducedShmt2expression impairs mitochondrial folate accumulation and respiration, and leads to uracil accumulation in mouse mitochondrial DNA
Authors: Fiddler Joanna L. , Xiu Yuwen , Blum Jamie E. , Lamarre Simon G. , Phinney Whitney N. , Stabler Sally P. , Brosnan Margaret E. , Brosnan John T. , Thalacker-Mercer Anna E. , Field Martha S.
Published: April 2021

Background

Adequate cellular thymidylate (dTMP) pools are essential for preservation of nuclear and mitochondrial genome stability. Previous studies have indicated that disruption in dTMP synthesis in the nucleus leads to increased uracil misincorporation into DNA affecting genome stability. To date, the effects of impaired mitochondrial dTMP synthesis in non- transformed tissues have been understudied.

Objective

This study aimed to determine the effects of decreased serine hydroxymethyltransferase 2 (Shmt2)expression and dietary folate deficiency on mitochondrial DNA integrity and mitochondrial function in mouse tissues.

Methods

Liver mitochondrial DNA (mtDNA) content, and uracil content in liver mtDNA was measured inShmt2+/-andShmt2+/+mice weaned onto either a folate-sufficient control diet (2 mg/kg folic acid, C) or a modified diet lacking folic acid (0 mg/kg folic acid, FD) for 7 wks.Shmt2+/-andShmt2+/+mouse embryonic fibroblasts (MEF cells) were cultured in defined culture medium containing either 0 or 25 nM folate to assess proliferative capacity and mitochondrial function.

Results

Shmt2+/-mice exhibited 48-67% reduction in SHMT2 protein levels in tissues. Interestingly,Shmt2+/-mice consuming the folate-sufficient C diet exhibited a 25% reduction in total folate in liver mitochondria. There was also a >20-fold increase in uracil in liver mtDNA inShmt2+/-mice consuming the C diet, and dietary folate deficiency also increased uracil content in mouse liver mtDNA from bothShmt2+/+andShmt2+/-mice. Furthermore, decreasedShmt2expression in MEF cells reduced cell proliferation, mitochondrial membrane potential, and oxygen consumption rate.

Conclusions

This study demonstrates thatShmt2heterozygosity and dietary folate deficiency impair mitochondrial dTMP synthesis, as evidenced by the increased uracil in mtDNA. In addition,Shmt2heterozygosity impairs mitochondrial function in MEF cells. These findings suggest that elevated uracil in mtDNA may impair mitochondrial function.
Vitamin C – protective role in oxidative stress conditions induced in human normal colon cells by label free Raman spectroscopy and imaging
Authors: Beton K. , Brozek-Pluska B.
Published: April 2021

Colorectal cancer is the second most frequently diagnosed cancer worldwide. Conventional diagnostics methods of colorectal cancer, can detect it in advanced stage.

Spectroscopic methods, including Raman spectroscopy and imaging, are becoming more and more popular in medical applications, and allow fast, precise and unambiguous differentiation of healthy and cancerous samples. the most important advantage of Raman spectroscopy is ability to identify biomarkers that help in differentiation of healthy and cancerous cells based on biochemistry of sample and spectra typical for: lipids, proteins, DNA.

The aim of the study was to evaluate the biochemical and structural features of human colon cell lines based on Raman spectroscopy and imaging: normal cells CCD-18 Co, normal cells CCD-18 Co under oxidative stress conditions, normal cells CCD-18 Co at first treated by using tert-Butyl hydroperoxide and then supplemented by vitamin C in high concentration to show the protective role of vitamin C in micromolar concentrations against ROS by spectroscopic methods. Raman data obtained for normal cells injured by ROS were compared with spectra typical for cancerous cells.

Statistically assisted analysis has shown that normal, ROS injured and cancerous human colon cells can be distinguished based on their unique vibrational properties.

The research carried out proves that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of normal and cancerous colon cells and may be a source of intraoperative information supporting histopathological analysis.
Phumdis-A Promising Alternative Energy Resource
Authors: Siddiqua Ayesha , Kanodia Sweekrity , Jacob Jincy , Khumanthem Darwilin , Thakhell Keke , Babu C.K Chandra , Vinjamuri Saisha
Published: April 2021

The inadequate sources of energy coupled with the increasing demands of power have necessitated the search for novel renewable energy resources. ‘Phumdis’ are one such promising alternative. Phumdis are floating mats of heterogeneous mass of vegetation, soil and organic matter found in Loktak Lake in Manipur, North Eastern India. This paper delineates the use of Phumdis as an alternative energy source. Phumdis from Loktak Lake, Manipur were processed and analyzed for their biofuel capabilities. The Results indicate that the phumdis have high calorific content, cloudpoint and flash point indicating that they are at par with other fuels.