bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive Symptoms and Overperception of Airflow Obstruction in Older Adults With Asthma
Authors: Feldman Jonathan M. , Becker Jacqueline , Arora Arushi , DeLeon Jesenya , Torres-Hernandez Tatiana , Greenfield Naomi , Wiviott Allyana , Jariwala Sunit , Shim Chang , Federman Alex D. , Wisnivesky Juan P.
Published: May 2021

Objective

Older adults are at increased risk for depression and poor asthma outcomes. We examined whether depressive symptoms are associated with overperception of airflow obstruction and a pattern of worse asthma control, but not pulmonary function.

Methods

We recruited a cohort of adults with asthma 60 years and older in East Harlem and the Bronx, New York. Baseline measures included the Geriatric Depression Scale, Asthma Control Questionnaire, and Mini Asthma Quality of Life Questionnaire. Spirometry was conducted at baseline to assess pulmonary function. Perception of airflow obstruction was assessed for 6 weeks following baseline by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter followed by PEF blows. Participants were blinded to actual PEF values. The percentage of time that participants were in the overperception zone was calculated as an average.

Results

Among the 334 participants (51% Hispanic, 25% Black), depressive symptoms were associated with overperception of airflow obstruction (β = 0.14, p = .029), worse self-reported asthma control (β = 0.17, p = .003), and lower asthma-related quality of life (β = −0.33, p < .001), but not with lung function (β = −0.01, p = .82). Overperception was also associated with worse self-reported asthma control (β = 0.14, p = .021), but not lung function (β = −0.05, p = .41).

Conclusions

Depressive symptoms were associated with greater perceived impairment from asthma, but not pulmonary function. Overperception of asthma symptoms may play a key role in the relationship between depression and asthma outcomes in older adults.
Patient Safety Monitoring in Acute Care in a Decentralized National Health Care System: Conceptual Framework and Initial Set of Actionable Indicators
Authors: Labella Barbara , De Blasi Roberta , Raho Vanda , Tozzi Quinto , Caracci Giovanni , Klazinga Niek Sieds , Carinci Fabrizio
Published: May 2021

Objectives

Monitoring patient safety is critical for continuous quality improvement in acute care. We carried out a national project to identify a conceptual framework with core indicators that could be uniformly applied in the decentralized health system of Italy.

Methods

We used key international references to identify a framework with a core list of indicators and data sources for calculation in 4 hospitals in the Lombardy region. Two different data processing methods were applied: (a) centralized analysis of national databases and (b) decentralized data extraction and calculation using different hospital data available in Lombardy.

Results

Agreement was reached on a conceptual framework for patient safety monitoring in acute care, including structures, processes, and outcomes as vertical dimensions and health care needs as horizontal axes. We were able to compute 15 of 32 indicators through the application of a range of methods. The calculation of indicators using national databases was based on international standards. The consistency of the estimates obtained through the use of different methods and data sources seemed limited.

Conclusions

We successfully identified a conceptual framework for patient safety in acute care including actionable indicators that can be calculated routinely using different data sources at national, regional, and hospital levels. Further work is required to compare methods and understand whether a combination of strategies at national and local levels could be proven effective.
The Expression Level of FOXO3a in Patients With Autoimmune Diseases
Authors: Xu Shanshan , Zhang Xiaoyi , Ma Yubo , Xu Shengqian , Pan Faming
Published: May 2021

Objective

Numerous studies have investigated the expression of forkhead box O3a (FOXO3a) in autoimmune diseases, but the results were inconsistent. This meta-analysis aims to synthetically evaluate the levels of FOXO3a in autoimmune diseases.

Methods

PubMed, Web of Science, and China National Knowledge Infrastructure were used to retrieve relevant articles. The pooled standard mean difference with 95% confidence interval was calculated.

Results

Totally, 10 studies from 7 publications were included. The levels of FOXO3a were significantly decreased in patients with autoimmune diseases compared with healthy controls (standard mean difference, −1.045; 95% confidence interval, −1.892 to −0.197). When stratified by disease, FOXO3a levels were significantly decreased in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but were significantly increased in systemic lupus erythematosus. FOXO3a levels of specific tissues or cells in patients with autoimmune diseases were significantly decreased, but no significant difference was observed in the subgroup of peripheral blood mononuclear cells. In the subgroup analysis combining disease and sample, significant differences of FOXO3a were observed in non-PMBCs of RA and IBD patients.

Conclusions

Our study indicated that FOXO3a were significantly decreased in patients with autoimmune diseases. FOXO3a levels was a potential therapeutic target of autoimmune diseases.
18F-FDG and 68GA–Prostate-Specific Membrane Antigen PET/CT Perform Better Than CT Alone in Restaging Papillary Renal Cell Carcinoma Recurrence
Authors: Gasparro Donatello , Scarlattei Maura , Manuguerra Roberta , Guglielmo Priscilla , Migliari Silvia , Sammartano Antonino , Baldari Giorgio , Maestroni Umberto , Silini Enrico Maria , Ruffini Livia
Published: May 2021

Renal cell carcinoma (RCC) shows variable FDG uptake; recently, PET/CT with prostate-specific membrane antigen (PSMA)–target radiotracers was demonstrated to be a promising tool in staging and restaging of RCC patients. We describe the case of a 77-year-old man with a lung metastasis of papillary RCC missed by CT scan who successfully underwent [18F]FDG PET/CT restaging. Targeted therapy with sunitinib was administered. A [68Ga]PSMA PET/CT performed during follow-up demonstrated, among the already known lesions, also a bone marrow metastasis, missed by previous CT scans. This case demonstrates that PET/CT molecular imaging with [18F]FDG and [68Ga]PSMA is superior to conventional imaging in RCC restaging and in assessing therapy response.
18F-Fluciclovine–Avid Pulmonary Hamartoma
Authors: Baldeosingh Sacha C. , Rowe Steven P. , Greco Stephen C. , Paller Channing J. , Goel Reema
Published: May 2021

A 73-year-old man with history of grade group 1/Gleason 3 + 3 = 6 prostate adenocarcinoma status post prostatectomy had subsequent biochemical recurrence with serum prostate-specific antigen level of 2.4 ng/mL. He underwent an 18F-fluciclovine PET/CT scan that demonstrated a left prostate bed recurrence and an incidental 18F-fluciclovine–avid smooth-edged solitary lung nodule with internal fat attenuation. Such uptake of 18F-fluciclovine in a lung hamartoma could be mistaken for prostate cancer metastasis. Given the increasing use of advanced imaging for prostate cancer, there is need for the imaging specialist to know about pitfalls and how to interpret them.
Evaluation of Nasal Mucociliary Clearance Time in COVID-19 Patients
Authors: Çeçen Ayse , Bayraktar Cem , Özgür Abdulkadir , Akgül Gökhan , Günal Özgür
Published: May 2021

Background:

Coronavirus Disease 2019 (COVID-19) is a viral pandemic emerging in East Asia and spreading rapidly to the rest of the world and continuing in our country. The number of studies examining the symptoms of the otolaryngology system and organs in COVID-19 patients is limited. The purpose of this study is to show whether COVID-19 infections cause any changes in nasal physiology in adult patients by measuring the mucociliary clearance (MCC) time with the saccharin test.

Methods:

One hundred one patients with laboratory-confirmed COVID-19 infection (group 1, n = 42 smokers and group 2, n = 59 nonsmokers) and 87 individuals without COVID-19 infection as the control group (group 3, n = 33 smokers and group 4, n = 54 nonsmokers) were included in the study. A saccharin test was used to evaluate the nasal MCC time.

Results:

Mucociliary clearance test averages of the groups were determined as 473.571 ± 263.684, 442.966 ± 228.463, 468.333 ± 267.367, 412.629 ± 192.179 seconds, respectively. When the test durations were examined, the group with the most prolonged MCC duration was determined as the smoking COVID (+) patient group (473.571 ± 263.684 seconds). The second group, with the most prolonged MCC duration, was determined as the smoking control group (468.333 ± 267.367 seconds). No statistically significant difference was found in intergroup mucociliary clearance time (P = 0.760).

Conclusion:

Although the authors found that smoking and viral infections prolong the MCC duration in our study, they did not find a statistically significant difference between the groups in terms of MCC duration.
Afferent and Efferent Neuro-Ophthalmic Complications of Coronavirus Disease 19
Authors: Tisdale Alanna K. , Dinkin Marc , Chwalisz Bart K.
Published: May 2021

Purpose:

To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19) documented in the literature thus far.

Methods:

The PubMed and Google Scholar databases were searched using the keywords: Neuro-Ophthalmology, COVID-19, SARS-CoV-2, and coronavirus. A manual search through reference lists of relevant articles was also performed.

Results/Conclusions:

The literature on COVID-associated neuro-ophthalmic disease continues to grow. Afferent neuro-ophthalmic complications associated with COVID-19 include optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. Efferent neuro-ophthalmic complications associated with COVID-19 include cranial neuropathies, Miller Fisher syndrome, Adie's pupils, ocular myasthenia gravis, nystagmus and eye movement disorders. Proposed mechanisms of neurologic disease include immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy, and direct viral neurotropism. When patients present to medical centers with new onset neuro-ophthalmic conditions during the pandemic, COVID-19 infection should be kept on the differential.
Uncovering the compounding effects of COVID-19 and racism on mental health disparities among biomedical PhD and MD students
Authors: Schad Allison , Layton Rebekah L. , Ragland Debra , Cook Jeanette Gowen
Published: May 2021

The increasing visibility of mental health challenges for academic and graduate trainee populations has led to discussion of the role higher education institutions should play to address trainee mental health, particularly during the COVID-19 pandemic and ongoing racial injustice. To address the growing concern about training impacts on medical and biomedical doctoral trainee mental health, a cross-sectional study (n=957) was conducted using institutional annual survey data analyzed by type of training program, race/ethnicity, and survey year on measures of depression, anxiety, hazardous alcohol use, problems related to substance use, and suicidal ideation. Results indicated significant differences for rates of depression, anxiety, and suicidal ideation, with biomedical doctoral trainees showing greater incidence than medical doctoral trainees, and underrepresented minority trainees showing greater incidence than well-represented trainees. The concerningly high rates of depression, anxiety, and suicidal ideation among these trainee populations suggest that medical and biomedical doctoral training environments must be transformed in addition to expanding mental health support resources.
Liver-specific polygenic risk score is more strongly associated than genome-wide score with Alzheimer’s disease diagnosis in a case-control analysis
Authors: Panyard Daniel J. , Deming Yuetiva K. , Darst Burcu F. , Van Hulle Carol A. , Blennow Kaj , Kollmorgen Gwendlyn , Suridjan Ivonne , Carlsson Cynthia M. , Johnson Sterling C. , Asthana Sanjay , Engelman Corinne D. , Lu Qiongshi
Published: May 2021

Although our understanding of Alzheimer’s disease (AD) has greatly improved in recent years, the root cause remains unclear, making it difficult to find effective diagnosis and treatment options. Our understanding of the pathophysiology underlying AD has benefited from genomic analyses, including those that leverage polygenic risk score (PRS) models of disease. In many aspects of genomic research the use of functional annotation has been able to improve the power of genomic models. Here, we leveraged genomic functional annotations to build tissue-specific PRS models for 13 tissues and applied the scores to two longitudinal cohort studies of AD. The PRS model that was most predictive of AD diagnosis relative to cognitively unimpaired participants was the liver tissue score: n = 1,116; odds ratio (OR) (95% confidence interval [CI]) = 2.19 (1.70-2.82) per standard deviation (SD) increase in PRS; P = 1.46 × 10−9. After removing theAPOElocus from the PRS models, the liver score was the only PRS to remain statistically significantly associated with AD diagnosis after multiple testing correction, although the effect was weaker: OR (95% CI) = 1.55 (1.19-2.02) per SD increase in PRS; P = 0.0012. In follow-up analysis, the liver PRS was statistically significantly associated with levels of amyloid (P = 3.53 × 10−6) and tau (P = 1.45 × 10−5) in the cerebrospinal fluid (CSF) (when theAPOElocus was included) and nominally associated with CSF soluble TREM2 levels (P = 0.042) (when theAPOElocus was excluded). These findings provide further evidence of the role of the liver-functional genome in AD and the benefits of incorporating functional annotation into genomic research.
COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes
Authors: Ciapponi Agustín , Bardach Ariel , Comandé Daniel , Berrueta Mabel , Argento Fernando J. , Cairoli Federico Rodriguez , Zamora Natalia , María Victoria Santa , Xiong Xu , Zaraa Sabra , Mazzoni Agustina , Buekens Pierre
Published: May 2021

Background

We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783).

Methods

We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR’s results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables.

Results

We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had “critically low” overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks.

Conclusion

This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Tweetable abstract

A new comprehensive overview of the best available systematic reviews about the harmful effects of COVID-19 on maternal/perinatal outcomes.
Understanding microvascular thrombosis in COVID-19 via massive single-cell imaging of circulating platelets
Authors: Kanno Hiroshi , Zhou Yuqi , Nishikawa Masako , Xiao Ting-Hui , Suzuki Takuma , Ibayashi Yuma , Harmon Jeffrey , Takizawa Shigekazu , Hiramatsu Kotaro , Nitta Nao , Kameyama Risako , Peterson Walker , Takiguchi Jun , Shifat-E-Rabbi Mohammad , Zhuang Yan , Yin Xuwang , Mohammad Rubaiyat Abu Hasnat , Deng Yunjie , Zhang Hongqian , Miyata Shigeki , Rohde Gustavo K. , Iwasaki Wataru , Yatomi Yutaka , Goda Keisuke
Published: May 2021

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we present a method for massive image-based profiling, temporal monitoring, and big data analysis of circulating platelets and platelet aggregates in the blood of COVID-19 patients at single-cell resolution, to provide previously unattainable insights into the disease. In fact, our analysis of the image data from 110 hospitalized patients shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, and respiratory condition of patients with COVID-19. Finally, high-dimensional analysis based on deep learning shows that the disease behaves as systemic thrombosis.
Seroprevalence of SARS-CoV-2 antibodies in broadcast media workers
Authors: Martins-Filho Paulo Ricardo , da Silva Danilo Nobre , Santos Danillo Menezes dos , Rezende Márcia Santos , Silva Jessica Paloma Rosa , da Silva Neto Josafá Bonifácio , Schimieguel Dulce Marta , Quintans-Júnior Lucindo José , de Souza Siqueira Quintans Jullyana , Nunes Paula Santos , de Sousa Araújo Adriano Antunes
Published: May 2021

In this cross-sectional study, we investigated the seroprevalence of SARS-CoV-2 antibodies in workers of radio and television (TV) in Sergipe state, Northeast Brazil. The study was conducted from December 1 to December 20, 2020, considered the beginning of the second wave of COVID-19 in the state. Our findings showed a high seroprevalence of SARS-CoV-2 antibodies in radio and TV workers, especially among those in the production and operation teams. Prevention and control protocols against COVID-19 should be revised and implemented by media companies. Broadcast media workers should be prioritized in COVID-19 vaccine strategies.
EDUCATIONAL NEEDS OF MEDICAL PRACTITIONERS ABOUT MEDICAL BILLING: A SCOPING REVIEW OF THE LITERATURE
Authors: Faux Margaret , Adams Jon , Wardle Jon
Published: May 2021

Introduction

The World Health Organization has suggested the solution to health system waste caused by incorrect billing and fraud is policing and prosecution. However, a growing body of evidence suggests leakage may not always be fraudulent or corrupt, with researchers suggesting medical practitioners may sometimes struggle to understand increasingly complex legal requirements around health financing and billing transactions, which may be improved through education. To explore this phenomenon further, we undertook a scoping review of the literature to identify the medical billing education needs of medical practitioners and whether those needs are being met.

Methods

Eligible records included English language materials published between 1 January 2000 and 4 May 2020. Searches were conducted on MEDLINE, PubMed, Google Scholar, CINAHL, LexisNexis and Heinonline.

Results

We identified 74 records as directly relevant to the search criteria. Despite undertaking a comprehensive, English language search, with no country restrictions, studies meeting the inclusion criteria were limited to three countries (Australia, Canada, U.S), indicating a need for further work internationally. The literature suggests the education needs of medical practitioners in relation to medical billing compliance are not being met and medical practitioners desire more education on this topic. Evidence suggests education may be effective in improving medical billing compliance and reducing waste in health systems. There is broad agreement amongst medical education stakeholders in multiple jurisdictions that medical billing should be viewed as a core competency of medical education, though there is an apparent inertia to include this competency in medical education curricula. Penalties for non-compliant medical billing are serious and medical practitioners are at risk of random audits and investigations for breaches of sometimes incomprehensible, and highly interpretive regulations they may never have been taught.

Conclusion

Despite acknowledged significance of waste in health systems due to poor practitioner knowledge of billing practices, there has been very little research to date on education interventions to improve health system efficiency at a practitioner level.
GP73 is a glucogenic hormone regulating SARS-CoV-2-induced hyperglycemia
Authors: Wan Luming , Yang Huan , Li Huilong , Gong Jing , Deng Yongqiang , Ke Yuehua , Yang Xiaopan , Lin Haotian , Zhang Yanhong , Wang Changjun , Li Dongyu , Wang Huapeng , Peng Yumeng , Yan Qiulin , Huang Linfei , Wang Xiaolin , Gao Qi , Lin Changqing , Zheng Fei , Xu Lei , Liu Jialong , Zhang Xuemiao , Yang Xiaoli , Qin Chengfeng , Sun Zhiwei , Wu Feixiang , Wei Congwen , Zhong Hui
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic condition increased the cellular secretion of GP73. Secreted GP73 trafficked to the liver and kidney to stimulate gluconeogenesis through cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of PKA kinase hub exerted by GP73. Notably, COVID-19 patients showed pathologically elevated plasma GP73, and neutralization of the secreted GP73 inhibited enhanced PKA signaling and glucose production associated with SARS-CoV-2 infection. GP73 blockade also reduced gluconeogenesis and lowered hyperglycemia in type 2 (T2D) diabetic mice. Therefore, our findings provide novel insight into the roles of GP73 as a key glucogenic hormone and mechanistic clues underlying the development of SARS-CoV-induced glucose abnormalities.
Dose-Related Effects of Ketamine for Antidepressant-Resistant Symptoms of Posttraumatic Stress Disorder in Veterans and Active Duty Military: A Double-blind, Randomized, Placebo-Controlled Multi-Center Clinical Trial
Authors: Abdallah Chadi G. , Roache John D. , Gueorguieva Ralitza , Averill Lynnette A. , Young-McCaughan Stacey , Shiroma Paulo R. , Purohit Prerana , Brundige Antoinette , Murff William , Ahn Kyung-Heup , Sherif Mohamed A. , Baltutis Eric J. , Ranganathan Mohini , D’Souza Deepak , Martini Brenda , Southwick Steven M. , Petrakis Ismene L. , Burson Rebecca R. , Guthmiller Kevin B. , López-Roca Argelio L. , Lautenschlager Karl A. , McCallin John P. , Hoch Matthew B. , Timchenko Alexandar , Souza Sergio E. , Bryant Charles E. , Mintz Jim , Litz Brett T. , Williamson Douglas E. , Keane Terence M. , Peterson Alan L. ,   Consortium to Alleviate PTSD, Krystal John H.
Published: May 2021

Background

This study tested the efficacy of repeated intravenous ketamine doses to reduce antidepressant-resistant symptoms of posttraumatic stress disorder (PTSD).

Methods

Veterans and service members with PTSD (n=158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n=54), low dose (0.2mg/kg; n=53) or standard dose (0.5mg/kg; n=51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS).

Results

There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard dose ketamine significantly reduced symptoms after the first infusion, while the low dose showed significant symptom reduction after the last infusion and at the 4-week follow-up. The standard ketamine dose also significantly ameliorated depression measured by the MADRS. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 hours and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability.

Conclusions

This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the low dose reduced PTSD symptoms and the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment.

ClinicalTrials.gov identifier

NCT02655692
How are sociodemographic factors associated with 2020/2021 seasonal influenza vaccination behavior under the COVID-19 pandemic?
Authors: Mori Takahiro , Nagata Tomohisa , Ikegami Kazunori , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa , Mori Koji ,   the CORoNaWork project
Published: May 2021

The 2020/2021 seasonal influenza vaccination was carried out under unique situations during the coronavirus disease 2019 (COVID-19) pandemic. Examining the factors affecting vaccine inoculation in a pandemic situation may provide valuable insights. The purpose of the current study was to investigate how the COVID-19 pandemic affected the 2020/2021 seasonal influenza vaccine intake. A cross-sectional study was conducted on workers aged 20–65 years on December 22–25, 2020, using data from an Internet survey. We set the presence or absence of 2020/2021 seasonal influenza vaccination as the dependent variable, and each aspect of sociodemographic factors, including gender, age, marital status, education, annual household income, and underlying disease, as independent variables. We performed a multilevel logistic regression analysis nested by residence. In total, 26,637 respondents (13,600 men, 13,037 women) participated, and a total of 11,404 individuals (42.8%) received the 2020/2021 influenza vaccine. Significantly more women than men were vaccinated, and the vaccination rate was higher among younger adults, married people, highly educated people, high-income earners, and those with underlying disease. The current results suggested that the relationship between seasonal influenza vaccination behavior and sociodemographic factors differed from the results reported in previous studies in terms of age. These findings suggest that, during the COVID-19 pandemic, young people may have become more aware of the risk of contracting influenza and of the effectiveness of the influenza vaccine. In addition, information interventions may have had a positive effect.
Transcriptome analyses reveal tau isoform-driven changes in transposable element and gene expression
Authors: Grundman Jennifer , Spencer Brian , Sarsoza Floyd , Rissman Robert A.
Published: May 2021

Alternative splicing of the gene MAPT produces several isoforms of tau protein. Overexpression of these isoforms is characteristic of tauopathies, which are currently untreatable neurodegenerative diseases. Though non-canonical functions of tau have drawn interest, the role of tau isoforms in these diseases has not been fully examined and may reveal new details of tau-driven pathology. In particular, tau has been shown to promote activation of transposable elements — highly regulated nucleotide sequences that replicate throughout the genome and can promote immunologic responses and cellular stress. This study examined tau isoforms’ roles in promoting cell damage and dysregulation of genes and transposable elements at a family-specific and locus-specific level. We performed immunofluorescence, Western blot and cytotoxicity assays, along with paired-end RNA sequencing on differentiated SH-SY5Y cells infected with lentiviral constructs of tau isoforms and treated with amyloid-beta oligomers. Our transcriptomic findings were validated using publicly available RNA-sequencing data from Alzheimer’s disease, progressive supranuclear palsy and control human samples from the Accelerating Medicine’s Partnership for AD (AMP-AD).

Significance for biochemical assays was determined using Wilcoxon ranked-sum tests and false discovery rate. Transcriptome analysis was conducted through DESeq2 and the TEToolkit suite available from the Hammell lab at Cold Spring Harbor Laboratory. Our analyses show overexpression of different tau isoforms and their interactions with amyloid-beta in SH-SY5Y cells result in isoform-specific changes in the transcriptome, with locus-specific transposable element dysregulation patterns paralleling those seen in patients with Alzheimer’s disease and progressive supranuclear palsy. Locus-level transposable element expression showed increased dysregulation of L1 and Alu sites, which have been shown to drive pathology in other neurological diseases. We also demonstrated differences in rates of cell death in SH-SY5Y cells depending on tau isoform overexpression. These results demonstrate the importance of examining tau isoforms’ role in neurodegeneration and of further examining transposable element dysregulation in tauopathies.
Distribution of GOPC:ROS1and otherROS1fusions in glioma types
Authors: Sievers Philipp , Stichel Damian , Sill Martin , Schrimpf Daniel , Sturm Dominik , Selt Florian , Ecker Jonas , Miele Evelina , Kranendonk Mariëtte E. G. , Tops Bastiaan B. J. , Kohlhof-Meinecke Patricia , Beschorner Rudi , Kramm Christof M. , Hasselblatt Martin , Reifenberger Guido , Capper David , Wesseling Pieter , Milde Till , Korshunov Andrey , Witt Olaf , Pfister Stefan M. , Wick Wolfgang , von Deimling Andreas , Jones David T. W. , Sahm Felix
Published: May 2021

The ROS proto-oncogene 1 (ROS1) gene is rearranged in various cancers. The translated fusion protein presents an attractive therapeutic target, since specific inhibitors have been approved for several tumor types. In glioma,ROS1fusions are frequent within infantile hemispheric glioma, and single case reports on occurrences in other glioma types exist. However, a comprehensive analysis spanning the full width of glioma types and subtypes is lacking. We here assessed the spectrum and distribution ofROS1fusions by screening >20,000 glioma cases for typical chromosomal alterations, with subsequent RNA-sequencing for confirmation of candidate cases.ROS1fusions were identified in 16 cases, from low grade pilocytic astrocytoma WHO grade 1 to glioblastoma, IDH wildtype WHO grade 4. Thus, despite being enriched in some tumor types,ROS1fusions are not pathognomonic for specific glioma types and may consitute a relevant target in a variety of cases.
Identification of Differentially Expressed Genes and associated pathways common to Eyelid and Non-Ocular Basal Cell Carcinoma to understand the Molecular Biology of BCC
Authors: Vats Pranjal , Jayaraj Perumal , Sen Seema , Dahiya Shefali , Mohindroo Vanshika
Published: May 2021

Background

Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive.

Objective

This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers.

Material and method

The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively.

Results

A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC.

Conclusion

The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non-Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC.
3D confinement regulates stem cell fate
Authors: Dudaryeva Oksana Y. , Bucciarelli Aurelia , Bovone Giovanni , Jaydev Shibashish , Broguiere Nicolas , al-Bayati Marwa , Lütolf Marco , Tibbitt Mark W.
Published: May 2021

Biophysical properties of the cellular microenvironment, including stiffness and geometry, influence cell fate. Recent findings have implicated geometric confinement as an important regulator of cell fate determination. Our understanding of how mechanical signals direct cell fate is based primarily on two-dimensional (2D) studies. To investigate the role of confinement on stem cell fate in three-dimensional (3D) culture, we fabricated a single cell microwell culture platform and used it to investigate how niche volume and stiffness affect human mesenchymal stem cell (hMSC) fate. The viability and proliferation of hMSCs in confined 3D microniches were compared with the fate of unconfined cells in 2D culture. Physical confinement biased hMSC fate, and this influence was modulated by the niche volume and stiffness. The rate of cell death increased, and proliferation markedly decreased upon 3D confinement. We correlated the observed differences in hMSC fate to YES-associated protein (YAP) localization. In 3D microniches, hMSCs displayed primarily cytoplasmic YAP localization, indicating reduced mechanical activation upon confinement. These results demonstrate that 3D geometric confinement can be an important regulator of cell fate, and that confinement sensing is linked to canonical mechanotransduction pathways.
NOVA2 regulates neural circRNA biogenesis
Authors: Knupp David , Cooper Daphne A. , Saito Yuhki , Darnell Robert B. , Miura Pedro
Published: May 2021

Circular RNAs (circRNAs) are highly expressed in the brain and their expression increases during neuronal differentiation. The factors regulating circRNAs in the developing mouse brain are unknown. NOVA1 and NOVA2 are neural-enriched RNA-binding proteins with well-characterized roles in alternative splicing. Profiling of circRNAs from RNA-seq data revealed that global circRNA levels were reduced in embryonic cortex ofNova2but notNova1knockout mice. Analysis of isolated inhibitory and excitatory cortical neurons lacking NOVA2 revealed an even more dramatic reduction of circRNAs and establish a widespread role for NOVA2 in enhancing circRNA biogenesis. To investigate thecis-elements controlling NOVA2-regulation of circRNA biogenesis, we generated a backsplicing reporter based on theEfnb2gene. We found that NOVA2-mediated backsplicing of circ-Efnb2was impaired when YCAY clusters located in flanking introns were removed. CLIP and additional reporter analysis demonstrated the importance of NOVA2 binding sites located in both flanking introns of circRNA loci. NOVA2 is the first RNA-binding protein identified to globally promote circRNA biogenesis in the developing brain.
Pyk2 in dorsal hippocampus plays a selective role in spatial memory and synaptic plasticity
Authors: Mastrolia Vincenzo , Massadi Omar al , de Pins Benoit , Girault Jean-Antoine
Published: May 2021

Pyk2 is a Ca2+-activated non-receptor tyrosine kinase enriched in the forebrain, especially in pyramidal neurons of the hippocampus. Previous reports suggested its role in hippocampal synaptic plasticity and spatial memory but with contradictory findings possibly due to experimental conditions. Here we address this issue and show that novel object location, a simple test of spatial memory induced by a single training session, is altered in Pyk2 KO mice and that re-expression of Pyk2 in the dorsal hippocampus corrects this deficit. Bilateral targeted deletion of Pyk2 in dorsal hippocampus CA1 region also alters novel object location. Long term potentiation (LTP) in CA1 is impaired in Pyk2 KO mice using a high frequency stimulation induction protocol nut not with a theta burst protocol, explaining differences between previous reports. The same selective LTP alteration is observed in mice with Pyk2 deletion in dorsal hippocampus CA1 region. Thus, our results establish the role of Pyk2 in specific aspects of spatial memory and synaptic plasticity and show the dependence of the phenotype on the type of experiments used to reveal it. In combination with other studies they provide evidence for a selective role of non-receptor tyrosine kinases in specific aspects of hippocampal neurons synaptic plasticity.
Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins
Authors: Nowicka Urszula , Chroscicki Piotr , Stroobants Karen , Sladowska Maria , Turek Michal , Uszczynska-Ratajczak Barbara , Kundra Rishika , Goral Tomasz , Perni Michele , Dobson Christopher M. , Vendruscolo Michele , Chacinska Agnieszka
Published: May 2021

Mitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol. These deposits then cause further cytosolic accumulation and consequently aggregation of other mitochondrial proteins and disease-related proteins, including α-synuclein and amyloid β. This aggregation triggers a cytosolic protein homeostasis imbalance that is accompanied by specific molecular chaperone responses at both the transcriptomic and protein levels. Altogether, our results provide evidence that mitochondrial dysfunction, specifically protein import defects, contributes to impairments in protein homeostasis, thus revealing a possible molecular mechanism by which mitochondria are involved in neurodegenerative diseases.
Negative Urgency as a Risk Factor for Hazardous Alcohol Use: Dual Influences of Cognitive Control and Reinforcement Processing
Authors: Rawls Eric , Wolkowicz Noah R. , Ham Lindsay S. , Lamm Connie
Published: May 2021

Negative Urgency (NU) is a prominent risk factor for hazardous alcohol use. While research has helped elucidate how NU relates to neurobiological functioning with respect to alcohol use, no known work has contextualized such functioning within existing neurobiological theories in addiction. Therefore, we elucidated mechanisms contributing to the NU–hazardous alcohol use relationship by combining NU theories with neurobiological dual models of addiction, which posit addiction is related to cognitive control and reinforcement processing. Fifty-five undergraduates self-reported NU and hazardous alcohol use. We recorded EEG while participants performed a reinforced flanker task. We measured cognitive control using N2 activation time-locked to the incongruent flanker stimulus, and we measured reinforcement processing using the feedback-related negativity (FRN) time-locked to better-than-expected negative reinforcement feedback. We modeled hazardous drinking using hierarchical regression, with NU, N2, and FRN plus their interactions as predictors. The regression model significantly predicted hazardous alcohol use, and the three-way interaction (NU×N2×FRN) significantly improved model fit. In the context of inefficient processing (i.e., larger N2s and FRNs), NU demonstrated a strong relationship with hazardous alcohol use. In the context of efficient processing (i.e., smaller N2s and FRNs), NU was unrelated to hazardous alcohol use. This analysis provides preliminary evidence that brain mechanisms of cognitive control and reinforcement processing influence the relationship between NU and hazardous alcohol use, and confirms a specific influence of negative reinforcement processing. Future clinical research could leverage these neurobiological moderators for substance misuse treatment.
Differential contributions of ventral striatum subregions to the motivational and hedonic components of the affective processing of the reward
Authors: Pool Eva R. , Munoz Tord David , Delplanque Sylvain , Stussi Yoann , Cereghetti Donato , Vuilleumier Patrik , Sander David
Published: May 2021

The ventral striatum is implicated in the affective processing of the reward, which can be divided into a motivational and a hedonic component. Here, we examined whether these two components rely on distinct neural substrates within the ventral striatum in humans. We used a high-resolution fMRI protocol targeting the ventral striatum combined with a Pavlovian-instrumental task and a hedonic reactivity task. Both tasks involved an olfactory reward, thereby allowing us to measure Pavlovian-triggered motivation and sensory pleasure for the same reward within the same participants. Our findings show that different subregions of the ventral striatum are dissociable in their contributions to the motivational and the hedonic component of the affective processing of the reward. Parsing the neural mechanisms and the interplay between Pavlovian incentive processes and hedonic processes might have important implications for understanding compulsive reward-seeking behaviors such as addiction, binge eating, or gambling.
Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
Authors: Wang Weisheng , Schuette Peter J. , La-Vu Mimi Q. , Tobias Brooke Christine , Čeko Marta , Kragel Philip A. , Reis Fernando Midea Cuccovia V. , Ji Shiyu , Sehgal Megha , Maesta-Pereira Sandra , Chakerian Meghmik , Silva Alcino J , Canteras Newton S. , Wager Tor D. , Kao Jonathan C. , Adhikari Avishek
Published: May 2021

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Lastly, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd as a central node of the escape network.
METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs
Authors: Lentini Jenna M. , Bargabos Rachel , Chen Chen , Fu Dragony
Published: May 2021

A subset of eukaryotic tRNAs is methylated in the anticodon loop to form the 3-methylcytosine (m3C) modification. In mammals, the number of tRNAs containing m3C has expanded to include mitochondrial (mt) tRNA-Ser-UGA and mt-tRNA-Thr-UGU. Whereas the enzymes catalyzing m3C formation in nuclear-encoded cytoplasmic tRNAs have been identified, the proteins responsible for m3C modification in mt-tRNAs are unknown. Here, we show that m3C formation in human mt-tRNAs is dependent upon the Methyltransferase-Like 8 (METTL8) enzyme. We find that METTL8 is a mitochondria-associated protein that interacts with mitochondrial seryl-tRNA synthetase along with mt-tRNAs containing m3C. Human cells deficient in METTL8 exhibit loss of m3C modification in mt-tRNAs but not nuclear-encoded tRNAs. Consistent with the mitochondrial import of METTL8, the formation of m3C in METTL8-deficient cells can be rescued by re-expression of wildtype METTL8 but not by a METTL8 variant lacking the N-terminal mitochondrial localization signal. Notably, METTL8-deficiency in human cells causes alterations in the native migration pattern of mt-tRNA-Ser-UGA suggesting a role for m3C in tRNA folding. Altogether, these findings demonstrate that METTL8 is required for m3C formation in mitochondrial tRNAs and uncover a potential role for m3C modification in mitochondrial tRNA structure.
Myosins generate contractile force and maintain organization in the cytokinetic contractile ring
Authors: McDargh Zachary , Wang Shuyuan , Chin Harvey F. , Thiyagarajan Sathish , Karatekin Erdem , Pollard Thomas D. , O’Shaughnessy Ben
Published: May 2021

During cytokinesis cells assemble an actomyosin contractile ring whose tension constricts and divides cells, but the ring tension was rarely measured. Actomyosin force generation is well understood for the regular sarcomeric architecture of striated muscle, but recent super-resolution studies of fission yeast contractile rings revealed organizational building blocks that are not sarcomeres but irregularly positioned plasma membrane-anchored protein complexes called nodes. Here we measured contractile ring tensions in fission yeast protoplast cells. The myosin II isoforms Myo2 and Myp2 generated the tension, with a ~2-fold greater contribution from Myo2. Simulations of a molecularly detailed ring model revealed a sliding node mechanism for tension, where nodes hosting tense actin filaments were pulled bidirectionally around the ring. Myo2 and Myp2 chaperoned self-assembling components into the ring organization, and anchored the ring against bridging instabilities. Thus, beyond force production, Myo2 and Myp2 are the principal organizers, bundlers and anchors of the contractile ring.