bluuebunny/crossref_metadata_2025 huggingface dataset:
Bcar1/p130Cas is essential for ventricular development and neural crest cell remodelling of the cardiac outflow tract
Authors: Mahmoud Marwa , Evans Ian , Wisniewski Laura , Tam Yuen , Walsh Claire , Walker-Samuel Simon , Frankel Paul , Scambler Peter , Zachary Ian
Published: July 2021

Aims

The adapter protein p130Cas, encoded by the Bcar1 gene, is a key regulator of cell movement, adhesion, and cell cycle control in diverse cell types. Bcar1 constitutive knockout mice are embryonic lethal by embryonic days (E) 11.5–12.5, but the role of Bcar1 in embryonic development remains unclear. Here, we investigated the role of Bcar1 specifically in cardiovascular development and defined the cellular and molecular mechanisms disrupted following targeted Bcar1 deletions.

Methods and results

We crossed Bcar1 floxed mice with Cre transgenic lines allowing for cell-specific knockout either in smooth muscle and early cardiac tissues (SM22-Cre), mature smooth muscle cells (smMHC-Cre), endothelial cells (Tie2-Cre), second heart field cells (Mef2c-Cre), or neural crest cells (NCC) (Pax3-Cre) and characterized these conditional knock outs using a combination of histological and molecular biology techniques. Conditional knockout of Bcar1 in SM22-expressing smooth muscle cells and cardiac tissues (Bcar1SM22KO) was embryonically lethal from E14.5–15.5 due to severe cardiovascular defects, including abnormal ventricular development and failure of outflow tract (OFT) septation leading to a single outflow vessel reminiscent of persistent truncus arteriosus. SM22-restricted loss of Bcar1 was associated with failure of OFT cushion cells to undergo differentiation to septal mesenchymal cells positive for SMC-specific α-actin, and disrupted expression of proteins and transcription factors involved in epithelial-to-mesenchymal transformation (EMT). Furthermore, knockout of Bcar1 specifically in NCC (Bcar1PAX3KO) recapitulated part of the OFT septation and aortic sac defects seen in the Bcar1SM22KO mutants, indicating a cell-specific requirement for Bcar1 in NCC essential for OFT septation. In contrast, conditional knockouts of Bcar1 in differentiated smooth muscle, endothelial cells, and second heart field cells survived to term and were phenotypically normal at birth and postnatally.

Conclusion

Our work reveals a cell-specific requirement for Bcar1 in NCC, early myogenic and cardiac cells, essential for OFT septation, myocardialization and EMT/cell cycle regulation and differentiation to myogenic lineages.
Ecology and biogeography of the ‘marine Geitlerinema’ cluster and a description of Sodalinema orleanskyi sp. nov., Sodalinema gerasimenkoae sp. nov., Sodalinema stali sp. nov. and Baaleninema simplex gen. et sp. nov. (Oscillatoriales, Cyanobacteria)
Authors: Samylina Olga S , Sinetova Maria A , Kupriyanova Elena V , Starikov Alexander Yu , Sukhacheva Marina V , Dziuba Marina V , Tourova Tatiana P
Published: July 2021

Filamentous cyanobacteria belonging to the ‘marine Geitlerinema’ cluster are spread worldwide in saline environments and considered to play an important ecological role. However, the taxonomy of this group remains unclear. Here, we analyzed the phylogeny, ecology and biogeography of the ‘marine Geitlerinema’ cluster representatives and revealed two subclusters: 1) an ‘oceanic’ subcluster containing PCC7105 clade and BBD clade with free-living and pathogenic strains distributed in Atlantic, Indian and Pacific Ocean-related localities, and 2) a Sodalinema subcluster containing free-living strains from marine, hypersaline, saline-alkaline and soda lake habitats from the Eurasian and African continents. Polyphasic analysis using genetic and phenotypic criteria demonstrated that these two groups represent separate genera. Representatives of Sodalinema subcluster were phylogenetically attributed to the genus Sodalinema. Our data expand the ecological and geographical distribution of this genus. We emended the description of the genus Sodalinema and proposed three new species differing in phylogenetic, geographic and ecological criteria: Sodalinema orleanskyi sp. nov., Sodalinema gerasimenkoae sp. nov. and Sodalinema stali sp. nov. Additionally, a new genus and species Baaleninema simplex gen. et sp. nov. was discribed within the PCC7105 clade. By this, we put in order the current confusion of the ‘marine Geitlerinema’ group and highlight its ecological diversity.
Response to sulfur in Schizosaccharomyces pombe
Authors: Ohtsuka Hokuto , Shimasaki Takafumi , Aiba Hirofumi
Published: July 2021

Sulfur is an essential component of various biologically important molecules, including methionine, cysteine and glutathione, and it is also involved in coping with oxidative and heavy metal stress. Studies using model organisms, including budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe), have contributed not only to understanding various cellular processes but also to understanding the utilization and response mechanisms of each nutrient, including sulfur. Although fission yeast can use sulfate as a sulfur source, its sulfur metabolism pathway is slightly different from that of budding yeast because it does not have a trans-sulfuration pathway. In recent years, it has been found that sulfur starvation causes various cellular responses in S. pombe, including sporulation, cell cycle arrest at G2, chronological lifespan extension, autophagy induction and reduced translation. This MiniReview identifies two sulfate transporters in S. pombe, Sul1 (encoded by SPBC3H7.02) and Sul2 (encoded by SPAC869.05c), and summarizes the metabolic pathways of sulfur assimilation and cellular response to sulfur starvation. Understanding these responses, including metabolism and adaptation, will contribute to a better understanding of the various stress and nutrient starvation responses and chronological lifespan regulation caused by sulfur starvation.
Melatonin in plants: what we know and what we don’t
Authors: Zhang Zixin , Zhang Yang
Published: July 2021

Melatonin is an endogenous micromolecular compound of indoleamine with multiple physiological functions in various organisms. In plants, melatonin is involved in growth and development, as well as in responses to biotic and abiotic stresses. Furthermore, melatonin functions in phytohormone-mediated signal transduction pathways. There are multiple melatonin biosynthesis pathways, and the melatonin content in plants is greatly affected by intrinsic genetic characteristics and external environmental factors. Although melatonin biosynthesis has been extensively studied in model plants, it remains uncharacterized in most plants. This article focuses on current knowledge on the biosynthesis, regulation and application of melatonin, particularly for fruit quality and preservation. In addition, it highlights the links between melatonin and other hormones, as well as future research directions.
Robotic total gastrectomy for carcinoma in the remnant stomach: a comparison with laparoscopic total gastrectomy
Authors: Li Zheng-Yan , Liu Jia-Jia , Yu Pei-Wu , Zhao Yong-Liang , Shi Yan , Luo Zi-Yan , Wu Bin , Wang Jun-Jie , Qian Feng
Published: July 2021

Background

Total gastrectomy for carcinoma in the remnant stomach (CRS) remains a technically demanding procedure. Whether robotic surgery is superior, equal, or inferior to laparoscopic surgery in patients with CRS is unclear. This study was designed to compare the efficacy and safety of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for the treatment of CRS.

Methods

In this cohort study, we retrospectively analysed the data from patients who underwent RTG or LTG for CRS at Southwest Hospital (Chongqing, China) between May 2006 and October 2019. The surgical outcomes, post-operative complications, and survival outcomes between the two groups were compared.

Results

Compared with LTG, RTG was associated with similar effective operation time (272.0 vs 297.9 min, P = 0.170), higher total costs (105,967.2 vs 81,629.5 RMB, P < 0.001), and less estimated blood loss (229.2 vs 288.8 mL, P = 0.031). No significant differences were found between the robotic and laparoscopic groups in terms of conversion rate, time to first flatus, time to first soft diet, post-operative hospital stay, post-operative complications, R0 resection rate, and number of retrieved lymph nodes (all P > 0.05). The 3-year disease-free survival and 3-year overall survival rates were comparable between the two groups (65.5% vs 57.5%, P = 0.918; 69.0% vs 60.0%, P = 0.850, respectively).

Conclusions

RTG is a safe and feasible procedure for the treatment of CRS and could serve as an optimal treatment for CRS.
Schistosomiasis: still a neglected disease
Authors: Meltzer Eyal
Published: July 2021

Schistosomiasis remains an infrequent travel-related disease, mostly affecting returnees from Sub-Saharan Africa. The neglect of schistosomiasis research and development has consequences not only for endemic populations but also for travellers. Recent studies highlight deficits in clinical recognition, diagnostics and therapy of travel-related schistosomiasis, with significant morbidity, both acute and chronic.
LncRNA LINC01088 inhibits the function of trophoblast cells, activates the MAPK-signaling pathway and associates with recurrent pregnancy loss
Authors: Zhao Hui , Li Yali , Dong Nana , Zhang Lei , Chen Xi , Mao Huihui , Al-Ameri Samed Ahmed Al-Ezzi , Wang Xiaoling , Wang Qun , Du Lutao , Wang Chuanxin , Mao Haiting
Published: July 2021

Long noncoding RNAs (lncRNAs) have been reported to be involved in various cellular processes and to participate in a variety of human diseases. Recently, increasing studies have reported that lncRNAs are related to many reproductive diseases, such as pathogenesis of recurrent pregnancy loss (RPL), preeclampsia (PE) and gestational diabetes mellitus (GDM). In this study, we aimed to investigate the effect of LINC01088 in trophoblast cells and its potential role in pathogenesis of RPL. LINC01088 was found to be upregulated in first-trimester chorionic villi tissues from RPL patients. Increased LINC01088 repressed proliferation, migration and invasion of trophoblast cells, and promoted apoptosis of trophoblast cells. Further exploration indicated that LINC01088 decreased the production of nitric oxide (NO) by binding and increasing Arginase-1 and decreasing eNOS protein levels. Importantly, JNK and p38 MAPK-signaling pathways were active after overexpression of LINC01088. In conclusion, our studies demonstrated that LINC01088 plays an important role in the pathogenesis of RPL, and is a potential therapeutic target for the treatment of RPL.
Plant-predominant eating patterns – how effective are they for treating obesity and related cardiometabolic health outcomes? – a systematic review
Authors: Remde Alan , DeTurk Stephen N , Almardini A , Steiner Lauren , Wojda Thomas
Published: July 2021

Context

The obesity epidemic is a main driver of the chronic disease epidemic; however, present treatment approaches have suboptimal efficacy.

Objectives

To assess the efficacy of plant-predominant (vegan, vegetarian, plant-based whole foods [PBWFs]) diets in treating obesity and its main cardiometabolic sequelae: hyperlipidemia (HLD); indices of insulin resistance, glycemic control, and diabetes mellitus type 2 (DM2); and cardiovascular disease (CVD), including hypertension (HTN).

Data Sources

A systematic search of multiple databases was conducted for articles published between November 2019 and February 2020; databases searched included: PubMed, Medline (Ovid), Cochrane, CENTRAL, and CINAHL.

Data Extraction and Analysis

All interventional trials (randomized controlled trials [RCTs] and trials of non-randomized experimental design) that met the inclusion criteria (English language, duration of at least 4 weeks, primary end point congruent with above objectives, no major flaws in research design that would prevent interpretation) were included in the review. A total of 3135 articles were scanned and 84 were selected. The articles were collated and summarized in 2 evidence tables. Risk of bias for RCTs was assessed using the Cochrane Risk-of-Bias tool 2 as a guide. For non-randomized trials, higher risk of bias was assumed, and the JBI Critical Appraisal tool was used as a guide to determine inclusion.

Results

Plant-based diets, in general, demonstrated improved weight control and cardiometabolic outcomes related to lipids, cardiovascular end points, blood pressure, insulin sensitivity, A1C, and fasting glucose, and a lower risk of diabetes compared with usual diets and in some cases standard health-oriented diets such as the American Heart Association (AHA), American Diabetic Association (ADA), and Mediterranean diets. Preliminary studies suggest plant-predominant diets practiced as part of healthy lifestyle interventions may stabilize or even reverse DM 2 and CVD. The acceptability and sustainability of plant-predominant diets where measured were generally similar to other health-oriented diets.

Conclusion

Plant-predominant diets can play a major role in reversing the obesity and chronic disease epidemics. In the setting of sustained lifestyle intervention programs, they may arrest or even reverse DM2 and CVD. Further higher-level RCTs are needed to confirm and expand on these findings.
Parent-administered Neurodevelopmental Follow up in Children After Picornavirus CNS Infections
Authors: Stephens Carol , Reynolds Clare , Cremin Molly , Barry Rachel , Morley Ursula , Gibson Louise , De Gascun Cillian F. , Felsenstein Susana
Published: July 2021

Background:

Data on the neurodevelopment of children who experienced central nervous system (CNS) infections with enteroviruses (EV) or parechoviruses (hPeV) is scarce and mostly limited to follow up of short-term outcomes.

Methods:

Parents of children who presented between 2014 and 2019, underwent a lumbar puncture and whose cerebrospinal fluid was polymerase chain reaction positive for EV or hPeV, were asked to complete a care-giver-administered neurodevelopmental assessment tool (The Ages and Stages Instrument [ASQ3]). Clinical data of the infective episode were collected from patient notes.

Results:

Of 101 children, 43 (10 hPeV+, 33 EV+) submitted ASQ3 results. Median age at assessment was 38.9 months (interquartile range, 15.4–54.8), the follow-up interval 3 years (median 37 months; interquartile range, 13.9–53.1). Age, inflammatory markers, and cerebrospinal fluid pleocytosis during the infective event were not associated with ASQ3 scores. In 23 children (17 EV+, 6 hPeV+), no neurodevelopmental concerns were reported. Two more had preexisting developmental delay and were excluded. Of the remaining, 18/41 (43.9%) reported ASQ3 scores indicating need for monitoring or professional review in at least 1 category, not differing by pathogen (EV 14/31, 45.2%; hPeV 4/10, 40%; P = 0.71). Seven children will require formal review, scoring ≥2 SD below the mean in at least 1 category (6/31 EV+, 1/10 hPeV+, P = 0.7), 3 scored ≥2 SD below the mean in more than 1 area.

Conclusions:

Parent-administered developmental assessment of children with a history of early picornavirus infection of the CNS identified a subgroup that requires formal neurodevelopmental review. Wider application of community-based developmental screening will complement our understanding of the impact of CNS infections in early childhood.
Advancing our understanding of genetic risk factors and potential personalized strategies in pelvic organ prolapse: largest GWAS to date reveals 19 novel associated loci
Authors: Pujol-Gualdo Natàlia , Läll Kristi , Lepamets Maarja ,   Estonian Biobank Research Team, Rossi Henna-Riikka , Arffman Riikka K , Piltonen Terhi T , Mägi Reedik , Laisk Triin
Published: July 2021

Objectives

To identify the genetic determinants of pelvic organ prolapse (POP) and assess the predictive ability of polygenic risk scores (PRS) alone or in combination with clinical risk factors.

Design

Meta-analysis of genome-wide association studies (GWAS) and PRS construction and validation.

Setting

GWAS summary statistics from three European datasets and individual-level data from Estonian Biobank, including phenotype questionnaire and measurement panel, together with follow-up data from linkage with national health-related registries.

Participants

A total of 28,086 women with POP and 546,321 controls of European ancestry. Genetic risk scores were derived from a dataset of 20,118 cases and 427,426 controls of European ancestry and validated in a target dataset of 7,896 cases and 118,895 controls. Cases were defined using ICD codes and classical risk factors were derived from questionnaire data and ICD10 codes.

Results

The identified novel loci reinforce the role of connective tissue abnormalities, urogenital tract development and point towards association with a range of cardiometabolic traits. A novel PRS combining 3,242,959 variants demonstrated that women in the top 5% have 1.63 (95% CI: 1.37 to 1.93) times the hazard of developing POP compared to the rest of the women. When analyzing PRS in incident POP, it showed similar predictive ability (Harrell C-statistic 0.583, sd=0.007) than five established clinical risk factors (number of children, body mass index (BMI), ever smoked, constipation and asthma) combined (Harrell C-statistic 0.588, sd=0.007) and demonstrated its incremental value in combination with these (Harrell C-statistic 0.630, sd=0.007).

Conclusions

The largest GWAS meta-analysis in POP to date identified 26 genetic loci which establish links between POP and connective tissue abnormalities, urogenital development and cardiometabolic health. We present a PRS for POP which provides the first potential tool for preventive strategies and early detection of higher risk susceptibility to POP including genetic risk factors.
Immunogenicity of Oxford-AstraZeneca COVID-19 vaccine in Vietnamese healthcare workers
Authors: Van Vinh Chau Nguyen , Nguyet Lam Anh , Truong Nguyen Thanh , Toan Le Mau , Dung Nguyen Thanh , Hung Le Manh , Nhan Mai Thanh , Huy Man Dinh Nguyen , Ngoc Nghiem My , Thao Huynh Phuong , Hoang Tu Tran Nguyen , Mai Huynh Kim , Hung Do Thai , Han Ny Nguyen Thi , Thanh Le Kim , Anh Nguyen To , Thu Hong Nguyen Thi , Truc Nhu Le Nguyen , Yen Lam Minh , Choisy Marc , Thanh Tran Tan , Thwaites Guy , Van Tan Le ,   OUCRU COVID-19 Research Group
Published: July 2021

We studied the immunogenicity of Oxford-AstraZeneca vaccine in Vietnamese healthcare workers. We collected blood samples before each dose, at 14 days after each dose, and month 1 and 3 after dose 1 from each participant alongside demographics data. We measured neutralizing antibodies using a surrogate virus neutralization assay. The 554 study participants (136 males and 418 females) were aged between 22-71 years (median: 36 years). 104 and 94 out of 144 selected participants were successfully followed up at 14 days after dose 2 and 3 months after dose 1, respectively. Neutralizing antibodies increased after each dose, with the sero-conversion rate reaching 98.1% (102/104) at 14 days after dose 2. At month 3 after dose 1, neutralizing antibody levels decreased, while 94.7% (89/94) of the study participants remained seropositive. Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese healthcare workers. The requirement for a third dose warrants further research.
Endothelial dysfunction determines severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks
Authors: Ruhl Louisa , Pink Isabell , Kühne Jenny F. , Beushausen Kerstin , Keil Jana , Christoph Stella , Sauer Andrea , Boblitz Lennart , Schmidt Julius , David Sascha , Jäck Hans-Martin , Roth Edith , Cornberg Markus , Schulz Thomas F. , Welte Tobias , Höper Marius M. , Falk Christine S.
Published: July 2021

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 and disease recovery in convalescent patients, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. Core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.
The Lived Experience of Implementing Infection Control Measures in Care Homes during two waves of the COVID-19 Pandemic. A mixed-methods study
Authors: Bunn Diane , Brainard Julii , Lane Kathleen , Salter Charlotte , Lake Iain
Published: July 2021

Context

During COVID-19 care-homes had to implement strict Infection Control Measures (ICMs), impacting on care and staff morale.

Objectives

To explore the lived experiences of care-home staff in implementing ICMs.

Methods

Mixed-methods study comprising 238 online survey responses and 15 in-depth interviews with care-home staff, November 2020-January 2021 in England.

Results

Three themes were identified: ‘Integrating COVID-19 ICMs with caring’, ‘Conveying knowledge and information’, ‘Professional and personal impacts of care-work during the pandemic’. Reported adherence to ICMs was high but fatalistic attitudes towards COVID-19 infection were present. Challenges of providing care using personal protective equipment (PPE), especially for residents with dementia, were highlighted. Interviewees reported dilemmas between strictly implementing ICMs and conflicts with providing best care to residents and preserving personal space. Nine months into COVID-19, official guidance was reported as confusing, constantly changing and poorly suited to care-homes. Care-home staff appreciated opportunities to work with other care-homes and experts to interpret and implement guidance. ICM training was undertaken using multiple techniques but with little evaluation of these or how to sustain behaviour change.

Limitations

Results may not be generalizable to other countries.

Implications

COVID-19 has had a profound effect on well-being of care-home staff. Despite challenges, participants reported broadly good morale, potentially a consequence of supportive colleagues and management. Nevertheless, clear, concise and care-home focussed ICM guidance is still needed. This should include evidence-based assessments on implementing and sustaining adherence. Groups of care-home staff and ICM experts working together to co-create, interpret and implement guidance were viewed positively.
COVID-19 and Black Fungus: Analysis of the Public Perceptions through Machine Learning
Authors: Islam Muhammad Nazrul , Khan Nafiz Imtiaz , Mahmud Tahasin
Published: July 2021

While COVID-19 is ravaging the lives of millions of people across the globe, a second pandemic ‘black fungus’ has surfaced robbing people of their lives especially people who are recovering from coronavirus. Again, the public perceptions regarding such pandemics can be investigated through sentiment analysis of social media data. Thus the objective of this study is to analyze public perceptions through sentiment analysis regarding black fungus during the time of the COVID-19 pandemic. To attain the objective, first, a Support Vector Machine model, with an average AUC of 82.75%, was developed to classify user sentiments in terms of anger, fear, joy, and sad. Next, this Support Vector Machine is used to supervise the class labels of the public tweets (n = 6477) related to COVID-19 and black fungus. As outcome, this study found that public perceptions belong to sad (n = 2370, 36.59 %), followed by joy (n = 2095, 32.34%), fear (n = 1914, 29.55 %) and anger (n = 98, 1.51%) towards black fungus during COVID-19 pandemic. This study also investigated public perceptions of some critical concerns (e.g., education, lockdown, hospital, oxygen, quarantine, and vaccine) and it was found that public perceptions of these issues varied. For example, for the most part, people exhibited fear in social media about education, hospital, vaccine while some people expressed joy about education, hospital, vaccine, and oxygen.
Beyond Low-Hanging Fruit: A Systematic Approach to Assessing Quality Improvement Needs in Healthcare Practices
Authors: Hysong Sylvia J. , Modi Varsha , Wichmann Melia J. , Murphy Daniel R.
Published: July 2021

Quality Improvement (QI) tools abound to help clinicians improve the quality of their care. Such tools, however, assume one knows the process that needs attention. A systematic approach is thus needed for selecting the QI activities that have the greatest impact on quality. This study applies Functional Job Analysis (FJA) to systematically identify areas in preventive care most suitable for high-impact QI efforts. Seven internal medicine practice personnel served as subject matter experts (SMEs) in multiple FJA style focus groups to identify the tasks required to ensure successful execution of eight preventive-care measures. Tasks with the greatest prevalence across measures and highest human error consequence ratings were deemed most suitable for QI. SMEs generated improvement recommendations for the identified tasks via focus groups. Tasks with greatest cross-measure prevalence centered on information gathering; tasks with the greatest potential consequence of error centered on medication management, testing and test follow-up (MMTTF). SMEs reported time, space, staffing, and equipment constraints as fundamental barriers impacting all aspects of primary care. Barriers to successful information gathering included issues with front desk staff and the electronic health record. Barriers to MMTTF included lab workflow and patient-related factors. Improvement recommendations included strategic staffing, technology-based solutions, and added in-house testing capabilities. FJA successfully identified two clear, distinct clinic workflow areas that could benefit from QI initiatives. Although our work is limited by its single-site design, results are consistent with prior multi-site FJA research. Contrary to traditional, disease-specific QI approaches, our work identified a core set of processes that, if optimized, can improve care across multiple clinical conditions, and presented a novel application of a classic HR tool to make more systematic QI decisions.
Self-reported word-finding complaints are associated with cerebrospinal fluid beta-amyloid and atrophy in cognitively normal older adults
Authors: Montembeault Maxime , Stijelja Stefan , Brambati Simona M. ,   For the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2021

Background and Objectives

Self-reported language complaints, and more specifically word-finding difficulties, are among the most frequent cognitive complaints in cognitively normal older adults (CN). The clinical significance of elevated self-reported word-finding complaints in CN is still a matter of debate. The present study aims at characterizing word-finding complaints in CN, establish their sociodemographic and psychological correlates, determine if they are predictive of lower levels of cerebrospinal fluid Aβ levels and finally, investigate if they are associated with brain atrophy in regions associated with naming impairments.

Methods

In this observational case-control study, 239 CN from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were selected. All participants completed the self-reported version of the Everyday Cognition (ECog) questionnaire, as well as a lumbar puncture for Aβ and a MRI.

Results

Word-finding complaints were rated equally severe as a few other memory items and significantly more severe compared to all the other cognitive complaints. Ecog-Lang1 (Forgetting the names of objects) was not related to any demographic (age, sex, years of education) or psychological variable (depression-related symptoms, anxiety-related symptoms), while Ecog-Lang3 (Finding the right words to use in a conversation) was significantly negatively associated with years of education and positively associated with depression-related symptoms. Ecog-Lang1 severity significantly predicted CSF Aβ levels in CN, and this result remained significant even when controlling for all demographic and psychological variables as well as general level of cognitive complaint. Individuals with high Ecog-Lang1 complaints showed atrophy in the left fusiform gyrus and the left rolandic operculum in comparison to CN with no or low Ecog-Lang1 complaints.

Discussion

Overall, our results support the fact that word-finding complaints are significant in CN and should be taken seriously. They have the potential to identify CN at risk of AD and support the need to include other cognitive domains in the investigation of subjective cognitive decline.
Modulation of a Stable Neurobehavioral Trait Using Repetitive Transcranial Magnetic Stimulation: A Preregistered Randomized Controlled Trial
Authors: Faerman Afik , Bishop James H. , Stimpson Katy H. , Phillips Angela , Gülser Merve , Amin Heer , Nejad Romina , DeSouza Danielle D. , Geoly Andrew D. , Kallioniemi Elisa , Jo Booil , Williams Nolan R. , Spiegel David
Published: July 2021

Hypnotizability, one’s ability to experience cognitive, emotional, behavioral, and physical changes in response to suggestions in the context of hypnosis, is a highly stable trait associated with increased functional connectivity between the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). We conducted a preregistered, triple-blinded, randomized controlled trial to test the ability of continuous theta-burst stimulation (cTBS) over a personalized neuroimaging-based L-DLPFC target to temporarily enhance hypnotizability. We tested our hypothesis in 78 patients with fibromyalgia syndrome (FMS), a functional pain disorder for which hypnosis has consistently been shown to be beneficial as a nonpharmacological treatment option. Pre-to-post cTBS change in Hypnotic Induction Profile scores (HIP; a standardized measure of hypnotizability) was significantly greater in the Active versus Sham group. Our findings suggest a causal relationship between L-DLPFC and dACC function and hypnotizability. Dose-response optimization should be further examined to formalize guidelines for future clinical utilization.

Trial registration

ClinicalTrials.govNCT02969707
Rivaroxaban is Comparable to Warfarin in Prevention of Thromboembolism in Patients with Non-Valvular Atrial Fibrillation with Valvular Heart Disease: A Systematic Review and Meta-analysis
Authors: Baral Nischit , Katel Anjan , Adhikari Govinda , Khan Mahin R. , Khan Hafiz M. W. , Rauniyar Rohit , Akanbi Maxwell , Malik Bilal , Ahmad Muhammad , Khan Ashiya , Abdelazeem Basel , Savarapu Pramod , Isa Sakiru O. , Kunadi Arvind , Sud Parul , Changezi Hameem U.
Published: July 2021

Objectives

While the use of novel oral anticoagulants (NOACs) has been approved in the treatment of non-valvular atrial fibrillation (NVAF), we are lacking studies on individual NOACs in NVAF with valvular heart disease (VHD) including bio-prosthetic valve and valve repair. We aimed to determine the efficacy and safety of rivaroxaban compared to warfarin in prevention of thromboembolism in patients with NVAF with VHD.

Methods

We searched PubMed, MEDLINE, and EMBASE including only RCTs and Cohort studies from inception till April 2021. Eligible studies compared rivaroxaban with warfarin in patients with NVAF with VHD. We excluded patients with valvular AF. We used Review Manager (version 5.4, Cochrane Collaboration, Oxford, UK) applying the Mantel-Haenszel test and followed PRISMA guidelines. Risk ratio (RR) and 95% confidence intervals (CIs) were estimated using a random-effects method and heterogeneity using I squared test.

Results

We had total of 23136 participants in both groups. Our results showed stroke and systemic thromboembolism in 88 of 4258 (2.06%) patients in the rivaroxaban group compared to 351 of 18878 (1.85%) patients in the warfarin group (RR 0.76; 95% CI, 0.55, 1.06; heterogeneity I2 = 35%, P = 0.10), major bleeding in 247 of 4258 (5.8%) patients in the rivaroxaban group compared to 270 of 18879 (1.4%) patients in the warfarin group (HR 1.68; 95% CI, 0.59, 4.77; heterogeneity I2 = 97%) and intracranial hemorrhage in 24 out of 2583 (0.9%) patients in the rivaroxaban group compared to 35 of 2160 (1.6%) in warfarin group (HR 0.49; 95% CI, 0.16, 1.56; heterogeneity I2 = 70%).

Conclusions

Our results show that rivaroxaban is comparable to warfarin in prevention of stroke and systemic thromboembolism in patients with NVAF with VHD. Rivaroxaban is also comparable to warfarin in bleeding risks in these patients.

REGISTRATION NUMBER

CRD42021222490
Confidence in government and rumors amongst international migrant workers involved in dormitory outbreaks of COVID-19: A cross-sectional survey
Authors: Tan Edina YQ , Albarazi Dalia , Saw Young Ern , Buvanaswari P , Doshi Kinjal , Liu Jean CJ
Published: July 2021

Background

In the coronavirus disease (COVID-19) pandemic, confidence in the government and access to accurate information have been critical to the control of outbreaks. Although outbreaks have emerged amongst communities of international migrant workers worldwide, little is known about how they perceive the government’s response or their exposure to rumors.

Methods

Between 22 June to 11 October 2020, we surveyed 1011 low-waged migrant workers involved in dormitory outbreaks within Singapore. Participants reported their confidence in the government; whether they had heard, shared, or believed widely-disseminated COVID-19 rumors; and their socio-demographics. Logistic regression models were fitted to identify factors associated with confidence and rumor exposure.

Results

1 in 2 participants (54.2%, 95% CI: 51.1-57.3%) reported that they believed at least one COVID-19 rumor. This incidence was higher than that observed in the general population for the host country (Singapore). Nonetheless, most participants (90.0%, 95% CI: 87.6-91.5%) reported being confident that the government could control the spread of COVID-19. Age was significantly associated with belief in rumors, while educational level was associated with confidence in government.

Conclusions

Our findings suggest that language and cultural differences may limit the access that migrant workers have to official COVID-19 updates. Correspondingly, public health agencies should use targeted messaging strategies to promote health knowledge within migrant worker communities.
Comparing genome-based estimates of relatedness for use in pedigree-based conservation management
Authors: Hauser Samantha , Galla Stephanie J. , Putnam Andrea S. , Steeves Tammy E. , Latch Emily K.
Published: July 2021

Researchers have long debated which estimator of relatedness best captures the degree of relationship between two individuals. In the genomics era, this debate continues, with relatedness estimates being sensitive to the methods used to generate markers, marker quality, and levels of diversity in sampled individuals. Here, we compare six commonly used genome-based relatedness estimators (kinship genetic distance (KGD), Wang Maximum Likelihood (TrioML), Queller and Goodnight (Rxy), Kinship INference for Genome-wide association studies (KING-robust), and Pairwise Relatedness (RAB), allele-sharing co-ancestry (AS)) across five species bred in captivity–including three birds and two mammals–with varying degrees of reliable pedigree data, using reduced-representation and whole genome resequencing data. Genome-based relatedness estimates varied widely across estimators, sequencing methods, and species, yet the most consistent results for known first order relationships were found using Rxy, RAB, and AS. However, AS was found to be less consistently correlated with known pedigree relatedness than either Rxy or RAB. Our combined results indicate there is not a single genome-based estimator that is ideal across different species and data types. To determine the most appropriate genome-based relatedness estimator for each new dataset, we recommend assessing the relative: (1) correlation of candidate estimators with known relationships in the pedigree and (2) precision of candidate estimators with known first-order relationships. These recommendations are broadly applicable to conservation breeding programs, particularly where genome-based estimates of relatedness can complement and complete poorly pedigreed populations. Given a growing interest in the application of wild pedigrees, our results and are also applicable to in-situ wildlife management.
Discovery of a simple two-gene expression biomarker in whole blood predictive of the need for treatment escalation in inflammatory bowel disease
Authors: Nowak Jan K. , Kalla Rahul , Adams Alex T. ,   IBD-Character Consortium, Halfvarson Jonas , Satsangi Jack
Published: July 2021

Background and aims

The IBD-Character consortium has recruited large internationally based inception cohorts of treatment-naïve inflammatory bowel disease (IBD) patients, providing a unique resource to derive a simple transcriptome signature in the field of prognostication.

Methods

The discovery cohort (n=160) was recruited in Norway, Sweden and Spain. The replication inception cohort from the United Kingdom (n=97) was followed-up for a mean (±SD) of 350±228 days. Treatment escalation was formally defined as the need for a biologic agent, ciclosporin and/or surgery, instituted for disease flare after initial remission, or colectomy during the index admission for ulcerative colitis. Whole blood RNA was subject to paired-end sequencing. In the discovery cohort a simple procedure was applied, which exploited differences of transcript ratios. The ten top performing ratios were tested using Cox regression models in the validation cohort.

Results

Newly diagnosed IBD patients with high CACNA1E/LRRC42 expression ratio had an increased risk of treatment intensification (validation cohort: HR=19.3, 95%CI 2.6–143.9, p=0.000005; AUC 0.76, 95%CI 0.66–0.86). In 51 patients with CRP < 3.5 mg/L, CACNA1E/LRRC42 still predicted escalation (HR=10.4; 95%CI 1.2-86.5, p=0.007). The second best performing transcript ratio was CACNA1E/CEACAM21 yielding a HR of 10.9 (95%CI 2.5-46.7, p=0.00002) and an AUC of 0.76 (95%CI 0.65-0.86) in the validation cohort.

Conclusion

Transcriptomic profiling of an IBD inception cohort identified gene expression ratios CACNA1E/LRRC42 and CACNA1E/CEACAM21 as prognostic biomarkers. These were validated in a replication cohort as strongly associated with short- and long-term risk of treatment intensification and may provide valuable information in clinical decision-making.
A Rapid Saliva Test for Monitoring Immune Protection against SARS -CoV-2 and its Variants
Authors: Momyer Victoria SA. , Dixon Samantha , Liu Q. John , Wee Brian , Chen Tiffany Y. , Petropoulos Anna , Sang L. Jessica
Published: July 2021

Given the ongoing transmission and emergence of SARS-Cov-2 variants globally, it is critical to have a timely assessment on individuals’ immune responses as well as population immunity. Important questions such as the durability of COVID-19 immunity or the efficacy of vaccines require large datasets to generate meaningful insights. However, due to the complexity and relatively high-cost of many immunity assays and the needs for blood-drawing specialists, these assays were mostly limited to small-scale clinical studies. Our work demonstrated the potential of a non-invasive, inexpensive and data-driven solution for large-scale immunity surveillance and for predictive modeling of vaccine efficacy. Combining a proprietary saliva processing method and an ultra-sensitive digital detection technology, we were able to rapidly gather information regarding personalized immune response following infection or vaccination, monitor temporal evolution, and optimize predictive models for variant protection.
WHY SOME HESITATE MORE: CROSS-CULTURAL VARIATION IN CONSPIRACY BELIEFS, BELIEF IN SCIENCE, AND VACCINE ATTITUDES
Authors: Salali Gul Deniz , Uysal Mete Sefa
Published: July 2021

Background

Countries differ in their levels of vaccine hesitancy (a delay in acceptance or refusal of vaccines), trust in vaccines, and acceptance of new vaccines. In this paper, we examine the factors contributing to the cross-cultural variation in vaccine attitudes, measured by levels of 1) general vaccine hesitancy, 2) trust in vaccines, and 3) COVID-19 vaccine acceptance.

Methods

We examined the relative effect of conspiracy mentality, belief in COVID-19 conspiracies, and belief in science on the above-mentioned vaccine attitudes in the UK (n= 1533), US (n= 1550), and Turkey (n= 1567) through a quota-sampled online survey to match the population for age, gender, ethnicity, and education level.

Results

We found that belief in COVID-19 conspiracies and conspiracy mentality were the strongest predictors of general vaccine hesitancy across all three countries. Belief in science had the largest positive effect on general vaccine trust and COVID-19 vaccine acceptance. Although participants in Turkey demonstrated the lowest level of vaccine trust, their belief in science score was significantly higher than participants in the US, suggesting that belief in science cannot explain the cross-cultural variation in vaccine trust. The mean levels of conspiracy mentality and agreement with COVID-19 conspiracies were consistent with the country-level differences in general and COVID-19 vaccine attitudes. Demographic variables did not predict vaccine attitudes as much as belief in conspiracies and science.

Conclusions

Our findings suggest that cross-cultural variation in vaccine hesitancy, vaccine trust, and COVID-19 vaccine acceptance rates are mainly driven by differences in the prevalence of conspiratorial thinking across countries.
Pandemic trends in health care use: From the hospital bed to the general practitioner with COVID-19
Authors: Methi Fredrik , Hernæs Kjersti Helene , Skyrud Katrine Damgaard , Magnusson Karin
Published: July 2021

Aim

To explore whether the acute 30-day burden of COVID-19 on health care use has changed from the beginning to the end of the pandemic.

Methods

In all Norwegians (N=122 699) who tested positive for SARS-CoV-2 in three pandemic waves (March 1st-July 31st 2020 (1st wave), August 1st-December 31st 2020 (2nd wave), and January 1st-May 31st 2021 (3rd wave)), we studied the age- and sex-specific share of patients (by age groups 1-19, 20-67, and 68 or more) who had: 1) Relied on self-care, 2) used primary care, and 3) used specialist care.

Results

We find that a remarkably high and stable share (70-80%) of patients with COVID-19 exclusively had contact with primary care in the acute phase, both in the 1st, 2nd and 3rd wave. The mean number of primary care visits ranged between 2 and 4. We also show that the use of specialist care in the acute 30-day phase of COVID-19 has decreased, from 14% being hospitalized at least once during spring 2020, to 4% during spring 2021. The mean number of hospital bed-days decreased significantly for men from the 1st to the 2nd wave (from 13 days, 95% CI=11.5-14.5 to 10 days (9-11) for men aged ≥68 years, and from 11 days (10-12) to 9 days (8-10) for men aged 20-67 years), but not for women.

Conclusion

COVID-19 places a continued high demand on the primary care services, and a decreasing demand on the specialist care services.
Gender-Specific Long-Term Prognostic Values of QRS Duration, QT Interval, and QTc from Automated ECG Analysis for Mortality and Adverse Outcomes in Patients Hospitalized for Heart Failure
Authors: Zhou Jiandong , Hothi Sandeep S , Kai Chan Jeffery Shi , Lee Sharen , Wong Wing Tak , Kit Leung Keith Sai , Chung Wai Abraham Ka , Jeevaratnam Kamalan , Liu Tong , Tse Gary , Zhang Qingpeng
Published: July 2021

Background

Gender-specific prognostic values of electrocardiographic (ECG) measurements in patients hospitalized for heart failure (HF) are lacking, which we hence investigated in this study.

Methods

Patients admitted to a single tertiary center for HF between 1 January 2010 and 31 December 2016 without atrial fibrillation and with at least one baseline ECG were included. Automated ECG measurements were performed. The primary outcomes were all-cause and cardiovascular (CAD) mortality, and the secondary outcomes were stroke, and ventricular arrhythmia and sudden cardiac death (VA/SCD). The prognostic values of the heart rate, PR segment, QRS duration, PT interval, QT interval, and QTc were assessed. Gender-specific optimal cutoffs of the above measurements were identified with the maximally selected rank statistics approach.

Results

In total, 2718 patients (median age 77 years; 1302 males) were included with a median follow-up of 4.8 years; the females were significantly older (p<0.0001). Females had higher rates of all-cause (p=0.04) and CAD mortality (p=0.02), while males had higher rates of VA/SCD (p=0.02). Higher heart rate, longer PT interval, wider QRS, and longer QT interval and QTc predicted all-cause mortality in males, while only shorter PR segment, longer QRS duration and QTc predicted the same in females. Longer QRS duration, QT interval, and QTc predicted CAD mortality in males, while longer PT interval, wider QRS and longer QTc predicted the same in females. ECG measurements also predicted the secondary outcomes to different extents depending on genders.

Conclusions

Selected ECG measurements have significant gender-specific prognostic value in patients admitted for heart failure.
Markers of immune activation and inflammation in individuals with post-acute sequelae of SARS-CoV-2 infection
Authors: Peluso Michael J. , Lu Scott , Tang Alex F. , Durstenfeld Matthew S. , Ho Hsi-en , Goldberg Sarah A. , Forman Carrie A. , Munter Sadie E. , Hoh Rebecca , Tai Viva , Chenna Ahmed , Yee Brandon C. , Winslow John W. , Petropoulos Christos J. , Greenhouse Bryan , Hunt Peter W. , Hsue Priscilla Y. , Martin Jeffrey N. , Kelly J. Daniel , Glidden David V. , Deeks Steven G. , Henrich Timothy J.
Published: July 2021

BACKGROUND

The biological processes associated with post-acute sequelae of SARS-CoV-2 infection (PASC) are unknown.

METHODS

We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of one or more COVID-19-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed effects models with terms for PASC and early and late recovery time periods.

RESULTS

During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including TNF-alpha (1.14-fold higher mean ratio, 95%CI 1.01-1.28, p=0.028) and IP-10 (1.28-fold higher mean ratio, 95%CI 1.01-1.62, p=0.038). Among those with PASC, there was a trend toward higher IL-6 levels during early recovery (1.28-fold higher mean ratio, 95%CI 0.98- 1.70, p=0.07) which became more pronounced in late recovery (1.44-fold higher mean ratio, 95%CI: 1.11-1.86, p<0.001). These differences were more pronounced among those with a greater number of PASC symptoms.

CONCLUSIONS

Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.