bluuebunny/crossref_metadata_2025 huggingface dataset:
The role for long-term use of dehydroepiandrosterone in adrenal insufficiency
Authors: Bennett Gillian , Cussen Leanne , O’Reilly Michael W.
Published: May 2022

Purpose of review

Dehydroepiandrosterone (DHEA) is an androgen produced by the zona reticularis of the adrenal gland. Patients with adrenal insufficiency will have a deficiency of DHEA. Unlike glucocorticoid and mineralocorticoid replacement, DHEA supplementation is not considered essential for life and is therefore not routinely replaced in adrenal failure. DHEA deficiency is associated with morbidity, including adverse impacts on metabolic function, quality of life and sexuality in multiple studies. The role for replacement, however, remains unclear.

Recent findings

The benefits of DHEA supplementation have been definitively demonstrated in a number of historical studies of patients with primary and secondary adrenal insufficiency. Beneficial impacts on quality of life, body composition, bone health and metabolic markers have been demonstrated. However, published data are inconsistent; controversies persist around the exact role of DHEA replacement and around which patient cohorts are most likely to benefit. There is also a paucity of recent randomized controlled trials in the medical literature to inform on optimal dose and duration of DHEA replacement in adrenal failure.

Here, we review the evidence for DHEA supplementation in patients with adrenal insufficiency. We highlight knowledge gaps in the medical literature and areas that should be prioritized for future research endeavours.
Stir, Shake or Blend: A Comparison of Methods Used to Reduce Viscosity of Blenderized Tube Feedings
Authors: Weston Sharon Coyle , Crespo Alex , Harwin Catharine
Published: May 2022

Blenderized tube feeding (BTF) refers to formula composed of whole foods and purees, blended to a consistency that can be administered through an enteral feeding device. BTFs have a higher viscosity than conventional enteral formulas and may be mixed with extra liquid to aid in administration via an enteral feeding device. This study compared changes in viscosity of commercially available BTF s when stirred, shaken, or blenderized. The International Dysphagia Diet Standardisation Initiative flow test was used to provide an objective level of viscosity. Our results indicate that the method chosen to thin BTFs results in significant differences in viscosity and varies depending on the percent of water by volume added to the formula as well as the presence of additional non-food ingredients such as synthetic supplements. We conclude that the method used to thin BTFs should be taken into account when a consistent viscosity level is desired.
Immature Platelet Fraction and Its Kinetics in Neonates
Authors: Kobayashi Jun , Takezawa Yuka , Saito Shoji , Kubota Noriko , Sakashita Kazuo , Nakazawa Yozo , Higuchi Yumiko , Tozuka Minoru , Ishida Fumihiro
Published: May 2022

Thrombocytopenia is a common abnormality encountered in the neonatal period, and immature platelet fraction (IPF) may be an informative indicator of thrombopoiesis; however, data on IPF in neonates are scarce. To define reference intervals (RIs) and factors affecting IPF in neonates, we measured the IPF of 533 consecutive neonates. With a multiple regression analysis of 330 newborns with normal platelet counts at birth, premature delivery, neonatal asphyxia, intrauterine infection, chromosomal abnormalities, and respiratory disorders were identified as independent factors for IPF%. The RIs of IPF% and absolute IPF value in neonates were determined to be 1.3% to 5.7% and 3.2 to 14.5×109/L, respectively. On day 14 after birth, IPF% increased to twice the value at birth and thereafter returned to the previous value on day 28. Reticulocyte counts, in contrast, were the lowest at day 14. IPF% was increased in 16 thrombocytopenic patients with various clinical conditions, especially those with immune-mediated thrombocytopenia. IPF in neonates may be evaluated essentially based on the same RIs as in adults, although some precautions must be taken when evaluating IPF in neonates in the first 2 weeks of life. IPF may be useful for evaluating thrombopoiesis and thrombocytopenia in neonates.
Nutrition Care Process of Surgical Patients in the Context of Enhanced Recovery After Surgery
Authors: Khalooeifard Razieh , Alemrajabi Mahdi , Yazdani Saeed Oraee , Hosseini Saeed
Published: May 2022

Dietitians and nutritionists play a key role in optimizing the nutritional status of the patients before and after performing surgery. The importance of nutrition is often overlooked because health professionals lack knowledge about nutritional problems, structured protocols for cooperation between surgeons and clinical nutritionists do not exist, dedicated resources are lacking, and preoperative and postoperative nutrition care protocols have not been disseminated. The purpose of this review is to describe various nutrition care guidelines for use during preoperative and postoperative periods for surgical patients to enhance recovery after surgery based on a review of the literature. It should help nutritionists and surgeons to make appropriate decisions on the management during preoperative and postoperative care, as well as facilitating the understanding and application of medical nutrition therapy.
Supporting the Pursuit of Quality Improvement Publication: What Your Organization Can Do Now
Authors: Matulis John C. , Manning Dennis M.
Published: May 2022

Many health care organizations encourage frontline staff to pursue quality improvement (QI), local spread of those improvements, and publication of their work. Although much has been written about building and sustaining a culture of continuous QI, less is known about how to support success in QI rigor, credibility, spread, and publication. In this perspective article, we offer QI leaders practical suggestions to identify challenges in publishing QI and strategies to overcome these challenges. Health care organizations can assist QI teams with publication by intentionally formalizing scholarship early in their QI project work, providing accountability, and connecting the QI team to necessary resources. A carefully designed program supporting QI publication can both improve the rigor of QI work and enhance the professional development of QI professionals.
An Independent Seizure-Onset Zone in Medial Temporal Lobe Found by 18F-FDG PET Imaging Besides Epileptogenic Periventricular Nodular Heterotopia
Authors: Guo Ruijie , Jin Liri , Dou Wanchen , Liu Linwen , Cui Ruixue
Published: May 2022

A 23-year-old man with drug-resistant epilepsy was admitted for presurgical evaluation. The epileptogenic zone could not be derived from seizure semiology and scalp electroencephalographic monitoring definitely. MRI showed periventricular nodular heterotopia in occipital horn of left lateral ventricle with high FDG uptake on interictal 18F-FDG PET scan, whereas the hypometabolic zone in the left medial temporal lobe was also found on PET with no abnormality on MRI. Stereoelectroencephalographic implantation was performed to identify the seizure-onset zone. Two independent epileptogenic foci located in periventricular nodular heterotopia and left hippocampus were validated by stereoelectroencephalographic monitoring and the outcome of subsequent thermocoagulation.
Lipid-Poor Renal Angiomyolipoma Mimicking Renal Cell Carcinoma on 68Ga-FAPI-04 PET/CT
Authors: Dong Aisheng , Yang Qing , Hua Meimian , Cheng Chao , Zuo Changjing
Published: May 2022

FAPI PET/CT findings of renal tumors have been rarely reported. We describe 68Ga-FAPI-04 PET/CT findings in 1 case with lipid-poor renal angiomyolipoma and 1 case with high-grade clear cell renal cell carcinoma. Both tumors showed intense 68Ga-FAPI-04 uptake. These 2 cases indicate that lipid-poor renal angiomyolipoma should be included in the differential diagnosis of FAPI-avid renal tumors.
FDG PET/CT in a Case With Cellular Schwannoma of the Kidney
Authors: Yu Zhongfei , Zhang Jian , Dong Aisheng , Zhu Yuzhao
Published: May 2022

Schwannoma of the kidney is exceedingly rare. We describe contrast-enhanced CT and FDG PET/CT findings in a case with renal cellular schwannoma. Contrast-enhanced CT showed the enhancing tumor was located in the anterior middle portion of the left kidney, encasing the renal vessels and compressing the renal pelvis. The tumor showed inhomogeneous FDG uptake with SUVmax of 8.6 mimicking renal cell carcinoma. This case indicates renal schwannoma should be included in the differential diagnosis of FDG-avid renal lesions.
Arachidicoccus terrestris sp. nov., isolated from greenhouse soil
Authors: Won Miyoung , Weon Hang-Yeon , Hong Seung-Beom , Han Byeong-Hak , Kwon Soon-Wo
Published: May 2022

A Gram-stain-negative, aerobic, non-motile, rod-shaped or occasionally filamentous-shaped bacterial strain, designated 5GH13-10T, was isolated from greenhouse soil sampled in Yeoju-si, Republic of Korea. Colonies were milky-coloured, round and convex, and catalase- and oxidase-positive. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5GH13-10T was related to the genus

Arachidicoccus

and had highest 16S rRNA gene sequence identity with

Arachidicoccus rhizosphaerae

Vu-144T (98.4 %). The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1
 ω6c and/or C16 : 1
 ω7c). The predominant quinone was menaquinone MK-7, and the polar lipids were composed of phosphatidylethanolamine, one unidentified aminolipid, three unidentified aminophospholipids, one unidentified phospholipid and five unidentified lipids. The genomic DNA G+C content of strain 5GH13-10T was 43.8 mol%. The average nucleotide identity values between strain 5GH13-10T and the closely related species

Arachidicoccus ginsenosidivorans

Gsoil 809T,

Arachidicoccus rhizosphaerae

Vu-144T and Archidicoccus soli KIS59-12T were 74.86, 74.74 and 69.52 %, and the digital DNA-DNA hybridization values were 20.0, 19.8 and 18.6 %, respectively. Combined phenotypic, phylogenetic and genomic data demonstrated that strain 5GH13-10T is representative of a novel species of the genus

Arachidicoccus

, for which we propose the name Arachidicoccus terrestris sp. nov. (type strain 5GH13-10T=KACC 18014T=NBRC 113162T).
Network pharmacology and experimental validation identify the potential mechanism of sophocarpine for COVID-19
Authors: Zhang Hui-xian , Zhang Xin
Published: May 2022

Introduction. Coronavirus disease 2019 (COVID-19) has caused a serious threat to public health worldwide, and there is currently no effective therapeutic strategy for treating COVID-19.

Hypothesis/Gap Statement. We propose that sophocarpine (SOP) might have potential therapeutic effects on COVID-19 through inhibiting the cytokine storm and the nuclear factor NF-κB signalling pathway.

Aim. The objective was to elucidate the potential mechanism of SOP against COVID-19 through a network pharmacology analysis and its experimental validation.

Methodology. The BATMAN-TCM database was used to identify the therapeutic targets of SOP, while the GeneCards and DisGeNET databases were used to identify the targets related to COVID-19. A protein–protein interaction (PPI) network was constructed from the STRING and analysed using Cytoscape software. Gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and disease ontology (DO) enrichment analyses of the co-targets were performed using Metascape. Autodock 4.2.6 and Pymol software were applied for molecular docking. Levels of the proinflammatory cytokines IL-6, TNFα and IL-1β were measured by ELISA, while mRNA expression levels of intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor A (VEGFA) and IFN gamma (IFNG) were detected by real-time quantitative reverse transcription PCR. The protein levels of the molecules involved in the NF-κB signalling pathway were validated by western blot analysis.

Results. A total of 65 co-targets of SOP and COVID-19 were determined. GO and KEGG enrichment analyses suggested that SOP affected COVID-19 by regulating the IL-17 signalling pathway, TNF signalling pathway and other signalling pathways. The PPI network and molecular docking showed that p65, ICAM-1 and VEGFA were key targets of SOP against COVID-19 and the underlying mechanism was validated in A549 cells in vitro. SOP attenuated the LPS-induced production of TNF-α and IL-6 and downregulated the LPS-induced mRNA expression of ICAM-1, VEGFA and IFNG. Mechanistically, SOP pretreatment inhibited the phosphorylation of p65 and facilitated the activation of Nrf2.

Conclusions. SOP has a potential therapeutic effect on COVID-19 through multiple pathways and targets, and inhibits the production of pro-inflammatory cytokines and molecules involved in the NF-κB signalling pathway.
Safety and feasibility of fecal microbiota transplantation for Parkinson’s disease patients: a protocol for a self-controlled interventional donor-FMT pilot study
Authors: Vendrik Karuna E.W. , Bekker-Chernova Vlada O. , Kuijper Ed J. , Terveer Elisabeth M. , van Hilten Jacobus J. , Contarino Maria Fiorella
Published: May 2022

Several experimental studies suggest a role of the gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut-brain axis. In addition, the gut microbiota can influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by fecal microbiota transplantation (FMT) could be a supportive treatment strategy. We developed a study protocol for a single center, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomization and double blinded allocation of donor feces. The primary objectives are to assess feasibility and safety of FMT in PD patients. Secondary objectives are to explore whether FMT leads to alterations of motor complications and PD symptoms in the short term, determine alterations in gut microbiota composition and donor-recipient microbiota similarities and their association with PD symptoms and motor complications, assess the ease of the study protocol and examine FMT-related adverse events in PD patients. The study population will consist of 16 idiopathic PD patients that use levodopa and experience motor complications. They will receive FMT with feces from one of two selected healthy human donors. Patients will be pretreated with vancomycin and bowel lavage to increase donor feces engraftment, and domperidone to prevent nausea and regurgitation. The FMT will be performed via direct injection of the fecal suspension into the duodenum via a gastroscope. There will be six follow-up moments during three months. Blood will be drawn on three occasions. Physical examination, filling in of questionnaires and a diary, and collection of stool samples are performed at baseline and each in-person follow-up visit (except for the FMT visit). This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087) and is registered in the Netherlands Trial Register (NL9438). Study results will be disseminated through publication in peer-reviewed journals and international conferences.
PK-RNN-V E: A Deep Learning Model Approach to Vancomycin Therapeutic Drug Monitoring Using Electronic Health Record Data
Authors: Nigo Masayuki , Tran Hong Thoai Nga , Xie Ziqian , Feng Han , Mao Bingyu , Rasmy Laila , Miao Hongyu , Zhi Degui
Published: May 2022

Vancomycin is a commonly used antimicrobial in hospitals, and therapeutic drug monitoring (TDM) is required to optimize its efficacy and avoid toxicities. Bayesian models are currently recommended to predict the antibiotic levels. These models, however, although using carefully designed lab observations, were often developed in limited patient populations. The increasing availability of electronic health record (EHR) data offers an opportunity to develop TDM models for real-world patient populations. Here, we present a deep learning-based pharmacokinetic prediction model for vancomycin (PK-RNN-V E) using a large EHR dataset of 5,483 patients with 55,336 vancomycin administrations. PK-RNN-V E takes the patient’s real-time sparse and irregular observations and offers dynamic predictions. Our results show that RNN-PK-V E offers a root mean squared error (RMSE) of 5.39 and outperforms the traditional Bayesian model (VTDM model) with an RMSE of 6.29. We believe that PK-RNN-V E can provide a pharmacokinetic model for vancomycin and other antimicrobials that require TDM.

Statement of Significance

Problem

Current traditional Bayesian models for vancomycin levels were tested in only a limited patient population and take limited patient-specific features. Hence, a more flexible and powerful model, such as deep-learning models, may provide significant advantages.

What is Already Known

The Bayesian models do not predict the vancomycin levels well in patient populations with unstable hemodynamic status and fluctuating kidney functions.

What this Paper Adds

Deep-learning based pharmacokinetic model for vancomycin (PK-RNN-V E) provided better prediction accuracy with integrating multiple patient-specific features from time sequence electronic health record data. This study proved the concept of model.
Atovaquone for Treatment of COVID-19: A Prospective Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Jain Mamta K. , Lemos James A. de , McGuire Darren K. , Ayers Colby , Eiston Jennifer L. , Sanchez Claudia L. , Kamel Dena , Meisner Jessica A. , Thomas Emilia V. , Hegde Anita A. , Mocherla Satish , Strebe Joslyn K. , Li Xilong , Williams Noelle S. , Xing Chao , Ahmed Mahmoud S. , Wang Ping , Sadek Hesham A. , Schoggins John W.
Published: May 2022

Background

An in-silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.

Methods

A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples.

Results

Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p=0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p= 0.005).

Conclusion

In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.

clincialtrials.gov (NCT04456153).
Real world costs and barriers to the successful implementation of rectal artesunate as pre-referral treatment for severe malaria in Sub-Saharan Africa
Authors: Lambiris Mark , Ndongala Guy , Ssempala Richard , Balogun Victor , Musiitwa Michael , Kagwire Fred , Olosunde Oluseyi , Emedo Emmanel , Luketa Sylvie , Sangare Moulaye , Buj Valentina , Delvento Giulia , Galactionova Katya , Okitawutshu Jean , Tshefu Antoinette , Omoluabi Elizabeth , Awor Phyllis , Signorell Aita , Hetzel Manuel W. , Lee Tristan T. , Brunner Nina C. , Cereghetti Nadja , Visser Theodoor , Napier Harriet G. , Burri Christian , Lengeler Christian
Published: May 2022

Background

Rectal artesunate (RAS), an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria and DR Congo. In addition to distributing RAS, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and barriers to RAS implementation.

Methods

We collected primary data on baseline health system gaps and subsequent RAS implementation expenditures. We calculated the equivalent annual cost of RAS implementation per child under 5 at risk of severe malaria, from a health system perspective, separating neglected routine health system components from incremental RAS introduction costs.

Findings

The largest baseline gaps were irregular health worker supervisions, inadequate referral facility worker training, and inadequate malaria commodity supplies. Health worker training and behaviour change campaigns were the largest startup costs, while supervision and supply chain management accounted for most annual routine costs. The equivalent annual costs of preparing the health system for treating severe malaria with RAS were $2.31, $2.20 and 4.15 per child at risk in Uganda, Nigeria and DRC. The incremental costs of introducing RAS, net of routine neglected components, accounted for a minority at $0.72, $0.59 and $0.94.

Interpretation

While RAS has been touted as a cost-effective pre-referral treatment for severe malaria in children, its real-world potential is limited by weak and under-financed continuums of care. Scaling up RAS or other interventions relying on community healthcare providers only makes sense alongside additional, essential health system investments sustained over the long-term.

Funding

Unitaid
Using the Excitation/Inhibition Ratio to Optimize the Classification of Autism and Schizophrenia
Authors: Uscătescu Lavinia Carmen , Hyatt Christopher J. , Dunn Jack , Kronbichler Martin , Calhoun Vince , Corbera Silvia , Pelphrey Kevin , Pittman Brian , Pearlson Godfrey , Assaf Michal
Published: May 2022

The excitation/inhibition (E/I) ratio has been shown to be imbalanced in individuals diagnosed with autism (AT) or schizophrenia (SZ), relative to neurotypically developed controls (TD). However, the degree of E/I imbalance overlap between SZ and AT has not been extensively compared. Our main objectives were (1) to quantify group differences in the E/I ratio between TD, AT, and SZ, (2) to assess the potential of the E/I ratio for differential diagnosis, and (3) to verify the replicability of our findings in a second, independently-acquired dataset. For each participant, we computed the Hurst exponent (H), an indicator of the E/I ratio, from the timecourses of 53 independent components covering the entire brain. Using Random Forest (RF), we ran a classification analysis using the largerof the two datasets (exploratory dataset; 519 TD, 200 AT, 355 SZ) to determine which of the 53 H would yield the highest performance in classifying SZ and AT. Next, taking the ten most important H from the exploratory dataset and the clinical and phenotypic information collected in the replication dataset (55 TD, 30 AT, 39 SZ), we used RF to compare classification performance using five feature sets: (a) H only; (b) Positive and Negative Syndrome Scale (PANSS) and the Autism Diagnostic Observation Schedule (ADOS) only; (c) PANSS, ADOS, Bermond–Vorst Alexithymia Questionnaire (BVAQ), Empathy Quotient (EQ), and IQ; (d) H, PANSS and ADOS; (e) H, PANSS, ADOS, BVAQ, EQ and IQ. Classification performance using H only was higher in the exploratory dataset (AUC = 84%) compared to the replication dataset (AUC = 72%). In the replication dataset, the highest classification performance was obtained when combining H with PANSS, ADOS, BVAQ, EQ and IQ (i.e., model e; AUC = 83%).
Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study in the United States
Authors: Yang Yuwen , Lu Yi , Jiang Bin
Published: May 2022

The COVID-19 outbreak has caused enormous deaths and profound social and economic disruption globally. Accumulating evidence suggests exposure to greenspace may reduce the risk of COVID-19 mortality. Greenspace exposure enhances immune functioning, reduces inflammation, and replenishes gut microbiota may protect against the risk of mortality among those with COVID-19. However, previous studies often fail to distinguish the health effect of different types of greenspace, explore the dose-response association and optimal buffer distance, and consider the spatial dynamics of population distribution and geographic locations of greenspace.

This study examined the associations among ratio of different types of greenspaces, population- weighted exposure to different types of greenspaces, and COVID-19 mortality rates using a negative binomial generalized linear mixed effects model across 3,025 counties in the United States, adjusted for socioeconomic, demographic, pre-existing chronic disease, policy and regulation, behavioral, and environmental factors. The population-weighted measure gave proportionally greater weight to greenspace near areas of higher population density.

Exposure to forest and pasture was negatively associated with COVID-19 mortality rates, while developed open space has insignificant or positive associations with mortality rates.Forest outside parkhas the largest effect size across all buffer distances, followed byforest inside park. The optimal exposure buffer distance is 1km forforest outside park, with 1 unit of increase in exposure associated with a 9.9% decrease in mortality rates (95% confidence interval: 6.9% -12.8%). The optimal exposure buffer distance offorest inside parkis 400m, with 1 unit of increase in exposure, associated with a 4.7% decrease in mortality rates (95% confidence interval: 2.4% - 6.9%).

Greenspaces, especially nearby forest, may be effective at lowering the mortality risk of COVID-19 patients. Our findings suggest that policymakers and planners should prioritize forestry within walking distance of residential clusters to mitigate mortality rates during current and future respiratory pandemics.
Facing the Omicron variant – How well do vaccines protect against mild and severe COVID-19? Third interim analysis of a living systematic review
Authors: Külper-Schiek Wiebe , Piechotta Vanessa , Pilic Antonia , Batke Madeleine , Dreveton Léa-Sophie , Geurts Brogan , Koch Judith , Köppe Stefan , Treskova Marina , Vygen-Bonnet Sabine , Waize Maria , Wichmann Ole , Harder Thomas
Published: May 2022

Background

The SARS-CoV-2 Omicron variant is currently the dominant variant globally. This 3rd interim analysis of a living systematic review summarizes evidence on COVID-19 vaccine effectiveness (VE) and duration of protection against Omicron.

Methods

We systematically searched the COVID-19 literature for controlled studies evaluating the effectiveness of COVID-19 vaccines approved in the European Union up to 14/01/2022, complemented by hand-searches of websites and metasearch engines up to 11/02/2022. We considered the following comparisons: full primary immunization vs. no vaccination; booster immunization vs. no vaccination; booster vs. primary immunization. VE against any confirmed SARS-CoV-2 infection, symptomatic, and severe COVID-19 (i.e. COVID-19-related hospitalization, ICU-admission, or death) was indicated providing estimate ranges. Meta-analysis was not performed due to high study heterogeneity. Risk of bias was assessed with ROBINS-I, certainty of evidence evaluated using GRADE.

Results

We identified 26 studies, including 430 to 2.2 million participants.

VE against any confirmed SARS-CoV-2 infection compared to no vaccination ranged between 0-62% after full primary immunization, and between 34-66% after a booster dose. VE-range for booster vs. primary immunization was 34-54.6%.

Against symptomatic COVID-19, VE ranged between 6-76% after full primary immunization, and between 19-73.9% after booster immunization, if compared to no vaccination. When comparing booster vs. primary immunization VE ranged between 56-69%.

VE against severe COVID-19 compared to no vaccination ranged between 3-84% after full primary immunization, and between 12-100% after a booster dose. One study compared booster vs. primary immunization (VE 100%, 95% CI 71.4-100).

VE was characterized by a moderate to strong decline within three to six months for SARS-CoV-2 infections and symptomatic COVID-19. Against severe COVID-19 protection remained robust at least for up to six months. Waning immunity was more profound after primary than booster immunization.

Risk of bias was moderate to critical across studies and outcomes. GRADE-certainty was very low for all outcomes.

Author’s conclusions

Under the Omicron variant, effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection or mild disease is low and only short-lasting after primary immunization, but can be improved by booster vaccination. VE against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.
Behavioural activation for co- morbid depression in people with non-communicable disease in India: Protocol for a randomised controlled feasibility trial (BEACON)
Authors: Zainab Rayeesa , Kandasamy Arun , Bhat Naseer Ahmad , Dsouza Chrishma Violla , Jennings Hannah , Jackson Cath , Mazumdar Papiya , Hewitt Catherine , Ekers David , Narayanan Gitanjali , Rao Girish N , Coales Karen , Muliyala Krishna Prasad , Chaturvedi Santosh Kumar , Murthy Pratima , Siddiqi Najma
Published: May 2022

Introduction

The increasing burden of depression and non-communicable disease (NCD) is a global challenge, especially in low- and middle-income countries (LMIC) considering the resource constraints and lack of manpower in these settings. Brief psychological therapies such as behavioural activation (BA), have shown to be effective for the treatment of depression. However, their feasibility and effectiveness for depression in people with NCDs in Indian community setting has not been systematically evaluated. Hence, in this study, we conceptualize to adapt BA into Indian NCD context, thus to improve the management of depression in people with NCD in India.

Aims

To (1) adapt BA for the Indian NCD context, (2) test the acceptability, feasibility and implementation of the adapted BA intervention (BEACON intervention package, BIP), and (3) test the feasibility of a randomised controlled trial evaluation of BIP for the treatment of depression compared with enhanced usual care.

Methods

Following well-established frameworks for intervention adaptation, we first adapted BA (to fit the linguistic, cultural and resource context) for delivery in India. The intervention was also adapted for potential remote delivery via telephone.

In a randomised controlled trial, we will then test acceptability, feasibility and implementation of the adapted BA intervention (BEACON Intervention package, BIP). We also test if a randomised controlled feasibility trial can be delivered effectively and estimate important parameters (e.g. recruitment and retention rates and completeness of follow up) needed to design a future definitive trial.

Findings will be used to refine procedures for a future definitive trial evaluation of the effectiveness (and cost-effectiveness) of the BIP compared with enhanced usual care for the treatment of depression in NCDs.

Ethics and dissemination

The study has received ethics approval by the University of York Health Sciences Research Governance Committee, UK; the Health Ministry Screening Committee, India; and the Ethics Committee (Behavioural Sciences Division), NIMHANS, Bangalore, India.

Trial Registration

CTRI/2020/05/025048 [Registered on: 06/05/2020], http://ctri.nic.in

This research was funded by the National Institute for Health Research (NIHR) (17/63/130) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK government.
Translation is a key determinant controlling the fate of cytoplasmic long non-coding RNAs
Authors: Andjus Sara , Szachnowski Ugo , Vogt Nicolas , Hatin Isabelle , Cornu David , Papadopoulos Chris , Lopes Anne , Namy Olivier , Wery Maxime , Morillon Antonin
Published: May 2022

Despite being predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes, which may result in the production of functional peptides. However, the landscape and biological relevance of lncRNAs translation remains poorly studied. In the budding yeastSaccharomyces cerevisiae, cytoplasmic Xrn1-sensitive lncRNAs (XUTs) are targeted by the Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs are translated, which impacts their abundance. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Translation also affects XUTs independently of NMD, in some cases interfering with their decapping. Ribo-Seq confirmed ribosomes binding to XUTs and identified actively translated small ORFs in their 5’-proximal region. Mechanistic analyses revealed that their NMD-sensitivity mainly depends on the 3’-untranslated region length. Finally, we detected the peptide derived from the translation of an NMD-sensitive XUT reporter in NMD-competent cells. Our work highlights the role of translation in the post-transcriptional metabolism of XUTs, acting as a modulator of their expression. We propose that XUT-derived peptides could be exposed to the natural selection, while NMD restricts XUTs levels.
A whole blood approach improves speed and accuracy when measuring mitochondrial respiration in intact avian hematocytes
Authors: Nord Andreas , Chamkha Imen , Elmér Eskil
Published: May 2022

Understanding mitochondrial biology and pathology is key to understanding the evolution of animal form and function. However, mitochondrial measurement often involves invasive, or even terminal, sampling, which can be difficult to reconcile in wild models or in longitudinal studies. Non-mammal vertebrates contain mitochondria in their red blood cells, which can be exploited for minimally invasive mitochondrial measurement. Several recent bird studies have measured mitochondrial function using isolated blood cells. Isolation adds time in the laboratory and might be associated with physiological complications. Inference may also be constrained on biological grounds by lack of tissue context. We developed and validated a protocol to measure mitochondrial respiration in bird whole blood. Endogenous respiration was comparable between isolated blood cells and whole blood. However, oxidative respiration was higher in whole blood, and whole blood mitochondria were better coupled and had higher maximum working capacity. Whole blood measurement was also more reproducible than measurement on isolated cells for all traits considered. Measurements were feasible over a 10-fold range of sample volumes, though both small and large volumes were associated with changes to respiratory traits. The protocol was compatible with long-term storage: after 24 h at 5 °C without agitation all respiration traits but maximum working capacity remained unchanged, the latter decreasing by 14%. Our study suggests that whole blood measurement provides faster, more reproducible, and more biologically (tissue context) and physiologically (mitochondrial integrity) relevant assessment of mitochondrial respiration. We recommend future studies to take a whole blood approach unless specific circumstances require the use of isolated blood cells.
Plasticity of mitochondrial function safeguards phosphorylating respiration during in vitro simulation of rest-phase hypothermia
Authors: García-Díaz Carmen C. , Chamkha Imen , Elmér Eskil , Nord Andreas
Published: May 2022

Many animals downregulate body temperature to save energy when resting (rest-phase hypothermia). Small birds that winter at high latitude have comparatively limited capacity for hypothermia and so pay large energy costs for thermoregulation during cold nights. Available evidence suggests this process is fuelled by adenosine triphosphate (ATP)-dependent mechanisms. Most ATP is produced by oxidative phosphorylation in the mitochondria, but mitochondrial respiration can be lower during hypothermia because of the temperature-dependence of biological processes. This can create conflict between increased organismal ATP demand and a lower mitochondrial capacity to provide it. We studied this in blood cell mitochondria of wild great tits (Parus major) by simulating rest-phase hypothermia via a 6°C reduction in assay temperature in vitro. The birds had spent the night preceding the experiment in thermoneutrality or in temperatures representing mild or very cold winter nights. Night temperature did not affect mitochondrial respiration. Across treatments, endogenous respiration was 14% lower in hypothermia. This did not reflect general thermal suppression because phosphorylating respiration was unaffected by thermal state. Instead, hypothermia was associated with a threefold reduction of leak respiration, from 17% in normothermia to 4% in hypothermia. Thus, coupling of total respiration to ATP production was 96% in hypothermia, compared to 83% in normothermia. Our study shows that thermal insensitivity of phosphorylation combined with short-term plasticity of leak respiration may safeguard ATP production when endogenous respiration is suppressed. This casts new light on the process by which small birds endure harsh winter cold and warrants future tests across tissues in vivo.
p53 mRNA availability during the cellular stress response is controlled by Cdc73 sequestration to stress granules
Authors: Lee Hojin , Kim Tae-Hyeon , Yoo Joo-Yeon
Published: May 2022

Cells trigger the assembly of stress granules (SGs) under various stress conditions. Among the many proteins recruited to SGs are RNA-binding proteins (RBPs) and regulators of transcription. Here, we report the translocation of hCdc73, a component of the PAF1 transcription complex, to cytosolic SGs in response to sodium arsenite, MG132, thapsigargin (TG) or heat treatment. The hCdc73 protein possesses a long intrinsically disordered region (IDR) from amino acids 256-416, the presence of which is required and essential for the translocation of hCdc73 to cytosolic SGs. The purified hCdc73 IDR formed droplets in vitro, and the light-activated assembly of hCdc73 IDR-Cry2 was also verified. Alone, the hCdc73 IDR, however, was not sufficient for the translocation of hCdc73 to SGs, as physical interactions with the scaffold proteins of SGs, such as FMR1, were needed. Selective sequestration of cytosolic hCdc73 into SGs coincided with the dissociation of p53 mRNA from the hCdc73/Ski8/eEF1Bγ complex, resulting in a transient rise in p53 mRNA at the posttranscriptional level. In conclusion, we propose that in addition to the storage of nontranslating mRNAs, SGs also function to control the availability of mRNAs for stress response genes by restraining their negative regulators within SGs.
The locus coeruleus directs sensory-motor reflex amplitude across environmental contexts
Authors: Witts Emily C. , Mathews Miranda A. , Murray Andrew J.
Published: May 2022

Animals possess a remarkable ability to quickly and accurately respond to challenges to their balance and posture. Postural corrections are the implementation of a motor act by the nervous system that counteracts a perturbation and returns the body to a stable state. These corrections must respect both the current position of the limbs and trunk, as well as the external environment. However, how motor circuits integrate multiple streams of information regarding both these internal and external factors, and adjust motor actions accordingly, are poorly understood. Here we show that the lateral vestibular nucleus in the brainstem generates motor corrections following perturbation, and that this reflex can be altered by manipulating the surrounding environment. The strength of the motor correction is influenced by noradrenergic signalling from the locus coeruleus, suggesting a potential link between forebrain structures which convey sensory information about the environment, and brainstem circuits that generate motor corrections.
Massive inversion polymorphisms shape the genomic landscape of deer mice
Authors: Harringmeyer Olivia S. , Hoekstra Hopi E.
Published: May 2022

Chromosomal inversions are an important form of structural variation that can affect recombination, chromosome structure and fitness. However, because inversions can be challenging to detect, the prevalence and hence significance of inversions segregating within species remains largely unknown, especially in natural populations of mammals. Here, by combining population-genomic and long-read sequencing analyses in a single, widespread species of deer mouse (Peromyscus maniculatus), we identified 21 polymorphic inversions, which are large (1.5-43.8 Mb) and cause near complete suppression of recombination when heterozygous (0-0.03 cM/Mb). We found that inversion breakpoints frequently occur in centromeric and telomeric regions and are often flanked by long inverted repeats (0.5-50 kb), suggesting that they likely arose via ectopic recombination. By genotyping the inversions in populations across the species’ range, we found that the inversions are often widespread, do not harbor deleterious mutational loads, and many are likely maintained as polymorphisms by divergent selection. Comparisons of forest and prairie ecotypes of deer mice revealed 13 inversions that contribute to differentiation between populations, of which five exhibit significant associations with traits implicated in local adaptation. Together, we found that inversion polymorphisms have a significant impact on recombination, genome structure and genetic diversity in deer mice, and likely facilitate local adaptation across this species’ widespread range.
Epidemiological Interactions of Influenza and SARS-CoV-2 within a University Population During Omicron B.1.1.529 Outbreak
Authors: Malampy Rachel Christine , Ganz Troy James , DeOliveira Gabriel M , Le Catherine T , Li Kurvin M , Auclair Jared
Published: May 2022

The COVID-19 Pandemic has prompted innovation and research to further understand not only SARS-CoV-2, but other respiratory viruses as well. Since the start of the pandemic there has been a lack in influenza collection and surveillance. In October 2021 the Life Sciences Testing Center at Northeastern University implemented the TaqPath™ COVID-19, Flu A, Flu B combo kit to test for multiple respiratory diseases among the University’s population. During this time the SARS-CoV-2 variant of concern, Omicron B.1.1.529, became the dominant strain in the greater Boston area. During this time an inverse correlation in the detection of positive SARS-CoV-2 and Influenza A was observed. More data is needed to determine if this observed inverse correlation on positivity rate is linked to public health measures or biological mechanism within the immune system.
Sexual and reproductive health service needs associated with underage initiation of selling sex among adult female sex workers in Guinea-Bissau
Authors: Grosso Ashley , Berg Lindsay , Rucinski Katherine , Rao Amrita , Djaló Mamadú Aliu , Diouf Daouda , Baral Stefan
Published: May 2022

Objective

To assess the prevalence and predictors of underage initiation of selling sex among female sex workers (FSW) in Guinea-Bissau.

Methods

505 adult FSW recruited using respondent-driven sampling were surveyed in 2017. Multivariable logistic regression was used to identify demographic, behavioral, and psychosocial characteristics associated with initiation of selling sex while underage (<18 years).

Results

26.3% (133/505) of FSW started selling sex before age 18. Underage initiation of selling sex was associated with experiencing forced sex before age 18 (adjusted odds ratio [aOR]:6.74;95% confidence interval [CI]:2.05-22.13], and never being tested for HIV (aOR:0.43;95%CI:0.02-0.91). Despite having lower odds of wanting to have children or more children (aOR:0.31;95%CI:0.17-0.56), FSW who started selling sex while underage had lower odds of using highly effective contraception such as implants (aOR:0.43;95%CI:0.24-0.77). Among those who were ever pregnant, a lower percentage of FSW who started selling sex while underage accessed antenatal care (56.6% v. 74.7%, p=0.008).

Conclusion

These data suggest that early initiation of selling sex among adult FSW in Guinea-Bissau is common. Social services for youth and integrated HIV and reproductive health services are critical to address the persisting sexual and reproductive health needs of FSW who started selling sex while underage.

Synopsis

Adult female sex workers in Guinea-Bissau who started selling sex while underage had lower uptake of health services including HIV testing and antenatal care.
A rapid One-Pot RNA-isolation method for simplified clinical detection of SARS-COV-2 infection in India
Authors: Jain Sonia , Bhowmick Arghya , Pandey Anil Kumar
Published: May 2022

Background

With the rapid increase in COVID-19 cases and the discovery of new viral variants within India over multiple waves, the expensive reagents and time-consuming sample pretreatment required for qPCR analysis have led to slower detection of the disease. The vast Indian population demands an inexpensive and competent sample preparation strategy for rapid detection of the disease facilitating early and efficient containment of the disease.

Methods

In this study, we have surveyed the spread of COVID-19 infection over Faridabad, Haryana, India for 6 months. We also devised a simple single-step method for total RNA extraction using a single tube and compared its efficacy with the commercially available kits.

Findings

Our findings suggest that determining Ct values for samples subjected to the One Pot (OP) RNA extraction method was as efficient as the commercially available kits but delivers a subtle advantage in a way, by minimizing the cost, labor, and sample preparation time.

Conclusion

This novel crude RNA extraction method is stable and capable of operating in developing countries like India for low resource settings, without the use of expensive reagents and instruments. Additionally, this method can be further adapted to pooling samples strategies owing to its high sensitivity.