bluuebunny/crossref_metadata_2025 huggingface dataset:
Numeric work: The efforts of calculation actors to make numbers count in climate and energy policy
Authors: Jørgensen Susanne , Sørensen Knut H
Published: November 2022

Policy documents suggest that quantitative information is important in the development of climate and energy policy. This is supported by quantitative studies research into the use of numbers in governance, which tends to assume that numbers have sufficient epistemic authority to be used by policymakers because they are believed to be trustworthy since they are produced through mechanical objectivity. This paper questions such assumptions, by analysing the extent of extra-calculative work when providing numeric information to policymakers. We term such efforts numeric work and analyse the extent and content of such work based on interviewed experts who are engaged with calculating climate and energy issues in the context of policymaking in Norway. Numeric work shares features with the actor–network theory concept of translation but differs due to the dialogic interaction between calculation actors and policymakers that includes efforts to improve the transparency of calculation, which counters a complete black-boxing of calculation results.
Can innovation vouchers promote SMEs’ innovation in China: A flexible conditional difference-in-differences analysis
Authors: Xu Nini , Guo Junhua
Published: November 2022

Innovation voucher is a market-oriented policy instrument to encourage the external resource utilization of small and medium enterprises (SMEs) so as to foster their innovation activities and outcomes. This study extends the extant literature on the effectiveness of innovation voucher policy by investigating whether this small innovation subsidy can promote the innovation output of SMEs in China, a typical emerging economy, and identifying policy-relevant heterogeneities. By using the samples of Chinese technology-based SMEs and a flexible conditional difference-in-differences approach, our results show that innovation vouchers generally do promote SMEs’ innovation output and exert a more salient effect on medium-sized enterprises. Furthermore, the incentive effect of innovation vouchers is stronger on the recipients in the regions where the institutional environment is more developed. This study has important implications for policy makers and SMEs.
Opportunities to advance implementation science and nutrition research: a commentary on the Strategic Plan for NIH Nutrition Research
Authors: Nicastro Holly L , Vorkoper Susan , Sterling Rene , Korn Ariella R , Brown Alison G M , Maruvada Padma , Oh April Y
Published: November 2022

Despite population-wide recommendations by the U.S. Dietary Guidelines for Americans and others to encourage health-promoting dietary patterns, the proportion of Americans following dietary recommendations remains low. The gaps in the adoption and integration of evidence-based dietary interventions, practices, programs, and policies (EBIs) into community and clinical settings signal the need to strengthen efforts in implementation science (IS) in nutrition research to understand and alleviate barriers to adopting and sustaining healthy dietary behaviors and practices. Equally important is the translation of this research into practice in a variety of settings and across the diversity of populations. Recognizing this need, the U.S. National Institutes of Health (NIH) 2020–2030 Strategic Plan for NIH Nutrition Research calls for the expansion of IS as a key opportunity to advancing nutrition research. This commentary highlights three scientific opportunities to stimulate IS in nutrition research and provides examples for each opportunity. These include: (a) Advance consideration of implementation and dissemination early in the design of interventions to facilitate opportunities for equitable scale-up and sustainability of EBIs, (b) Develop and test strategies for equitable implementation of nutrition and diet EBIs in health care and community settings, and (c) Build and strengthen the infrastructure, capacity, and expertise needed to increase use of IS in clinical and community nutrition research to swiftly move the research into practice. By advancing the three opportunities identified in this commentary, the scientific community has the potential to advance the field of nutrition research and IS with the ultimate goal of improving public health.
Genotoxicity, acute, and subchronic toxicity evaluation of dried Neurospora crassa protein-rich biomass
Authors: Lozy Fred , Meetro Jwar , Simon Ryan , Calabrese Philip , Whiteley Justin M
Published: November 2022

Filamentous fungus biomass is a protein-rich food, which can serve as an alternative to animal, plant, and legume protein sources. Neurospora crassa is a filamentous fungus that typically grows in tropical and sub-tropical regions. Traditionally, N. crassa has served as a model eukaryotic organism due to its ease of growth and propagation and suitability for genetic manipulation. However, filamentous fungi, such as Neurospora, have also been consumed or used to produce fermented foods for centuries and have been developed into protein-rich biomass ingredients to be used in conventional foods and meat substitutes. A panel of toxicological tests including genotoxic, acute, and subchronic studies were conducted on dried N. crassa biomass to support its safe use in food. The dried N. crassa biomass was found to be not genotoxic in a bacterial reverse mutation (Ames) assay, an in vitro chromosomal aberration test, and an in vivo micronucleus test. In the acute and subchronic toxicity studies, rats were orally gavaged with N. crassa biomass at concentrations of 0, 1,000, 2,500, and 5,000 mg/kg body weight/day for 14 and 90 days, respectively. At the conclusion of the studies, there were no test article-related toxicity results observed in clinical observations, body weight, food consumption, ophthalmology, hematology, clinical chemistry, coagulation, thyroid hormone, urinalysis, and macroscopic and microscopic findings. The no-observed-adverse-effect level for the dried N. crassa biomass ingredient was determined to be 5,000 mg/kg body weight/day, the highest dose tested.
Revealing the cryptic diversity of the widespread and poorly known South American blind snake genusAmerotyphlops(Typhlopidae: Scolecophidia) through integrative taxonomy
Authors: Graboski Roberta , Arredondo Juan C , Grazziotin Felipe G , Guerra-Fuentes Ricardo Arturo , Da Silva Ariane A A , Prudente Ana L C , Pinto Roberta R , Rodrigues Miguel T , Bonatto Sandro L , Zaher Hussam
Published: November 2022

Morphological stasis is generally associated with relative constancy in ecological pressures throughout time, producing strong stabilizing selection that retains similar shared morphology. Although climate and vegetation are commonly the main key factors driving diversity and phenotypic diversification in terrestrial vertebrates, fossorial organisms have their morphology mostly defined by their fossorial lifestyle. Among these secretive fossorial organisms, blind snakes of the South American genus Amerotyphlops are considered poorly studied when compared to other taxa. Here, we evaluate the cryptic diversity of Amerotyphlops using phylogenetic and multivariate approaches. We based our phylogenetic analysis on a molecular dataset composed of 12 gene fragments (eight nuclear and four mitochondrial) for 109 species of Typhlopidae. The multivariate analysis was implemented using 36 morphological variables for 377 specimens of Amerotyphlops. Additionally, we contrast our phylogenetic result with the morphological variation found in cranial, external and hemipenial traits. Our phylogenetic results recovered with strong support the following monophyletic groups within Amerotyphlops: (1) a clade formed by A. tasymicris and A. minuisquamus; (2) a clade composed of A. reticulatus; (3) a north-eastern Brazilian clade including A. yonenagae, A. arenensis, A. paucisquamus and A. amoipira; and (4) a clade composed of A. brongersmianus and a complex of cryptic species. Based on these results we describe four new species of Amerotyphlops from north-eastern and south-eastern Brazil, which can be distinguished from the morphologically similar species, A. brongersmianus and A. arenensis.
Prospective evaluation of dRAST for selecting optimal targeted antibiotics in positive blood culture with Gram-positive organisms
Authors: Kim Jeong-Han , Kim Taek Soo , Kang Chang Kyung , Han Sangkwon , Kim Dong Young , Kwon Sunghoon , Choe Pyeong Gyun , Kim Nam Joong , Park Wan Beom , Oh Myoung-don
Published: November 2022

Empirical antibiotic selection often fails to be optimal targeted in the era of increasingly common resistant organisms. We prospectively evaluated the usefulness or rapid AST for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteremia of Gram-positive organisms. QMAC-dRAST results led to optimal antibiotic treatment in 33 (89.2%) of the 37 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 133 (97.1%) of the 137 cases. In conclusion, the introduction of rapid phenotypic AST can help increase the selection of optimal targeted antibiotics during the early period of bacteremia.
Heterogeneity and Risk-of-Biases are No Longer the Issues to Conclude the Effectiveness of Baricitinib in Reducing COVID-19 Related Mortality: A Systematic Review and Meta-Analysis of Eight Randomised Controlled Trials
Authors: Manoharan Sivananthan , Ying Lee Ying
Published: November 2022

Background

Due to high heterogeneity and risk of bias (RoB) in previously published meta-analysis, a concrete conclusion on the efficacy of baricitinib in reducing mortality in COVID-19 patients was unable to form.

Methods

Search engines PubMed/MEDLINE, ScienceDirect and other sources like preprints and reference lists were searched with appropriate keywords. The included evidence was graded with GRADEpro. The RoB, heterogeneity and meta-analysis were studied through RevMan 5.4.1 software. The heterogeneity was evaluated based on the generatedp-value or I² test.

Results

Eight (8) RCTs were included in current analysis. Five studies had low RoB. Based on grading the evidence, the inclusion and exclusion of high RoB articles led to moderate and high certainty of evidence, respectively. Based on 8 RCTs (with high RoB), baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.84 [95% CI: 0.76 to 0.92;p= 0.0002; I2= 23%;p= 0.25]. The heterogeneity was insignificant but the RoB was high. We did subgroup analysis of low and high RoB articles and found out baricitinib statistically significantly reduced mortality with the RR = 0.68 [95% CI: 0.56 to 0.82;p< 0.0001; I2= 0%;p= 0.85] and RR = 0.89 [95% CI: 0.80 to 0.99;p= 0.04; I2= 0%;p= 0.43], respectively. The heterogeneity was 0% with insignificantp-values in both subgroup analyses. The percentage of mortality reduction was 31.31% and 7.79%, respectively whereas it was 13.95% in main group analysis.

Conclusion

With the presence of optimal sample size of 3944 from 5 low RoB studies which represents a minimum of 300 million population of people and with 0% of heterogeneity, the effectiveness of baricitinib in reducing the mortality in COVID-19 patients is concretely proven.
Selection of long COVID symptoms influences prevalence estimates in a prospective cohort
Authors: Wynberg Elke , de Bree Godelieve J. , Leenstra Tjalling , Verveen Anouk , van Willigen Hugo D.G. , de Jong Menno D. , Prins Maria , Boyd Anders ,   the RECoVERED Study Group
Published: November 2022

Background

Studies on long COVID differ in the selection of symptoms used to define the condition. We aimed to assess to what extent symptom selection impacts prevalence estimates of long COVID.

Methods

In a prospective cohort of patients who experienced mild to critical coronavirus disease 2019 (COVID-19), we used longitudinal data on the presence of 20 different symptoms to evaluate changes in the prevalence of long COVID over time when altering symptom selection.

Results

Changing symptom selection resulted in wide variation in long COVID prevalence, even within the same study population. Long COVID prevalence at 12 months since illness onset ranged from 39.6% (95%CI=33.4-46.2) when using a limited selection of symptoms to 80.6% (95%CI=74.8-85.4) when considering any reported symptom to be relevant.

Conclusions

Comparing the occurrence of long COVID is already complex due to heterogeneity in study design and population. Disparate symptom selection may further hamper comparison of long COVID estimates between populations. Harmonised data collection tools could be one means to achieve greater reproducibility and comparability of results.
No changes in diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography score from before to after mechanical thrombectomy for anterior circulation occlusion are associated with good outcomes
Authors: Hashimoto Hiroaki , Maruo Tomoyuki , Kimoto Yuki , Nakamura Masami , Fujinaga Takahiro , Nakamura Hajime , Ushio Yukitaka
Published: November 2022

Background

Although preoperative diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) is well known as a predictor of outcomes after mechanical thrombectomy (MT) for large-vessel occlusion (LVO), assessment of changes in DWI-ASPECT from before to after MT is rare. Therefore, we clarified the relationship between the change in DWI-ASPECTS and clinical outcomes.

Methods

In this retrospective single-center study, we enrolled 63 cases of anterior LVOs treated with MT between April 2015 and March 2022. Preoperative and postoperative DWI-ASPECTSs were calculated. DWI-ASPECTSs were categorized into cortical-ASPECTSs (c-ASPECTSs) and subcortical ASPECTSs and assessed. Additionally, medical variables related to patients, such as sex, age, National Institutes of Health Stroke Scale (NIHSS) score, and premorbid modified Rankin Scale (mRS) score, were evaluated. A good outcome was defined as an mRS score of 0 or 2 at 3 months.

Results

Forty-five patients met the inclusion criteria. Among the patients, 9 (20%) had a good outcome. The good outcome group showed significantly higher postoperative DWI-ASPECTs (median 8 vs. 5,p= 0.012) and c-ASPECTSs (median 4 vs. 3,p= 0.020) than the not-good outcome group. No changes in DWI-ASPECTSs and c-ASPECTSs from before to after MT were significantly associated with the good outcome (p= 0.017,p= 0.016, respectively). The cut-off values for the good outcome on receiver operating characteristic curve analysis for differences between DWI-ASPECTSs and c-ASPECTSs was 0 [area under the curve (AUC) 0.77, sensitivity 0.67, specificity 0.78] and 0 [AUC 0.74, sensitivity 0.44, specificity 1.00]. Logistic regression analyses showed that baseline NIHSS score (odds ratio, 0.69; 95% confidence interval 0.48–1.00;p= 0.046) and postoperative DWI-ASPECTS (odds ratio, 2.27; 95% confidence interval 1.02–5.04;p= 0.039) were independent factors for the good outcome.

Conclusions

The good outcome of patients with anterior LVO was not associated with any changes in DWI-ASPECTSs and c-ASPECTSs from before to after MT.
Hip and knee joint kinematics predict quadriceps hyperreflexia in people with post-stroke Stiff-Knee gait
Authors: Lee Jeonghwan , Akbas Tunc , Sulzer James
Published: November 2022

Wearable assistive technology for the lower extremities has shown great promise towards improving gait function in people with neuromuscular injuries. But common secondary impairments, such as hyperreflexia, have been often neglected. Adding hyperreflexia prediction to the control loop would require expensive or complex measurement of muscle fiber characteristics. In this study, we explore a clinically accessible biomechanical predictor set that can accurately predict rectus femoris (RF) reaction after knee flexion assistance in pre-swing by a powered orthosis. We examined a total of 14 gait parameters based on gait kinematic, kinetic, and simulated muscle-tendon states from 8 post-stroke individuals with Stiff-Knee gait (SKG) wearing a knee exoskeleton robot. We independently performed both parametric and non-parametric variable selection approaches using machine learning regression techniques. Both models revealed the same four kinematic variables relevant to knee and hip joint motions were sufficient to effectively predict RF hyperreflexia. These results suggest that control of knee and hip kinematics may be a more practical method of incorporating quadriceps hyperreflexia into the exoskeleton control loop than the more complex acquisition of muscle fiber properties.
Screening, diagnosis and hospitalization of breast and cervical cancer in Brazil from 2010 to 2022: a time-series study
Authors: Capistrano Gustavo Nepomuceno , de Morais Thiffany Nayara Bento , Silva Costa Ketyllem Tayanne da , Santos Quirino Ana Luiza , da Costa Roberta Letícia Pimentel , de Andrade Fábia Barbosa
Published: November 2022

In Brazil, during the pandemic caused by COVID-19, screening for breast and cervical cancers was postponed or interrupted due to the prevailing health conditions. These neoplasms, however, are responsible for high morbidity and mortality among women in Brazil and have a major impact on the quality of life of this population and on public health. Thus, this study aims to evaluate the epidemiological behavior of hospitalization for cervical and breast cancer in Brazilian women, as well as the trend of screening tests and diagnosis of breast and cervical cancer in the years 2010 to 2022 in Brazil. This is an ecological research of time series, based on secondary data obtained from information systems of the country, about hospital admissions for breast and cervical cancer and screening methods used for these tumors. The data were analyzed in the Joinpoint Regression Program, to obtain the linear regression and temporal analysis of the variables. As results, there is a decrease in hospitalization rates for cervical cancer between the years 2010 and 2015 and a subsequent increase in 2019. Regarding breast cancer, there was an increase in hospitalizations, until reaching a peak in 2019. For both, in the pandemic years, between 2020 and 2022, there is a decrease in Brazil and in all its regions. As for the tracking of these diseases, it was observed that the performance of mammograms and preventive tests showed a similar behavior, in which there is a higher supply of these tests until 2019 and a drop during the pandemic period. This leads to the conclusion that even though Brazil has several policies for screening and early diagnosis of these diseases, there is still instability in the offer of tests and that there was a precariousness in this area during the pandemic.
Aromatic L-Amino Acid Decarboxylase is a novel fluid biomarker of Parkinson’s disease
Authors: Rutledge Jarod , Lehallier Benoit , Zarifkar Pardis , Losada Patricia Moran , Ryman Sephira , Yutsis Maya , Deutsch Gayle , Mormino Elizabeth , Trelle Alexandra , Wagner Anthony D , Kerchner Geoffrey , Tian Lu , Henderson Victor W. , Montine Thomas J , Borghammer Per , Wyss-Coray Tony , Poston Kathleen L
Published: November 2022

There are currently limited molecular markers of Parkinson’s disease, and there is an urgent need for new markers to guide clinical care, support earlier diagnosis, and hasten drug development. Here, we performed CSF and plasma proteomics in 5 Parkinson’s disease cohorts to identify novel protein biomarkers for these purposes, resulting in one of the largest such resources for Parkinson’s disease to date. We discovered a consistent upregulation of the protein L-Aromatic Acid Decarboxylase (AADC, EC 4.1.1.28, DDC) in the CSF and plasma of Parkinson’s disease patients. AADC is a key protein in the synthesis of dopamine and other monoamine neurotransmitters. We found that higher CSF AADC levels are associated with greater motor symptom severity in Parkinson’s patients. We replicated and extended these findings in another undescribed proteomics cohort ofde novoParkinson’s disease participants from the Parkinson’s Progression Marker Initiative, where we found that AADC expression is upregulated in treatment naïve participants and is associated with motor and cognitive symptoms. We found that AADC expression can accurately distinguish Parkinson’s disease from healthy participants and Alzheimer’s disease participants in multiple independent cohorts, and developed a panel of 16 proteins that achieves 95% receiver operator area under the curve (ROC AUC) in distinguishing these three states. Our results suggest that CSF AADC is a marker of the underlying disease process in Parkinson’s disease with potential utility in multiple contexts.
Use of Sociodemographic Information in Clinical Vignettes of Multiple-Choice Questions for Preclinical Medical Students
Authors: Carey-Ewend Kelly , Feinberg Amir , Flen Alexis , Williamson Clark , Gutierrez Carmen , Cykert Samuel , Beck Dallaghan Gary L. , Gilliland Kurt O.
Published: November 2022

Purpose

To characterize the use of demographic data in multiple-choice questions from a commercial preclinical question bank and determine if there is appropriate use of different distractors.

Background

Multiple-choice questions for medical students often include vignettes describing a patient’s presentation to help guide students to a diagnosis, but overall patterns of usage between different types of nonmedical patient information in question stems has yet to be determined.

Methods

380 of 453 randomly selected questions were included for analysis after determining they contained a clinical vignette and required a diagnosis. The vignettes and following explanations were then examined for the presence/absence of 11 types of demographic information, including age, sex/gender, and socioeconomic status. We compared both the usage frequency and relevance between the 11 information types.

Results

Most information types were present in less than 10% of clinical vignettes, but age and sex/gender were present in over 95% of question stems. Over 50% of questions included irrelevant information about age and sex/gender, but 75% of questions did not include any irrelevant information of other types. Patient weight and environmental exposures were significantly more likely to be relevant than age or sex/gender.

Discussion

Students using the questions in this study will frequently gain practice incorporating age and sex/gender into their clinical reasoning while receiving little exposure to other demographic information. Based on our findings, we posit that questions could include more irrelevant information, outside age and sex/gender, to better approximate real clinical scenarios and ensure students do not overvalue certain demographic data.
Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study
Authors: Löwensteyn Yvette N. , Zheng Zhe , Rave Neele , Bannier Michiel A.G.E. , Billard Marie-Noëlle , Casalegno Jean-Sebastien , Pitzer Virginia E. , Wildenbeest Joanne G. , Weinberger Daniel M. , Bont Louis
Published: November 2022

A nationwide prospective study showed year-round RSV transmission in the Netherlands after an initial 2021 summer outbreak. The pattern was unprecedented and distinct from neighboring countries. Our dynamic simulation model suggests that this transmission pattern could be associated with waning immunity because of low RSV circulation during the COVID-19 pandemic.
Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients: A Multicenter Randomized Controlled Trial: The REPLENISH Trial Protocol
Authors: Arabi Yaseen M , Al-Dorzi Hasan M. , Sadat Musharaf , Muharib Dina , Algethamy Haifa , Al-Hameed Fahad , Mady Ahmed , AlGhamdi Adnan , Al Mekhlafi Ghaleb. A. , Al-Fares Abdulrahman A , Kharaba Ayman , Bshabshe Ali Al , Maghrabi Khalid , Ghamdi Khalid Al , Rasool Ghulam , Chalabi Jamal , AlHumedi Haifaa Ibrahim , Sakkijha Maram Hasan , Alamrey Norah Khalid , Alhutail Rabeah Hamad , Sifaoui Kaouthar , Almaani Mohammed , Alqahtani Rakan , Qureshi Ahmad S , Hejazi Mohammed Moneer , Arishi Hatim , AlQahtani Samah , Ghazi Amro Mohamed , Baaziz Saleh T , Azhar Abeer Othman , Alabbas Sara Fahad , AlAqeely Mohammed , AlOrabi Ohoud , Al-Mutawa Alia , AlOtaibi Maha , Aldibaasi Omar , Jose Jesna , Starkopf Joel , Preiser Jean-Charles , Perner Anders , Al-Dawood Abdulaziz ,   the Saudi Critical Care Trials Group
Published: November 2022

Background

Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.

Methods

The REPLENISH (Replacing Protein ViaEnteralNutrition in aStepwise Approachin Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the Supplemental protein group or the Control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The Supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The Control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients.

Discussion

The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2024

Trial Registration

ClinicalTrials.govIdentifier:NCT04475666. Registered on July 17, 2020https://clinicaltrials.gov/ct2/show/NCT04475666
SEVERITY AND MORPHOLOGICAL CLASSIFICATION OF ANAEMIA AMONG CHILDREN AGED 2- 59 MONTHS IN DAR ES SALAAM, TANZANIA: A CROSS SECTIONAL STUDY PROTOCOL
Authors: Omary Salha Ally , Kalabamu Florence Salvatory , Fataki Maulid Rashid , Salum Shani Shamsi , Mohamed Ummulkheir Hamid , Kimaro Joseph Gasper , Leshabari Kelvin Melkizedeck
Published: November 2022

Background

Anaemia is a clinically significant secondary diagnosis in children under the age of five in most parts of developing world, including Tanzania. Studies that assess clinical conditions associated with prenatal and postnatal era are highly relevant to global health as they tend to reflect patterns of significant health challenges across the entire human lifespan.

Objective

To assess for morphological characteristics and severity of anaemia among under-five population seen at Dar es Salaam regional referral facilities in Tanzania.

Design & Methods

A cross-sectional hospital based study will be conducted at Temeke Regional Referral and Mbagala Rangi Tatu district hospitals in Dar es Salaam, Tanzania. All children aged 2-59 months will be eligible to participate in the study. All children aged 2 – 59 months with anaemia will be the target population. The study main tool will be a self-administered questionnaire with five distinct parts. Data analysis will commence with summarisation. Specifically, continuous data will be summarised using median (with inter-quartile range) and categorical data will be summarised using frequency (and proportion by %) Graphical tools will also be employed where by important correlations as well as +/- outliers will be assessed. Besides, univariate and bivariate statistics will be computed for all clinically relevant data. Main outcome measure will be severity and morphological classification of anaemia. Unless otherwise stated, an alpha-level of 5% will be used as a limit of type 1 error in findings. Written informed consent will be sought from the parent/guardian of each participant child prior to inclusion into the study.
WHAT IS THE RISK OF DEVELOPING A SEVERE FORM OF COVID-19 INFECTION AMONG ADULTS WHO CURRENTLY SMOKE COMPARED TO EX-SMOKERS? A protocol for systematic review and meta-analysis
Authors: Abaate Taagbara Jolly , Prince Abueh Nukoamene
Published: November 2022

Introduction

Smoking is one of the lifestyle choices associated with an increased risk of chronic health conditions and poorer COVID-19 outcomes. Because it is known that the lungs recover after quitting smoking, a direct comparison of the severity of COVID-19 infection in current and former smokers needs to be investigated.

Methods and analysis

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 Checklist was used. Non-randomized studies will be searched in PubMed, Cochrane CENTRAL library, Embase, and Epistemonikos from December 2019 to the present. Hand-searching of grey literature, key journals, and reference lists will be conducted

This review will include studies of current and former smokers, with the main outcome being ICU admission, assisted respiration, or death. Two independent reviewers will select primary studies and abstract data from them. The Newcastle-Ottawa checklist will be used to assess the risk of bias, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework will be used to assess the quality of cumulative evidence. RevMan 5.4 will be used for data analysis.

The I2statistic will be used to evaluate heterogeneity. For similar studies, the fixed-effect method of a meta-analysis will be used; otherwise, a random-effect model will be used. The qualitative synthesis will be used for studies that are ineligible for the quantitative approach.

Ethical consideration and dissemination

Because published data will be reviewed, no ethical approval is required. Our findings will be presented at national and/or international conferences, and they will be published in a peer-reviewed journal.

PROSPERO registration number CRD42022368552

ARTICLE SUMMARY

Strengths and limitations of this study

This is a focused research question comparing the current and ex-smokers risk of contracting the severe form of COVID-19.

This systematic review and meta-analysis will provide evidence of the dangers of smoking during the COVID-19 pandemic.

The PRISMA-P reporting guidelines were strictly followed while writing this protocol.

Study selection will be carried out by two independent reviewers and a third person will intervene if a disagreement arises.

A potential limitation is that an observational study design will be used in this systematic review.
Sepsis Transcriptomic Trajectory and Phenotypic Correlation Using Time Series Gene Expression from Childhood Meningococcal Infection
Authors: Rashid Asrar , Toufiq M. , Khilnani Praveen , Malik Zainab A. , Hussain Z. , Alkhazaimi Hoda , Sharief Javed , Kadwa Raziya , Brusletto Berit S. , Sarpal Amrita , Chaussabel Damien , Malik Rayaz , Quraishi Nasir , Benakatti Govind , Zaki Syed A. , Nadeem Rashid , Shaikh Guftar , Al-Dubai Ahmed , Hussain Amir
Published: November 2022

Sepsis remains a leading cause of in-hospital morbidity and mortality. In the acute phase sepsis is described as a dysregulated process. The objective was to track temporal transcriptomic changes in infants with meningococcal disease (MSS). Therefore, two datasets underwent secondary analysis using temporal transcriptomic data. Methods applied to analysis included Principal Component Analysis (PCA), Transcript Time Course Analysis (TTCA) and Gene Set Expression Analysis (GSEA). Gene expression clustering algorithm for both datasets suggested three phases from the time of admission, and PCA plots indicated a gene-expression trajectory for both datasets. The data set from Kwan et al., showed that 410 genes differentiated survivors from the non-survivor, which included various cytokine, TNF, and apoptosis-associated pathways (normalized expression scores = −1.60, p = 0.02, and q = 0.15). Additionally, GSEA demonstrated gene sets significantly associated with disease severity. The genes for the cytokines CLC, HFE, HLA-F, NLRP3, and TNFRSF1B were significant. The Gene-sets elicited by GSEA in the Kwan and Emonts dataset had a high degree of molecular signature crossover (89.2% overlap), although a comparison of gene-expression trajectories across both datasets was difficult due to differing sample timing. Transcriptomic analysis demonstrated temporal trajectories in MSS-related gene expression. Larger studies using transcriptome expression are required could enhance the understanding of sepsis pathogenesis, improving prognostication and enable the development of precision therapies.
The reovirus σ1 attachment protein influences the stability of its entry intermediate
Authors: Garcia Maximiliano L. , Danthi Pranav
Published: November 2022

Structural metastability of viral capsids is pivotal for viruses to survive in harsh environments and to undergo timely conformational changes required for cell entry. Mammalian orthoreovirus (reovirus) is a model to study capsid metastability. Following initial disassembly of the reovirus particle mediated by proteases, a metastable intermediate called the infectious subvirion particle (ISVP) is generated. Using a σ1 monoreassortant virus, we recently showed that σ1 properties affect its encapsidation on particles and the metastability of ISVPs. How metastability is impacted by σ1 and whether the lower encapsidation level of σ1 is connected to this property is unknown. To define a correlation between encapsidation of σ1 and ISVP stability, we generated mutant viruses with single amino acid polymorphisms in σ1 or those that contain chimeric σ1 molecules composed of σ1 portions from Type 1 and Type 3 reovirus strains. We found that under most conditions where σ1 encapsidation on the particle was lower, ISVPs displayed lower stability. By separating wild-type particles based on the level of encapsidated σ1, we also found that lower σ1 encapsidation leads to lower ISVP stability. Characterization of mutant viruses selected for enhanced stability via a forward genetic approach also revealed that in some cases, σ1 properties influence stability without influencing σ1 encapsidation. These data indicate that σ1 can also influence ISVP stability independent of its level of incorporation. Together, our work reveals an underappreciated effect of the σ1 attachment protein on the properties of the reovirus capsid.
A hole in Turing’s theory: pattern formation on the sphere with a hole
Authors: Borgqvist Johannes G. , Gerlee Philip , Lundholm Carl
Published: November 2022

The formation of buds on the cell membrane of budding yeast cells is thought to be driven by reactions and diffusion involving the protein Cdc42. These processes can be described by a coupled system of partial differential equations known as the Schnakenberg system. The Schnakenberg system is known to exhibit diffusion-driven pattern formation, thus providing a mechanism for bud formation. However, it is not known how the accumulation of bud scars on the cell membrane affect the ability of the Schnakenberg system to form patterns. We have approached this problem by modelling a bud scar on the cell membrane with a hole on the sphere. We have studied how the spectrum of the Laplace–Beltrami operator, which determines the resulting pattern, is affected by the size of the hole, and by numerically solving the Schnakenberg system on a sphere with a hole using the finite element method. Both theoretical predictions and numerical solutions show that pattern formation is robust to the introduction of a bud scar of considerable size, which lends credence to the hypothesis that bud formation is driven by diffusion-driven instability.
Transcription-independent hold of the G1/S transition is exploited to cope with DNA replication stress
Authors: Jin Yue , Lan Guoqing , Zhang Jiaxin , Sun Haoyuan , Xin Li , Cao Qinhong , Tang Chao , Yang Xiaojing , Lou Huiqiang , Hou Wenya
Published: November 2022

RB1 (retinoblastoma) members control the G1/S commitment as transcriptional repressors in eukaryotic cells. Here we uncover that an extra copy ofRB1equivalent (WHI7orWHI5) is sufficient to bypass the indispensability of the central genomic checkpoint kinases Mec1ATR-Rad53CHK1inSaccharomyces cerevisiae. Mec1-Rad53 directly phosphorylate Whi7/5, antagonizing their nuclear export or protein turnover upon replication stress. Through in vitro reconstitution, we show that Whi7 C-terminus directly binds and hinders S-CDK-Cks1 from processively phosphorylating Sic1. By microfluidic single-cell real-time quantitative imaging, we demonstrate that both Whi7 and Whi5 are required to flatten the degradation curve of the major S-CDK inhibitor Sic1 in vivo. These findings reveal an eclipsed transcription-independent role of Whi7 homologs, which is highlighted by genome integrity checkpoints to hold the G1/S transition instantly as a rapid response to unforeseeable replication threats.

Key points

Whi7 overexpression bypasses the essential function of Mec1 and Rad53 in a transcription-independent way.

Whi7 is stabilized by checkpoint-mediated phosphorylation.

Whi7 binds and hinders S-CDK-Cks1 from multi-phosphorylation of Sci1, thereby prolonging Sic1 degradation and G1/S transition.
Integrated multi-omics reveals minor spliceosome inhibition causes molecular stalling and developmental delay of the mouse forelimb
Authors: Drake Kyle D. , Springer Saren M. , Afriyie Kevon O. , Lopes Tomas D. , Girardini Kaitlin N. , Kanadia Rahul N.
Published: November 2022

Developmental insults causing limb progenitor cell cycle defects or death tend to produce micromelic limbs with maintained segmentation. This suggests that the developing limb is plastic yet has a bias towards proximo-distal patterning. Here we use a minor spliceosome-deficient (U11-null) mouse forelimb, which has severe micromelia yet maintains proximo-distal segmentation, to decipher the mechanism(s) underlying this form of developmental robustness. We show that U11 loss triggers transcriptomic stalling upon spatially heterogenous mis-splicing of minor intron-containing genes. Through spatial transcriptomics, we detected a failure of the U11-null forelimb to separate its distal patterning program from its proximal differentiation program, which was supported by single-cell RNAseq-determined developmental delay of U11-null chondroprogenitors. Ultimately, these molecular and cellular deficits culminated in perturbed chondrogenesis, myogenesis, and axonogenesis. Taken together, we suggest that, upon sensing depletion of progenitors, the limb halts its transcriptional networks to pause its cellular trajectory, affording time to restructure its developmental program.
Production of recombinant heterotrimeric mini-procollagen I and homotrimeric mini-procollagen II reveals new cleavage sites for BMP-1
Authors: Mariano Natacha , Dieryckx Cindy , Tessier Agnès , Vincourt Jean-Baptiste , Goff Sandrine Vadon-Le , Moali Catherine
Published: November 2022

The proteolytic conversion of soluble procollagens into mature collagen monomers is a critical step to decrease their solubility and trigger collagen fibril formation. In the case of collagens I, II and III, this maturation process is driven by several extracellular metalloproteinases such as BMP-1, tolloid-like proteinases, meprin α, meprin β, ADAMTS-2 and ADAMTS-14 but the extensive characterization of these proteolytic events has been hampered by the lack of recombinant procollagens. We previously reported the production and partial characterization of recombinant homotrimeric proteins derived from procollagen III (mini-procollagens III) and, in this study, we describe how we have extended this previous work to the production of heterotrimeric mini-procollagen I and homotrimeric mini-procollagen II. These mini-procollagens include truncated triple helices and intact C-telopeptide and C-propeptide domains and were produced in suspension in HEK293-F cells with yields ranging from 2.5 mg/L to 10 mg/L after purification. They proved very useful tools to analyze the effect of calcium on the stability of the procollagen C-terminal region and to compare the procollagen C-proteinase activity of BMP-1 on the three major fibrillar procollagens or their ability to interact with various partners such as PCPE-1. Using mass spectrometry to map BMP-1 cleavage sites on the mini-procollagens, we confirmed all previously described sites but also revealed two additional cleavage sites in the α1 chain of procollagens I and II. This result shows that the mini-procollagen toolkit offers a broad range of perspectives to make functional studies but also possibly structural analyses or to develop drug screening assays.
Calaxin stabilizes the docking of outer arm dyneins onto ciliary doublet microtubule in vertebrates
Authors: Yamaguchi Hiroshi , Morikawa Motohiro , Kikkawa Masahide
Published: November 2022

Outer arm dynein (OAD) is the main force generator of ciliary beating. Although OAD loss is the most frequent cause of human primary ciliary dyskinesia, the docking mechanism of OAD onto the ciliary doublet microtubule (DMT) remains elusive in vertebrates. Here, we analyzed the functions of Calaxin/Efcab1 and Armc4, the components of vertebrate OAD-DC (docking complex), using zebrafish spermatozoa and cryo-electron tomography. Mutation ofarmc4caused complete loss of OAD, whereas mutation ofcalaxincaused only partial loss of OAD. Detailed structural analysis revealed thatcalaxin-/-OADs are tethered to DMT through DC components other than Calaxin, and that recombinant Calaxin can autonomously rescue the deficient DC structure and the OAD instability. Our data demonstrate the discrete roles of Calaxin and Armc4 in the OAD-DMT interaction, suggesting the stabilizing process of OAD docking onto DMT in vertebrates.
THE COMMERCIAL PROMOTION OF ELECTRONIC CIGARETTES ON SOCIAL MEDIA AND ITS INFLUENCE ON VAPING INITIATION AND POSITIVE PERCEPTIONS OF VAPING IN ANGLOPHONE COUNTRIES: A SCOPING REVIEW PROTOCOL
Authors: Chacon L , Mitchell G , Golder S.
Published: November 2022

Introduction

Social media plays a protagonist role in the promotion of addictive substances targeting vulnerable and susceptible groups including adolescents and young adults in contemporary times. Despite the broad evidence of tobacco promotion on popular social media, electronic cigarette advertisement remains a recent public health concern, as is considered an emerging phenomenon. Further research must be developed to address this topic, contributing to improved regulation of the marketing of vaping products.

Aims and Objectives

The proposed scoping review aims to clarify key concepts related to e-cigarette promotion on social media, synthesise the relevant evidence related to the topic, and identify gaps that will contribute to further research and policymaking enhancement.

Identifying Studies

The databases Embase, MEDLINE, PsycINFO, Epistemonikos, Science Citation Index, Cochrane Database of Systematic (CDSR) and CENTRAL will be used to search for relevant studies by using a range of keywords in the search strategy.

Study Selection

Studies must comprise individuals over 10 years old living in core anglophone countries. Eligible studies must evaluate the promotion of e-cigarettes on accessible social media platforms, and its influence on vaping uptake and positive perception among the research population. The screening and extraction stage will be held on Covidence through three independent reviews and results will be displayed via a PRISMA flowchart.

Reporting the results

Extracted data will be reported through a table and the results presented using a narrative summary. No assessment for risk bias or formal synthesis will be included as this is a scoping review. The results will provide relevant information and recommendations for prospective research.
Orbital Magnetic Resonance Imaging of Ocular Giant Cell Arteritis: A Systematic Review and Individual Participant Data Meta-Analysis
Authors: Guggenberger Konstanze V. , Pavlou Athanasios , Cao Quy , Bhatt Ishaan J , Cui Qi N. , Bley Thorsten A. , Curtin Hugh D. , Savatovsky Julien , Song Jae W.
Published: November 2022

Objectives

We conducted a systematic review and individual participant data meta-analysis of publications reporting the ophthalmologic presentation, clinical exam, and orbital MRI findings in ocular giant cell arteritis.

Methods

PubMed and Cochrane databases were searched up to January 16, 2022. Publications reporting patient-level data on patients with ophthalmologic symptoms, imaged with orbital MRI and diagnosed with biopsy-proven giant cell arteritis were included. Demographics, clinical symptoms, exam, lab, imaging, and outcomes data were extracted. Methodological quality and completeness of reporting of case reports were assessed.

Results

Thirty-two studies were included comprising 51 patients (females=24; median age, 76 years). Vision loss (78%) and headache (45%) were commonly reported visual and cranial symptoms. Ophthalmologic presentation was unilateral (41%) or bilateral (59%). Fundus examination most commonly showed disc edema (64%) and pallor (49%). Average visual acuity was very poor (2.28 logMAR ± 2.18). Diagnoses included anterior (61%) and posterior (16%) ischemic optic neuropathy, central retinal artery occlusion (8%) and orbital infarction syndrome (2%). On MRI, enhancement of the optic nerve sheath (53%), intraconal fat (25%), and optic nerve/chiasm (14%) was most prevalent. Among patients with monocular visual symptoms, 38% showed pathologic enhancement in the asymptomatic eye. Six of seven cases reported imaging resolution after treatment on follow-up MRIs.

Conclusions

Vision loss, pallid disc edema, and optic nerve sheath enhancement are the most common clinical, fundoscopic and imaging findings reported in patients diagnosed with ocular giant cell arteritis, respectively. MRI may detect subclinical inflammation in the asymptomatic eye and may be an adjunct diagnostic tool.

Key Points

Among 32 publications comprising 51 patients with biopsy-proven giant cell arteritis, vision loss, pallid disc edema, and optic nerve sheath enhancement were the most commonly reported clinical, fundoscopic and orbital MRI findings, respectively.

Orbital MRI detected subclinical inflammation in the asymptomatic orbit in 38% of giant cell arteritis patients presenting with monocular visual symptoms.

MRI may have a diagnostic role in patients with suspected giant cell arteritis and presenting with acute visual symptoms.
Warmer water temperature and epizootic shell disease reduces diversity but increases cultivability of bacteria on the shells of American Lobster (Homarus americanus)
Authors: Ishaq Suzanne L. , Turner Sarah M. , Lee Grace , Tudor M. Scarlett , MacRae Jean D. , Hamlin Heather , Bouchard Deborah
Published: November 2022

The American lobster,Homarus americanus, is an economically valuable and ecologically important crustacean along the North Atlantic coast of North America. Populations in southern locations have declined in recent decades due to increasing ocean temperatures and disease, and these circumstances are progressing northward. We monitored 57 adult female lobsters, healthy and shell-diseased, under three seasonal temperature cycles for a year, to track shell bacterial communities using culturing and 16S rRNA gene sequencing, progression of ESD using visual assessment, and antimicrobial activity of hemolymph. The richness of bacterial taxa present, evenness of abundance, and community similarity between lobsters was affected by water temperature at the time of sampling, water temperature over time based on seasonal temperature regimes, shell disease severity, and molt stage. Several bacteria were prevalent on healthy lobster shells but missing or less abundant on diseased shells, although putative pathogens were found on all shells regardless of health status.

Graphical abstract