bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundProtein 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.MethodsThe 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.DiscussionThe 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 2024Trial RegistrationClinicalTrials.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

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

ABSTRACTIntroductionSmoking 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 analysisThe 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 conductedThis 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 disseminationBecause 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 CRD42022368552ARTICLE SUMMARYStrengths and limitations of this studyThis 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

ABSTRACTSepsis 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

ABSTRACTStructural 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

AbstractThe 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

AbstractRB1 (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 pointsWhi7 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

SummaryDevelopmental 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

AbstractThe 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

AbstractOuter 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

ABSTRACTIntroductionSocial 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 ObjectivesThe 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 StudiesThe 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 SelectionStudies 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 resultsExtracted 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

AbstractObjectivesWe 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.MethodsPubMed 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.ResultsThirty-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.ConclusionsVision 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 PointsAmong 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.