The fragmented COVID-19 therapeutics research landscape: a living systematic review of clinical trial registrations evaluating priority pharmacological interventions. [version 1; peer review: 1 approved]

Background: Many available medicines have been evaluated as potential repurposed treatments for coronavirus disease 2019 (COVID-19). We summarise the registered study landscape for 32 priority pharmacological treatments identified following consultation with external experts of the COVID-19 Clinical Research Coalition. Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed. Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The sample size of the RCTs identified was typically small (median (25th, 75th percentile) sample size = 140 patients (70, 383)), i.e. individually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14; 1.3%). A minority of studies (348, 26%) indicated a willingness to share individual participant data. The living systematic review data are available at https://iddo.cognitive.city Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of individual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data

Effect of Graft Choice on the Outcome of Revision Anterior Cruciate Ligament Reconstruction in the Multicenter ACL Revision Study (MARS) Cohort

Most surgeons believe that graft choice for ACL reconstruction is an important factor related to outcome. Although graft choice may be limited in the revision setting based on previously used grafts, it is still felt to be important

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluation of the Impact of Information and Communication Technology in Real Estate Project Management, in South-East, Nigeria

&lt;p&gt;&lt;strong&gt;Abstract:&lt;/strong&gt;&lt;i&gt;&nbsp;&lt;/i&gt;Real estate development has witnessed remarkable growth in recent years, In South East, Nigeria, as the world becomes increasingly interconnected, the impact of information and communication technology (ICT) on various industries is undeniable, the integration of ICT in real estate project management has significantly transformed the industry, enhancing efficiency, speed, and accuracy in various processes. This article evaluates the impact of ICT in real estate project management in South-East, Nigeria, highlighting the benefits it brings to the sector. To conduct this evaluation, a mixed-methods research approach was employed using two different data collection instruments viz: mixture of structured and open-ended questionnaire and&nbsp;semi-structured interviews with the selected project teams which include architects, quantity surveyors, real estate project managers and real estate developers were used to gather information on the study. The collected data were analyzed using appropriate statistical methods for the quantitative survey. The study revealed that real estate project management in the South-East Nigeria has experienced increased transparency and accountability through the use of ICT. Online project tracking systems have made it easier for stakeholders to monitor project progress and ensure compliance with regulations even from afar. Adoption of ICT in real estate project management has resulted in significant cost savings and increased profitability. ICT impacts positively on real estate project management in the South-East Nigeria especially in term of increased efficiency, collaboration to analysis and cost savings, ICT has become an indispensable tool in this industry and has transformed traditional project management practices by streamlining processes, enhancing communication, and providing stakeholders with real-time project information. As the real estate market in Nigeria continues to grow, it is imperative for professionals in the sector to embrace ICT integration to remain competitive and ensure project success.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords:&lt;/strong&gt;&nbsp;Evaluation, Impact, Information and Communication Technology, Real Estate Project Management.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Title:&lt;/strong&gt; Evaluation of the Impact of Information and Communication Technology in Real Estate Project Management, in South-East, Nigeria&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Author:&lt;/strong&gt; CHIEMEZIE C. NWOSU, CHARLES C. EGOLUM, ESTHER I. OLADEJO&lt;/p&gt;&lt;p&gt;&lt;strong&gt;International Journal of Recent Research in Mathematics Computer Science and Information Technology&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;ISSN 2350-1022&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Vol. 10, Issue 2, October 2023 - March 2024&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Page No: 1-10&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Paper Publications&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Website: www.paperpublications.org&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Published Date: 13-November-2023&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;DOI: &lt;/strong&gt;&lt;a href="https://doi.org/10.5281/zenodo.10118356"&gt;&lt;strong&gt;https://doi.org/10.5281/zenodo.10118356&lt;/strong&gt;&lt;/a&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Paper Download Link (Source)&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;a href="https://www.paperpublications.org/upload/book/Evaluation%20of%20the%20Impact%20of%20Information-13112023-5.pdf"&gt;&lt;strong&gt;https://www.paperpublications.org/upload/book/Evaluation%20of%20the%20Impact%20of%20Information-13112023-5.pdf&lt;/strong&gt;&lt;/a&gt;&lt;/p&gt

In-Gel Nonspecific Proteolysis for Elucidating Glycoproteins: A Method for Targeted Protein-Specific Glycosylation Analysis in Complex Protein Mixtures

Determining protein-specific glycosylation in protein mixtures remains a difficult task. A common approach is to use gel electrophoresis to isolate the protein followed by glycan release from the identified band. However, gel bands are often composed of several proteins. Hence, release of glycans from specific bands often yields products not from a single protein but a composite. As an alternative, we present an approach whereby glycans are released with peptide tags allowing verification of glycans bound to specific proteins. We term the process in-gel nonspecific proteolysis for elucidating glycoproteins (INPEG). INPEG combines rapid gel separation of a protein mixture with in-gel nonspecific proteolysis of protein bands followed by tandem mass spectrometry (MS) analysis of the resulting N- and O-glycopeptides. Here, in-gel digestion is shown for the first time with nonspecific and broad specific proteases such as Pronase, proteinase K, pepsin, papain, and subtilisin. Tandem MS analysis of the resulting glycopeptides separated on a porous graphitized carbon (PGC) chip was achieved via nanoflow liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (nano-LC/Q-TOF MS). In this study, rapid and automated glycopeptide assignment was achieved via an in-house software (Glycopeptide Finder) based on a combination of accurate mass measurement, tandem MS data, and predetermined protein identification (obtained via routine shotgun analysis). INPEG is here initially validated for O-glycosylation (κ casein) and N-glycosylation (ribonuclease B). Applications of INPEG were further demonstrated for the rapid determination of detailed site-specific glycosylation of lactoferrin and transferrin following gel separation and INPEG analysis on crude bovine milk and human serum, respectively

Automated Assignments of N- and O‑Site Specific Glycosylation with Extensive Glycan Heterogeneity of Glycoprotein Mixtures

Site-specific glycosylation (SSG) of glycoproteins remains a considerable challenge and limits further progress in the areas of proteomics and glycomics. Effective methods require new approaches in sample preparation, detection, and data analysis. While the field has advanced in sample preparation and detection, automated data analysis remains an important goal. A new bioinformatics approach implemented in software called GP Finder automatically distinguishes correct assignments from random matches and complements experimental techniques that are optimal for glycopeptides, including nonspecific proteolysis and high mass resolution liquid chromatography/tandem mass spectrometry (LC/MS/MS). SSG for multiple N- and O-glycosylation sites, including extensive glycan heterogeneity, was annotated for single proteins and protein mixtures with a 5% false-discovery rate, generating hundreds of nonrandom glycopeptide matches and demonstrating the proof-of-concept for a self-consistency scoring algorithm shown to be compliant with the target-decoy approach (TDA). The approach was further applied to a mixture of N-glycoproteins from unprocessed human milk and O-glycoproteins from very-low-density-lipoprotein (vLDL) particles