Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

Dynamics of Single-Cell Protein Covariation during Epithelial-Mesenchymal Transition.

Physiological processes, such as the epithelial-mesenchymal transition (EMT), are mediated by changes in protein interactions. These changes may be better reflected in protein covariation within a cellular cluster than in the temporal dynamics of cluster-average protein abundance. To explore this possibility, we quantified proteins in single human cells undergoing EMT. Covariation analysis of the data revealed that functionally coherent protein clusters dynamically changed their protein-protein correlations without concomitant changes in the cluster-average protein abundance. These dynamics of protein-protein correlations were monotonic in time and delineated protein modules functioning in actin cytoskeleton organization, energy metabolism, and protein transport. These protein modules are defined by protein covariation within the same time point and cluster and, thus, reflect biological regulation masked by the cluster-average protein dynamics. Thus, protein correlation dynamics across single cells offers a window into protein regulation during physiological transitions.

Feasibility of awake craniotomy for brain arteriovenous malformations: A scoping review.

Background: Brain Arteriovenous Malformations (AVMs) located in proximity to eloquent brain regions are associated with poor surgical outcomes, which may be due to higher rates of postoperative neurological deterioration. Current treatment protocols include stereotactic radiosurgery, transarterial embolization, and surgical resection under general anesthesia. Awake Craniotomy (AC) allows intraoperative mapping of eloquent areas to improve post-operative neurologic outcomes. Objectives: We reviewed the current literature reporting surgical outcomes and assessed the feasibility of AC for AVM resection. Methods: The PRISMA guidelines were utilized as a template for the review. Three databases including PubMed, Scopus, and Cochrane Library were searched using a predefined search strategy. After removing duplicates and screening, full texts were analyzed. Outcomes including the extent of resection, intra-operative and post-operative complications, and long-term neurologic outcomes were assessed. Results: 12 studies were included with a total of 122 AVM cases. Spetzler-Martin grading was used for the classification of the AVMs. The asleep-awake-asleep protocol was most commonly used for AC. Complete resection was achieved in all cases except 5. Intraoperative complications included seizures (n = 2) and bleeding (n = 4). Short-term post-operative complications included hemorrhage (n = 3), neurologic dysfunctions including paresis (n = 3), hemiplegia (n = 10), dysphasia/aphasia (n = 6), cranial nerve dysfunction (n = 3), and pulmonary embolism (n = 1). Almost all neurological deficits after surgery gradually improved on subsequent follow-ups. Conclusion: AVMs may shift the anatomical location of eloquent brain areas which may be mapped during AC. All studies recommended AC for the resection of AVMs in close proximity to eloquent areas as mapping during AC identifies the eloquent cortex thus promoting careful tissue handling which may preserve neurologic function and/or predict the postoperative functional status of the patients We, therefore, conclude that AC is a viable modality for AVMs resection near eloquent language and motor areas.

Glioblastoma-infiltrating CD8+ T cells are predominantly a clonally expanded GZMK+ effector population.

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) with paired V(D)J sequencing, respectively, on TIL from two cohorts of patients totaling 15 patients with high grade glioma, including GBM or astrocytoma, IDH mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared to matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T cell subset within the GBM microenvironment and which may harbor potential therapeutic implications.

THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-ß driven Alzheimer's disease in mice.

The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-ß (Aß) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4 + antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4 + B cells and gut-specific IgA + cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aß plaques and overall frailty. These changes corresponded to an expansion of gut IgA + cells and rescued peripheral T regs levels. Our study points to a key glia-gut axis and potential targets against AD. Study Highlights: AD is associated with altered immune parameters in the gut of 5XFAD mice. 5 XFAD colon has reduced ASCs, including CXCR4 + cells with a migratory gene signature. 5XFAD brain gliosis includes increased CXCL12 expression. CXCR4 + B cells and gut-specific IgA + ASCs accumulate in the 5XFAD brain and/or dura mater. Inulin diet attenuates AD disease parameters while boosting IgA + cell and T reg levels.

Early coronary angioplasty fails to lower all-cause mortality in patients with out-of-hospital cardiac arrest without ST-segment elevation: A systematic review and meta-analysis.

Introduction: Out-of-hospital cardiac arrest (OHCA) is defined as the loss of functional mechanical activity of the heart in association with an absence of systemic circulation, occurring outside of a hospital. Immediate coronary angiography (CAG) with percutaneous coronary intervention is recommended for OHCA with ST-elevation. We aimed to evaluate the effect of early CAG on mortality and neurological outcomes in OHCA patients without ST-elevation. Methods: This meta-analysis and systemic review was conducted as per principles of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) group. A protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, Ref No. = CRD42022327833). A total of 674 studies were retrieved after scanning several databases (PubMed Central, EMBASE, Medline, and Cochrane Central Register of Controlled Trials). Results: A total of 18 studies were selected for the final analysis, including 6 randomized control trials and 12 observational studies. Statistically, there was no significant difference in primary outcome, i.e., mortality, between early and delayed CAG. In terms of the grade of neurological recovery as a secondary outcome, early and delayed CAG groups also showed no statistically significant difference. Conclusion: Early CAG has no survival benefits in patients with no ST elevations on ECG after OHCA.

Dynamics of single-cell protein covariation during epithelial-mesenchymal transition.

Physiological processes, such as epithelial-mesenchymal transition (EMT), are mediated by changes in protein interactions. These changes may be better reflected in protein covariation within cellular cluster than in the temporal dynamics of cluster-average protein abundance. To explore this possibility, we quantified proteins in single human cells undergoing EMT. Covariation analysis of the data revealed that functionally coherent protein clusters dynamically changed their protein-protein correlations without concomitant changes in cluster-average protein abundance. These dynamics of protein-protein correlations were monotonic in time and delineated protein modules functioning in actin cytoskeleton organization, energy metabolism and protein transport. These protein modules are defined by protein covariation within the same time point and cluster and thus reflect biological regulation masked by the cluster-average protein dynamics. Thus, protein correlation dynamics across single cells offer a window into protein regulation during physiological transitions.

Challenging diagnosis of Wilson's disease: A case report.

Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver, brain, a nd other tissues. Diagnosi s of Wilson's is delayed in Pak ist an by many ye a rs on average due to va riabl e presen tations. In ad olescents, the initial s igns a re more likely to b e neuropsychiatric. Here we present a case of Wilso n's disease that pre sented initially with he patic symptoms and did not have signs specific to the di sea s e such as Kayser-Fleischer rings. Our case was diagnosed to be Wilson's Disease on ly on further investigat ions and s ubsequently the patient was treated with chela tion therapy using D-Penicillamine.Wilson's Disease should be kept in mind as a differential diagno sis in adolesce nt patients that present with unexplained acute liver failure and cytopenias without any neurological symptoms, as a missed diagnosis can prove to be fatal.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Patients' Readiness Towards Teledentistry in the Malaysian Urban Population Attending an Undergraduate Teaching University.

Introduction: COVID-19 disease has resulted in suspension of all nonurgent routine dental treatments. In view of COVID-19 situation, social distancing, movement restriction orders, and affected health care systems, there is an urgent need to resume and deliver oral health care remotely. Hence, alternative means of dental care should be available for both patients and dentists. Therefore, this study aims to assess patients' readiness for teledentistry in Malaysian urban population attending an undergraduate teaching university. Methods: A cross-sectional study was conducted among 631 adult patients visiting the Faculty of Dentistry, SEGi University, from January 2020 to May 2021 in Selangor, Malaysia. A validated, self-administered, 5-point Likert scale online questionnaire comprising five domains was administered. (1) Patients' demographics and dental history, (2) patients' access to teledentistry, (3) patients' understanding towards teledentistry, (4) patients' willingness, and (5) barriers in using teledentistry were used to collect the required information. Results: Six hundred and thirty-one (n = 631) participants responded to the questionnaire. Ninety percent of patients were able to connect to Wi-Fi services independently and 77% participants were comfortable using online communication platforms. Seventy-one percent of the participants agreed that video and telephone clinics can reduce chances of infection rather than face-to-face consultation during the pandemic. Fifty-five percent of patients felt that virtual clinics would save time and 60% thought it could reduce travelling costs. Fifty-one percent showed their willingness to use video or telephone clinics when implemented at onsite clinics. Conclusion: Our study shows the readiness of patients to accept teledentistry as an alternative method of oral care if appropriate training and education are provided. The results of this study have prompted an increase in patients' education and shown a need to train clinicians and patients to integrate this technology at SEGi University. This might facilitate unhindered dental consultation and care in all situations.

Characterization and biological evaluation of a novel flavonoid-collagen antioxidant hydrogel with cytoprotective properties.

Reactive oxygen species (ROS) play a critical and important role during wound healing but excess ROS at the wound site can lead to cellular damage and sub-optimal healing. Minimizing oxidative damage to the wound site and any supplemental therapeutic cells can be achieved by delivering exogenous antioxidants. Collagen hydrogels are ideal wound care materials due to their biocompatibility, high water content, and porous, three-dimensional architecture. Yet, they lack the inherent antioxidant activity that could help mitigate excess ROS at a wound site. This work formulates and evaluates the in vitro biocompatibility and antioxidant capabilities of collagen-fibroblast hydrogels combined with the polyphenolic antioxidant luteolin. Collagen solutions mixed with luteolin readily assembled into robust hydrogels with increasing gel strength due to increasing concentrations of luteolin. SEM images confirmed a mean pore size of 2.2 µm and a drastically different macromolecular ultrastructure with extensive fine crosslinking relative to collagen. Adequate cell viability and metabolic activity of dermal fibroblasts cultured within the gels were measured across all formulations, resulting in higher antioxidant activity and more than double the protection to cells from oxidative damage than traditional collagen hydrogels. Given these results, luteolin-collagen hydrogels demonstrate the potential for superior wound-healing properties when compared to collagen alone.

Machine learning (ML) techniques as effective methods for evaluating hair and skin assessments: A systematic review.

Machine Learning (ML) techniques provide the ability to effectively evaluate and analyze human skin and hair assessments. The aim of this study is to systematically review the effectiveness of applying Machine Learning (ML) methods and Artificial Intelligence (AI) techniques in order to evaluate hair and skin assessments. PubMed, Web of Science, IEEE Xplore, and Science Direct were searched in order to retrieve research publications between 1 January 2010 and 31 March 2020 using appropriate keywords such as "hair and skin analysis." Following accurate screening, 20 peer-reviewed publications were selected for inclusion in this systematic review. The analysis demonstrated that prevalent Machine Learning (ML) methods comprised of Support Vector Machine (SVM), k-nearest Neighbor, and Artificial Neural Networks (ANN). ANN's were observed to yield the highest accuracy of 95% followed by SVM generating 90%. These techniques were most commonly applied for drafting framework assessments such as that of Melanoma. Values of parameters such as Sensitivity, Specificity, and Area under the Curve (AUC) were extracted from the studies and with the help of comparisons, relevant inferences were also made. ANN's were observed to yield the highest sensitivity of 82.30% as well as a 96.90% specificity. Hence, with this systematic review, a summarization of the studies was drafted that encapsulated how Machine Learning (ML) techniques have been employed for the analysis and evaluation of hair and skin assessments.

Comparing Efficacy and Safety of Different Doses of Tirzepatide for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Our study assessed the efficacy and safety of the three primary tirzepatide (TZP) doses, 5 mg, 10 mg, and 15 mg using network meta-analysis to assess their relative impact on type 2 diabetes mellitus (T2DM) treatment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Two authors independently screened online databases, including PubMed, Cochrane Library, and Embase. We employed the keywords "Type 2 diabetes OR T2DM or diabetes" AND "Tirzepatide OR LY3298176 OR twincretin OR dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist" AND "randomized controlled trial". The outcomes evaluated in this study comprised changes in hemoglobin (Hb)A1c levels from baseline (%), changes in weight from baseline (Kg), changes in fasting serum glucose from baseline (mg/dL), and occurrences of serious adverse events (SAE), adverse events (AE) and major adverse cardiovascular events (MACE). A total of eight studies met the inclusion criteria and were included in this meta-analysis. Our findings suggest that among the evaluated doses, TZP at 15 mg demonstrated superior effectiveness in reducing HbA1c, weight, and fasting serum glucose compared to doses of 10 mg and 5 mg. Notably, the reduction in HbA1c and weight showed a dose-dependent trend, with the 15 mg dose achieving the most substantial benefits. The safety analysis indicated that while serious adverse events and major adverse cardiovascular events (MACE) did not significantly differ among the three doses, the risk of overall adverse events was notably higher in the 10 mg and 15 mg TZP groups compared to the 5 mg group.

Effectiveness of Rifaximin on the Outcomes of Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder that impacts the lives of many individuals worldwide. We conducted a systemic review and meta-analysis of randomized controlled trials (RCTs) to assess both the effectiveness of rifaximin in alleviating IBS symptoms and its potential adverse effects. PubMed, Web of Science, Embase, the Cochrane Library, Scopus, and Google Scholar were searched from inception until August 20, 2023, for studies comparing rifaximin with placebo in the resolution of symptoms among IBS patients. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were derived for all the outcomes of interest. Six RCTs were pooled in this analysis. The results showed improved abdominal distension with rifaximin over the control group. Overall symptom relief at the end of the treatment period and follow-up period was also observed in the patients receiving rifaximin. However, no significant differences were found between the rifaximin group and the control group for the outcomes of abdominal pain, nausea, headache, vomiting, diarrhea, sinusitis, bronchitis, and upper respiratory tract infection. The results of our meta-analysis support the use of rifaximin in the treatment of IBS, owing to its safety and effectiveness. Future RCTs should be conducted to assess this topic of interest more extensively.

Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions.

Oxygen (O2) tension plays a key role in tissue function and pathophysiology. O2-controlled cell culture, in which the O2 concentration in an incubator's gas phase is controlled, is an indispensable tool to study the role of O2 in vivo. For this technique, it is presumed that the incubator setpoint is equal to the O2 tension that cells experience (i.e., pericellular O2). We discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0.0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to anoxic exposure followed by rapid reoxygenation. To better understand the relationship between incubator gas phase and pericellular O2 tensions, we developed a reaction-diffusion model that predicts pericellular O2 tension a priori. This model revealed that the effect of cellular O2 consumption is greatest in smaller volume culture vessels (e.g., 96-well plate). By controlling pericellular O2 tension in cell culture, we discovered that MCF7 cells have stronger glycolytic and glutamine metabolism responses in anoxia vs. hypoxia. MCF7 also expressed higher levels of HIF2A, CD73, NDUFA4L2, etc. and lower levels of HIF1A, CA9, VEGFA, etc. in response to hypoxia vs. anoxia. Proteomics revealed that 4T1 cells had an upregulated epithelial-to-mesenchymal transition (EMT) response and downregulated reactive oxygen species (ROS) management, glycolysis, and fatty acid metabolism pathways in hypoxia vs. anoxia. Collectively, these results reveal that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable to model hypoxia. We demonstrate that controlling atmospheric O2 tension in cell culture incubators is insufficient to control O2 in cell culture and introduce the concept of pericellular O2-controlled cell culture.

Comparison of Long-Term Outcomes of Patients With Myocardia Infarction (MI) With Non-obstructive Coronary Arteries and MI With Obstructive Coronary Arteries: A Systematic Review and Meta-Analysis.

The aim of this study was to compare long-term outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and patients with myocardial infarction with obstructive coronary arteries (MIOCA). This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search was conducted in online databases including PubMed and Web of Science from 2010 onwards. Primary outcomes assessed in this meta-analysis included major adverse cardiovascular events (MACE) and all-cause mortality. Secondary outcomes included cardiovascular mortality and myocardial infarction. A total of 16 studies were included in the meta-analysis. Pooled analysis showed that the risk of MACE was higher in MIOCA patients (risk ratio (RR): 1.47, 95%CI: 1.43-1.52, p-value: 0.001) compared to MINOCA patients. Additionally, the risk of all-cause mortality was also significantly higher in MIOCA patients compared to MINOCA (RR: 1.33, 95%CI: 1.14-1.56, p-value: 0.001). Our findings also indicate that patients with MIOCA are at a significantly higher risk of recurrent myocardial infarction and cardiovascular-related mortality compared to patients with MINOCA. Overall, the insights gained from this meta-analysis have significant clinical implications, guiding decision-making in the management of patients with MINOCA.

Disclosing the locale of transmembrane proteins within cellular alcove by machine learning approach: systematic review and meta analysis.

Protein subcellular localization is a promising research question in Proteomics and associated fields, including Biological Sciences, Biomedical Engineering, Computational Biology, Bioinformatics, Proteomics, Artificial Intelligence, and Biophysics. However, computational techniques are preferred to explore this attribute for a massive number of proteins. The byproduct of this conjunction yields diversified location identifiers of proteins. These protein subcellular localization identifiers are unique regarding the database used, organisms, Machine Learning Technique, and accuracy. Despite the availability of these identifiers, the majority of the work has been done on the subcellular localization of proteins and, less work has been done specifically on locations of transmembrane proteins. This systematic review accounts for computational techniques implemented on transmembrane protein localization. Moreover, a literature search on PubMed, Science Direct, and IEEE Databases disclosed no systematic review or meta-analysis on the cell's transmembrane protein locale. A Systematic review was formed under the guidelines of PRISMA by using Science Direct, PubMed, and IEEE Databases. Journal publications from 2000 to 2023 were taken into consideration and screened. This review has focused only on computational studies rather than experimental techniques. 1004 studies were reviewed and were categorized as relevant and non-relevant according to inclusion and exclusion criteria. All the screening was done through Endnote after importing citations. This systematic review characterizes the gap in targeting the locale of the transmembrane protein and will aid researchers in exploring its new horizons.Communicated by Ramaswamy H. Sarma.

The NWRD Dataset: An Open-Source Annotated Segmentation Dataset of Diseased Wheat Crop.

Wheat stripe rust disease (WRD) is extremely detrimental to wheat crop health, and it severely affects the crop yield, increasing the risk of food insecurity. Manual inspection by trained personnel is carried out to inspect the disease spread and extent of damage to wheat fields. However, this is quite inefficient, time-consuming, and laborious, owing to the large area of wheat plantations. Artificial intelligence (AI) and deep learning (DL) offer efficient and accurate solutions to such real-world problems. By analyzing large amounts of data, AI algorithms can identify patterns that are difficult for humans to detect, enabling early disease detection and prevention. However, deep learning models are data-driven, and scarcity of data related to specific crop diseases is one major hindrance in developing models. To overcome this limitation, in this work, we introduce an annotated real-world semantic segmentation dataset named the NUST Wheat Rust Disease (NWRD) dataset. Multileaf images from wheat fields under various illumination conditions with complex backgrounds were collected, preprocessed, and manually annotated to construct a segmentation dataset specific to wheat stripe rust disease. Classification of WRD into different types and categories is a task that has been solved in the literature; however, semantic segmentation of wheat crops to identify the specific areas of plants and leaves affected by the disease remains a challenge. For this reason, in this work, we target semantic segmentation of WRD to estimate the extent of disease spread in wheat fields. Sections of fields where the disease is prevalent need to be segmented to ensure that the sick plants are quarantined and remedial actions are taken. This will consequently limit the use of harmful fungicides only on the targeted disease area instead of the majority of wheat fields, promoting environmentally friendly and sustainable farming solutions. Owing to the complexity of the proposed NWRD segmentation dataset, in our experiments, promising results were obtained using the UNet semantic segmentation model and the proposed adaptive patching with feedback (APF) technique, which produced a precision of 0.506, recall of 0.624, and F1 score of 0.557 for the rust class.

The Golden Patient Initiative: A Systematic Review.

Operating theatres and surgical resource consumption comprise a significant proportion of healthcare costs. Inefficiencies in theatre lists remain an important focus for cost management, along with reducing patient morbidity and mortality. With the emergence of the coronavirus disease 2019 (COVID-19) pandemic, the number of patients on theatre waiting lists has surged. Hence, there is a pressing need to utilise the already limited theatre time and fraught resources with innovative methods. In this systematic review, we discuss the Golden Patient Initiative (GPI), in which the first patient on the operating list is pre-assessed the day prior to surgery, and we aim to assess its impact and overall efficacy. A literature search using the following four databases was conducted to identify and select all clinical research concerning the GPI: Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), and the Cochrane library. Two independent authors screened articles against the eligibility criteria, using a process adapted from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data extracted included outcomes measured, follow-up period, and study design. The results showed significant heterogeneity, and hence a narrative review was conducted; 13 of the 73 eligible articles were included for analysis. Outcomes included delay in theatre start time, number of surgical case cancellations, and changes to total case numbers. Across the studies, a 19-30-minute improvement in theatre start time was reported (p<0.05), as well as a statistically significant decrease in case cancellations. Our analysis provides encouraging conclusions with regard to greater theatre efficiency following the application of GPI, a low-cost solution that can easily be implemented to help improve patient safety and lead to cost savings. However, at present, it is largely implemented among local trusts, and hence larger multi-centre studies are required to gather conclusive evidence about the efficacy of the initiative.