Histopathology-driven prostate cancer identification: A VBIR approach with CLAHE and GLCM insights.

Efficient extraction and analysis of histopathological images are crucial for accurate medical diagnoses, particularly for prostate cancer. This research enhances histopathological image reclamation by integrating Visual-Based Image Reclamation (VBIR) techniques with contrast-limited adaptive Histogram Equalization (CLAHE) and the Gray-Level Co-occurrence Matrix (GLCM) algorithm. The proposed method leverages CLAHE to improve image contrast and visibility, crucial for regions with varying illumination, and employs a non-linear Support Vector Machine (SVM) to incorporate GLCM features. Our approach achieved a notable success rate of 89.6%, demonstrating significant improvement in image analysis. The average execution time for matched tissues was 41.23 s (standard deviation 36.87 s), and for unmatched tissues, 21.22 s (standard deviation 29.18 s). These results underscore the method's efficiency and reliability in processing histopathological images. The findings from this study highlight the potential of our method to enhance image reclamation processes, paving the way for further research and advancements in medical image analysis. The superior performance of our approach signifies its capability to significantly improve histopathological image analysis, contributing to more accurate and efficient diagnostic practices.

Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease.

BACKGROUND: Kidney disease is a severe complication of diabetes that often leads to end-stage renal disease. Early diagnosis is crucial for prevention or delay. However, the current diagnostic methods, with their limitations in detecting the disease in its early stages, underscore the urgency and importance of finding new solutions. miRNAs encapsulated inside urinary exosomes (UEs) have potential as early biomarkers for kidney diseases. The need for reference miRNAs for accurate interpretation currently limits their translational potential. AIM: To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus (T2DM) and biopsy-confirmed kidney diseases. METHODS: miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased method. The UEs were isolated from urine samples collected from healthy individuals (n = 6), patients with T2DM (n = 13), and T2DM patients who also had kidney diseases (including diabetic nephropathy, n = 5; membranous nephropathy, n = 5; and IgA nephropathy, n = 2) through differential ultracentrifugation. After characterizing the UEs, miRNA expression profiling using microarray technology was conducted. RESULTS: Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples, representing various kidney conditions: diabetic controls, diabetic nephropathy, membrane nephropathy, IgA nephropathy, and healthy controls. Through in silico analysis, we determined that 10 of these miRNAs had significant potential to serve as reference genes in UEs. CONCLUSION: We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

The evolving pathophysiology of TBI and the advantages of temporally-guided combination therapies.

Several clinical and experimental studies have demonstrated that traumatic brain injury (TBI) activates cascades of biochemical, molecular, structural, and pathological changes in the brain. These changes combine to contribute to the various outcomes observed after TBI. Given the breadth and complexity of changes, combination treatments may be an effective approach for targeting multiple detrimental pathways to yield meaningful improvements. In order to identify targets for therapy development, the temporally evolving pathophysiology of TBI needs to be elucidated in detail at both the cellular and molecular levels, as it has been shown that the mechanisms contributing to cognitive dysfunction change over time. Thus, a combination of individual mechanism-based therapies is likely to be effective when maintained based on the time courses of the cellular and molecular changes being targeted. In this review, we will discuss the temporal changes of some of the key clinical pathologies of human TBI, the underlying cellular and molecular mechanisms, and the results from preclinical and clinical studies aimed at mitigating their consequences. As most of the pathological events that occur after TBI are likely to have subsided in the chronic stage of the disease, combination treatments aimed at attenuating chronic conditions such as cognitive dysfunction may not require the initiation of individual treatments at a specific time. We propose that a combination of acute, subacute, and chronic interventions may be necessary to maximally improve health-related quality of life (HRQoL) for persons who have sustained a TBI.

Rethinking Measures and Mortality Attribution in Health Care: The ENT Example.

National performance metrics ultimately enhance patient decision-making and promote meaningful improvements in health care delivery, which makes having valid and reliable measures essential. This study examined US News and World Report metrics from 2019 to 2012 and used electronic health record data, combined with detailed chart review across 3 in-system hospitals, to assess the provision of care compared to the attribution of patients assigned to the ear, nose, and throat (ENT) mortality group. Of the initial 47 ENT-attributed deaths, 23 of those were verified, dimensioning the mortality rate from 1.7% to just 0.8%. These results underscore the necessity of rethinking measures and mortality attribution methodologies to be more accurate. Current methods use Medicare Severity Diagnosis Related Group billing coding to map the attribution. We suggest transitioning away from specialty ranking approaches and towards a procedure and condition "rating" approach to ensure that these ranking types capture data about the provision of care within a given encounter.

Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain.

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a pro-aerobic shift in energy metabolism that persists through ETC inhibition and enhances glycolytic flux, glycolytic ATP production, and cellular generation of lactate, a crucial auxiliary substrate for energy metabolism. To address specific mechanisms of iron injury from hemorrhage, OCNs with the iron chelator, deferoxamine (DEF), covalently-linked were synthesized. DEF-linked OCNs induce a glycolytic shift in-vitro and in-vivo in tissue sections from a rat model of TBI complicated by hemorrhagic contusion. OCNs further reduced hemorrhage volumes 3 days following TBI. These results suggest OCNs are promising as pleiotropic mediators of cell and tissue resilience to injury.

A Qualitative Study Exploring Experiences in Caregiving for Patients With Advanced Wilson Disease.

ABSTRACT: BACKGROUND: Wilson disease (WD) is a rare disease characterized by impaired copper metabolism. It is usually diagnosed in children and has several distinct attributes that can make the caregiving experience different. The advanced stage of the illness is quite challenging, and caregiver experiences during this phase of the disease are underexplored. METHODS: The present study is an exploratory qualitative investigation with in-depth interviews aiming to understand the experiences of family caregivers of children with advanced WD receiving neuropalliative care services at a tertiary care hospital. Interviews from 7 family caregivers were recorded, transcribed, and analyzed using an inductive and interpretive approach. RESULTS: Family caregivers in the study were predominantly mothers. The major themes that emerged are: being a parent and the caregiver, uncertainty related to illness, financial implications, understanding the disease dynamics, constructive coping strategies, and extended family networks and societal influences. CONCLUSION: The experiences and the encounters of family caregivers of children with advanced WD are multifaceted. Their challenging experiences underscore the need for extended supportive services and neuropalliative nursing care to assist the caregivers and families, and navigate the process of treatment and rehabilitation for the child.

Stable Efficient Solid-State Supercapacitors and Dye-Sensitized Solar Cells Using Ionic Liquid-Doped Solid Biopolymer Electrolyte.

As synthetic and nonbiodegradable compounds are becoming a great challenge for the environment, developing polymer electrolytes using naturally occurring biodegradable polymers has drawn considerable research interest to replace traditional aqueous electrolytes and synthetic polymer-based polymer electrolytes. This study shows the development of a highly conducting ionic liquid (1-hexyl-3-methylimidazolium iodide)-doped corn starch-based polymer electrolyte. A simple solution cast method is used to prepare biopolymer-based polymer electrolytes and characterized using different electrical, structural, and photoelectrochemical studies. Prepared polymer electrolytes are optimized based on ionic conductivity, which shows an ionic conductivity as high as 1.90 × 10-3 S/cm. Fourier transform infrared spectroscopy (FTIR) confirms the complexation and composite nature, while X-ray diffraction (XRD) and polarized optical microscopy (POM) affirm the reduction of crystallinity in biopolymer electrolytes after doping with ionic liquid (IL). Thermal and photoelectrochemical studies further affirm that synthesized material is well stable above 200 °C and shows a wide electrochemical window of 3.91 V. The ionic transference number measurement (t ion) confirms the predominance of ionic charge carriers in the present system. An electric double-layer capacitor (EDLC) and a dye-sensitized solar cell (DSSC) were fabricated by using the highest conducting corn starch polymer electrolyte. The fabricated EDLC and DSSC delivered an average specific capacitance of 130 F/g and an efficiency of 1.73% in one sun condition, respectively.

Clinico-genetic profile of seven patients with PARK-PINK1: A case series from a tertiary care centre from India and review of literature.

Background: Recessive variants in the PINK1 gene is a known cause of early-onset Parkinson's disease (EOPD). Objective: To describe the clinical features and genetic profile of patients of PARK-PINK1. Methods: Retrospective chart review of demographic, clinical and genetic details of patients carrying biallelic PINK1 variants from our database. Result: Seven cases were recruited with median age at onset 33 years (Range: 20-49). All had asymmetrical onset, tremor in four, abnormal posturing in two and slowness in one patient. Parkinsonism phenotype was noted in six patients (with dystonia in four) and isolated dystonia in one. Among 6 patients with parkinsonism, five had rest tremor, all had good levodopa-response, and four had motor-fluctuation with choreiform-dyskinesia. Exome-sequencing revealed bi-allelic pathogenic/likely pathogenic variants in all of which five were novel. Conclusion: PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

Clinical and radiological outcome following arthroscopic Latarjet with cerclage FiberTape fixation with a minimum 1-year follow-up.

Background: The rates of implant-related complications are significant following the Latarjet procedure using metal screws in patients with recurrent shoulder dislocation and bone loss. The purpose of this study is to evaluate the short-term outcome following the arthroscopic Latarjet procedure using cerclage FiberTape (Arthrex, Naples, FL, USA) combined with remplissage and capsulolabral repair. It was hypothesized that performing the procedure with cerclage FiberTape would provide sturdy fixation, comparable to the conventional method of using metal screws, while averting hardware-related complications attributed to the latter in published literature. Methods: A prospective study was performed in a single institution between 2020 and 2022, with all surgeries performed by a single fellowship-trained shoulder surgeon who has ample experience in performing arthroscopic screw Latarjet procedures. Patient demographics, number of dislocations before surgery, arm dominance, ligamentous laxity, type of sporting activity, Instability Severity Index Score, and percentage of bone loss on the glenoid and humeral sides were recorded. The patients were followed up with visual analog scale, American Shoulder and Elbow Surgeons score, Rowe score, and Walch-Duplay score preoperatively and postoperatively. The coracoid graft position, healing, and remodeling were assessed with computed tomography scans at 3 months postoperatively. Minimum clinical follow-up was for a period of one year. Results: Overall, 10 patients (all males, average age 28 ± 8.8 years) were operated on with an arthroscopic Latarjet procedure using cerclage FiberTape. The minimum follow-up period was 12 months, and the mean follow-up was 13.2 months. The median and individual visual analog scores during arm motion, American Shoulder and Elbow Surgeons scores, Rowe scores, and Walch-Duplay scores improved in the follow-up period. Computed tomography scans at 3 months showed flushed graft position in 5 patients, medial graft position in two patients, and three patients showed graft nonunion with migration. Out of 10 patients, seven had good graft union in follow-up scans. None of the patients required revision surgery. All three patients with graft nonunion were kept under follow-up beyond the study period for recurrence of instability. Conclusion: Our study demonstrated that arthroscopic Latarjet using cerclage FiberTape fixation combined with remplissage and capsulolabral repair resulted in high rate of graft loosening and migration (30%). Nonetheless, patients in whom the coracoid graft had united, as well as those in whom it had not, all had good to excellent functional and clinical outcomes, no complications, and did not require any revision surgery.

Mechanistic Regulation of Epidermal Growth Factor and Hormonal Receptors by Kinase Inhibitors and Organofluorines in Breast Cancer Therapy.

Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC50 of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

Geochemical and mineralogical assessment of environmentally sensitive elements in Neyveli lignite deposits, Cauvery Basin, India.

This research work presents an examination of the concentrations and modes of occurrence of environmentally sensitive elements within lignite deposits, located in Neyveli, within the Cauvery Basin of India. Coal is one of the most complex geologically formed materials, consisting of organic and inorganic matter. The inorganic mineral matter including the crystalline minerals, non-crystalline mineraloids, and elements with non-mineral associations. These lignite samples underwent complete analysis encompassing macroscopic, microscopic and geochemical assessments. The analysis reveals that the total mineral matter (MM) content, comprising significant proportions of sulphides, carbonate and argillaceous components. Geochemical characterization further elucidates the lignite's properties, with proximate analysis yielding values such as ash, volatile matter and fixed carbon and the Ultimate components analysis reveals the carbon, hydrogen, nitrogen, sulphur and oxygen. Inorganic mineral matters play a significant role in coal utilization, and also such modes of occurrence of elements provide useful geochemical information on coal formation and coal-bearing basin evolution. In this paper, we assess the associations of elements and minerals, as well as the associations of selected elements including environmentally-sensitive (e.g., S, As, U, and Hg), and some major elements (e.g., Ca, Mg, Fe, Al, and Ti) that have largely occurred in non-mineral forms in these low-rank coals. And also, comparative analysis is conducted between the concentrations of elements within the lignite samples and the values reported for World Clarke Brown Coals (WCBC). Particularly, some of these elements exhibit significantly high environmental sensitivity, demanding careful consideration in lignite extraction and utilization practices.

Extracorporeal Membrane Oxygenation-Supported Patient Outcome Undergoing Transcatheter Aortic Valve Replacement.

The efficacy and safety of extracorporeal membrane oxygenation (ECMO) support during transcatheter aortic valve replacement (TAVR) remains unknown. We conducted a meta-analysis to compare benefit and risk of ECMO in TAVR patients. Bibliographic databases were searched from inception to January 1, 2024. Included studies involved patients ≥18 years old undergoing TAVR and using ECMO emergently or prophylactically. Mortality and procedure success were primary outcomes. Peri- or postoperative complications were the secondary outcomes. We identified 11 observational studies, including 2,275 participants (415 ECMO and 1,860 non-ECMO). The unadjusted mortality risk in ECMO-supported patient was higher than non-ECMO patients (odds ratio [OR] 1.73). The mortality unadjusted risk remained high (OR 3.89) and statistically significant for prophylactic ECMO. Prophylactic ECMO had lower mortality risk compared with emergent ECMO (OR 0.17). Extracorporeal membrane oxygenation-supported patients had lower procedural success rate (OR 0.10). Extracorporeal membrane oxygenation patients undergoing TAVR had significantly increased risk of bleeding (OR 3.32), renal failure (OR 2.38), postoperative myocardial infarction (OR 1.89), and stroke (OR 2.32) compared with non-ECMO patients. Clinical results are not improved by ECMO support in patients with high-risk TAVR. Prophylactic ECMO outperforms emergent. Overall, ECMO support increases mortality and postoperative complications. Transcatheter aortic valve replacement outcomes may improve with prophylactic ECMO in high-risk situations.

Adverse outcomes with left atrial appendage occlusion device implantation in chronic and end stage kidney disease: A systemic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) and end stage renal disease (ESRD) are associated with increased risk of bleeding events, including hemorrhagic stroke, and periprocedural and gastrointestinal bleeding among patients with atrial fibrillation who are on anticoagulation. Safety of percutaneous left atrial appendage occlusion (LAAO) among this patient population has been uncertain with studies showing contradictory results. METHODS: PubMed and Google Scholar databases were queried for studies comparing outcomes among patients with and without significant CKD, and with and without ESRD who underwent LAAO device implantation. Data on outcomes from the selected studies were extracted and analyzed using random effects model. Heterogeneity was assessed using I2 test. RESULTS: Data from eleven studies with 61,724 patients with and without kidney disease were included in the final analyses. There was an increased risk of in-hospital mortality (OR 2.76, 95 % CI [1.15-6.64]; p = 0.02) and peri-procedural bleeding (1.51 [1.33-1.71]; p < 0.01) associated with kidney disease. There was no significant difference in risk of stroke (1.19 [0.70-2.03]; p = 0.53), pericardial effusion (1.22 [0.77-1.92]; p = 0.40), vascular complications (1.18 [0.92-1.52]; p = 0.20), or device related thrombus (1.13 [0.53-2.40]; p = 0.75). CONCLUSIONS: This study shows an increased risk of complications among patients with kidney disease, who undergo LAAO device implantation. These findings suggest the need for studies with randomized control design specifically designed to compare outcomes with LAAO versus anticoagulation in the CKD and ESRD populations.

Graphene oxide nanoribbons conjugated with 1, 2-distearoyl-sn-glycero-3 phosphoethanolamine-poly (ethylene glycol)-transferrin enhanced targeted delivery and cytotoxicity of raloxifene against breast cancer.

The clinical utility of raloxifene (RLX), a selective estrogen receptor modulator (SERM), has been compromised by severe side effects and unfavorable drug properties. To address these, a transferrin (Tf) conjugated graphene oxide nanoribbon (GONR) platform was tried for RLX. The stability of GONRs in biological media was improved by surface modification with 1, 2-Distearoyl-sn-glycero-3 phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG). The Tf molecule was covalently attached to DSPE-PEG (DPT) using EDC-NHS chemistry. The surface of GONR was then modified with DSPE-PEG (DP) or DPT and loaded with RLX (GDP-RLX and GDPT-RLX). The final formulations were characterized for drug loading and stability. The anticancer activities of pure RLX, GDP-RLX, and GDPT-RLX were evaluated and compared in all the in vitro and in vivo studies. In vitro cell line studies showed that GDPT-RLX have significantly high cytotoxicity, cellular uptake, apoptosis induction, G2/M phase arrest, anti-migration properties, and apoptotic protein expression, followed by GDP-RLX and RLX. Pharmacokinetics and tumor biodistribution were also found to be excellent with GDPT-RLX. The in vivo tumor therapy and tumor evaluation outcomes were also consistent with the in vitro data. The Tf conjugated GDPT-RLX represents a promising approach for targeted and sustained delivery of RLX with enhanced therapeutic efficacy.

Identifying resource-conscious and low-carbon agricultural development pathways through land use modelling.

Increasing agricultural production with current resources and technology may lead to increased GHG emissions. Additionally, large population countries like India face substantial challenges in terms of food demand, agro-ecological heterogeneity, carbon footprint and depleting natural resources, thus increasing the decision complexities for policymakers and planners. We aim to examine the potential of producing more food from available agricultural land with low-carbon (reduced GHG emissions) and resource-conscious (optimal resource use) options. The current study develops multiple calorie production and emission-centric land use using a land use optimization model wherein the calorie production and emission objective, resource and emissions constraints, and food production targets interact across multiple spatial levels. The capabilities of the developed model are demonstrated with a case study in India targeting ten crops (grown over two seasons) covering three food groups (cereals, legumes, and oilseeds). Three hypothetical scenarios for each objective of maximizing calories production (Calories-nation, Calories-group, Calories-crop) and minimizing GHG emissions (Emissions-nation, Emissions-group, Emissions-crop) are developed concerning targets of national crop production (Calories-nation, Emissions-nation), state food groups production (Calories-group, Emissions-group), and state crop production(Calories-crop, Emissions-crop), with different spatial levels of constraints. A maximum growth of 11% in calorie production is observed in Calories-nation while mitigating 2.5% emissions. Besides, the highest emission reduction of around 30% is observed in Emissions-group but with no change in calorie production. Emission scenarios can spare up to 14.8% land and 18.2% water, while calorie production-maximization scenarios can spare a maximum of 4.7% land and 6.5% water. The optimization-based methodology identifies the regions of altered land use by proposing appropriate crop substitution strategies, such as increasing oilseeds in Rajasthan and soybean in east Maharashtra. Many states show conservative production growth and emission reduction with state-level crop production targets (Calories-crop), suggesting crop redistribution within the state alone will not be sufficient unless improved technologies are introduced. The maximum growth and mitigation potential estimated in this study may be affected by climate shocks; therefore, introducing the improved technologies needs to be coupled with a crop redistribution mechanism to design climate-resilient and futuristic land use systems. The proposed land use model can be modified to incorporate climate change effects through consideration of scenarios of changed crop yields or through direct/indirect coupling with dynamic crop simulation models.

T1 relaxation and axon fibre configuration in human white matter.

Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f1), second (f2) and third (f3) fibre configuration; and fibre density cross-section images for the first (fdc1), second (fdc2) and third (fdc3) fibres. T1 values were plotted as a function of FA, f1, f2, f3, fdc1, fdc2 and fdc3 to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f1 and f2 in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc1 values in a nonlinear fashion. Instead, only a small T1 change as a function of either f3 or fdc3 was observed. In WM areas selected by fdc1 only masks, T1 was shorter than in those with fdc2/fdc3. In WM areas with high single fibre populations, as delineated by f1/fdc1 masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f2/fdc2 or f3/fdc3 masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease.

Association of estimated plasma volume with new onset acute kidney injury in hospitalized COVID-19 patients.

PURPOSE: To explore the association of estimated plasma volume (ePV) and plasma volume status (PVS) as surrogates of volume status with new-onset AKI and in-hospital mortality among hospitalized COVID-19 patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and longitudinal analysis was performed to find the association of ePV and PVS with new-onset AKI during hospitalization as the primary outcome and in-hospital mortality as a secondary outcome. RESULTS: Our analysis included 7616 COVID-19 patients with new-onset AKI occurring in 1365 (17.9%) and a mortality rate of 25.96% among them. A longitudinal multilevel multivariate analysis showed both ePV (OR 1.162; 95% CI 1.048-1.288, p=0.004) and PVS (OR 1.032; 95% CI 1.012-1.050, p=0.001) were independent predictors of new onset AKI. Higher PVS was independently associated with increased in-hospital mortality (OR 1.038, 95% CI 1.007-1.070, p=0.017), but not ePV (OR 0.868, 95% CI 0.740-1.018, p=0.082). CONCLUSION: A higher PVS correlated with a higher incidence of new-onset AKI and worse outcomes in our cohort of hospitalized COVID-19 patients. Further large-scale and prospective studies are needed to understand its utility.

Association of antibiotics with the outcomes in COVID-19 pneumonia patients with elevated PCT levels.

OBJECTIVE: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. METHODS: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. RESULTS: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. CONCLUSION: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

ERAMER: A novel in silico tool for prediction of ERAP1 enzyme trimming.

MHC class I pathway consists of four main steps: proteasomal cleavage in the cytosol in which precursor proteins are cleaved into smaller peptides, which are then transported into the endoplasmic reticulum by the transporter associated with antigen processing, TAP, for further processing (trimming) from the N-terminal region by an ER resident aminopeptidases 1 (ERAP1) enzyme, to generate optimal peptides (8-10 amino acids in length) to produce a stable MHCI-peptide complex, that get transited via the Golgi apparatus to the cell surface for presentation to the cellular immune system. Several studies reported specificities related to the ERAP1 trimming process, yet there is no in silico tool for the prediction of the trimming process of the ERAP1 enzyme. In this paper, we provide and implement a prediction model for the trimming process of the ERAP1 enzyme.