A Framework for Quality Control in Quantitative Proteomics.

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow, from planning to analysis. We share vignettes applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at the protein and peptide levels allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis (Skyline), longitudinal QC metrics (AutoQC), and server-based data deposition (PanoramaWeb). We propose that this integrated approach to QC is a useful starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible. Data are available on Panorama Public and ProteomeXchange under the identifier PXD051318.

Advancements in Targeted Therapies for the Management of Crohn's Disease: A Comprehensive Review.

Crohn's disease (CD) is a complex clinical condition characterized by persistent gastrointestinal inflammation that leads to episodes of flare-ups and subsequent healing. The treatment options for this disease are heterogeneous as its impact on different patients is also different. This study aims to evaluate the effectiveness of recently approved drugs that specifically target certain pathways within cells that are involved in CD pathogenesis. These medicines include biologics like anti-TNF agents, interleukin inhibitors, and small molecule inhibitors; they work by altering the modulation of immune responses and reducing inflammation. These drugs seem promising in terms of inducing remission in moderate to severe CD among various patient populations. Conversely, it is possible to examine how well these drugs perform using gene expression and molecular markers. By understanding these results along with other ongoing trials, personalized medicine can be used more frequently by doctors who will adopt a strategy for an individual patient, maximizing benefits while minimizing adverse effects. There are still some issues that need to be worked out like the high cost associated with these drugs or immunogenicity risk and infectious complications too. In conclusion, there has been a remarkable improvement in CD management over the past decade with customized drugs leading toward a precision medical era. Further understanding of molecular mechanisms implicated in CD pathogenesis and new therapeutic approaches could potentially improve treatment outcomes among affected individuals. This research is crucial in understanding how CD therapeutics are changing, thus facilitating selection by doctors on the most appropriate methods for individualized patient care.

A framework for quality control in quantitative proteomics.

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow from planning to analysis. We share vignettes applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at protein and peptide-level allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis (Skyline), longitudinal QC metrics (AutoQC), and server-based data deposition (PanoramaWeb). We propose that this integrated approach to QC is a useful starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible. Data are available on Panorama Public and on ProteomeXchange under the identifier PXD051318.

LentiGlobin Administration to Sickle Cell Disease Patients: Effect on Serum Markers and Vaso-Occlusive Crisis.

LentiGlobin, an innovative gene therapy, introduces a modified beta-globin gene that yields an anti-sickling hemoglobin variant. It boosts total hemoglobin levels, mitigates hemolysis, curtails inflammation, and addresses iron overload by reducing transfusion requirements. These changes, in turn, provide insights into disease mechanisms and treatment outcomes. Alterations in serum markers, such as hemoglobin levels and inflammatory biomarkers, can illuminate the therapeutic effectiveness of LentiGlobin and its impact on mitigating complications such as vaso-occlusive crises. Therefore, the purpose of this narrative review is to discuss the effects of LentiGlobin administration on diverse serum biomarkers and its correlation with vaso-occlusive crises in individuals with sickle cell disease (SCD).

Divided by borders, united by rabies: A call for integrated rabies control in India and Pakistan.

•India and Pakistan share a common public health concern: rabies, which affects both humans and animals.•Both countries have established national rabies control initiatives, but these programs face challenges such as inadequate funding and limited access to healthcare in rural areas.•Non-governmental organizations (NGOs) are also working to control rabies in both India and Pakistan.•Cross-Border Cooperation Crucial in Rabies Fight: SAARC Initiatives Promoting Regional Prevention.•Crucial Steps: Raising Rabies Awareness and Accessible PEP in Both Countries.

Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature.

The repercussions of coronavirus disease 2019 (COVID-19) have been devastating on a global scale. Long COVID, which affects patients for weeks or even months after their initial infection, is not limited to individuals with severe symptoms and can affect people of all ages. The condition can impact various physiological systems, leading to chronic health conditions and long-term disabilities that present significant challenges for healthcare systems worldwide. This review explores the link between long COVID and cardiovascular complications such as myocardial injury and myocarditis. It also highlights the prevalence of these complications and identifies risk factors for their development in long COVID patients. Myocardial injury occurs due to direct cellular damage and T-cell-mediated cytotoxicity resulting in elevated cardiac biomarkers. Diagnostic techniques like electrocardiogram, troponin level testing, and magnetic resonance imaging can help identify myocarditis, but endomyocardial biopsy is considered the gold-standard diagnostic technique. Guideline-directed medical therapy is recommended for COVID-19 myocarditis patients for better prognosis while being monitored under comprehensive care management approaches. Therefore, it's critical to develop effective screening techniques specifically for vulnerable populations while conducting further research that addresses the effects of long COVID on society's physical health.

Transesophageal Echocardiogram Before Cardioversion in Atrial Fibrillation Patients.

Transesophageal echocardiography (TEE) offers an invaluable, non-invasive avenue for diagnosing and managing various cardiac conditions, including atrial fibrillation (AF). As the most common cardiac arrhythmia, AF affects millions and can lead to severe complications. Cardioversion, a procedure to restore the heart's normal rhythm, is frequently conducted on AF patients resistant to medication. Due to inconclusive data, TEE's utility prior to cardioversion in AF patients remains ambiguous. Understanding TEE's potential benefits and limitations in this population could significantly influence clinical practice. This review aims to scrutinize the current literature on the use of TEE before cardioversion in AF patients. The principal objective is to understand TEE's potential benefits and limitations comprehensively. The study seeks to offer a clear understanding and practical recommendations for clinical practice, thereby improving the management of AF patients before cardioversion using TEE. A literature search of databases was conducted using the keywords "Atrial Fibrillation," "Cardioversion" and "Transesophageal echocardiography," resulting in 640 articles. These were narrowed to 103 following title and abstract reviews. After applying exclusion and inclusion criteria with a quality assessment, 20 papers were included: seven retrospective studies, 12 prospective observational studies, and one randomized controlled trial (RCT). Stroke risk associated with direct-current cardioversion (DCC) potentially results from post-cardioversion atrial stunning. Thromboembolic events occur post cardioversion, with or without prior atrial thrombus or cardioversion complications. Generally, cardiac thrombus localizes in the left atrial appendage (LAA), a clear contraindication to cardioversion. Atrial sludge without LAA thrombus in TEE is a relative contraindication. TEE before electrical cardioversion (ECV) in anticoagulated AF individuals is uncommon. In AF patients planned for cardioversion, contrast enhancement facilitates thrombus exclusion in TEE images, reducing embolic events. Left atrial thrombus (LAT) frequently occurs in AF patients, necessitating TEE examination. Despite the increased use of pre-cardioversion TEE, thromboembolic events persist. Notably, patients with post-DCC thromboembolic events had no LA thrombus or LAA sludge. The use of TEE-guided DCC has grown due to its ability to detect atrial thrombi pre-cardioversion, aiding risk stratification. Thrombus in the left atrium also signals an elevated risk of future thromboembolic events in AF patients. While atrial stunning post cardioversion detected by TEE is a significant risk factor for future thromboembolic events, further evidence is required. Therapeutic anticoagulation is essential during and post cardioversion, even if no atrial thrombus is detected. Current data recommends cardioversion guided by TEE, particularly in outpatient settings.

Coronary allograft vasculopathy in post-heart transplant patients: pathogenesis and role of cardiac computed tomography in diagnosis-a comprehensive review.

Coronary allograft vasculopathy, often known as cardiac allograft vasculopathy (CAV), is a substantial source of morbidity and mortality in people who have had heart transplants. Early detection and monitoring of CAV are crucial for improving outcomes in this population. Although cardiac computed tomography (CT) has emerged as a possible method for finding and evaluating CAV, invasive coronary angiography has long been thought of as the gold standard for recognizing CAV. This study focuses on the utility of cardiac CT for CAV diagnosis and treatment in the post-heart transplant population. It provides an overview of recent studies on the application of cardiac CT in CAV and highlights the advantages and disadvantages of this imaging modality. The potential application of cardiac CT for CAV risk assessment and care is also examined in the study. Overall, the data point to a potential role for cardiac CT in the detection and treatment of CAV in post-heart transplant patients. It enables evaluation of the whole coronary tree and low-radiation, high-resolution imaging of the coronary arteries. Hence, further study is required to determine how best to employ cardiac CT in treating CAV in this group.

Pre-pandemic autonomic function as a predictor of the COVID clinical course in young adults.

Long coronavirus disease (COVID) is emerging as a common clinical entity in the current era. Autonomic dysfunction is one of the frequently reported post-COVID complications. We hypothesize a bi-directional relationship between the autonomic function and the COVID course. This postulation has been inadequately addressed in the literature. A retrospective cohort (pre and post-comparison) study was conducted on 30 young adults whose pre-COVID autonomic function test results were available. They were divided into case and control groups based on whether they tested reverse transcription polymerase chain reaction positive for COVID-19. Autonomic function tests were performed in both the case and control groups. COVID infection in healthy young adults shifts the sympatho-vagal balance from the pre-disease state. Postural orthostatic tachycardia syndrome was present in 35% of the COVID-affected group. COVID course parameters were found to be associated with parasympathetic reactivity and the baroreflex function. Baseline autonomic function (parasympathetic reactivity represented by Δ heart rate changes during deep breathing and 30:15 ratio during lying-to-standing test) was also associated with the COVID course, the post-COVID symptoms and the post-COVID autonomic function profile. Additionally, multiple regression analysis found that the baseline parasympathetic reactivity was a very important determinant of the clinical course of COVID, the post-COVID symptoms and the post-COVID autonomic profile. Sympatho-vagal balance shifts to parasympathetic withdrawal with sympathetic predominance due to COVID infection in healthy young adults. There is a bi-directional relationship between the autonomic function and the COVID course.

Acute Upper Limb Ischemia and Amputation Post Antecubital Fossa Cannulation: A Report of Two Postpartum Patients.

Upper extremity arterial thrombosis is less common than that in the lower extremity. Upper extremity arterial thrombosis, when present, is more likely to occur on the ulnar side of the circulation. Severe ischemia resulting from radial artery thrombosis is rare, but iatrogenic cannulation is the most common etiology when it occurs. The risk factors underlying this dreadful presentation are numerous and still under investigation. Pregnancy and the immediate postpartum period are physiological hypercoagulable states. Here we present unusual cases of acute limb ischemia post iatrogenic cannulation in two patients within six weeks postpartum. At four weeks postpartum, a 26-year-old para-1 live-1 female presented to the emergency department with swelling in her right upper limb for four weeks and its blackish discoloration for one week. A 24-year-old primigravida female who had a termination of a blighted ovum 12 days ago presented to the emergency department with gangrenous changes in her right hand and forearm. Both patients reported recent antecubital fossa cannulation within six weeks postpartum, triggering gangrenous hand changes. Both patients had to undergo amputation of the digits and hand ultimately. Thus we postulate the need for extra care and education of healthcare workers in the cannulation of pregnant and post-pregnancy patients to prevent limb-threatening complications.

The ProteomeXchange consortium at 10 years: 2023 update.

Mass spectrometry (MS) is by far the most used experimental approach in high-throughput proteomics. The ProteomeXchange (PX) consortium of proteomics resources (http://www.proteomexchange.org) was originally set up to standardize data submission and dissemination of public MS proteomics data. It is now 10 years since the initial data workflow was implemented. In this manuscript, we describe the main developments in PX since the previous update manuscript in Nucleic Acids Research was published in 2020. The six members of the Consortium are PRIDE, PeptideAtlas (including PASSEL), MassIVE, jPOST, iProX and Panorama Public. We report the current data submission statistics, showcasing that the number of datasets submitted to PX resources has continued to increase every year. As of June 2022, more than 34 233 datasets had been submitted to PX resources, and from those, 20 062 (58.6%) just in the last three years. We also report the development of the Universal Spectrum Identifiers and the improvements in capturing the experimental metadata annotations. In parallel, we highlight that data re-use activities of public datasets continue to increase, enabling connections between PX resources and other popular bioinformatics resources, novel research and also new data resources. Finally, we summarise the current state-of-the-art in data management practices for sensitive human (clinical) proteomics data.

Glycemic Control and Mucormycosis during COVID-19 Pandemic in India a Study of Stage and Outcome.

INTRODUCTION: Mucormycosis mostly targets immunocompromised patients or those with uncontrolled diabetes but is now an important complication after coronavirus disease 2019 (COVID-19) infection. The stage of mucormycosis at presentation greatly impacts its treatment course and prognosis. Prior research has failed to evaluate an association of patient factors, especially glycated hemoglobin (HbA1c) levels and random blood sugar (RBS) at presentation, with the stage and outcome of mucormycosis. OBJECTIVES: To investigate the relationship between glycemic control and the stage of mucormycosis at presentation and to investigate various factors affecting mucormycosis outcome. MATERIALS AND METHODS: All patients with clinicopathologically confirmed mucormycosis presenting to Safdarjung Hospital, New Delhi, during the COVID-19 pandemic were enrolled in the study. A questionnaire consisting of demographic information, comorbidities, history, and treatment of COVID-19 and diabetes was filled out at the time of admission. Blood glucose and HbA1c levels at presentation were noted. The above-noted parameters were compared with the stage and outcome of mucormycosis. The data obtained was analyzed. RESULTS: A total of 75 mucormycosis patients were enrolled in the study. The mean age of the participants was 45.17 years, and 85.33% of them survived the disease course. There was no statistically significant difference between the survivors and nonsurvivors concerning mean HbA1c and RBS levels. But there was a statistically significant correlation such that the stage of mucormycosis increased with progressive worsening glycemic control markers HbA1c and RBS. The most common comorbid condition was diabetes mellitus (72%); however, only coronary artery disease in the patient was significantly correlated with mortality. A history of COVID-19 infection was reported in 67.6% of the patients, but this was not significantly associated with mortality outcomes. Patients without a history of COVID-19 reported significantly higher RBS and HbA1c levels at presentation than the COVID-19-associated mucormycosis group. CONCLUSION: The study showed a positive correlation between the stage of mucormycosis and serum glycemic control markers at presentation. Clinicians must order blood sugar and HbA1c levels at presentation as cues for a better understanding of disease severity. A thorough clinical examination and history taking for patient risk factors predisposing to mucormycosis are also crucial since the presence of proptosis and coronary artery disease are significantly correlated with the mortality outcomes. The extent of poor glycemic control at presentation was not associated with mortality outcomes. How to cite this article: Sharma V, Kriplani K, Tuli IP, et al. Glycemic Control and Mucormycosis during COVID-19 Pandemic in India a Study of Stage and Outcome. J Assoc Physicians India 2023;71(9):61-66.

Skyline Batch: An Intuitive User Interface for Batch Processing with Skyline.

Skyline Batch is a newly developed Windows forms application that enables the easy and consistent reprocessing of data with Skyline. Skyline has made previous advances in this direction; however, none enable seamless automated reprocessing of local and remote files. Skyline keeps a log of all of the steps that were taken in the document; however, reproducing these steps takes time and allows room for human error. Skyline also has a command-line interface, enabling it to be run from a batch script, but using the program in this way requires expertise in editing these scripts. By formalizing the workflow of a highly used set of batch scripts into an intuitive and powerful user interface, Skyline Batch can reprocess data stored in remote repositories just by opening and running a Skyline Batch configuration file. When run, a Skyline Batch configuration downloads all necessary remote files and then runs a four-step Skyline workflow. By condensing the steps needed to reprocess the data into one file, Skyline Batch gives researchers the opportunity to publish their processing along with their data and other analysis files. These easily run configuration files will greatly increase the transparency and reproducibility of published work. Skyline Batch is freely available at https://skyline.ms/batch.url.

Proteomic profiling dataset of chemical perturbations in multiple biological backgrounds.

While gene expression profiling has traditionally been the method of choice for large-scale perturbational profiling studies, proteomics has emerged as an effective tool in this context for directly monitoring cellular responses to perturbations. We previously reported a pilot library containing 3400 profiles of multiple perturbations across diverse cellular backgrounds in the reduced-representation phosphoproteome (P100) and chromatin space (Global Chromatin Profiling, GCP). Here, we expand our original dataset to include profiles from a new set of cardiotoxic compounds and from astrocytes, an additional neural cell model, totaling 5300 proteomic signatures. We describe filtering criteria and quality control metrics used to assess and validate the technical quality and reproducibility of our data. To demonstrate the power of the library, we present two case studies where data is queried using the concept of "connectivity" to obtain biological insight. All data presented in this study have been deposited to the ProteomeXchange Consortium with identifiers PXD017458 (P100) and PXD017459 (GCP) and can be queried at https://clue.io/proteomics .

Audit logs to enforce document integrity in Skyline and Panorama.

SUMMARY: Skyline is a Windows application for targeted mass spectrometry method creation and quantitative data analysis. Like most graphical user interface (GUI) tools, it has a complex user interface with many ways for users to edit their files which makes the task of logging user actions challenging and is the reason why audit logging of every change is not common in GUI tools. We present an object comparison-based approach to audit logging for Skyline that is extensible to other GUI tools. The new audit logging system keeps track of all document modifications made through the GUI or the command line and displays them in an interactive grid. The audit log can also be uploaded and viewed in Panorama, a web repository for Skyline documents that can be configured to only accept documents with a valid audit log, based on embedded hashes to protect log integrity. This makes workflows involving Skyline and Panorama more reproducible. AVAILABILITY AND IMPLEMENTATION: Skyline is freely available at https://skyline.ms. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A proteomic atlas of senescence-associated secretomes for aging biomarker development.

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the "SASP Atlas," a comprehensive proteomic database of soluble proteins and exosomal cargo SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo.

Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics.

Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method development and data processing with a 10 year history supporting six major instrument vendors. Designed initially for proteomics analysis, we describe the expansion of Skyline to data for small molecule analysis, including selected reaction monitoring, high-resolution mass spectrometry, and calibrated quantification. This fundamental expansion of Skyline from a peptide-sequence-centric tool to a molecule-centric tool makes it agnostic to the source of the molecule while retaining Skyline features critical for workflows in both peptide and more general biomolecular research. The data visualization and interrogation features already available in Skyline, such as peak picking, chromatographic alignment, and transition selection, have been adapted to support small molecule data, including metabolomics. Herein, we explain the conceptual workflow for small molecule analysis using Skyline, demonstrate Skyline performance benchmarked against a comparable instrument vendor software tool, and present additional real-world applications. Further, we include step-by-step instructions on using Skyline for small molecule quantitative method development and data analysis on data acquired with a variety of mass spectrometers from multiple instrument vendors.

The ProteomeXchange consortium in 2020: enabling 'big data' approaches in proteomics.

The ProteomeXchange (PX) consortium of proteomics resources (http://www.proteomexchange.org) has standardized data submission and dissemination of mass spectrometry proteomics data worldwide since 2012. In this paper, we describe the main developments since the previous update manuscript was published in Nucleic Acids Research in 2017. Since then, in addition to the four PX existing members at the time (PRIDE, PeptideAtlas including the PASSEL resource, MassIVE and jPOST), two new resources have joined PX: iProX (China) and Panorama Public (USA). We first describe the updated submission guidelines, now expanded to include six members. Next, with current data submission statistics, we demonstrate that the proteomics field is now actively embracing public open data policies. At the end of June 2019, more than 14 100 datasets had been submitted to PX resources since 2012, and from those, more than 9 500 in just the last three years. In parallel, an unprecedented increase of data re-use activities in the field, including 'big data' approaches, is enabling novel research and new data resources. At last, we also outline some of our future plans for the coming years.