Polymeric optical fiber biosensor with PAMAM dendrimer-based surface modification and PlGF detection for pre-eclampsia diagnosis.

Pre-eclampsia (PE) is a life-threatening complication that occurs during pregnancy, affecting a large number of pregnant women and newborns worldwide. Rapid, on-site and affordable screening of PE at an early stage is necessary to ensure timely treatment and minimize both maternal and neonatal morbidity and mortality rates. Placental growth factor (PlGF) is an angiogenic blood biomarker used for PE diagnosis. Herein, we report the plasmonic fiber optic absorbance biosensor (P-FAB) strategy for detecting PlGF at femtomolar concentration using polymethyl methacrylate (PMMA) based U-bent polymeric optical fiber (POF) sensor probes. A novel poly(amidoamine) (PAMAM) dendrimer based PMMA surface modification is established to obtain a greater immobilization of the bioreceptors compared to a linear molecule like hexamethylenediamine (HMDA). Plasmonic sandwich immunoassay was realized by immobilizing the mouse anti-PlGF (3H1) on the U-bent POF sensor probe surface and gold nanoparticles (AuNP) labels conjugated with mouse anti-PlGF (6H9). The POF sensor probes could measure PlGF within 30 min using the P-FAB strategy. The limit-of-detection (LoD) was found to be 0.19 pg/mL and 0.57 pg/mL in phosphate-buffered saline and 10× diluted serum, respectively. The clinical sample testing, with eleven positive and eleven negative preeclamptic pregnancy samples, successfully confirmed the accuracy, reliability, specificity, and sensitivity of the P-FAB based POF sensor platform, thereby paving the way for cost-effective technology for PlGF detection and its potential for pre-eclampsia diagnosis.

Point-of-care device for the noninvasive assessment of hepatic macrosteatosis in liver donors.

BACKGROUND: Quantification of macrosteatosis (MS) in the liver is important given that it has shown to directly correlate with adverse post-liver transplant (LT) outcomes. With advances in medical technology and an implicit understanding of pathology, noninvasive methods of quantitatively assessing MS are in various stages of development. Each of these methods is based on the physical principles of differences between a fat-laden hepatocyte and a normal one. METHODS: In this regard, after a proof-of-concept study on a prototype for a simple, real-time, handheld device using the principle of diffuse reflectance spectroscopy, this study presents an upgraded point-of-care (POC) device for the noninvasive assessment of hepatic MS in liver donors. RESULTS: The device was validated on cohort of donor livers and showed a sensitivity (0.0021 V/% fat) and highly correlated (r = 0.9868, P < .0001) with gold-standard liver biopsy. Results showed that this upgraded POC device provides a reliable method for the noninvasive assessment of hepatic MS, which is crucial for selecting suitable donor livers for LT. CONCLUSION: The device has the potential to be an invaluable apparatus at the hands of the organ-retrieving surgeon. It is noninvasive, portable (handheld), and economic; provides real-time readings of the percentage of MS; and can be efficaciously handled by any member of the organ-retrieving team.

Attempted repair of chest wall injury following penetrating injury with surgical stabilization rib and autologous bone graft: A case report.

Rib fractures are one of the most common injuries following blunt trauma. When associated with penetrating trauma, the projectile velocity and immense energy transfer cause significant rib fracture displacement and fragmentation. As a result, these patients are potentially exposed to an even higher risk of complications compared to those seen in more simple rib fractures. Unfortunately, there is limited research regarding technical considerations for surgical stabilization of rib fractures (SSRF) in severely displaced rib fractures with bone loss following penetrating injury. We present the case of a 21-year-old male gunshot wound victim with severely displaced and comminuted rib fractures in which we utilized an autologous bone graft bridge during SSRF to enhance fracture unionization, chest wall stability, and cosmesis. Unfortunately, the bone graft failed to incorporate into surrounding tissue.

Vesiclepedia 2024: an extracellular vesicles and extracellular particles repository.

Vesiclepedia (http://www.microvesicles.org) is a free web-based compendium of DNA, RNA, proteins, lipids and metabolites that are detected or associated with extracellular vesicles (EVs) and extracellular particles (EPs). EVs are membranous vesicles that are secreted ubiquitously by cells from all domains of life from archaea to eukaryotes. In addition to EVs, it was reported recently that EPs like exomeres and supermeres are secreted by some mammalian cells. Both EVs and EPs contain proteins, nucleic acids, lipids and metabolites and has been proposed to be implicated in several key biological functions. Vesiclepedia catalogues proteins, DNA, RNA, lipids and metabolites from both published and unpublished studies. Currently, Vesiclepedia contains data obtained from 3533 EV studies, 50 550 RNA entries, 566 911 protein entries, 3839 lipid entries, 192 metabolite and 167 DNA entries. Quantitative data for 62 822 entries from 47 EV studies is available in Vesiclepedia. The datasets available in Vesiclepedia can be downloaded as tab-delimited files or accessible through the FunRich-based Vesiclepedia plugin.

The E3 ubiquitin ligase NEDD4 regulates chemoresistance to 5-fluorouracil in colorectal cancer cells by altering JNK signalling.

Colorectal cancer (CRC) is the second leading cause of cancer deaths. Though chemotherapy is the main treatment option for advanced CRC, patients invariably acquire resistance to chemotherapeutic drugs and fail to respond to the therapy. Although understanding the mechanisms regulating chemoresistance has been a focus of intense research to manage this challenge, the pathways governing resistance to drugs are poorly understood. In this study, we provide evidence for the role of ubiquitin ligase NEDD4 in resistance developed against the most commonly used CRC chemotherapeutic drug 5-fluorouracil (5-FU). A marked reduction in NEDD4 protein abundance was observed in a panel of CRC cell lines and patient-derived xenograft samples that were resistant to 5-FU. Knockout of NEDD4 in CRC cells protected them from 5-FU-mediated apoptosis but not oxaliplatin or irinotecan. Furthermore, NEDD4 depletion in CRC cells reduced proliferation, colony-forming abilities and tumour growth in mice. Follow-up biochemical analysis highlighted the inhibition of the JNK signalling pathway in NEDD4-deficient cells. Treatment with the JNK activator hesperidin in NEDD4 knockout cells sensitised the CRC cells against 5-FU. Overall, we show that NEDD4 regulates cell proliferation, colony formation, tumour growth and 5-FU chemoresistance in CRC cells.

Unravelling the Role of Cancer Cell-Derived Extracellular Vesicles in Muscle Atrophy, Lipolysis, and Cancer-Associated Cachexia.

Cancer-associated cachexia is a metabolic syndrome that causes significant reduction in whole-body weight due to excessive loss of muscle mass accompanied by loss of fat mass. Reduced food intake and several metabolic abnormalities, such as increased energy expenditure, excessive catabolism, and inflammation, are known to drive cachexia. It is well documented that cancer cells secrete EVs in abundance which can be easily taken up by the recipient cell. The cargo biomolecules carried by the EVs have the potential to alter the signalling pathways and function of the recipient cells. EV cargo includes proteins, nucleic acids, lipids, and metabolites. Tumour-secreted EVs have been found to alter the metabolic and biological functions of adipose and muscle tissue, which aids in the development of the cachexia phenotype. To date, no medical intervention or FDA-approved drug exists that can completely reverse cachexia. Therefore, understanding how cancer-derived EVs contribute to the onset and progression of cancer-associated cachexia may help with the identification of new biomarkers as well as provide access to novel treatment alternatives. The goal of this review article is to discuss the most recent research on cancer-derived EVs and their function in cellular crosstalk that promotes catabolism in muscle and adipose tissue during cancer-induced cachexia.

Proteomics analysis of C2C12 myotubes treated with atrophy inducing cancer cell-derived factors.

Cancer-associated cachexia is a wasting syndrome that results in dramatic loss of whole-body weight, predominantly due to loss of skeletal muscle mass. It has been established that cachexia inducing cancer cells secrete proteins and extracellular vesicles (EVs) that can induce muscle atrophy. Though several studies examined these cancer-cell derived factors, targeting some of these components have shown little or no clinical benefit. To develop new therapies, understanding of the dysregulated proteins and signaling pathways that regulate catabolic gene expression during muscle wasting is essential. Here, we sought to examine the effect of conditioned media (CM) that contain secreted factors and EVs from cachexia inducing C26 colon cancer cells on C2C12 myotubes using mass spectrometry-based label-free quantitative proteomics. We identified significant changes in the protein profile of C2C12 cells upon exposure to C26-derived CM. Functional enrichment analysis revealed enrichment of proteins associated with inflammation, mitochondrial dysfunction, muscle catabolism, ROS production, and ER stress in CM treated myotubes. Furthermore, strong downregulation in muscle structural integrity and development and/or regenerative pathways were observed. Together, these enriched proteins in atrophied muscle could be utilized as potential muscle wasting markers and the dysregulated biological processes could be employed for therapeutic benefit in cancer-induced muscle wasting.

Assessment of the USG Detection of Abdominal Pathologies in HIV and Aids and its Association with CD4 Counts - An Original Research.

Introduction: In individuals with acquired immunodeficiency syndrome (HIV/AIDS), abdominal pathologies rank second in frequency only to pulmonary illnesses. An essential imaging method for assessing abdominal diseases is ultrasonography (USG). In this study, abdominal pathologies in HIV/AIDS patients were evaluated using USG, and their relationship to CD4 count was further examined. Materials and Techniques: 400 HIV+ subjects with aberrant abdominal USG participated in the current investigation. The subjects were assessed and graded as per the CD4 counts. Later the comparisons were drawn between the USG, and its relationship to CD4 count using SPSS 16.0 software, and all data were examined using appropriate statistical tools. Results: Men were over 60% of the 400 subjects. The average age of these subjects was 35.6 years; the range for this age group was 6 to 63 years. Spleen involvement was found on ultrasonographic examination in 45.1% of subjects, while liver and lymph node involvement was seen in 43.6% of subjects. Substantial correlations between CD4 counts and findings such as periportal & mesenteric lymphadenopathy, localized pancreatic lesion, splenic microabscess, splenomegaly, and hepatomegaly were found. One percent of individuals had lymphoma, which affected the retroperitoneal lymph nodes, pancreas, and liver. Conclusion: Present research demonstrates the significance of abdominal ultrasonographic examination in HIV+ patients. CD4 counts have a big impact on how an HIV/AIDS patient's differential diagnosis is determined. The interpretation of USG results in relation to CD4 levels may aid in accurate diagnosis.

Proteomic analysis of the small extracellular vesicles and soluble secretory proteins from cachexia inducing and non-inducing cancer cells.

Cancer cachexia is a wasting syndrome characterised by the loss of fat and/or muscle mass in advanced cancer patients. It has been well-established that cancer cells themselves can induce cachexia via the release of several pro-cachectic and pro-inflammatory factors. However, it is unclear how this process is regulated and the key cachexins that are involved. In this study, we validated C26 and EL4 as cachexic and non-cachexic cell models, respectively. Treatment of adipocytes and myotubes with C26 conditioned medium induced lipolysis and atrophy, respectively. We profiled soluble secreted proteins (secretome) as well as small extracellular vesicles (sEVs) released from cachexia-inducing (C26) and non-inducing (EL4) cancer cells by label-free quantitative proteomics. A total of 1268 and 1022 proteins were identified in the secretome of C26 and EL4, respectively. Furthermore, proteomic analysis of sEVs derived from C26 and EL4 cancer cells revealed a distinct difference in the protein cargo. Functional enrichment analysis using FunRich highlighted the enrichment of proteins that are implicated in biological processes such as muscle atrophy, lipolysis, and inflammation in both the secretome and sEVs derived from C26 cancer cells. Overall, our characterisation of the proteomic profiles of the secretory factors and sEVs from cachexia-inducing and non-inducing cancer cells provides insights into tumour factors that promote weight loss by mediating protein and lipid loss in various organs and tissues. Further investigation of these proteins may assist in highlighting potential therapeutic targets and biomarkers of cancer cachexia.

In- and out-of-hospital outcomes following surgical stabilization of rib fractures in 80 years and older: A single-institution experience.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) has demonstrated benefit in patients with flail chest and multiple displaced fractures. There is mounting evidence for SSRF following chest wall injury (CWI) for the geriatric trauma population. A recent multi-center retrospective study highlighted a mortality benefit even for those patients aged 80 years and older. The objective of this investigation was to review our institutional experience with both in- and out-of-hospital outcomes within this patient population following SSRF. METHODS: A retrospective review of patients 80 years and older was performed at a high-volume level 2 trauma center from 2017 to 2021. SSRF volume is routinely >60 cases per year. Perioperative, inpatient, and outpatient data were collected as available. Primary outcomes were inpatient and 90-day mortality. Secondary outcomes included discharge on narcotics and freedom from narcotics at 30 days. RESULTS: 50 patients were included for review. Mean age was 86 years and mechanism of injury was most often fall. 28 of 50 (56%) patients had flail chest (radiographic). Mean number of ribs fixated was 4.7 and time to surgery 2.5 days. Inpatient mortality was 3/50 (6%), 90-day mortality was 9/50 (18%) of which three were attributable primarily to CWI (6/50, 12%). Of patients with follow-up of 1 year and beyond, 27/28 were alive (96%). With respect to narcotic consumption, 45% (21/47) were discharged on narcotics with 90% (28/31; N limited by missing data) being narcotic-free at 30 days. CONCLUSION: In this high-risk patient population, inpatient mortality was comparably low to prior reports, though 90-day mortality was doubled when incorporating CWI-related deaths. Narcotic use was seen in the minority of patients upon discharge, and most progressed to being narcotic-free at 30 days post-hospitalization. Inpatient outcomes alone may not adequately define both the benefit and risk of SSRF performed in patients 80 years and older.

A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons.

Introduction: Human-derived induced pluripotent stem cell (iPSC) models of brain promise to advance our understanding of neurotoxic consequences of drug use. However, how well these models recapitulate the actual genomic landscape and cell function, as well as the drug-induced alterations, remains to be established. New in vitro models of drug exposure are needed to advance our understanding of how to protect or reverse molecular changes related to substance use disorders. Methods: We engineered a novel induced pluripotent stem cell-derived model of neural progenitor cells and neurons from cultured postmortem human skin fibroblasts, and directly compared these to isogenic brain tissue from the donor source. We assessed the maturity of the cell models across differentiation from stem cells to neurons using RNA cell type and maturity deconvolution analyses as well as DNA methylation epigenetic clocks trained on adult and fetal human tissue. As proof-of-concept of this model's utility for substance use disorder studies, we compared morphine- and cocaine-treated neurons to gene expression signatures in postmortem Opioid Use Disorder (OUD) and Cocaine Use Disorder (CUD) brains, respectively. Results: Within each human subject (N = 2, 2 clones each), brain frontal cortex epigenetic age parallels that of skin fibroblasts and closely approximates the donor's chronological age; stem cell induction from fibroblast cells effectively sets the epigenetic clock to an embryonic age; and differentiation of stem cells to neural progenitor cells and then to neurons progressively matures the cells via DNA methylation and RNA gene expression readouts. In neurons derived from an individual who died of opioid overdose, morphine treatment induced alterations in gene expression similar to those previously observed in OUD ex-vivo brain tissue, including differential expression of the immediate early gene EGR1, which is known to be dysregulated by opioid use. Discussion: In summary, we introduce an iPSC model generated from human postmortem fibroblasts that can be directly compared to corresponding isogenic brain tissue and can be used to model perturbagen exposure such as that seen in opioid use disorder. Future studies with this and other postmortem-derived brain cellular models, including cerebral organoids, can be an invaluable tool for understanding mechanisms of drug-induced brain alterations.

Understanding online ratings of joint arthroplasty surgeons: A national cross-sectional analysis.

Background: Patient reviews provide an important referral source for physicians and an opportunity to improve practice performance. This study's objective was to characterize the online reviews of hip and knee arthroplasty surgeons published by three of the industry's leading platforms. Methods: A random sample of 1000 hip and knee arthroplasty surgeons across all 50 US states (10 hip and 10 knee surgeons per state) was generated using Google Search. A total of 7842 online reviews posted for those surgeons on Healthgrades, Vitals, and Google were analyzed. A range of surgeons, affiliated hospitals, and reviewer attributes was compared to identify significant predictors of patient satisfaction. Results: The study cohort had 98.1% male surgeons with a mean age of 53.55 ± 8.94 years and mean experience of 26.43 ± 9.21 years. Younger age (p < 0.001), shorter years of experience (p < 0.001), and arthroplasty fellowship training (p < 0.001) were associated with more positive ratings. Reviewer anonymity, observed in 30.93% of all reviews, tended to correlate with more negative ratings (p < 0.001). Overall, 86.93% of patient remarks were positive, and only 74.81% of remarks centered on physician attributes. The five leading components of patient satisfaction were perceptions of physician competence (34.81%, p < 0.001), bedside manner (23.83%, p = 0.002), and communication (16.17%, p = 0.94); interactions with physician extenders (14.75%, p < 0.001); and wait time (2.73%, p < 0.001). Conclusion: While most ratings of hip and knee arthroplasty surgeons were positive, more than a quarter of reviews were either not directly related to the individual surgeons or were submitted anonymously. Caution is advised regarding overreliance on patient experience surveys as predictors of physician performance.

Ayurvedic medicine for the treatment of chronic rhinosinusitis: a systematic review of randomized and non-randomized trials.

OBJECTIVES: This article provides a comprehensive systematic review and qualitative analysis of the current research investigating Ayurveda chronic rhinosinusitis (CRS) treatment. CONTENT: PRISMA guidelines for systematic reviews was followed and our search utilized MEDLINE, Embase, Ayush Portal, and Cochrane Library databases. Articles published prior to March 2022, 10 or more patients that investigated Ayurveda as a treatment for CRS in humans were included. This resulted in thirteen articles meeting inclusion criteria. Ayurvedic treatments included herbal medications for oral consumption, nasal instillation, and steam inhalation used alone or in combination. All studies concluded that Ayurvedic therapy led to improvements in subjective CRS symptoms and objective radiographic and hematologic criteria. However, all 13 studies had a significant risk of bias due to study design and statistical methods utilized. SUMMARY: Ayurvedic therapy may be a useful CRS treatment for some patients and overall appears to be well tolerated. However, definitive recommendation for when Ayurvedic treatments would be beneficial in the treatment of CRS remains not possible. OUTLOOK: Given the overall positive effects shown in the current published evidence and growing interest in complementary and integrative therapies, Ayurvedic treatments for CRS deserve further investigation in the form of well-designed controlled trials.

Metal-Organic Framework-Based Fiber Optic Sensor for Chromium(VI) Detection.

This study demonstrates a novel fiber optic sensing strategy for selective adsorption and rapid detection of Cr(VI) ions by exploiting a suitable metal-organic framework matrix and the characteristic spectral absorption of Cr(VI) at 395 nm wavelength, respectively. U-bent fiber optic sensor (U-FOS) probes that exhibit remarkably high evanescent wave-based absorbance sensitivity were employed to efficiently detect the Cr(VI) ions that are adsorbed to a stable zeolitic imidazolate framework (ZIF-67) matrix immobilized on the probe surface. A facile technique was developed for the fabrication of ZIF-67-coated U-FOS probes (FOS/ZIF-67) involving an in situ deposition process followed by heat treatment. Selectivity of the FOS/ZIF-67 probes to Cr(VI) was confirmed by optical absorption spectral investigations with 14 other heavy metals and interfering ions. The sensor performance was evaluated with a compact light-emitting diode-photodetector-based setup. FOS/ZIF-67 probes demonstrate an ability to detect Cr(VI) ions with a limit of detection of 1 ppb and a wide linear dynamic range from 0.005 to 100 ppm within a short response time of 5 to 10 min. These sensors show good recovery rates with real water samples and a shelf-life of at least 4 weeks under ambient conditions, thereby demonstrating their viability for real-world application.

Peak performance and cardiometabolic responses of modern US army soldiers during heavy, fatiguing vest-borne load carriage.

INTRODUCTION: Physiological limits imposed by vest-borne loads must be defined for optimal performance monitoring of the modern dismounted warfighter. PURPOSE: To evaluate how weighted vests affect locomotion economy and relative cardiometabolic strain during military load carriage while identifying key physiological predictors of exhaustion limits. METHODS: Fifteen US Army soldiers (4 women, 11 men; age, 26 ± 8 years; height, 173 ± 10 cm; body mass (BM), 79 ± 16 kg) performed four incremental walking tests with different vest loads (0, 22, 44, or 66% BM). We examined the effects of vest-borne loading on peak walking speed, the physiological costs of transport, and relative work intensity. We then sought to determine which of the cardiometabolic indicators (oxygen uptake, heart rate, respiration rate) was most predictive of task failure. RESULTS: Peak walking speed significantly decreased with successively heavier vest loads (p < 0.01). Physiological costs per kilometer walked were significantly higher with added vest loads for each measure (p < 0.05). Relative oxygen uptake and heart rate were significantly higher during the loaded trials than the 0% BM trial (p < 0.01) yet not different from one another (p > 0.07). Conversely, respiration rate was significantly higher with the heavier load in every comparison (p < 0.01). Probability modeling revealed heart rate as the best predictor of task failure (marginal R2, 0.587, conditional R2, 0.791). CONCLUSION: Heavy vest-borne loads cause exceptional losses in performance capabilities and increased physiological strain during walking. Heart rate provides a useful non-invasive indicator of relative intensity and task failure during military load carriage.

Extracellular Vesicles as Drug Targets and Delivery Vehicles for Cancer Therapy.

Extracellular vesicles (EVs) are particles that are released from cells into the extracellular space both under pathological and normal conditions. It is now well established that cancer cells secrete more EVs compared to non-cancerous cells and that, captivatingly, several proteins that are involved in EV biogenesis and secretion are upregulated in various tumours. Recent studies have revealed that EVs facilitate the interaction between cancer cells and their microenvironment and play a substantial role in the growth of tumours. As EVs are involved in several aspects of cancer progression including angiogenesis, organotropism, pre-metastatic niche formation, fostering of metastasis, and chemoresistance, inhibiting the release of EVs from cancer and the surrounding tumour microenvironment cells has been proposed as an ideal strategy to treat cancer and associated paraneoplastic syndromes. Lately, EVs have shown immense benefits in preclinical settings as a novel drug delivery vehicle. This review provides a brief overview of the role of EVs in various hallmarks of cancer, focusing on (i) strategies to treat cancer by therapeutically targeting the release of tumour-derived EVs and (ii) EVs as valuable drug delivery vehicles. Furthermore, we also outline the drawbacks of the existing anti-cancer treatments and the future prospective of EV-based therapeutics.

Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: A Case Report.

Hypertriglyceridemia-induced acute pancreatitis is a rare and serious condition that places both the mother and the fetus at severe risk for morbidity and mortality. The goal of this case report is to describe the management of a pregnant patient with severely elevated triglycerides in the setting of acute pancreatitis. A 28-year-old female G2P1001 at 29 weeks of gestational age presented with epigastric abdominal pain. A computed tomography scan of the abdomen and pelvis with contrast demonstrated acute interstitial edematous pancreatitis. A lipid panel was performed, revealing a serum triglyceride level of 3,949 mg/dL. Insulin and maternal bowel rest reduced her serum triglyceride levels; however, additional medical therapy including fibrate and statin drugs were initiated to achieve goal levels of triglycerides and improve patient symptoms. The patient ultimately recovered and remained on treatment until delivery. Initial management addresses acute pancreatitis and involves fluid resuscitation, pain control, and bowel rest. Triglyceride-lowering drug therapies are rarely used during pregnancy due to the potential for fetal teratogenicity; however, given the severity of hypertriglyceridemia fenofibrate and atorvastatin were prescribed. Additional medical treatment included insulin, omega-3, and ethyl eicosapentaenoic acid.

Diffuse Reflectance Spectroscopy for The Assessment of Steatosis in Liver Phantom and Liver Donors - A Pilot Study.

This paper reports the application of a low-cost diagnostic modality for fat analysis in a liver phantom as well as human liver donors. The device works on the principle of diffuse reflectance spectroscopy, which absorbs and/or scatters depending upon the molecules that compose a tissue. Here, we describe the development of liver phantom of varying fat concentration using saturated fat mimicking liver steatosis. Followed by a pilot study in the human liver donor setting. Later, handheld device based on Infrared-LED and Photodetector for real-time time assessment of live donor liver and fat assessment. Clinical Relevance- This device can be used in the development of an accurate and non-invasive for quantification of liver fat in the deceased donor selection process. It has an error margin of 10% in the quantification of fat which is comparable to a standard biopsy technique.

Pep2Graph: A standalone tool to analyse proteolytic cleavages by proteases from gel-based mass spectrometry data.

Proteases are enzymes that regulate substrates via proteolytic activation and coordinate essential cellular functions including DNA replication, DNA transcription, cell proliferation, differentiation, migration and apoptosis. However, techniques to identify proteolytic events in a high-throughput manner is limited. PROtein TOpography and Migration Analysis Platform (PROTOMAP) is a technique that relies on mass spectrometry-based proteomics to globally identify the shifts in the in-gel migration of proteins and their corresponding fragments that are obtained by proteolysis. However, user-friendly software tool to analyse the proteomic data to identify proteolytic events is needed. Here, we report Pep2Graph, a user-friendly standalone tool that integrates peptide sequence information from in-gel proteomics and presents the data as two-dimensional peptographs with in-gel migration, sequence coverage and MS/MS spectra counts. Pep2Graph (http://www.mathivananlab.org/Pep2Graph) allows users to utilize in-gel proteomics data to study proteolytic events that may play a significant role in normal physiology and pathology.

Inferior Survival Is Associated With Socioeconomic Deprivation in Hepatocellular Carcinoma.

INTRODUCTION: Pernicious health disparities have been reported in patients with hepatocellular carcinoma (HCC). Few tools exist to screen patients in order to facilitate educational and outreach initiatives. We hypothesize that neighborhood-level socioeconomic metrics such as the Area Deprivation Index (ADI) can predict inferior outcomes in patients with early-stage HCC. METHODS: A single institution's retrospective review of patients with Surveillance, Epidemiology, and End Results Stage I HCC between 2000 and 2020 was conducted. Univariate and multivariate models were constructed to identify clinical and socioeconomic variables correlated with treatment-specific survival. Kaplan-Meier analysis was performed to compare survival differences between cohorts. RESULTS: A total of 558 patients were included in this study with newly diagnosed Surveillance, Epidemiology, and End Results Stage I HCC. Multivariate models demonstrated native model of end-stage liver disease, largest tumor size, insurance type, the distance to our transplant center, and the ADI score, a validated metric for a patient's socioeconomic status, are independent risk factors for worse overall survival (all P-values < 0.05). Concerningly, despite similar maximal tumor size, number of tumors, and native model of end-stage liver disease scores, patients from high ADI neighborhoods are 20% less likely to receive surgical treatment, especially liver transplantation. CONCLUSIONS: The ADI is a useful tool for identifying patients at the time of presentation who are at risk for inferior treatment for early stage HCC, and the ADI should be incorporated as a social vital sign.