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Nous presentons une methode d'estimation de la moyenne mensuelle du rayonnement global regu au sol par jour sous un ciel clair et moyen. Elle permet de valider des modeles meteorologiques cites dans la litterature. Ces derniers utilisent des relations qui permettent de transformer les donnees mesurees d'insolation en flux global d'irradiation solaire. Ceci est en parfaite adequation avec la nature du reseau de mesures algerien, caracterise par une faible densite de stations radiometriques, mais qui fournit des donnees de duree d'ensoleillement. Notre etude prend en charge deux modeles : le modele d'Angstrom et le modele de Coppolino. Les resultats obtenus montrent que ce dernier modele permet de predire la moyenne mensuelle du rayonnement journalier avec une bonne fiabilite. PACS Nos : 02.00.B, 05.00 We present a method to estimate the monthly average of the daily global radiation received at ground level under clear and average sky conditions, which helps validate meteorological models cited in the literature. These models use relations to transform the measured insolation data into the flux of global solar radiation. This suits the nature of the Algerian measurement network, characterized by a lack of radiometric stations, but which provide sunshine duration data. Our study deals with two models: Angstrom's model and Coppolino's model. The results we obtained show that the latter model is useful to predict the monthly mean of the daily global solar radiation with good reliability. [Journal translation], 1. Introduction En Algerie, malgre les efforts accomplis par l'Office national de la meteorologie pour developper dans son reseau (56 stations, dont 35 qui sont regulierement fonctionnelles) des bancs de [...]

Lymphocyte-transendothelial cell migration is a complex event, and although much is known about the receptor-ligand interactions involved, little is understood about the intracellular events which accompany these interactions, or their regulation by inflammatory mediators. In this study we have shown that activation oft lymphocytes increased the proportion of cells migrating across monolayers of cultured retinal microvascular endothelial cells by both lymphocyte function associated antigen-1 (LFA-1)-dependent and LFA-1-independent mechanisms. In preliminary experiments, it was found that activation of T cells with mitogens such as concanavalin (Con A) increased significantly T-cell migration across the endothelial monolayers. In contrast, activation of the endothelial monolayer with intefferon-γ (IFN-γ) (96 hr) had no effect on transendothelial migration. Investigation of adhesion molecule requirements for transendothelial migration indicated that LFA-1 was necessary (P < 0.02) but that intracellular adhesion molecule-1 did not appear to be involved. Investigation of the role of prostaglandins in transendothelial migration revealed that, while prostaglandin E2 (PGE2) did not affect adhesion molecule expression on endothelial cells or T cells, treatment of either cell significantly blocked transendothelial migration (P < 0.05). Pretreatment with PGE2 combined with LFA-1 blockade had an additive effect on inhibition of T-cell transendothelial migration, indicating that two independent mechanisms were operative. PGE2 also had a direct inhibitory effect on T-cell adhesion to the endothelium. These results highlight the importance of considering non-adhesion receptor-mediated mechanisms, perhaps involving cytoskeletal and/or motility, in the migration of T cells across endothelial monolayers. [ABSTRACT FROM AUTHOR]

Examines the effects of monoclonal antibodies to rat adhesion/accessory molecules on the binding of normal and concanavalin A-activated rat spleen lymphocytes to cultured unstimulated and interferon-gamma-stimulated endothelium and pigment epithelium. Data demonstrating that the system is important in lymphocyte trafficking into the eye only after lymphocyte activation.

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas., Competing Interests: Declaration of interests T.M.Y. is a co-founder, stockholder, and member of the board of directors of DESTROKE, Inc., an early stage start-up developing mobile technology for automated clinical stroke detection. J.L.J. has received consulting fees from Scorpion Therapeutics and Volastra Therapeutics. L.C.C. is a founder and member of the board of directors of Agios Pharmaceuticals and is a founder of Petra Pharmaceuticals. L.C.C. is an inventor on patents (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment. L.C.C. is a co-founder and shareholder in Faeth Therapeutics. P.W. is a statistical consultant for Sema4. M.G.C. receives research support from Merck, Orbus Therapeutics, and NeoimmuneTech Inc, and royalties from UpToDate., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC., Competing Interests: Declaration of interests A.I.N., F.Y., and D.A.P. receive royalties from the University of Michigan for the sale of MSFragger software licences to commercial entities. All licence transactions are managed by the University of Michigan Innovation Partnerships office and all proceeds are subject to university technology transfer policy. Related to this work a provisional patent has been filed by University of Michigan, where A.M.C., A.I.N., S.M.D., R. Mannan, R. Mehra, Y.Z., S.C., A.D., X.W., G.X.L., and Y.H. are named as inventors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Organophosphorus agents are easily absorbed via respiratory, gastrointestinal, and dermal routes, and inhibit the acetylcholine transferase enzyme (AChE), which is responsible for the majority of toxicity caused by organophosphates in the body. A comprehensive search was conducted across three prominent databases, namely Google Scholar, PubMed, and Science Direct, to identify relevant articles published. The search focused on the keywords "MgSO4" or "magnesium sulfate" in conjunction with "organophosphate" or "organophosphate poisoning." Inhibition of AChE results in the accumulation of acetylcholine (ACh) in synapses and stimulation of cholinergic receptors. Considering that several studies have shown the use of magnesium sulfate (MgSO4) in inhibiting the release of ACh in the central and peripheral sympathetic and parasympathetic synapses, this study was conducted to review the role of MgSO4 in the treatment of OP. The intravenous administration of MgSO4 exhibits favorable tolerability and clinical efficacy in alleviating cardiac toxicity associated with OP exposure.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated with immune response driven by acetylation, affected kinase specificity by crosstalk between acetylation and phosphorylation, and modified histone regulation. Overall, this resource highlights the rich biology governed by PTMs and exposes potential new therapeutic avenues., Competing Interests: Declaration of interests Y.G. is a consultant for Oriel Research Therapeutics. T.M.Y. is a co-founder, stockholder, and on the board of directors of DESTROKE, Inc., an early-stage start-up developing mobile technology for automated clinical stroke detection. J.L.J. has received consulting fees from Scorpion Therapeutics and Volastra Therapeutics. Y.E.M. is a consultant for ForseeGenomics and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, and MSIDetect. N.J.H. is a consultant for MorphoSys. F.A. is an inventor on a patent application related to SignatureAnalyzer-GPU and has been an employee of Illumina, Inc., since 8 November 2021. L.C.C. is a founder and member of the board of directors of Agios Pharmaceuticals and is a founder of Petra Pharmaceuticals. L.C.C. is an inventor on patents (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment. L.C.C. is a co-founder and shareholder in Faeth Therapeutics. G.G. receives research funds from IBM, Pharmacyclics, and Ultima Genomics, and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, MSIDetect, and MinimuMM-Seq. He is also a founder, consultant, and privately held equity in Scorpion Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities., Competing Interests: Declaration of interests M.J.B. has participated in advisory boards for the following companies: Clovis, Astra Zeneca, and GSK-Tesaro. A.N.H. is the Associate Editor of Clinical Chemistry and has a financial interest in the company Seattle Genetics. A.G.P. is the founder of Precision Assays, LLC. A.B.B. is employed by Synapse. S.Y. is an employee and shareholder of Sema4. B.J.W. has stock interests in Verastem and Exact Sciences., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The European Association of Endoscopic Surgery (EAES) is a surgical society who promotes the development and expansion of minimally invasive surgery to surgeons and surgical trainees. It does so through its activities in education, training, and research. The EAES research committee aims to promote the highest quality clinical research in endoscopic and minimally invasive surgery. They have provided grant funding since 2009 in education, surgery, and basic science. Despite the success and longevity of the scheme, the academic and non-academic impact of the research funding scheme has not been evaluated., Aims: The primary aim of this project is to assess the short, long term academic and real world impact of the EAES funding scheme. The secondary aims are to identify barriers and facilitators for achieving good impact., Methods: This will be a mixed qualitative and quantitative study. Semi-structured interviews will be performed with previous grant recipients. The questions for the interviews will be selected after a consensus is achieved amongst the members of the steering committee of this project. The responses will be transcribed and thematic analysis will be applied. The results of the thematic analysis will be used to populate a questionnaire which will be disseminated to grant recipients. This study is kindly funded by the EAES., Discussion: The first question this project is expected to answer is whether the EAES research funding scheme had a significant positive impact on research output, career progression but also non-academic output such as change in clinical guidelines, healthcare quality and cost-effectiveness improvement. This project however is also expected to identify facilitators and barriers to successful completion of projects and to achieving high impact. This will inform EAES and the rest of the surgical and academic communities as to how clinicians would like to be supported when conducting research. There should also be a positive and decisive change towards removing factors that hinder the timely and successful completion of projects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 McClean, Huo, Kwan, Long, Walshaw, Mesri, Francis, Arulampalam, Chetter and Yiasemidou.)

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis., (© 2023. The Author(s).)

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in PDAC for proteomic and genomic analyses., Methods: Three fresh frozen PDAC tumors and their tumor-matched normal adjacent tissues (NATs) were obtained from three sampling techniques using bulk, coring, and LMD; and analyzed by TMT-based quantitative proteomics. The protein profiles and characterizations of differentially expressed proteins in three sampling groups were determined. These three PDACs and samples of five additional PDACs obtained by the same three sampling techniques were also subjected to genomic analysis to characterize KRAS mutations., Results: The neoplastic cellularity of eight PDACs ranged from less than 10% to over 80% based on morphological review. Distinctive proteomic patterns and abundances of certain tumor-associated proteins were revealed when comparing the tumors and NATs by different sampling techniques. Coring and bulk tissues had comparable proteome profiles, while LMD samples had the most distinct proteome composition compared to bulk tissues. Further genomic analysis of bulk, cored, or LMD samples demonstrated that KRAS mutations were significantly enriched in LMD samples while coring was less effective in enriching for KRAS mutations when bulk tissues contained a relatively low neoplastic cellularity., Conclusions: In addition to bulk tissues, samples from LMD and coring techniques can be used for proteogenomic studies. The greatest enrichment of neoplastic cellularity is obtained with the LMD technique., (© 2022. The Author(s).)

Background: Incomplete data are often presented for determining the role of vitamin A supplement therapy for improving treatment outcomes in patients with COVID-19., Aims: We compared treatment effects between a group that received vitamin A added to the standard COVID-19 treatment and another group that received the standard drug treatment alone., Methods: Participants in this triple-blind controlled trial comprised 182 COVID-19 outpatients in Saveh City, Markazi Province, Islamic Republic of Iran, in 2020. Patients were randomly divided into experimental (n = 91) and control (n = 91) groups. Patients in the control group received the national standard treatment for COVID-19 (hydroxychloroquine), and those in the intervention group received 25 000 IU/d oral vitamin A for 10 days in addition to the standard treatment recommended by the national protocol. We evaluated the clinical symptoms, paraclinical criteria, and hospitalization status before and after 10 days of interventions., Results: The treatment groups did not differ significantly in clinical and paraclinical symptoms before the intervention. However, clinical symptoms such as fever, body ache, weakness and fatigue, paraclinical symptoms, white blood cell count, and C-reactive protein showed significantly greater decreases in the experimental group 10 days post-intervention compared with the standard treatment alone (P < 0.05)., Conclusion: Vitamin A supplementation demonstrated efficacy in improving some clinical and paraclinical symptoms in patients with COVID-19. Future studies should evaluate vitamin A supplementation with a larger sample size and compare different dosages, especially in hospitalized patients., (Copyright © World Health Organization (WHO) 2022. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Defunctioning stomas (ileostomy and colostomy) may be used prior to commencement of neoadjuvant therapy in patients with locally advanced colon or rectal cancer, in order to prevent clinical large bowel obstruction caused by radiotherapy associated oedema or progression of disease in patients who are not obstructed. However, the exact rate of clinical obstruction in patients undergoing neoadjuvant therapy who do not receive a defunctioning stoma is not known. Furthermore, it is not clear which factors predispose patients to developing clinical large bowel obstruction. Given that defunctioning stomas are associated with post operative and intra-operative risks, it is not currently possible to tailor defunctioning stomas to patients who have the greatest risk of developing obstruction. This systematic review which is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA), aims to define the role of defunctioning stomas in prevention of obstruction patients with locally advanced colon or rectal cancer while undergoing neoadjuvant therapy. Two researchers will perform the literature search which will include all published and "in process" articles published in the English language between 2002-2022 in the following databases: EMBASE (OVID), MEDLINE (EBSCO), CINHAL complete, Web of Science, Cochrane Central Registry of Controlled Trials, Clinical Trials Registry. The full text of the selected articles will be independently screened by two researchers against the inclusion criteria. Data will be extracted from each article regarding: study design, participants, type of intervention and outcomes. The effect size will be expressed in incidence rates and when appropriate in relative risk with 95% confidence intervals. If possible, we will perform a meta-analysis. Heterogeneity will be assessed using I2 statistics. We will pool the data extracted from the randomised controlled trials to perform a meta-analysis using the Review Manager 5 software (RevMan 5). The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system will be used to assess the certainty of the evidence., Competing Interests: The authors have declared that no competing interests exist.

Background: Nurses are in close contact with COVID-19 patients and due to the high risk of infection, they experience fear and anxiety that can result in burnout. This study aimed to review the studies on burnout among nurses during the COVID-19 epidemic., Materials and Methods: The study followed the guideline for Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). Using the keywords: "burnout," "nurse," and "COVID-19" and with the help of Boolean operators, "AND" and "OR" the online databases, namely PubMed, Scopus, Google Scholar, Web of Science, and Science Direct were searched. Articles published from the first of February 2020 to 30 October, 2020 were retrieved. After the quality appraisal, the required data were extracted and analyzed., Results: Out of 85 articles identified in the initial search, and after removing duplicates and those that did not have the required data, seven articles entered the analysis. Among these articles, four (57.14%) reported moderate burnout and three articles (42.86) reported high level of burnout among nurses during the COVID-19 pandemic., Conclusions: A majority of the studies reported that nurses experienced a moderate level of burnout during the COVID-19 pandemic. Given the prevalence of burnout in nurses and because nurses are the largest portion of the healthcare providers who are in close contact with patients infected by COVID-19, it is necessary for health care policymakers to adopt strategies for preventing or reducing burnout among nurses., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Education and Health Promotion.)

Background: There is no valid and reliable tool to measure COVID-19 healthcare stress felt by healthcare students. A scale was developed to assess COVID-19 stress in healthcare students and its psychometrics was examined., Methods: This is a two phases mixed-method study including a qualitative stage consisting of student interview and literature review to develop content of the tool. In the quantitative stage, the psychometrics of the scale was examined in 2020-2021., Results: The COVID-19 related healthcare student stress scale (CHSSS) featured five factors including fear of catching coronavirus, social constraints, changes in education, non-compliance of health protocols and worrying news and overload information, which totally explained 51.75% of the total variance., Conclusion: Validity and reliability of CHSSS with 17 items were supported to measure COVID-19 stress in healthcare students as a self-assessment tool. Researchers can utilize this tool to assess COVID-19 stress in healthcare students and introduce policies and intervention especially designed for healthcare students., (© 2022. The Author(s).)

Background: There are no reports on nationwide trends in subtotal cholecystectomy (STC) and cholecystostomy in England. We hypothesized that, as in the United States, a substantial increase in the utilization of these surgical procedures, over time, may be observed. We aimed to generate a reliable report on 4 of the most common gallbladder surgical procedures in England to allow cross-procedure comparisons and highlight significant changes in the management of benign gallbladder disease over time., Methods: We obtained data from NHS Digital and extracted population estimates from the Office of National Statistics. We examined the trends in the use of STC, cholecystostomy, cholecystolithotomy and total cholecystectomy (TC) between 2000 and 2019., Results: Of the 1,234,319 gallbladder surgeries performed, TC accounted for 96.8% (n = 1,194,786) and the other 3 surgeries for 3.2% (n = 39,533). The total number of gallbladder surgeries performed annually increased by 80.4% from 2000 to 2019. We detected increases in the counts of cholecystostomies by 723.1% (n = 290 in 2000 vs n = 2,387 in 2019) and STCs by 716.6% (n = 217 in 2000 vs n = 1,772 in 2019). Consequently, there was a decrease in the ratio of TC to STC (180:1 in 2000 vs 38:1 in 2019). A similar decrease was observed in the ratio of cholecystectomy to cholecystostomy (135:1 in 2000 vs 29:1 in 2019)., Conclusion: Increased utilization of STC and cholecystostomy was detected in England. These findings highlight the importance of regular monitoring of nationwide trends in gallbladder surgery and the associated clinical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Subtotal cholecystectomy is recognized as a rescue procedure performed in grossly suboptimal circumstances that would deem a total cholecystectomy too risky to execute. An earlier systematic review based on 30 studies published between 1985 and 2013 concluded that subtotal cholecystectomy had a morbidity rate comparable to that of total cholecystectomy. This systematic review appraises 17 clinical outcomes in patients undergoing subtotal cholecystectomy., Methods: The study protocol was registered with the International Prospective Register for Systematic Reviews (CRD42020172808). MEDLINE, Embase, Cochrane bibliographic databases, and Google Scholar were used to identify papers published between 1985 and June 2020. Data related to the surgical setting, approach, intervention on the hepatic wall of the gallbladder, type of completion of subtotal cholecystectomy, year of study, and study design were collected. Seventeen clinical outcomes were considered. Meta-analyses were performed using a random-effects model, and the effect size was presented as risk ratios with 95% confidence intervals., Results: From 1,017 records, 85 eligible studies were identified and included. These included 3,645 patients who underwent subtotal cholecystectomy. Laparoscopic (80.1%, n = 2,918) and reconstituting (74.6%, n = 2,719) approaches represented the majority of all subtotal cholecystectomy cases. Seven (0.2%) cases of injury to the bile duct were reported. Bile leak was reported in 506 (13.9%) patients. Reconstituting subtotal cholecystectomy was associated with a lower risk for 11 clinical outcomes. Open subtotal cholecystectomy was associated with an increased rate of 30-day mortality and wound infections., Conclusion: Subtotal cholecystectomy is associated with significant morbidity. Laparoscopic and reconstituting surgery may reduce the risks of some perioperative complications and long-term sequelae after subtotal cholecystectomy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets., Competing Interests: Declaration of interests R.H.H. has the potential of receiving royalty payments from Thrive Earlier Diagnosis for the GNAS invention in a relationship overseen by Johns Hopkins University. The remaining authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment., Competing Interests: Declaration of interests S.Y. is employed by Sema4. A.H.K. consults for Monteris Medical. P.W. is a statistical consultant for Sema4. M.G.C. receives research support from Orbus Therapeutics and NeoimmuneTech Inc, and royalties from UpToDate., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Herbal medicines, as a treatment method, have received a great deal of attention. The effects of two herbal medicines namely Zingiber officinale and Echinacea on alleviation of clinical symptoms and hospitalization rate of suspected COVID-19 outpatients were examined., Methods: A clinical trial with 100 suspected COVID-19 outpatients as participants was conducted. The participants were allocated randomly to two groups of 50 members. The intervention group received concurrent Zingiber officinale (Tablet Vomigone 500 mg II tds) and Echinacea (Tablet Rucoldup I tds) for seven days in addition to the standard treatment. The control group only received the standard treatment (Hydroxychloroquine). After seven days, alleviation of clinical symptoms and hospitalization rate were examined. In addition, 14 days after treatment, the hospitalization was assessed again by telephone follow up., Results: The two groups were identical in terms of basic characteristics. Improvement level as to coughing, dyspnea, and muscle pain was higher in the intervention group (p value <0.05). There was no significant difference between the two groups in terms of the other symptoms. In addition, the hospitalization rate in the intervention and control groups were 2 and 6% respectively, which are not significantly different (p value >0.05)., Conclusions: Taking into account the efficiency and trivial side-effects of Zingiber officinale and Echinacea, using them for alleviation and control of the clinical symptoms in COVID-19 outpatients is recommended., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

This study examined the trends and patterns of major trauma (MT) activities, causes, mortality and survival at the Aintree Major Trauma Centre (MTC), Liverpool, between 2011 and 2018. The number of trauma team activations (TTAs) rose sharply over time (n = 699 in 2013; n = 1522 in 2018). The proportion of TTAs that involved MT patients decreased from 75.1% in 2013 to 67.4% in 2018. The leading cause of MT was a fall from less than 2 m (36%). There has been a fivefold increase in the overall number of trauma procedures between 2011 and 2018. Orthopaedic surgeons have performed 80% of operations (n = 7732), followed by neurosurgeons, oral and maxillofacial surgeons, and general trauma surgeons. Both types of fall (> 2 m and < 2 m) and road traffic accidents were the three leading causes of death during the study period. The observed mortality rates exceeded that of expected rates in years 2012, 2014, 2016 and 2017. The all-cause observed to expected mortality ratio was 1.08 between 2012 and 2018. A change in care for MT patients was not directly associated with improved survival, although the marginally ascending trend line in survival rates between 2012 and 2018 reflects a gradual positive change.

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment., Competing Interests: Declaration of interests S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, and Seer and a scientific advisor to Pfizer and Biogen. The other authors have no conflicts of interest to declare. M.J.E. reports ownership and royalties associated with Bioclassifier LLC through sales by Nanostring LLC and Veracyte for the "Prosigna" breast cancer prognostic test. M.J.E. also reports ad hoc consulting for AstraZeneca, Foundation Medicine, G1 Therapeutics, Novartis, Sermonix, Abbvie, Lilly and Pfizer., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Cholecystectomy is the most frequently performed procedure in general surgery. The consent procedure for cholecystectomy needs to inform patients about the possibility of subtotal cholecystectomy (STC) as an alternative procedure used for "difficult gallbladders" as it is associated with increased postoperative morbidity. We sought to determine the quality of informed consent for patients who were scheduled for cholecystectomy but underwent STC, and evaluate whether patient or procedural factors influenced the information discussed in consenting. Materials and Methods: We classified 57 components of information necessary for a patient to give informed consent for cholecystectomy. We retrospectively reviewed the consent forms of patients scheduled for conventional cholecystecomy but instead undergoing STC between 2011 and 2017. Consent quality was measured as the percentage of components completed. Subgroup analyses were conducted to determine whether age, gender, American Society of Anesthesiologists grade, setting (elective/nonelective), operation mode (open/laparoscopic), or the responsible surgeon affected consent quality. Results: Across 174 patients, just 9 (5.2%) had been informed about the possibility of undergoing STC, whereas the overall quality of consent was 37.5%. Patient and setting-specific factors affected the completion of specific consent components. Patients were more likely to receive a patient information leaflet if they were female (relative risk [RR] 2.76; 95% confidence interval [CI] 1.09-7.00), <60 years (RR 3.32; 95% CI 1.39-7.90) or undergoing laparoscopic surgery (RR 8.04; 95% CI 2.50-25.88). Conclusion: The suboptimal quality of consent and multiple inconsistencies in the information disclosed to different patient cohorts emphasize the need for a more transparent and consistent consenting process.

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection., Competing Interests: Declaration of Interests E.E.S. serves as chief executive officer for Sema4 and has an equity interest in this company., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The current Coronavirus disease 2019 (COVID-19) pandemic has had a huge impact on emergency surgical services in the UK. The Royal College of Surgeons (RCS) published guidelines about COVID-19 pandemic in March, 2020 to aid decision making for the surgeons. These guidelines recommended that all patients requiring urgent surgery should have reverse transcriptase polymerase chain reaction (RT-PCR) and/or computed tomography (CT) thorax pre-operatively. However, it is currently unclear whether the use of CT thorax is a sensitive and specific diagnostic test. The objective of this study was to find out whether CT thorax is a reliable and accurate test in the diagnosis of COVID-19 compared to RT-PCR. This is particularly important in surgical patients where there is no time to wait for RT-PCR results. A prospective cohort study of patients presented with acute surgical emergencies at a University Teaching Hospital was conducted. Data was collected from March 23, to May 15, 2020, during the peak of the crisis in the UK. All adult patients presented with operable general surgical emergencies were considered eligible. Another group of patients, admitted with acute medical emergencies but with suspected COVID-19 infection, was used for comparison. Data was manually collected, and sensitivity, specificity and predictive value were calculated using the MedCalc statistical software version 19.2.6. Standard reporting for COVID-19 infection for CT chest based on guidelines from British Society of Thoracic Imaging (BSTI) and Radiological Society of North America (RSNA) was used. Patients who had their CT thorax reported as typical or classic of COVID 19 (high probability) were treated as infected cases with extra precautions in the wards and surgical theatres as suggested by health and safety executive (HSE). These patients had serial RT-PCR during their admissions or in the post-operative phase, if the first swab was negative. For the study, 259 patients were considered eligible for inclusion from both groups. Patients admitted for acute surgical emergencies were treated according to RCS guidelines and subjected to RT-PCR test and/or CT scan of the thorax. There were 207 patients with high clinical suspicion of COVID-19. Of those 207 patients, 77 patients had CT thorax with radiographic features consistent with COVID-19 pneumonia. However, only 40 patients had a positive RT-PCR result. CT thorax was normal in 130 patients, out of which 29 patients were found to have COVID-19 diagnosis after swab test. Sensitivity of CT scan to diagnose COVID-19 infection was found to be 58% (95% CI; 45.48% to 69.76%) whilst specificity was 73% (95% CI; 64.99% to 80.37%) with a negative predictive value of 77.69% (95% CI; 72.17% to 82.39%). CT scan was found to be a reliable tool in the diagnosis of COVID-19. With a negative predictive value of up to 82.4%, CT thorax can play an important role to help surgeons in their decision making for asymptomatic suspected cases of COVID-19. However, over-reliance on CT scan which also has a high false positive rate for diagnosis of COVID-19 infections can lead to overtreatment, overuse of resources and delays in decision-making process. Hence, results should be interpreted with caution and correlated with clinical presentation and swab test results., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Association of Surgeons of India 2020.)

The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy., Competing Interests: Declaration of Interests M.J.E reports ownership and royalties associated with Bioclassifier LLC through sales by Nanostring LLC and Veracyte for the “Prosigna” breast cancer prognostic test. He also reports ad hoc consulting for AstraZeneca, Foundation Medicine, G1 Therapeutics, Novartis, Sermonix, Abbvie, Lilly and Pfizer. B.Z. has received research funding from Bristol-Myers Squibb. S.A.C. is a scientific advisory board member of Kymera, PTM BioLabs, and Seer and ad hoc consultant to Pfizer and Biogen., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)