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Geant4-DNA modeling of nanodosimetric quantities in the jet counter for alpha particles.

Phys Med Biol 2021 Oct 27. Epub 2021 Oct 27.

Biomedical Physics Division, University of Warsaw Faculty of Physics, Pasteura 5, Warszawa, 00-681, POLAND.

The purpose of this work was to validate the calculation accuracy of nanodosimetric quantities in Geant4-DNA track structure simulation code. We implemented the Jet Counter (JC) nanodosimeter geometry in the simulation platform and quantified the impact of the Geant4-DNA physics models and JC detector performance on the ionization cluster size distributions (ICSD). ICSD parameters characterize the quality of radiation field and are supposed to be correlated to the complexity of the initial DNA damage in nanoscale and eventually the response of biological systems to radiation. Read More

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October 2021

Genetic factors controlling nTiO2 nanoparticles stress tolerance in barley (Hordeum vulgare) during seed germination and seedling development.

Funct Plant Biol 2021 Oct 28. Epub 2021 Oct 28.

Titanium dioxide nanoparticle (nTiO2) is one of the most produced nanoparticles worldwide. Its mechanism on crop development and performance is unclear as it is hard to predict their toxicity or benefit. Therefore, understanding the genetics of crop development under nTiO2 is a prerequisite for their applications in agriculture and crop improvement. Read More

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October 2021

Biomimic Binding Affinity Gradients Triggered GSH-Response of Core-shell Nanoparticles for Cascade Chemo/Chemodynamic Therapy.

Adv Healthc Mater 2021 Oct 27:e2101634. Epub 2021 Oct 27.

Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Engineering Research Center of Hierarchical NanomaterialsSchool of Materials Science and Engineering, East China University of Science & Technology, Shanghai, 200237, China.

In eukaryotes and prokaryotes, some copper transportations driven by gradient copper-binding affinities exhibit typical glutathione (GSH)-responsive features. Inspired by these delicate endogenous processes, we herein design a biomimic copper-ion mediated GSH-responsive nanomedicine based on the gradient copper-binding strengths between polydopamine species and GSH. The nanomedicine is constructed as core/shell structure with copper-polydopamine (Cu-PDA) coordinated shell and micellar core encapsulating chemotherapeutic drug of β-lapachone (β-lapa). Read More

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October 2021

Non-cultured epidermal cells suspended in either platelet-rich plasma or ringer lactate for stable vitiligo: A prospective comparative study.

J Cosmet Dermatol 2021 Oct 27. Epub 2021 Oct 27.

Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background: Noncultured epidermal cell suspension (NCES) transplantation is a commonly used surgical treatment for resistant stable vitiligo. The combination of platelet-rich plasma (PRP) with different therapeutic modalities for vitiligo yielded higher repigmentation response, probably due to platelet-derived growth factors.

Aim: To evaluate the efficacy of PRP-suspended NCES compared to NCES suspended in Ringer's lactate (RL) solution in the treatment of stable vitiligo. Read More

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October 2021

Cytoreductive nephrectomy and exposure to sunitinib - a post-hoc analysis of the SURTIME trial.

BJU Int 2021 Oct 27. Epub 2021 Oct 27.

Royal Free London NHS Foundation Trust and UCL Division of Surgery and Interventional Science, London.

Objective: To analyze if exposure to sunitinib in the SURTIME trial which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy is associated with the overall survival (OS) benefit observed in the deferred CN arm.

Subjects And Methods: A post-hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate (ORR) by RECIST 1. Read More

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October 2021

High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance.

Int J Cancer 2021 Oct 27. Epub 2021 Oct 27.

Clinical Cooperation Unit, Translational Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400.000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analyzed. Read More

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October 2021

Resound Trial: A phase 2 study of regorafenib in patients with thymoma (type B2-B3) and thymic carcinoma previously treated with chemotherapy.

Cancer 2021 Oct 27. Epub 2021 Oct 27.

Department of Oncology, IRCCS, Humanitas Research Hospital, Milan, Italy.

Background: Angiogenesis has an important role in thymic epithelial tumors (TETs). Regorafenib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor β (PDGFR-β), and fibroblast growth factor receptors (FGFRs). This study explored the activity of regorafenib as monotherapy in patients with advanced or recurrent B2-B3 thymoma (T) and thymic carcinoma (TC) previously treated with platinum-containing chemotherapy. Read More

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October 2021

Experiments and Application of Reclamation of High-Mineralized Mine Wastewater for Confecting Grouting Slurry.

An Acad Bras Cienc 2021 25;94(1):e20190057. Epub 2021 Oct 25.

Liupanshui Normal University, School of Mining & Civil Engineering, Liupanshui, 553000, Guizhou Province, China.

Owing to the high mineralization and high treatment cost, Ordovician limestone water is often regarded as a mine wastewater. In order to make rational use of mine water with high mineralization and turn waste into treasure. In this work, the natural water quality of Ordovician mine water in the Weibei coalfield had been tested, and the suspended matter and trace elements of Ordovician mine water in the selected deep detained area had been further tested. Read More

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October 2021

Interactive effects of light, CO2 and temperature on growth and resource partitioning by the mixotrophic dinoflagellate, Karlodinium veneficum.

PLoS One 2021 27;16(10):e0259161. Epub 2021 Oct 27.

College of Earth, Ocean, and Environment, University of Delaware, Lewes, Delaware, United States of America.

There is little information on the impacts of climate change on resource partitioning for mixotrophic phytoplankton. Here, we investigated the hypothesis that light interacts with temperature and CO2 to affect changes in growth and cellular carbon and nitrogen content of the mixotrophic dinoflagellate, Karlodinium veneficum, with increasing cellular carbon and nitrogen content under low light conditions and increased growth under high light conditions. Using a multifactorial design, the interactive effects of light, temperature and CO2 were investigated on K. Read More

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October 2021

Validation of a spatial agent-based model for Taenia solium transmission ("CystiAgent") against a large prospective trial of control strategies in northern Peru.

PLoS Negl Trop Dis 2021 Oct 27;15(10):e0009885. Epub 2021 Oct 27.

School of Public Health, Oregon Health & Science University and Portland State University, Portland, Oregon, United States of America.

Background: The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. Read More

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October 2021

NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction.

Cancer Biol Ther 2021 Oct 27:1-11. Epub 2021 Oct 27.

Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, USA.

Nop2/Sun RNA methyltransferase (NSUN6) is an RNA 5-methyl cytosine (5mC) transferase with little information known of its function in cancer and response to cancer therapy. Here, we show that NSUN6 methylates both large and small RNA in glioblastoma and controls glioblastoma response to temozolomide with or without influence of the MGMT promoter status, with high NSUN6 expression conferring survival benefit to glioblastoma patients and in other cancers. Mechanistically, our results show that NSUN6 controls response to TMZ therapy via 5mC-mediated regulation of NELFB and RPS6BK2. Read More

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October 2021

miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition.

Am J Physiol Cell Physiol 2021 Oct 27. Epub 2021 Oct 27.

Nutrition, Exercise Physiology and Sarcopenia Laboratory; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States.

Our laboratory has discovered that dysregulation in microRNA (miRNA) that target anabolic signaling between younger and older adults is a potential molecular mechanism resulting in age-associated decreases in skeletal muscle mass and function (sarcopenia). Whether differences in miRNA expression profiles account for inter-individual variability in exercise adaptation in older adults is unclear. Understanding paradoxical responses to anabolic stimulation and identifying the mechanisms for this inconsistency in mobility-limited older adults may provide new targets for the treatment of sarcopenia. Read More

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October 2021

Tumor-infiltrating lymphocytes predict improved overall survival after post-mastectomy radiotherapy: a study of the randomized DBCG82bc cohort.

Acta Oncol 2021 Oct 27:1-10. Epub 2021 Oct 27.

Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.

Background: The predictive value of tumor-infiltrating lymphocytes (TILs) on the benefit from radiotherapy (RT) remains unclear. Our aim was to investigate the association between TILs and post-mastectomy RT (PMRT) regarding the risk of recurrence and survival in a randomized cohort.

Material And Methods: Stromal TILs were histologically estimated in 1011 tumors from high-risk breast cancer (BC) patients from the DBCG82bc trial. Read More

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October 2021

Systematic Analyses of a Chemokine Family-Based Risk Model Predicting Clinical Outcome and Immunotherapy Response in Lung Adenocarcinoma.

Cell Transplant 2021 Jan-Dec;30:9636897211055046

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Chemokines exhibited complicated functions in antitumor immunity, with their expression profile and clinical importance of lung adenocarcinoma (LUAD) patients remaining largely undetermined. This study aimed to explore the expression patterns of chemokine family in LUAD and construct a predictive chemokine family-based signature. A total of 497 samples were downloaded from the Cancer Genome Atlas (TCGA) data portal as the training set, and the combination of 4 representative Gene Expression Omnibus (GEO) datasets, including GSE30219, GSE50081, GSE37745, and GSE31210, were utilized as the validation set. Read More

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October 2021

Methicillin-Resistant Proteome Response to Antibiotic Stress Provides Insights for New Therapeutic Strategies.

OMICS 2021 Oct 27. Epub 2021 Oct 27.

Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.

Antimicrobial resistance is a global threat, with methicillin-resistant (MRSA) being one of the most representative drug-resistant pathogens. MRSA spread is increasing due to its ability to establish new reservoirs. To this end, the clonal complex (CC)-130 is an emerging genetic lineage, generally regarded as animal adapted and carrying the gene, and sporadically found in humans. Read More

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October 2021

Comparison of mineral oil, insecticidal and biopesticide spraying regimes for reducing spread of three potato virus Y (PVY) strains in potato crops.

Plant Dis 2021 Oct 27. Epub 2021 Oct 27.

Agricultural Certification Services, 1030 Lincoln Road, Fredericton, Fredericton, New Brunswick, Canada, E3B 8B7;

In-field management of potato virus Y (PVY) faces challenges by changing availability and environmental acceptability of chemical agents to control aphid vectors of the virus, and by proliferation of PVY strains with different symptomology and rates of spread. Over 2018-2020, foliar spray treatments were compared in field experiments in New Brunswick, Canada, to measure effectiveness at reducing spread of PVYO, PVYN:O and PVYNTN strains. Mineral oil, insecticide, combined oil and insecticide spray and a biopesticide (i. Read More

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October 2021

Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction.

J Med Chem 2021 Oct 27. Epub 2021 Oct 27.

Astex Pharmaceuticals, 436 Cambridge Science Park, Cambridge CB4 0QA, U.K.

The NRF2-mediated cytoprotective response is central to cellular homoeostasis, and there is increasing interest in developing small-molecule activators of this pathway as therapeutics for diseases involving chronic oxidative stress. The protein KEAP1, which regulates NRF2, is a key point for pharmacological intervention, and we recently described the use of fragment-based drug discovery to develop a tool compound that directly disrupts the protein-protein interaction between NRF2 and KEAP1. We now present the identification of a second, chemically distinct series of KEAP1 inhibitors, which provided an alternative chemotype for lead optimization. Read More

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October 2021

Highly Stable Red-Emissive Ratiometric Probe for Monitoring β-Galactosidase Activity Using Fluorescence Microscopy and Flow Cytometry.

Anal Chem 2021 Oct 27. Epub 2021 Oct 27.

Department of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 16499, Korea.

β-Galactosidase (β-gal), well known as a useful reporter enzyme, is a potent biomarker for various diseases such as colorectal and ovarian cancers. We have developed a highly stable red-emissive ratiometric fluorescent probe () for quantitatively monitoring the β-gal enzyme activity in live cells and tissues. This ratiometric probe showed a fast emission color change (620-662 nm) in response to β-gal selectively, which was accompanied by high enzyme reaction efficacy, cell-staining ability, and outstanding stability with minimized cytotoxicity. Read More

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October 2021

Microenvironment-Responsive Prodrug-Induced Pyroptosis Boosts Cancer Immunotherapy.

Adv Sci (Weinh) 2021 Oct 27:e2101840. Epub 2021 Oct 27.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.

The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage-associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor-specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Read More

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October 2021

Citrus heat shock transcription factor CitHsfA7-mediated citric acid degradation in response to heat stress.

Plant Cell Environ 2021 Oct 27. Epub 2021 Oct 27.

College of Agriculture & Biotechnology, Zhejiang University, Zijingang Campus, Hangzhou, China.

Heat stress is a major abiotic stress for plants which can generate a range of biochemical and genetic responses. In "Ponkan" mandarin fruit, Hot Air Treatment (HAT) accelerates the degradation of citric acid. However, the transcriptional regulatory mechanisms of citrate degradation in response to HAT remain to be elucidated. Read More

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October 2021

Joint modeling and simulation of M-protein dynamics and progression-free survival for alternative isatuximab dosing with pomalidomide/dexamethasone.

Br J Clin Pharmacol 2021 Oct 27. Epub 2021 Oct 27.

Data and Data Science, Sanofi, France.

Aims: Addition of isatuximab to pomalidomide/dexamethasone (Pd) significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). We aimed to characterize the relationship between serum M-protein kinetics and PFS in the Phase 3 ICARIA-MM trial (NCT02990338), and to evaluate an alternative dosing regimen of isatuximab by simulation.

Methods: Data from the ICARIA-MM trial comparing isatuximab 10 mg/kg weekly for 4 weeks then every 2 weeks (QW-Q2W) in combination with Pd versus Pd in 256 evaluable RRMM patients were used. Read More

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October 2021

Physiological mechanisms of unexplained (functional) gastrointestinal disorders.

J Physiol 2021 Oct 27. Epub 2021 Oct 27.

School of Biomedical Sciences & Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia.

Functional gastrointestinal disorders (FGIDs) encompass a range of complex conditions with similar clinical characteristics and no overt pathology. Recent recognition of sub-clinical pathologies in FGIDs, in conjunction with physiological and biochemical abnormalities including increased intestinal permeability, microbial profile alterations, differences in metabolites and extra-intestinal manifestations of disease call into question the designation of these conditions as 'functional'. This is despite significant heterogeneity in both symptom profile and specifics of reported physiological abnormalities hampering efforts to determine defined mechanisms that drive onset and chronicity of symptoms. Read More

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October 2021

Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real-world data (KCSG LU20-11).

Cancer 2021 Oct 27. Epub 2021 Oct 27.

Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non-small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration.

Methods: This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020. Read More

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October 2021

Photodynamic disinfection and its role in controlling infectious diseases.

Photochem Photobiol Sci 2021 Oct 27. Epub 2021 Oct 27.

Chemistry Department, University of Coimbra, 3004-535, Coimbra, Portugal.

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Read More

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October 2021

Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1β in the Lung Tissue and Blood Serum of Mice with Experimental Influenza.

Bull Exp Biol Med 2021 Oct 27. Epub 2021 Oct 27.

I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1β levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 μg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. Read More

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October 2021

Outcomes of esophagectomy for patients with esophageal squamous cell carcinoma accompanied by recurrent laryngeal nerve palsy at diagnosis.

Esophagus 2021 Oct 27. Epub 2021 Oct 27.

Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.

Background: Hoarseness is one of the classical symptoms in patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC), and it results from recurrent laryngeal nerve palsy, which is caused by nodal metastasis along the recurrent laryngeal nerve or by main tumors. We reviewed the short-term and long-term results of esophagectomy for patients with locally advanced ESCC and hoarseness at diagnosis.

Patients: Patients who initially presented with hoarseness from recurrent laryngeal nerve palsy between 2009 and 2018 and underwent esophagectomy for thoracic ESCC were eligible for this study. Read More

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October 2021

Paradoxical manifestations during tuberculous meningitis treatment among HIV-negative patients: a retrospective descriptive study and literature review.

Neurol Sci 2021 Oct 27. Epub 2021 Oct 27.

Department of Neurology and Psychiatry, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Col. Sección XVI Belisario Domínguez, 14080, Tlalpan, Mexico City, Mexico.

Background: Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids.

Methods: Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. Read More

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October 2021

Choroidal involvement in non-infectious posterior scleritis.

J Ophthalmic Inflamm Infect 2021 Oct 27;11(1):41. Epub 2021 Oct 27.

Moorfields Eye Hospital, National Health Service Foundation Trust, 162 City Rd, Old Street, London, EC1V 2PD, UK.

Purpose: To provide a comprehensive overview of choroidal involvement in non-infectious posterior scleritis; including different imaging modalities and their clinical usefulness.

Methods: Narrative review.

Results: Posterior scleritis is an uncommon yet potentially sight-threatening inflammation of the sclera. Read More

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October 2021

Anogenital lichen sclerosus et atrophicus lesions in a case series of cancer patients on immunotherapy.

Cancer Immunol Immunother 2021 Oct 27. Epub 2021 Oct 27.

Skin Cancer Unit, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Lichenoid reactions are one of the most frequently observed toxicities with anticancer agents and, recently, a rapid emergence of immunotherapies in oncology has hastened the need to better characterize their unique toxicity profiles, particularly for less common skin toxicities, including anogenital lichen sclerosus et atrophicus (LSA). This case series describes four patients with advanced cancer (one melanoma, two lung cancers, and one kidney tumor) developing LSA lesions while receiving an immunotherapy. Medical records from 2017 to 2020 were retrospectively reviewed. Read More

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October 2021

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

Eur J Nutr 2021 Oct 27. Epub 2021 Oct 27.

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark.

Context And Purpose: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D.

Methods: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Read More

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October 2021