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A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma.

Neoplasia 2021 Jul 28;23(9):939-950. Epub 2021 Jul 28.

Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; Institute for Biomedical Sciences Molecular Pathophysiology, Iwate Medical University, Yahaba, Iwate, Japan; Division of Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Iwate, Japan. Electronic address:

An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Read More

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Generating dHAND homozygous knockout human embryonic stem cell line (WAe009-A-59) by episomal vector-based CRISPR/Cas9 system.

Stem Cell Res 2021 Jul 20;55:102471. Epub 2021 Jul 20.

Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

In order to determine the function of dHAND in a specific subset of cardiomyocyte progenitor cells responsible for the heart and its function in the cellular mechanism of Hand2-/- mouse ventricular hypoplasia, we established an allelic knockout model of dHAND in human embryonic stem cells (hESCs-H9) by an episomal vector-based CRISPR/Cas9 system. This dHAND KO hESC line maintained normal karyotype and typical primed pluripotent human stem cell morphology, and maintained pluripotency, could differentiate into all three germ layers in vivo. Read More

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Activation of κ-opioid receptor inhibits inflammatory response induced by sodium palmitate in human umbilical vein endothelial cells.

Cytokine 2021 Jul 28;146:155659. Epub 2021 Jul 28.

Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Air Force Medical University, No. 169 West Changle Road, Xi'an 710032, Shaanxi Province, People's Republic of China; School of Life Sciences, Northwest University, No.1 North Taibai Road, Xi'an 710069, Shaanxi Province, People's Republic of China. Electronic address:

Objectives: The current study aims to investigate the effect of κ-opioid receptor (κ-OR) activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) inflammatory response and elucidate the underlying mechanisms.

Methods: A hyperlipidemic cell model was established and treated with κ-OR agonist (U50,488H), and antagonist (norbinaltorphimine, nor-BNI), or inhibitors targeting PI3K, Akt or eNOS (LY294002, MK2206-2HCl or L-NAME, respectively). Furthermore, the expression levels of NLRP3, caspase-1, p-Akt, Akt, p-eNOS, and total eNOS were evaluated. Read More

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Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial.

Brain Stimul 2021 Jul 28. Epub 2021 Jul 28.

Epworth Centre for Innovation in Mental Health, Epworth Healthcare and Department of Psychiatry, Monash University, Camberwell, Victoria, Australia.

Introduction: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. Read More

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Quantitative proteomic and metabolomic profiling reveals altered mitochondrial metabolism and folate biosynthesis pathways in the aging Drosophila eye.

Mol Cell Proteomics 2021 Jul 28:100127. Epub 2021 Jul 28.

Department of Biochemistry; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

Aging is associated with increased risk of ocular disease, suggesting that age-associated molecular changes in the eye increase its vulnerability to damage. Although there are common pathways involved in aging at an organismal level, different tissues and cell types exhibit specific changes in gene expression with advanced age. Drosophila melanogaster is an established model system for studying aging and neurodegenerative disease, that also provides a valuable model for studying age-associated ocular disease. Read More

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Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs.

Nanomedicine 2021 Jul 28:102450. Epub 2021 Jul 28.

Department of Surgery, National Cheng Kung University, Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Epigenetic inhibitors have shown anticancer effects. Combination chemotherapy with epigenetic inhibitors has shown high effectiveness in gastric cancer clinical trials, but severe side effect and local progression are the causes of treatment failure. Therefore, we sought to develop an acidity-sensitive drug delivery system to release drugs locally to diminish unfavorable outcome of gastric cancer. Read More

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Anti-atopic effect of Viola yedoensis ethanol extract against 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction.

J Ethnopharmacol 2021 Jul 28:114474. Epub 2021 Jul 28.

National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: Viola yedoensis Makiho (VY, Violaceae) is a well-known medicinal herb in Chinese medicine, which is traditionally used to treat inflammation-related disorders, including allergic skin reactions. Although studies have uncovered its anti-inflammatory effects and corresponding bioactive constituents, the exact mechanism of action is still unclear in treating allergic skin reactions.

Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe pruritus, dry, edema and inflamed skin. Read More

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Vorinostat targets UBE2C to reverse epithelial-mesenchymal transition and control cervical cancer growth through the ubiquitination pathway.

Eur J Pharmacol 2021 Jul 28:174399. Epub 2021 Jul 28.

Foshan Maternal and Child Health Research Institute, South Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, 528000, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Vorinostat is a histone deacetylase inhibitor (HDACi) that was demonstrated in our previous study to inhibit the proliferation, migration, and invasion of cervical cancer cells by regulating the PI3K/Akt signaling pathway. However, the molecular mechanism of vorinostat in cervical cancer treatment remains to be further elucidated. A nude mouse xenograft model was established to analyze the antitumor effect of vorinostat in vivo. Read More

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Definitive evidence for Club cells as progenitors for mutant Kras/Trp53-deficient lung cancer.

Int J Cancer 2021 Jul 31. Epub 2021 Jul 31.

Institute of Translational Immunology (TIM), University Medical Center, Johannes Gutenberg-University, Mainz, Germany.

Accumulating evidence suggests that both the nature of oncogenic lesions and the cell-of-origin can strongly influence cancer histopathology, tumor aggressiveness and response to therapy. However and although oncogenic Kras expression and loss of Trp53 tumor suppressor gene function have been demonstrated to initiate murine lung adenocarcinomas (LUADs) in alveolar type II (AT2) cells, clear evidence that Club cells, representing the second major subset of lung epithelial cells, can also act as cells-of-origin for LUAD is lacking. Equally, the exact anatomic location of Club cells that are susceptible to Kras transformation and the resulting tumor histotype remain to be established. Read More

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Dynamics of Decision-Making in Medical Pluralism: A Systematic Review of Conceptual Models.

Altern Ther Health Med 2021 Jul 31. Epub 2021 Jul 31.

Purpose: Plurality of treatment choice is often observed, as in many instances people choose to use both conventional and complementary and alternative medicine (CAM). The existing models of healthcare utilization or healthcare behavior do not specifically address this medical pluralism. Hence, to understand an individual's pluralistic choice of treatment, major studies describing this have been systematically reviewed in this study in order to extract the principal factors driving such choice. Read More

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Addressing Gender Inequities: Creation of a Multi-Institutional Consortium of Women Physicians in Academic Emergency Medicine.

Acad Emerg Med 2021 Jul 31. Epub 2021 Jul 31.

Department of Emergency Medicine, Harvard Medical School, USA.

Gender inequity is pervasive in medicine, including emergency medicine (EM), and is well documented in workforce representation, leadership, financial compensation, and resource allocation. The reasons for gender inequities in medicine, including academic EM, are multi-factorial and include disadvantageous institutional parental, family, and promotion policies, workplace environment and culture, implicit biases, and a paucity of women physician leader role models, mentors, and sponsors. To address some of the challenges of gender inequities and career advancement for women in academic EM, we established an innovative, peer-driven, multi-institutional consortium of women EM faculty employed at 4 distinct hospitals affiliated with one medical school. Read More

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From occupational to existential class: How to analyze class structure in hybrid societies (The case of Serbia).

Br J Sociol 2021 Jul 31. Epub 2021 Jul 31.

School of Social Sciences and Humanities, Loughborough University, Loughborough, UK.

In this article, we propose a model to analyze the class structure of hybrid post-socialist societies in South-East Europe (SEE), using the case of Serbia. We argue that, in such hybrid societies, social inequalities are generated by several mechanisms of similar strength: exploitative market mechanisms (based on economic capital) and different types of social closure mechanisms (based on political and social capital). Their influences are intertwined and cannot be analytically isolated or reduced to a common foundation. Read More

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A clinical variable-based nomogram could predict the survival for advanced NSCLC patients receiving second-line atezolizumab.

Cancer Med 2021 Jul 31. Epub 2021 Jul 31.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Objective: A nomogram model based on clinical variables was conducted to predict the survival in patients with non-small cell lung cancer (NSCLC) receiving second-line atezolizumab.

Methods: Four hundred and twenty-four patients with NSCLC receiving atezolizumab from OAK study were regarded as the training cohort. Next, a nomogram model based on clinical variables in the training cohort was established to predict the survival of patients receiving atezolizumab. Read More

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Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes in a "Prickle1-mTORC2" Dependent Manner.

Mol Nutr Food Res 2021 Jul 30:e2100367. Epub 2021 Jul 30.

Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.

Scope: To investigate the effect and detailed mechanisms of morin, an anti-arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast-like synoviocytes (FLS).

Methods And Results: The migration of FLS collected from arthritis rats and MH7A cells was induced by platelet-derived growth factor, and an arthritis model in rats was established by Freund's complete adjuvant. The results showed that morin remarkably restrained FLS migration but slightly affected FLS apoptosis and proliferation. Read More

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Implication of immune cell signature of tumor microenvironment in diffuse large B-cell lymphoma.

Hematol Oncol 2021 Jul 31. Epub 2021 Jul 31.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with complex tumor microenvironment (TME) alterations. However, immune cell signatures of TME and their prognostic value remain unclear in DLBCL. We aimed to identify high-risk DLBCL with specific immune cell signatures in TME. Read More

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Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease.

Eur J Neurol 2021 Jul 31. Epub 2021 Jul 31.

The University of Edinburgh, Centre for Discovery Brain Sciences, UK Dementia Research Institute, Edinburgh.

Background: Synapse degeneration in Alzheimer's disease (AD) correlates strongly with cognitive decline. There is well-established excitatory synapse loss in Alzheimer's disease with known contributions of pathological amyloid beta (Aβ) to excitatory synapse dysfunction and loss. Despite clear changes in circuit excitability in AD and model systems, relatively little is known about pathology in inhibitory synapses. Read More

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Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae based on mass spectrometry.

J Clin Lab Anal 2021 Jul 31:e23915. Epub 2021 Jul 31.

College of Medical Technology, Xuzhou Medical University, Xuzhou, China.

Background: Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive. Read More

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Optimizing the Differentiation of Cardiomyocytes from Human Induced Pluripotent-Derived Stem Cells.

Methods Mol Biol 2021 ;2319:51-60

Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Cardiovascular disease is a worldwide health issue that affects millions of lives every year, and thus, researchers are in need of high-throughput model systems with which to investigate mechanisms of disease and to develop and test potential therapies. The use of human-derived induced pluripotent stem cells (iPSCs) differentiated into cardiomyocytes aims to address this need. While cardiac differentiation protocols have been established previously in iPSCs, optimization of cardiac differentiation remains crucial to obtaining high quality cardiomyocytes for future experimental analyses. Read More

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January 2021

[email protected]: A New Manualized Intervention to Improve Job Tenure in Psychosis Based on Scoping Review and Logic Model.

J Occup Rehabil 2021 Jul 30. Epub 2021 Jul 30.

Centre de Recherche de L'Institut Universitaire en Santé Mentale de Montréal, 7331 Hochelaga, Montreal, QC, H1N 3V2, Canada.

Introduction A significant proportion of people experiencing psychosis are unemployed, despite a strong desire to work. Current supported employment programs appear effective in helping them obtain employment, yet job tenure remains an arduous challenge. The objective of this study was to review the literature and model the results to inform the development of a new manualized group psychosocial intervention-'[email protected]'-aimed specifically at improving job tenure in psychosis. Read More

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miR-130-CYLD Axis Is Involved in the Necroptosis and Inflammation Induced by Selenium Deficiency in Pig Cerebellum.

Biol Trace Elem Res 2021 Jul 30. Epub 2021 Jul 30.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Selenium (Se) is an essential trace element in creatures which deficiency can cause necroptosis and inflammation of multiple tissues. MicroRNAs (miRNAs) have been identified to participate multiple biological processes by regulating the expression of target genes. In the present study, the Se-deficient pig cerebellar model was established and conducted by light microscopy, qRT-PCR, and Western blot. Read More

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Optimal Control Strategies and Sensitivity Analysis of an HIV/AIDS-Resistant Model with Behavior Change.

Acta Biotheor 2021 Jul 30. Epub 2021 Jul 30.

School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Durban, South Africa.

Despite several research on HIV/AIDS, it is still incumbent to investigate more effective control measures to mitigate its infection level. Therefore, we introduce an HIV/AIDS-resistant model with behavior change and study its basic properties. In order to determine the most sensitive parameters that are responsible for disease transmission with respect to the basic reproduction number and those responsible for disease prevalence with respect to the endemic equilibrium, the sensitivity analysis was established and it was confirmed that the influx rate of people into the infected population and total abstinence from all risk practices and endemic areas are some of the most sensitive parameters for disease spread and disease eradication, respectively. Read More

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Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss.

Oncogene 2021 Jul 30. Epub 2021 Jul 30.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant melanomas harboring PTEN loss. MEK or PI3K inhibitors show little activity when given alone due to cross-talk between the pathways, and high toxicity when given together. Read More

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Longitudinal analysis of human pancreatic adenocarcinoma development reveals transient gene expression signatures.

Mol Cancer Res 2021 Jul 30. Epub 2021 Jul 30.

Cell and Developmental Biology, University of Pennsylvania.

Previous transcriptome studies of human pancreatic ductal adenocarcinoma (PDAC) compare non-cancerous pancreatic intraepithelial neoplasias (PanINs) with late-stage PDAC obtained from different patients, thus have limited ability to discern network dynamics that contribute to the disease progression. We demonstrated previously that the 10-22 cell line, an induced pluripotent stem cell (iPS)-like line reprogrammed from late-stage human PDAC cells, recapitulated the progression from PanNs to PDAC upon transplantation into NOD/LtSz-scid/IL2R-gammanull mice. Herein, we investigated the transition from precursor to PDAC using the isogenic model. Read More

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Characterisation of seizure induction methods in .

eNeuro 2021 Jul 30. Epub 2021 Jul 30.

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK

Epilepsy is one of the most common neurological disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. Read More

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Preoperative and perioperative intervention reduces the risk of recurrence of endometriosis in mice caused by either incomplete excision or spillage and dissemination.

Reprod Biomed Online 2021 Apr 29. Epub 2021 Apr 29.

Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China. Electronic address:

Research Question: Can preoperative or perioperative intervention reduce the risk of recurrence of endometriosis caused by either incomplete excision or spillage and dissemination?

Design: A mouse model of endometriosis recurrence caused by spillage and dissemination was first established using 24 female Balb/c mice. The spillage and dissemination model was used to test the efficacy of preoperative use of ketorolac, perioperative use of aprepitant and combined use of propranolol and andrographolide in a prospective, randomized mouse experiment involving 75 mice. The efficacy of these preoperative and perioperative interventions in a mouse recurrence model caused by incomplete excision was also tested using 72 mice. Read More

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The status quo of early burn wound excision: Insights from the German burn registry.

Burns 2021 Jul 10. Epub 2021 Jul 10.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery, University of Heidelberg, Germany. Electronic address:

Background: There is a common, well-known and established recommendation to excise burn wounds within 24-72 h in order to mitigate the systemic inflammatory and immunomodulatory response, shorten length of hospitalization through early grafting and optimize patient survival. Despite this apparent consensus, surprisingly few systematic studies have evaluated the actual adherence to this practice and its implications on patient outcomes. In this registry study, we sought to objectify the current status of early burn wound excision, its influencing factors and impact on patient outcomes for all German burn centers. Read More

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A Comparative Analysis of Nutritional Assessment Using Global Leadership Initiative on Malnutrition Versus Subjective Global Assessment and Malnutrition Inflammation Score in Maintenance Hemodialysis Patients.

J Ren Nutr 2021 Jul 27. Epub 2021 Jul 27.

Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institute, Stockholm, Sweden.

Objective: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS).

Design And Methods: We investigated 2 cohorts: MHD (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m) and MHD (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m), followed for all-cause mortality for median 40 and 17 months, respectively. Read More

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Evaluation of techniques used to assess skeletal muscle quantity in patients with cirrhosis.

Clin Nutr ESPEN 2021 Aug 11;44:287-296. Epub 2021 Jun 11.

School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Translational Research Institute, Brisbane, Australia.

Introduction: Loss of skeletal muscle mass is a well-recognised complication of cirrhosis. Bedside methods to assess skeletal muscle mass including anthropometrics and bioelectrical impedance analysis (BIA) are negatively impacted by fluid overload in advanced cirrhosis and thus there is a need to identify alternatives. There is a paucity of data on the accuracy of commonly used radiological methods such as dual X-ray absorptiometry (DXA) to assess appendicular lean mass (ALM), and computed tomography (CT) skeletal muscle area in patients with cirrhosis. Read More

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Establishment of particulate matter-induced lung injury model in mouse.

Lab Anim Res 2021 Jul 30;37(1):20. Epub 2021 Jul 30.

College of Pharmacy, Gachon University, Incheon, 21936, South Korea.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. Read More

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Molecular features and vulnerabilities of recurrent chordomas.

J Exp Clin Cancer Res 2021 Jul 30;40(1):244. Epub 2021 Jul 30.

Institute of Pathology, University Hospital Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

Background: Tumor recurrence is one of the major challenges in clinical management of chordoma. Despite R0-resection, approximately 50% of chordomas recur within ten years after initial surgery. The underlying molecular processes are poorly understood resulting in the lack of associated therapeutic options. Read More

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