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Stress Fracture of the Femoral Shaft in Paget's Disease of Bone: A Case Report.

J Bone Metab 2021 May 31;28(2):171-178. Epub 2021 May 31.

Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Paget's disease of bone (PDB) is a progressive bone disorder characterized by increased osteoclast-mediated bone resorption and abnormal bone formation. Incomplete atypical femoral fracture, appearing radiographically as a stress fracture at the lateral aspect of the femur, is an uncommon low-trauma fracture frequently seen in association with long-term bisphosphonate therapy. We describe the case of a 61-year-old female patient with PDB who developed a stress fracture at the lateral femoral cortex after 5 doses of intravenous bisphosphonate. Read More

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Differentiation of Brain Tumor Microvasculature From Normal Vessels Using Optical Coherence Angiography.

Lasers Surg Med 2021 Jun 15. Epub 2021 Jun 15.

Department of Biomedical Engineering, The University of Texas Austin, Austin, Texas, 78712, USA.

Background And Objectives: Despite rapid advances and discoveries in medical imaging, monitoring therapeutic efficacy for malignant gliomas and monitoring tumor vasculature remains problematic. The purpose of this study is to utilize optical coherence angiography for vasculature characterization inside and surrounding brain tumors in a murine xenograft brain tumor model. Features included in our analysis include fractional blood volume, vessel tortuosity, diameter, orientation, and directionality. Read More

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Is Lupus Anticoagulant a Significant Feature of COVID-19? A Critical Appraisal of the Literature.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

The term "lupus anticoagulant (LA)" identifies a form of antiphospholipid antibodies (aPLs) causing prolongation of clotting tests in a phospholipid concentration-dependent manner. LA is one of the laboratory criteria identified in patients with antiphospholipid (antibody) syndrome (APS). The presence of LA in patients with APS represents a significant risk factor for both thrombosis and pregnancy morbidity. Read More

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Contemporary Clinical Use of Aspirin: Mechanisms of Action, Current Concepts, Unresolved Questions, and Future Perspectives.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.

The ability of aspirin to inhibit platelet aggregation has positioned this agent within the most frequently used drugs worldwide. The aim of this article is to review the contemporary clinical use of aspirin and also to discuss unresolved issues not yet translated into clinical practice. Results from several clinical trials have led to strong guideline recommendations for aspirin use in the acute management and secondary prevention of cardiovascular disease. Read More

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MrgprdCre lineage neurons mediate optogenetic allodynia through an emergent polysynaptic circuit.

Pain 2021 Jul;162(7):2120-2131

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States.

Abstract: Most cutaneous C fibers, including both peptidergic and nonpeptidergic subtypes, are presumed to be nociceptors and respond to noxious input in a graded manner. However, mechanically sensitive, nonpeptidergic C fibers also respond to mechanical input in the innocuous range, so the degree to which they contribute to nociception remains unclear. To address this gap, we investigated the function of nonpeptidergic afferents using the MrgprdCre allele. Read More

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Methyltransferase-like 3 contributes to inflammatory pain by targeting TET1 in YTHDF2-dependent manner.

Pain 2021 Jul;162(7):1960-1976

Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China.

Abstract: The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation. Although RNA m6A is enriched in mammalian neurons, its regulatory function in nociceptive information processing remains elusive. Here, we reported that Complete Freund's Adjuvant (CFA)-induced inflammatory pain significantly decreased global m6A level and m6A writer Mettl3 in the spinal cord. Read More

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Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review.

Urol Int 2021 Jun 15:1-6. Epub 2021 Jun 15.

First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. Read More

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Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury.

Gerontology 2021 Jun 15:1-9. Epub 2021 Jun 15.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Introduction: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI).

Methods: Wild-type (WT) mice and IDO knockout (IDO-/-) mice were divided into the sham group and acute kidney injury (AKI) group. Read More

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Zebrafish Minichromosome Maintenance Protein 5 Gene Regulates the Development and Migration of Facial Motor Neurons via Fibroblast Growth Factor Signaling.

Dev Neurosci 2021 Jun 15:1-11. Epub 2021 Jun 15.

Department of Histology and Embryology, Department of Pathology, Development and Regeneration Key Lab of Sichuan Province, Chengdu Medical College, Chengdu, China.

Minichromosome maintenance protein 5 (MCM5), a member of the microchromosomal maintenance protein family, plays an important role in the initiation and extension of DNA replication. However, its role in neural development in zebrafish remains unclear. Here, we used morpholino (MO) and CRISPR/Cas9 to knock down mcm5 and investigated the developmental features of facial motor neurons (FMNs) in the hindbrain of zebrafish. Read More

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Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

Fetal Diagn Ther 2021 Jun 15:1-9. Epub 2021 Jun 15.

Center for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial.

Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7. Read More

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Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation.

Eur J Cancer 2021 Jun 12;153:27-39. Epub 2021 Jun 12.

Department of Medical Microbiology, University Medical Centre Groningen, The University of Groningen, Groningen, the Netherlands.

Background: Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them. Read More

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Alteration of brain structural connectivity in progression of Parkinson's disease: A connectome-wide network analysis.

Neuroimage Clin 2021 Jun 6;31:102715. Epub 2021 Jun 6.

Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disease, Beijing, China. Electronic address:

Pinpointing the brain dysconnectivity in idiopathic rapid eye movement sleep behaviour disorder (iRBD) can facilitate preventing the conversion of Parkinson's disease (PD) from prodromal phase. Recent neuroimage investigations reported disruptive brain white matter connectivity in both iRBD and PD, respectively. However, the intrinsic process of the human brain structural network evolving from iRBD to PD still remains largely unknown. Read More

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Reward mechanism of depressive episodes in bipolar disorder: Enhanced theta power in feedback-related negativity.

J Affect Disord 2021 May 29;292:217-222. Epub 2021 May 29.

Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address:

Introduction: This study aimed to explore the reward-related neural mechanism in patients with depressive mood in bipolar disorder (BD) using event-related potentials. It remains unknown whether or not different neurobiological markers underlying depression symptoms in BD depression and major depression disorder (MDD).

Methods: 24 patients with BD depression and 20 healthy controls were included. Read More

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Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing.

Biomaterials 2021 Jun 7;275:120954. Epub 2021 Jun 7.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea. Electronic address:

Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties. Read More

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Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models.

Biomed Pharmacother 2021 Jun 12;141:111815. Epub 2021 Jun 12.

Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.

Breast cancer remains one of the leading cancers among women. Cancer stem cells (CSCs) are tumor-initiating cells which drive progression, metastasis, and reoccurrence of the disease. CSCs are resistant to conventional chemo- and radio-therapies and their ability to survive such treatment enables tumor reestablishment. Read More

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Why is the mesencephalic nucleus of the trigeminal nerve situated inside the brain?

Authors:
Kohji Sato

Med Hypotheses 2021 Jun 5;153:110626. Epub 2021 Jun 5.

Department of Organ & Tissue Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address:

Primary sensory neurons are usually situated in ganglia outside the brain, while the mesencephalic nucleus of the trigeminal nerve (Me5) is situated inside the brain. However, it remains unknown why only Me5 situated inside the brain is. The neurons of Me5 are the cell bodies of primary afferent fibers concerned with the muscles of mastication and periodontal receptors of both maxillary and mandibular teeth. Read More

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Early multidrug treatment of SARS-CoV-2 infection (COVID-19) and reduced mortality among nursing home (or outpatient/ambulatory) residents.

Med Hypotheses 2021 Jun 5;153:110622. Epub 2021 Jun 5.

Concerned Ontario Doctors, Toronto, ON, Canada. Electronic address:

The outbreak of COVID-19 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world with tremendous morbidity and mortality in the elderly. In-hospital treatment addresses the multifaceted nature of the illness including initial viral replication, cytokine storm, and endothelial injury with thrombosis. We identified nine reports of early treatment outcomes in COVID-19 nursing home patients. Read More

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Diagnosing Strongylus vulgaris in pooled fecal samples.

Vet Parasitol 2021 Jun 8;296:109494. Epub 2021 Jun 8.

Texas Tech University, School of Veterinary Medicine, Amarillo, TX, USA.

Strongylus vulgaris is the most pathogenic intestinal helminth parasite infecting horses. The migrating larvae in the mesenteric blood vessels can cause non-strangulating intestinal infarctions, which have a guarded prognosis for survival. Infections are typically diagnosed by coproculture, but a PCR test is available in some countries. Read More

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Facile and rapid detection of SARS-CoV-2 antibody based on a noncompetitive fluorescence polarization immunoassay in human serum samples.

Biosens Bioelectron 2021 Jun 5;190:113414. Epub 2021 Jun 5.

Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, 060-8628, Japan; Innovative Research Centre for Preventive Medical Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan; Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan. Electronic address:

Antibody detection methods for viral infections have received broad attention due to the COVID-19 pandemic. In addition, there remains an ever-increasing need to quantitatively evaluate the immune response to develop vaccines and treatments for COVID-19. Here, we report an analytical method for the rapid and quantitative detection of SARS-CoV-2 antibody in human serum by fluorescence polarization immunoassay (FPIA). Read More

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Influence of current and previous smoking on current phenotype in Parkinson's disease.

J Neurol Sci 2021 Jun 8;427:117534. Epub 2021 Jun 8.

Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan; Epilepsy Center, Hiroshima University Hospital, Hiroshima, Japan.

Introduction: Although an inverse correlation between smoking and Parkinson's disease (PD) has been reported, research into the effect of smoking on current clinical progression remains limited for PD patients. Elucidation of a specific PD population who would benefit from smoking is challenging.

Methods: We evaluated 110 consecutive PD patients (mean age; 71. Read More

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Annual Costs Incurred in Managing Adverse Drug Reactions Attributable to Fixed-Dose Combination Highly Active Antiretroviral Therapy in an Outpatient Antiretroviral Clinic in Gauteng: A Budget Impact Analysis.

Value Health Reg Issues 2021 Jun 12;25:142-149. Epub 2021 Jun 12.

School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

Objectives: This study aimed to identify adverse drug reactions (ADRs) attributable to tenofovir (TDF)- and zidovudine (AZT)-based fixed-dose combinations of highly active antiretroviral (ARV) therapy and subsequently determine the annual costs incurred in managing these ADRs and the budget implications in an outpatient ARV clinic in Mamelodi, Pretoria.

Methods: This retrospective cohort study reviewed deidentified clinical data for ADRs. Medical charts of human immunodeficiency virus-positive patients, who were receiving either TDF- or AZT-based fixed-dose combinations of ARV therapy, were analyzed. Read More

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Silicon influenced ripening metabolism and improved fruit quality traits in apples.

Plant Physiol Biochem 2021 Jun 8;166:270-277. Epub 2021 Jun 8.

Institute of Soil and Water Resources, ELGO-DEMETER, Thessaloniki, 57001, Greece. Electronic address:

The benefits of silicon against abiotic stress in different annual plant species have been described in many studies, however the regulation of ripening of fruit tree crops by silicon remains largely uncharacterized. Therefore, the present study aimed to explore the impact of foliar silicon application in the apple (cv. 'Fuji') fruit ripening traits along with the effect of silicon in the nutrient and metabolic changes in the fully expanded leaves, annual shoots, fruit outer pericarp (peel) and fruit mesocarp (skin) tissues. Read More

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Micronutrient deficiencies in critical illness.

Clin Nutr 2021 May 11;40(6):3780-3786. Epub 2021 May 11.

Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, the Netherlands; Division of Human Nutrition and Health, Wageningen University & Research, HELIX (Building 124), Stippeneng 4, 6708 WE, Wageningen, the Netherlands. Electronic address:

Background & Aims: Low micronutrient levels in critical illness have been reported in multiple studies. Because of the antioxidant properties of various micronutrients, micronutrient deficiency may augment oxidative stress in critical illness. However, it remains unclear whether micronutrient concentrations in ICU patients are different from those in healthy age-matched controls. Read More

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The role of systemic inflammation in the association between serum 25-hydroxyvitamin D and type 2 diabetes mellitus.

Clin Nutr 2021 Apr 27;40(6):3661-3667. Epub 2021 Apr 27.

Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background & Aims: The association between serum 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes mellitus (T2DM) remains inconclusive. Moreover, whether inflammatory biomarkers are involved in this association has not been explored. This study aims to investigate serum 25(OH)D in relation to T2DM in a Chinese population and provide clues for the inflammatory mechanism whereby serum 25(OH)D deficiency increases T2DM risk. Read More

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Getting back to the grass roots: harnessing specialized metabolites for improved crop stress resilience.

Curr Opin Biotechnol 2021 Jun 11;70:174-186. Epub 2021 Jun 11.

Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA, USA. Electronic address:

Roots remain an understudied site of complex and important biological interactions mediating plant productivity. In grain and bioenergy crops, grass root specialized metabolites (GRSM) are central to key interactions, yet our basic knowledge of the chemical language remains fragmentary. Continued improvements in plant genome assembly and metabolomics are enabling large-scale advances in the discovery of specialized metabolic pathways as a means of regulating root-biotic interactions. Read More

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UCP1 expression in the mouse adrenal gland is not upregulated by thermogenic conditions.

Biochem Biophys Res Commun 2021 Jun 12;566:184-189. Epub 2021 Jun 12.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan. Electronic address:

The uncoupling protein 1 (UCP1) gene is known to be highly expressed in brown adipose tissue (BAT) that functions in thermogenesis. It has been shown that UCP1 mRNA is localized to the mouse adrenal gland, but its significance remains elusive. To explore how UCP1 expression in the adrenal gland is regulated, we generated a reporter knock-in mouse in which the GFP gene was inserted into the UCP1 locus using CRISPR-Cas9 system. Read More

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Human spatial navigation: Neural representations of spatial scales and reference frames obtained from an ALE meta-analysis.

Neuroimage 2021 Jun 12:118264. Epub 2021 Jun 12.

Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education; School of Psychology, Center for Studies of Psychological Application, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, Guangdong, 510631, China. Electronic address:

Humans use different spatial reference frames (allocentric or egocentric) to navigate successfully toward their destination in different spatial scale spaces (environmental or vista). However, it remains unclear how the brain represents different spatial scales and different spatial reference frames. Thus, we conducted an activation likelihood estimation (ALE) meta-analysis of 47 fMRI articles involving human spatial navigation. Read More

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Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer.

Mol Cell Proteomics 2021 Jun 12:100115. Epub 2021 Jun 12.

Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics and Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China. Electronic address:

The occurrence and prevalence of colorectal cancer (CRC) is closely associated with age. More than 90% of CRC patients are diagnosed after 50 years old. However, CRC incidence of young individuals has been increasing since 1990s as overall CRC frequency declining. Read More

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Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury.

Mol Cell Proteomics 2021 Jun 12:100096. Epub 2021 Jun 12.

Division of Neurosurgery, University of British Columbia, Vancouver, BC, Canada.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Read More

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Combining gene expression signature with clinical features for survival stratification of gastric cancer.

Genomics 2021 Jun 12;113(4):2683-2694. Epub 2021 Jun 12.

Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China; Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, P.R. China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, P.R. China; Department of Molecular Genetics, University of Toronto, Toronto, ONM5S 1A8, Canada. Electronic address:

The AJCC staging system is considered as the golden standard in clinical practice. However, it remains some pitfalls in assessing the prognosis of gastric cancer (GC) patients with similar clinicopathological characteristics. We aim to develop a new clinic and genetic risk score (CGRS) to improve the prognosis prediction of GC patients. Read More

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