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Genome-wide Association and Meta-analysis of Age-at-Onset in Parkinson Disease: Evidence From COURAGE-PD Consortium.

Neurology 2022 May 26. Epub 2022 May 26.

Sorbonne Université (SU) Unité Mixte de Recherche (UMR) 1127, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Background And Objectives: Considerable heterogeneity exists in the literature concerning genetic determinants of the age of onset (AAO) of Parkinson's disease (PD), which could be attributed to lack of well-powered replication cohorts. The previous largest GWAS identified nd loci on chromosome (Chr) 4 with a significant influence on AAO of PD, these have not been independently replicated. The present study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Read More

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Emerging Concepts in Managing Malignancy in Kidney Transplant Patients.

Semin Nephrol 2022 Jan;42(1):63-75

Transplant Research Center, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Cancer remains a significant cause of morbidity and mortality in kidney transplant recipients, due to long-term immunosuppression. Salient issues to consider in decreasing the burden of malignancy among kidney transplant recipients include pretransplant recipient evaluation, post-transplant screening and monitoring, and optimal treatment strategies for the kidney transplant recipients with cancer. In this review, we address cancer incidence and outcomes, approaches to cancer screening and monitoring pretransplant and post-transplant, as well as treatment strategies, immunosuppressive management, and multidisciplinary approaches in the kidney transplant recipients with cancer. Read More

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January 2022

Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction.

J Am Coll Cardiol 2022 May;79(21):2097-2115

State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai, China. Electronic address:

Background: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.

Objectives: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI. Read More

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Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study.

Int J Gynecol Cancer 2022 May 26. Epub 2022 May 26.

Dipartimento Universitario Scienze della Vita e Sanità Pubblica - Sezione di Ginecologia ed Ostetricia - Università Cattolica del Sacro Cuore, Rome, Italy.

Objective: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes.

Methods: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. Read More

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Tumor-associated Tregs obstruct antitumor immunity by promoting T cell dysfunction and restricting clonal diversity in tumor-infiltrating CD8+ T cells.

J Immunother Cancer 2022 May;10(5)

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

Background: Accumulation of regulatory T cells (Treg) has been described to often correlate with poor prognosis in many solid tumors. How Treg presence impinges on limited functionality and clonal composition of tumor-associated CD8 +T cells has important implications for their therapeutic targeting in the tumor microenvironment. In the present study, we investigated how accumulation of Tregs contributes to T cell dysfunction and clonal constriction of tumor-infiltrating CD8 +T cells. Read More

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Spatial transcriptomics of macrophage infiltration in non-small cell lung cancer reveals determinants of sensitivity and resistance to anti-PD1/PD-L1 antibodies.

J Immunother Cancer 2022 May;10(5)

Department of Medecine, Institut Bergonié, Bordeaux, France

Background: Tumor-associated macrophages (TAMs) having immunosuppressive properties are one of the most abundant immune cells in the tumor microenvironment (TME). Preclinical studies have highlighted the potential role of TAMs in resistance to immune checkpoint blockers (ICBs). Here, we investigated the predictive value of TAM infiltration in patients with non-small cell lung cancer (NSCLC) treated with ICBs and characterized their transcriptomic profiles. Read More

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Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial.

J Immunother Cancer 2022 May;10(5)

Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity of immune checkpoint inhibitors in CUP is lacking. Therefore, we evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with CUP. Read More

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Constructing and Validating a Prognosis Predictive Nomogram for Cancer-Specific Survival in Rectal Cancer Patients Receiving Preoperative Radiotherapy.

J Invest Surg 2022 May 26:1-10. Epub 2022 May 26.

Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

A predictive tool is required to identify the cancer-specific survival in rectal cancer (RC) patients who have opted to receive preoperative radiotherapy. A database containing the data on RC patients' records of Surveillance, Epidemiology, and End Results (SEER) receiving surgery during 2000-2014 was selected. All patients received neoadjuvant radiotherapy (NR). Read More

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The Supportive Care Clinic: a novel model of embedded pediatric palliative oncology care.

J Pain Symptom Manage 2022 May 23. Epub 2022 May 23.

Aflac Cancer & Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Emory University. Atlanta, GA, USA.

Context: Pediatric palliative care (PPC) improves quality of life and end-of-life outcomes for children with cancer, but often occurs late in the disease course. The Supportive Care Clinic (SCC) was launched in 2017 to expand outpatient PPC access.

Objectives: To describe the inaugural four years (2017-2021) of an academic, consultative, embedded SCC within pediatric oncology. Read More

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"Calling the Spirit Back:" Spiritual Needs Among Great Plains American Indians.

J Pain Symptom Manage 2022 May 23. Epub 2022 May 23.

Massachusetts General Hospital, Division of Palliative Care and Geriatric Medicine, Boston, MA, USA.

Context: American Indians (AIs) are disproportionately affected by serious illness such as cancer. Colonization, cultural genocide, and trauma have adversely affected AIs' ability to attain health and well-being, and in many cases led to the loss of the right to practice traditional ceremonies and rituals. Still many AIs describe well-being as being rooted in spirituality. Read More

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The Applications of Plasma Cell-free DNA in Cancer Detection: Implications in the Management of Breast Cancer Patients.

Crit Rev Oncol Hematol 2022 May 23:103725. Epub 2022 May 23.

Department of Surgery, Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA; Samuel Oschin Comprehensive Cancer Institute and Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, West Hollywood, CA, 90048, USA.

Liquid biopsy probes DNA, RNA, and proteins in body fluids for cancer detection and is one of the most rapidly developing areas in oncology. Tumor-derived DNA (circulating tumor DNA, ctDNA) in the context of cell-free DNA (cfDNA) in blood has been the main target for its potential utilities in cancer detection. Liquid biopsy can report tumor burden in real-time without invasive interventions, and would be feasible for screening tumor types that lack standard-of-care screening approaches. Read More

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Vorinostat combined with Busulfan, Fludarabine, and Clofarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia: Long-term Study Outcomes.

Transplant Cell Ther 2022 May 23. Epub 2022 May 23.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address:

Background: Conditioning regimens play a major role in determining disease outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of intravenous (IV) busulfan (Bu) as part of the conditioning chemotherapy has been shown to be effective in controlling disease relapse. However, disease relapse remains a major cause of death following allo-HSCT. Read More

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Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

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Advances in Modular Control of CAR-T Therapy with Adapter-Mediated CARs.

Adv Drug Deliv Rev 2022 May 23:114358. Epub 2022 May 23.

Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27514, USA. Electronic address:

Protein engineering has contributed to successes in the field of T cell-based immunotherapy, including chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy has become a pillar of cancer immunotherapy, demonstrating clinical effectiveness against B cell malignancies by targeting the B cell antigen CD19. Current gene editing techniques have limited safety controls over CAR T cell activity, which presents a hurdle for control of CAR T cells in patients. Read More

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Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

CRUK & UCL Cancer Trials Centre, London, United Kingdom.

Background: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival.

Patients And Method: SCORAD is a randomised trial of 686 patients comparing a single dose of 8Gy radiotherapy with 20Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). Read More

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Machine learning to refine prognostic and predictive nodal burden thresholds for post-operative radiotherapy in completely resected stage III-N2 non-small cell lung cancer.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, United States. Electronic address:

Background: The role of post-operative radiotherapy (PORT) for completely resected N2 non-small-cell lung cancer (NSCLC) is controversial in light of recent randomized data. We sought to utilize machine learning to identify a subset of patients who may still benefit from PORT based on extent of nodal involvement.

Materials/methods: Patients with completely resected N2 NSCLC were identified in the National Cancer Database. Read More

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PROPHYLACTIC EFFECT OF NITRIC OXIDE DONORS ON RAT MODELS OF EGFR INHIBITORS-INDUCED CUTANEOUS TOXICITIES.

J Invest Dermatol 2022 May 23. Epub 2022 May 23.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China. Electronic address:

Epidermal growth factor receptor inhibitors (EGFRIs) have been established as first-line standard-of-care therapies for non-small cell lung cancer (NSCLC) but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. Here, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Read More

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IMPROVING DIAGNOSTIC ACCURACY AND APPROPRIATE INDICATIONS FOR SURGERY IN PANCREATIC CYSTIC NEOPLASMS: THE ROLE OF ENDOSCOPIC ULTRASOUND.

Gastrointest Endosc 2022 May 23. Epub 2022 May 23.

Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita Salute San Raffaele University, Milan, Italy.

Background And Aims: Pancreatic Cystic Neoplasms (PCNs) represent a difficult preoperative diagnosis despite imaging improvement. In this study, we compare preoperative and final pathological diagnosis in a large cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of Endoscopic Ultrasound (EUS).

Methods: A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Read More

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COVID-19 vaccine effectiveness in patients with cancer: remaining vulnerabilities and uncertainties.

Lancet Oncol 2022 May 18. Epub 2022 May 18.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. Electronic address:

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Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

Lancet Oncol 2022 May 18. Epub 2022 May 18.

Population Health Sciences, University of Bristol, Bristol, UK.

Background: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level.

Methods: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Read More

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Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study.

Lancet Gastroenterol Hepatol 2022 May 23. Epub 2022 May 23.

Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Unresectable solitary very early to early stage hepatocellular carcinoma is managed with ablation for curative intent. Radiation segmentectomy is a treatment option that delivers radioactive yttrium (Y)-bound microspheres transarterially to a segment of liver. The aim of this study was to assess the safety and efficacy of radiation segmentectomy in patients with unresectable hepatocellular carcinoma deemed unfavourable for ablation. Read More

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Heterogeneity of Drug Allergies and Reaction Lists in Two U.S. Healthcare Systems' Electronic Health Records.

Appl Clin Inform 2022 May 26. Epub 2022 May 26.

Medicine, Brigham and Women's Hospital, Boston, United States.

Background: Healthcare institutions have their own "picklist" for clinicians to document adverse drug reactions (ADRs) into the electronic health record (EHR) allergy list. Whether the lack of a nationally standardized picklist impacts clinician data entries is unknown.

Objectives: To assess the impact of defined reaction picklists on clinical documentation and, therefore, downstream analytics and clinical research using these data at two institutions. Read More

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Colposcopic multimodal fusion for the classification of cervical lesions.

Phys Med Biol 2022 May 26. Epub 2022 May 26.

Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Kuiwen District, Weifang City, Shandong Province, Weifang, Shandong, 261031, CHINA.

Objective: Cervical cancer is one of the two biggest killers of women and early detection of cervical precancerous lesions can effectively improve the survival rate of patients. Manual diagnosis by combining colposcopic images and clinical examination results is the main clinical diagnosis method at present. Developing an intelligent diagnosis algorithm based on artificial intelligence is an inevitable trend to solve the objectification of diagnosis and improve the quality and efficiency of diagnosis. Read More

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A comparative efficacy study of diagnostic digital breast tomosynthesis and digital mammography in BI-RADS 4 breast cancer diagnosis.

Eur J Radiol 2022 May 17;153:110361. Epub 2022 May 17.

Dept. of Systems Medicine and Bioengineering, Houston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, USA; Department of Radiology, Houston Methodist Hospital, Houston, TX, USA. Electronic address:

Purpose: Probability of malignancy for BI-RADS 4-designated breast lesions ranges from 2% to 95%, contributing to high false-positive biopsy rates. We compare clinical performance of digital breast tomosynthesis (DBT) versus digital mammography (2D) among our BI-RADS 4 population without prior history of breast cancer.

Methods: We extracted retrospective data i. Read More

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Pathophysiologic and clinical implications of molecular profiles resultant from deletion 5q.

EBioMedicine 2022 May 23;80:104059. Epub 2022 May 23.

Department of Translational Hematology and Oncology Research, Lerner Research Institute Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address:

Background: Haploinsufficiency (HI) resulting from deletion of the long arm of chromosome 5 [del(5q)] and the accompanied loss of heterozygosity are likely key pathogenic factors in del(5q) myeloid neoplasia (MN) although the consequences of del(5q) have not been yet clarified.

Methods: Here, we explored mutations, gene expression and clinical phenotypes of 388 del(5q) vs. 841 diploid cases with MN [82% myelodysplastic syndromes (MDS)]. Read More

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New dosimetric parameters to predict ano-rectal toxicity during radiotherapy treatment.

Phys Med 2022 May 23;99:55-60. Epub 2022 May 23.

UO Radioterapia Oncologica, Villa Santa Teresa, Bagheria, Italy.

Purpose: Radiotherapy is essential in the treatment of locally advanced rectal cancer. Side effects of radiotherapy in the treatment of rectal cancer have a great effect on quality of life. The aim of this retrospective study is to evaluate the correlation between dosimetric parameters and acute toxicity in rectal cancer patients. Read More

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Aromatherapy with inhalation can effectively improve the anxiety and depression of cancer patients: A meta-analysis.

Gen Hosp Psychiatry 2022 May 18;77:118-127. Epub 2022 May 18.

The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China; School of Nursing, Medical College of Soochow University, Suzhou 215006, PR China.

Purpose: This meta-analysis was to critically evaluate the effects of aromatherapy on the symptoms of anxiety and depression in cancer patients.

Methods: Eight Chinese and English databases (CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed, Embase, and PsycINFO) were systematically searched from the inception of databases to October 2021 for randomized controlled trials (RCTs). According to Cochrane Collaboration criteria, two reviewers independently assessed the risk of bias and extract data from included studies. Read More

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