tbuckley/cabot-search huggingface dataset:
Sex and Gender Differences Research Design for Basic, Clinical, and Population Studies: Essentials for Investigators
Authors: Janet W Rich-Edwards, Ursula B Kaiser, Grace L Chen, JoAnn E Manson, Jill M Goldstein
Journal: Endocrine Reviews (2018)

Abstract A sex- and gender-informed perspective increases rigor, promotes discovery, and expands the relevance of biomedical research. In the current era of accountability to present data for males and females, thoughtful and deliberate methodology can improve study design and inference in sex and gender differences research. We address issues of motivation, subject selection, sample size, data collection, analysis, and interpretation, considering implications for basic, clinical, and population research. In particular, we focus on methods to test sex/gender differences as effect modification or interaction, and discuss why some inferences from sex-stratified data should be viewed with caution. Without careful methodology, the pursuit of sex difference research, despite a mandate from funding agencies, will result in a literature of contradiction. However, given the historic lack of attention to sex differences, the absence of evidence for sex differences is not necessarily evidence of the absence of sex differences. Thoughtfully conceived and conducted sex and gender differences research is needed to drive scientific and therapeutic discovery for all sexes and genders.
CD70 as a critical mediator of tumor progression and immunosuppression in gliomas.
Authors: Changlin Yang, Haitao Ge, Linchun Jin, Qiong J. Wang, James C. Yang, Yu Long, Yifan(Emily) Chang, Jeffrey Drake, Luyan Mu, Elias Joseph Sayour, Gabriel De leon, Paul Kubilis, Jesse Kresak, Dunyue Lu, Yingjun Kong, Li Hu, Jiahang Sun, Duane Anthony Mitchell, Zhiguo Lin, Jianping Huang
Journal: Journal of Clinical Oncology (2017)

18 Background: For malignant gliomas, current treatment modalities are rarely curative, necessitating development of novel therapies. Cancer immunotherapy has represented one of the most promising new treatment strategies for patients with gliomas based on the evidence that patients with brain tumors are able to mount immune responses against the autologous tumors. However, very few tumor specific targets have been discovered in this malignancy. Thus, identifying clinical useful targets for immunotherapeutic approaches is desperately needed. Methods: CD70 expression was tested from primary GBM and low grade gliomas patient tissues. CD70 gene expression and clinical outcomes were culled from TCGA datasets. CD70 inducing CD8 T cells death was performed by flowcytometry. Results: We demonstrate that CD70, a member of the TNF ligand family, was constitutively overexpressed by primary IDH-wild-type LGG and GBMs with mesenchymal gene signatures. Elevated CD70 expression was also found in recurrent tumors and correlated with tumor progression and poor survival outcome in LGGs and GBMs. CD70 was shown to be directly involved in tumor-chemokine production and associated with sustained T regulatory cells in tumor. Importantly, CD70 played a role inducing CD8 + T- specific cell death via engagement of the EREG-EGFR axis in glioma. Conclusions: CD70 is a multi-pronged modulator of immunosuppression in gliomas and enhances tumor progression.
A targeting theranostics nanomedicine as an alternative approach for hyperthermia perfusion
Authors: Tao Sun, Guangping Zhang, Qingbing Wang, Qinjun Chen, Xinli Chen, Yifei Lu, Lisha Liu, Yu Zhang, Xi He, Chunhui Ruan, Yujie Zhang, Qin Guo, Chen Jiang
Journal: Biomaterials (2018)
The health, poverty, and financial consequences of a cigarette price increase among 500 million male smokers in 13 middle income countries: compartmental model study
Journal: BMJ (2018)

To examine the impact of a 50% increase in market prices of cigarettes on health, poverty, and financial protection.Compartmental model study.13 middle income countries, totalling two billion men.500 million male smokers.Life years gained, averted treatment costs, number of men avoiding catastrophic healthcare expenditures and poverty, and additional tax revenue by income group.A 50% increase in cigarette prices would lead to about 450 million years of life gained across the 13 countries from smoking cessation, with half of these in China. Across all countries, men in the bottom income group (poorest 20% of the population) would gain 6.7 times more life years than men in the top income group (richest 20% of the population; 155 v 23 million). The average life years gained from cessation for each smoker in the bottom income group was 5.1 times that of the top group (1.46 v 0.23 years). Of the $157bn (£113bn; €127bn) in averted treatment costs, the bottom income group would avert 4.6 times more costs than the top income group ($46bn v $10bn). About 15.5 million men would avoid catastrophic health expenditures in a subset of seven countries without universal health coverage. As result, 8.8 million men, half of them in the bottom income group, would avoid falling below the World Bank definition of extreme poverty. These 8.8 million men constitute 2.4% of people living in extreme poverty in these countries. In contrast, the top income group would pay twice as much as the bottom income group of the $122bn additional tax collected. Overall, the bottom income group would get 31% of the life years saved and 29% each of the averted disease costs and averted catastrophic health expenditures, while paying only 10% of the additional taxes.Higher prices of cigarettes provide more health and financial gains to the poorest 20% than to the richest 20% of the population. Higher excise taxes support the targets of the sustainable development goals on non-communicable diseases and poverty, and provides financial protection against illness.
Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer.
Authors: Michael Adam Poch, MacLean S Hall, Krithika Nandakumar Kodumudi, Cortlin Croft, Mayer N. Fishman, John Mullinax, James J Mule', Amod Sarnaik, Shari Pilon-Thomas
Journal: Journal of Clinical Oncology (2017)

142 Background: Patients with advanced bladder cancer have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. At our institution, adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has resulted in a durable median OS of 52 months in patients with metastatic melanoma. Immune-mediated anti-tumor responses have been previously shown in bladder cancer, therefore we investigated the phenotype and function of TIL expanded from bladder tumors to establish feasibility of ACT for the treatment of bladder cancer. Methods: Tumor specimens, including primary bladder tumors and lymph node metastases, were collected from 29 bladder cancer patients having standard of care tumor resection, who also had consented to an IRB-approved protocol for TIL generation. The tissue was minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. TIL were considered expanded if they propagated to fill ≥2 wells. The remaining tumor material was digested into a single cell suspension and frozen. TIL were phenotyped by flow cytometry and assessed for autologous tumor reactivity through co-culture with tumor digest and IFN-gamma ELISA. Results: Transitional cell bladder tumors were cultured from 23 patients, of whom 19 (83%) demonstrated TIL expansion. Microbial contamination precluded TIL growth in six specimens. TIL were cultured from 9/12 (75%) patients with preceding chemotherapy and 10/11 (91%) who were chemotherapy naive. Expanded TIL were predominantly CD3 + (median 63%, range 10-87%) with a median of 30% CD8+ T cells (range 5-70%). Eight of 15 tested samples (53%) contained TIL that secreted IFN-gamma in response to autologous tumor. Conclusions: The study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer. Human bladder cancer tissue can be used to expand tumor-specific TIL in vitro. TIL were also expanded from patients that received chemotherapy prior to tumor resection. Future efforts will explore the ability to further expand bladder TIL cultures to clinically meaningful numbers to develop novel ACT strategies for patients with this diagnosis.
Helping Colorectal Cancer Survivors Benefit From Changing Lifestyle Behaviors
Authors: Michael J. Fisch, Lorna H. McNeill, Karen M. Basen-Engquist
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
National and regional under-5 mortality rate by economic status for low-income and middle-income countries: a systematic assessment
Authors: Fengqing Chao, Danzhen You, Jon Pedersen, Lucia Hug, Leontine Alkema
Journal: The Lancet Global Health (2018)

The progress to achieve the fourth Millennium Development Goal in reducing mortality rate in children younger than 5 years since 1990 has been remarkable. However, work remains to be done in the Sustainable Development Goal era. Estimates of under-5 mortality rates at the national level can hide disparities within countries. We assessed disparities in under-5 mortality rates by household economic status in low-income and middle-income countries (LMICs).
Abstract 12540: High-Dose Statins Reduce the Risk of Contrast-Induced Nephropathy in Patients Undergoing Angiography: Meta-Analysis of 27 Randomized Controlled Trials
Authors: Firas Rabbat, Shadi Al Halabi, Mehdi H Shishehbor
Journal: Circulation (2015)

Introduction: Contrast-induced nephropathy (CIN) is a common complication of contrast administration during angiography. Short-term high-dose statins have been suggested for the prevention of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Hypothesis: Multiple randomized controlled trials (RCT) have examined the role of statin in preventing CIN with conflicting results. We expanded on previous meta-analyses by including additional RCTs to provide a better outlook on the efficacy of statins in the prevention of CIN. Methods: We searched Pubmed, Medline, Embase, Cochrane, and conference abstracts for prospective RCTs that compared short-term high-dose statins to low-dose statins or placebo in patients undergoing CAG, PCI, computed tomography angiography, or peripheral angiography. High-dose statin was defined as Atorvastatin 40-80 mg, Simvastatin 40 mg, and Rosuvastatin 10-40 mg. Study quality was assessed using the Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mantel Haenszel relative risk was calculated using the random effect model. Results: Twenty seven trials (N=9559) were included in the analysis. Eight of the included trials enrolled patients with acute coronary syndrome (ACS) exclusively. High-dose statin was associated with statistically significant reduction in the incidence of CIN (RR=0.56; 95% CI 0.46, 0.69; P&lt;001) compared to low-dose statin or placebo. This protective effect remained significant upon looking on trials that enrolled patients with ACS only (RR=0.40; 95% CI 0.29, 0.56; P&lt;001). Subgroup analysis based on the type of statin showed no significant difference between simvastatin, atorvastatin, or rosuvastatin. No heterogeneity was detected among the studied outcomes (I2=0%). Conclusions: Peri-procedural Short-term high-dose statin administration significantly reduces the incidence of CIN in patients undergoing angiography.
Birch pollen‐related foods can cause late eczematous reactions in patients with atopic dermatitis
Authors: A. Wassmann‐Otto, A. Heratizadeh, K. Wichmann, T. Werfel
Journal: Allergy (2018)

Previous studies have indicated that in patients with atopic dermatitis (AD) and birch pollen allergy pollen-related foods are able to cause late eczematous response. However, the relevance of AD worsening by ingestion of birch pollen-related foods is still a matter of debate.The purpose of this retrospective study was to determine how frequently birch pollen-related foods induce a deterioration of eczema. Additionally, the diagnostic value of specific IgE (sIgE) determination was evaluated.A total of 182 children and adults with AD and suspected birch pollen-related food allergy underwent 261 double-blind placebo-controlled food challenges (DBPCFC). Total and sIgE levels were determined prior to DBPCFC.Sixty-five patients developed allergic reactions (responders) upon DBPCFC with birch pollen-related foods (n = 103 DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined as a median increase of 15.4 severity scoring of atopic dermatitis index points (95% CI 12.4-16.3) from baseline making up 37% of all positive reactions. Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to nonresponders (P < .05). However, patients with late eczematous response could not be differentiated from those with isolated immediate-type reactions by sIgE levels.In a subpopulation of patients with AD and birch pollen sensitization, related foods should be considered as a trigger for an aggravation of eczema. As sufficient markers for prediction of late eczematous reactions are still lacking, DBPCFC cannot be replaced in diagnosis of birch pollen-related foods in patients with AD.In patients with AD and birch pollen allergy, birch pollen-related foods should be considered as a provocation factor for an aggravation of disease signs and symptoms.
Genome-wide, CRISPR-Cas9-based genetic screening for regulators of interferon-induced PD-L1 expression in AML cells.
Authors: William T. Tse, Joshua B. Bland
Journal: Journal of Clinical Oncology (2017)

116 Background: Expression of PD-L1 in AML cells is induced by pro-inflammatory signals, but how the induction is regulated is incompletely known. Genome-wide screening using the CRISPR-Cas9 technology could provide a strategy to interrogate the regulators of PD-L1 expression. Methods: A lentiviral CRISPR-Cas9 library, containing 3 sgRNA targeting each of 19,050 human genes (Nat Methods 2014, 11:783), was used to transduce THP-1 AML cells. Transduced cells were treated with IFN-γ and stained with an anti-PD-L1 antibody. Two subsets of cells were isolated by cell sorting according to their levels of PD-L1 expression. One subset consisted of cells that showed the median 5% of PD-L1 expression and the other subset, the lowest 5%. sgRNA integrated in the sorted subsets were amplified and their frequencies quantified by deep sequencing. Results: As expected, sgRNA targeting the PD-L1 gene itself were highly enriched in the subset that expressed a low level of PD-L1. sgRNA that targeted IFNGR2, β-chain of the IFN-γ receptor, were also enriched in this subset, whereas those for IFNGR1 were not. sgRNA targeting both JAK1 and JAK2 were enriched. By contrast, those for JAK3 and TYK2 were not. Enrichment was seen for sgRNA that targeted STAT1, a transcriptional activator downstream of JAK1/2, whereas sgRNA targeting the other STAT activators (STAT-2, 3, 4, 5A, 5B and 6) showed no enrichment. sgRNA targeting several serine kinases that regulate STAT1 phosphorylation (PKCδ, PKCε, PKCα, CAMKII, ERK, JNK, and CDK8) were not enriched. Nor were sgRNA targeting several phosphatases that modulate STAT1 activity (TC-PTP, PTPN1, SHP1 and SHP2). sgRNA targeting IRF1 (IFN regulatory transcription factor 1) were highly enriched, whereas sgRNA for IRF-2 to IRF-9 were not. In each of the affected genes, at least 2 out of the 3 sgRNA targeting the gene were enriched, indicating a generality of the findings. Conclusions: A CRISPR-Cas9-based screening strategy provided an unbiased interrogation of genes essential for PD-L1 expression on AML cells. It confirmed the importance of the IFNGR2-JAK1/2-STAT1-IRF1 axis, which could serve as targets for the development of drugs to suppress the ability of AML cells to evade host immunity.
Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens
Authors: Pamela F. Marcott, Sheng Gong, Prashant Donthamsetti, Steven G. Grinnell, Melissa N. Nelson, Amy H. Newman, Lutz Birnbaumer, Kirill A. Martemyanov, Jonathan A. Javitch, Christopher P. Ford
Journal: Neuron (2018)
Identification of somatic mutations and neoantigens to predict development of autoimmune adverse events to immune therapy in melanoma.
Authors: Keith Ryan Wells, Carol M Amato, Jennifer Hintzsche, William Robinson
Journal: Journal of Clinical Oncology (2017)

19 Background: Immunotherapy has quickly altered the treatment paradigm for advanced melanoma. Prior studies using whole exome sequencing (WES) in immunotherapy have shown limited correlation with clinical response to immunotherapy, but not an evaluation of autoimmune side effects. Understanding mechanisms of immune-related adverse events (irAE) at a genomic level may lead to improved rational treatment design and better patient selection. Methods: DNA was extracted from 87 tumor samples from 49 patients with metastatic melanoma treated with ipilimumab (anti-CTLA-4) or with nivolumab or pembrolizumab (anti-PD-1) immunotherapy. WES was performed with exome capture on an Illumina HiSeq sequencer. Statistical analysis was performed with Chi-squared testing. Computational neoantigen analysis has been performed on the sequencing data. Results: 27 patients with advanced or metastatic melanoma were treated with only ipilimumab, 11 with only anti-PD1, and 11 patients were treated with both anti-CLTA-4 and anti-PD1 either sequentially or in combination. irAE evaluated included cutaneous, colitis, endocrinopathies, hepatitis, and pneumonitis. In 10 patients who developed colitis, 14 mutated genes were enriched in their tumor samples (p=0.01-0.046) compared with patients without colitis. Analyzing all patients with any irAE versus no irAE treated with anti-CTLA-4, anti-PD1, or both (either sequential or combination) revealed 7 mutated genes enriched in patient samples who developed irAE (p=0.02-0.05). Preliminary neoantigen analysis has identified possible irAE associated neoantigens and further analysis of additional samples are ongoing. Overall mutational burden of the tumor samples did not correlate with development of irAE. Conclusions: Autoimmune side effects are frequent and often serious side effects of immunotherapy for melanoma. Genetic analysis may provide insight in prediction of these side effects and help direct therapeutic decisions.
High-Dose Ifosfamide and Mitoxantrone (HDIM) as Cytoreductive and Mobilisation Protocol for Relapsed and Refractory Lymphoma
Authors: Damir Nemet, Ivo Radman, Igor Aurer, Ines Bojanić, Branka Golubić-Čepulić, Drago Batinić, Silva Zupančić-Šalek, Dubravka Sertić, Vinko Bogdanić, Ranka Serventi-Seiwerth, Boris Labar
Journal: Blood (2003)
Countrywide implementation of whole genome sequencing: an opportunity to improve tuberculosis management, surveillance and contact tracing in low incidence countries
Authors: Andrea Maurizio Cabibbe, Alberto Trovato, Maria Rosaria De Filippo, Arash Ghodousi, Laura Rindi, Carlo Garzelli, Simonetta Baretti, Guendalina Allodi, Roberta Mannino, Gian Maria Rossolini, Alessandro Bartoloni, Enrico Tortoli, Daniela Maria Cirillo
Journal: European Respiratory Journal (2018)

<b>Whole genome sequencing can be adopted at national level as routine assay for diagnosis, universal drug susceptibility testing and epidemiological investigation of TB cases in low incidence countries</b>http://ow.ly/KA7I30jr0Wo
Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria in Pregnant Women in the United States
Authors: Sarah-Blythe Ballard, Allison Salinger, Paul M. Arguin, Meghna Desai, Kathrine R. Tan
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications.In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1).However, limited availability of quinine and increasing resistance to mefloquine restrict these options.Strong evidence now demonstrates that artemetherlumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy.The World Health Organization (WHO) has endorsed artemisinin-based combination therapies (ACTs), such as AL, for treatment of uncomplicated malaria during the second and third trimesters of pregnancy and is currently considering whether to add ACTs, including AL, as an option for malaria treatment during the first trimester (2,3).This policy note reviews the evidence and updates CDC recommendations to include AL as a treatment option for uncomplicated malaria during the second and third trimesters of pregnancy and during the first trimester of pregnancy when other treatment options are unavailable.These updated recommendations reflect current evidence and are consistent with WHO treatment guidelines.