tbuckley/cabot-search huggingface dataset:
Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?
Authors: Mariana Rocha, Fátima Leite-Pinheiro, Beatriz Cardoso, Maria José Del Rio, Antonio Lojo Teira, Maria Anjos Pires, Estela Bastos, Ricardo Ribeiro
Journal: Journal of Clinical Oncology (2019)

603 Background: Lymphotoxin alpha (LTa) is a proinflammatory cytokine expressed by inflammatory cells with a role in the regulation of tumor microenvironment (TM). A putatively functional genetic polymorphism in LTA, at locus +80 (Thr26Asn, rs1041981), has been associated with altered expression of LTa. Here, we sought to evaluate whether this polymorphism associates with two main endpoints (progression-free survival (PFS) and overall survival(OS)) in colorectal cancer (CRC). Methods: This retrospective cohort study was conducted in 166 CRC patients from a single tertiary hospital. Whole blood was used to isolate genomic DNA. Genotyping of LTA + 80 C &gt; A was performed through real time-PCR allelic discrimination using specific Taqman probes, and confirmed by sequencing. Retrospective data and long-term outcomes were reviewed. Age and gender-adjusted logistic regression analyses were undertaken. Analyses were conducted after stratification by baseline lymphocyte count (LC) (LC &lt; 1x10 3 /µL vs. &gt; 1x10 3 /µL). Kaplan-Meier curves with Log-Rank test were used. Subsequent multivariate Cox regression proportional hazards models were calculated (P for retention &gt; 0.1). Results: Participants’ median age was 65.9 (IR, 57.5-74.3) years, the majority were males (63%), and 58% with colon cancer. At diagnosis, 45,2% were stage III and 18,1% stage IV. The median follow up time was approximately four years (IQR, 25.5-67.0 months). We found a significant association in carriers of the A-allele to have lower LC on linear trend analysis (P for trend = 0.013). Multivariate comparisons between LTA genotypes of additive model showed an independent protective effect for heterozygous compared with C-homozygous in the association with disease progression (HR = 0.5, 95 CI = 0.3-0.97, P = 0.041), only in subjects with baseline LC &gt;1x10 3 /µL. In this group, a significant independent protective effect for all-cause mortality was observed in A-carriers (HR = 0.4, 95 CI = 0.1-0.97, P = 0.042). Conclusions: This LTA genetic variant in subjects with baseline LC &gt; 1x10 3 /µL is associated with PFS and OS in CRC. The understanding of the impact of this polymorphisms on the evolution of the disease can bring us new information on TM regulation.
Glucocorticoids Paradoxically Induce Intrinsic Steroid Resistance through a STAT5-Mediated Survival Mechanism in T-Cell Acute Lymphoblastic Leukemia
Authors: Lauren K. Meyer, Benjamin Huang, Ritu Roy, Aaron Hechmer, Anica Wandler, Cristina Delgado-Martin, Adam B. Olshen, Terzah M. Horton, David T Teachey, Kevin M. Shannon, Michelle L. Hermiston
Journal: Blood (2018)
Tumor microenvironment modulation enhances immunologic benefit of chemoradiotherapy
Authors: Aurelie Hanoteau, Jared M. Newton, Rosemarie Krupar, Chen Huang, Hsuan-Chen Liu, Angelina Gaspero, Robyn D. Gartrell, Yvonne M. Saenger, Thomas D. Hart, Saskia J. Santegoets, Damya Laoui, Chad Spanos, Falguni Parikh, Padmini Jayaraman, Bing Zhang, Sjoerd H. Van der Burg, Jo A. Van Ginderachter, Cornelis J. M. Melief, Andrew G. Sikora
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Chemoradiotherapy (CRT) remains one of the most common cancer treatment modalities, and recent data suggest that CRT is maximally effective when there is generation of an anti-tumoral immune response. However, CRT has also been shown to promote immunosuppressive mechanisms which must be blocked or reversed to maximize its immune stimulating effects. <h3>Methods</h3> Therefore, using a preclinical model of human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), we developed a clinically relevant therapy combining CRT and two existing immunomodulatory drugs: cyclophosphamide (CTX) and the small molecule inducible nitric oxide synthase (iNOS) inhibitor L-n6-(1-iminoethyl)-lysine (L-NIL). In this model, we treated the syngeneic HPV-HNSCC mEER tumor-bearing mice with fractionated (10 fractions of 3 Gy) tumor-directed radiation and weekly cisplatin administration. We compared the immune responses induced by CRT and those induced by combinatory treatment (CRT + CTX/L-NIL) with flow cytometry, quantitative multiplex immunofluorescence and by profiling immune-related gene expression changes. <h3>Results</h3> We show that combination treatment favorably remodels the tumor myeloid immune microenvironment including an increase in anti-tumor immune cell types (inflammatory monocytes and M1-like macrophages) and a decrease in immunosuppressive granulocytic myeloid-derived suppressor cells (MDSCs). Intratumoral T cell infiltration and tumor antigen specificity of T cells were also improved, including a 31.8-fold increase in the CD8<sup>+</sup> T cell/ regulatory T cell ratio and a significant increase in tumor antigen-specific CD8<sup>+</sup> T cells compared to CRT alone. CTX/LNIL immunomodulation was also shown to significantly improve CRT efficacy, leading to rejection of 21% established tumors in a CD8-dependent manner. <h3>Conclusions</h3> Overall, these data show that modulation of the tumor immune microenvironment with CTX/L-NIL enhances susceptibility of treatment-refractory tumors to CRT. The combination of tumor immune microenvironment modulation with CRT constitutes a translationally relevant approach to enhance CRT efficacy through enhanced immune activation.
Abstract 14490: Pre-transplant Mitral Annular Calcification is Associated With Increased Risk of Cardiac Death and Myocardial Infarction in Renal Transplant Recipients
Authors: Meron Teshome, Addis Asfaw, Ibtihaj Fughhi, Rami Doukky
Journal: Circulation (2017)

Introduction: Mitral annular calcification (MAC) is a common finding in the elderly and in patients with chronic kidney disease. MAC has been shown to be associated with increased rates of cardiovascular disease and mortality. The impact of MAC on cardiovascular outcomes after renal transplantation is unknown. Hypothesis: Pre-transplant MAC is associated with increased risk of major adverse cardiac events (MACE) in renal transplant recipients. Methods: In a retrospective cohort of consecutive renal transplant recipients, pre-transplant MAC was assessed using transthoracic echocardiography performed within 1 y prior to transplant. Clinical risk was assessed using the sum of risk factors (range 0 - 8) set-forth by the AHA/ACCF consensus statement on the assessment of kidney transplant candidates. These include: age > 60 y, hypertension, diabetes, dyslipidemia, smoking, known cardiovascular disease, dialysis > 1 y, and left ventricular hypertrophy. Patients were followed post-transplant for MACE (cardiac dea...
A Neuropsychologist’s Odyssey
Authors: Eben S. Schwartz
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Suicide Reduction and Research Efforts in Service Members and Veterans—Sobering Realities
Authors: Charles W. Hoge
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Finland’s sports physiotherapy conference—athlete training and loading: Helsinki 7–8 June 2019
Authors: Peter Halén, Karim M Khan
Journal: British Journal of Sports Medicine (2019)

As we were finalising this Warm Up on New Year’s Day, we two authors, one from Finland the other from Canada, undertook a bet as our teams were opponents in the Quarter Finals of the International Ice Federation World Junior Championships. By the time we finalised our work, on 6 January 2019, Finland (population 5.5 million) had beaten the USA (population 325 million) and were World Champions. Some will have forgotten the event by the time this issue goes to print but those folks won’t live in Finland. ‘World Champion’ provides a theme for the fifth international sports physiotherapy congress being held in Helsinki in June 2019 (figure 1). There is a world-class academic programme complemented by a world-famous social programme. And good reason to celebrate.



Figure 1 
The  Finnish Sports Physiotherapy Association  (FSPA) Annual Congress will be held in Helsinki on …
Circular RNA 100146 functions as an oncogene through direct binding to miR-361-3p and miR-615-5p in non-small cell lung cancer
Authors: Lijian Chen, Aruo Nan, Nan Zhang, Yangyang Jia, Xin Li, Yihui Ling, Jiabin Dai, Shaozhu Zhang, Qiaoyuan Yang, Yanni Yi, Yiguo Jiang
Journal: Molecular Cancer (2019)

Circular RNAs are widely expressed in eukaryotic cells and associated with cancer. However, limited studies to date have focused on the potential role of circRNAs in progression of lung cancer. Data from the current investigation showed that circRNA 100146 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and the chemically induced malignant transformed bronchial cell line, 16HBE-T, as well as 40 paired tissue samples of NSCLC. Suppression of circRNA 100146 inhibited the proliferation and invasion of cells and promoted apoptosis. Furthermore, circRNA 100146 could interact with splicing factors and bind miR-361-3p and miR-615-5p to regulate multiple downstream mRNAs. Our collective findings support a role of circRNA 100146 in the development of NSCLC and further demonstrate endogenous competition among circRNA 100146, SF3B3 and miRNAs, providing novel insights into the mechanisms underlying non-small cell lung cancer.
Ibrutinib Plus Obinutuzumab and Venetoclax in Relapsed/Refractory Mantle Cells Lymphoma Patients, Results of the OASIS Phase I Clinical Trial
Authors: Steven Le Gouill, Franck Morschhauser, Krimo Bouabdallah, Guillaume Cartron, Rene-Olivier Casasnovas, Noel-Jean Milpied, Thomas Gastinne, Andrew John Davies, Charles Herbaux, David Chiron, Mary Callanan, Simon Rule
Journal: Blood (2018)
Abstract 20611: Knowledge to Action: Rationale and Design of the Patient-Centred Care Transitions in Heart Failure (PACT-HF) Pragmatic Trial
Authors: Harriette G Van Spall, Shun Fu Lee, Feng Xie, Dennis Ko, Ibrahim Quazi, Lehana Thabane, Peter Mitoff, Michael Heffernan, Manish Maingi, Liane Porepa, Michael Tjandrawidjaja, Mohammad Zia, Mohammad Panju, Ian Graham, Dilys Haughton, Stuart J Connolly
Journal: Circulation (2017)

Introduction: Heart Failure (HF) is a common cause of hospitalization in older adults, and gaps in transitional care can increase the risk of readmission. Informed by the results of our network met...
Epidemiology and Etiology
Authors: Melissa L. Bondy, Yanhong Liu, Michael E. Scheurer
Journal: Neuro-Oncology (2012)

Brain tumors are relatively rare but often fatal diseases. Currently, the etiology of brain tumors remains largely unknown, and the relationship between and the contribution of heritable conditions and environmental exposures are unclear. In this review, we summarize the recent advance in the descriptive and analytic epidemiologic research studies on brain tumor.
Abstract 032: Life-Course Socioeconomic Position Relates to Higher Arterial Stiffness in Adults From the ELSA-Brasil Cohort Study
Authors: Debora M Coelho, Lidyane V Camelo, Luisa C Brant, Luana G Giatti, Antonio L Ribeiro, Joanna M Guimaraes, Dora Chor, Sandhi M Barreto
Journal: Circulation (2018)

Background: Although the association between socioeconomic adversity and risk for cardiovascular disease (CVD) is established, little is known about the effect of socioeconomic disadvantages across the life-course on arterial stiffness, an important marker of subclinical cardiovascular disease (CVD). Objective: To investigate whether exposure to adverse socioeconomic position (SEP) throughout the life course and especially in early life, is associated with increased arterial stiffness in adults. In addition, we assessed whether increasing number of unfavorable SEP events during the life course is associated with higher arterial stiffness. Methods: A total of 14,497 adults from the ELSA-Brasil cohort study baseline (2008-2010), aged between 34 and 75 years (45.5% men, mean age: 51.9, SD: 9.09), with validated values of femoral carotid pulse wave velocity (cfPWV), and with information available about maternal education were included. ELSA-Brazil is a multicenter cohort of civil servants from universities and research institutions of six Brazilian cities that aims to investigate the determinants of cardiovascular disease. Arterial stiffness was measured by cfPWV. Childhood and adulthood SEP was measured by maternal education and participants’ own education, respectively. Accumulation of SEP disadvantages across the life course was evaluated using a score including maternal and participants’ own education. The following variables were used for adjustments: age, sex, race, mean arterial pressure, heart rate, smoking, physical activity, diabetes, antihypertensive use. Multiple linear regression models were used. Results: Both lower childhood and adulthood SEP were associated with higher cfPWV in adult life, although the association with childhood SEP was not independent of adulthood SEP. However, cfPWV increased with increasing number of unfavorable SEP during the life course. Individuals exposed to low SEP in childhood and adulthood presented an average increase of 0.23m/s (95% CI: 0.13-0.34) in cfPWV in relation to individuals with high SEP in both periods of life. After all adjustments this association remained statically significant (β = 0.18, 95% CI: 0.07-0.29). Conclusion: Accumulation of exposures to socioeconomic disadvantages throughout life was associated with higher cfPWV in adults. Thus, it may imply that longer exposure to social disadvantages throughout life accelerates arterial aging.
A 3D Macroporous Alginate Graphene Scaffold with an Extremely Slow Release of a Loaded Cargo for In Situ Long‐Term Activation of Dendritic Cells
Authors: Arjyabaran Sinha, Youngjin Choi, Minh Hoang Nguyen, Thanh Loc Nguyen, Seung Woo Choi, Jaeyun Kim
Journal: Advanced Healthcare Materials (2019)

Abstract Ex vivo manipulation of autologous antigen‐presenting cells and their subsequent infusion back into the patient to dictate immune response is one of the promising strategies in cancer immunotherapy. Here, a 3D alginate scaffold embedded with reduced graphene oxide (rGO) is proposed as a vaccine delivery platform for in situ long‐term activation of antigen‐presenting dendritic cells (DCs). High surface area and hydrophobic surface of the rGO component of the scaffold provide high loading and a very slow release of a loaded antigen, danger signal, and/or chemoattractant from the scaffold. This approach offers long‐term bioavailability of the loaded cargo inside the scaffold for manipulation of recruited DCs. After mice are subcutaneously vaccinated with the macroporous alginate graphene scaffold (MAGS) loaded with ovalbumin (OVA) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), this scaffold recruits a significantly high number of DCs, which present antigenic information via major histocompatibility complex class I for a long period. Furthermore, an MAGS loaded with OVA, GM‐CSF, and CpG promotes production of activated T cells and memory T cells, leading to the suppression of OVA‐expressing B16 melanoma tumor growth in a prophylactic vaccination experiment. This study indicates that an MAGS can be a strong candidate for long‐term programming and modulating immune cells in vivo.
A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease
Authors: David L. Wirta, Gail L. Torkildsen, Helen R. Moreira, John D. Lonsdale, Joseph B. Ciolino, Garrit Jentsch, Michael Beckert, George W. Ousler, Philipp Steven, Sonja Krösser
Journal: Ophthalmology (2019)

To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy.An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator.Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53).After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks.The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire.CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups.CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.
Challenges with Novel Clinical Trial Designs: Master Protocols
Authors: Michael Cecchini, Eric H. Rubin, Gideon M. Blumenthal, Kassa Ayalew, Howard A. Burris, Michele Russell-Einhorn, Hildy Dillon, H. Kim Lyerly, Gregory H. Reaman, Scott Boerner, Patricia M. LoRusso
Journal: Clinical Cancer Research (2019)

The 2018 Accelerating Anticancer Agent Development (AAADV) Workshop assembled a panel of experts for an in-depth discussion session to present "Challenges with Novel Clinical Trial Designs." This panel offered assessments of the challenges faced by industry, the FDA, investigators, institutional review boards, and patients. The panel focused on master protocols, which include umbrella trials, platform trials, and basket trials. Umbrella trials and platform trials share many commonalities, whereas basket trials are more distinct. Umbrella and platform trials are generally designed with multiple arms where patients of the same histology or other unifying characteristics are enrolled into different arms and multiple investigational agents are evaluated in a single protocol. In contrast, basket studies generally enroll patients with different tumor types based on the presence of a specific mutation or biomarker regardless of histology; these trials may include expansion cohorts. These novel designs offer the promise of expedited drug assessment and approval, but they also place new challenges on all the stakeholders involved in the drug development process. Only by identifying the challenges of these complex, innovative clinical trial designs and highlighting challenges from each perspective can we begin to address these challenges. The 2018 AAADV Workshop convened a panel of experts from relevant disciplines to highlight the challenges that are created by master protocols, and, where appropriate, offer strategies to address these challenges.