tbuckley/cabot-search huggingface dataset:
A Validation Study on IDO Immune Biomarkers for Survival Prediction in Non–Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease
Authors: Weili Wang, Lei Huang, Jian-Yue Jin, Wenhu Pi, Susannah G. Ellsworth, Shruti Jolly, Andrew L. Mellor, Mitchell Machtay, Feng-Ming (Spring) Kong
Journal: Clinical Cancer Research (2019)

We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC.Methods: Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed. Levels of two key molecules associated with the IDO immune checkpoint, serum kynurenine and the kynurenine:tryptophan ratio (K:T ratio), were measured at pre-RT, during-RT, and 3-month post-RT. The relationship between disease control outcomes [overall survival (OS), progression free survival, and local/regional/distant failure rates] and absolute levels of these markers, as well as dynamic changes in their levels during RT, was studied.Fifty-six patients (SBRT = 28, 3DCRT = 28) with early-stage NSCLC were studied. In all patients, higher kynurenine post-RT was significantly associated with worse OS ([HR, 1.25; 95% confidence interval (CI), 1.01-1.55; P = 0.044). No statistically significant differences in absolute kynurenine levels or the K:T ratio were observed in patients treated with 3DCRT or SBRT at any of the three time points. However, the absolute kynurenine levels rose significantly more post-RT in the 3DCRT patients with a median increase 0.721 ng/mL, compared to that of SBRT patients (0.115 ng/mL); P = 0.022.This study validated that elevated IDO activity correlated with worse survival outcomes in patients with early-stage NSCLC treated with definitive RT. Hypofractionated SBRT may have less immunosuppressive effect than 3DCRT, as measured by IDO.
WHO updates guidance on hormonal contraceptive use for women at high HIV risk
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The World Health Organization has revised its guidance on contraceptive use to take into account new evidence that women at high risk of HIV can use any form of reversible contraception without an increased risk of HIV infection.

Previously, WHO recommended extra consideration when giving the progestogen only injectable contraception Depo-Provera to women at high risk of HIV because it increased the risk of HIV transmission. But WHO said it no longer considered that there is sufficient evidence of negative health effects.

But the new advice1 recommends “correct and consistent” use of condoms where there is a risk of sexually transmitted infections (STIs), including HIV, because progestogen only …
Vitamin D Doesn’t Protect Against Diabetes
Authors: Anita Slomski
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Improved quantification of plasma lipopolysaccharide (LPS) burden in sepsis using 3-hydroxy myristate (3HM): a cohort study
Authors: Auguste Dargent, Jean-Paul Pais De Barros, Elea Ksiazek, Isabelle Fournel, Alois Dusuel, Anne Laure Rerole, Hélène Choubley, David Masson, Laurent Lagrost, Jean-Pierre Quenot
Journal: Intensive Care Medicine (2019)
Structural Basis for Allosteric Modulation of Class B G Protein–Coupled Receptors
Authors: Denise Wootten, Laurence J. Miller
Journal: The Annual Review of Pharmacology and Toxicology (2019)

Recent advances in our understanding of the structure and function of class B G protein-coupled receptors (GPCRs) provide multiple opportunities for targeted development of allosteric modulators. Given the pleiotropic signaling patterns emanating from these receptors in response to a variety of natural agonist ligands, modulators have the potential to sculpt the responses to meet distinct needs of different groups of patients. In this review, we provide insights into how this family of GPCRs differs from the rest of the superfamily, how orthosteric agonists bind and activate these receptors, the potential for allosteric modulators to interact with various regions of these targets, and the allosteric influence of endogenous proteins on the pharmacology of these receptors, all of which are important considerations when developing new therapies.
A three-gene signature to predict survival in pediatric osteosarcoma (OS) to follow patients toward liquid biopsy: A collaborative work in OS2006 protocol.
Authors: Natacha Entz-Werle, Aurelien Tripp, Noëlle Weingertner, Francoise Redini, Anne Brouchet, Nathalie Gaspar, Laurence Brugieres, Sophie Piperno Neumann, Perrine Marec-Berard, Monique Dontenwill
Journal: Journal of Clinical Oncology (2019)

11014 Background: The survival of pediatric OS is stable worldwide since two decades. The management of OS is lacking new approaches to classify closely the patients and adapt thereafter the treatments. The objectives of our molecular study, using allelotyping, quantitative PCR (qPCR) and droplet digital PCR (ddPCR), were to determine the survival impact of tumor molecular profiling in the initial tumor biopsy, in the tumor resection after neoadjuvant chemotherapy and on circulating DNA at different treatment steps. The gene panel based on biomarkers of bone dedifferentiation was already identified in the large tumor cohort of the French national protocol OS94 and demonstrated a significant prognostic impact of 3 genes MET, TWIST and APC. To go further and understand its significance throughout protocols, the same study was performed in OS2006 tumors. Methods: We applied retrospectively in the cohort of OS2006 protocol (135 patients) the same molecular assessment comprising the targeting of those 3 genes with 3 techniques evaluating their rearrangement by allelotyping, their copy number variations by qPCR and ddPCR. A preliminary cohort of 20 patients with liquid biopsies at diagnosis, before tumor surgery and at the end of chemotherapy was screened by ddPCR. Results: We were able to determine frequent rearrangements in the regions containing these 3 genes and a statistically significant correlation was made between the presence of a gene rearrangement and a worst outcome. The 3-gene signature was significantly predicting the outcome of more than 85% of patients diagnosed for an OS. Furthermore, the persistence of those genes’ rearrangements in the primitive tumor after neoadjuvant chemotherapy comparatively to the initial biopsy was correlated to a higher risk of relapse. This 3-gene signature was also used for assessment of residual disease (RD) in liquid biopsies and was able to determine before tumor surgery the level of RD. Conclusions: This molecular signature seems to be clearly associated with patient outcome and was able to provide evidence that this approach is a powerful tool to be used in pediatric OS follow up to determine early relapse or progression.
In vitro fertilization faces 'R &amp; R': (more) research and regulation
Authors: C. A. Raymond
Journal: JAMA (1988)

A CARROT-AND-STICK approach describes two developments that could alter the future direction of in vitro fertilization technology. They promise to renew public debate among right-to-life groups and organizations representing infertile couples. And they come on the heels of some soul-searching within the specialty about accountability and regulation. The carrot is a reversal of the de facto moratorium on government funding of in vitro fertilization research. That has been in effect for eight years. As a result of a recent decision by Robert Windom, MD, assistant secretary, Department of Health and Human Services (DHHS), the gears are in motion to change that situation by next year. The stick is a two-pronged effort to institute at least some degree of federal oversight into an industry that, because of the lack of government funding and the control that often goes with it, is essentially unregulated. Even within the profession, concern is being raised
Investigating serum β-HCG as an independent prognostic factor in patients (pts) receiving chemotherapy (Ct) for transitional cell carcinoma (TCC) of the urothelial tract.
Authors: Simon J. Crabb, Adam Sharp, Julia Head, Caroline Chau, Matthew Wheater, Thomas R. Geldart, Graham Mead
Journal: Journal of Clinical Oncology (2013)

4549 Background: Serum human chorionic gonadotrophin β subunit (β-HCG) has prognostic value in TCC but has not been investigated in pts receiving Ct for this disease. Furthermore prior studies lacked statistical power to test independence from other prognostic variables. Methods: A single institution retrospective clinical database was constructed of pts receiving Ct between 2005 and 2011 for cancer of the urothelial tract. Eligible pts had pure or a component of TCC. Prognostic variables were tested by univariate Kaplan Meier analyses. Statistically significant variables were then assessed by multivariate cox regression analysis. A prospectively defined β-HCG cut-point of &lt; versus ≥ 2 iu/L, either prior to (β-HCGp), or on completion of (β-HCGc) Ct was used. Results: 235 pts were eligible (72% male, 55% ≤70 years, 83% bladder primary). Initial Ct was perioperative (CtPeri) in 46% (7% adjuvant, 39% neoadjuvant). 63% had first line palliative Ct for metastatic disease (CtMet). For CtPeri, ECOG performance status (PS), haemoglobin (Hb), CtPeri regimen and T stage were statistically significant prognostic factors in univariate analyses for overall survival (OS), as were β-HCGp (median OS (mOS) 8.50 v. 1.86 years, p&lt;0.001) and β-HCGc (mOS 4.27 v. 0.66 years, p=0.003). β-HCGp and β-HCGc after CtPeri were also prognostic for relapse free survival and in multivariable analysis remained statistically significant as a prognostic factor for OS (β-HCGp: hazard ratio (HR) 3.13, p=0.001; β-HCGc: HR 4.26, p=0.007). In pts treated with CtMet, PS, alkaline phosphatase, prior CtPeri, visceral metastases, CtMet regimen and β-HCGc (mOS 1.70 v. 1.07 years, p=0.005) were prognostic in univariate analyses for OS. β-HCGc after CtMet was also prognostic for progression free survival and in multivariable analysis remained statistically significant as a prognostic factor for OS (HR 3.47, p&lt;0.001). Conclusions: β-HCG, and specifically its post-Ct level, is an independent prognostic factor for TCC treated with Ct in both curative and palliative settings. Prospective evaluation is warranted for incorporation into treatment selection strategies.
Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study
Authors: Francesc Bosch, Guy Cantin, Agostino Cortelezzi, Wolfgang Knauf, Mourad Tiab, Mehmet Turgut, Andrey Zaritskey, Jean-Louis Merot, Eugen Tausch, Kerstin Trunzer, Susan Robson, Ekaterina Gresko, Sebastian Böttcher, Robin Foà, Stephan Stilgenbauer, Véronique Leblond
Journal: Leukemia (2019)

GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1‒2), D8 and D15 of Cycle (C)1, and D1 of C2–6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1–3 of C1–6. Overall, 87.1% of patients experienced grade ≥ 3 adverse events (AEs), including neutropenia (67.1%) and thrombocytopenia (17.1%). Serious AEs were experienced by 42.1% of patients. Rates of grade ≥ 3 infusion-related reactions and infections were 19.3% and 15.7%, respectively. Overall response rate was observed in 90.0%, with 46.4% of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3% in peripheral blood and 35.7% in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91%. Frontline G-FC represents a promising treatment option for fit patients with CLL.
Mohs Micrographic Surgery for Melanoma
Authors: Christopher J. Miller, Cerrene N. Giordano, H. William Higgins
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Utility of repeat latent tuberculosis testing with the Quanti <scp>FERON</scp> ‐ <scp>TB</scp> Gold test in patients with psoriasis treated with tumour necrosis factor‐α inhibitors at a single U.S. institution
Authors: J. Ya, U. Khanna, S. Havele, A.P. Fernandez
Journal: British Journal of Dermatology (2019)
Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline <i>BRCA</i> Pathogenic Variant
Authors: Jennifer K. Litton, Marion E. Scoggins, Kenneth R. Hess, Beatriz E. Adrada, Rashmi K. Murthy, Senthil Damodaran, Sarah M. DeSnyder, Abenaa M. Brewster, Carlos H. Barcenas, Vicente Valero, Gary J. Whitman, Jill Schwartz-Gomez, Elizabeth A. Mittendorf, Alastair M. Thompson, Thorunn Helgason, Nuhad Ibrahim, Helen Piwnica-Worms, Stacy L. Moulder, Banu K. Arun
Journal: Journal of Clinical Oncology (2019)

Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (gBRCA-positive) and operable breast cancer.Eligibility included 1 cm or larger invasive tumor and gBRCA-positive disease. Human epidermal growth factor receptor 2-positive tumors were excluded. Twenty patients underwent a pretreatment biopsy, 6 months of once per day oral talazoparib (1 mg), followed by definitive surgery. Patients received adjuvant therapy at physician's discretion. The primary end point was residual cancer burden (RCB). With 20 patients, the RCB-0 plus RCB-I response rate can be estimated with a 95% CI with half width less than 20%.Twenty patients were enrolled from August 2016 to September 2017. Median age was 38 years (range, 23 to 58 years); 16 patients were gBRCA1 positive and 4 patients were gBRCA2 positive. Fifteen patients had triple-negative breast cancer (estrogen receptor/progesterone receptor < 10%), and five had hormone receptor-positive disease. Five patients had clinical stage I disease, 12 had stage II, and three had stage III, including one patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma. One patient chose to receive chemotherapy before surgery and was not included in RCB analyses. RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%. Eight patients (40%) had grade 3 anemia and required a transfusion, three patients had grade 3 neutropenia, and 1 patient had grade 4 thrombocytopenia. Common grade 1 or 2 toxicities were nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea. Toxicities were managed by dose reduction and transfusions. Nine patients required dose reduction.Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports the larger, ongoing neoadjuvant trial (ClinicalTrials.gov identifier: NCT03499353).
Feedback-Driven Assembly of the Axon Initial Segment
Authors: Amélie Fréal, Dipti Rai, Roderick P. Tas, Xingxiu Pan, Eugene A. Katrukha, Dieudonnée van de Willige, Riccardo Stucchi, Amol Aher, Chao Yang, A.F. Maarten Altelaar, Karin Vocking, Jan Andries Post, Martin Harterink, Lukas C. Kapitein, Anna Akhmanova, Casper C. Hoogenraad
Journal: Neuron (2019)

Highlights•Ankyrin-G in complex with EBs recruits microtubule bundles to the plasma membrane•TRIM46 is a rescue factor that forms stable parallel microtubule bundles•TRIM46-bound microtubules direct Neurofascin-186 trafficking to the proximal axon•Ankyrin-G controls Neurofascin-186 retention in the axon initial segmentSummaryThe axon initial segment (AIS) is a unique neuronal compartment that plays a crucial role in the generation of action potential and neuronal polarity. The assembly of the AIS requires membrane, scaffolding, and cytoskeletal proteins, including Ankyrin-G and TRIM46. How these components cooperate in AIS formation is currently poorly understood. Here, we show that Ankyrin-G acts as a scaffold interacting with End-Binding (EB) proteins and membrane proteins such as Neurofascin-186 to recruit TRIM46-positive microtubules to the plasma membrane. Using in vitro reconstitution and cellular assays, we demonstrate that TRIM46 forms parallel microtubule bundles and stabilizes them by acting as a rescue factor. TRIM46-labeled microtubules drive retrograde transport of Neurofascin-186 to the proximal axon, where Ankyrin-G prevents its endocytosis, resulting in stable accumulation of Neurofascin-186 at the AIS. Neurofascin-186 enrichment in turn reinforces membrane anchoring of Ankyrin-G and subsequent recruitment of TRIM46-decorated microtubules. Our study reveals feedback-based mechanisms driving AIS assembly.
Combination of olanzapine and aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients.
Authors: Mukesh Shanthilal, Sathya M, Akshay Jk
Journal: Journal of Clinical Oncology (2019)

11577 Background: Olanzapine and Aprepitant have been shown to be a safe and effective agent for the prevention of CINV. This study aims to compare Olanzapine, Aprepitant and their combination in the prevention of CINV. Methods: Prospective randomized controlled study in breast cancer patients receiving doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 chemotherapy. Female patient; age, ≥ 18; chemotherapy naïve; were included. Patients with seizure disorder, brain metastasis were excluded. Olanzapine group received Tablet Olanzapine 10 mg on day 1 to 3. Aprepitant group received Tablet. Aprepitant 125mg on day 1, 80mg on days 2-3. The combination group received Aprepitant 125mg on day 1, 80mg on days 2-3 and Olanzapine 10mg on day 1. All groups received Palnosteron 0.25mg and Dexamethasone 8mg on day 1. The primary end point of the study was complete response (CR) for nausea that is no nausea in the acute, delayed and overall periods. Secondary endpoint was CR for vomiting and no use of rescue drugs in all periods. Beginning with the first day of chemotherapy and daily through day 5, patients were asked to record daily episodes of nausea using a visual analogue scale from 0 to 10, with 0 indicating no nausea and 10 indicating a maximal level of nausea. They were asked to record daily episodes of vomiting (number and time) and the utilization of rescue therapy. Results: A total of 141 patients were evaluated and consented for the study. The median age was 47 years; range 29-80; CR for nausea in the acute period (within 24 hours) was 83%, 63.8% and 78.7% (p=0.078); for the delayed period (days 2-5) 59.6%, 55.3% and 63.8% (p=0.702); for the overall period (0-120 hours) 57.4%, 53.2% and 59.6% (p=0.817) for the Olanzapine, Aprepitant and combination arm respectively. CR for vomiting in the acute period was 91.5%, 91.5% and 97.9.7% (p=0.344); for the delayed period 74.5%, 85.1% and 97.9% (p=0.005); for the overall period 70.2%, 85.1% and 97.9% (p=0.001) for the Olanzapine, Aprepitant and combination arm respectively. There were no Grade 3/4 toxicities. Conclusions: The combination strategy shows trend towards better prevention of CINV. Clinical trial information: CTRI/2017/12/010864.
Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline
Authors: Chadi A. Hage, Eva M. Carmona, Oleg Epelbaum, Scott E. Evans, Luke M. Gabe, Qusay Haydour, Kenneth S. Knox, Jay K. Kolls, M. Hassan Murad, Nancy L. Wengenack, Andrew H. Limper
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<ContentsOverviewSummary of Recommendation...MethodsRecommendations for Speci...ConclusionsReferencesCITING ARTICLES