tbuckley/cabot-search huggingface dataset:
Thinking bigger: How early‐life environmental exposures shape the gut microbiome and influence the development of asthma and allergic disease
Authors: Hind Sbihi, Rozlyn CT. Boutin, Chelsea Cutler, Mandy Suen, B. Brett Finlay, Stuart E. Turvey
Journal: Allergy (2019)

Imbalance, or dysbiosis, of the gut microbiome of infants has been linked to an increased risk of asthma and allergic diseases. Most studies to date have provided a wealth of data showing correlations between early-life risk factors for disease and changes in the structure of the gut microbiome that disrupt normal immunoregulation. These studies have typically focused on one specific risk factor, such as mode of delivery or early-life antibiotic use. Such "micro-level" exposures have a considerable impact on affected individuals but not necessarily the whole population. In this review, we place these mechanisms under a larger lens that takes into account the influence of upstream "macro-level" environmental factors such as air pollution and the built environment. While these exposures likely have a smaller impact on the microbiome at an individual level, their ubiquitous nature confers them with a large influence at the population level. We focus on features of the indoor and outdoor human-made environment, their microbiomes and the research challenges inherent in integrating the built environment microbiomes with the early-life gut microbiome. We argue that an exposome perspective integrating internal and external microbiomes with macro-level environmental factors can provide a more comprehensive framework to define how environmental exposures can shape the gut microbiome and influence the development of allergic disease.
Abstract 17226: Latin American Patients With Atrial Fibrillation Have a Higher Risk Profile but Similar Response With Rivaroxaban versus Warfarin: A ROCKET AF Substudy
Authors: Ramon Corbalan, Anne S Hellkamp, Richard C Becker, Scott D Berkowitz, Günter Breithardt, Keith A Fox, Werner Hacke, Jonathan L Halperin, Graeme J Hankey, Kenneth W Mahaffey, Christopher C Nessel, Jonathan P Piccini, Daniel E Singer, Manesh R Patel
Journal: Circulation (2017)

Background: We hypothesized that the clinical characteristics and outcomes of Latin American patients with AF enrolled in a global trial may be different from the rest of the world (ROW). Methods: ...
Retraction: FRA-1 Expression in Hyperplastic and Neoplastic Thyroid Diseases
Authors: Gennaro Chiappetta, Giovanni Tallini, Maria Cristina De Biasio, Francesca Pentimalli, Filomena de Nigris, Simona Losito, Monica Fedele, Sabrina Battista, Pasquale Verde, Massimo Santoro, Alfredo Fusco
Journal: Clinical Cancer Research (2019)

[This article][1] ([1][2]) has been retracted at the request of the editors. In Fig. 4, the GADPH lanes appear to be repeated as triplets, and Fra-1 lanes 6 through 15 appear to be duplicated and rotated in the same blots. The authors provided RT-PCR images that exhibit results similar to the claims
Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation
Authors: Taro Kato, Santosh Pothula, Rong-Jian Liu, Catharine H. Duman, Rosemarie Terwilliger, George P. Vlasuk, Eddine Saiah, Seung Hahm, Ronald S. Duman
Journal: Journal of Clinical Investigation (2019)

Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly selective small molecule modulator of sestrin that penetrates the blood brain barrier. The results demonstrate that a single dose of NV-5138 produced rapid and long-lasting antidepressant effects, and rapidly reversed anhedonia caused by chronic stress exposure. The antidepressant actions of NV-5138 required BDNF release as the behavioral responses are blocked by infusion of a BDNF neutralizing antibody into the medial prefrontal cortex (mPFC) or in mice with a knock-in of a BDNF polymorphism that blocks activity dependent BDNF release. NV-5138 administration also rapidly increased synapse number and function in the mPFC, and reversed the synaptic deficits caused by chronic stress. Together, the results demonstrate that NV-5138 produced rapid synaptic and antidepressant behavioral responses via activation of the mTORC1 pathway and BDNF signaling, indicating that pharmacological modulation of sestrin is a novel approach for development of rapid acting antidepressants.
FRI-103-A sublethal dose of acetaminophen suffices to induce the unfolded protein response in hepatocytes through an IRE1alpha-JNK1-XBP1s-dependent mechanism
Authors: Hui Ye, Kang Zheng, Yulia Nevzorova, Beatriz Martin, Leonard J Nelson, Manuel Gómez del Moral, Iris Asensio, Javier Vaquero, Rafael Bañares, Eduardo Martínez-Naves, Francisco Javier Cubero
Journal: Journal of Hepatology (2019)
Linear accelerator based blood irradiation for pediatric oncology practice in limited resource setting: Illumination and innovation.
Authors: Sujith Kumar Mullapally, Sandeep Madhavan, Aswathi Raj, Bindu K Sathi, Sathish Padmanabhan, Narayanankutty Edavalath Warrier
Journal: Journal of Clinical Oncology (2015)

e21001 Background: Blood Component Irradiation is the only proven method of preventing Transfusion associated graft versus host disease (TA-GVHD). The option of dedicated blood product irradiator is difficult in low resource settings due to the cost .We aim to assess efficacy of Linear Accelerator based blood product irradiation protocol for prevention of TA-GVHD in Pediatric Oncology patients. Methods: A dedicated Pediatric Oncology department was started in our hospital in January 2014. In the absence of blood product irradiator and with limited resources, Linac based blood irradiation practice was reviewed and Standard Operating Procedure prepared. The medical physics team developed indigenous radiation basin using phantom blocks and treatment planning done in Eclipse TPS, version 10. After Quality Assurance measurements for dose delivery and dose homogeneity,blood products issued were irradiated for individual pediatric patients as necessary. Single session of 2500cGy was delivered using 6 MV X rays. At completion of 50 sessions,patient profile, clinical indications, blood irradiation data and clinical results were statistically analyzed. Results: 50 sessions of blood irradiation was done for total of 103 blood products (packed RBC-35, platelets-78) Mean time taken for each session was 8 minutes and mean MU delivered was 2404. A total of 15 patients required irradiated blood products. For 5 patients, repeated transfusions were done. Median age was 4 years (range: 3months - 17yrs) .The most common diagnosis was Acute Lymphoblastic Leukemia on chemotherapy. The incidence of TA-GVHD was 0% with no patient having any transfusion related complications and no interruption of intended treatment even after repeated transfusions. Conclusions: In low resource settings, Linear Accelerator based blood product irradiation is a safe and effective method for prevention of TA-GVHD especially for pediatric oncology patients. Linear accelerator can be used for this without any significant delay for patients on routine radiotherapy treatments.This strategy can contribute in large scale implementation of irradiated blood product use for pediatric oncology.
HRQoL in medulloblastoma patients enrolled on a prospective phase II study of proton radiation.
Authors: Torunn I. Yock, Elizabeth A. Weyman, Saveli Goldberg, Bree Ruppert Eaton, Hallie Bieber Kasper, Shannon M. MacDonald, Margaret B. Pulsifer, David Ebb, Sean P Srichankij, Jennifer Delahaye, Nancy Tarbell, Karen Kuhlthau
Journal: Journal of Clinical Oncology (2015)

e21029 Background: Though the majority of pediatric medulloblastoma patients treated with surgery, radiotherapy and chemotherapy are cured, HRQoL is impaired. Methods: Patients enrolled on a phase II study of PT in pediatric medulloblastoma were offered enrollment on a prospective HRQoL study including child self report (CSR) and parent proxy report (PPR). The PedQL Core questionnaire was administered during PT (baseline, BL) and at annual follow up (FU). Clinical and demographic variables were tested for correlation in both univariate and multivariate (MVA) analyses over time comparing, physical (PS) and psychosocial (PSS) summary scores and total core scores(TCS). Results: 47 of 59 eligible patients participated in the HRQoL component. BL median age was 6.5 yrs. (3-16); median follow-up (FU) 7 yrs. (1-10); 42.6% were female and 89%caucasion. 77% standard risk, and median household annual income (HI) $88.1K. CSR scores were 4-7 points higher than PPRs at baseline but were highly correlated. PPR and CSR TCS rose from BL to FU in excess of 10 points. On univariate analysis, CSR TCS were not associated with gender, age at treatment, HI, boost volumes, risk status or posterior fossa syndrome (PFS). PPR TCS showed a significant positive correlation with higher HI at FU. On MVA, higher M stage correlated with worse TCS in the CSR. In contrast, lower HI at FU correlated with lower TCS in the PPR. Conclusions: HRQOL scores rise with time after treatment for medulloblastoma. Children report higher QOL scores than their parents, but scores reliably track together. Higher household income at follow-up correlated with higher HRQoL scores. Clinical trial information: NCT00105560. Group TCS BL TCS FU PS BL PS FU PSS BL PSS FU CSR all 64.4 77.6 60.1 70.4 67.4 76.2 PPR all 59.9*# 70.6*# 53.7*# 58.0*# 63.5*# 69.3**# CSR Age < 8 69.0 78.9 70.7 80.7 68.9 77.5 CSR Age 8 + 58.1 73.4 45.6* 78.1 65.3 72.2 PPR Age < 8 64.3 73.2 59.0 74.8 68.0 72.4 PPR Age 8 + 48.7** 64.6 40.3 68.4 52.4** 62.6 HI CSR < 90K 66.5 78.8 68.8 80.5 64.5 76.7 HI CSR 90K+ 61.2 76.4 48.0* 79.1 70.8 75.8 HI PPR < 90K 56.4 65.3 51.1 67.1 59.1 64.3 HI PPR 90K+ 63.9 76.2* 56.7 79.0 68.8 74.8 PFS PPR No 63.1 72.1 58.6 76.0 65.2 69.9 PFS PPR Yes 45.0 63.4 31.3** 57.5 55.8 66.5 *P<0.05; **p=0.5-0.1; # paired t-test
Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region
Authors: Rebecca C. Philips, Paige E. Hoyer, Skyler M. White, Katherine T. Tinkey, Michael Loeffelholz, Clark R. Andersen, Michael G. Wilkerson, Bernard R. Gibson, Brent C. Kelly
Journal: Journal of the American Academy of Dermatology (2019)
THU-384-Clinical Performance of determine TM HBsAg 2 rapid test for hepatitis B detection
Authors: Ana Avellon Calvo, Aftab Ala, Antonio Diaz, Daniel Domingo, Rosario Gonzalez, Lorena Hidalgo, Paul Kooner, Sabarinathan Loganathan, Loli Martin, Stuart McPherson, Milagros Munoz-Chimeno, Stephen Ryder, Gabrielle Slapak, Pablo Ryan, Marta Valbuena, Patrick Kennedy
Journal: Journal of Hepatology (2019)
Do surgical clips really indicate the tumor bed margins for radiotherapy planning?
Authors: Erkin Aribal, Ozlem Demircioglu, Meral Olduz, Zerrin Ozgen
Journal: Journal of Clinical Oncology (2015)

e12067 Background: Radiotherapy after breast-conserving surgery (BCS) is standard treatment in different stages of breast cancer. Currently, the surgical clips are used to determine the tumor bed. This study aimed to evaluate the displacement of these clips in surgical cavity with mammography. Methods: The study was conducted on 121 female cases underwent BCS for breast cancer. MLO and CC mammograms of all cases were evaluated regarding clips. The center of the area indicated by clips was determined visually on both MLO and CC views. The center of post operative architectural distortion was also designated in both views. The distance between both centers were measured. Displacements ≤ 10 mm were recorded as no displacement. Procedure was performed separately for MLO and CC views. Displacements in MLO and CC plane were recorded separately. Results: In CC projection, the clips were out of the image in 45 cases (37,2%) and evaluation was not made. While no clips displacement was observed in 37 (30,6%) cases, displacement was determined in 39 (32,2%). The amount of displacement ranged from 11 mm to 56 mm and mean displacement was 24.38 mm. In MLO projection, evaluation could not be performed since clips were partially out of view in 9 cases (7,4%). While no clips displacement was observed in 43 (35,5%) cases, displacement was found in 69 (57%). The amount of displacement ranged from 11 mm to 66 mm and mean displacement was 24,42 mm. There were no difference between CC and MLO views in terms of clips displacement (p > 0.05). Conclusions: Clips displacement depending on tissue remodeling and its reliability for determination of the tumor bed are controversial. Furthermore when the artifacts caused by these clips on MR images taken in consideration, we believe that there is a need of further studies on the reliability of clips and clips placement should be reconsidered.
TCTAP C-182 Recurrent Right Subclavian Artery Total Occlusion Due to Compression of Right Fractured Clavicle Treated by Rotarex Mechanical Thrombectomy in Combination with Catheter Directed Thrombolysis and Further Subclavian Artery Stenting
Authors: Wei-Sheng Liao, Nai-Yu Chi, Wen-Hsien Lee, Ho-Ming Su, Po-Chao Hsu
Journal: Journal of the American College of Cardiology (2019)
Cost-effectiveness of Short-Course Radiation Therapy vs Long-Course Chemoradiation for Locally Advanced Rectal Cancer
Authors: Ann C. Raldow, Aileen B. Chen, Marcia Russell, Percy P. Lee, Theodore S. Hong, David P. Ryan, James C. Cusack, Jennifer Y. Wo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Although both short-course radiotherapy and long-course chemoradiotherapy have been practiced in parallel for more than 15 years, no cost-effectiveness analysis comparing these 2 approaches in patients with locally advanced rectal cancer has been published. <h3>Objective</h3> To analyze the cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy for the treatment of patients with locally advanced rectal cancer. <h3>Design, Setting, and Participants</h3> This economic evaluation used a cost-effectiveness model simulating 10-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with either short-course radiotherapy or long-course chemoradiotherapy, followed by surgery and chemotherapy. Utilities and probabilities from the literature and costs from the Healthcare Bluebook and Medicare fee schedules were used to determine incremental cost-effectiveness ratios. It was assumed that long-course chemoradiotherapy would result in higher rates of low anterior resection (LAR). To model preference-sensitive care, a 2-way sensitivity analysis was conducted in which the utilities of the no-evidence-of-disease (NED) states with LAR and abdominoperineal resection (APR) were simultaneously varied. The analysis was repeated for patients with distal rectal tumors. Analysis was conducted from January to October 2018. <h3>Exposures</h3> Short-course radiotherapy and long-course chemoradiotherapy. <h3>Main Outcomes and Measures</h3> Incremental cost-effectiveness ratios. <h3>Results</h3> Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy (incremental cost-effectiveness ratio, $133 495 per quality-adjusted life-year). Two-way sensitivity analysis revealed that the cost-effective approach for a given patient depended on the utilities for the NED-LAR and NED-APR states. Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the cost-effective approach (incremental cost-effectiveness ratio, $61 123 per quality-adjusted life-year). <h3>Conclusions and Relevance</h3> Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy for patients with locally advanced rectal cancer. The cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy was sensitive to the utilities of the NED-LAR and NED-APR health states, highlighting the importance of care that is sensitive to patient preference. Long-course chemoradiotherapy was the cost-effective approach for patients with distal tumors.
ERGR-TKIs combined with chemotherapy delays intracranial progression in EGFR-mutant lung adenocarcinoma patients
Authors: C. Li, B. Zhang, J. Guo, F. Hu, W. Nie, X. Zheng, Y. Lou, Y. Shen, X. Zhang
Journal: Annals of Oncology (2019)

Background: The aim of this study was to evaluate if the combination of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) plus chemotherapy could delay the presence and decrease the incidence of brain metastases (BM) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods: 100 eligible patients who developed BM were retrospectively reviewed. Patients received treatment with either EGFR-TKI monotherapy or EGFR-TKI plus chemotherapy. Intracranial progression-free survival (iPFS), systemic progression-free survival (PFS) and overall survival (OS) were evaluated. Results: The median OS in the whole group was 37 months (interquartile range 6 to 94 months). Patients treated with EGFR-TKI plus chemotherapy had longer PFS compared with EGFR-TKI alone (16 vs. 10 months; P=0.030). Moreover, addition of chemotherapy showed an obvious iPFS advantage over EGFR-TKI alone (21 vs. 14 months; P=0.026). In all initial progression, less patients in the combination group developed BM compared to patients treated with EGFR-TKI monotherapy (15 vs. 27, P=0.002), with a hazard ratio (HR) of 0.64 (95% CI, 0.43−0.96) for BM in the combination group versus the EGFR-TKI monotherapy group. Conclusions: The combination of EGFR-TKI plus chemotherapy demonstrated prolonged iPFS as well as PFS and reduced the occurrence and progression risk of intracranial metastases compared to EGFR-TKI monotherapy. EGFR-TKI plus chemotherapy is recommended for lung adenocarcinoma patients with EGFR-sensitive mutations. Legal entity responsible for the study: The authors. Funding: Science and Technology Commission of Shanghai Municipality, China (No.18441904700). Disclosure: All authors have declared no conflicts of interest.
Association of lung adenocarcinoma expression of Trop-2 protein with tumor infiltrating CD8<sup>+</sup> T lymphocytes.
Authors: Joseph Mounir Obeid, Yinin Hu, Nolan Wages, Anne Stowman, Donna Deacon, Craig L. Slingluff
Journal: Journal of Clinical Oncology (2015)

e18509 Background: Trop-2, a component of tight junctions, is highly expressed in many epithelial cancers, and its intracellular expression has been associated with prolonged survival in breast adenocarcinoma. However, there is discrepancy regarding the clinical impact of Trop-2 expression in adenocarcinomas of the lung (AdCL). Trop-2 has immunologic relevance, as a target for tumor reactive T-cells. We performed a pilot study of non-small cell lung cancers to test whether Trop-2 expression may be associated with infiltration by CD8+T Lymphocytes. Methods: We evaluated 24 non-small cell lung cancer specimens (12 AdCLs and 12 squamous cell carcinomas (SCC-L)) for expression of CD8, Trop-2 and 4 other proteins (periplakin, dystonin, filaggrin, arginase-1) by immunohistochemistry of formalin-fixed, paraffin-embedded tissues. Slides were imaged on a Leica SCN400 ScanScope and analyzed using the Leica Digital Image Hub. Trop-2 expression in each tissue section was captured as staining intensity per unit area (square Angstrom). CD8+T cell infiltrates were quantified either as (a) density per unit area, or (b) percent of nucleated cells. Each measure was assessed both for the whole tumor section and for the tumor cell nests only. Automated counts were analyzed using the Spearman rank correlation coefficient (r), with a Bonferroni correction for multiple comparisons, designating a p value of < 0.0125 as significant. Results: Trop-2 expression correlated positively with CD8+ T cell infiltration in AdCL tumor nests, based on CD8 density (r = 0.8, p < 0.002) and percentage (r = 0.88, p < 0.001). In most tumors with Trop-2+ staining (7/10) the malignant cells displayed intracellular staining. In SCC-L, Trop-2 was highly expressed and was not associated with CD8+Tcell infiltration. None of the other proteins were associated with T cell infiltration in the study sample. Conclusions: CD8+ lymphocytic infiltration in AdCL tumors, but not SCC-L, tumors is significantly associated with higher levels of Trop-2 expression. A larger study of AdCLs that accounts for Trop-2’s intracellular and membrane distributions, patient survival and TIL subsets is justified to explore further this protein’s clinical implications.
Risky behaviors during cancer therapy: A report from the “Resilience in Adolescents and Young adults with Cancer” study.
Authors: Abby R. Rosenberg, Miranda Bradford, Kira O'Neil Bona, Michele Shaffer, Joanne Wolfe, Karen Syrjala, Kevin Scott Baker
Journal: Journal of Clinical Oncology (2015)

e21035 Background: Adolescent and Young Adult (AYA) development includes experimentation and sometimes engagement risky health behaviors; the prevalence of such behaviors among AYAs during cancer therapy has not previously been described. Methods: The “Resilience in Adolescents and Young Adults with Cancer” study was a prospective, multi-center, mixed-methods cohort study. Participants were English-speaking patients aged 14-22 years with newly diagnosed cancer and their caregiver(s). All were invited to complete a comprehensive patient-reported outcomes survey at the time of enrollment (T1) and 3-6 months later (T2). Risky health behaviors were assessed with questions adapted from the Guidelines for Adolescent Preventative Services risk assessment. Descriptive statistics were used to characterize the prevalence of sexual and substance-related behaviors at each time point. Results: To date, data are available from 32 patients at T1 and 21 at T2 (mean age at diagnosis 18 years [SD=2], 57% female). One-third reported being sexually active at each time point and half of those stated they “never” used birth control. At T1 and T2, respectively, 26% and 30% reported using illicit drugs, and 52% and 50% reported drinking alcohol; 13% and 25% reported engaging in these activities “a lot.” Conclusions: Risky health behaviors among AYAs are highly prevalent, even during cancer therapy. Comprehensive assessments should query these behaviors and future studies may address the impact of these behaviors on health and psychosocial outcomes. Activity T1 (N=32) T2 (N=21) Currently Dating 43% (13/30) 40% (8/20) Sexually Active 29% (9/31) 37% (7/19) “Never” use birth control 56% (5/9) 43% (3/7) “Always” use birth control 22% (2/9) 57% (4/7) “Never” use condoms 0% (0/9) 0% (0/7) “Always” use condoms 44% (4/9) 43% (3/7) Use illicit drugs 26% (8/31) 30% (6/20) Drink Alcohol 52% (16/31) 50% (10/20) Use drugs or alcohol “a lot” 10% (3/31) 10% (2/20)