tbuckley/cabot-search huggingface dataset:
Child Health Promotion in Underserved Communities
Authors: Rodrigo Fernandez-Jimenez, Risa Jaslow, Sameer Bansilal, Maribel Santana, Raquel Diaz-Munoz, Jacqueline Latina, Ana V. Soto, Rajesh Vedanthan, Mohamed Al-Kazaz, Chiara Giannarelli, Jason C. Kovacic, Emilia Bagiella, Andrew Kasarskis, Zahi A. Fayad, Roger J. Hajjar, Valentin Fuster
Journal: Journal of the American College of Cardiology (2019)

Preschool-based interventions offer promise to instill healthy behaviors in children, which can be a strategy to reduce the burden of cardiovascular disease later. However, their efficacy in underserved communities is not well established.The purpose of this study was to assess the impact of a preschool-based health promotion educational intervention in an underserved community.This cluster-randomized controlled study involved 15 Head Start preschools in Harlem, New York. Schools and their children were randomized 3:2 to receive either a 4-month (50 h) educational intervention to instill healthy behaviors in relation to diet, physical activity, body/heart awareness, and emotion management; or their standard curriculum (control). The primary outcome was the change from baseline in the overall knowledge, attitudes, and habits (KAH) score of the children at 5 months. As secondary outcomes, we evaluated the changes in KAH subcomponents and emotion comprehension. Linear mixed-effects models were used to test for intervention effects.The authors enrolled 562 preschool children age 3 to 5 years, 51% female, 54% Hispanic/Latino, and 37% African-American. Compared with the control group, the mean relative change from baseline in the overall KAH score was ∼2.2 fold higher in the intervention group (average absolute difference of 2.86 points; 95% confidence interval: 0.58 to 5.14; p = 0.014). The maximal effect was observed in children who received >75% of the curriculum. Physical activity and body/heart awareness components, and knowledge and attitudes domains, were the main drivers of the effect (p values <0.05). Changes in emotion comprehension trended toward favoring intervened children.This multidimensional school-based educational intervention may be an effective strategy for establishing healthy behaviors among preschoolers from a diverse and socioeconomically disadvantaged community. Early primordial prevention strategies may contribute to reducing the global burden of cardiovascular disease. (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA]; NCT02343341).
The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study
Authors: W.J.A. Witlox, B. Ramaekers, H.J.M. Groen, A.-M.C. Dingemans, J. Praag, J. Belderbos, V. Van der Noort, H. Van Tinteren, M.A. Joore, D. De Ruysscher
Journal: Annals of Oncology (2019)

Background: The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses. Methods: Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgroups: age, gender, performance status, disease stage and tumour type, prior surgery, chemotherapy cycles, thoracic RT dose and total concurrent chemo-RT treatment time. For continuous variables, the median was used as a cut-off value. The effect of PCI was only examined if the initial result was significant. Results: In total, 174 patients were analysed. The symptomatic BM incidence was significantly lower in the subgroup of older (>61 years) versus younger (= <61 years) patients (7% vs 26% [HR 0.25]). Stratified by age, PCI only significantly reduced the symptomatic BM incidence in younger patients (9% vs 42% [HR 0.18])(Table).Table86O Time to symptomatic BM per subgroupSubgroupHazard ratio95% CIAge (>61 years vs ≤ 61 years)All0.250.10 - 0.60≤61 PCI vs observation0.180.06 - 0.53>61 PCI vs observation0.470.09 - 2.52Female vs Male1.310.92 - 1.88WHO performance status0––10.860.41 - 1.8322.120.59 - 7.63Squamous vs non-squamous0.760.34 - 1.66Stage IIIb vs IIIa0.970.47 - 1.98Prior vs no prior surgery1.210.45 - 3.29Chemotherapy cycles (>3 vs ≤ 3)0.970.42 - 2.22Thoracic RT dose (>60 Gy vs ≤ 60 Gy)1.150.57 - 2.36Total concurrent chemo-RT time (>64 days vs ≤ 64 days)1.430.70 - 2.94 Open table in a new tab Conclusions: The symptomatic BM incidence was significantly lower in older (>61 years) compared to younger (= <61 years) patients, likely due to higher numbers of adenocarcinoma in the younger patients group. The effect of PCI was only significant in younger patients. This study was randomized based on treatment allocation and subgroups might be too small to detect significant differences. Therefore, our results are hypothesis generating and should be prospectively tested. Clinical trial identification: NCT01282437. Legal entity responsible for the study: Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT). Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Metabolic Culprits in Obese Pregnancies and Gestational Diabetes Mellitus: Big Babies, Big Twists, Big Picture
Authors: Linda A. Barbour
Journal: Diabetes Care (2019)

Pregnancy has been equated to a “stress test” in which placental hormones and growth factors expose a mother’s predisposition toward metabolic disease, unleashing her previously occult insulin resistance (IR), mild β-cell dysfunction, and glucose and lipid surplus due to the formidable forces of pregnancy-induced IR. Although pregnancy-induced IR is intended to assure adequate nutrition to the fetus and placenta, in mothers with obesity, metabolic syndrome, or those who develop gestational diabetes mellitus, this overnutrition to the fetus carries a lifetime risk for increased metabolic disease. Norbert Freinkel, nearly 40 years ago, coined this excess intrauterine nutrient exposure and subsequent offspring developmental risk “fuel-mediated teratogenesis,” not limited to only excess maternal glucose. Our attempts to better elucidate the causes and mechanisms behind this double-edged IR of pregnancy, to metabolically characterize the intrauterine environment that results in changes in newborn body composition and later childhood obesity risk, and to examine potential therapeutic approaches that might target maternal metabolism are the focus of this article. Rapidly advancing technologies in genomics, proteomics, and metabolomics offer us innovative approaches to interrogate these metabolic processes in the mother, her microbiome, the placenta, and her offspring that contribute to a phenotype at risk for future metabolic disease. If we are successful in our efforts, the researcher, endocrinologist, obstetrician, and health care provider fortunate enough to care for pregnant women have the unique opportunity to positively impact health outcomes not only in the short term but in the long run, not just in one life but in two—and possibly, for the next generation.
TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease
Authors: Matthew J. Haney, Natalia L. Klyachko, Emily B. Harrison, Yuling Zhao, Alexander V. Kabanov, Elena V. Batrakova
Journal: Advanced Healthcare Materials (2019)

Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV-producing macrophages with TPP1-encoding plasmid DNA (pDNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1-encoding pDNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV-TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV-TPP1 (≈70%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late-infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV-TPP1.
Circulating tumor cells (CTCs) in breast cancer without distant metastases.
Authors: Vera Gabaraeva, Oleg Ivanovich Kit, Inna Arnoldovna Novikova, Elena Alekseevna Nikipelova, Yuliana Sergeyevna Shatova, Andrey Vladimirovich Bakhtin, Elena N. Chernikova, Elizaveta A. Komova
Journal: Journal of Clinical Oncology (2015)

e22016 Background: The purpose of the study was to assessprobability of detecting CTCs in breast cancer without distant metastases. Methods: 25 stage IIa-IIIa stage breast cancer patients were recruited: 23 - infiltrating ductal carcinoma, 1 - infiltrative lobular carcinoma, 1 - mixed cancer. CellSearch Veridex system, Janssen, was used for the detection. CellTracks Analyzer II was used for scanning the material. Cells with EpCAM+/CD45-/CK8, 18, 19+ immunophenotype were registered as CTCs taking into account morphologic characteristics. CTCs < 5 were considered as the reference value. Results: The study showed single CTCs in 28% of the cases, the number did not reach the reference value in any case. Quantity of tumor cells varied from 1 to 4 cells in 7.5 ml of blood sample. Maximum content of tumor cells (4 cells) was registered in 4% of cases, 1 cell – 8%, 2 cells – 12%, 3 cells – 4%. Of 7 patients with CTCs, 42.9% had IIa stage of the disease, 28.6% - IIb, 28.6% - IIIa. Tendency for increased probability of CTCs detection in blood of patients with metastases to lymph nodes or other organs was noted (systemic cancer with bone metastases was found in a patient). CTCs were detected in blood of 3 of 15 patients (20%) without metastases and in 4 of 10 patients (40%) with metastases to lymph nodes or other organs. Increase in CTCs content from 1 to 4 cells was found in 1 patient after radical surgery which was probably associated with the surgery invasiveness and the release of single tumor cells into the blood stream; that will probably be important for choosing the following treatment strategy. Conclusions: CellSearch system allows detecting and phenotyping epithelial CTCs responsible for hematogenous metastasis. CTCs could be detected in patients with non-systemic breast cancer.
Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study
Authors: Caicun Zhou, Sang-We Kim, Thanyanan Reungwetwattana, Jianying Zhou, Yiping Zhang, Jianxing He, Jin-Ji Yang, Ying Cheng, Se-Hoon Lee, Lilian Bu, Tingting Xu, Li Yang, Chao Wang, Ting Liu, Peter N Morcos, You Lu, Li Zhang
Journal: The Lancet Respiratory Medicine (2019)
SAT-242-Liver stiffness measurement is not a predictive factor of HCC in HCV patients with severe fibrosis who achieved SVR by DAA
Authors: Aline Le Cleach, Violaine Ozenne, Marie Lequoy, nicolas Carbonell, Tony Andreani, Sara Lemoinne, Armelle Poujol-Robert, Christophe Corpechot, Olivier Chazouillères
Journal: Journal of Hepatology (2019)
The effect of proton pump inhibitors (PPI) on dacomitinib (DACO) pharmacokinetics and efficacy in non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutation
Authors: J. Li, D.J. Nickens, K. Wilner, W. Tan
Journal: Annals of Oncology (2019)

Background: Concomitant use of PPIs has been shown to decrease DACO AUClast and Cmax by approximately 39% and 51% in a healthy volunteer study. ARCHER-1050 (A1050) was a phase 3 study to evaluate DACO as first-line treatment for patients with EGFR-positive advanced NSCLC. A considerable number of patients in A1050 used concomitant PPIs. This analysis evaluates the effects of concomitant PPI use on DACO exposure and progression free survival (PFS) in NSCLC patients treated with DACO using data from A1050. Methods: Steady-state DACO trough concentrations (Ctrough) were collected on Day 1 of Cycles 2-6 (1 cycle = 28 days). Patients started DACO at 45 mg once daily (QD), but were permitted to dose reduce to 30 then 15 mg QD. The geometric mean of Ctrough (CGM) for each patient per dose level was calculated to represent the patient's Ctrough. Patients who reported using PPIs at least one dose before and at least one dose after starting DACO treatment were grouped as PPI users, while all other patients were grouped as non-PPI users. The DACO exposure, measured as geometric mean of CGM, was compared between the 2 groups. Statistical analyses were performed using the Kaplan-Meier method and Cox Regression adjusted for several confounding factors. All data processing and analyses were conducted in R, version 3.5.1 (R studio). Results: Of the 227 patients who were treated with DACO, baseline characteristics were similar between PPI user (n = 28) and non-PPI user (n = 199) groups, except that PPI user group had a higher percentage of non-Asian patients (61% vs. 20%) than the non-PPI use group. DACO exposure was similar in the 2 groups for each dose level. The median PFS values for PPI users and non-users were 13.1 and 14.9 months, respectively. The Cox Regression Model demonstrated no statistically significant difference in PFS (p > 0.05) between the 2 groups. Conclusions: PPI use appeared to have no impact on DACO exposure or on PFS in patients with EGFR-positive advanced NSCLC treated with DACO. Clinical trial identification: The data used in this abstract were from the multinational, multicenter, randomized, open-label, phase III ARCHER 1050 study (NCT01774721). Legal entity responsible for the study: Pfizer. Funding: Pfizer. Disclosure: D.J. Nickens, K. Wilner, W. Tan: Employee: Pfizer. All other authors have declared no conflicts of interest.
Living with boys
Authors: Vicki Mottram
Journal: BMJ (1999)

I have a confession to make. I have been thinking about this for some time, and I cannot live with it on my conscience any longer. It is time for the truth: I do not understand the opposite sex.

Until June of this year I was not even aware I had this problem. I subscribed, in blissful ignorance, to that modern day, politically correct myth that, aside from varying fleshy appendages, men and women are essentially the same. I firmly believed that I could do anything a man could. Then in June I moved into my new house, sharing with three lads. I still believe that I can do anything a man …
The First Multicenter Evidence for Ocular Point-of-Care Ultrasonography for Retinal Detachment by Emergency Physicians
Authors: John Bailitz
Journal: JAMA Network Open (2019)

Shadi Lahham, MD, MS; Inna Shniter, MD; Maxwell Thompson, MD; Dana Le, BS; Tushank Chadha, BS; Thomas Mailhot, MD; Tarina Lee Kang, MD; Alan Chiem, MD, MPH; Stephanie Tseeng, MD; John C. Fox, MD
SAT-401-Necroptosis signaling molecules regulate hepatic stellate cell activation via MLKL oligomerization-cell death independent pathway
Authors: Joo Hyun Sohn, Dae Won JUN, Jinhwa Park, Bo-Kyeong Kang, Mi Mi Kim, Jaeyoon Jeong, Hyunwoo Oh, Hyo Young Lee, Sang Bong Ahn, Yong Kyun Cho, Dong Hee Koh
Journal: Journal of Hepatology (2019)
A new bioinformatic pipeline allows the design of small, targeted gene panels for efficient TMB estimation
Authors: P. Manca, I. Mallona, D. Santini, G. Tonini, C.D. Rolfo, M.D. Robinson, F. Pantano
Journal: Annals of Oncology (2019)

Background: The tumor mutation burden (TMB) is emerging as a prognostic and predictive marker for the response to immune checkpoint blockade (ICB) drugs. We aimed to develop a new method for the definition of gene panels that can precisely estimate the TMB with a considerably lower amount of genome. Methods: We developed a bioinformatic pipeline which allows the design of gene panels suited for TMB estimation. The method is particularly efficient in optimizing the balance between the precision of the TMB estimate and the length of the gene panel created. We tested in silico the efficiency of different panels obtained with our method in an independent cohort of patients with lung adenocarcinoma (LUAD). We also compared in the same cohort of patients the performance of our panels with the performance of existing gene panels. Results: We designed a 0.080 Megabases (Mb) long gene panel which estimated TMB in an independent LUAD cohort with an acceptable precision (adjusted R2=0.745; Spearman ρ = 0.827, Pearson ρ = 0.864). The panel showed 0.89 accuracy in the identification of TMB-high patients (25/28 patients, CI: 0.73 – 0.96). Every unitary increase of our TMB estimate was associated with lower risk of disease progression (univariate analysis: HR = 0.78; CI: 0.65-0.93; p = 0.006; multivariate analysis: HR = 0.8; CI: 0.63-1.01; p = 0.0621). Different existing panels of less than 1 Mb long showed a lower adjusted R2 when compared to our gene panel (Table). Two other commercial panels of 1.9 Mb and 1.1 Mb showed a similar adjusted R2 to panels of the same lengths built with our method; nevertheless, they showed a lower accuracy in TMB-high patients definition (ROC curves AUC of 0.862, 0.870, 0.946 and 0.967 were observed, respectively, for the commercial 1.9 Mb panel, the commercial 1.1 Mb panel, our 0.080 Mb panel and our 2.0 Mb panel).Table24PPerformance (adjusted R2) in TMB estimation of existing gene panels and gene panels built with our method of similar length.Other panels IDs (length)Other panels performanceOur panels performance (length)panel #1 (0.187 Mb)0.760.83 (0.187 Mb)panel #2 (0.240 Mb)0.580.85 (0.25 Mb)panel #3 (0.300 Mb)0.690.85 (0.25 Mb)panel #4 (0.98 Mb)0.810.91 (0.98 Mb)panel #5 (1.1 Mb)0.920.92 (1.1 Mb)panel #6 (1.9 Mb)0.930.93 (2.0 Mb) Open table in a new tab Conclusions: Our method allows the design of gene panels particularly suitable for the TMB estimation in patients with LUAD and outperforms existing gene panels less than 1 Mb long. Legal entity responsible for the study: Paolo Manca. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 15108: Outcomes in Patients With Pericardial Effusion Requiring Drainage After Electrophysiology Procedures
Authors: Amgad Mentias, Samuel Horr, Ahmed El-Telbany, Mohamed Kanj, Allan Klein
Journal: Circulation (2015)

Background: Pericardial effusion (PE) is a known complication of electrophysiological procedures (EPP). We sought to describe patient characteristics and outcomes in PE requiring drainage after EPP. Methods: We identified 114 patients who underwent EPP at our center from 2000 to 2012 and had an intervention for new pericardial effusion up to 1 month after the EPP. Baseline demographic and clinical data were recorded. Primary outcome was 30 days mortality after PE drainage. Secondary outcome was major bleeding (drop in hemoglobin ≥ 3 gm/dl or requiring blood transfusion) after PE drainage. Results: Mean age was 65±13 years (48% men). Mean ejection fraction (EF) was 53±12. Hypertension and diabetes mellitus were found in 54 and 49%. Heart failure (HF) and coronary artery disease were present in 26 and 27%. Dual antiplatelet therapy was used in 6.7%, while combined Aspirin, Clopidogrel and oral anticoagulant was used in 1.7%. Intra-procedural heparin was used in 62%. Presenting symptoms were chest pain, shortness of breath and altered mental status in 51, 42 and 26%. Pulmonary vein isolation was done in 50% while pacemaker insertion and ventricular tachycardia ablation were done in 8.8 and 9.7%. Drainage of PE was done by emergent and elective pericardiocentesis in 65 and 28% while elective pericardial window and emergent sternotomy for exploration was done in 2.6 and 4.4%. Re-accumulation occurred in 12.3% and a second intervention was required in 57% of those patients. The primary outcome occurred in 2.6% and secondary outcome occurred in 45.6%. Predictors of mortality were older age, higher drop in hemoglobin, and lower EF (all p&lt;0.05). Predictors of secondary outcome were HF and higher INR at time of procedure (both p=&lt;0.05). Conclusion: Pericardial effusion after an electrophysiology procedures requiring intervention is associated with a mortality of 2.6% within 30 days. Older age, lower ejection fraction and higher drop in hemoglobin were associated with worse outcomes.
Survival outcome of cancer patients with pericardial effusions.
Authors: Danielle El Haddad, Cezar Iliescu, William Nassib William, Elie Mouhayar
Journal: Journal of Clinical Oncology (2015)

9573 Background: Pericardial effusion is a common finding in cancer patients and can be related to the tumor infiltration of the pericardial space or can be secondary to cancer therapy (chemotherapy or chest radiation). Impact of mechanism of effusions (malignant versus non-malignant effusions) on cancer patient’s outcome is not well defined. Our aim was to evaluate survival outcome of these patients based on the presence or absence of malignant cells in their effusions. Methods: A total of 212 cancer patients who underwent pericardiocentesis for pericardial effusion between November 2009 and October 2014 at UT/MDACC were included in the study. Results: Overall median survival of the cohort was 143 days (95% CI, 95 to 221) and 130 (61%) patients died within 2 years from the procedure. The two most common solid tumors associated with pericardial effusions were lung [61(29%)] and breast [22 (10%)] cancer. In a multivariable analysis model, age > 65y, lung cancer, platelet counts < 20.000, and the presence of malignant cells in the pericardial fluid were independently associated with poor prognosis. Malignant pericardial effusion was pathologically confirmed in 37 (61%) patients with lung cancer and 16 (73%) patients with breast cancer. Lung cancer patients with proven malignant effusions had a significantly shorter overall median survival compared to those with non-malignant effusions (24 patients or 39% of lung cancer patients) (1-year survival estimate of 16.2% (95% CI, 5.6%-31.6%) versus 49.0% (95% CI, 26.7%-68.0%) respectively. Log-rank test p-value = 0.0101). Such finding was not observed in the subgroups of breast cancer patients (1-year survival estimate of 40.2% (95% CI, 16.0%-63.6%) versus 40.0% (95% CI, 5.2%-75.3%) respectively. Log-rank test p-value = 0.4170). Conclusions: The presence of proven malignant cells in pericardial effusion appears to significantly impact survival outcome of patients with lung cancer, but not those with breast cancer.