tbuckley/cabot-search huggingface dataset:
Evaluation of whole body MRI for early detection of cancers in subjects with germ-line TP53 mutation (Li-Fraumeni syndrome).
Authors: Olivier Caron, Thierry Frébourg, Emmanuelle Bourbouloux, Valérie Bonadona, Véronique Mari, Christine Maugard, François Eisinger, Emmanuelle Barouk-Simonet, Marion Gauthier-Villars, Julie Tinat, Catherine Nogues, Catherine Dugast, Sandra Canale, Claire Guillemeau, Patrick R. Benusiglio, Laurence Brugieres
Journal: Journal of Clinical Oncology (2013)

TPS1607 Background: The TP53 germline mutation carriers have a huge increase of cancer risk. The cancer spectrum is particularly broad (breast, sarcoma, brain tumour, leukaemia, …). The clinical management of these people is challenging, mainly concerning sarcoma screening. Moreover, some data let speculate that normal cells of these carriers are particular hypersensitive to X-rays. Among major breakthroughs in radiology, whole-body MRI (WBMRI) may contribute to TP53 carriers surveillance. In order to update the french guidelines on Li-Fraumeni families management, the LIFSCREEN study ( NCT01464086 ) was designed to assess its usefulness in France. Methods: This open, randomized, multicentric trial will evaluate the efficacy and tolerability of two screening schemes, avoiding irradiating exams. In the standard arm, people undergo clinical exam, abdominal sonography, brain MRI, Complete Blood Count, breast MRI, breast sonography, depending on the age) at inclusion, Month 12, Month 24, and a study visit at Month 36. In the experimental arm, people included undergo the same scheme, completed by a diffusion WBMRI at M0, M12, M24. At each round, quality of life and psychological impact will be assessed by self-questionnaires and semi-structured qualitative interviews. In an ancillary study, serums will be collected at each step. Subjects meeting these criteria are eligible: any TP53 germline mutation carrier, with or without personal cancer history, aged &gt;5 and &lt;71. A hundred people will be enrolled and randomized. The primary objective is to assess the efficiency of each scheme, evaluated by the cancer incidence at 3 years. Notably, sensitivity and specificity of each exam will be studied. As a secondary objective, the acceptability of each scheme will be assessed by quality of life / psychological questionnaires interpretation (SF-36, HADS, TAS 20, CBCL, CDI, R-CMAS, depending on subject’s age). Recruitment began in December, 2011. To date, 32 patients have been enrolled on 8 french study sites. The study will soon be implemented in another 12 sites. This academic study is, to our knowledge, the first randomized trial on this topic, and supported by the french “Ligue contre le cancer.” Clinical trial information: NCT01464086.
A phase II trial of weekly cisplatin and docetaxel in advanced non-small cell lung cancer (NSCLC)
Authors: M. A. Sovak, S. Lutzker, L. Guensch, M. Joyce, S. Schwartz, Y. Wu, L. Zheng, J. Aisner
Journal: Journal of Clinical Oncology (2007)

18150 Background: Every 3-week cisplatin doublets used to treat advanced NSCLC carry a significant risk of renal and other toxicities and can be difficult for patients with co-morbidities. To reduce these toxicities, we conducted a phase II study to evaluate the efficacy and toxicity of weekly cisplatin and docetaxel in advanced NSCLC. Methods: Eligibility included patients with advanced or recurrent NSCLC, ECOG PS of 0–1, and no prior chemotherapy for metastatic disease. This Cancer Institute of New Jersey network, single stage phase II clinical trial was designed to give 3 weekly doses of cisplatin at 25 mg/m 2 and docetaxel at 35 mg/m 2 , followed by 1 week of rest, for a total of 6 cycles of therapy. Toxicity was monitored weekly, and disease evaluation was performed every 2 cycles. The primary endpoint was response rate (RR); secondary endpoints included time to progression (TTP), median and 1-year survival. Results: From 12/03 to 11/06, 36 patients were enrolled so far. The median age of patients is 63 (range 47–78), the majority is white (n=33), 29 have stage IV disease, and half (n=18) are women. Fourteen have an ECOG PS=0 and 22 with PS=1. Histologic subtypes are: adenocarcinoma (n=24), NSCLC NOS (n=7), squamous (n=5). Eleven patients received = 4 cycles of therapy; median number of cycles delivered is 2.5. Reasons for treatment discontinuation include completion of therapy (n=5), progression of disease (n=16), adverse events (n=8), and patient preference (n=4). Three patients continue on therapy at this time. No complete responses were yet observed; 8 patients (22%) achieved a partial response; 10 patients had stable disease, 10 patients progressed, and 8 came off study before first disease evaluation. Median TTP was 3.1 months (mo) (95% CI 2, 5.5), median survival is 8.3 mo (95% CI 5,16.2) and 1-year survival is 39% (95% CI 20, 57). Most toxicities were mild but also included neutropenia (grade 3, n=1; grade 4, n=1), neutropenic fever (n=1), renal toxicity (grade 3, n=2), nausea (grade 3, n=1), fatigue (grade 3, n=3), diarrhea (grade 3, n=4) and metabolic abnormalities (grade 3, n=3). Conclusion: Weekly cisplatin and docetaxel is well tolerated with a low incidence of toxicity and demonstrates activity similar to every 3-week treatment in patients with advanced NSCLC. No significant financial relationships to disclose.
Need for an International Consensus on the Definition of Bronchopulmonary Dysplasia
Authors: Tetsuya Isayama, Prakesh S. Shah
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

respiratory failure and parenchymal lung disease.Few clinicians would question the fact that an infant who requires 50% oxygen has worse lung function than one who is receiving 25% oxygen to maintain normal arterial oxygenation.Before concluding that the need for oxygen at 36 weeks postmenstrual age is not informative about the severity of lung disease or long-term morbidities, we need to thoroughly evaluate the association between different fractions of inspired oxygen and long-term respiratory or neurologic outcomes while adjusting for other confounding factors.Another limitation of the proposed definition is that it is based on a one-time assessment.In this situation, a preterm infant who exhibits acute respiratory deterioration at approximately 36 weeks and needs mechanical ventilation would be labeled as having severe BPD even if his or her lungs were normal.This limitation can be easily avoided by including an indicator of the chronicity of the parenchymal lung disease.Although the proposed definition may work in a large population base and predict long-term outcomes, it will not always reflect the severity of lung disease and therefore will not be appropriate for research or benchmarking focused on pulmonary outcomes.Although most clinicians would agree that more contemporary definitions of BPD are necessary, these definitions must be based on the premise that BPD is secondary to chronic parenchymal lung disease.Therefore, any definition of BPD, whether based on diagnostic or therapeutic criteria, should reflect the severity of lung disease and exclude nonpulmonary indications for respiratory support.The proposed definition, though marginally better at predicting outcomes, will not consistently meet the challenge of defining BPD.
Clinical differences in sarcoidosis patients with and without lymphoma: a single-centre retrospective cohort analysis
Authors: Stefania Cerri, Matteo Fontana, Sara Balduzzi, Leonardo Potenza, Paola Faverio, Mario Luppi, Roberto D'Amico, Paolo Spagnolo, Enrico Clini, Fabrizio Luppi
Journal: European Respiratory Journal (2019)

<b>Patients with sarcoidosis showed a more frequent lung involvement and a restrictive ventilatory defect. Serum ACE was markedly higher in patients with sarcoidosis–lymphoma syndrome, indicating that those patients should be monitored over longer periods.</b>http://bit.ly/327WBUM
Metachronous Advanced Neoplasia on Surveillance Colonoscopy in Patients With Young- vs Older-onset of Colorectal Cancer
Authors: Jamie Tjaden, Charles Muller, Gina Wideroff, Karen Ma, Jinendra Satiya, Daniel Sussman, Eugene Yen, Sonia S. Kupfer, Joshua Melson
Journal: Clinical Gastroenterology and Hepatology (2019)
Tumor necrosis factor-inducible gene 6 reprograms hepatic stellate cells into stem-like cells, which ameliorates liver damage in mouse
Authors: Sihyung Wang, Jieun Kim, Chanbin Lee, Dayoung Oh, Jinsol Han, Tae-Jin Kim, Sang-Woo Kim, Young-Su Seo, Seh-hoon Oh, Youngmi Jung
Journal: Biomaterials (2019)
Impact of complete lymphadenectomy in stage I melanoma: SEER analysis, 2004-2009.
Authors: Victoria Stager, Elizabeth Anne Arena, Joslyn Albright, Mark B. Faries
Journal: Journal of Clinical Oncology (2013)

9101 Background: Stage I melanoma has excellent prognosis, yet it remains a treacherous entity leading to fatal disease progression in a small and ill-defined population of patients. Role of complete lymphadenectomy in early melanoma is not determined. Methods: We used the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2009 to identify patients who underwent wide local excision (WLE) with or without nodal surgery for management of AJCC Stage I primary cutaneous melanoma. Patients with complete data on age, race, sex, and primary tumor histology and anatomic site were categorized by type of surgical treatment into WLE, WLE+sentinel node biopsy (SNB), or WLE+complete lymphadenectomy (CLND) groups. Five-year disease-specific survival (DSS) was determined by treatment group and by sentinel node status. Specific risk factors were identified using multivariate analysis. Results: During the selected time period, 51,573 patients were diagnosed with AJCC Stage I cutaneous melanoma. Rate of SNB was 22%, and out of this group, 2% of patients had metastases to the regional lymph nodes. Five-year DSS was decreased in the node-positive group compared to the patients who had a negative SNB or WLE only (HR=4.95). Rate of CLND was 67%, and it did not improve survival of the patients with positive SNB (5-year DSS 83% vs. 79%, p=0.29). Performance of CLND did not correlate with age, histological type, presence of ulceration, or Breslow depth. Conclusions: SEER database suggests that a clinical equipoise regarding the utility of CLND in patients with positive SLN remains. These findings justify ongoing MSLT II.
Ebola: calls for second experimental vaccine in DRC after WHO declares emergency
Authors: Sophie Arie
Journal: BMJ (2019)

Experts and aid agencies are calling for a second experimental vaccine to be used now that the World Health Organization has declared the rapidly expanding outbreak of Ebola in the Democratic Republic of Congo (DRC) to be a public health emergency of international concern (PHEIC).

Almost a year after the outbreak began, “the disease is not under control and we need a change of gear,” said Joanne Liu, international president of Medecins Sans Frontieres.

Traditional methods of controlling the disease have not worked and “a large scale approach is needed for prevention, this means better access to vaccination for the population to reduce transmission,” said Liu.

WHO announced a PHEIC, the highest level of global health alarm, on Wednesday1 after Ebola reached the major transport …
Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease
Authors: Hiroyuki Ishiura, Shota Shibata, Jun Yoshimura, Yuta Suzuki, Wei Qu, Koichiro Doi, M. Asem Almansour, Junko Kanda Kikuchi, Makiko Taira, Jun Mitsui, Yuji Takahashi, Yaeko Ichikawa, Tatsuo Mano, Atsushi Iwata, Yasuo Harigaya, Miho Kawabe Matsukawa, Takashi Matsukawa, Masaki Tanaka, Yuichiro Shirota, Ryo Ohtomo, Hisatomo Kowa, Hidetoshi Date, Aki Mitsue, Hiroyuki Hatsuta, Satoru Morimoto, Shigeo Murayama, Yasushi Shiio, Yuko Saito, Akihiko Mitsutake, Mizuho Kawai, Takuya Sasaki, Yusuke Sugiyama, Masashi Hamada, Gaku Ohtomo, Yasuo Terao, Yoshihiko Nakazato, Akitoshi Takeda, Yoshio Sakiyama, Yumi Umeda-Kameyama, Jun Shinmi, Katsuhisa Ogata, Yutaka Kohno, Shen-Yang Lim, Ai Huey Tan, Jun Shimizu, Jun Goto, Ichizo Nishino, Tatsushi Toda, Shinichi Morishita, Shoji Tsuji
Journal: Nature Genetics (2019)
Novel treatment options in the management of metastatic castration-naïve prostate cancer; which treatment modality to choose?
Authors: B.P.S. Belderbos, R. de Wit, M.P.J. Lolkema, R.H.J. Mathijssen, R.J. van Soest
Journal: Annals of Oncology (2019)

Androgen-deprivation therapy (ADT) has been the mainstay of treatment of metastatic prostate cancer since the first report of its hormonal dependence in the 1940s. Since 2015, the addition of docetaxel and the addition of abiraterone to ADT have conferred substantial overall survival benefit in men with metastatic castration-naïve prostate cancer (mCNPC). The shift of these treatment options for metastatic prostate cancer from the castration-resistant setting to the castration-naïve setting has led to new challenges in the management of this disease. It remains to be determined which patients may benefit most from either early concomitant docetaxel or from abiraterone with ADT, since biomarkers for early therapy response and risk stratification are currently lacking. Therefore, the ability to personalize medicine is hampered. Furthermore, the earlier detection of metastatic prostate cancer by using new imaging modalities makes the application of clinical trial results in daily practice increasingly challenging. Recently, both local radiotherapy to the primary tumor combined with ADT and abiraterone combined with ADT showed a survival benefit in low-volume disease patients. The latest data also demonstrated a survival benefit with the addition of apalutamide or enzalutamide to ADT. The extent of metastatic disease may become one of the most important factors to determine treatment choice. In this review article, we summarize trial data to provide guidance for treatment selection in metastatic castration-naïve prostate cancer.
A prognostic model for predicting overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) after docetaxel.
Authors: Kim N. Chi, Thian San Kheoh, Charles J. Ryan, Arturo Molina, Joaquim Bellmunt, Nicholas J. Vogelzang, Dana E. Rathkopf, Karim Fizazi, Philip W. Kantoff, Jinhui Li, Johann Sebastian De Bono, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

5013 Background: COU-AA-301 was a multinational, randomized, controlled, phase III trial comparing AA + prednisone (P) (n = 797) versus placebo + P (n = 398) in mCRPC pts post-docetaxel. Using data from that trial, we developed a prognostic model for predicting OS in pts treated with AA post-chemotherapy, with a focus on readily assessable clinical parameters. Methods: The analyses used data from pts treated with AA in the COU-AA-301 trial for whom relevant baseline data were available (n = 729). Baseline variables were assessed for association with OS through a univariate Cox proportional hazards regression model. High/low values for accepted normal ranges were used for laboratory parameters. The Cox proportional hazards regression was used with a stepwise procedure to identify independent prognostic factors for OS. The model was subject to sensitivity analyses and the C-index was utilized as a measure of model accuracy. Results: The following risk factors were associated with a poor prognosis: ECOG performance status (only pts with scores of ≤ 2 were eligible for this trial) of 2 (HR = 2.19, p &lt; 0.0001), presence of liver metastases (HR = 2.00, p &lt; 0.0001), time from start of initial LHRH agonist therapy to start of AA treatment ≤ 36 months (HR = 1.30, p = 0.0078), low albumin (HR = 1.54, p &lt; 0.0001), high ALP (HR = 1.38, p = 0.0016), and high LDH (HR = 2.31, p &lt; 0.0001). Patients were categorized into 3 risk groups (good prognosis, n = 369; intermediate prognosis, n = 321; poor prognosis, n = 107) based on total number of risk factors and median OS calculated for each group (table). The C-index was 0.74 (95% CI: 0.68, 0.80). Conclusions: This prognostic model uses readily available clinical parameters to conveniently assess risk for mCRPC pts previously treated with docetaxel and initiating treatment with AA + P. If validated, the model will be useful in clinical practice and clinical trials. Clinical trial information: NCT00638690. [Table: see text]
Comment on Nanditha et al. Secular TRends in DiabEtes in India (STRiDE–I): Change in Prevalence in 10 Years Among Urban and Rural Populations in Tamil Nadu. Diabetes Care 2019;42:476–485
Authors: Thaddäus Tönnies, Annika Hoyer, Ralph Brinks
Journal: Diabetes Care (2019)

Nanditha et al. (1) recently reported on time trends in diabetes prevalence in Tamil Nadu, India, between 2006 and 2016. They found stronger increases in prevalence in periurban villages (PUVs) and towns compared with cities, while the absolute prevalence was still highest in cities. Based on these results, we estimate the incidence of diabetes in Tamil Nadu in order to provide further insights into the diabetes epidemic in India.

It has been shown that mathematical relationships can be used to estimate the age-specific incidence rate using input values for the prevalence, its temporal change, the mortality rate of the general population, and the mortality …
The Histone Methyltransferase Setdb2 Modulates Macrophage Phenotype and Uric Acid Production in Diabetic Wound Repair
Authors: Andrew S. Kimball, Frank M. Davis, Aaron denDekker, Amrita D. Joshi, Matthew A. Schaller, Jennifer Bermick, Xianying Xing, Charles F. Burant, Andrea T. Obi, Dylan Nysz, Scott Robinson, Ron Allen, Nicholas W. Lukacs, Peter K. Henke, Johann E. Gudjonsson, Bethany B. Moore, Steve L. Kunkel, Katherine A. Gallagher
Journal: Immunity (2019)
Abstract P369: Hepatocyte Growth Factor is Positively Associated With Progression of Atherosclerosis: the Multi-Ethnic Study of Atherosclerosis
Authors: Elizabeth J Bell, Paul A Decker, James H Stein, Michael Y Tsai, James S Pankow, Naomi Q Hanson, Christina L Wassel, Nicholas B Larson, Kevin Cohoon, Matthew Budoff, Joseph F Polak, Suzette J Bielinski
Journal: Circulation (2017)

Introduction: Hepatocyte growth factor (HGF) is released in response to endothelial injury, and higher levels of circulating HGF are associated with atherosclerosis. However, the association of HGF with atherosclerosis progression is unknown. Hypothesis: Circulating HGF is positively associated with atherosclerosis progression, measured as progression of 1) carotid artery plaque and 2) coronary artery calcium (CAC). Methods: The Multi-Ethnic Study of Atherosclerosis is a large, population-based cohort study of adults aged 45-84 and free of clinical cardiovascular disease. Participants had HGF measured in serum at baseline (2000-02), and were followed for progression of carotid plaque and CAC through 2012. We defined CAC and carotid plaque progression as dichotomous variables (progression, no progression). Carotid plaque progression is an increase in the number of carotid plaques. We used the Hokanson method to define CAC progression as an increase of ≥ 2.5 mm 3 in the square root-transformed calcium volume score. Relative risk regression quantified the association between HGF and carotid plaque progression. Cox regression models using inverse-probability-of-attrition weights estimated the association of HGF with progression of CAC. All effect estimates are adjusted for potential confounding variables. Results: The cohort included 6714 Americans with HGF measurements: 2593 non-Hispanic white, 797 Chinese, 1848 black, and 1476 Hispanic Americans. In 3363 participants with measurements for both carotid plaque and HGF, each standard deviation (259 pg/ml) increase in HGF was associated with a 4% greater risk (95% CI: 1.01-1.07) of carotid plaque progression (n=1875), which did not differ by race/ethnicity (interaction p = 0.3). Out of 6714 participants with measurements for both CAC and HGF, 2994 had CAC progression during follow-up. The association of HGF with CAC progression differed by race/ethnicity (interaction p = 0.01). Each standard deviation increase of HGF was associated with a 10% greater risk of CAC progression in non-Hispanic white (95% CI: 1.05-1.16) and black Americans (95% CI: 1.03-1.17), while HGF was not associated with CAC progression in Chinese (p = 0.5) nor Hispanic (p = 0.7) American participants. Conclusions: Circulating HGF was associated with a modestly increased risk of atherosclerosis progression in this large and diverse population, with the strongest associations between HGF and CAC progression in non-Hispanic white and black Americans. Our results suggest that HGF may have utility as a marker of atherosclerosis progression in some populations.
Decoding cancer heterogeneity: studying patient-specific signaling signatures towards personalized cancer therapy
Authors: Efrat Flashner-Abramson, Swetha Vasudevan, Ibukun Adesoji Adejumobi, Amir Sonnenblick, Nataly Kravchenko-Balasha
Journal: Theranostics (2019)

The past years have witnessed a rapid increase in the amount of large-scale tumor datasets.The challenge has now become to find a way to obtain useful information from these masses of data that will allow to determine which combination of FDA-approved drugs is best suited to treat the specific tumor.Various statistical analyses are being developed to extract significant signals from cancer datasets.However, tumors are still being assigned to pre-defined categories (breast luminal A, triple negative, etc.), conceptually contradicting the vast heterogeneity that is known to exist among tumors, and likely overlooking unique tumors that must be addressed and treated individually.We present herein an approach based on information theory that, rather than searches for what makes a tumor similar to other tumors, addresses tumors individually and unbiasedly, and impartially decodes the critical patient-specific molecular network reorganization in every tumor.Methods: Using a large dataset obtained from ~3500 tumors of 11 types we decipher the altered protein network structure in each tumor, namely the patient-specific signaling signature.Each signature can harbor several altered protein subnetworks.We suggest that simultaneous targeting of central proteins from every altered subnetwork is essential to efficiently disturb the altered signaling in each tumor.We experimentally validate our ability to dissect sample-specific signaling signatures and to rationally design personalized drug combinations.Results: We unraveled a surprisingly simple order that underlies the extreme apparent complexity of tumor tissues, demonstrating that only 17 altered protein subnetworks characterize ~3500 tumors of 11 types.Each tumor was described by a specific subset of 1-4 subnetworks out of 17, i.e. a tumor-specific altered signaling signature.We show that the majority of tumor-specific signaling signatures are extremely rare, and are shared by only 5 tumors or less, supporting a personalized, comprehensive study of tumors in order to design the optimal combination therapy for every patient.We validate the results by confirming that the processes identified in the 11 original cancer types characterize patients harboring a different cancer type as well.We show experimentally, using different cancer cell lines, that the individualized combination therapies predicted by us achieved higher rates of killing than the clinically prescribed treatments.Conclusions: We present a new strategy to deal with the inter-tumor heterogeneity and to break down the high complexity of cancer systems into simple, easy to crack, patient-specific signaling signatures that guide the rational design of personalized drug therapies.