tbuckley/cabot-search huggingface dataset:
Association of tumor mutational burden in cutaneous squamous cell carcinoma with genomic alterations in Notch family receptors.
Authors: Eric Allan Severson, Shakti Ramkissoon, Sugganth Daniel, Jo-Anne Vergilio, Laurie M. Gay, Julia Andrea Elvin, James Suh, Garrett Michael Frampton, Siraj Mahamed Ali, Vincent A. Miller, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

e13031 Background: In Cutaneous Squamous Cell Carcinoma (cSqCC), Notch1, Notch2, and Notch3 have been identified as tumor suppressors with a high rate of inactivating mutations early in cSqCC pathogenesis. Despite the high frequency of alterations, the biologic and therapeutic implications of Notch genomic alterations (GAs) in cSqCC are incompletely understood. Methods: 232 FFPE samples of cSqCC were evaluated by comprehensive genomic profiling (CGP) of 315 genes and analyzed for all classes of GAs, with diagnoses confirmed by central pathology review. Notch GAs with unknown functional impact were excluded. Tumor mutational burden (TMB) was calculated from 1.11 Mb of sequenced DNA and reported as mutations/Mb. Results: The cohort of 232 samples was 78% male and 22% female, aged from 17 to 88, with confirmed metastatic disease in 32% of cases. 115 (50%) samples had a Notch family member GA with a known or predicted functional impact. 96 cases had Notch1 GAs, 43 cases had Notch2 GAs, and 14 cases had Notch3 GAs with 40 cases having GAs in multiple Notch family members. These mutations were 41% missense, 34% nonsense, 15% splice site, 9% frameshift indels, and 1% non-frameshift indels alterations. Patients with Notch GAs were significantly older (median 70 years old vs median 64, p &lt; 0.01). TMB was increased among samples with Notch GAs (median TMB of 63 mutations/mb versus 20 mutations/mb, p &lt; 1x10 -6 ), with similar differences for primary and metastatic samples. Cases with Notch GAs had more total GAs per case (mean 10.4 vs 7.4, p &lt; 1.5x10 -10 ); however, the top co-mutated genes were the same (TP53, CDKN2A, FAT1, MLL2). Both groups had a high proportion of C- &gt; T/G- &gt; A transitions, consistent with UV damage; however, the proportion was higher in cases with Notch GAs (median 83% vs 80%) - a difference seen in primary and metastatic samples. Conclusions: 50% of cSqCC cases had a Notch family member loss of function GA, which was associated with increased TMB in the primary and metastatic setting. With pre-clinical models and case studies showing responses to PD-1 inhibitors in cSqCC, further investigations are warranted into the associations of Notch GAs with mutational burden and response to immunotherapy.
Prognostic Significance of a Polymerase Chain Reaction–Detectable Dominant T-Lymphocyte Clone in Cutaneous Lesions of Patients With Mycosis Fungoides
Authors: Marie-Hélène Delfau-Larue, Sophie Dalac, Eric Lepage, Tony Petrella, Janine Wechsler, Jean-Pierre Farcet, Martine Bagot
Journal: Blood (1998)
Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial
Authors: Seth F Oliveria, Ramon L Rodriguez, Dawn Bowers, Daniel Kantor, Justin D Hilliard, Erin H Monari, Bonnie M Scott, Michael S Okun, Kelly D Foote
Journal: The Lancet Neurology (2017)
Feasibility of molecular profiling based assignment of cancer treatment (MPACT): A randomized NCI precision medicine study.
Authors: Alice P. Chen, Mickey Williams, Shivaani Kummar, Chih-Jian Lih, Vivekananda Datta, Eric Polley, Yingdong Zhao, Larry Rubinstein, Geraldine Helen O'Sullivan Coyne, Robert S. Meehan, Nancy Moore, Elad Sharon, Alida Palmisano, David Sims, Robin Harrington, Courtney Bouk, Kneshay N Harper, Richard Simon, Barbara A. Conley, James H. Doroshow
Journal: Journal of Clinical Oncology (2016)

2539 Background: The NCI is conducting a double blind, randomized trial to evaluate whether refractory cancer patients (pts) are more likely to derive clinical benefit if treated with agents targeting a molecular abnormality in their tumors than if treated with non-matched therapeutic agents. The MPACT Trial (NCT01827384) was opened at the Developmental Therapeutics Clinic, NCI to test the feasibility of the design in 60 pts prior to opening as a multicenter study. Methods: Pts with progressive solid tumors after treatment (tx) with ≥ one line of standard therapy, with adequate organ function, KPS ≥ 70%, tumor amenable to percutaneous biopsy (bx) were eligible. Bx specimens were evaluated for mutations in one of 3 genetic pathways (DNA repair, PI3K, or RAS/RAF/MEK). If an actionable mutation (aMOI) was found in ≥ one pathway, pts were assigned tx using a rules-based algorithm (Genemed) that used a 2:1 randomization favoring agents potentially active in the mutational pathway versus the other drugs used for this trial that targeted other pathways. The tx arms are: AZD 1775 + carboplatin; or veliparib + temozolomide (DNA repair); everolimus (PI3K); and trametinib (RAS/RAF/MEK). Response rate (CR+PR) and/or 4-month PFS will be compared between the randomized groups. At first progression, pts molecular profiles are unblinded to clinicians. If a pt was treated with an agent from the unmatched drug set, pt is crossed over to targeted therapy. Results: Sixty pts have been enrolled and screened with NGS using a panel of 20 genes between February 2014 & July 2015. Pt characteristics: 33 pts male, median age 55 years (range 23-76), KPS 80-90%, 1-4 (range) of prior treatments. Most common bx site was liver. Eight pts had sarcomas, 52 had carcinomas. One pt had PE prior to bx. Only 4 bx failed to yield sufficient tumor and nucleic acid for the NGS assay. Two additional pts were successfully rebx. Of 55 pts, 29 (52%) had tx assignment. Average time from bx to assay report has been 6.6 days (range 5 – 12 days). 21 pts started assigned tx. Conclusions: These results demonstrate the feasibility of assigning tx based on real-time molecular profiling in the setting of a randomized study design. MPACT will open in other centers in 2016. Clinical trial information: NCT01827384.
Erratum: Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11 (Nature Genetics (2007) 39, (1434-1436))
Authors: H Houlden, J Johnson, C Gardner-Thorpe, T Lashley, D Hernandez, P Worth, AB Singleton, DA Hilton, J Holton, T Revesz, MB Davis, P Giunti, NW Wood
Journal: Nature Genetics (2008)
Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of influenza virus infection through activation of heme oxygenase-1
Authors: Jinqiu Yin, Linlin Ma, Huiqiang Wang, Haiyan Yan, Jin Hu, Wen Jiang, Yuhuan Li
Journal: Acta Pharmaceutica Sinica B (2017)

As a leading cause of respiratory disease, influenza A virus (IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH) is a famous traditional Chinese medicine (TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB), which subsequently upregulated heme oxygenase-1 (HO-1) expression. Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions, CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.
Evaluation des pratiques d'hygiène en endoscopie digestive. Résultats d'un audit clinique portant sur 277 établissements du sud-ouest
Authors: JL Payen, JL Payen, E Galy, D Zaro-Goni, C Barrue
Journal: Endoscopy (2006)

L'audit clinique est une méthode d'évaluation qui permet à l'aide de critères déterminés, de comparer des pratiques de soins à des références admises en vue de mesurer la qualité de ces pratiques et des résultats de soins avec l'objectif de les améliorer (ANDEM).<o: p></o: p> Le but du travail a été de faire un état des lieux sur l'appropriation des recommandations applicables pour la maîtrise du risque infectieux au cours des actes d'endoscopie digestive, afin de repérer le non respect des règles de bonne pratique et d'y apporter des mesures correctrices.<o: p></o: p>.
Efficacité des dilatations pneumatiques itératives pour le maintien en rémission de l'achalasie de l'œsophage
Authors: V Thetiot, F Richy, L Message, D Benajah, H Lamouliatte, F Zerbib
Journal: Endoscopy (2005)

Les dilatations pneumatiques (DP) du cardia représentent le traitement de première intention de l'achalasie de l'œsophage, permettant une rémission clinique à court terme dans 60 à 90% des cas, à long terme dans seulement 40 à 50%. Le but de cette étude était d'évaluer les résultats à long terme des DP itératives pour le maintien en rémission.
Pilot trial of an implantable microdevice for In Vivo drug sensitivity testing in patients with early stage, triple negative breast cancer receiving neoadjuvant therapy.
Authors: Tiffany A. Traina, George Plitas, Jorge S. Reis-Filho, Elizabeth Ann Morris, Mary Hughes, Janice S. Sung, Sujata Patil, Salvatore Piscuoglio, Samuel Park, Cynthia Greenberg, Oliver Jonas, Clifford A. Hudis, Jose Baselga
Journal: Journal of Clinical Oncology (2016)

TPS1101 Background: Available in vitro chemosensitivity models are time consuming, difficult to scale and fail to recapitulate the complexities of the tumor microenvironment. As a result, ASCO advises against use of such assays to select treatment for patients (pts) based on lack of evidence that in vitro assays improve outcome rather than standard options guided by clinical trial data. We now pilot an in vivo methodology to test drug sensitivity in triple negative breast cancer (TNBC). An implantable, 820µm-diameter, cylindrical device has been created which contains 16 reservoirs, each loaded with either a single drug or combination. Using methods by Jonas et al (Sci Transl Med 2015), the device is implanted within a tumor via 18 gauge biopsy needle, and is retrieved 24 hours later by concentric needle biopsy using image guidance to capture the device and a surrounding column of tumor. Using multiparameter immunohistochemistry, the patient-specific antineoplastic effect for each drug/regimen may be assessed by staining the tumor surrounding the reservoirs for biomarkers such as cleaved-caspase3, ki67, phospho-H2AX and RAD51. Methods: This first-in-human study will assess the feasibility of device placement, retrieval, and in vivo measurement of drug activity in the pre-operative setting for 12 pts with ≥ T2 TNBC. Feasibility is defined as the ability to collect device data from at least 6 of the 12. Pts will then receive a standard of care neoadjuvant regimen, independent of device readout. We will obtain preliminary data regarding the ability of the device to predict response to neoadjuvant doxorubicin and cyclophosphamide (AC) by correlating histologic response of the tumor surrounding the AC-containing reservoir with residual tumor viability on a post-AC biopsy. Secondary endpoints include safety, reproducibility, interobserver variability. All analyses will be primarily descriptive and graphical in nature. If feasible, we plan a larger study to test whether the device-predicted response correlates with outcome, defined by residual cancer burden. Three patients have been enrolled. Clinical trial information: NCT02521363.
The promise of non-invasive prenatal testing needs to be monitored scientifically
Authors: F. Lonardo, S. Gioacchino
Journal: BMJ (2015)

Chitty and Kroese’s editorial on realising the promise of non-invasive prenatal testing (NIPT) based on cell-free DNA in maternal plasma reaffirms the concept of superior performance compared with conventional screening.1 However, the comparison was performed with standard first trimester …
A Phase 1 study of RAD1901, an oral selective estrogen receptor degrader, in ER positive, HER2 negative, advanced breast cancer patients.
Authors: Elisabeth De Vries, Clasina Marieke Venema, Andor W. J. M. Glaudemans, Lorraine Fitzpatrick, Dinesh Purandare, Gary Hattersley, Fiona Garner
Journal: Journal of Clinical Oncology (2016)

TPS627 Background: RAD1901 is a novel, orally available selective estrogen receptor degrader (SERD) that binds to both mutant and wild type forms of the ER leading to ER degradation and inhibition of cellular proliferation. RAD1901 demonstrated greater growth inhibition of human breast cancer xenograft models compared to fulvestrant. In addition, RAD1901 inhibited the growth of patient-derived xenograft (PDx) models harboring ESR1 mutations. RAD1901 was evaluated in a phase 1 dose escalation study (200 mg to 1000 mg of oral RAD1901 daily) in healthy postmenopausal female volunteers (N = 52). They tolerated RAD1901 well and a dose-proportional exposure was observed based on pharmacokinetic analyses. ER occupation was assessed using 18F-fluoroestradiol positron emission tomography (FES-PET) imaging which showed that after 6 days of RAD1901 treatment the mean decrease of FES uptake ER in the uterus was 83% for the 200 mg (n = 3) and 92% at the 500 mg (n = 4) dose levels. A previously published FES-PET study, using serial imaging of tumor FES uptake during treatment with the SERD fulvestrant, demonstrated that significant residual FES binding uptake in tumor lesions was associated with early disease progression in patients with metastatic breast cancer (1). Methods: RAD1901-106 is Phase 1 study of RAD1901 in metastatic breast cancer patients to explore the use of FES-PET imaging as an early indicator of clinical response of RAD1901 treatment. Serial FES-PET imaging will be used to evaluate the effect of RAD1901 treatment on the availability of ER binding sites in tumor lesions. For patients demonstrating a attenuation of ER binding in tumor lesions after 14 days of RAD1901, RAD1901 treatment will continue to be administered until disease progression, unacceptable toxicity or patient’s choice and several dose levels may be explored. Key inclusion criteria include patients aged ≥ 18 years, with advanced ER positive, HER2 negative breast cancer, who have received ≤ 3 prior line of endocrine therapy in the metastatic setting. Patient enrollment started in early 2016 and is ongoing. ClinicalTrials.gov identifier: NCT02650817 (1) van Kruchten m et al, Cancer Discov. 2015:72-81 Clinical trial information: NCT02650817.
The loss of Krüppel-like factor 15 in Foxd1+ stromal cells exacerbates kidney fibrosis
Authors: Xiangchen Gu, Sandeep K. Mallipattu, Yiqing Guo, Monica P. Revelo, Jesse Pace, Timothy Miller, Xiang Gao, Mukesh K. Jain, Agnieszka B. Bialkowska, Vincent W. Yang, John C. He, Changlin Mei
Journal: Kidney International (2017)
Contents, Vol. 43, 1985
Authors: John B. Martin, R.O. Pihl, W.D. TenHouten, K.D. Hoppe, J.E. Bogen, D.O. Walter, Rishun Sinzato, Osamu Fukino, Hajime Tamai, Hitoshi Isizu, Tetsuya Nakagawa, Manfred Beutel, H.M. van der Ploeg, E.T. van Buuren, P. van Brummelen, Giovanni A. Fava, Thomas N. Wise, George Molnar, Maria Zielezny, Han Kutz, Jane Leserman, Claudia Dorrington, Catherine H. Morrison, Joan Z. Borysenko, Herbert Benson, Yujiro Ikemi
Journal: Psychotherapy and Psychosomatics (1985)
The impact of stereotactic radiotherapy to metastatic site on systemic treatment decision in oligometastatic breast cancer patients.
Authors: Ali Ayberk Besen, Huseyin Mertsoylu, Fatih Kose, Berna Yıldırım, Sedat Gozel, Ali Murat Sedef, Aysenur Ucar, Cem Onal
Journal: Journal of Clinical Oncology (2017)

e12564 Background: Patients with oligometastatic disease achieve long-term survival with multimodality treatment strategies. However, little attention has been paid to the effect of adjusting systemic therapy after local therapy in clinical studies. The aim of this study was to investigate the effects of changing or continuing the same treatment regimen following local therapy on survival parameters. Methods: Out of 350 metastatic breast cancer patients, treated between 2012 and 2016, 43 patients (12%) with oligometastatic disease were included in our study. Oligometastasis was defined as &lt; 5 metastatic sites in the same or different organs. Results: At a median follow-up of 32 months (7–53 months), 29 (67.4 %) patients had died. The one- and two-year overall survival (OS) rates were 95% and 78%, respectively, and the one- and two-year progression-free survival (PFS) rates were 77% and 51%, respectively. Following stereotactic body radiotherapy (SBRT) to oligometastatic sites, systemic treatment protocols were changed in 28 (65.1%) patients, while systemic treatment was continued unchanged in 15 (34.9%) patients. Changes to systemic treatment were significantly higher in patients with two organ metastases compared to patients with one organ metastasis ( p= 0.04). In the univariate analysis, estrogen receptor (ER) status and triple negative disease were significantly predictive of OS. The ER status and the number of metastatic organs were identified as significant predictors of PFS. In the multivariate analysis, only age emerged as a significant independent predictor of OS, while the number of initial organs involved and triple negative disease were significant factors for PFS. Conclusions: A hybrid treatment strategy is associated with higher survival rates in oligometastatic breast cancer patients. Post-SBRT systemic treatment change had no significant impact on OS and PFS in this study.
Demographic variables and risk factors associated with 30-day readmission following bone marrow transplant: Analysis of nationwide inpatient sample data.
Authors: Hardik Satish Chhatrala, Yashwant Agrawal, Shreya Ghetiya, Chintan Shah, Sreenivas Chandana
Journal: Journal of Clinical Oncology (2016)

e13080 Background: Bone marrow transplant (BMT) is becoming increasingly common procedure for the treatment of various hematologic malignancies. Short term hospital readmissions account for a significant portion of health care budget and much of the focus recently has been on reducing 30-day readmission rate. BMT is a high risk and expensive procedure performed in immunocompromised patients. This study was done to determine demographic parameters and risk factors associated with 30-day readmission rate after index BMT. Methods: Nationwide Inpatient Sample (NIS) data was used to extract data of patients discharged after BMT during index admission for years 2009-2013. Patients were identified by Clinical Classification Software (CCS) code 64, corresponding to ICD 9 procedure codes of 410, 4100-4109. NIS represents 20% of all hospital data in the US. Patients readmitted within 30 days were identified and demographic parameters and risk factors associated with high readmission rate identified. Chi-square test was performed to assess for differences between variables. Results: We identified a total of 83,384 hospitalizations for BMT during this 5-year period where 23.76% patients were readmitted within 30 days after index hospitalizations. Patients under age 17 years (45.07%, p < 0.001), female gender (25%, p < 0.01), Medicaid insurances (32%, p < 0.001), low median income for zip code (27.14%, p < 0.001) were associated with high 30-day readmission rate. The most common identified causes of readmission were complication of graft (20.94 ± 3.09%, p < 0.001), followed by disease of white blood cells(11.24% ± 3.24%), fever of unknown origin (6.66% ± 1.95%), septicemia (6.2% ± 2.31%) and pneumonia (3.8% ± 0.43%). Conclusions: This national database study identifies the demographic variables and risk factors associated with high 30-day readmission rate for BMT. Strategies to reduce morbidity and healthcare cost should be targeted more on these high risk groups and the identified causes with increased readmission rate. Further studies might be needed to supplement these results.
Ambient Temperature and Stillbirth: A Multi-Center Retrospective Cohort Study
Authors: Sandie Ha, Danping Liu, Yeyi Zhu, Sung Soo Kim, Seth Sherman, Katherine L. Grantz, Pauline Mendola
Journal: Environmental Health Perspectives (2017)

Background: Climate change is expected to have adverse health effects, but the association between extreme ambient temperatures and stillbirth is unclear. Objectives: We investigated acute and chronic associations between extreme ambient temperatures and stillbirth risk, and estimated the attributable risk associated with local temperature extremes in the United States. Methods: We linked 223,375 singleton births ≥23 weeks of gestation (2002–2008) from 12 U.S. sites to local temperature. Chronic exposure to hot (>90th percentile), cold (<10th percentile), or mild (10th–90th percentile) temperatures was defined using window- and site-specific temperature distributions for three-months preconception, first and second trimester, and whole-pregnancy averages. For acute exposure, average temperature for the week preceding delivery was compared to two alternative control weeks in a case-crossover analysis. Results: In comparison with mild, whole-pregnancy exposure to cold [adjusted odds ratio (aOR) = 4.75; 95% confidence interval (CI): 3.95, 5.71] and hot (aOR = 3.71; 95% CI: 3.07, 4.47) were associated with stillbirth risk, and preconception and first and second trimester exposures were not. Approximately 17–19% of stillbirth cases were potentially attributable to chronic whole-pregnancy exposures to local temperature extremes. This is equivalent to ∼1,116 cold-related and ∼1,019 hot-related excess cases in the United States annually. In the case-crossover analysis, a 1°C increase during the week preceding delivery was associated with a 6% (3–9%) increase in stillbirth risk during the warm season (May–September). This incidence translates to ∼4 (2–6) additional stillbirths per 10,000 births for each 1°C increase. Conclusions: Extremes of local ambient temperature may have chronic and acute effects on stillbirth risk, even in temperate zones. Temperature-related effects on pregnancy outcomes merit additional investigation. https://doi.org/10.1289/EHP945
Incidence of colorectal cancer in a population-based cohort of patients with Barrett's oesophagus
Authors: SJ Murphy, LA Anderson, I Mohan Lal Mainie, DA Fitzpatrick, BT Johnston, RGP Watson, LJ Murray
Journal: Endoscopy (2005)

Aims: Previous studies have shown a positive association between colorectal cancer and Barrett's oesophagus, but this association is disputed. To date, no population-based studies have examined the incidence of this cancer in patients with Barrett's oesophagus; we carried out such a study.