tbuckley/cabot-search huggingface dataset:
Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial
Authors: Stephen Kanes, Helen Colquhoun, Handan Gunduz-Bruce, Shane Raines, Ryan Arnold, Amy Schacterle, James Doherty, C Neill Epperson, Kristina M Deligiannidis, Robert Riesenberg, Ethan Hoffmann, David Rubinow, Jeffrey Jonas, Steven Paul, Samantha Meltzer-Brody
Journal: The Lancet (2017)
Outcome of Multiple Myeloma Patients Treated with Carrd-PACE Chemomobilization: A Single-Center Experience
Authors: Andrew J. Cowan, Mehdi Karami, Edward N. Libby, Pamela S. Becker, David G. Coffey, Damian J. Green, Teresa S. Hyun, Sherilyn Tuazon, Mazyar Shadman, Ajay K Gopal, Leona A Holmberg
Journal: Blood (2016)
BECAM: A salvage protocol with bevacizumab, capecitabin, and mitomycin C for patients with refractory metastatic colorectal cancer (CRC) or gastric cancer (GC)
Authors: S. Peinert, D. Arnold, R. Siewczynski, T. Kegel, C. Heider, H. Nietsch, H. Schmoll
Journal: Journal of Clinical Oncology (2006)

13554 Background: Bevacizumab (Bev), a monoclonal antibody targeted against VEGF, has shown to improve efficacy in CRC when combined with chemotherapy. Combination schedules of fluoropyrimidines with mitomycin C (MMC) are active in both CRC and GC. This study was to explore the combination of Bev with a previously reported schedule of Capecitabine (Cap) and MMC (BECAM) in heavily pretreated patients (pts) with GC or CRC. Methods: Pts had to be refractory to at least 3 treatment lines, incl. 5-FU, oxaliplatin, irinotecan, and cetuximab in CRC; 2 lines with 5-FU, platinum, irinotecan or taxane in GC. A treatment cycle consisted of a 1-hour-infusion of Bev 7.5 mg/kg d1, bolus MMC 7mg/m 2 d1 and Cap 1000mg/m 2 bid d1–14, all qd22. Toxicity was assessed every 3 weeks (wk) and tumor evaluation (CT/MRI) was done every 9 wk. Results: 19 pts were included: m/f 8/11; GC 4, CRC 15, age 63 yrs [42–76], Karnofsky PS 80% [70–100]. Median no. of preceding regimens was 3 [2–6]. A total of 87 cycles were given. Median no. of cycles per pt. was 3 [2–15]. 18 pts were evaluable for toxicity (WHO scale) and efficacy: Grade 3/4 toxicities were thrombocytopenia (5/0), hypertension (1/0), and hemorrhage (0/1). The latter caused cessation of further administration of Bev. Gastrointestinal and other hematologic toxicities did not exceed grade 2. Response: PR was seen in 3 pts (16%; 1/4 GC, 2/14 CRC), stable disease for &gt; 9 wk in 5 pts (1 GC, 4 CRC), leading to a tumor control rate of 44%. Median progression free and overall survival were 3.0 [2–11] and 5.0 [2.5–13] months. However, duration of objective response was remarkable in lasting 7.4–10.0 months. Conclusions: BECAM shows considerable activity in this group of heavily pretreated pts with CRC or GC. Toxicity was generally mild except for MMC-induced thrombocytopenia and (probably) Bev-induced bleeding (gastric tumor site). Despite previous reports of limited activity with Bev/5-FU in refractory pts (NCI TRC trial), BECAM is able to induce long lasting objective responses and therefore merits further investigation in both tumor types. [Table: see text]
Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project
Authors: A.M. Drucker, A.A. Qureshi, T.J.B. Dummer, L. Parker, W.-Q. Li
Journal: British Journal of Dermatology (2017)

Atopic dermatitis (AD) has been associated with cardiovascular risk factors and diseases, but epidemiological studies to date have found conflicting results. To determine the associations of AD with hypertension, type 2 diabetes (T2D), myocardial infarction (MI) and stroke. We conducted a cross‐sectional analysis of baseline data from the Canadian Partnership for Tomorrow Project, which includes Canadian residents aged 30–74 years living in British Columbia, Alberta, Ontario, Quebec and the Atlantic Provinces. We excluded participants with incomplete data on AD, hypertension, T2D, MI or stroke, who had type 1 or gestational diabetes or who developed any of the outcomes at an age prior to a diagnosis of AD. This left 259 119 participants in our analysis. We used logistic regression to calculate age‐ and sex‐, and multivariable‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between AD and subsequent hypertension, T2D, MI and stroke. AD was reported by 21 379 (8·4%) participants. In total, 52 787 cases of hypertension, 12 739 cases of T2D, 4390 cases of MI and 2235 cases of stroke were reported by participants at enrolment. In the multivariable‐adjusted model, AD was associated with decreased odds of hypertension (OR 0·87, 95% CI 0·83–0·90), T2D (OR 0·78, 95% CI 0·71–0·84), MI (OR 0·87, 95% CI 0·75–1·00) and stroke (OR 0·79, 95% CI 0·66–0·95). We did not find evidence of a positive association between AD and subsequent hypertension, T2D, MI or stroke; AD was inversely associated with these outcomes in our study. Given our findings and the conflicting literature, AD is likely not a major risk factor for cardiovascular disease.
Entospletinib drug interaction profile and mass balance.
Authors: Michael Dolton, Shringi Sharma, Fu-Chih Cheng, Michelle Robeson, Angela Worth, Thomas Tarnowski, Srini Ramanathan, Jeffrey Alan Silverman
Journal: Journal of Clinical Oncology (2016)

e14097 Background: Entospletinib (ENTO), a Syk inhibitor, has shown clinical activity in R/R CLL subjects. In vitro, ENTO inhibited OATP1B1/1B3, BCRP, P-gp and UGT1A1; ENTO metabolism is mediated by CYP2C9 and CYP3A. These studies evaluate the drug interaction (DDI) profile and mass balance (MB) of ENTO. Methods: Healthy subjects received ENTO alone, or with cobicistat (COBI; CYP3A inhibitor), rifampin (RIF; CYP3A inducer), fluconazole (FLU; CYP2C9/CYP3A inhibitor), rosuvastatin (ROS; OATP1B1/1B3, BCRP substrate) or digoxin (DIG, P-gp substrate). For the MB study, healthy subjects received a single dose of ENTO containing [14C]-labeled ENTO. Results: DDI results are shown below. ENTO was extensively metabolized to 14 metabolites in the MB study; ~91% and ~2% of the dose was recovered in feces and urine, respectively. The majority of circulating radioactivity was associated with unchanged ENTO. ENTO was generally well tolerated in these studies. Conclusions: Co-administration with strong CYP3A inducers may decrease ENTO exposures; strong CYP3A inhibitors do not significantly affect ENTO exposures. ENTO may increase exposures of OATP1B1/1B3/BCRP and P-gp substrates. ENTO is extensively metabolized and excreted in feces. Comparison Dose aParameter bGMR (90% CI) ENTO+COBI vs ENTO ENTO: 100 mg BID COBI: 150 mg QD ENTO Cmax ENTO AUCtau 108 (97, 121) 117 (106, 130) ENTO+RIF vs ENTO ENTO: 400 mg BID RIF: 600 mg QD ENTO Cmax ENTO AUCtau 42 (36, 49) 29 (25, 34) ENTO+FLU vs ENTO ENTO: 100 mg BID FLU: c400/200 mg QD ENTO Cmax ENTO AUCtau 132 (119, 147) 141 (127, 157) ROS+ENTO vs ROS dROS: 10 mg SD ENTO: 400 mg BID ROS Cmax ROS AUCinf 368 (298, 456) 381 (316, 460) DIG+ENTO vs DIG dDIG: 0.5 mg SD ENTO: 400 mg BID DIG Cmax DIG AUCinf 139 (114, 169) 138 (128, 148) a Cmax (ng/mL); AUC (ng.h/mL) bGMR: geometric mean ratio, CI: confidence interval c 400 mg dose Day 1 then 200 mg QD d SD: single dose
Acetylation of Mastermind-like 1 by p300 Drives the Recruitment of NACK to Initiate Notch-Dependent Transcription
Authors: Ke Jin, Wen Zhou, Xiaoqing Han, Zhiqiang Wang, Bin Li, Shawn Jeffries, Wensi Tao, David J. Robbins, Anthony J. Capobianco
Journal: Cancer Research (2017)

Abstract Although it has long been appreciated that p300 acts as a critical Notch coactivator, the mechanistic details of p300 in Notch-mediated transcription remain unclear. We previously demonstrated that PEAK1-related kinase activating pseudokinase 1 (NACK), also known as SGK223, is a critical coactivator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate Mastermind-like 1 (Maml1) on amino acid residues K188 and K189 to recruit NACK to the Notch1 ternary complex, which results in the recruitment of RNA polymerase II to initiate transcription. NACK is recruited to the ternary complexes containing Maml1 and Maml3, but not Maml2. Simultaneous inhibition of p300/CBP and Notch has a synergistic effect in esophageal adenocarcinoma. In summary, this study provides a deeper mechanistic understanding of the assembly of the Notch transcriptional complex and provides rationale and proof of concept for a combinatorial therapeutic attack on Notch-dependent cancers. Cancer Res; 77(16); 4228–37. ©2017 AACR.
Sofosbuvir/Velpatasvir (Epclusa) for Hepatitis C
Authors: Randi Sokol
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Glioblastoma targeted therapy: updated approaches from recent biological insights
Authors: M. Touat, A. Idbaih, M. Sanson, K.L. Ligon
Journal: Annals of Oncology (2017)

Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response. Moreover, recent identification and validation of prognostic and predictive biomarkers have allowed implementation of modern trial designs based on matching molecular features of tumors to targeted therapeutics. However, while occasional targeted therapy responses have been documented in patients, to date no targeted therapy has been formally validated as effective in clinical trials. The lack of knowledge about relevant molecular drivers in vivo combined with a lack of highly bioactive and brain penetrant-targeted therapies remain significant challenges. In this article, we review the most promising biological insights that have opened the way for the development of targeted therapies in glioblastoma, and examine recent data from clinical trials evaluating targeted therapies and immunotherapies. We discuss challenges and opportunities for the development of these agents in glioblastoma.
State-Independent and Dependent Neural Responses to Psychosocial Stress in Current and Remitted Depression
Authors: Qingsen Ming, Xue Zhong, Xiaocui Zhang, Weidan Pu, Daifeng Dong, Yali Jiang, Yidian Gao, Xiang Wang, John A. Detre, Shuqiao Yao, Hengyi Rao
Journal: American Journal of Psychiatry (2017)

Objective: Stress is a strong risk factor for major depressive disorder, while sensitization to stress in remitted individuals plays a key role in depression recurrence. The present study explored the state-independent (trait) and dependent (state) neural responses to psychosocial stress in major depressive disorder. Method: Thirty-six patients with medication-naive first-episode current depression, 33 patients with remitted depression, and 36 demographically matched healthy control participants were administered the Montreal Imaging Stress Task during functional MRI. One-way analyses of variance were used to assess differences in stress responses in the three groups. Results: Both currently depressed and remitted patients exhibited higher stress levels and cortisol responses than control subjects. Compared with control subjects, both depressed and remitted patients exhibited reduced activation in the ventromedial prefrontal cortex and increased activation in the precuneus. The stress-induced ventromedial prefrontal cortex activation changes negatively correlated with cortisol increases in all three groups. Additional increased activations were found in the dorsolateral prefrontal cortex and bilateral striatum in remitted patients compared with control subjects, and activation in these regions correlated inversely with depressive symptoms in the remitted group. Conclusions: These findings provide novel evidence regarding the trait and state markers of depression on neural responses to psychosocial stress. Regional activation changes in the ventromedial prefrontal cortex and precuneus may reflect the trait markers of depression. Hyperactivation in the dorsolateral prefrontal cortex and striatum may represent a state-dependent compensatory mechanism during depression remission.
Mutation analysis of the zinc finger protein MIZ-1 (ZNF151), a potential candidate gene at chromosome 1p36 in pheochromocytomas
Authors: Diana E. Benn, Leigh Delbridge, Bruce G. Robinson, Deborah J. Marsh
Journal: Cancer Research (2004)

2698  Pheochromocytomas are rare tumors associated with the sympathetic neuroendocrine system, arising in the chromaffin cells of the adrenal gland, but may also be found in extra-adrenal sites. Up to 24% of pheochromocytomas may be familial, with germline mutations in one of six known cancer susceptibility genes-RET, VHL, NF1, SDHB, SDHC or SDHD. However the molecular pathogenesis of sporadic disease remains largely unknown. Previous work by our group has identified 3 regions (designated PC1, PC2 and PC3) on chromosome 1p in familial and sporadic pheochromocytomas, showing loss of heterozygosity (LOH), suggesting that these regions may contain loci for tumor suppressor genes. Miz-1 in the PC2 (D1S228 to D1S507) region was chosen for further study. Miz-1 encodes an 803 amino acid zinc finger protein with 13 zinc finger domains and a potent growth arrest function, which can be attenuated by Myc. Mutation analysis was undertaken in 18 pheochromocytomas (12 with 1p LOH) by PCR and sequencing of the 14 exons and intronic/exonic boundaries of Miz-1. Two intronic polymorphisms were identified, both in intron 6, IVS6+12A>G and IVS6+36G>T and their frequency in 50 normal controls was also determined. Two silent mutations, one in exon 4 (A207A) and the other in exon 6 (F334F) were also identified. Interestingly, the phenylalanine (F) at codon 334 is a hydrophobic residue which is predicted to be important for protein folding. No specific point mutations or microdeletions have been identified in Miz-1 indicating that somatic Miz-1 mutations are not involved in the development of these tumors. This could also indicate that a different tumor suppressor gene at this site is involved, or functional abrogation of Miz-1 might be via a regulatory mechanism such as hypermethylation of the promoter region.
New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study
Authors: Otavio T. Ranzani, Elena Prina, Rosario Menéndez, Adrian Ceccato, Catia Cilloniz, Raul Méndez, Albert Gabarrus, Enric Barbeta, Gianluigi Li Bassi, Miquel Ferrer, Antoni Torres
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown.Objectives: To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia.Methods: This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality.Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the “treat-all” strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality.Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.
Hematopoietic Stem Cell Transplantation with Reduced Intensity Conditioning in Older Patients with Myelodysplastic Syndromes
Authors: Orhan Kemal Yucel, Rima M Saliba, Gabriela Rondon, Sairah Ahmed, Amin Alousi, Qaiser Bashir, Stefan O. Ciurea, Uday R. Popat, David Marin, Katy Rezvani, Partow Kebriaei, Elizabeth J. Shpall, Richard E. Champlin, Betul Oran
Journal: Blood (2016)
"THE TRANSFORMING GROWTH FACTOR- /SMAD2,3 SIGNALLING AXIS IS IMPAIRED IN EXPERIMENTAL PULMONARY HYPERTENSION". A. ZAKRZEWICZ, F.M. KOURI, B. NEJMAN, G. KWAPISZEWSKA, M. HECKER, R. SANDU, E. DONY, W. SEEGER, R.T. SCHERMULY, O. EICKELBERG AND R.E. MORTY. EUR RESPIR J 2007; 29: 1094 1104.
Journal: European Respiratory Journal (2007)
Hereditary factors are unlikely behind unusual pattern of early - Onset colorectal cancer in Egyptians: A study of family history and pathology features in Egyptians with large bowel cancer (cross-sectional study)
Authors: Ahmed A. Abou-Zeid, Wael A. Jumuah, Essam F. Ebied, Karim Sabry Abd El Samee Atia, Yasser El Ghamrini, Dina A. Somaie
Journal: International Journal of Surgery (2017)
Household Preparedness for Public Health Emergencies—14 States, 2006-2010
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pull method percutaneous endoscopic gastrostomy using transnasal ultrathin endoscopy in head and neck cancer
Authors: Jia-Ming Chang, Yi-Ting Yen, Chao-Chun Chang, Yau-Lin Tseng, Wu-Wei Lai, Kam-Hong Kam
Journal: Endoscopy (2017)

Dysphagia due to tumor ulcers and stomatitis induced by chemoradiotherapy is painful; it is therefore crucial and urgent to establish a surgical enteral feeding route in patients with head and neck cancer to avoid malnutrition and improve treatment compliance [1]. However, common trismus caused by surgical resection, reconstruction, and, mostly, radiation fibrosis often compromise flexible endoscope passage; furthermore, an oral tumor would raise concern of cancer contamination and inoculation upon percutaneous endoscopic gastrostomy (PEG) [2] [3]. Herein, we demonstrate the use of an ultrathin endoscope (5.3 mm diameter; Olympus VISERA Transnasal Esophagovideoscope, PEF-V; Olympus Medical Systems, Tokyo, Japan), via the transnasal route as a good alternative for better instrument passage in patients with head and neck cancer with trismus or when buccal reconstruction integrity would be a concern.
The RNA-Binding Protein Musashi 2 Is Upregulated in the Proliferative Fraction of CLL Clones, Particularly in U-CLL Patients, and Its Silencing Induces Programmed Cell Death
Authors: Florencia Palacios, Xiao J. Yan, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2016)
Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling
Authors: Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti, David Wu, Rajib Mukherjee, Calvin C Chan, Matthew J Lawson, Jared Klarquist, Annika Sünderhauf, Samir Softic, C Ronald Kahn, Kerstin Stemmer, Yoichiro Iwakura, Bruce J Aronow, Rebekah Karns, Kris A Steinbrecher, Christopher L Karp, Rachel Sheridan, Shiva K Shanmukhappa, Damien Reynaud, David B Haslam, Christian Sina, Jan Rupp, Simon P Hogan, Senad Divanovic
Journal: Nature Medicine (2017)