tbuckley/cabot-search huggingface dataset:
Characterization of 298 Patients with Lung Cancer Harboring MET Exon 14 Skipping Alterations
Authors: Alexa B. Schrock, Garrett M. Frampton, James Suh, Zachary R. Chalmers, Mark Rosenzweig, Rachel L. Erlich, Balazs Halmos, Jonathan Goldman, Patrick Forde, Kurt Leuenberger, Nir Peled, Gregory P. Kalemkerian, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, Siraj M. Ali, Sai-Hong Ignatius Ou
Journal: Journal of Thoracic Oncology (2016)

The hepatocyte growth factor receptor gene (MET) exon 14 skipping (METex14) has recently been described a potential driver alteration in lung cancer targetable by mesenchymal-to-epithelial transition factor (MET) tyrosine kinase inhibitors (TKIs).Well-validated hybrid capture-based comprehensive genomic profiling was performed at the request of individual treating physicians.Of 11,205 lung cancers profiled by comprehensive genomic profiling, 298 (2.7%) carcinomas harbored alterations predicted to cause METex14, including adenosquamous (8.2%), sarcomatoid (7.7%), histologic subtype not otherwise specified (3.0%), adenocarcinoma (2.9%), squamous cell (2.1%), large cell (0.8%), and SCLC (0.2%). Acinar features were present in 24% of the METex14 samples. Six cases (2%) harbored MET Y1003X mutations affecting binding of the MET-negative regulator, E3 ubiquitin protein ligase. The median age of all patients with METex14 was 73 years (range 43-95) and 60% were female. Concurrent, murine double minute gene (MDM2) amplification, cyclin-dependent kinase 4 gene (CDK4) amplification, and EGFR amplification were observed in 35%, 21%, and 6.4% of patients with METex14, respectively. KRAS mutation was observed in 3% of cases. Concurrent MET amplification (METamp) (median copy number 10) was identified in 15% of METex14 samples. Significant differences in tumor mutational burden and type of the METex14 alterations were observed between the METamp and non-METamp samples. Response to MET TKI was observed in both in patients with METamp and in patients without METamp METex14.Diverse targetable METex14 alterations were identified in patients with NSCLC across age groups, including elderly patients, and in all major NSCLC histologic subtypes with an overall frequency of 2.7%. These findings support the use of hybrid capture-based molecular profiling across NSCLC subtypes to identify patients who will potentially benefit from MET TKIs.
Optical Aptasensors for Adenosine Triphosphate
Authors: Stella Ng, Hui Si Lim, Qian Ma, Zhiqiang Gao
Journal: Theranostics (2016)

Nucleic acids are among the most researched and applied biomolecules.Their diverse two-and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications.Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays.Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices.The use of aptamers in sensors -aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP).This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives.
Lack of Agreement With What We Think Is Right Does Not Necessarily Equal an Ethical Problem: Respecting Patients' Goals of Care
Authors: Colleen K. McIlvennan, Keith M. Swetz
Journal: The American Journal of Bioethics (2016)

Implantable cardioverter defibrillators (ICDs) have proven effective in preventing sudden cardiac death for appropriately selected patients, and are implanted under guidelines that recommend them f...
Dystrophin
Authors: Lewis P. Rowland
Journal: New England Journal of Medicine (1988)

THE paper by Hoffman et al.1 in this issue of the Journal is one of a series of landmark papers from the laboratory of Louis M. Kunkel. "Dystrophin" is the name that Kunkel and colleagues have given to a "new" protein, the product of the gene that is affected in Duchenne's muscular dystrophy.2 Hoffman et al. now report abnormalities of dystrophin in two similar but not identical disorders, Duchenne's and Becker's muscular dystrophy. Severe myopathy defines the Duchenne phenotype, which is detectable at birth because serum levels of creatine kinase and other sarcoplasmic enzymes are high and which becomes clinically . . .
In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery
Authors: V.G. Deepagan, Seunglee Kwon, Dong Gil You, Van Quy Nguyen, Wooram Um, Hyewon Ko, Hansang Lee, Dong-Gyu Jo, Young Mo Kang, Jae Hyung Park
Journal: Biomaterials (2016)
Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment
Authors: Peter Dongmin Sohn, Tara E. Tracy, Hye-In Son, Yungui Zhou, Renata E. P. Leite, Bruce L. Miller, William W. Seeley, Lea T. Grinberg, Li Gan
Journal: Molecular Neurodegeneration (2016)

Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood.
Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure: a cohort study
Authors: William Bernal, Yanzhong Wang, James Maggs, Christopher Willars, Elizabeth Sizer, Georg Auzinger, Nicholas Murphy, Damian Harding, Ahmed Elsharkawy, Kenneth Simpson, Fin Stolze Larsen, Nigel Heaton, John O'Grady, Roger Williams, Julia Wendon
Journal: The Lancet. Gastroenterology & hepatology (2016)
Membrane Markers in “Histiocytic” Lymphomas (Reticulum Cell Sarcomas) 2
Authors: J. C. Brouet, J. L. Preud'Homme, G. Flandrin, N. Chelloul, M. Seligmann
Journal: JNCI Journal of the National Cancer Institute (1976)

Neoplastic cells from 9 patients affected with a "histiocytic" lymphoma were studied with 5 membrane markers of B or T lymphocytes. In 2 patients a monoclonal B-cell proliferation was found; they had been affected previously with well documented B-cell proliferations: chronic lymphocytic leukemia or Waldenström's macroglobulinemia. The blast cells of 2 other patients had T-cell features; in a fifth case, the abnormal cells carried only a strong receptor for the Fc fragment of IgG, which suggested their truly monocytic origin. In 4 patients, the cells had no detectable surface markers. These findings demonstrated that this group of lymphomas is heterogenous, that the term "histiocytic" appears to be wrong in most instances, and that the cellular origin of the malignant cells frequently remains unidentified and thus prevents a satisfactory new classification.
Effect of Castration and Sex Hormones on the Induction of Tumors in Mice with &lt;italic&gt;o&lt;/italic&gt;-Aminoazotoluene
Authors: Andervont, Howard B., Dunn, Thelma B.
Journal: JNCI Journal of the National Cancer Institute (1947)

Journal Article Effect of Castration and Sex Hormones on the Induction of Tumors in Mice with o-Aminoazotoluene Get access Howard B. Andervont, Howard B. Andervont biologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Thelma B. Dunn Thelma B. Dunn pathologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 7, Issue 6, June 1947, Pages 455–461, https://doi.org/10.1093/jnci/7.6.455 Published: 01 June 1947 Article history Received: 01 April 1947 Published: 01 June 1947
Injuries sustained in National Collegiate Athletic Association men's and women's basketball, 2009/2010–2014/2015
Authors: Scott L Zuckerman, Adam M Wegner, Karen G Roos, Aristarque Djoko, Thomas P Dompier, Zachary Y Kerr
Journal: British Journal of Sports Medicine (2016)

Background/aim Recent rule changes regarding the safety of basketball athletes necessitate up-to-date reports of injury incidence. This study describes the epidemiology of injuries in men's and women's National Collegiate Athletic Association (NCAA) basketball during the 2009/2010–2014/2015 seasons. Methods Basketball injury data originate from the 2009/2010–2014/2015 academic years from the NCAA Injury Surveillance Program (NCAA-ISP) from 78 men's and 74 women's NCAA basketball programmes which provided 176 and 181 team-seasons, respectively. A reportable injury occurred during organised practice or competition and required attention from an athletic trainer (AT) or physician. Injury rates, injury proportions and rate ratios (RRs) were calculated. All 95% CIs not containing 1.0 were considered statistically significant. Results A total of 2308 and 1631 injuries were reported in men's and women's basketball, respectively, for injury rates of 7.97 and 6.54/1000 athlete-exposures (AEs). The rate was higher in men than women (RR=1.22; 95% CI 1.15 to 1.30). Non-time-loss (NTL) injuries (resulting in participation restriction time under 24 hours) accounted for 64.8% and 53.6% of men's competition and practice injuries, respectively, and 53.9% and 51.3% of women's competition and practice injuries, respectively. Injuries to the lower extremity were the most common in competitions (men: 54.9%; women: 59.0%) and practices (men: 62.4%; women: 67.3%). The most common injury in men's and women's basketball was ankle sprain (17.9% and 16.6%, respectively). Conclusions NTL injuries account for over half of all injuries in basketball. Most injuries were lower extremity injuries, specifically ankle sprains. While rule changes have been implemented to make basketball safer, continued research is needed to assess the effectiveness of these changes.
Are hysterical seizures more than hysteria? A research diagnostic criteria, DMS-III, and psychometric analysis
Authors: R S Stewart, R Lovitt, R M Stewart
Journal: American Journal of Psychiatry (1982)

In a double-blind study the authors compared severity of psychopathology and personality organization in three groups of patients: those with organic (neurogenic) seizures alone (N = 11), those who exhibited both neurogenic and psychogenic ("hysterical") seizures (N = 13), and those with pure psychogenic ("hysterical") seizures (N = 13). Patients with neurogenic seizures were found to have alcoholism, anxiety disorder, and minor affective disorder. Patients with mixed and psychogenic seizures had more severe psychopathology, including major affective disorders and major character pathology. Patients with mixed and psychogenic seizures also had a markedly higher incidence of suicide attempts and past history of psychiatric treatment.
Controversy of treatment strategy for dialysis patients with unilateral upper urinary tract urothelial carcinoma.
Authors: Yu-Jun Chang, Thomson Tai, Brent Tai, Wen-Miin Liang
Journal: Journal of Clinical Oncology (2015)

e15604 Background: In general, the treatment policy of unilateral upper urinary tract urothelial carcinoma (UUT-UC) for end stage renal disease (ESRD) patients under dialysis will receive ipsilateral radical nephroureterectomy (NU) and bladder cuff resection. But some reported the bladder UC occurrence rate is high after standard treatment. They recommended 1-step bilateral NU with radical cystectomy (total urinary exenteration) as a better choice for ESRD patients with UUT-UC. Herein, we presented our study to compare the surgical outcome of ESRD patients with unilateral UUT-UC who underwent unilateral NU with bladder cuff resection, bilateral NU with bladder cuff resection or total urinary exenteration. Methods: We conducted a population-based nationwide retrospective cohort study in Taiwan. It comprised of 1352 ESRD patients who had diagnosed unilateral UUT-UC after dialysis at least one year. These patients' data were collected from national health insurance bureau (2000-2007). They were divided into three groups: group I: unilateral NU cohort (N = 1320); group II: bilateral NU cohort (N = 13); group III: total urinary exenteration cohort (N = 19). Results: The ratio of postoperative sepsis was higher in group III (15.79%) (p < 0.05). The mortality during 30 days after operation did not show significant difference (p = 0.812). The operation cost (including admission) was higher in group III (p < 0.05). The average 3 years related cost postoperatively was higher in group II (p < 0.05). 656 (49.7%) patients in group I had urinary bladder UC. It occurred in 414 patients during 1 year. 8 (61.54%) in group II had bladder UC and it occurred in 5 during 1 year. 305 (23.11%) in group I and 6 (31.58%) in group III died during 3 years. After 3 years follow-up, the survival rate between these three groups did not show significant difference and age is the only factor which influence the mortality. Conclusions: Although high rates of occurrence of bladder UC postoperatively in group I and II, analysis of postoperative cost, the mortality and survival rate after 3 years followup. We do not recommend total urinary exenteration for all unilateral UUT-UC patients. Age factor must be considered.
Lysosomal Proteins as a Therapeutic Target in Neurodegeneration
Authors: Jessica M. Mc Donald, Dimitri Krainc
Journal: Annual Review of Medicine (2017)

Several proteins that are mutated in lysosomal storage diseases are linked to neurodegenerative disease. This review focuses on some of these lysosomal enzymes and transporters, as well as current therapies that have emerged from the lysosomal storage disease field. Given the deeper genetic understanding of lysosomal defects in neurodegeneration, we explore why some of these orphan disease drug candidates are also attractive targets in subpopulations of individuals with neurodegenerative disease.
Neoadjuvant capecitabine and oxaliplatin (XELOX) with bevacizumab for locally advanced rectal cancer.
Authors: Junichi Hasegawa, Tsunekazu Mizushima, Ho Min Kim, Yasuhiro Miyake, Hiroyoshi Takemoto, Hiroshi Tamagawa, Shingo Noura, Masayuki Ohue, Makoto Fujii, Yuichiro Fujie, Hirofumi Ota, Takeshi Kato, Mutsumi Fukunaga, Ichiro Takemasa, Masataka Ikeda, Hirofumi Yamamoto, Mistugu Sekimoto, Riichiro Nezu, Yuichiro Doki, Masaki Mori
Journal: Journal of Clinical Oncology (2013)

566 Background: Chemoradiotherapy (CRT) followed by surgery is a standard treatment for locally advanced rectal cancer. Although preoperative CRT decreases local recurrence (LR), pelvic radiation is associated with long-term morbidity. We conducted this study to evaluate the feasibility of neoadjuvant XELOX with bevacizumab (Bmab) in patients (pts) with locally advanced rectal cancer. Methods: Pts with T4 or lymph node (LN) positive rectal cancer were treated with 3 cycles of XELOX with Bmab and one additional cycle of XELOX. Total mesorectal excision was performed 3-8 weeks after the last chemotherapy. The primary endpoint was to assess feasibility and secondary endpoints were R0 resection rate, down staging rate, pathological complete response (pCR) rate and pathological effect over grade 2 (tumor cell death in more than two-thirds of the entire lesion). Results: Twenty five pts were recruited between December 2009 and November 2011. Characteristics of pts were as the following: male/female, 18/7; median age, 63 years (range, 37-75); median diameter of tumor, 52.8mm (range, 38.3-110); T2-T3/T4a/T4b, 7/8/10 and N0/N1/N2, 3/14/8. In 4% of the pts (7 pts), following grade 3-4 adverse events occurred; neutropenia, hypertension, bleeding, rectal obstruction, pelvic infection, anorexia and nausea. The down staging rate of T2-T3/T4a/T4b and N1/N2 were 29/63/50 % and 86/63 %, respectively. Seven pts (28%) discontinued the treatment after 2-3 cycles of XELOX with Bmab (13% in T2-T4a, 50% in T4b). The rate of conducting surgery was 92% and all of them had R0 resections. Postoperative complications were found in 9 pts (39%). The pCR rate was 4%, and the rate of pathological effect over grade 2 was 61%. Two LR (LN positive) and two distant recurrences (1 lung, 1 liver) were reported. Conclusions: XELOX with Bmab followed by surgery was safely performed for locally advanced rectal cancer. The down staging rate was 50% even in T4b pts although half of T4b pts discontinued the study treatment. Based on these preliminary results, we are planning a phase II trial of perioperative XELOX and surgery in locally advanced rectal cancer. Clinical trial information: 000003219.
The father's parenting experience in divorce
Authors: H J Friedman
Journal: American Journal of Psychiatry (1980)

The author discusses the father-child relationship as it is influenced by divorce. Psychiatrists are often consulted by individuals considering dovorce who are concerned about its probable impact on their children. Data gathered from the treatment of fathers during divorce indicate that there can be positive changes in their parental bonds as a result of increased opportunities to relate to children in a conflict-free atmosphere. In such a setting, the father's nurturing experience provides him with a new perspective on parenting. Psychotherapeutic help can lead to a strengthening of parental bonds, with subsequent benefits to both father and child. The author encourages professionals to support men in improving their fathering during the postdivorce period.
Use of alemtuzumab as graft-versus-host disease prophylaxis in myeloablative unrelated donor transplants
Authors: K. L. Young, D. Howard, L. Lekakis
Journal: Journal of Clinical Oncology (2008)

7045 Background: Graft-versus-host disease(GvHD) remains a frequent, morbid, and costly complication of allogeneic stem cell transplant (alloSCT) when using unrelated donors(URD). Optimal prophylaxis remains uncertain. With standard post-alloSCT tacrolimus and mini-mtx the incidence of acute GvHD (aGvHD) approaches 50–75%. Severe aGvHD occurs in about 30%, with mortality >80%. T-cell depletion is commonly employed but associated with high risk of disease relapse and graft rejection. Methods: We report observations from 43 pts who received Alemtuzumab pre-alloSCT for GvHD prevention with myeloablative conditioning and URD in a phase II study. The accrual of >30pts allowed us to demonstrate with significance (90% power; 5% 1-sided α) that Alemtuzumab is associated with less aGvHD in this setting. Eligible pts had hematologic malignancies and were scheduled for alloSCT on protocol. There were 2 cohorts of patients: 1–10(A) were treated with 5 days of Alemtuzumab (20mg/d); 11–43(B) were treated with 3. Cohort B was created due to frequency and severity of infections. 25/43 (58%) had >CR2 or refractory disease at the time of conditioning. CMV PCR was obtained weekly with any positive prompting therapy. Results: Pts were evaluated for engraftment, presence of GvHD before and after day 100, and DFS at day 100. 2 had primary engraftment failure. One had a sustained partial chimerism. 33/43 (76.7%) treated were alive and evaluable at day 100: 2 died due to progressive disease, 6 of severe infections, 1 had a probable PE and 1 TTP. Only 1/43 had severe aGvHD; 7/43 had grade 1–2 (16.2%). 13/43 had any chronic GvHD (30%), 7/43 of these were extensive (16.3%). Two deaths are attributed to chronic GvHD. At this report 11/43 are alive at a median f/u of 25 months. 12/43 (27.9%) died of progressive disease. CMV reactivation occurred in 17/43, and was a major factor in death in 5. 70% of cohort A, vs 42% of cohort B succumbed to infections. Conclusions: Alemtuzumab given prior to alloSCT from URD is effective in preventing severe acute and chronic GvHD and does not compromise engraftment rates. The frequency and severity of viral infections require aggressive monitoring and therapy. Disease control is not adversely affected. Consideration should be given to the lower dose use as GvHD prophylaxis. No significant financial relationships to disclose.
Abstract 179: Atypical protein kinase C inhibition in prostate cancer cells: a study of ICA-1 and ACPD
Authors: Andre H. Apostolatos
Journal: Cancer Research (2016)

Abstract Aggressive and metastatic prostate cancers are highly lethal tumors and are one of the leading causes of death among men. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant cancer cells. There is a gap in knowledge relating to which intracellular chemicals confer the emergence of therapy-resistant prostate cancer cells, which intracellular chemicals are responsible for prostate cancer survival and which chemicals regulate intracellular signaling pathways in prostate cancer. To address this critical problem, we investigated two drugs that act as inhibitors of atypical Protein Kinase C Iota. The objective of this study was to test the effectiveness of ACPD as an atypical PKC inhibitor and ICA-1 as an inhibitor of PKC iota. [The Inter. J. Biochem. &amp; Cell Biol. 43:784-794(2011)] DU-145 and PC-3 prostate carcinoma cells and non-malignant prostate RWPE-1 cells were each cultivated in separate flasks. They were treated with drugs of interest for three consecutive days. The cells were counted before and after the treatments and a statistical analysis was performed. The cells were lysed and levels of PKC iota and PKC zeta were measured by Western blotting and immunoprecipitation. Our preliminary results show that treatment of DU-145 and PC-3 showed a statistically significant decrease in cells that was proportional to the concentration in both drugs. Treatment of the RWPE-1 cells showed no statistically significant change in population. The Western blotting showed both drugs decreased PKC iota. In conclusion ACPD and ICA1 are effective inhibitors of PKC iota and PKC zeta and consequently significantly reduced the neogenesis of the prostate DU-145 and PC-3 carcinoma cells while having negligible effect on the non-malignant prostate RWPE-1 cells. Citation Format: Andre H. Apostolatos. Atypical protein kinase C inhibition in prostate cancer cells: a study of ICA-1 and ACPD. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 179.