tbuckley/cabot-search huggingface dataset:
Abstract 2041: High-throughput chemical screening for sensitization of bladder cancer to gemcitabine and cisplatin chemotherapy
Authors: Yuki Kita, Takashi Kobayashi, Ryouichi Saito, Toshinari Yamasaki, Takahiro Inoue, Osamu Ogawa
Journal: Cancer Research (2017)

Abstract Introduction and Objectives Gemcitabine and cisplatin chemotherapy (GC) is the current standard regimen for locally advanced and metastatic bladder cancer (BC). Despite a relatively high initial response rate, some cases do not regress (intrinsic resistance) and the remaining cases often show regrowth after initial shrinkage (acquired resistance). To identify novel therapeutic agents for overcoming these resistances, we applied a high-throughput screening of chemicals administered in combination with GC. Methods As a high-throughput screening, 2100 compounds were administered alone or in combination with GC to human BC cell lines (J82, UMUC-3). Cell viability was determined after 3-day incubation and chemicals that enhanced inhibitory effect of GC were screened. The in vivo effect of disulfiram (DSF) was studied in UMUC-3 cell xenografts, and western blot, immunofluorescence, induced coupled plasma spectrometry and measurement of reactive oxygen species (ROS) were done in vitro for mechanistic exploration. Results The initial screening identified 26 compounds and further validation narrowed them into the most synergistic agent DSF, an FDA-approved drug for alcoholism. Combination index assay showed synergistic effects of DSF with cisplatin but not with gemcitabine in J82, UMUC-3, T24, HT1197 and HT1376 cells. Co-administration of DSF significantly increased DNA-platinum adducts by regulating cisplatin efflux transporter ATP7A and enhanced apoptosis by GC treatment in UMUC-3 cells, with significant increase of ROS production. Use of DSF in combination with GC (GCD) significantly inhibited tumor growth of UMUC-3 subcutaneous xenograft on athymic mice (by 39% compared with GC alone, p = 0.02). GCD regimen was as tolerable as GC and no significant differences were observed in body weight of treated mice between the two regimens. Conclusions Repositioning of DSF to a chemotherapy sensitizer is a promising treatment strategy, which can be translated rapidly in the future. Citation Format: Yuki Kita, Takashi Kobayashi, Ryouichi Saito, Toshinari Yamasaki, Takahiro Inoue, Osamu Ogawa. High-throughput chemical screening for sensitization of bladder cancer to gemcitabine and cisplatin chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2041. doi:10.1158/1538-7445.AM2017-2041
<i>JAMA Neurology</i>Peer Reviewers in 2014
Authors: Roger N. Rosenberg
Journal: JAMA Neurology (2015)

On behalf of the editors and editorial board of JAMA Neurology, I want to express our most sincere thanks to our reviewers for their commitment to provide scientifically excellent reviews of the papers sent to us. These reviews serve a vital function, making sure that only the best clinical and basic research, reviews, and comments are published. The peer review process is an arduous one and there is no substitute. Reviewers earn 3 American Medical Association Physician’s Recognition Award Category 1 Credits for accepted reviews submitted on time. The reviewers listed belowwith an asterisk have reviewed4ormore papers.We thank themverymuch for their support of our efforts and JAMA Neurology. We are most grateful.
Abstracts From the Emerging Science Series, June 20, 2012
Journal: Circulation (2012)

Vorapaxar is a novel platelet inhibitor that potently and selectively inhibits thrombin mediated platelet activation through antagonism of the platelet protease-activated receptor (PAR)-1.Patients with peripheral artery disease (PAD) are at high risk of atherothrombotic events and warrant new strategies for secondary prevention.Few medical therapies have been shown to reduce the risk of limb ischemia in patients with PAD. Methods:The TRA2P-TIMI 50 trial was a randomized, doubleblind, placebo controlled trial of vorapaxar 2.5 mg daily in addition to standard care in 26,449 patients with stable atherosclerotic vascular disease (History of myocardial infarction, stroke, or PAD).Eligible patients with PAD (Nϭ3,787) had a history of symptoms of claudication and either an ABI of Ͻ0.85 or prior peripheral revascularization for limb ischemia.The first efficacy endpoint was a composite of cardiovascular death, MI, or stroke and the principal safety endpoint was GUSTO moderate or severe bleeding.All hospitalizations for limb ischemia were also reviewed and adjudicated by a blinded Clinical Events Committee.Results: In patients who qualified for the trial with PAD, the primary endpoint did not differ significantly between patients allocated to vorapaxar compared with placebo (11.3% vs 11.9%, HR 0.94, 95% CI 0.78 -1.14, pϭ0.53, p-interactionϭ0.16for PAD vs MI qualifying cohorts).In contrast, rates of hospitalization for acute limb ischemia (2.3% vs 3.9%, HR 0.58, 95% CI 0.39 -0.86, pϭ0.006) and peripheral arterial revascularization (18.4% vs 22.2%, HR 0.84, 95% CI 0.73-0.97,pϭ0.017) were significantly lower in patients randomized to vorapaxar.Moderate or severe bleeding was increased with vorapaxar (7.4% vs 4.5%, HR 1.62, 95% CI 1.21-2.18,pϭ0.001) including ICH (0.9% vs 0.4%, HR 2.03, 95% CI 0.82-5.02,pϭ0.13).Conclusions: Vorapaxar did not significantly reduce the risk cardiovascular death, MI, or stroke in patients who qualified for the trial with PAD without a recent myocardial infarction, and increased the risk of moderate or severe bleeding.However, vorapaxar significantly reduced hospitalization for acute limb ischemia and arterial revascularization.These findings highlight a novel therapeutic approach to reduce limb ischemia in patients with PAD.
De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study
Authors: V. Guarneri, M.V. Dieci, G. Bisagni, A. Frassoldati, G.V. Bianchi, G.L. De Salvo, E. Orvieto, L. Urso, T. Pascual, L. Paré, P. Galván, M. Ambroggi, C.A. Giorgi, G. Moretti, G. Griguolo, R. Vicini, A. Prat, P.F. Conte
Journal: Annals of Oncology (2019)

BackgroundIn human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole.Patients and methodsPerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented.ResultsSixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P= 0.042).ConclusionsThe primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared.EUDRACT number2013-002662-40ClinicalTrials.gov IdentifierNCT02411344
Chronic Lymphocytic Leukemia B Cells Display IgM and IgD Isotype-Restricted Features That Affect Association with Co-Receptors, BCR Signaling, and Leukemic B-Cell Growth In Vivo
Authors: Andrea Nicola Mazzarello, Marcus Dühren-von Minden, Eva Gentner, Palash Chandra Maity, Gerardo Ferrer, Tatyana Tarasenko, Stefano Vergani, Jacqueline C Barrientos, Kanti R Rai, Peter McGuire, Hassan Jumaa, Nicholas Chiorazzi
Journal: Blood (2018)
Direct Detection of Expressed Mutations in AML Cells Using Single Cell RNA-Sequencing, and Its Impact on Defining Sources of Expression Heterogeneity
Authors: Allegra A Petti, Stephen R Williams, Christopher A Miller, Ian T Fiddes, David Chen, Sridhar Nonavinkere Srivatsan, Catrina Fronick, Robert Fulton, Deanna M Church, Timothy J Ley
Journal: Blood (2018)
An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation
Authors: Emile C. A. Nyns, René H. Poelma, Linda Volkers, Jaap J. Plomp, Cindy I. Bart, Annemarie M. Kip, Thomas J. van Brakel, Katja Zeppenfeld, Martin J. Schalij, Guo Qi Zhang, Antoine A. F. de Vries, Daniël A. Pijnappels
Journal: Science Translational Medicine (2019)

An implanted light source coupled with local gene therapy generates an automated shock-free system to treat atrial fibrillation in rats.
Robust Methods Are Needed to Evaluate the Pharmacologic Treatment of Obstructive Sleep Apnea
Authors: Sanjay R. Patel, Andrew D. Althouse
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

of interstitial lung abnormalities to a subset of individuals with serial chest computed tomography data from the Framingham Heart Study and reported accelerated loss of FVC among individuals with radiographic progression of interstitial changes (relative to individuals without interstitial lung abnormalities or with stable interstitial lung abnormalities) (3).Within COPDGene, individuals who developed "incident PRISm" (i.e., transitioned from normal spirometry ["GOLD 0"] at phase 1 to PRISm at phase 2) also exhibited higher rates of lung function decline, albeit in both FEV 1 and FVC rather than isolated declines in FVC (1).The degree to which interstitial lung abnormalities contribute to this transition has not yet been fully characterized.Assessment of the de novo development of interstitial lung abnormalities as well as progression of existing interstitial lung abnormalities are active areas of investigation within COPDGene.Notably, a significant number of subjects with PRISm in COPDGene had anatomical abnormalities that were not limited to interstitial parenchymal changes, including chest wall and diaphragmatic deformities as well as a smaller internal transverse thoracic diameter in phase 1 (4).In addition to anatomical and parenchymal changes, functional differences, such as small airway disease (5) and gas transfer abnormalities, represent additional domains that should be explored in PRISm.We continue to assert that the PRISm cohort is heterogeneous and is likely composed of subgroups with distinct pathobiological processes (6); interstitial lung abnormalities likely contribute to the development and progression of lung disease in a subset of subjects with PRISm.Future studies, both within and beyond COPDGene, to characterize the predictors and risks associated with distinct subgroups within PRISm are needed.
Combination of TREC Measurement and Next-Generation Sequencing in Newborn Screening for Severe Combined Immunodeficiency: A Pilot Program in Japan
Authors: Hideki Muramatsu, Daiei Kojima, Yusuke Okuno, Shinsuke Kataoka, Yoko Nakajima, Tetsuya Ito, Ikuya Tsuge, Sakai Yoshimi, Tomoaki Kato, Seiji Kojima, Yoshiyuki Takahashi
Journal: Blood (2018)
Vaccination Coverage Among Children in Kindergarten — United States, 2014–15 School Year
Authors: Ranee Seither, Kayla Calhoun, Cynthia L. Knighton, Jenelle Mellerson, Seth Meador, Ashley Tippins, Stacie M. Greby, Vance Dietz
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

State and local jurisdictions require children to be vaccinated before starting school to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. State vaccination requirements, which include school vaccination and exemption laws and health department regulations, permit medical exemptions for students with a medical contraindication to receiving a vaccine or vaccine component and may allow nonmedical exemptions for religious reasons or philosophic beliefs. To monitor state and national vaccination coverage and exemption levels among children attending kindergarten, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage estimates in 49 states and the District of Columbia (DC) and vaccination exemption estimates in 46 states and DC that reported the number of children with at least one exemption among kindergartners during the 2014-15 school year. Median vaccination coverage* was 94.0% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 94.2% for the local requirements for diphtheria, tetanus, and acellular pertussis vaccine (DTaP); and 93.6% for 2 doses of varicella vaccine among the 39 states and DC with a 2-dose requirement. The median percentage of any exemptions† was 1.7%. Although statewide vaccination coverage among kindergartners was high during the 2014-15 school year, geographic pockets of low vaccination coverage and high exemption levels can place children at risk for vaccine-preventable diseases. Appropriate school vaccination coverage assessments can help immunization programs identify clusters of low coverage and develop partnerships with schools and communities to ensure that children are protected from vaccine-preventable diseases.
Influenza Vaccination Coverage Among Pregnant Women — United States, 2012–13 Influenza Season
Authors: Sarah Ball, Sara Donahue, David Izrael, Deborah K. Walker, Rachel Martonik, Charles DiSogra, Helen Ding, Stacie M. Greby, Katherine Kahn, Peng-Jun Lu, Walter W. Williams, James A. Singleton, Erin D. Kennedy, Carolyn B. Bridges, Lisa A. Grohskopf, Denise J. Jamieson, Indu Ahluwalia
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Central Nervous System Cancers, Version 2.2014
Authors: Louis Burt Nabors, Jana Portnow, Mario Ammirati, Henry Brem, Paul Brown, Nicholas Butowski, Marc C. Chamberlain, Lisa M. DeAngelis, Robert A. Fenstermaker, Allan Friedman, Mark R. Gilbert, Jona Hattangadi-Gluth, Deneen Hesser, Matthias Holdhoff, Larry Junck, Ronald Lawson, Jay S. Loeffler, Paul L. Moots, Maciej M. Mrugala, Herbert B. Newton, Jeffrey J. Raizer, Lawrence Recht, Nicole Shonka, Dennis C. Shrieve, Allen K. Sills, Lode J. Swinnen, David Tran, Nam Tran, Frank D. Vrionis, Patrick Yung Wen, Nicole R. McMillian, Maria Ho
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.
Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways
Authors: Philip R. Jansen, Kyoko Watanabe, Sven Stringer, Nathan Skene, Julien Bryois, Anke R. Hammerschlag, Christiaan A. de Leeuw, Jeroen S. Benjamins, Ana B. Muñoz-Manchado, Mats Nagel, Jeanne E. Savage, Henning Tiemeier, Tonya White, Joyce Y. Tung, David A. Hinds, Vladimir Vacic, Xin Wang, Patrick F. Sullivan, Sophie van der Sluis, Tinca J. C. Polderman, August B. Smit, Jens Hjerling-Leffler, Eus J. W. Van Someren, Danielle Posthuma
Journal: Nature Genetics (2019)
A Randomized Trial of Lymphadenectomy in Patients with Advanced Ovarian Neoplasms
Authors: Philipp Harter, Jalid Sehouli, Domenica Lorusso, Alexander Reuss, Ignace Vergote, Christian Marth, Jae-Weon Kim, Francesco Raspagliesi, Björn Lampe, Giovanni Aletti, Werner Meier, David Cibula, Alexander Mustea, Sven Mahner, Ingo B. Runnebaum, Barbara Schmalfeldt, Alexander Burges, Rainer Kimmig, Giovanni Scambia, Stefano Greggi, Felix Hilpert, Annette Hasenburg, Peter Hillemanns, Giorgio Giorda, Ingo von Leffern, Carmen Schade-Brittinger, Uwe Wagner, Andreas du Bois
Journal: New England Journal of Medicine (2019)

Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence from randomized clinical trials has been limited.
Abnormal Sleep Spindles, Memory Consolidation, and Schizophrenia
Authors: Dara S. Manoach, Robert Stickgold
Journal: Annual Review of Clinical Psychology (2019)

There is overwhelming evidence that sleep is crucial for memory consolidation. Patients with schizophrenia and their unaffected relatives have a specific deficit in sleep spindles, a defining oscillation of non-rapid eye movement (NREM) Stage 2 sleep that, in coordination with other NREM oscillations, mediate memory consolidation. In schizophrenia, the spindle deficit correlates with impaired sleep-dependent memory consolidation, positive symptoms, and abnormal thalamocortical connectivity. These relations point to dysfunction of the thalamic reticular nucleus (TRN), which generates spindles, gates the relay of sensory information to the cortex, and modulates thalamocortical communication. Genetic studies are beginning to provide clues to possible neurodevelopmental origins of TRN-mediated thalamocortical circuit dysfunction and to identify novel targets for treating the related memory deficits and symptoms. By forging empirical links in causal chains from risk genes to thalamocortical circuit dysfunction, spindle deficits, memory impairment, symptoms, and diagnosis, future research can advance our mechanistic understanding, treatment, and prevention of schizophrenia.
Reducing the number of surveillance colonoscopies with faecal immunochemical tests
Authors: Erin L Symonds, Kathryn Cornthwaite, Robert J L Fraser, Peter Bampton, Charles Cock, Graeme P Young
Journal: Gut (2019)

We read with interest the article by Cross et al ,1 which examined the use of FIT in intermediate risk patients undergoing 3 yearly surveillance colonoscopies. The investigators assessed the diagnostic accuracy of this approach, together with the number of advanced adenomas and colorectal cancers missed, and the potential cost savings.

The results indicate that replacing 3 yearly colonoscopy with annual FIT (with a positivity threshold of 40 µg Hb/g faeces) would result in cost savings over the screening cycle of £4.7 million reflecting an 87% reduction in colonoscopies. However, such an approach would miss up to 41% of interval cancers and 67% of advanced adenomas. Modelling a lower FIT positivity threshold (10 µg Hb/g faeces) suggests that the strategy would reduce colonoscopies by 71% but would still miss 28% of cancers and 43% of advanced adenomas. …
Association of Racial and Socioeconomic Diversity With Implicit Bias in Acute Care Surgery
Authors: Laura Zebib, Bethany Strong, Gabrielle Moore, Gabriel Ruiz, Rishi Rattan, Tanya L. Zakrison
Journal: JAMA Surgery (2019)

17.3%; 95% CI, 13.8%-20.7%),although the upper extremity was the most frequently fractured region overall (52.1%; 95% CI, 48.1%-56.1%);28.7% of patients (95% CI, 23.7%-33.8%)required hospital admission.Discussion | To our knowledge, this study is the first to identify and characterize leash-dependent dog walking as an activity that imparts a significant and rising injury risk in older adults.The gravity of this burden is exemplified by the hip being most frequently fractured, because this injury is associated with long-term decreases in quality of life and functional capabilities, as well as mortality rates approaching 30%. 5 Combined with the sex disparity in injury burden, older women considering dog ownership must be made aware of this risk.Clinicians may play a role in identifying at-risk patients and minimizing fracture risk by advocating for preventive actions, such as obedience training to ensure dogs do not lunge while leashed, or suggesting smaller dog breeds for individuals contemplating ownership. 6 The study has limitations.Despite the validated nature of the source database, our findings likely underestimate the morbidity associated with elderly Americans walking leashed dogs: only emergency department cases are contained within the National Electronic Injury Surveillance System, and our analysis excluded less severe, nonfracture injuries.Moreover, the database does not include comparative dog sizes, cases requiring operative intervention, or disposition after discharge; future research may clarify the consequences of these variables.This study draws attention to an activity that can result in significant injury.For older adults-especially those living alone and with decreased bone mineral density-the risks associated with walking leashed dogs merit consideration.Even one such injury could result in a potentially lethal hip fracture, lifelong complications, or loss of independence.
Global Routine Vaccination Coverage, 2015
Authors: Rebecca M. Casey, Laure Dumolard, M. Carolina Danovaro-Holliday, Marta Gacic-Dobo, Mamadou S. Diallo, Lee M. Hampton, Aaron S. Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). Based on 2015 WHO and United Nations Children's Fund (UNICEF) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (DTP3), the first dose of measles-containing vaccine (MCV1) and the third dose of polio vaccine (Pol3) has remained stable (84%-86%) since 2010. From 2014 to 2015, estimated global coverage with the second MCV dose (MCV2) increased from 39% to 43% by the end of the second year of life and from 58% to 61% when older age groups were included. Global coverage was higher in 2015 than 2010 for newer or underused vaccines, including rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b (Hib) vaccine, and 3 doses of hepatitis B (HepB3) vaccine. Coverage estimates varied widely by WHO Region, country, and district; in addition, for the vaccines evaluated (MCV, DTP3, Pol3, HepB3, Hib3), wide disparities were found in coverage by country income classification. Improvements in equity of access are necessary to reach and sustain higher coverage and increase protection from vaccine-preventable diseases for all persons.