tbuckley/cabot-search huggingface dataset:
PDTM-41. INHIBITION OF DNA DOUBLE STRAND BREAK REPAIR PATHWAYS AS A PROMISING THERAPEUTIC TARGET IN DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPGs)
Authors: Sharmistha Pal, Jie Bian, Brendan Price, Dipanjan Chowdhury, Daphne Haas-Kogan
Journal: Neuro-Oncology (2019)

Abstract New approaches to the treatment of diffuse intrinsic pontine gliomas (DIPGs) are desperately needed. DNA damage response is essential for cells to maintain genome integrity as DNA is damaged by both endogenous and exogenous stressors. Many cancer cells exhibit hyper-dependency on specific DNA repair pathways due to either defects in DNA repair mechanisms and/or high levels of endogenous stress leading to accumulation of DNA damage lesions. Identification of DIPG-specific DNA repair deficiencies and resultant dependencies may establish novel therapeutic strategies for DIPGs. METHODS To identify pathways critical for DIPG cell survival, genome wide CRISPR-Cas9 screen was performed on patient derived DIPG cell lines followed by gene set enrichment analyses. To monitor the effects of pathway inhibition on survival, apoptosis, DNA damage and repair, assays were performed to measure cell proliferation, cleaved-caspase3, gamma-H2AX and reporter based-DNA repair efficiency. RESULTS Our unbiased CRISPR approach to uncover vulnerabilities in DIPGs identified DNA double strand break (DSBs) repair pathways as essential for DIPG cell proliferation and survival. Further studies revealed high basal DSBs in DIPG cells compared to neural stem cells and primary astrocytes that suggest dependence of DIPG cell survival on specific DSB repair pathways. We confirmed the intrinsic reliance of DIPG cells on the specific DSB repair pathway of mutagenic end-joining, and defined a key role for DNA repair in suppressing endogenous DNA damage-induced apoptotic cell death. CONCLUSION DIPG cells have high endogenous DNA damage levels and escape catastrophic genomic instability and cell death by engaging DNA repair pathways, in particular the mutagenic end-joining DNA repair pathway. Inhibition of this specific DNA repair pathway represents a promising new avenue for the treatment of DIPGs.
Genome-Wide CRISPR Screening in Acute Myeloid Leukemia Cells Identifies Genes in the PI3K/AKT/mTOR and MEK/ERK Pathways That Define Sensitivity to Trametinib
Authors: Tamilla Nechiporuk, Alisa Damnernsawad, Daniel Bottomly, Quinlan Morrow, Suyoun Choi, Sofia Beer, Stephen E Kurtz, Shannon K. McWeeney, Jeffrey W. Tyner
Journal: Blood (2019)
Oral Contraceptives and Liver Damage
Authors: L. I. Swaab
Journal: BMJ (1964)

STUDY OBJECTIVE--The aim was to analyse the relationship between partial gastrectomy and gastric cancer risk. DESIGN--This was a case control study, using a structured questionnaire to obtain problem orientated medical history and sociodemographic data. SETTING--The study was conducted in a network of hospitals in the Greater Milan area between January 1985 and February 1990. SUBJECTS--Subjects were 563 incident cases of histologically confirmed gastric carcinoma (347 males, 216 females, median age 60 years, range 28 to 74) and 1501 controls (885 males, 626 females, median age 58 years, range 23 to 74) in hospital for acute, non-neoplastic, non-digestive-tract disorders. Less than 3% of cases or controls refused to be interviewed. MEASUREMENTS AND MAIN RESULTS--Relative risks (RR) and the corresponding 95% confidence intervals (CI) were determined, adjusted for age and sex plus area of residence, education, and smoking when specified. Within 20 years after gastrectomy, the relative risk of gastric cancer was not significantly raised (RR = 1.2, 95% CI 0.5-2.8), but a positive association emerged after longer time intervals. The RR was 1.6 (95% CI 0.7-4.1) after 20 to 29 years, and 3.5 (95% CI 1.3-10.0) after 30 years or more. These results were consistent in the two sexes and in the subsequent age groups, and not materially influenced by allowance for a number of identified potential confounding factors using multivariate analysis. CONCLUSIONS--The risk of gastric cancer is increased in the long term (20 years or more) after gastrectomy. This is explainable in terms of increased intragastric carcinogen formation following gastrectomy, and/or potential similarities in aetiological correlates of gastric ulcer and carcinoma of the stomach.
[150] CADAVERIC WHOLE LIVER TRANSPLANTATION FOR NON-ACETAMINOPHEN FULMINANT HEPATIC FAILURE: A 20-YEAR EXPERIENCE
Authors: O. Detry, A. De Roover, C. Coimbra, J.P. Squifflet, J. Delwaide, A. Kaba, J. Joris, M.F. Hans, M.H. Delbouille, J. Monnard, J. Belaiche, M. Meurisse, P. Honore
Journal: Journal of Hepatology (2007)
Oral Contraceptives and Liver Damage
Authors: O. Lovgren
Journal: BMJ (1965)

Some comments on the conclusions reached in an article involving a study of steroids and liver function are presented.  The study in question did not utilize the bromsulphalein test (B.S.P.) which would have undoubtedly altered the results if it had been used.  The author has found a strong correlation between rheumatoid arthritis and B.S.P.  retention with the 20-mg B.S.P. test.  The excretion of B.S.P. in some patients was equally as low as in patients with severe liver cirrhosis.  It is noted that steroids can block the passage of the B.S.P. test dye through the liver and that there is a connection between the metabolism of estrogen and bilirubin.
QOLP-15. LONGITUDINAL PERCEPTION OF PROGNOSIS OF PATIENTS WITH HIGH GRADE GLIOMA COMPARED TO THEIR CAREGIVERS AND CLINICIANS
Authors: Akanksha Sharma, Eric Wolfe, Celina Barrera, Samantha Williamson, Hannah Farfour, Maciej Mrugala, Mark Edwin, Jeff Sloan, Alyx Porter
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Treatment options and prognosis are limited for patients with high grade glioma (pwHGG), underscoring the importance of patient and caregiver understanding to prioritize goals of care and quality of life (QOL). Although addressed by multiple providers, patients and caregivers may experience discordance in understanding the prognosis. This may be related to patient/caregiver perception, cognitive decline as a result of the tumor and/or treatment, or failure by the clinician to clearly articulate this information under emotional circumstances. AIMS: To evaluate the longitudinal perception of prognosis of patients compared to their caregivers and their providers during the adjuvant treatment of newly diagnosed HGG. METHODS After IRB approval, 16 pwHGG, their caregivers and their providers reported an overall survival estimate at each monthly visit during adjuvant treatment, as part of a larger survey. Options included “weeks,” “weeks to several months,” “several months to years,” “indefinite number of years”, or “I do not wish to answer.” RESULTS Seven of the sixteen patient/caregiver clusters have completed the appropriate duration of the study with the remaining completing in November. The perception of the patient differs from the caregiver at almost each visit. Regardless of the counseling provided by provider, the perception of both tends to change at each visit and can vary from dismal to overtly optimistic. There does not appear to be discrepancy between the neuro-oncology and palliative care provider’s perception of prognosis. CONCLUSION Newly diagnosed pwHGG and caregivers vary in their perception of prognosis, deviating not only from each other but also differing at each visit throughout the course of their illness. The providers’ perception appeared to remain consistent but often varied from that of the patient and caregiver. Providers need to be aware that prognostic understanding appears to fluctuate throughout the course of illness and cannot be clarified via a single discussion.
Thermal ablation versus cryotherapy or loop excision to treat women positive for cervical precancer on visual inspection with acetic acid test: pilot phase of a randomised controlled trial
Authors: Leeya F Pinder, Groesbeck P Parham, Partha Basu, Richard Muwonge, Eric Lucas, Namakau Nyambe, Catherine Sauvaget, Mulindi H Mwanahamuntu, Rengaswamy Sankaranarayanan, Walter Prendiville
Journal: The Lancet Oncology (2019)
Bleeding Control Training for the Lay Public: Keep it Simple—Reply
Authors: Justin C. McCarty, Edward J. Caterson, Eric Goralnick
Journal: JAMA Surgery (2019)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Primary Analysis of Anti-CD19 Tafasitamab (MOR208) Treatment in Combination with Idelalisib or Venetoclax in R/R CLL Patients Who Failed Prior BTK Inhibitor Therapy (COSMOS Trial)
Authors: Philipp Bernhard Staber, Wojciech Jurczak, Wolfram Brugger, Asher A. Chanan-Khan, Richard Greil, Andrzej Hellmann, Maren Dirnberger-Hertweck, Peter Kelemen, Jan Moritz Middeke, Marco Montillo, Marina Motta, Talha Munir, Peter Neumeister, Dietger Niederweiser, Sameer A. Parikh, Johannes Schetelig, Stephan Stilgenbauer, Vladan Vucinic, Johannes Weirather, Jennifer Woyach, Clemens-Martin Wendtner
Journal: Blood (2019)
Are Daylight Saving Time Changes Bad for the Brain?
Authors: Beth A. Malow, Olivia J. Veatch, Kanika Bagai
Journal: JAMA Neurology (2019)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Association between asthma, corticosteroids and allostatic load biomarkers: a cross-sectional study
Authors: Luke Evan Barry, Ciaran O’Neill, Liam G Heaney
Journal: Thorax (2020)

Background Allostatic load, a measure of early ageing or ‘wear and tear’ from adapting to environmental challenges, has been suggested as a framework with which to understand the stress-related disruption of multiple biological systems which may be linked to asthma. Considering the socioeconomic context is also critical given asthma and allostatic overload are more common in lower socioeconomic groups. Aims Estimate the relationship between allostatic load and its constituent biomarkers, asthma and corticosteroid prescribing while controlling for socioeconomic status. Methods Data from Understanding Society (a nationally representative survey of UK community-dwelling adults) waves 1–3 (2009–2012) allowed the identification of a sex-specific risk profile across 12 biomarkers used to construct an Allostatic Load Index for a sample of 9816 adults. Regression analyses were used to examine the association of asthma status and corticosteroid prescriptions with allostatic load and its constituent biomarkers while controlling for socioeconomic status (n=9805). Results Subjects with currently treated asthma and no corticosteroid prescription have an allostatic load 1.21 times higher than those without asthma (p&lt;0.001). Asthmatic subjects in receipt of inhaled corticosteroids had an allostatic load, approximately 1.12 times higher than those without asthma (p&lt;0.001). This association persisted in sensitivity analyses and appeared to be driven by an association with specific biomarkers (dehydroepiandrosterone-sulfate, waist-to-height ratio and C-reactive protein). Conclusion Early ageing, in the form of a higher allostatic load, was present even in the mildest asthma group not receiving inhaled corticosteroids. Allostatic load is helpful in understanding the increased all-cause mortality and multimorbidity observed in asthma.
Hydrogel scaffolds based on blood plasma cryoprecipitate and collagen derived from various sources: Structural, mechanical and biological characteristics
Authors: Marfa N. Egorikhina, Diana Ya Aleynik, Yulia P. Rubtsova, Grigory Ya Levin, Irina N. Charykova, Ludmila L. Semenycheva, Marina L. Bugrova, Evgeniy A. Zakharychev
Journal: Bioactive Materials (2019)

At present there is a growing need for tissue engineering products, including the products of scaffold-technologies. Biopolymer hydrogel scaffolds have a number of advantages and are increasingly being used to provide means of cell transfer for therapeutic treatments and for inducing tissue regeneration. This work presents original hydrogel biopolymer scaffolds based on a blood plasma cryoprecipitate and collagen and formed under conditions of enzymatic hydrolysis. Two differently originated collagens were used for the scaffold formation. During this work the structural and mechanical characteristics of the scaffold were studied. It was found that, depending on the origin of collagen, scaffolds possess differences in their structural and mechanical characteristics. Both types of hydrogel scaffolds have good biocompatibility and provide conditions that maintain the three-dimensional growth of adipose tissue stem cells. Hence, scaffolds based on such a blood plasma cryoprecipitate and collagen have good prospects as cell carriers and can be widely used in regenerative medicine.
Deleterious Germline Variants, Especially in the DNA Repair Pathway, Are Common in Patients with Non-Related Multiple Cancers, One of Them Being Hematological Malignancy
Authors: Deepak Singhal, Christopher N Hahn, Luke D Moma, Li Yan A Wee, Rakchha Chhetri, Milena Babic, Monika M Kutyna, Smita Hiwase, Wendy T Parker, Jinghua Feng, Andreas W Schreiber, Joel Geoghegan, Peer Arts, Raghu Gowda, Nimit Singhal, Anna L Brown, Richard J D'Andrea, Ian D Lewis, Hamish S Scott, Lucy A Godley, Devendra K Hiwase
Journal: Blood (2019)
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Authors: Shuang Qin, Linping Xu, Ming Yi, Shengnan Yu, Kongming Wu, Suxia Luo
Journal: Molecular Cancer (2019)

Abstract The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.
Paroxysmal Nocturnal Hemoglobinuria Clones Are Infrequent in Hepatitis-Associated Aplastic Anemia at the Time of Diagnosis
Authors: Wenrui Yang, Xin Zhao, Guangxin Peng, Li Zhang, Liping Jing, Kang Zhou, Yang Li, Lei Ye, Yuan Li, Jianping Li, Huihui Fan, Lin Song, Yang Yang, Youzhen Xiong, Fengkui Zhang, Jianxiang Wang
Journal: Blood (2019)
Comprehensive Mutational Analysis of Juvenile Myelomonocytic Leukemia Using Whole-Genome Sequencing
Authors: Yusuke Okuno, Hideki Muramatsu, Norihiro Murakami, Nozomu Kawashima, Manabu Wakamatsu, Hironobu Kitazawa, Tomoo Ogi, Yoshiyuki Takahashi
Journal: Blood (2019)
Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets
Authors: Thong H. Cao, Donald J.L. Jones, Adriaan A. Voors, Paulene A. Quinn, Jatinderpal K. Sandhu, Daniel C.S. Chan, Helen M. Parry, Mohapradeep Mohan, Ify R. Mordi, Iziah E. Sama, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos Filippatos, Hans L. Hillege, Marco Metra, Piotr Ponikowski, Nilesh J. Samani, Dirk J. Van Veldhuisen, Faiez Zannad, Chim C. Lang, Leong L. Ng
Journal: European Journal of Heart Failure (2019)

To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis.The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI-MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up-regulated and 46 down-regulated with more than two-fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein-protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised.Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.
Ongoing Spontaneous DNA Damage Creates Synthetic Lethality Targeted By Novel RAD51 Inhibitors in Multiple Myeloma
Authors: Subodh Kumar, Maria Gkotzamanidou, Srikanth Talluri, Melinda Day, Mychell Neptune, Lakshmi B. Potluri, Chandraditya Chakraborty, Kevin Mills, Masood A. Shammas, Nikhil C. Munshi
Journal: Blood (2019)
Safety, Tolerability and Efficacy of Orelabrutinib, Once a Day, to Treat Chinese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Cell Leukemia
Authors: Wei Xu, Yongping Song, Zengjun Li, Shenmiao Yang, Lihong Liu, Yu Hu, Wei Zhang, Jianfeng Zhou, Sujun Gao, Kaiyang Ding, Huilai Zhang, Zunmin Zhu, Shunqing Wang, Bing Xu, Jianda Hu, Ting Liu, Chunyan Ji, Zhongjun Xia, Yan Li, Xin Wang, Zhixin Xu, Renbin Zhao, Bin Zhang, Alan Zhu, Jianyong Li
Journal: Blood (2019)
Association of metastatic pattern and molecular status in metastatic lung non-small cell lung cancer adenocarcinomas
Authors: A. Dormieux, L. Mezquita, P-H Cournede, L. Lacroix, E. Rouleau, J. Adam, F. Facchinetti, F. Aboubakar, M-V Bluthgen, C. Naltet, P. Lavaud, A. Gazzah, C. Le Pechoux, C. Balleyguier, D. Planchard, B. Besse, C. Caramella
Journal: Annals of Oncology (2019)
Invincible arrogance--and patients suffer
Authors: T. Dinning
Journal: BMJ (1981)

sprinters lack stamina, but I imagine that no one would question their cardiopulmonary fitness-while in training.I am also worried by the modified physical fitness index, as this fails to take account of the resting pulse rate.Surely a formula based on percentage increase over resting rate at two, five, and 10 minutes would seem more reasonable, since the normal resting pulse rate can vary from the 40s to the 90s at least-or does a naturally slow pulse rate confer a fitness advantage ?Interestingly, Lieutenant-ColonelPearn referred to Zatopek's fitness index of 172; he was a distance runner with a resting pulse rate of about 40 per minute.But I wonder how Zatopek would have fared on the squash court, where explosive bursts of energy are required, or in gymnastics, in which a completely different sort of fitness and body control is demanded, or in the swimming pool.He certainly would have been
Ending the HIV Epidemic in the United States—The Roles of Increased Testing and Preexposure Prophylaxis
Authors: Julia M. Janssen, Mitchell H. Katz
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal