tbuckley/cabot-search huggingface dataset:
Cancer treatment impact on cognitive functioning and quality of life in lung cancer survivors.
Authors: S. Kohli, P. J. Novotny, J. A. Sloan, J. C. Buckner, P. D. Brown, P. Yang
Journal: Journal of Clinical Oncology (2010)

9112 Background: Relatively little research has examined the impact of cancer treatment on cognitive functioning (CF) and quality of life (QOL) in lung cancer survivors. We conducted an eight-year longitudinal study of lung cancer (LC) patients (pts) to systematically evaluate how changes in CF may affect their QOL. Methods: Between 2005-2008, we followed 1,757 primary LC pts who responded to CF questions at least once within 8 years of diagnosis. Overall QOL measured by LCSS (Lung Cancer Symptom Scale) and LASA (Linear Analogue Self Assessment) were assessed among 1,604 of 1,757 (91%) who completed the questionnaire at one or both of two time periods: short-term (T1-within 3 years of diagnosis) and long-term follow-up (T2-beyond 5 years of diagnosis). Questions rated overall CF and problems in thinking clearly. The primary endpoint, the percentage of the 1600 pts reporting they had a problem with cognitive functioning was accurate to within 2.5% with 95% confidence. Chi-square tests of 800 pts each has 80% power to detect a 7% difference in rates with a 5% Type I error. Results: 28% of pts reported a problem thinking clearly at T1 and T2. Seven percent of pts at T1 had been told by a doctor they had cognitive dysfunction. At T2, this was 8%. Males were more likely to have CF concerns (8% vs. 5%, p=0.04). Pts with SCLC were more likely to report CF problems (13% vs. 6%, p=0.04). Stage I patients had a 5% problem rate; stages II, III, and IV rates were 7%, (p=0.01). Surgical pts were less likely to report having problems thinking clearly (24% vs. 31%, p=0.03). Mean QOL scores differed >10 points between T1 and T2 of patients reporting CF, indicating clinical significance (p<0.01). Conclusions: Patient-reported assessments verify that impaired CF is a prevalent and debilitating side effect of cancer and its treatment that affects patient QOL. Self-report assessments are crucial and are needed to identify the impact that lung cancer and its treatments have on QOL. Funding Source:NIH grants: CA 115857, CA 84354>, CA 80127 and CA 77118. No significant financial relationships to disclose.
Ovarian ageing: the role of mitochondria in oocytes and follicles
Authors: Pascale May-Panloup, Lisa Boucret, Juan-Manuel Chao de la Barca, Valérie Desquiret-Dumas, Véronique Ferré-L'Hotellier, Catherine Morinière, Philippe Descamps, Vincent Procaccio, Pascal Reynier
Journal: Human Reproduction Update (2016)

There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures.Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations.PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA'; 'ovarian reserve', 'oocyte', 'ovary' or 'cumulus cells'; and 'ageing' or 'ovarian ageing'. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles.There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality.A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future.
Recent advances in malaria genomics and epigenomics
Authors: Sebastian Kirchner, B. Joanne Power, Andrew P. Waters
Journal: Genome Medicine (2016)

Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines.
Effectively Targeting Burkitt Lymphoma By Anti-CD20 Chimeric Antigen Receptor (CAR) Modified Expanded Natural Killer Cells Combined with a Histone Deacetylase Inhibitor, Romidepsin in-Vitro and in Humanized NSG Mice
Authors: Yaya Chu, Ashlin Yahr, Janet Ayello, Mitchell S. Cairo
Journal: Blood (2014)
The ever-expanding ERS fellowship programmes: achievements over the past 3 years
Authors: Maria G. Belvisi, Rory E. Morty, Gernot Rohde, Marc Miravitlles, Kathryn A. Forrest, Céline Genton, Nathalie Ritter, Nikoleta Luludi, Albert Jimenez, David Rigau, Thomy Tonia, Valérie Vaccaro, Carine Pannetier, Guy G. Brusselle, Stephen T. Holgate
Journal: European Respiratory Journal (2016)

The fellowship programmes are fundamental to the European Respiratory Society's (ERS) mission to promote lung health and drive standards for respiratory medicine globally. These programmes have been considerably expanded over the past 3 years and offer a wide range of training opportunities to boost early career scientists' competitiveness, enhance transnational mobility and promote scientific networks. The past 3 years have seen expansion of ERS fellowship programmes, driven by the 2013–2016 ERS fellowship strategy <http://ow.ly/6r9D30279J7> ERS would like to thank all the organisations providing funding and support towards the ERS fellowship programmes, as presented in [table 1][1]. ERS would also like to thank members of the ERS Fellowships and Awards Working Group and of the ERS College of Experts. [1]: #T1
The Evolution of Innate Immune Genes: Purifying and Balancing Selection on β-Defensins in Waterfowl
Authors: Joanne R. Chapman, Olof Hellgren, Anu S. Helin, Robert H. S. Kraus, Ruth L. Cromie, Jonas Waldenström
Journal: Molecular Biology and Evolution (2016)

In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. β-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five β-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific β-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated β-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of β-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian β-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.
Therapy for Mental Stress–Induced Myocardial Ischemia
Authors: Matthew M. Burg, Robert Soufer
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
What Is Obstructive Sleep Apnea in Adults?
Authors: James A Rowley, Suzanne Lareau, Bonnie F Fahy, Chris Garvey, Marianna Sockrider
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Obstructive sleep apnea (OSA) is a common problem that affects a person's breathing during sleep. A person with OSA has times during sleep in which air cannot flow normally into the lungs. The block in airflow (obstruction) is usually caused by the collapse of the soft tissues in the back of the throat (upper airway) and tongue during sleep.
Updated results for the advanced esophageal carcinoma cohort of the phase Ib KEYNOTE-028 study of pembrolizumab (MK-3475).
Authors: Toshihiko Doi, Sarina Anne Piha-Paul, Shadia Ibrahim Jalal, Hieu Mai-Dang, Sanatan Saraf, Minori Koshiji, Ildiko Csiki, Jaafar Bennouna
Journal: Journal of Clinical Oncology (2016)

7 Background: PD-L1 and PD-L2 expression have been associated with poor prognosis in esophageal cancer. Pembrolizumab (pembro) is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. The multicohort, phase Ib KEYNOTE-028 (NCT02054806) trial was designed to evaluate the safety and efficacy of pembro in patients (pts) with PD-L1 + advanced solid tumors. We report updated results from the esophageal carcinoma cohort of this study. Methods: Key eligibility criteria included advanced squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction, PD-L1 expression in tumor or stroma determined centrally by IHC, failure of standard therapy, and ECOG PS 0-1. Pts received pembro 10 mg/kg every 2 wk for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end point was ORR per RECIST v1.1 by investigator review. Results: Of the 23 pts enrolled, median age was 65 y, 82.6% were men, 73.9% had squamous histology, and 87.0% received ≥ 2 prior therapies for metastatic disease. As of the Aug 4, 2015 data cutoff date, median follow-up duration was 31 wk (range 5.7-71). Nine pts (39.1%) had drug-related adverse events (DRAEs), most commonly decreased appetite (n = 3, 13.0%). Four pts (17.4%) had grade 3 DRAEs, with only decreased lymphocytes reported in &gt; 1 pt (n = 2, 8.7%). No pts died or discontinued pembro due to a DRAE. Immune-mediated AEs, regardless of attribution by investigator, were grade 2 hypothyroidism (n = 2, 8.7%) and adrenal insufficiency (n = 1, 4.3%). ORR was 30.4% (95% CI 13.2-52.9), and the stable disease rate was 13.0% (n = 3, 95% CI 2.8-33.6); 6-mo and 12-mo PFS rates were 30.4% and 21.7%. Five of 7 responses were ongoing at data cutoff, with a median duration of response of 40.0 wk (range 24.1+ to 46.1+). Analysis of the relationship between PD-L1 expression level and antitumor activity is ongoing. Conclusions: Pembro continued to show manageable toxicity and durable antitumor activity in pts with heavily pretreated, PD-L1 + advanced esophageal carcinoma. Phase II and III trials of pembro in pts with esophageal carcinoma are ongoing. Clinical trial information: NCT02054806.
Discordant Interpretations of Breast Biopsy Specimens by Pathologists
Authors: George Leonard
Journal: JAMA (2015)

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
How to obtain the raw sample of non-small cell lung cancer for mutation screening in a tertialy hospital
Authors: Sawako Hosokawa, Yuki Kataoka, Nobuko Maehashi, Mariko Shinomiya, Takemura Tomoyasu, Katsuya Hirano, Kazuo Endo, Masataka Hirabayashi, Naoki Nakajima, Kosyo Takasu
Journal: Annals of Oncology (2015)
LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity
Authors: Irina Proekt, Corey N. Miller, Marion Jeanne, Kayla J. Fasano, James J. Moon, Clifford A. Lowell, Douglas B. Gould, Mark S. Anderson, Anthony L. DeFranco
Journal: Journal of Clinical Investigation (2016)

Studies of the genetic factors associated with human autoimmune disease suggest a multigenic origin of susceptibility; however, how these factors interact and through which tolerance pathways they operate generally remain to be defined. One key checkpoint occurs through the activity of the autoimmune regulator AIRE, which promotes central T cell tolerance. Recent reports have described a variety of dominant-negative AIRE mutations that likely contribute to human autoimmunity to a greater extent than previously thought. In families with these mutations, the penetrance of autoimmunity is incomplete, suggesting that other checkpoints play a role in preventing autoimmunity. Here, we tested whether a defect in LYN, an inhibitory protein tyrosine kinase that is implicated in systemic autoimmunity, could combine with an Aire mutation to provoke organ-specific autoimmunity. Indeed, mice with a dominant-negative allele of Aire and deficiency in LYN spontaneously developed organ-specific autoimmunity in the eye. We further determined that a small pool of retinal protein-specific T cells escaped thymic deletion as a result of the hypomorphic Aire function and that these cells also escaped peripheral tolerance in the presence of LYN-deficient dendritic cells, leading to highly destructive autoimmune attack. These findings demonstrate how 2 distinct tolerance pathways can synergize to unleash autoimmunity and have implications for the genetic susceptibility of autoimmune disease.
Chronic Lymphocytic Leukemia with Stereotyped IGHV4-59/IGKV3-20 B Cell Receptors: Another Manifestation of Hepatitis C Virus-Associated B Cell Lymphoproliferation?.
Authors: Efterpi Kostareli, Agnieszka Janus, Maria Gounari, Chrysoula Belessi, Sarka Pospisilova, David Oscier, Letizia Foroni, Paola Francia di Celle, Jesper Jurlander, Richard Rosenquist, Frederic Davi, Keith Thompson, Paolo Ghia, Kostas Stamatopoulos
Journal: Blood (2009)
Prognostic Significance Of S-Phase Kinase-Associated Protein 2 (Skp2) In DLBCL Patients Treated With Upfront Autologous Peripheral Blood Stem Cell Transplantation
Authors: Takashi Okamura, Ritsuko Seki, Koji Nagafuji, Kisato Nosaka, Takeshi Tsuchiya, Hiroyuki Tsuda, Toshihiro Miyamoto, Masakazu Higuchi, Hitoshi Suzushima, Michihiro Hidaka, Abe Yasunobu, Yuji Yufu, Yutaka Imamura, Masahiro Iwahashi, Tomoaki Fujisaki, Naokuni Uike, Moriuchi Yukiyoshi, Tetsuya Eto, Gondo Hisashi, Tomohiko Kamimura, Yasushi Takamatsu, Ohshima Koichi
Journal: Blood (2013)
GP receptionists could do more to relieve “burden” on patients, study finds
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Receptionists in general practice surgeries could help patients by offering clearer advice and a wider range of options when handling requests over the telephone, a study has found.

Research published in the British Journal of General Practice analysed audio recordings of over 2000 telephone calls between patients and receptionists to examine how patients could be best served.1 It identified a “burden” on some patients to push for effective service when trying to …
Effect of a novel cross-talk mechanism on the RAF/MEK/ERK and PI3K/AKT/mTOR pathways in melanoma: Role of ERK-mediated suppression of PTEN expression.
Authors: L. Ciuffreda, C. Di Sanza, M. Desideri, M. Ricciardi, U. Cesta Incani, A. Tafuri, F. Cognetti, G. Zupi, D. Del Bufalo, M. Milella
Journal: Journal of Clinical Oncology (2010)

8574 Background: The RAF/MEK/ERK pathway is a promising therapeutic target in melanoma. However, molecular determinants of sensitivity/resistance to pharmacological MEK inhibitors need to be identified. Methods: MEK and mTOR were inhibited using PD0325901 (PD) and temsirolimus (Tem), respectively, in melanoma, acute myeloid leukemia (AML), breast and pancreatic cancer cell lines. VEGF production was assessed by ELISA. Cell growth/proliferation, apoptosis, and expression/phosphorylation of pathway elements were assessed by MTT, flow cytometry, and Western blot (WB). Specific pathway elements were modulated by transduction with constitutively active (CA) or dominant negative (DN) constructs or by RNA interference. Results: In melanoma and AML models, PD and Tem had synergistic inhibitory effects on cell growth and VEGF production at suboptimal concentrations, but became frankly antagonistic at higher PD concentrations, suggesting competition for the same downstream target(s). PD time- and dose-dependently inhibited AKT, mTOR, p70S6K, and 4E-BP1 phosphorylation; consistently, PD increased PTEN expression in multiple tumor models. PTEN upregulation was dependent upon PD-mediated downregulation of c-jun, which relieved transcriptional PTEN suppression. These effects were not due to off-target activities of PD, as they were also observed using DN-MEK-1. Moreover, c-jun/PTEN regulation by ERK appears to be a general phenomenon, as it could be reproduced in NIH-3T3 cells overexpressing CA-ERK or c-jun, both of which resulted in PTEN downregulation. PTEN upregulation was central to the therapeutic effects of PD in melanoma, since M14 cells expressing DN-PTEN were more resistant to PD-mediated inhibition of cell growth and VEGF production. Conclusions: These results identify a novel cross-talk pathway that, through ERK-dependent upregulation of c-jun, leads to suppression of PTEN expression and concomitant activation of the PI3K/AKT/mTOR pathway. This notion may be helpful in selecting appropriate cellular contexts for the design of rational therapeutic strategies based on the single/combined inhibition of these two pathways. No significant financial relationships to disclose.
Treatment of Patients With Stable Ischemic Heart Disease
Authors: Fernando Civeira, Rocío Mateo-Gallego
Journal: JAMA (2016)

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