tbuckley/cabot-search huggingface dataset:
Exercise genomics—a paradigm shift is needed: a commentary
Authors: Claude Bouchard
Journal: British Journal of Sports Medicine (2015)

The overarching goal of exercise genomics is to illuminate exercise biology and behaviour in order to better understand the preventive and therapeutic values of exercise. An ancillary aim is to understand the role of genomic variation in human physical attributes and sports performance. The aim of this report is to briefly comment on the current status of exercise genetics and genomics and to suggest potential improvements to the research agenda and translational activities. First, the genomic features of interest to the biology of exercise are defined. Then, the limit of the current focus on common variants and their implications for exercise genomics is highlighted. The need for a major paradigm shift in exercise genomics research is discussed with an emphasis on study designs and appropriately powered studies as well as on more mechanistic and functional research. Finally, a summary of current practices in translational activities compared with what best practice demands is introduced. One suggestion is that the research portfolio of exercise genomics be composed of a larger fraction of experimental and mechanistic investigations and a smaller fraction of observational studies. It is also recommended that research should shift to unbiased exploration of the genome using all the power of genomics, epigenomics and transcriptomics in combination with large observational but preferably experimental study designs, including Mendelian randomisation. In all cases, emphasis on replications is of paramount importance. This represents an extraordinary challenge that can only be met with large-scale collaborative and multicentre research programmes.
Interobserver agreement for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT
Authors: Simon L F Walsh, Lucio Calandriello, Nicola Sverzellati, Athol U Wells, David M Hansell
Journal: Thorax (2015)

Objectives To establish the level of observer variation for the current ATS/ERS/JRS/ALAT criteria for a diagnosis of usual interstitial pneumonia (UIP) on CT among a large group of thoracic radiologists of varying levels of experience. Materials and methods 112 observers (96 of whom were thoracic radiologists) categorised CTs of 150 consecutive patients with fibrotic lung disease using the ATS/ERS/JRS/ALAT CT criteria for a UIP pattern (3 categories—UIP, possibly UIP and inconsistent with UIP). The presence of honeycombing, traction bronchiectasis and emphysema was also scored using a 3-point scale (definitely present, possibly present, absent). Observer agreement for the UIP categorisation and for the 3 CT patterns in the entire observer group and in subgroups stratified by observer experience, were evaluated. Results Interobserver agreement across the diagnosis category scores among the 112 observers was moderate, ranging from 0.48 (IQR 0.18) for general radiologists to 0.52 (IQR 0.20) for thoracic radiologists of 10–20 years’ experience. A binary score for UIP versus possible or inconsistent with UIP was examined. Observer agreement for this binary score was only moderate. No significant differences in agreement levels were identified when the CTs were stratified according to multidisciplinary team (MDT) diagnosis or patient age or when observers were categorised according to experience. Observer agreement for each of honeycombing, traction bronchiectasis and emphysema were 0.59±0.12, 0.42±0.15 and 0.43±0.18, respectively. Conclusions Interobserver agreement for the current ATS/ERS/JRS/ALAT CT criteria for UIP is only moderate among thoracic radiologists, irrespective of their experience, and did not vary with patient age or the MDT diagnosis.
3.0T iMRI-guided resection of eloquent high-grade gliomas: preliminary results of a randomised controlled trial
Authors: Xiu Gong, Cheng-Jun Yao, Shi-Wen Yuan, Dong-Xiao Zhuang, Tian-Ming Qiu, Jun-Feng Lu, Jie Zhang, Yan-Yan Song, Wei Zhu, Ying Mao, Jin-Song Wu, Liang-Fu Zhou
Journal: The Lancet (2015)
Determinants of Metabolite Disposition
Authors: K S Pang, X Xu, M V St-Pierre
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Doing Less Is Sometimes Enough
Authors: Aaron E. Carroll
Journal: JAMA (2015)

There is increasingconcern thatphysiciansarepracticing toomuch medicine. For instance, statinswere originally intended to treat patients with the most significant risk factors for cardiovascular disease, but new criteriawill result in treatment of substantially larger numbers of adults. Likewise, the number of women screened with mammograms, and then receiving invasive surgery, seems to have increased.1 Accordingly, it is encouraging thatwitha commondisorder like appendicitis, that trendmay be reversing. Before the 1990s,when computed tomographic (CT) scanning began to be considered as a diagnostic aid for appendicitis, surgeons tended to be relatively aggressive in their treatment, especially in children. Diagnosing appendicitis in children can be difficult, and the risksof anappendectomywere considered tobemuch less concerning thandelayinganoperationand increasing the riskof appendix rupture. Physicians were willing to accept a noninsignificant number of operative procedures performed on childrenwhowere foundnot tohaveappendicitis, termednegative appendectomies, to avoid a complicated case. Avoiding a worse outcome has contributed to a significant amount of care in children. Newborns with fever are often hospitalized, and sometimes treated empirically with antibiotics, because of the concern that a small percentageof these infantsmight have a serious bacterial infection. When CT was studied for use in appendicitis, it was hoped that its use would help avoid undesired outcomes, by reducing the rates of perforated appendices in children. However, that reduction did not clearly occur2; what did occur was a decrease in the rate of negative appendectomies.3 Because of its high sensitivity, use of CTwas considered effective to ruleout appendicitis to anextent that left surgeons comfortable watching more children with symptoms while not operating. But this avoidance of surgery came with a cost: the ionizing radiation associated with an abdominal CT has been of increasing concern.4 Ultrasound, on the other hand, does not involve use of radiation but does have other limitations. It is user dependent and requires a trained technician at the bedside to achieve high levels of diagnostic accuracy.Even inoptimal cases, the sensitivity andspecificity of ultrasound are not as good as those of CT scans.5 Despite thesedeficiencies,ultrasoundhasbecomethepreferred imagingmoRelated article at jamapediatrics.com JAMAPEDIATRICS
Evolution of Class-I MHC Genes and Proteins: From Natural Selection to Thymic Selection
Authors: D A Lawlor, J Zemmour, P D Ennis, P Parham
Journal: Annual Review of Immunology (1990)

Article de synthese sur les genes de classe I du systeme majeur d'histocompatibilite (CMH) et les produits de ces genes: analyse de l'evolution du polymorphisme genetique des molecules de classe I en rapport avec leurs fonctions, a la fois dans la presentation de l'antigene aux cellules T matures et dans la selection positive ou negative du repertoire des cellules T dans le thymus. Comparaison des genes de classe I du CMH de l'homme avec ceux d'une espece tres proche, le chimpanze, et ceux d'une espece plus eloignee, la souris
Transparency and the Supreme Court — Can Employers Refuse to Disclose How Much They Pay for Health Care?
Authors: Nicholas Bagley, Christopher Koller
Journal: New England Journal of Medicine (2015)

Eighteen U.S. states have all-payer databases on the prices insurers pay for medical care, providing transparency for regulators, policy researchers, and consumers. But an impending Supreme Court case, Gobeille v. Liberty Mutual threatens to cripple such initiatives.
Feasibility study of cyclodextrins as active pharmaceutical ingredients for the treatment of GM1-gangliosidosis
Authors: Yuki Maeda, Keiichi Motoyama, Taishi Higashi, Yuka Horikoshi, Toru Takeo, Naomi Nakagata, Yuki Kurauchi, Hiroshi Katsuki, Yuki Kondo, Yoichi Ishitsuka, Tetsumi Irie, Takumi Era, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Intensive care provided by local hospitals should be improved
Authors: A Raffles
Journal: BMJ (1996)

EDITOR,—Joseph Britto and colleagues give a convincing argument for the further development of retrieval teams for critically ill children.1 But what of the quality of intensive care provided locally? The main interventions performed by the retrieval team were maintaining an airway (57%), ventilation (26%), and obtaining vascular access (86%). These interventions, however, should have been performed …
Pathogenesis of Membranous Nephropathy
Authors: William G. Couser, Christine K. Abrass
Journal: Annual Review of Medicine (1988)

Membranous nephropathy is the most common cause of idiopathic nephrotic syndrome in adults. Recent studies of the pathogenesis of the sub-epithelial glomerular immune deposits that characterize this disease have revealed new mechanisms of glomerular immune deposit formation involving cell surface antigens and have documented the role of the C5b-9 membrane attack complex of complement in mediating renal injury. Understanding these mechanisms may help us understand the pathogenesis of several other immune-mediated diseases and has implications for possible therapeutic interventions in MN.
Learning to Modulate Transmitter Release: Themes and Variations in Synaptic Plasticity
Authors: Robert D. Hawkins, Eric R. Kandel, Steven A. Siegelbaum
Journal: Annual Review of Neuroscience (1993)

Learning is the modification of behavior by experience, and memory is the retention of that modification over time. As learning and memory have become accessible to study with the techniques of cellular and molecular biology, a variety of cellular mechanisms of neuronal plasticity have now been identified that are thought to contribute to different forms of learning in invertebrates and vertebrates (for reviews, see Alkon & Rasmussen 1988; Byrne 1987; Carew & Sahley 1986; Hawkins et al 1987; Ito 1 989; Nicoll et a11988; Thompson 1986). Therefore, researchers can now attempt to define basic principles of learning by comparing these mechanisms and asking: What do they have in common, and how are they different? Until quite recently, these questions proved surprisingly difficult to answer. Different forms of neuronal plasticity appeared to predominate in different forms oflearning, in different regions of the brain, and in different species. In mammals, for example, at least two quite different synaptic mechanisms appeared to operate in different regions of the hippocampus, a structure critical for learning. Moreover, these two mechanisms seemed to differ from those encountered in such invertebrates as Aplysia, Her­ missenda, and Drosophila. However, recent cellular studies on hippo-
Nanomedicine-based enhancement of chemotherapy
Authors: Lonnie Myer, Douglas Jones, Lawrence Tamarkin, Giulio Paciotti
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5718 

CYT-6091 is a tumor-targeting nanomedicine that is assembled on 27 nm particles of pegylated colloidal gold (cAu). Our preclinical data in tumor-burdened mice reveal that CYT-6091 improves the safety of systemically administered TNF by altering the biodistribution of the cytokine. Additionally pegylation shields the nanoparticles from clearance by the reticuloendothelial system, while the size of cAu particles limits the drug’s biodistribution to the tumor due to the unique leakiness of the tumor vasculature. Ample preclinical and clinical data have shown that TNF is most effective as an anticancer therapy when given in combination with a chemotherapeutic agent, such as doxorubicin (Dox). Given that CYT-6091 is currently in a Phase I single agent clinical trial, its use in combination with Dox is a logical next step for an anticipated Phase Ib combinational clinical trial.    The first experiment, conducted in B16/F10 tumor burdened C57BL/6 mice, was designed to establish a baseline response of these tumors to a single intravenous injection of TNF, CYT-6091 or a sub-optimal dose of Dox (2.5 mg/kg). In a second study, tumor-burdened animals received multiple injections of TNF or CYT-6091 alone. A separate group of animals received multiple treatments of CYT-6091 in combination with Dox (2.5 mg/kg; administered two hours after CYT-6091 injection). In each study, tumor volume was monitored over time.    Single treatments with TNF, CYT-6091 or Dox were ineffective at slowing the growth of B16/F10 tumors. This held true for CYT-6091 although the nanodrug caused significant accumulation of TNF within these tumors. In contrast, repeated treatments with either TNF or CYT-6091 significantly inhibited tumor growth, resulting in a near 70% reduction in the size of the tumors when compared to controls. Consistent with previous observations, repeated injections with TNF proved very toxic resulting in a 75% mortality rate. Although multiple injections with Dox proved ineffective, the combination of CYT-6091 with Dox induced a synergistic response that was significantly more effective than either treatment alone. Compared to untreated controls, tumor growth for Dox alone, CYT-6091 alone and the CYT-6091/Dox combination group was inhibited by 24%, 62% and 94%, respectively. No overt signs of toxicity were noted for any group.    CYT-6091 was recently shown to cause the selective disruption of the tumor neovasculature. These studies build upon those data and demonstrate that repeated exposure to CYT-6091 may, not only induce anti-angiogenic responses in tumors, but also selectively breakdown the tumor neovasculature to significantly improve the efficacy of chemotherapy.
Needle Exchange Programs for HIV Outbreaks—Reply
Authors: Josiah D. Rich, Eli Y. Adashi
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 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
Gradually Worsening Tattoo Lesion
Authors: Ashish Bhargava, Pranatharthi H. Chandrasekar
Journal: JAMA (2015)

A 37-year-old woman presented with worsening swelling and itching in the red ink area of a recent tattoo. There was no abnormality over the black ink area. She had a white blood cell count of 10 000 cells/µL, normal hemoglobin level, and normal platelet count.What would you do next?
Let Food Be Thy Medicine
Authors: Rashi Minocha
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
NON-CONVULSIVE ELECTRIC (FARADIC) SHOCK THERAPY OF PSYCHOSES ASSOCIATED WITH ALCOHOLISM, DRUG INTOXICATION AND SYPHILIS
Authors: NATHANIEL J. BERKWITZ
Journal: American Journal of Psychiatry (1942)

Psyche and soma, interrelated, contribute to the "reaction of delirium" in toxic-organic psychoses. Delirious behavior is determined more by the type of personality of the individual than by the somatic changes in the brain. Since the psychogenic psychoses showing delirious behavior appear to respond best to shock therapy, this method was employed in the treatment of acute toxic-organic psychoses. Non-convulsive electric (faradic) shock therapy, a safe, simple and, inexpensive procedure, was given daily in conjunction with psychotherapy and the usual routine therapeutic measures. Thus "reaction of delirium" and the underlying organic disturbances were treated concurrently. In 67 cases of psychoses associated with alcohol and other drug intoxications, the duration of "reaction of delirium" was definitely shortened. In five cases of psychoses associated with syphilis of the central nervous system (general paresis), the acute delirious reactions responded favorably to this type of treatment. One patient showed complete remission. Subsequent malarial therapy given to the other four patients failed to produce further striking clinical or serological improvement. This preliminary study indicates that in "reaction of delirium" (toxic-organic psychoses) more effective results can be obtained by administering non-convulsive electric (faradic) shock therapy in conjunction with the customary routine medical procedures. Further investigations are being made.
Psychosocial correlates of cancer survival: a subsequent report 3 to 8 years after cancer diagnosis.
Authors: B R Cassileth, W P Walsh, E J Lusk
Journal: Journal of Clinical Oncology (1988)

Professional and public interest in possible relationships between psychosocial factors and disease outcome continues to increase. Published research in this area, however, is marked by contradictory results. Positive relationships between a variety of psychosocial factors and length of survival from cancer are reported, but other studies uncover no such associations. In a previously reported prospective investigation of 359 patients with newly diagnosed malignant diseases, we found no relationship between clinical outcome and any psychosocial factor studied. We have continued to observe these patients, who are now up to 8 years post-diagnosis, and report here additional data on their disease outcomes as they relate to psychosocial factors assessed at diagnosis. Two groups of patients were studied: 204 patients with advanced, prognostically poor malignant disease at diagnosis; and 155 patients with intermediate or high-risk melanoma or breast cancer. Shortly after diagnosis, patients completed a self-report questionnaire that assessed seven psychosocial factors previously reported to predict longevity in the general population. Factors included social ties and marital history, job satisfaction, use of psychotropic drugs, general life satisfaction, subjective view of adult health, hopelessness, and perception of amount of adjustment required to cope with the new diagnosis. Clinical factors--performance status and extent of disease at diagnosis--predicted clinical outcome. No psychosocial factor consistently was associated with length of survival or remission. Results of additional exploratory analyses also are reported.
Principles for Adoptive T Cell Therapy of Human Viral Diseases
Authors: Stanley R. Riddell, Philip D. Greenberg
Journal: Annual Review of Immunology (1995)

The development of successful adoptive immunotherapy for human virus infections is predicated on an understanding of the effector cells and mechanisms essential for providing the host with a protective response to acute infection and the requirements for long-term in vivo survival of transferred cells that will be necessary to provide memory responses to persistent and latent viral infections. In this review, we discuss the results of recent studies examining the effector mechanisms mediated by virus-specific αβ + T cells and the strategies viruses have evolved to evade recognition by such T cells and/or to interfere with the expression of T cell effector functions. The evasion strategies employed by individual viruses can render T cell subsets or T cells of particular specificities less effective in eliminating virally infected cells, and consequently they are less desirable choices for use in adoptive therapy. Insights derived from described studies of the pathogenesis and immunobiology of virus infections have resulted in the development of clinical adoptive immunotherapy studies for infections with CMV, EBV, and HIV. Although the results from such studies are preliminary, the principle that virus-specific T cells can be successfully transferred and can mediate therapeutic efficacy in humans has already been affirmed. The use of recently developed methods, such as retroviral-mediated gene transfer, to genetically modify antigen-specific T cell clones provides a novel approach to overcome limitations and improve on the safety and efficacy observed in these initial studies, suggesting that more widespread use of adoptive transfer of specific T cells as a therapeutic regimen should be feasible in the near future.
Efficiency of mechanical activation of inspiratory muscles in COPD using sample entropy
Authors: Leonardo Sarlabous, Abel Torres, José A. Fiz, Joaquim Gea, Juana M. Martínez-Llorens, Raimon Jané
Journal: European Respiratory Journal (2015)

Respiratory muscle dysfunction is a common problem in patients with chronic obstructive pulmonary disease (COPD) and has mostly been related to pulmonary hyperinflation [1, 2]. Associated diaphragm shortening and deleterious changes in the muscle force-length relationship cause a reduction in the muscles' capacity to generate pressure, placing them at a mechanical disadvantage [1, 3]. Specifically, both inspiratory muscle strength and mechanical efficiency may be reduced in COPD patients [1, 4–6], although, at isovolume, the contractile strength of the diaphragm in COPD is preserved or may even be improved in some cases [7]. The ratio between transdiaphragmatic pressure and electrical diaphragm activity has been used as a measure of respiratory muscle efficiency [8, 9]. However, in clinical practice, it is complex to measure this parameter directly, as invasive measures are required and these are uncomfortable for patients [4]. Respiratory muscle mechanomyogram exhibits significant differences between severe and very severe COPD patients <http://ow.ly/SdV6Y>