tbuckley/cabot-search huggingface dataset:
Effect of chronic exercise in healthy young male adults: a metabolomic analysis
Authors: Yen Chin Koay, Kelly Stanton, Vivian Kienzle, Mengbo Li, Jean Yang, David S Celermajer, John F O’Sullivan
Journal: Cardiovascular Research (2020)

Abstract Aims To examine the metabolic adaptation to an 80-day exercise intervention in healthy young male adults where lifestyle factors such as diet, sleep, and physical activities are controlled. Methods and results This study involved cross-sectional analysis before and after an 80-day aerobic and strength exercise intervention in 52 young, adult, male, newly enlisted soldiers in 2015. Plasma metabolomic analyses were performed using liquid chromatography, tandem mass spectrometry. Data analyses were performed between March and August 2019. We analysed changes in metabolomic profiles at the end of an 80-day exercise intervention compared to baseline, and the association of metabolite changes with changes in clinical parameters. Global metabolism was dramatically shifted after the exercise training programme. Fatty acids and ketone body substrates, key fuels used by exercising muscle, were dramatically decreased in plasma in response to increased aerobic fitness. There were highly significant changes across many classes of metabolic substrates including lipids, ketone bodies, arginine metabolites, endocannabinoids, nucleotides, markers of proteolysis, products of fatty acid oxidation, microbiome-derived metabolites, markers of redox stress, and substrates of coagulation. For statistical analyses, a paired t-test was used and Bonferroni-adjusted P-value of &amp;lt;0.0004 was considered to be statistically significant. The metabolite dimethylguanidino valeric acid (DMGV) (recently shown to predict lack of metabolic response to exercise) tracked maladaptive metabolic changes to exercise; those with increases in DMGV levels had increases in several cardiovascular risk factors; changes in DMGV levels were significantly positively correlated with increases in body fat (P = 0.049), total and LDL cholesterol (P = 0.003 and P = 0.007), and systolic blood pressure (P = 0.006). This study was approved by the Departments of Defence and Veterans’ Affairs Human Research Ethics Committee and written informed consent was obtained from each subject. Conclusion For the first time, the true magnitude and extent of metabolic adaptation to chronic exercise training are revealed in this carefully designed study, which can be leveraged for novel therapeutic strategies in cardiometabolic disease. Extending the recent report of DMGV’s predictive utility in sedentary, overweight individuals, we found that it is also a useful marker of poor metabolic response to exercise in young, healthy, fit males.
Historical overview of the interleukin-6 family cytokine
Authors: Sujin Kang, Masashi Narazaki, Hozaifa Metwally, Tadamitsu Kishimoto
Journal: The Journal of Experimental Medicine (2020)

Interleukin-6 (IL-6) has been identified as a 26-kD secreted protein that stimulates B cells to produce antibodies. Later, IL-6 was revealed to have various functions that overlap with other IL-6 family cytokines and use the common IL-6 signal transducer gp130. IL-6 stimulates cells through multiple pathways, using both membrane and soluble IL-6 receptors. As indicated by the expanding market for IL-6 inhibitors, it has become a primary therapeutic target among IL-6 family cytokines. Here, we revisit the discovery of IL-6; discuss insights regarding the roles of this family of cytokines; and highlight recent advances in our understanding of regulation of IL-6 expression.
Metabolite identification of ADH-10001 (Exherin™) in human plasma by LC/MS/MS
Authors: Mark J. Bednarcik, Mukur R. Gupta, Brian E. Huber, Jan K. Losos
Journal: Cancer Research (2006)

1135  ADH-10001 (Exherin ™) is a cyclic pentapeptide (Ac-CHAVC-NH2) which functionally inhibits N-cadherin, a cell adhesion protein present on certain tumor cells and established tumor blood vessels, resulting in the rapid disruption of tumor vasculature and tumor cell apoptosis. The HAV moiety is critical for potency and is stabilized by a disulfide bridge (S-S), the most labile bond in a biological system. ADH-10001 has shown a relatively short half-life in humans (2.5 hours). Determining the plasma stability of ADH-10001, and if the HAV moiety remains intact, will provide information related to potency and how to chemically modify ADH-10001 to increase its stability and half-life. In this study, ADH-10001 was incubated in human plasma up to 48 hours. Following extraction, ADH-10001 and its metabolites were qualitatively determined by LC/MS/MS analysis. The fragmentation patterns of these MS/MS ions were analyzed for the specific identification of metabolites using the Metabolite ID software. Incubation in human plasma for 48 hours yielded both hydrophilic and hydrophobic metabolites of ADH-10001. All products were the consequence of oxidation and rearrangement of the disulfide bond. In addition, the parallel dimer of ADH-10001, ADH-100230, and the anti-parallel dimer, ADH-100231 were generated. Importantly the metabolites of ADH-10001 identified in human plasma all contained the intact HAV moiety found in the parent peptide which may suggest the formation of active metabolites. Thus, the pharmacodynamic half-life of ADH-10001 and its metabolites could be longer than the pharmacokinetic half-life of 2.5 hours and may explain why ADH-10001 demonstrated clinical activity following a single dose. In addition, the disulfide bond of ADH-10001 is metabolically unstable and will be the focus of strategies for chemical modification to increase its circulating half-life.
Standing Up against Gender Bias and Harassment — A Matter of Professional Ethics
Authors: Michelle M. Mello, Reshma Jagsi
Journal: New England Journal of Medicine (2020)

Interview with Prof. Michelle Mello on health professionals' moral duty to intervene in response to sexual harassment and gender bias. (10:02)Download Health professionals have a moral duty to practice "upstanding" — intervening as bystanders — in response to sexual harassment and gender bias, an obligation that should be described in codes of medical professional ethics and supported with institutional training.
A moderate thermal dose is sufficient for effective free and TSL based thermochemotherapy
Authors: G.C. van Rhoon, M. Franckena, T.L.M. ten Hagen
Journal: Advanced Drug Delivery Reviews (2020)

Hyperthermia, i.e. heating the tumor to a temperature of 40–43 °C is considered by many a valuable treatment to sensitize tumor cells to radiotherapy and chemotherapy. In recent randomized trials the great potential of adding hyperthermia to chemotherapy was demonstrated for treatment of high risk soft tissue sarcoma: +11.4% 5 yrs. overall survival (OS) and for ovarian cancer with peritoneal involvement nearly +12 months OS gain. As a result interest in combining chemotherapy with hyperthermia, i.e. thermochemotherapy, is growing. Extensive biological research has revealed that hyperthermia causes multiple effects, from direct cell kill to improved oxygenation, whereby each effect has a specific temperature range. Thermal sensitization of the tumor cell for chemotherapy occurs for many drugs at temperatures ranging from 40 to 42 °C with little additional increase of sensitization at higher temperatures. Increasing perfusion/oxygenation and increased extravasation are two other important hyperthermia induced mechanisms. The combination of free drug and hyperthermia has not been found to increase tumor drug concentration. Hence, enhanced effectiveness of free drug will depend on the thermal sensitization of the tumor cells for the applied drug. In contrast to free drugs, experimental animal studies combining hyperthermia and thermo-sensitive liposomal (TSL) drugs delivery have demonstrated to result in a substantial increase of the drug concentration in the tumor. For TSL based chemotherapy, hyperthermia is critical to both increase perfusion and extravasation as well as to trigger TSL drug release, whereby the temperature controlled induction of a local high drug concentration in a highly permeable vessel is driving the enhanced drug uptake in the tumor. Increased drug concentrations up to 26 times have been reported in rodents. Good control of the tissue temperature is required to keep temperatures below 43 °C to prevent vascular stasis. Further, careful timing of the drug application relative to the start of heating is required to benefit optimal from the combined treatment. From the available experimental data it follows that irrespective whether chemotherapy is applied as free drug or using a thermal sensitive liposomal carrier, the optimal thermal dose for thermochemotherapy should be 40–42 °C for 30–60 min, i.e. equivalent to a CEM43 of 1–15 min. Timing is critical: most free drug should be applied simultaneous with heating, whereas TSL drugs should be applied 20–30 min after the start of hyperthermia.
Physiologically-based pharmacokinetic models for children: Starting to reach maturation?
Authors: Laurens F.M. Verscheijden, Jan B. Koenderink, Trevor N. Johnson, Saskia N. de Wildt, Frans G.M. Russel
Journal: Pharmacology & Therapeutics (2020)

Developmental changes in children can affect the disposition and clinical effects of a drug, indicating that scaling an adult dose simply down per linear weight can potentially lead to overdosing, especially in very young children. Physiologically-based pharmacokinetic (PBPK) models are compartmental, mathematical models that can be used to predict plasma drug concentrations in pediatric populations and acquire insight into the influence of age-dependent physiological differences on drug disposition. Pediatric PBPK models have generated attention in the last decade, because physiological parameters for model building are increasingly available and regulatory guidelines demand pediatric studies during drug development. Due to efforts from academia, PBPK model developers, pharmaceutical companies and regulatory authorities, examples are now available where clinical studies in children have been replaced or informed by PBPK models. However, the number of pediatric PBPK models and their predictive performance still lags behind that of adult models. In this review we discuss the general pediatric PBPK model principles, indicate the challenges that can arise when developing models, and highlight new applications, to give an overview of the current status and future perspective of pediatric PBPK modeling.
Waste, Worry, and the Seven Sins of Medicine
Authors: Brendan M. Reilly
Journal: New England Journal of Medicine (2020)

"Stupidity" and "mental laziness" are two of the seven sins of medicine enumerated by Richard Asher decades ago. In his time, these and other transgressions were usually "due to thoughtlessness and not deliberate." In today's wasteful system, the distinction is less clear.
Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2020
Authors: Jeanin E. van Hooft, Joyce V. Veld, Dirk Arnold, Regina G.H. Beets-Tan, Simon Everett, Martin Götz, Emo E. van Halsema, James Hill, Gianpiero Manes, Soren Meisner, Eduardo Rodrigues-Pinto, Charles Sabbagh, Jo Vandervoort, Pieter J. Tanis, Geoffroy Vanbiervliet, Alberto Arezzo
Journal: Endoscopy (2020)

Main Recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 ESGE recommends colonic stenting to be reserved for patients with clinical symptoms and radiological signs of malignant large-bowel obstruction, without signs of perforation. ESGE does not recommend prophylactic stent placement. Strong recommendation, low quality evidence. 2 ESGE recommends stenting as a bridge to surgery to be discussed, within a shared decision-making process, as a treatment option in patients with potentially curable left-sided obstructing colon cancer as an alternative to emergency resection. Strong recommendation, high quality evidence. 3 ESGE recommends colonic stenting as the preferred treatment for palliation of malignant colonic obstruction. Strong recommendation, high quality evidence. 4 ESGE suggests consideration of colonic stenting for malignant obstruction of the proximal colon either as a bridge to surgery or in a palliative setting. Weak recommendation, low quality evidence. 5 ESGE suggests a time interval of approximately 2 weeks until resection when colonic stenting is performed as a bridge to elective surgery in patients with curable left-sided colon cancer. Weak recommendation, low quality evidence. 6 ESGE recommends that colonic stenting should be performed or directly supervised by an operator who can demonstrate competence in both colonoscopy and fluoroscopic techniques and who performs colonic stenting on a regular basis. Strong recommendation, low quality evidence. 7 ESGE suggests that a decompressing stoma as a bridge to elective surgery is a valid option if the patient is not a candidate for colonic stenting or when stenting expertise is not available. Weak recommendation, low quality evidence.
Uncertain Association Between Concussion and Hypogonadism
Authors: Jacqueline Lopez, Mandeep Ghuman
Journal: JAMA Neurology (2020)

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
Cost-effectiveness of omalizumab in real world uncontrolled allergic asthma patients
Authors: A. Arrobas, M.P. Barbosa, S. Rabiais, B. Vandewalle, J. Félix
Journal: Pulmonology (2020)

To estimate the cost-effectiveness of omalizumab compared with standard of care in the treatment and control of severe persistent asthma, using the outcomes from the Portuguese subpopulation of the eXpeRience registry. This was a pragmatic cost-effectiveness analysis based on real world data from the eXpeRience registry which recruited 62 patients with uncontrolled persistent allergic asthma from 20 participating centers in Portugal. Response to omalizumab treatment was measured prospectively up to 24 months by the physician's Global Evaluation of Treatment Effectiveness (GETE). Retrospective data on patients' clinical symptoms, asthma control, lung function, exacerbations, and healthcare utilization were available for up to 12 months before omalizumab initiation and served as the standard of care comparator. The number of exacerbations (severe and non-severe), the number of clinical episodes, the number of days absent from work and/or school, and GETE response to therapy were considered as effectiveness outcomes. Following a societal perspective, as cost indicators, both direct and indirect costs were considered. Direct costs relate to the cost of omalizumab, standard of care and clinical episodes (emergency room visits, hospitalizations, and unscheduled doctor visits). Indirect costs relate to the societal cost of work absenteeism. Unit costs for clinical episodes and drugs were taken from official sources within the Portuguese Health Authority. A univariate sensitivity analysis was performed. A rate of 1.5 exacerbations per patient-year was estimated following omalizumab treatment compared with 8.2 exacerbations per patient-year prior to omalizumab initiation, implying an 82.1% reduction in the incidence of exacerbations following omalizumab treatment relative to standard of care alone. A 54.1% reduction in GETE score was also observed in favor of omalizumab treatment. The mean cost per person-year was 3023є in the 12 months of standard of care prior to omalizumab and 16,111є in the period of treatment with omalizumab. The incremental cost-effectiveness ratios were 2244є/exacerbation avoided, and 1750є/unit decrease in GETE classification. Our results demonstrate that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations, improving overall treatment effectiveness at an acceptable cost from a societal perspective.
An invited commentary on “Comparative analysis of weight loss and resolution of comorbidities between laparoscopic sleeve gastrostomy and Roux-en-Y gastric bypass: A systematic review and meta-analysis based on 18 studies” [Int. J. Surg. 76 (2020) 101–10]
Authors: Qurat Ul Ain, Numan Majeed
Journal: International Journal of Surgery (2020)
Will Legalization and Commercialization of Cannabis Use Increase the Incidence and Prevalence of Psychosis?
Authors: Robin M. Murray, Wayne Hall
Journal: JAMA Psychiatry (2020)

This Viewpoint assesses the repercussions of legalization and commercialization of cannabis use on the mental health of individuals, particularly those with a preexisting history of psychosis, and describes potential means to control cannabis price, consumption, and potency.
Positron Emission Tomography: A Novel Approach to Detect Pulmonary Artery Hypertension at the Early Stage?
Authors: Ruidi Tang, Yingkang Jin, Jing Liao, Lingdan Chen, Chunli Liu, Shaoqiang Li, Jian Wang, Tao Wang, Wenju Lu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China
Authors: Jing-Chun Song, Shu-Yuan Liu, Feng Zhu, Ai-Qing Wen, Lin-Hao Ma, Wei-Qin Li, Jun Wu
Journal: Military Medical Research (2020)

Abstract Thrombocytopenia is a common complication of critical care patients. The rates of bleeding events and mortality are also significantly increased in critical care patients with thrombocytopenia. Therefore, the Critical Care Medicine Committee of Chinese People’s Liberation Army (PLA) worked with Chinese Society of Laboratory Medicine, Chinese Medical Association to develop this consensus to provide guidance for clinical practice. The consensus includes five sections and 27 items: the definition of thrombocytopenia, etiology and pathophysiology, diagnosis and differential diagnosis, treatment and prevention.
BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma
Authors: Chengzhang Shi, Zhao Ye, Jie Han, Xiaoqing Ye, Wenchao Lu, Chenxing Ji, Zizhou Li, Zengyi Ma, Qilin Zhang, Yichao Zhang, Wenqiang He, Zhengyuan Chen, Xiaoyun Cao, Xuefei Shou, Xiang Zhou, Yongfei Wang, Zhaoyun Zhang, Yiming Li, Hongying Ye, Min He, Hong Chen, Haixia Cheng, Jun Sun, Jianyong Cai, Chuanxin Huang, Fei Ye, Cheng Luo, Bing Zhou, Hong Ding, Yao Zhao
Journal: Neuro-Oncology (2020)

Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA.
Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy
Authors: Stephanie M van der Voorn, Anneline S J M te Riele, Cristina Basso, Hugh Calkins, Carol Ann Remme, Toon A B van Veen
Journal: Cardiovascular Research (2020)

Abstract Arrhythmogenic cardiomyopathy (ACM) is a life-threatening cardiac disease caused by mutations in genes predominantly encoding for desmosomal proteins that lead to alterations in the molecular composition of the intercalated disc. ACM is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, and heart failure but mostly dominated by the occurrence of life-threatening arrhythmias and sudden cardiac death (SCD). As SCD appears mostly in apparently healthy young individuals, there is a demand for better risk stratification of suspected ACM mutation carriers. Moreover, disease severity, progression, and outcome are highly variable in patients with ACM. In this review, we discuss the aetiology of ACM with a focus on pro-arrhythmic disease mechanisms in the early concealed phase of the disease. We summarize potential new biomarkers which might be useful for risk stratification and prediction of disease course. Finally, we explore novel therapeutic strategies to prevent arrhythmias and SCD in the early stages of ACM.
Tailoring Common Hydrogels into 3D Cell Culture Templates
Authors: Aurélien Pasturel, Pierre‐Olivier Strale, Vincent Studer
Journal: Advanced Healthcare Materials (2020)

Abstract Physiologically relevant cell‐based models require engineered microenvironments which recapitulate the topographical, biochemical, and mechanical properties encountered in vivo. In this context, hydrogels are the materials of choice. Here a light‐based toolbox is able to craft such microniches out of common place materials. Extensive use of benzophenone photoinitiators and their interaction with oxygen achieves this. First, the oxygen inhibition of radicals is harnessed to photoprint hydrogel topographies. Then the chemical properties of benzophenone are exploited to crosslink and functionalize native hydrogels lacking photosensitive moieties. At last, photoscission is introduced: an oxygen‐driven, benzophenone‐enabled reaction that photoliquefies Matrigel and other common gels. Using these tools, soft hydrogel templates are tailored for cells to grow or self‐organize into standardized structures. The described workflow emerges as an effective microniche manufacturing toolset for 3D cell culture.
Correction to: Planning and reporting of quality-of-life outcomes in cancer trials
Authors: S. Schandelmaier, K. Conen, E. von Elm, J.J. You, A. Blümle, Y. Tomonaga, R. Saccilotto, A. Amstutz, T. Bengough, J.J. Meerpohl, M. Stegert, K.K. Olu, K.A.O. Tikkinen, I. Neumann, A. Carrasco-Labra, M. Faulhaber, S.M. Mulla, D. Mertz, E.A. Akl, X. Sun, D. Bassler, J.W. Busse, I. Ferreira-González, F. Lamontagne, A. Nordmann, V. Gloy, H. Raatz, L. Moja, R. Rosenthal, S. Ebrahim, P.O. Vandvik, B.C. Johnston, M.A. Walter, B. Burnand, M. Schwenkglenks, L.G. Hemkens, H.C. Bucher, G.H. Guyatt, M. Briel, B. Kasenda
Journal: Annals of Oncology (2015)
Neuroimmune modulation of pain and regenerative pain medicine
Authors: Thomas Buchheit, Yul Huh, William Maixner, Jianguo Cheng, Ru-Rong Ji
Journal: Journal of Clinical Investigation (2020)

Regenerative pain medicine, which seeks to harness the body's own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.