tbuckley/cabot-search huggingface dataset:
Targeting the Temporal Dynamics of Hypoxia-Induced Tumor-Secreted Factors Halts Tumor Migration
Authors: Manjulata Singh, Xiao-Jun Tian, Vera S. Donnenberg, Alan M. Watson, JingYu Zhang, Laura P. Stabile, Simon C. Watkins, Jianhua Xing, Shilpa Sant
Journal: Cancer Research (2019)

Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding of the emergence of migratory phenotypes impedes pharmaceutical drug development. Using our three-dimensional microtumor model with tight control over tumor size, we recapitulated the tumor size-induced hypoxic microenvironment and emergence of migratory phenotypes in microtumors from epithelial breast cells and patient-derived primary metastatic breast cancer cells, mesothelioma cells, and lung cancer xenograft cells. The microtumor models from various patient-derived tumor cells and patient-derived xenograft cells revealed upregulation of tumor-secreted factors, including matrix metalloproteinase-9 (MMP9), fibronectin (FN), and soluble E-cadherin, consistent with clinically reported elevated levels of FN and MMP9 in patient breast tumors compared with healthy mammary glands. Secreted factors in the conditioned media of large microtumors induced a migratory phenotype in nonhypoxic, nonmigratory small microtumors. Subsequent mathematical analyses identified a two-stage microtumor progression and migration mechanism whereby hypoxia induces a migratory phenotype in the initialization stage, which then becomes self-sustained through a positive feedback loop established among the tumor-secreted factors. Computational and experimental studies showed that inhibition of tumor-secreted factors effectively halts microtumor migration despite tumor-to-tumor variation in migration kinetics, while inhibition of hypoxia is effective only within a time window and is compromised by tumor-to-tumor variation, supporting our notion that hypoxia initiates migratory phenotypes but does not sustain it. In summary, we show that targeting temporal dynamics of evolving microenvironments, especially tumor-secreted factors during tumor progression, can halt tumor migration. SIGNIFICANCE: This study uses state-of-the-art three-dimensional microtumor models and computational approaches to highlight the temporal dynamics of tumor-secreted microenvironmental factors in inducing tumor migration.
Comparative Analysis of Gene Expression Status to Predict Response to Initial Multiple Myeloma Treatment: Utility of the Mmrf Commpass Database in Validating Historical Findings
Authors: Aneel Paulus, Marie Coignet, Alak Manna, Mayank Sharma, Taimur Sher, Vivek Roy, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2017)
THE RATIONALE OF GERIATRIC MEDICINE
Authors: E J STIEGLITZ
Journal: Annals of Internal Medicine (1951)

Article1 October 1951THE RATIONALE OF GERIATRIC MEDICINEEDWARD J. STIEGLITZ, M.S., M.D., F.A.C.P.EDWARD J. STIEGLITZ, M.S., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-35-4-848 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGeriatric medicine, an area of clinical practice, is part of the larger scientific field of gerontology, which is the study of aging. The phenomena and processes of aging affect all things, inanimate as well as living. Geologic structures age, crystals and gels are changed by aging, and cultures and species mature, become senescent and disappear. As biologic aging in an individual begins with conception and terminates only with death, gerontology is properly interested in all phases of life. Growth, development and evolution are just as much associated with the passage of time as atrophy and involution. Both processes continue throughout...Bibliography1. Stieglitz EJ: The orientation of geriatrics, Geriatrics 4: 127, 1949. MedlineGoogle Scholar2. Galdston I (Editor): Social medicine: its derivations and objectives, 1949, Commonwealth Fund, New York. Google Scholar3. Stieglitz EJ: The second forty years, 1946, Lippincott, Philadelphia. Google Scholar4. Stieglitz EJ: A future for preventive medicine, 1945, Commonwealth Fund, New York. Google Scholar5. Stieglitz EJ: Pertinent problems of geriatric medicine, Ann. Int. Med. 18: 89, 1943. LinkGoogle Scholar6. Stieglitz EJ (Editor): Geriatric medicine: the care of the aging and the aged, Ed. 2, 1949, W. B. Saunders Company, Philadelphia. Google Scholar7. GesellIlg AFL: The child from five to ten, 1946, Harper and Brothers, New York. Google Scholar8. Stieglitz EJ: Nutrition problems of geriatric medicine, J. A. M. A. 142: 1070, 1950. CrossrefGoogle Scholar9. Stieglitz EJ: Factors contributing to mental disease in the aged, J. Gerontol. 2: 280, 1947. CrossrefGoogle Scholar10. Kaplan O (Editor): Mental disorders in later life, 1945, Stanford University Press, Stanford, California. Google Scholar11. Stieglitz EJ: Medicine in an aging population, M. Clin. North America 33: 295 (March) 1949. CrossrefMedlineGoogle Scholar12. Stieglitz EJ: Difficulties in the clinical recognition of degenerative diseases, Biological Symposia XI, Aging and degenerative diseases, Edited by R. Moore, 1945, Jacques Cattell Press, Lancaster. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C.*Presented at the Thirty-second Annual Session of the American College of Physicians, St. Louis, Mo., April 13, 1951. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1951Volume 35, Issue 4Page: 848-856KeywordsAgingAtrophyBiologicsGeriatrics ePublished: 1 December 2008 Issue Published: 1 October 1951 PDF downloadLoading ...
Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study
Authors: Madeleine K D Scott, Katie Quinn, Qin Li, Robert Carroll, Hayley Warsinske, Francesco Vallania, Shirley Chen, Mary A Carns, Kathleen Aren, Jiehuan Sun, Kimberly Koloms, Jungwha Lee, Jessika Baral, Jonathan Kropski, Hongyu Zhao, Erica Herzog, Fernando J Martinez, Bethany B Moore, Monique Hinchcliff, Joshua Denny, Naftali Kaminski, Jose D Herazo-Maya, Nigam H Shah, Purvesh Khatri
Journal: The Lancet Respiratory Medicine (2019)

There is an urgent need for biomarkers to better stratify patients with idiopathic pulmonary fibrosis by risk for lung transplantation allocation who have the same clinical presentation. We aimed to investigate whether a specific immune cell type from patients with idiopathic pulmonary fibrosis could identify those at higher risk of poor outcomes. We then sought to validate our findings using cytometry and electronic health records.
一组丹麦献血者中自我报告 HS 的患者
Authors: P. Theut Riis, O.B. Pedersen, V. Sigsgaard, C. Erikstrup, H.M. Paarup, K.R. Nielsen, K.S. Burgdorf, H. Hjalgrim, K. Rostgaard, K. Banasik, H. Ullum, G.B. Jemec
Journal: British Journal of Dermatology (2019)

化脓性汗腺炎 (HS) 是一种痛苦的皮肤病,患者在腋窝、腹股沟、乳房下和会阴部反复发生脓肿。估计每 100 人中约有 1 人患有此病,但关于实际有多少人患有此病,研究结果不一。此病的特殊性使其有可能通过问卷进行诊断。对丹麦献血者进行了问卷调查,有 27,765 人作答。约有 1.8%(几乎每 50 人中有 1 人)献血者患有 HS。HS 献血者比无 HS 的献血者的体重指数更高且更年轻;女性与男性比例大约为 1:1。HS 献血者的吸烟频率和体重指数介于无 HS 献血者和来自其他研究 HS 患者的数值之间。该问卷还显示,HS 患者抑郁更为严重,但他们的生活质量与非 HS 献血者相同。丹麦唯一的户籍号码使我们能够比较参与者的公开登记信息。接受教育支持和现金补助(均为政府支持)的 HS 捐献者人数多于非 HS 捐献者。但是,HS 似乎不影响献血者的收入。只有 2.2% HS 献血者登记该疾病。我们对此的解释是,需要改进此病轻症病例的诊断。如果献血者继续献血,我们可以追踪他们,从而了解他们的 HS 对他们的生活有多大影响。
Empowering ASCI’s support of physician-scientists through stronger institutional connections
Authors: Kieren A. Marr, W. Kimryn Rathmell, John B. Hawley, Karen D. Guth
Journal: Journal of Clinical Investigation (2019)

The American Society for Clinical Investigation (ASCI), a nonprofit honorary society, was established to support physician-scientists by serving as a benchmark of excellence in medical research, a forum to celebrate advances in medicine, and a vehicle to communicate advances that bridge basic and translational research and their implementation across the growing myriad of medical specialties. A core intention of the Society is to engage the medical research community broadly through transparent communications of our activities and initiatives with the institutions that comprise the base for our membership. Recognizing the importance in identifying and actuating a strategy to support the Society's broad mission, the current leadership has undertaken a strategic plan that initiates with the goal of revamping its Institutional Representatives program. While the Society has grown with the historical privilege of close connections to institutions through an informal web created largely by the elected membership, we aim to improve institutional engagement towards overall goals of embracing and enhancing diversity of our community and implementing future collaborative programs to support physician-scientists. We briefly review ASCI's history, mission, and structure, and present the blueprint of the new Institutional Representatives program.
Abstract 20340: Defect of Ca <sup>2+</sup> -activated Cl <sup>-</sup> Channel in Intestinal Nodose Neurons Contributes to Impaired Satiety Signal in High-Fat Diet Induced Obesity
Authors: Runping Wang, Yongjun Lu, Michael Z Cicha, Kamal Rahmouni, Mark W Chapleau, Christopher J Benson, François M Abboud
Journal: Circulation (2014)

High fat diet inhibits the cholecystokinin (CCK) induced satiety signal in vagal afferents, which may contribute to the associated increased food intake. We hypothesized that a defect of Ca 2+ -activated chloride channel (CaCC) in high fat (HFD) fed mice leads to the reduction of CCK responses in intestinal vagal afferent nodose neurons. By using the whole cell patch-clamp in cultured nodose ganglia neurons isolated from C57BL/6 mice, we found that CCK (10nM) induced large inward chloride (Cl - ) currents (36.0±11pA/pF) that were eliminated with the fast Ca 2+ chelator BAPTA (1.0±0.5pA/pF, n=7), and reduced significantly by the CaCC channel inhibitor niflumic acid (100 μM, 13.6±2.0pA/pF, p&lt;0.05, n=8). The response to CCK in DiI-labeled proximal intestinal nodose neurons from obese mice fed a 60% HFD for 10 weeks was reduced significantly (6.1±2.9pA/pF, n=7, p&lt;0.01) relative to control lean mice (24.8±4.9pA/pF, n=7). The underlying molecular mechanism of the reduced CCK response in mice fed a HFD did not involve altered expression of CCK receptors in nodose neurons. We found that the relative mRNA (qPCR) of CCK receptor B was not significantly changed (1.01±0.13 in control vs. 1.18±0.31 in HFD nodose ganglia, n=4, p&gt;0.05) and the mRNA of CCK receptor A was even increased from 1.06±0.37 in control to 1.54±0.41 in HFD ganglia (n=4, p&lt;0.05). In contrast, the CaCC channel mRNA (Ano I) was decreased to 0.61±0.09 relative to 1.01±0.20 (n=4, p&lt;0.001), and Ano II mRNA was decreased to 0.31±0.07 relative to 1.02±0.22 (n=4, p&lt;0.001) in nodose ganglia from HFD fed vs. control lean mice. Since the maximum current induced by a saturation level of ligand reflects the level of protein expressed on the cytoplasmic membrane, we tested the CaCC current induced by a high level of intracellular Ca 2+ (20μM). We found that the maximum current was smaller in DiI labeled intestinal nodose neurons from HFD fed mice (13.7±2.9 pA/pF vs. 26.9±3.6 pA/pF in control mice, n=10, p&lt;0.05). Our results indicate that CCK-activated currents recorded from intestinal vagal afferent nodose neurons are reduced in mice fed a HFD, and are associated with reduced expression of a CCK-activated Ca 2+ -dependent Cl - channel. This mechanism may contribute significantly to HFD-induced suppression of the satiety reflex.
The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism?
Authors: Hamdi A Jama, Anna Beale, Waled A Shihata, Francine Z Marques
Journal: Cardiovascular Research (2019)

Over the past decade, the immune system has emerged as an important component in the aetiology of hypertension. There has been a blooming interest in the contribution of the gut microbiota, the microbes that inhabit our small and large intestine, to blood pressure (BP) regulation. The gastrointestinal tract houses the largest number of immune cells in our body, thus, it is no surprise that its microbiota plays an important functional role in the appropriate development of the immune system through a co-ordinated sequence of events leading to immune tolerance of commensal bacteria. Importantly, recent evidence supports that the gut microbiota can protect or promote the development of experimental hypertension and is likely to have a role in human hypertension. One of the major modulators of the gut microbiota is diet: diets that emphasize high intake of fermentable fibre, such as the Mediterranean diet and the Dietary Approaches to Stop Hypertension, promote expansion of protective microbes that release gut metabolites such as short-chain fatty acids, which are immune-, BP-, and cardio-protective, likely acting through G-coupled protein receptors. In contrast, diets lacking fibre or high in salt and fat, such as the Western diet, reduce prevalence of commensal microbial species and support a pathogenic and pro-inflammatory environment, including the release of the pro-atherosclerotic trimethylamine N-oxide. Here, we review the current understanding of the gut microbiota-driven immune dysfunction in both experimental and clinical hypertension, and how these changes may be addressed through dietary interventions.
The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
Authors: Khalil Bouyakdan, Hugo Martin, Fabienne Liénard, Lionel Budry, Bouchra Taib, Demetra Rodaros, Chloé Chrétien, Éric Biron, Zoé Husson, Daniela Cota, Luc Pénicaud, Stephanie Fulton, Xavier Fioramonti, Thierry Alquier
Journal: Journal of Clinical Investigation (2019)

Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA–binding protein–derived (ACBP-derived) endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes, and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP+ astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons, and ODN selectively activated POMC neurons through the ODN GPCR but not GABAA, and suppressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
Going Beyond the Sequences: TCR Binding Patterns at the Service of Cancer Detection
Authors: Vincent Zoete, George Coukos
Journal: Cancer Research (2019)

Abstract Deep sequencing of T-cell receptors enables the comprehensive profiling of lymphocyte populations and the characterization of the repertoire of T-cell responses against tumors, which could be applied to diagnose cancers. Ostmeyer and colleagues introduce a novel approach to characterize TCR patterns correlating with antigen recognition. By projecting the large TCR sequence space into a handful of biophysicochemical descriptors for key residues and seeking TCRs with similar antigen-binding capabilities even in the absence of identical amino acids, this approach presents several advantages over current methods. See related article by Ostmeyer et al., p. 1671
Overcoming Language Barriers in Mental and Behavioral Health Care for Children and Adolescents—Policies and Priorities
Authors: Katherine Yun, Gabriela Jenicek, Marsha Gerdes
Journal: JAMA Pediatrics (2019)

This Viewpoint describes the experiences of children and adolescents with low English proficiency seeking mental and behavioral health care in the US health care system and suggests strategies to improve care for this population.
Transposable elements drive widespread expression of oncogenes in human cancers
Authors: Hyo Sik Jang, Nakul M. Shah, Alan Y. Du, Zea Z. Dailey, Erica C. Pehrsson, Paula M. Godoy, David Zhang, Daofeng Li, Xiaoyun Xing, Sungsu Kim, David O’Donnell, Jeffrey I. Gordon, Ting Wang
Journal: Nature Genetics (2019)
US Supreme Court rejects plea not to give lethal injection to prisoner with rare medical condition
Authors: Owen Dyer
Journal: BMJ (2019)

The new conservative majority on the US Supreme Court has ruled 5-4 against a request for a stay of execution from a Missouri death row inmate who argued that his rare medical condition meant that a lethal injection would make his death more painful and frightening.1

Lawyers for Russell Bucklew, 50, argued that his execution by lethal injection with pentobarbital would violate the US Constitution’s eighth amendment, which prohibits the imposition of “cruel and unusual punishments,” because the injection might cause fragile blood vessel tumours in his head and neck to rupture.

Bucklew has the rare congenital disease cavernous hemangioma, which leads to the proliferation of vascular tumours. Justice Stephen Breyer, seen as one of the four liberal leaning judges …
Higher Dose of Tofacitinib for Rheumatoid Arthritis Poses Risks
Authors: Rebecca Voelker
Journal: JAMA (2019)

Patients with rheumatoid arthritis who take 10 mg of tofacitinib twice a day are at increased risk of dying or developing blood clots in the lungs compared with patients who take 5 mg twice a day, the FDA has warned.
Tobacco Smoking in Asia—A Public Health Threat
Authors: Bo-Yi Yang, Guang-Hui Dong
Journal: JAMA Network Open (2019)

Jae Jeong Yang, PhD; Danxia Yu, PhD; Wanqing Wen, MD; Xiao-Ou Shu, PhD; Eiko Saito, PhD; Shafiur Rahman, MSc; Prakash C. Gupta, PhD; Jiang He, PhD; Shoichiro Tsugane, PhD; Yong-Bing Xiang, MD; Yu-Tang Gao, MD; Woon-Puay Koh, PhD; Akiko Tamakoshi, PhD; Fujiko Irie, PhD; Atsuko Sadakane, PhD; Ichiro Tsuji, PhD; Seiki Kanemura, PhD; Keitaro Matsuo, PhD; Chisato Nagata, PhD; Chien-Jen Chen, ScD; Jian-Min Yuan, PhD; Myung-Hee Shin, PhD; Sue K. Park, PhD; Wen-Harn Pan, PhD; You-Lin Qiao, PhD; Mangesh S. Pednekar, PhD; Dongfeng Gu, PhD; Norie Sawada, PhD; Hong-Lan Li, MD; Jing Gao, MD; Hui Cai, PhD; Eric Grant, PhD; Yasutake Tomata, PhD; Yumi Sugawara, PhD; Hidemi Ito, PhD; Keiko Wada, PhD; Chen-Yang Shen, PhD; Renwei Wang, MD; Yoon-Ok Ahn, PhD; San-Lin You, PhD; Keun-Young Yoo, PhD; Habibul Ashan, MD; Kee Seng Chia, MD; Paolo Boffetta, MD; Manami Inoue, PhD; Daehee Kang, PhD; John D. Potter, PhD; Wei Zheng, MD, PhD
The D‐dimer assay
Authors: Eric D. Johnson, John C. Schell, George M. Rodgers
Journal: American Journal of Hematology (2019)

Abstract D‐dimer is an indirect marker of fibrinolysis and fibrin turnover; this molecule exhibits unique properties as a biological marker of hemostatic abnormalities as well as an indicator of intravascular thrombosis. D‐dimer is a soluble fibrin degradation product that results from the systematic degradation of vascular thrombi through the fibrinolytic mechanism. Because of this, the D‐dimer serves as a valuable marker of activation of coagulation and fibrinolysis in a number of clinical scenarios. Most commonly, D‐dimer has been extensively investigated for excluding the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D‐dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and for monitoring other conditions in which the patient is at high risk of bleeding or thrombosis. Limitations of the assay include D‐dimer elevation in a constellation of clinical scenarios (age, pregnancy, and cancer) and lack of clinical standardization.
Erratum. Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes. Diabetes Care 2018;41:2361–2369
Authors: Tomas Vaisar, Blythe Durbin-Johnson, Kathryn Whitlock, Ilona Babenko, Rajnish Mehrotra, David M. Rocke, Maryam Afkarian
Journal: Diabetes Care (2019)

In the article cited above, changes have been made in Table 2 on page 480 (for values under "Self-reported" and "New") and in the text under the RESULTS section on page 481 under the heading "Diabetes," where the final sentence was revised to read: Percentage of new diabetes increased in both the urban and rural areas (P , 0.0001).The changes do not modify the overall results of the study.
Phase I/II Trial Of Immucin a Pan HLA, Anti-MUC1 Signal Peptide Vaccine, In Multiple Myeloma Patients With Residual Disease Or Progression Following Autologous Stem Cell Transplantation
Authors: Lior Carmon, Irit Avivi, Kovjazin Riva, Lillian Dary, Michael Y Shapira
Journal: Blood (2013)
The Aire family expands
Authors: Adrian Liston, James Dooley
Journal: The Journal of Experimental Medicine (2019)

T cell tolerance depends upon Aire-expressing cells to purge the T cell repertoire of autoreactive clones. Once thought to be the exclusive domain of thymic epithelial cells, a new study by Yamano et al. (https://doi.org/10.1084/jem.20181430) in this issue of JEM identifies ILC3-like cells in the lymph nodes with similar properties.
Patient-Physician Relationship
Authors: Avinoam Shiran
Journal: JAMA Cardiology (2019)

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