tbuckley/cabot-search huggingface dataset:
Income inequality and population health
Authors: R. Wilkinson
Journal: BMJ (2002)

Editor—Mackenbach's editorial reads like an obituary for the hypothesis that income inequality is related to population health.1 But a substantial body of evidence of such a relation has accumulated over the past 20 years, not only in the United States but also in Brazil, Russia, Taiwan, and England. Attempts to explain away this relation are rarely relevant to more than one of the many contexts in which it occurs.

The fact that health is more closely related to income in developed societies than to differences in income between them suggests effects of relative income or social status.2 But if income distribution has its main effect through differences in social status, and individual income (or education) is a proxy for individual social status, controlling income distribution for individual income makes little sense.3 It is a difference without a distinction, and more status equality is likely to improve average health.

As with individual income, the assumption that the median income of small areas measures material consumption rather than social relativities is unwarranted. Differences in median income between small areas are components of the income inequality of the larger areas. Choosing smaller areas converts variance, which would be income inequality in larger areas, into what is naively taken to be absolute income. Hence associations between income inequality and health tend to be strongest in larger areas and weakest in smaller areas, while the opposite is true of associations between median income and health.

Poor social affiliations and low status carry high population attributable risks. More unequal societies not only suffer more relative deprivation but tend to have lower rates of trust and of community involvement and—as over 40 studies show—more violence. More unequal societies will be more differentiated by social rank into relations of dominance and subordination and less able to enjoy more egalitarian and inclusive relations consistent with higher social capital and less class and racial prejudice.4 The links with violence show that inequality has psychosocial effects, and, given the powerful association between violence and other causes of death, critics should tread with caution.

Income may work better as a proxy for difference in social status in the United States than elsewhere. European differences in status ranking may be smaller and need more subtle markers. To test hypotheses that are fundamentally about differences in social status we need better measures of social differentiation and the importance of hierarchy in a society. The social dominance orientation scale might be a good place to start.5
Development of a clinical instrument to estimate suicide risk
Authors: Jerome A. Motto, David C. Heilbron, Richard P. Juster
Journal: American Journal of Psychiatry (1985)

This report details the development of an empirical suicide risk scale for adults hospitalized due to a depressive or suicidal state. The authors studied 2,753 such subjects prospectively regarding 101 psychosocial variables. In a 2-year follow-up, 136 (4.94%) of the subjects had committed suicide. Rigorous statistical analysis, including a validation procedure, identified 15 variables as significant predictors of suicidal outcome. These were translated into a paper-and-pencil scale that gives an estimated risk of suicide within 2 years. Such an instrument can provide a valuable supplement to clinical judgment and a quantitative expression of suicide risk.
Abstract 17939: Lack of the Alpha-11 Integrin in the Heart is Associated With Progressive Diastolic Dysfunction, Myofibrillar Disarray and Impaired Cardiomyocyte Growth
Authors: Robert A Civitarese, Ilana Talior-Volodarsky, Melissa Mitchell, Jean-François Desjardins, Golam Kabir, Donald Gullberg, Christopher A McCulloch, Kim A Connelly
Journal: Circulation (2014)

BACKGROUND: Integrins, transmembrane receptors, play crucial roles in diverse cellular and developmental processes due to critical interactions with the extracellular matrix (ECM). During fetal development and towards adulthood, heart growth and function is suggested to depend on forming and remodeling the ECM and its connection to the myocyte. Currently however, the role of integrins in cardiovascular development (CVD) is poorly defined. Thus, we hypothesized that the α11 integrin (α11), which is expressed by fibroblasts and binds preferentially to type I collagen fibers, plays a vital role in CVD. METHODS: α11 KO and wildtype littermate mice (both n = 8) were examined at 4 weeks and 8 weeks of age. Animals underwent function assessments, including echocardiography and invasive pressure volume (PV) loop analysis, and structural examination via histological and electron microscopy (EM) analysis. RESULTS: At 4 weeks, heart weight (HW) and HW indexed to tibial length were decreased in α11 KO mice (P &lt; 0.05), which were normalized at 8 weeks. Echocardiography revealed reduced end-diastolic area (EDA) at 4 weeks (P &lt; 0.05). Despite normalization of EDA at 8 weeks, PV loop revealed impaired diastolic function as evidence by increased EDP, prolonged Tau and steeper EDPVR (all P &lt; 0.05). No differences in HR or systolic parameters were evident. α11 KO mice also demonstrated structural changes. WGA staining revealed evidence of myofibrillar disarray. Connexin 43 and desmin staining showed increased Z-disk and intermediate filament clustering, respectively. LV myocyte size was also reduced (P &lt; 0.05). Similarly, EM analysis showed reduced cardiomyocyte thickness and distance between end plates (both P &lt; 0.05). CONCLUSION: Loss of α11 resulted in progressively worsening diastolic function that was associated with myofibrillar disarray and impaired cardiomyocyte growth. These findings suggest that α11 is required for the development of normal heart structure and function.
Abstract 101: WHSC1L1 as a therapeutic target in squamous cell carcinoma of the head and neck
Authors: Vassiliki Saloura, Theodore Vougiouklakis, Mark Lingen, Tanguy Seiwert, Everett Vokes, Yusuke Nakamura, Ryuji Hamamoto
Journal: Cancer Research (2015)

Abstract Background: Squamous cell carcinoma of the head and neck (SCCHN) is a common malignancy with high recurrence rates and poor survival, thus new therapies are eagerly awaited. Protein lysine methyltransferases (PKMTs) have recently become one of the most important targets for drug discovery efforts, but only a few studies have explored their role in the pathogenesis of SCCHN. WHSC1L1, a nuclear SET-Suppressor of variegation 3-9, Enhancer of zeste and Trithorax-domain (NSD) PKMT and chromatin modifier, was reported to be amplified (8p11.23) in 6% of SCCHN tumors. This study aims to elucidate the pathophysiological role of WHSC1L1 as an oncogenic force in SCCHN and provide rationale for the development of inhibitors targeting WHSC1L1. Methods: Cytotoxicity assays (MTTs) were conducted in one HPV-positive and one HPV-negative SCCHN cell line with WHSC1L1-specific siRNAs. Quantitative polymerase chain reaction (qPCR) and Western blotting were performed to examine WHSC1L1 expression levels in 14 SCCHN cell lines in comparison to a normal keratinocyte cell line (KGM). Immunohistochemistry (IHC) for WHSC1L1 in 115 patients with SCCHN and correlation of its expression with H3K36me2 was also performed. To identify candidate substrates that are directly methylated by WHSC1L1, in vitro methyltransferase assays using a recombinant protein library were conducted. Results: siRNA-mediated knockdown of WHSC1L1 caused significant cell death in 2 SCCHN cell lines. Approximately 30% of SCCHN cell lines overexpressed WHSC1L1 compared to normal keratinocytes. WHSC1L1 expression as evaluated by IHC was significantly stronger in SCCHN compared to normal epithelium (Kruskal-Wallis test, p = 0.002) and 24% of SCCHN sections expressed high levels of WHSC1L1, compared to 6% of dysplastic lesions and 0% of normal epithelium sections. Interestingly, no association between WHSC1L1 expression levels and H3K36me2 was observed. Conclusions: WHSC1L1 is genetically altered in multiple cancer types. In SCCHN, it is significantly overexpressed in 24% of the tumors and its knockdown caused significant growth suppression of both HPV-positive and HPV-negative SCCHN cell lines. Taken together, WHSC1L1 merits further investigation as a potential therapeutic target in SCCHN. Citation Format: Vassiliki Saloura, Theodore Vougiouklakis, Mark Lingen, Tanguy Seiwert, Everett Vokes, Yusuke Nakamura, Ryuji Hamamoto. WHSC1L1 as a therapeutic target in squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 101. doi:10.1158/1538-7445.AM2015-101
Blood: A Textbook of Hematology.
Authors: James H. Jandl
Journal: Annals of Internal Medicine (1988)

This edition of the benchmark text is more a complete revitalization than a revision: over 75 per cent of the text and 80 per cent of the references are new. Clearly written and abundantly illustrated, it presents the pathogenesis, clinical manifestations, and management of all hematologic disorders. It follows a logical organization from definition to treatment, and descriptions are written in language common to both clinical and basic science, making it as accessible to the general internist as to the specialist
Abstract 3344: Long-Term Clinical Outcome of Treating Long, Diffuse (>30mm) Lesions with Sirolimus-Eluting Stent.: From One-Year Clinical Outcome Of the j-Cypher Registry
Authors: Shinichi Shirai, Kenji Ando, Yoshimitsu Soga, Hiroyoshi Yokoi, Masashi Iwabuchi, Hitoshi Yasumoto, Hideyuki Nosaka, Masakiyo Nobuyoshi, Takeshi Kimura, Kazuaki Mitsudo
Journal: Circulation (2007)
The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009
Authors: T Ducomble, K Tolksdorf, I Karagiannis, B Hauer, B Brodhun, W Haas, L Fiebig
Journal: Eurosurveillance (2013)

Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main organ affected is the lung. This might lead to underestimate extrapulmonary TB (EPTB) forms, where in addition to the lung other sites are affected by TB. In Germany, TB notification data provide the main site and the secondary site of disease. To gain an overview of all the different EPTB forms, we analysed German TB notification data between 2002 and 2009 using information on both main and secondary disease site to describe all individual EPTB forms. Further, we assessed factors associated with meningitis using multivariable logistic regression. Solely analysing the main site of disease, lead to one third of EPTB manifestations being overlooked. Case characteristics varied substantially across individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis as main or secondary site. Of those, 105 (25%) of the 415 with available information had died. Multivariable analysis showed that meningitis was more likely in children younger than five years and between five and nine years-old (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40–7.07 and OR: 2.65; 95% CI: 1.40–5.00), in females (OR: 1.42; 95% CI: 1.17–1.73), and in those born in the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI: 1.66–3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02–2.23). Overall, EPTB manifestations, including meningitis, which is often fatal, were underestimated by routine analysis. We thus recommend using all information on disease manifestation generated by surveillance to monitor severe forms and to transfer the gained knowledge to TB case management where awareness of EPTB is most important.
Moscatilin induces apoptosis in human colorectal cancer cells: A crucial role of JNK activation caused by tubilin depolymerization and DNA damage.
Authors: Tzu-hsuan Chen, Shiow-Lin Pan, Jih-Hwa Guh, Chien-Chih Chen, Che-Ming Teng
Journal: Clinical Cancer Research (2007)

C39    Abstract   Moscatilin (4,49-dihydroxy-3,39,5-trimethoxybibenzyl), purified from the stem of  Dendrobrium loddigesii , inhibited the proliferation of human colorectal cancer HCT-116 cells in a concentration- and time-dependent manner by mitochondrial MTT reduction and sulforhodamine B assays. FACScan flow cytometric analysis of PI staining showed that Moscatilin induced a time-dependent arrest of the cell-cycle at G2/M phase associated with a declined proportion at G1 phase and followed by a subsequent increase at sub-G1 phase. The  in vitro  tubulin polymerization of turbidity assay showed that Moscatilin induced an inhibitory effect on tubulin polymerization, indicating that moscatilin may directly bind to tubulins and inhibit their polymerization. Moscatilin also induced the phosphorylation of JNK1/2 and downstream protein c-jun. SP600125 (a specific JNK inhibitor) significantly inhibited the activation of caspase-9 and -3, and the subsequent apoptosis induced by moscatilin. The data suggest that JNK activation may contribute to moscatilin-mediated apoptosis signaling. A parallel experiment showed that SP600125 could significantly inhibit HCT-116 cell apoptosis caused by taxol and vincristine, suggesting that the JNK activation may be a common mechanism for tubulin-binding agents. Moreover, the comet assay demonstrated that moscatilin could induce DNA damage and the activation of p53 and downstream effector p21 WAF1/CIP1 . In summary, the data suggest that moscatilin induces apoptosis of colorectal HCT-116 cells through tubulin depolymerization and DNA damage stress, leading to the activation of JNK and mitochondria-involved intrinsic apoptosis pathway. The nude mice xenograft models show the  in vivo  efficacy of moscatilin. The data also provide evidence for further development of this potential component.
Tamoxifen: Over 6000 scientific papers and still a hot topic Tamoxifen: Beyond the antiestrogen Edited by John A. Kellen. Boston, Birkhäuser, 1996, $94.50 (x + 377 pages), ISBN 0-8176-3842-3
Authors: J PEZZUTO
Journal: Trends in Endocrinology and Metabolism (1997)
Abstract 13344: Higher Ambient Fine Particulate Matter Air Pollution and Temperature Levels Adversely Impact Cardiopulmonary Exercise Performance Among Patients Beginning Cardiac Rehabilitation
Authors: Paolo Giorgini, Melvyn Rubenfire, Ritabrata Das, Robert L Bard, Theresa Gracik, Lu Wang, Masako Morishita, Elizabeth Jackson, Claudio Ferri, Robert D Brook
Journal: Circulation (2014)

Introduction: Fine particulate matter (PM 2.5 ) air pollution increases the risk for acute cardiovascular (CV) events. Extreme levels of ambient temperature (T) have also been linked to heightened CV risk. While several mechanisms have been proposed, no large-scale study has assessed the effect of PM 2.5 and T on directly-measured aerobic functional capacity among high-risk patients. Methods: We evaluated the effects of ambient PM 2.5 and T levels (during the prior 1 to 7 days at a local monitoring station) on cardiopulmonary exercise testing results performed among 2078 patients during enrollment into a cardiac rehabilitation program at the University of Michigan (from January 2003 to August 2011) using multiple linear regression analyses (controlling for age, sex, body mass index). Results: Peak exercise oxygen consumption (VO 2peak ) was significantly decreased by approximately 14.9% per 10 μg/m 3 increase in ambient PM 2.5 levels (lag days 6-7) (Figure). Increases in PM 2.5 were also related to significant decreases in anaerobic threshold (AT) (lag days 5-7), peak heart rate (lag days 2-3) and increases in peak systolic blood pressure (lag days 4-5). A 10°C increase in T was associated with reductions in VO 2peak (20.6% to 27.3%) (Figure) and AT (22.9% to 29.2%) during all 7 lag days. While PM 2.5 results were attenuated by adjusting for T due to co-linearity, the effects of ambient T remained significant after adjusting for same-day PM 2,5 and accounting for season. Conclusions: Short-term elevations in ambient PM 2.5 and/or T were associated with detrimental effects upon several aerobic exercise parameters among this cohort of cardiac rehabilitation patients. Both environmental factors may thus be important public health risk factors for an impaired exercise performance linked to an adverse quality of life and worse CV prognosis.
Abstract 19163: Implication of DNA Damage Signaling and Epigenetic Readers in Metabolic Disorder Observed in Vascular Wall of Ischemic Patients
Authors: Jolyane Meloche, Sarah Henry, Marie Le Guen, Eric Charbonneau, Steeve Provencher, Sebastien Bonnet
Journal: Circulation (2014)

Background: Coronary artery stenosis is characterized by coronary artery smooth muscle cell (CoASMC) proliferation and survival in detrimental conditions (increased inflammation, oxidized lipids, shear stress) known to cause DNA damage. In cancer, increased cell proliferation was attributed to DNA damage signaling activation secondary to mitochondrial/metabolic dysfunction. This leads to the upregulation of Poly(ADP)ribose-polymerase 1 (PARP-1), a critical enzyme acting as a DNA damage sensor, and the epigenetic reader Bromodomain-containing protein 4 (BRD4), both known to contribute to cell survival and proliferation. In light of these observations, we hypothesized that impaired mitochondria/metabolism triggers DNA damage signaling in coronary artery stenosis leading to CoASMC proliferation and thus vessel narrowing. Method/Results: Primary cultured human CoASMC from patients with stenosis (n=3) exhibit signs of mitochondrial dysfunction including hyperpolarization (TMRM; n=3, p&lt;0.05), downregulation metabolic sensors Sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1 (PGC1-α) expression (western blot (WB); n=3, p&lt;0.05). These cells also exhibit enhanced glycolysis compared to control hCoASMC (Seahorse Bioscience XF24e; n=3, p&lt;0.05). These mitochondrial/metabolic abnormalities enhance DNA damage signaling in human coronary arteries with stenosis (53BP1; n=8, p&lt;0.05), as well as PARP-1 and BRD4 expression (WB; n=4, p&lt;0.05) compared to control arteries. This pathogenic phenotype is also present in isolated hCoASMC issued from stenosis, as they have more DNA damage sites (γH2AX; n=5, p&lt;0.05) and exhibit increased PARP-1 and BRD4 expression (WB; n=4, p&lt;0.05) compared to control hCoASMC. PARP-1 and BRD4 activation in pathologic hCoASMC promote proliferation (Ki67; n=5, p&lt;0.05) by downregulating cell cycle inhibitors p300 and p21 (WB; n=3, p&lt;0.05), leading to cell survival (MTT assay; n=3, p&lt;0.05). This pathological phenotype was reversed upon treatment with a PARP-1 (Veliparib, 10μM) or a BRD4 (JQ1, 1μM) inhibitor. Conclusion: Our study suggests an important role for BRD4 signaling and metabolic disorder in coronary diseases and opens the door to new avenues of investigation and treatment.
Systematic Review of Bariatric Surgery
Authors: C David Sjöström
Journal: JAMA (2005)

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Phase II study of the histone-deacetylase inhibitor ITF2357 in relapsed/refractory Hodgkin’s lymphoma patients
Authors: S. Viviani, V. Bonfante, C. Fasola, P. Valagussa, A. M. Gianni
Journal: Journal of Clinical Oncology (2008)

8532 Background: Although great progress has been made in the last decades in the treatment of Hodgkin's lymphoma (HL), new therapeutic agents are still needed, in particular to treat patients (pts) relapsing or progressing after salvage chemotherapy. ITF2357 (Italfarmaco S.p.A Milan-Italy)) is a new hydroxamate histone deacetylases inhibitor that has inhibitory activity in the production of pro-inflammatory cytokines, as well as cytotoxic activity both in vitro on several human tumor cell lines and in vivo in pts with hematologic malignancies. Methods: To evaluate the efficacy, safety and tolerability of daily 100 mg oral doses of ITF2357 in 3 four-week cycles, a phase II open label non randomised study was started at the National Tumor Institute of Milan using the drug as third-line or higher treatment of heavily pretreated, relapsed or refractory, HL pts. Results: From May 2007, 15 out of 23 planned pts have been enrolled. Characteristics at start of ITF 2357 were as follows: median age 26 years (range: 21–54), Nodular Sclerosis histology 93%, advanced stage 73%, B symptoms 40%, extranodal±nodal involvement 47%, >3 involved sites 47%, median number of prior therapy lines 4 (range 2–4). Thirteen pts (87%) had a prior autologous transplant and 4 of them received an additional allogeneic transplant. The median mumber of ITF 2357 cycles administered was 2 (range 1–3).Thirteen pts completed at least one cycle of therapy and were evaluable for response. Seven pts (54%) had stable disease by CT scan that was associated with a significant reduction in FDG-PET uptake in 6 pts (46%) lasting a median of 3 months (range: 1–5). Six pts had progressive disease. Toxicity included: grade 1 leukopenia in 30%, grade 2 thrombocytopenia in 33%, fatigue in 50%, grade 1 diarrhea and/or abdominal pain in 40%; prolongation of QTc interval prompting transient drug discontinuation in 20%. Conclusions: Preliminary results in this series of very heavily preatreated HL pts showed that oral ITF 2357 has antitumor activity and a good safety profile. The drug warrants additional studies, alone and in combination, as salvage treatment for HL even at a less advanced status of disease. No significant financial relationships to disclose.
Establishment and characterization of an erythropoietin-dependent subline, UT-7/Epo, derived from human leukemia cell line, UT-7
Authors: N Komatsu, M Yamamoto, H Fujita, A Miwa, K Hatake, T Endo, H Okano, T Katsube, Y Fukumaki, S Sassa
Journal: Blood (1993)