tbuckley/cabot-search huggingface dataset:
The Joint Action and Learning Initiative: Towards a Global Agreement on National and Global Responsibilities for Health
Authors: Lawrence O. Gostin, Eric A. Friedman, Gorik Ooms, Thomas Gebauer, Narendra Gupta, Devi Sridhar, Wang Chenguang, John-Arne Røttingen, David Sanders
Journal: PLoS Medicine (2011)

A decade into the 21st century, billions of people have yet to benefit from the health advances of the 20th century. Life expectancy at birth in sub-Saharan Africa is 53 years [1]—only two years higher than in the United States a century ago [2], and 27 years lower than in high-income countries today [1]. The most basic human needs continue to elude the world's poorest people. In 2010, approximately 925 million people were suffering from chronic hunger [3], 884 million people lacked access to clean water, and 2.6 billion people were without access to proper sanitation facilities [4].

Such global health disparities will likely persist until there is fair and effective global governance for health—the organization of national and global norms, institutions, and processes that collectively shape the health of the world's population. Global governance for health goes beyond the health sector. It requires remediating the currently unfair and detrimental health impacts of international regimes (e.g., trade, intellectual property, and finance), and developing stable, responsive, democratic political institutions.

A coalition of civil society and academics, with a shared vision of the “right of everyone to the enjoyment of the highest attainable standard of physical and mental health” [5] (“right to health”), is therefore launching the Joint Action and Learning Initiative on National and Global Responsibilities for Health (JALI). JALI seeks to develop a post–Millennium Development Goal (MDG) framework for global health, one rooted in the right to health and aimed at securing universal health coverage for all people. We seek to clarify the health goods and services to which all people are entitled, national and global responsibilities to secure the health of the world's population, and governance structures required to realize these responsibilities. Our goal is a global agreement, such as a Framework Convention on Global Health, which sets priorities, clarifies national and international responsibilities, ensures accountability, and develops corresponding institutions, such as a Global Health Fund [6],[7].
Hyperlipidemia and glucose intolerance in the post-renal transplant patient.
Authors: M S Markell, V Armenti, G Danovitch, N Sumrani
Journal: Journal of the American Society of Nephrology (1994)

This review examines the relationship between renal transplantation and two important metabolic consequences: hyperlipidemia and glucose intolerance. Before cyclosporine, hypertriglyceridemia and hypercholesterolemia were common abnormalities that worsened in the cyclosporine era. In addition to obesity, steroid use, and reduced renal function, cyclosporine plays an independent role in elevating cholesterol levels, with particular reference to the modulation of the low-density lipoprotein receptor. Management includes maintaining low levels of steroid, manipulation of cyclosporine appropriately, diets low in fat and cholesterol, and an exercise program. Pharmacologic management in general revolves around the HMG-COA reductase drugs, which can be used safely if liver function tests and muscle enzymes are monitored. The unmasking of clinically important glucose intolerance occurs in 5 to 10% of patients in the cyclosporine era, not different from the earlier experience. Steroids and cyclosporine independently can worsen glucose tolerance to unmask a genetic predisposition to Type II diabetes in some and to even create glucose intolerance in otherwise normal individuals. Management is based on dietary and immunosuppressive drug dosing manipulations and the judicious use of oral hypoglycemic agents. Half of these recipients may ultimately need insulin. In summary, hyperlipidemia and glucose intolerance remain important metabolic consequences of renal transplantation that affect long-term patient survival unless recognized and treated.
Intrahepatic accumulation of nitric oxide-derived reactive species associates with histological severity of nonalcoholic steatohepatitis
Authors: C. García-Monzón, E. Martin-Pérez, O. Lo Iacono, M. Fernández Bermejo, P. Sanz, P.L. Majano, A. Apolinario, E. Larrañaga, R. Moreno-Otero
Journal: Journal of Hepatology (2000)
Evolution of Trace Amine–Associated Receptor (TAAR) Gene Family in Vertebrates: Lineage-Specific Expansions and Degradations of a Second Class of Vertebrate Chemosensory Receptors Expressed in the Olfactory Epithelium
Authors: Yasuyuki Hashiguchi, Mutsumi Nishida
Journal: Molecular Biology and Evolution (2007)

The trace amine–associated receptors (TAARs) form a specific family of G protein–coupled receptors in vertebrates. TAARs were initially considered neurotransmitter receptors, but recent study showed that mouse TAARs function as chemosensory receptors in the olfactory epithelium. To clarify the evolutionary dynamics of the TAAR gene family in vertebrates, near-complete repertoires of TAAR genes and pseudogenes were identified from the genomic assemblies of 4 teleost fishes (zebrafish, fugu, stickleback, and medaka), western clawed frogs, chickens, 3 mammals (humans, mice, and opossum), and sea lampreys. Database searches revealed that fishes had many putatively functional TAAR genes (13–109 genes), whereas relatively small numbers of TAAR genes (3–22 genes) were identified in tetrapods. Phylogenetic analysis of these genes indicated that the TAAR gene family was subdivided into 5 subfamilies that diverged before the divergence of ray-finned fishes and tetrapods. In tetrapods, virtually all TAAR genes were located in 1 specific region of their genomes as a gene cluster; however, in fishes, TAAR genes were scattered throughout more than 2 genomic locations. This possibly reflects a whole-genome duplication that occurred in the common ancestor of ray-finned fishes. Expression analysis of zebrafish and stickleback TAAR genes revealed that many TAARs in these fishes were expressed in the olfactory organ, suggesting the relatively high importance of TAARs as chemosensory receptors in fishes. A possible evolutionary history of the vertebrate TAAR gene family was inferred from the phylogenetic and comparative genomic analyses.
Is there any evidence for forward modeling in language production?
Authors: Myrto I. Mylopoulos, David Pereplyotchik
Journal: Behavioral and Brain Sciences (2013)

Abstract The neurocognitive evidence that Pickering &amp; Garrod (P&amp;G) cite in favor of positing forward models in speech production is not compelling. The data to which they appeal either cannot be explained by forward models, or can be explained by a more parsimonious model.
CNS-specific Therapy for Ongoing EAE by Silencing IL-17 Pathway in Astrocytes
Authors: Yaping Yan, Xiaoli Ding, Ke Li, Bogoljub Ciric, Shuai Wu, Hui Xu, Bruno Gran, Abdolmohamad Rostami, Guang-Xian Zhang
Journal: Molecular Therapy (2012)

The interleukin-17 (IL-17) cytokine family is crucial to the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). It has been shown in a neuroectoderm-specific knockout study that astrocyte-restricted ablation of Act1, a key and common transcription factor for signals mediated by IL-17 family members (IL-17A, IL-17F, and IL-17C), ameliorates EAE. However, the effect of Act1 deficiency in astrocytes on ongoing disease, which is of clinical relevance for MS therapy, has not been investigated. Here we report that intracerebroventricular (i.c.v.) injection of a novel lentiviral vector (shAct1) to knockdown Act1 expression in astrocytes effectively inhibited disease progression at EAE induction, clinical onset, and peak of disease (ongoing phases), with significantly reduced numbers of infiltrating inflammatory cells and percentage of Th17 cells in the central nervous system (CNS). This was mainly due to the suppressed expression of Th17-related chemokines in astrocytes, while neurotrophic factors in the CNS and immune responses in the periphery were not affected. These results demonstrate that blocking the IL-17 pathways in astrocytes is a promising therapeutic approach for MS in a CNS-specific manner, which does not interfere with systemic immune responses, a major concern in conventional MS therapy. The interleukin-17 (IL-17) cytokine family is crucial to the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). It has been shown in a neuroectoderm-specific knockout study that astrocyte-restricted ablation of Act1, a key and common transcription factor for signals mediated by IL-17 family members (IL-17A, IL-17F, and IL-17C), ameliorates EAE. However, the effect of Act1 deficiency in astrocytes on ongoing disease, which is of clinical relevance for MS therapy, has not been investigated. Here we report that intracerebroventricular (i.c.v.) injection of a novel lentiviral vector (shAct1) to knockdown Act1 expression in astrocytes effectively inhibited disease progression at EAE induction, clinical onset, and peak of disease (ongoing phases), with significantly reduced numbers of infiltrating inflammatory cells and percentage of Th17 cells in the central nervous system (CNS). This was mainly due to the suppressed expression of Th17-related chemokines in astrocytes, while neurotrophic factors in the CNS and immune responses in the periphery were not affected. These results demonstrate that blocking the IL-17 pathways in astrocytes is a promising therapeutic approach for MS in a CNS-specific manner, which does not interfere with systemic immune responses, a major concern in conventional MS therapy.
Murine Cell Lines Derived from <i>Pten</i> Null Prostate Cancer Show the Critical Role of PTEN in Hormone Refractory Prostate Cancer Development
Authors: Jing Jiao, Shunyou Wang, Rong Qiao, Igor Vivanco, Philip A. Watson, Charles L. Sawyers, Hong Wu
Journal: Cancer Research (2007)

Abstract PTEN mutations are among the most frequent genetic alterations found in human prostate cancers. Our previous works suggest that although precancerous lesions were found in Pten heterozygous mice, cancer progression and metastasis only happened when both alleles of Pten were deleted. To understand the molecular mechanisms underlying the role of PTEN in prostate cancer control, we generated two pairs of isogenic, androgen receptor (AR)–positive prostate epithelial lines from intact conditional Pten knock-out mice that are either heterozygous (PTEN-P2 and -P8) or homozygous (PTEN-CaP2 and PTEN-CaP8) for Pten deletion. Further characterization of these cells showed that loss of the second allele of Pten leads to increased anchorage-independent growth in vitro and tumorigenesis in vivo without obvious structural or numerical chromosome changes based on SKY karyotyping analysis. Despite no prior exposure to hormone ablation therapy, Pten null cells are tumorigenic in both male and female severe combined immunodeficiency mice. Furthermore, knocking down PTEN can convert the androgen-dependent Myc-CaP cell into androgen independence, suggesting that PTEN intrinsically controls androgen responsiveness, a critical step in the development of hormone refractory prostate cancer. Importantly, knocking down AR by shRNA in Pten null cells reverses androgen-independent growth in vitro and partially inhibited tumorigenesis in vivo, indicating that PTEN-controlled prostate tumorigenesis is AR dependent. These cell lines will serve as useful tools for understanding signaling pathways controlled by PTEN and elucidating the molecular mechanisms involved in hormone refractory prostate cancer formation. [Cancer Res 2007;67(13):6083–91]
Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer
Authors: Marc Buyse, Sherene Loi, Laura van't Veer, Giuseppe Viale, Mauro Delorenzi, Annuska M. Glas, Mahasti Saghatchian d'Assignies, Jonas Bergh, Rosette Lidereau, Paul Ellis, Adrian Harris, Jan Bogaerts, Patrick Therasse, Arno Floore, Mohamed Amakrane, Fanny Piette, Emiel Rutgers, Christos Sotiriou, Fatima Cardoso, Martine J. Piccart
Journal: JNCI Journal of the National Cancer Institute (2006)

A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients.Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups.The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively.The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.
Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis
Authors: Nitin J. Karandikar, Steven H. Kroft, Subramanian Yegappan, Beverly B. Rogers, Victor M. Aquino, Kyung-Mi Lee, Vinay Kumar, F. Javier Guenaga, Elaine S. Jaffe, Daniel C. Douek, Robert W. McKenna
Journal: Blood (2004)
Severe perianal ulceration
Authors: N. K. Webber, A. Robson, E. Macmahon, A.-M. Powell
Journal: BMJ (2010)

A 34 year old woman presented to the dermatologists with a five month history of severe perianal and vulval ulceration associated with debilitating pain. She had no vaginal discharge. She was referred by the gastroenterologists who were investigating her for recurrent episodic diarrhoea. Her medical history included end stage renal failure, deep vein thrombosis, and cerebrovascular accident secondary to systemic lupus erythematosus. Her treatments included prednisolone 7.5 mg once daily, mycophenolate mofetil 500 mg twice daily, warfarin, and haemodialysis. She had not been sexually active in recent years.

Examination showed extensive discrete areas of perianal ulceration extending to the posterior labia majora that were painful to touch (fig 1⇓). She had no abnormality of the hair, nails, oral mucosa, or skin elsewhere.



Fig 1 Perianal ulceration extending to the posterior labia majora



In addition to profound renal impairment and positive lupus serology, blood tests showed haemoglobin of 7.9 g/l (normal range 130-180) and lymphocyte count of 0.5×109/l (1.2-3.5). HIV-1 and HIV-2 antigen and antibody tests were negative.



### 1 What are the differential diagnoses and the likely diagnosis in this patient?

#### Short answer

Differential diagnoses are herpes simplex infection (HSV) of the genitals, tuberculosis, and infection with atypical mycobacteria. Other possibilities include inflammatory dermatoses such as metastatic Crohn’s disease; pyoderma gangrenosum; vasculitis; lichen planus; Behcet’s syndrome; autoimmune blistering disease, such as pemphigus vulgaris; and drug reactions. The history of lymphopenia and immunocompromise make HSV the most likely …
Multiple organ infection and the pathogenesis of SARS
Authors: Jiang Gu, Encong Gong, Bo Zhang, Jie Zheng, Zifen Gao, Yanfeng Zhong, Wanzhong Zou, Jun Zhan, Shenglan Wang, Zhigang Xie, Hui Zhuang, Bingquan Wu, Haohao Zhong, Hongquan Shao, Weigang Fang, Dongshia Gao, Fei Pei, Xingwang Li, Zhongpin He, Danzhen Xu, Xeying Shi, Virginia M. Anderson, Anthony S.-Y. Leong
Journal: The Journal of Experimental Medicine (2005)

After &amp;gt;8,000 infections and &amp;gt;700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.
Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model
Authors: S. Amado, M.J. Simões, P.A.S. Armada da Silva, A.L. Luís, Y. Shirosaki, M.A. Lopes, J.D. Santos, F. Fregnan, G. Gambarotta, S. Raimondo, M. Fornaro, A.P. Veloso, A.S.P. Varejão, A.C. Maurício, S. Geuna
Journal: Biomaterials (2008)
Pulmonary hemodynamics and right ventricular function in hypertension.
Authors: M T Olivari, C Fiorentini, A Polese, M D Guazzi
Journal: Circulation (1978)

Pulmonary and systemic hemodynamics in 16 hypertensive subjects (group I) with left ventricular (LV) hypertrophy (ECG and echo criteria) and in 17 hypertensive subjects with ECG signs of LV strain (group II), were compared with those in 14 normal individuals. An augmented pulmonary arteriolar resistance (PAR) in group I and to a larger extent in group II accounted for the pulmonary pressure elevation in both groups. Increase in PAR was unrelated to pulmonary blood flow and volume, pleural pressure, arterial PO2, PCO2 and pH, and could not be explained entirely by the left ventricular end-diastolic pressure changes. In group I, left (L.MSEJR) and right (R;MSEJR) mean systolic ejection rate, stroke index (SI) and mean velocity of circumferential fiber shortening (VCF) were enhanced in spite of the heightened pressure load on both sides of the heart. In group II, a large reduction of SI, L.MS.EJR, R.MSEJR and VCF, as well as the relationship between ventricular filling pressures and SI, documented a compromised performance of both ventricles, Findings indicate that: systemic hypertension is associated with elevation of pulmonary arterial pressure and of PAR which is not necessarily a consequence of impairment in LV function; LV hypertrophy is associated with enhanced performance of either ventricle; in coincidence with development of ECG signs of LV strain, the performance of both sides of the heart deteriorates. A functional interdependence of the two ventricles is suggested.
Nuclear Mechanics in Disease
Authors: Monika Zwerger, Chin Yee Ho, Jan Lammerding
Journal: Annual Review of Biomedical Engineering (2011)

Over the past two decades, the biomechanical properties of cells have emerged as key players in a broad range of cellular functions, including migration, proliferation, and differentiation. Although much of the attention has focused on the cytoskeletal networks and the cell's microenvironment, relatively little is known about the contribution of the cell nucleus. Here, we present an overview of the structural elements that determine the physical properties of the nucleus and discuss how changes in the expression of nuclear components or mutations in nuclear proteins can not only affect nuclear mechanics but also modulate cytoskeletal organization and diverse cellular functions. These findings illustrate that the nucleus is tightly integrated into the surrounding cellular structure. Consequently, changes in nuclear structure and composition are highly relevant to normal development and physiology and can contribute to many human diseases, such as muscular dystrophy, dilated cardiomyopathy, (premature) aging, and cancer.
Hypothalamic beta 2-adrenoceptor control of renal sympathetic nerve activity and urinary sodium excretion in conscious, spontaneously hypertensive rats.
Authors: J P Koepke, S Jones, G F DiBona
Journal: Circulation Research (1986)

The contributions of beta 1-, B2-, and alpha 2-adrenoceptors in the posterior hypothalamus to the increased renal sympathetic nerve activity and decreased urinary sodium excretion resulting from environmental stress (air jet) in conscious spontaneously hypertensive rats were examined. Air stress increased mean arterial pressure and renal sympathetic nerve activity (54% from 7.0 +/- 0.7 integrator resets/min), and decreased urinary sodium excretion (44% from 2.7 +/- 0.4 microEq/min per 100 g body weight). After bilateral injection of ICI 118,551 (beta 2-adrenoceptor antagonist) into the posterior hypothalamus of the same spontaneously hypertensive rats, air stress had no effect on renal sympathetic nerve activity (8% from 4.8 +/- 0.7 integrator resets/min) or urinary sodium excretion (2% from 5.2 +/- 0.8 microEq/min per 100 g body weight), but still increased mean arterial pressure. Bilateral injection of isoproterenolol (beta-adrenoceptor agonist) into the posterior hypothalamus enhanced the renal sympathetic nerve activity and urinary sodium excretion (but not mean arterial pressure) responses to air stress. Air stress had no effect on renal sympathetic nerve activity or urinary sodium excretion when ICI 118,551 was given into the posterior hypothalamus before isoproterenol. Atenolol (beta 1-adrenoceptor antagonist) had no effect on the renal responses to air stress when given alone or before isoproterenol. Similarly, ICI 118,551 administered into the lateral hypothalamus or lateral cerebral ventricle, or guanabenz (alpha 2-adrenoceptor agonist) given into the posterior hypothalamus, had no effects on the renal or mean arterial pressure responses to air stress. Thus, beta 2-adrenoceptors in the posterior hypothalamus mediate the increased renal sympathetic nerve activity and antinatriuresis resulting from environmental stress in conscious spontaneous hypertensive rats.