tbuckley/cabot-search huggingface dataset:
Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease
Authors: Archana Raman, Gail A. Reif, Yuqiao Dai, Aditi Khanna, Xiaogang Li, Lindsay Astleford, Stephen C. Parnell, James P. Calvet, Darren P. Wallace
Journal: Journal of the American Society of Nephrology (2017)

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation in vitro Homozygous deletion of ILK in renal collecting ducts (CD) of Ilkfl/fl ;Pkhd1-Cre mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, Ilkfl/+ ;Pkhd1-Cre mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in Pkd1fl/fl ;Pkhd1-Cre mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of pcy/pcy mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.
ACCF/AHA/ACP 2009 Competence and Training Statement: A Curriculum on Prevention of Cardiovascular Disease
Authors: C. Noel Bairey Merz, Mark J. Alberts, Gary J. Balady, Christie M. Ballantyne, Kathy Berra, Henry R. Black, Roger S. Blumenthal, Michael H. Davidson, Sara B. Fazio, Keith C. Ferdinand, Lawrence J. Fine, Vivian Fonseca, Barry A. Franklin, Patrick E. McBride, George A. Mensah, Geno J. Merli, Patrick T. O'Gara, Paul D. Thompson, James A. Underberg
Journal: Journal of the American College of Cardiology (2009)
Making Recommendations for Limiting Care in the ICU Based on Sound Prognosis
Authors: Jesse B. Hall
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Targeting CCl4‐induced liver fibrosis by RNA interference–mediated inhibition of cyclin E1 in mice
Authors: Jörg‐Martin Bangen, Linda Hammerich, Roland Sonntag, Maike Baues, Ute Haas, Daniela Lambertz, Thomas Longerich, Twan Lammers, Frank Tacke, Christian Trautwein, Christian Liedtke
Journal: Hepatology (2017)

Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSCs). Cyclin E1 (CcnE1) is the regulatory subunit of the cyclin‐dependent kinase 2 (Cdk2) and controls cell cycle re‐entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation, and survival of HSCs and protects from liver fibrogenesis. The aim of the present study was to translate these findings into preclinical applications using an RNA interference (RNAi)‐based approach. CcnE1‐siRNA (small interfering RNA) efficiently inhibited CcnE1 gene expression in murine and human HSC cell lines and in primary HSCs, resulting in diminished proliferation and increased cell death. In C57BL/6 wild‐type (WT) mice, delivery of stabilized siRNA using a liposome‐based carrier targeted approximately 95% of HSCs, 70% of hepatocytes, and 40% of CD45 + cells after single injection. Acute CCl 4 ‐mediated liver injury in WT mice induced endogenous CcnE1 expression and proliferation of surviving hepatocytes and nonparenchymal cells, including CD45 + leukocytes. Pretreatment with CcnE1‐siRNA reverted CcnE1 induction to baseline levels of healthy mice, which was associated with reduced liver injury, diminished proliferation of hepatocytes and leukocytes, and attenuated overall inflammatory response. For induction of liver fibrosis, WT mice were challenged with CCl 4 for 4‐6 weeks. Co‐treatment with CcnE1‐siRNA once a week was sufficient to continuously block CcnE1 expression and cell‐cycle activity of hepatocytes and nonparenchymal cells, resulting in significantly ameliorated liver fibrosis and inflammation. Importantly, CcnE1‐siRNA also prevented progression of liver fibrosis if applied after onset of chronic liver injury. Conclusion : Therapeutic targeting of CcnE1 in vivo using RNAi is feasible and has high antifibrotic activity. (H epatology 2017;66:1242‐1257).
The CLASH model lacks evolutionary and archeological support
Authors: Agustin Fuentes, Marc Kissel, Rahul Oka, Susan Sheridan, Nam Kim, Matthew Piscitelli
Journal: Behavioral and Brain Sciences (2017)

Abstract Data from archaeology and paleoanthropology directly challenge the validity of the basic assumptions of the CLASH model. By not incorporating a “deep time” perspective, the hypothesis lacks the evolutionary baseline the authors seek to infer in validating the model.
Sustainability of antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens: Results of a randomized phase III trial.
Authors: Ralph V. Boccia, William Cooper, Erin O'Boyle
Journal: Journal of Clinical Oncology (2013)

9626 Background: Patients receiving MEC or HEC were administered subcutaneous (SC) APF530 500 mg, a sustained delivery formulation of granisetron (10 mg). The complete antiemetic response rates (CR; no emetic episodes and no rescue medication) were non-inferior to those of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) (Grous et al. ASCO 2009, #9627). We report on sustainability of CR with APF530 (10 mg) during multiple chemotherapy cycles in this study. Methods: 1428 patients scheduled to receive single doses of MEC or HEC were randomized to APF530 SC (5 or 10 mg granisetron) or 0.25 mg palonosetron intravenously (IV) prior to cycle 1 (C1). In C2-4, patients who received palonosetron in C1 were randomized to APF530 5 or 10 mg; those who received APF530 continued with their C1 APF530 dose. Treatment cycles were separated by 7-28 days. CR rates were compared between cycles using McNemar’s test. Results: No significant differences in within-cycle CR occurred between APF530 doses during acute and delayed phases in C2-4 for MEC and HEC, but a trend toward higher CR rates was seen in successive cycles. For the 2 doses, CR was sustained across all 4 cycles in 56.5-62.6% and 68.4-71.7% in acute phase, and 41.8-42.4% and 57.5-57.9% in delayed phase with MEC and HEC, respectively. Examination of CR rates in C2, C3, or C4 compared with the rate in C1 showed that CR rates were sustained and that the proportion of patients with no CR in C1 but CR in later cycles was consistently higher than that of patients with CR in C1 but no CR later. For illustration, the table shows C4 CR and C1 CR for patients who received APF530 10 mg in C1 and C4. Conclusions: CR rates achieved with APF530 during acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. Clinical trial information: NCT00343460. [Table: see text]
Chronic Thromboembolic Pulmonary Hypertension
Authors: Peter F. Fedullo, William R. Auger, Kim M. Kerr, Lewis J. Rubin
Journal: New England Journal of Medicine (2001)

One cause of pulmonary hypertension is chronic thromboembolic obstruction of the pulmonary arteries. If this condition is recognized, thromboendarterectomy can lead to improvements in hemodynamics and in survival.
Scarcity of Safe Water a Looming Threat to Children
Authors: M.J. Friedrich
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Treatment of Men with Paraphilia with a Long-Acting Analogue of Gonadotropin-Releasing Hormone
Authors: Ariel Rösler, Eliezer Witztum
Journal: New England Journal of Medicine (1998)

Men with deviant sexual behavior, or paraphilia, are usually treated with psychotherapy, antidepressant drugs, progestins, and antiandrogens, but these treatments are often ineffective. Selective inhibition of pituitary–gonadal function with a long-acting agonist analogue of gonadotropin-releasing hormone may abolish the deviant sexual behavior by reducing testosterone secretion.
Surgical Management of Complicated Diverticulitis
Authors: Bentley P. Colcock
Journal: New England Journal of Medicine (1958)

THE morbidity associated with the surgical treatment of diverticulitis remains high. In the experience of the Lahey Clinic some complication has developed in 30 per cent of the patients with diverticulitis — obstruction or perforation of the colon, or a fistula between the colon and bladder, or colon and vagina. When these complications do occur, a long period in the hospital, multiple operations and months of disability are all too frequently the result. There are two ways in which this situation can and should be improved. In the first place, one must avoid inadequate surgical procedures in patients with complicated . . .
Association of brain metastasis in non-small cell lung cancer.
Authors: Yu Zhao, Huiqin Guo, Jiangyang Lu, David C. Christiani, Xihong Lin, Zhaoxi Wang
Journal: Journal of Clinical Oncology (2013)

e19081 Background: Brain metastases are the main cause of non-small cell lung cancer (NSCLC) relapse and death. However, it is difficult to predict which NSCLC patient will develop brain metastasis. We have observed and summarized the relationship between the clinical and molecular biological features including EGFR mutation status and brain metastases in a prospectively enrolled case series, and developed a multivariable model in this study. Methods: The study enrolled 184 Chinese NSCLC patients with at least 18 months follow-up period. Clinical information including age, smoking history, lymph node status, pathological stage, primary location and histological type of the tumor and EGFR (including exon 19 and 21) and KRAS mutation status were collected and analyzed. Univariate and multivariate Cox regression analysis was run to investigate risk factors of brain metastasis from these features. A risk model based on these risk factors was constructive. Results: 13.0% (24/184) patients were diagnosed as brain metastasis. EGFR mutation (P=0.026), younger age (P=0.034) and lymph node metastasis (P=0.038) were associated with brain metastasis. A Cox model based on these 3 factors was founded and the risk of brain metastasis was 1.9% (1/53), 8.3% (5/60) and 25.4 % (18/71) in low, intermediate and high risk group, respectively (P&lt;0.001). Conclusions: EGFR mutation, younger age and lymph node metastasis are associated with brain metastasis in NSCLC patients. If confirmed in clinical trials, high risk patients may be considered for prophylactic cranial irradiation therapy in future clinical trials
Why the CLASH model is an unconvincing evolutionary theory of crime
Authors: Brian B. Boutwell, Bo Winegard
Journal: Behavioral and Brain Sciences (2017)

Abstract The CLASH model is not convincing for two reasons. First, it ignores prior research proposing very similar ideas in a more compelling fashion. Second, it dismisses the role of genetic factors in shaping criminal propensities across population groups, opting for a facultative view of life history evolution that does not seem to square with current evidence.
Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients
Authors: R Cervera, M A Khamashta, Y Shoenfeld, M T Camps, S Jacobsen, E Kiss, M M Zeher, A Tincani, I Kontopoulou-Griva, M Galeazzi, F Bellisai, P L Meroni, R H W M Derksen, P G de Groot, E Gromnica-Ihle, M Baleva, M Mosca, S Bombardieri, F Houssiau, J-C Gris, I Quéré, E Hachulla, C Vasconcelos, B Roch, A Fernández-Nebro, J-C Piette, G Espinosa, S Bucciarelli, C N Pisoni, M L Bertolaccini, M-C Boffa, G R V Hughes
Journal: Annals of the Rheumatic Diseases (2008)

To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance.The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed.200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected.Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).
Could Albumin be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin on Guillain-Barré Syndrome?—Reply
Authors: Willem-Jan R. Fokkink, Bart C. Jacobs
Journal: JAMA Neurology (2017)

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
Last Nail in the Coffin for Propensity Scores in Observational Cardiovascular Studies?
Authors: Giuseppe Biondi-Zoccai, Antonino G.M. Marullo, Mariangela Peruzzi, Tullio Palmerini, Leonardo Schirone, Silvia Palmerio, Arturo Giordano, Giacomo Frati
Journal: Journal of the American College of Cardiology (2017)
Abstract 184: TNF-TNFR1/p55 or TNFR2/p75 Receptor-Ligand Interactions Inhibit Early and Increase Delayed Radio-Biological Bystander Responses in BM-Derived EPCs
Authors: Sujatha Muralidharan, Sharath Sasi, Xinhua Yan, Heiko Enderling, David Goukassian
Journal: Circulation Research (2012)

TNF-α (TNF) binds two receptors TNFR1-p55 and TNFR2-p75. Ionizing radiation (IR) increases tissue TNF levels. TNF signaling regulates numerous cyto- and chemokines, known to mediate radiation-induced non-targeted effects (NTE), a phenomenon where cells that are not directly “hit” by IR exhibit IR effects as a result of signals received from nearby or distant IR cells. Little is known about the role of p55 or p75 in regulating NTEs in bone marrow (BM)-derived EPCs. We hypothesized that inhibition of TNF signaling either via p55, or p75 may alter TNF-mediated inflammatory responses, inducing NTEs. Medium transfer experiments (MTE) were performed in WT, p55 knockout(KO) and p75KO BM-derived EPC ex-vivo, where one set of EPCs was irradiated with 1Gy of γ-IR, then IR-conditioned medium (CM) was collected from these dishes at 1, 5, 24h and 3, 5d post-IR. Filtered (0.22µm) IR-CM was transferred to naïve non-IR same genotype EPCs and 24h post-incubation naïve EPCs were processed for p-y-H2AX staining for presence and decay of double strand breaks (DSB). CM from IR EPCs were processed for ELISA profiling (16 genes) and IR EPCs were processed for transcriptional profiling. In WT EPC the peak of detectable mean p-y-H2AX foci/cell were at 24h, whereas in p55 and p75KOs p-y-H2AX were the lowest at 24h (9±0.8 vs 4.8±0.6 and 3.7±0.5, p&lt;0.01 and 0.001, WT vs p55 and p75KOs). This finding indicates that altered TNF signaling inhibits early NTEs (hours) in EPCs. Compared to WT, delayed (5 days) NTEs were amplified in naïve p55 and p75KO EPCs (3.8±0.4 vs 8.5±1 and 5.9±0.8, p&lt;0.02 and 0.01, WT vs p55 and p75KOs), suggesting significant role for TNF signaling in mediating delayed NTEs. ELISA profiling of 16 proteins in CM over 5 days post-IR showed 200-1600% increases (p&lt;0.002, p55KO vs WT) in cumulative levels of TNF, IFNr, IL6, EGF, MIP-1α, GM-SCF, Rantes, and 200-1000%, increases (p&lt;0.05, p75KO vs WT) in IL1α, IL1β, G -CSF, MCP-1, SCF. Transcriptional profiling of γ-IR EPC revealed 139 genes (&gt;2 fold) up or down regulated, clustered into 9 groups. Other aspects of gene array data are being considered. We conclude that TNF ligand-receptor axis regulates NTEs in naïve EPCs and suggest that restoring TNF signaling balance could be used to prevent delayed NTEs in distant from primary IR target tissues.
Drug use and pregnancy – challenges for public health
Authors: V A Gyarmathy, I Giraudon, D Hedrich, L Montanari, B Guarita, L Wiessing
Journal: Eurosurveillance (2009)

Problem drug use in pregnancy affects a sizeable population in Europe. A literature review was carried out of articles in PubMed, European Monitoring Centre for Drugs and Drug Addiction publications, and related documents in order to assess public health challenges and possible intervention strategies related to problem drug use and pregnancy in Europe. It revealed the following: Involving pregnant drug users in drug treatment is likely to decrease the chances of pre- and perinatal complications related to drug use and to increase access to prenatal care. Timely medical intervention can effectively prevent vertical transmission of human immunodeficiency virus, hepatitis B virus as well as certain other sexually transmitted diseases, and would allow newborns infected with hepatitis C virus during birth to receive immediate treatment. Pregnancy may be a unique opportunity to also help women with dual diagnosis (substance use combined with mental illness) and enrol them into special treatment and support programmes. Issues related to homelessness and intimate partner violence can also be addressed with appropriate interventions. Treatment and care for pregnant drug users should offer coordinated interventions in several areas: drug use, infectious diseases, mental health, personal and social welfare, and gynaecological/obstetric care.
Neuroblastoma Presenting as Non–MIBG-Avid Widespread Soft Tissue Metastases Without Bone Involvement Revealed by FDG PET/CT Imaging
Authors: Nelleke Tolboom, Sabah E. Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

Soft tissue metastases from neuroblastoma very rarely occur without concurrent osseous metastases. We report 1 case of non-MIBG-avid, high-risk neuroblastoma in a pediatric patient who had widespread soft tissue metastases without concurrent osseous lesion on FDG PET/CT imaging.