tbuckley/cabot-search huggingface dataset:
The Impact of Comorbid Chronic Conditions on Diabetes Care
Authors: John D. Piette, Eve A. Kerr
Journal: Diabetes Care (2006)

Effective diabetes management often presents enormous challenges. Not surprisingly, clinicians and patients alike can be overwhelmed by the need to address comorbid chronic conditions in addition to patients’ diabetes-specific treatment goals. Ignoring concurrent disease management, however, can lead to ineffective control of diabetes-specific risk factors and may miss opportunities to improve patients’ functioning, quality of life, and mortality risk.

Other chronic conditions are common among people with diabetes and account for much of the morbidity these patients face. According to the Medical Expenditure Panel Survey, most adults with diabetes have at least one comorbid chronic disease (1) and as many as 40% have at least three (2,3). The increasing prevalence of multimorbidity among older diabetic adults is at least in part an unintended consequence of our success in improving diabetes treatment quality. Improvements in HbA1c (A1C) monitoring and glycemic control have been documented in several large systems of care (4–7). More widespread use of treatments such as ACE inhibitors and aspirin have decreased patients’ risk of cardiovascular death (8–10). Diabetic patients are living longer, and like all Americans, this increases their chance of acquiring one of the many chronic diseases associated with aging.

Other more troubling trends have conspired to increase the impact of multimorbidity on diabetes management. In many health care systems, providers see patients during brief office visits and are overwhelmed by the number of health maintenance activities recommended by guidelines and quality monitoring agencies (11,12). When diabetic patients have multiple chronic conditions, screening, counseling, and treatment needs can far exceed the time available for patient-provider visits. Health problems that used to be treated in inpatient settings are increasingly managed within outpatient care, further straining providers’ resources for addressing diabetes-specific management goals (13). With inadequate health system support and …
ECG findings in competitive rowers: normative data and the prevalence of abnormalities using contemporary screening recommendations
Authors: Meagan M Wasfy, James DeLuca, Francis Wang, Brant Berkstresser, Kathryn E Ackerman, Aaron Eisman, Gregory D Lewis, Adolph M Hutter, Rory B Weiner, Aaron L Baggish
Journal: British Journal of Sports Medicine (2014)

Background/aim The international governing body for competitive rowing recently mandated the inclusion of 12-lead ECG during preparticipation screening. We therefore sought to describe normative ECG characteristics and to examine the prevalence of abnormal ECG findings as defined by contemporary athlete ECG interpretation criteria among competitive rowers. Methods Competitive rowers (n=330, 56% male) underwent standard 12-lead ECG at the time of collegiate preparticipation screening. ECGs were analysed quantitatively to develop a sport-specific normative database and then for the presence of abnormalities in accordance with the 2010 European Society of Cardiology (ESC) recommendations and 2013 ‘Seattle Criteria.’ Results 94% of rowers had one or more training-related ECG patterns including sinus bradycardia (51%), sinus arrhythmia (55%), and incomplete right bundle branch block (42%). Males were more likely than females to have isolated voltage criteria for left ventricular hypertrophy (LVH) (51% vs 8%, p&lt;0.001) and early repolarisation pattern (76% vs 23%, p&lt;0.001). Application of the 2010 ESC criteria, compared to the Seattle criteria, resulted in the classification of a significantly greater number of abnormal ECGs (47% vs 4%; p&lt;0.001). The detection of true pathology, accomplished by both interpretation criteria, was confined to a single case of ventricular pre-excitation. Conclusions Training-related ECG patterns with several gender-based differences are common among competitive rowers. The diagnostic accuracy and down-stream clinical implications of ECG-inclusive preparticipation screening among rowers will be dictated by the choice and future refinement of ECG interpretation criteria.
Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implications for treatment.
Authors: F C Henderson, J F Geddes, H A Crockard
Journal: Annals of the Rheumatic Diseases (1993)

To study the detailed histopathological changes in the brainstem and spinal cord in nine patients with severe end stage rheumatoid arthritis, all with clinical myelopathy and craniocervical compression.At necropsy the sites of bony pathology were related exactly to cord segments and histological changes, and correlated with clinical and radiological findings.Cranial nerve and brainstem pathology was rare. In addition to the obvious craniocervical compression, there were widespread subaxial changes in the spinal cord. Pathology was localised primarily to the dorsal white matter and there was no evidence of vasculitis or ischaemic changes.Myelopathy in rheumatoid arthritis is probably caused by the effects of compression, stretch, and movement, not ischaemia. The additional subaxial compression may be an important component in the clinical picture, and may explain why craniocervical decompression alone may not alleviate neurological signs.
Prostaglandins are necessary for osteoclast-activating factor production by activated peripheral blood leukocytes.
Authors: T Yoneda, G R Mundy
Journal: The Journal of Experimental Medicine (1979)

The production of osteoclast-activating factor (OAF) by normal human peripheral blood leukocytes stimulated by phytohemagglutinin was inhibited by a series of structurally unrelated inhibitors of prostaglandin synthetase. Inhibition of OAF production by these agents was reversed by adding prostaglandins of the E series back to the leukocyte suspension. These results indicate that prostaglandin synthesis is necessary for OAF production.
APOL1 Risk Variants Predict Histopathology and Progression to ESRD in HIV-Related Kidney Disease
Authors: Derek M. Fine, Walter G. Wasser, Michelle M. Estrella, Mohamed G. Atta, Michael Kuperman, Revital Shemer, Arun Rajasekaran, Shay Tzur, Lorraine C. Racusen, Karl Skorecki
Journal: Journal of the American Society of Nephrology (2011)

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.
Estrogen- and Progesterone-Receptor Status in ECOG 2197: Comparison of Immunohistochemistry by Local and Central Laboratories and Quantitative Reverse Transcription Polymerase Chain Reaction by Central Laboratory
Authors: Sunil S. Badve, Frederick L. Baehner, Robert P. Gray, Barrett H. Childs, Tara Maddala, Mei-Lan Liu, Steve C. Rowley, Steven Shak, Edith D. Perez, Lawrence J. Shulman, Silvana Martino, Nancy E. Davidson, George W. Sledge, Lori J. Goldstein, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2008)

Central and local laboratory concordance for hormone receptor measurement is therapeutically important. This study compares estrogen receptor (ER) and progesterone receptor (PR) measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcriptase polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay.
Evolving Prosocial and Sustainable Neighborhoods and Communities
Authors: Anthony Biglan, Erika Hinds
Journal: Annual Review of Clinical Psychology (2009)

In this review, we examine randomized controlled trials of community interventions to affect health. The evidence supports the efficacy of community interventions for preventing tobacco, alcohol, and other drug use; several recent trials have shown the benefits of community interventions for preventing multiple problems of young people, including antisocial behavior. However, the next generation of community intervention research needs to reflect more fully the fact that most psychological and behavioral problems of humans are interrelated and result from the same environmental conditions. The evidence supports testing new comprehensive community interventions that focus on increasing nurturance in communities. Nurturing communities will be ones in which families, schools, neighborhoods, and workplaces (a) minimize biologically and socially toxic events, (b) richly reinforce prosocial behavior, and (c) foster psychological acceptance. Such interventions also have the potential to make neighborhoods more sustainable.
Nuclear Factor-κB is an Important Modulator of the Altered Gene Expression Profile and Malignant Phenotype in Squamous Cell Carcinoma
Authors: Amy Loercher, Tin Lap Lee, Justin L. Ricker, April Howard, Joel Geoghegen, Zhong Chen, John B. Sunwoo, Raquel Sitcheran, Eric Y. Chuang, James B. Mitchell, Albert S. Baldwin, Carter Van Waes
Journal: Cancer Research (2004)

Abstract We reported previously that transcription factor nuclear factor (NF)-κB is constitutively activated in human and murine squamous cell carcinomas (SCCs). The role of NF-κB in the cumulative changes in gene expression with transformation and progression of the murine SCC Pam 212 and after switching off NF-κB by a dominant negative inhibitor κB mutant (IκBαM) was explored by profiling with a 15,000-element cDNA micoarrray. Remarkably, NF-κB modulated the expression of &amp;gt;60% of the 308 genes differentially expressed between normal keratinocytes and metastatic SCCs. NF-κB directly or indirectly modulated expression of programs of genes functionally linked to proliferation, apoptosis, adhesion, and angiogenesis. Among these, changes in expression of cyclin D1, inhibitor of apoptosis-1, mutant Trp53, and β-catenin detected with modulation of NF-κB by microarray were confirmed by Western and Northern blot. NF-κB DNA binding motifs were detected in the promoter of ∼63% of genes showing increased expression and 33% of the genes showing decreased expression. The ACTACAG motif implicated in the NF-κB-dependent down-regulation of mRNA expression of MyoD and Sox9 was detected in the coding portion of about 15% of genes showing increased or decreased expression. Inactivation of NF-κB inhibited malignant phenotypic features including proliferation, cell survival, migration, angiogenesis, and tumorigenesis. These results provide evidence that NF-κB is an important modulator of gene expression programs that contribute to the malignant phenotype of SCC.
Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003)
Authors: Nancy U. Lin, Hao Guo, Jeffrey T. Yap, Ingrid A. Mayer, Carla I. Falkson, Timothy J. Hobday, E. Claire Dees, Andrea L. Richardson, Rita Nanda, Mothaffar F. Rimawi, Nicole Ryabin, Julie S. Najita, William T. Barry, Carlos L. Arteaga, Antonio C. Wolff, Ian E. Krop, Eric P. Winer, Annick D. Van den Abbeele
Journal: Journal of Clinical Oncology (2015)

Lapatinib plus trastuzumab improves outcomes relative to lapatinib alone in heavily pretreated, human epidermal growth factor receptor 2-positive metastatic breast cancer (MBC). We tested the combination in the earlier-line setting and explored the predictive value of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for clinical outcomes.Two cohorts were enrolled (cohort 1: no prior trastuzumab for MBC and ≥ 1 year from adjuvant trastuzumab, if given; cohort 2: one to two lines of chemotherapy including trastuzumab for MBC and/or recurrence < 1 year from adjuvant trastuzumab). The primary end point was objective response rate by RECIST v1.0; secondary end points included clinical benefit rate (complete response plus partial response plus stable disease ≥ 24 weeks) and progression-free survival. [(18)F]FDG-PET scans were acquired at baseline, week 1, and week 8. Associations between metabolic response and clinical outcomes were explored.Eighty-seven patients were registered (85 were evaluable for efficacy). The confirmed objective response rate was 50.0% (95% CI, 33.8% to 66.2%) in cohort 1 and 22.2% (95% CI, 11.3% to 37.3%) in cohort 2. Clinical benefit rate was 57.5% (95% CI, 40.9% to 73.0%) in cohort 1 and 40.0% (95% CI, 25.7% to 55.7%) in cohort 2. Median progression-free survival was 7.4 and 5.3 months, respectively. Lack of week-1 [(18)F]FDG-PET/computed tomography ([(18)F]FDG-PET/CT) response was associated with failure to achieve an objective response by RECIST (negative predictive value, 91% [95% CI, 74% to 100%] for cohort 1 and 91% [95% CI, 79% to 100%] for cohort 2).Early use of lapatinib and trastuzumab is active in human epidermal growth factor receptor 2-positive MBC. Week-1 [(18)F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.
LONG-TERM OUTCOME FOLLOWING ATRIAL FIBRILLATION ABLATION WITH ROBOTIC VS. MANUAL ABLATION
Authors: Agnes Pump, Luigi Di Biase, Prasant Mohanty, Pasquale Santangeli, Rong Bai, Sanghamitra Mohanty, G. Gallinghouse, Rodney Horton, Javier Sanchez, Andrea Natale
Journal: Journal of the American College of Cardiology (2012)
Nonlinear Analysis of Aortic Flow in Living Dogs
Authors: SUNG C. LING, H. BÜLENT ATABEK, WILLIAM G. LETZING, DALI J. PATEL
Journal: Circulation Research (1973)

A nonlinear theory which considered the convective accelerations of blood and the nonlinear elastic behavior and taper angle of the vascular wall was used to study the nature of blood flow in the descending thoracic aorta of living dogs under a wide range of pressures and flows. Velocity profiles, wall friction, and discharge waves were predicted from locally measured input data about the pressure-gradient wave and arterial distention. Precision pressure-gradient waves free of static errors were obtained through forward and backward pressure-gradient measurements, and the arterial pressure-radius relation was obtained through cinematography using a telephoto lens. The results indicated that a major part of the mean pressure gradient was balanced by convective accelerations; the theory, which took this factor into account, predicted the correct velocity distributions and flow waves. The results also showed that for high flow rates the magnitude of the peak wall-shear stress became comparable to the yield stress of the endothelial surface and that radial flows of significant magnitude existed with respect to the arterial wall.
Arginase: marker, effector, or candidate gene for asthma?
Authors: Donata Vercelli
Journal: Journal of Clinical Investigation (2003)

Microarray analysis of the expression profiles of lung tissue in two murine models of asthma revealed high levels of arginase I and arginase II activity, in association with IL-4 and IL-13 overexpression, suggesting that arginine pathways are critical in the pathogenesis of asthma.
Kindlin-2 Mediates Activation of TGF-β/Smad Signaling and Renal Fibrosis
Authors: Xiaofan Wei, Yang Xia, Feng Li, Yan Tang, Jing Nie, Youhua Liu, Zhanmei Zhou, Hongquan Zhang, Fan Fan Hou
Journal: Journal of the American Society of Nephrology (2013)

Activation of TGF-β/Smad signaling plays a central role in the pathogenesis of tubulointerstitial fibrosis, but the mechanisms underlying the initial interaction of the TGF-β receptor with Smads, leading to their activation, remain unclear. Here, we found that Kindlin-2, an integrin-binding protein, physically mediated the interaction of the TGF-β type I receptor (TβRI) with Smad3 in human kidney tubular epithelial cells. Kindlin-2 bound to TβRI through its FERM domain and to Smad3 through its N terminus. Overexpression of Kindlin-2 increased TGF-β-induced Smad3 activation. Knockdown of Kindlin-2 significantly suppressed the engagement of TβRI with Smad3 and inhibited TGF-β-induced Smad3 activation, as well as the expression of its target genes. Neither transfection of a Kindlin-2 mutant incapable of binding to β1 integrin nor knockdown of β1 integrin influenced the effect of Kindlin-2 on TGF-β1-induced Smad3 activation, indicating that this effect is independent of integrin. Kindlin-2 expression was markedly increased, predominantly in renal tubular epithelial cells, both in the unilateral ureteral obstruction model of kidney fibrosis and in human tissue exhibiting tubulointerstitial fibrosis. Furthermore, in the unilateral ureteral obstruction model, knocking down Kindlin-2 significantly inhibited activation of TGF-β/Smad signaling, decreased the expression of matrix genes, and ameliorated fibrosis. In summary, Kindlin-2 physically interacts with both TβRI and Smad3, promoting the activation of TGF-β/Smad signaling and contributing to the pathogenesis of tubulointerstitial fibrosis. Blockade of Kindlin-2 might be a rational therapeutic strategy for the treatment of fibrotic kidney diseases.
Anticancer Activity of BIM-46174, a New Inhibitor of the Heterotrimeric Gα/Gβγ Protein Complex
Authors: Grégoire P. Prévost, Marie O. Lonchampt, Susan Holbeck, Samir Attoub, Daniel Zaharevitz, Mike Alley, John Wright, Marie C. Brezak, Hélène Coulomb, Ann Savola, Marion Huchet, Sophie Chaumeron, Quang-Dé Nguyen, Patricia Forgez, Erik Bruyneel, Mark Bracke, Eric Ferrandis, Pierre Roubert, Danièle Demarquay, Christian Gespach, Philip G. Kasprzyk
Journal: Cancer Research (2006)

A large number of hormones and local agonists activating guanine-binding protein-coupled receptors (GPCR) play a major role in cancer progression. Here, we characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a selective inhibitor of heterotrimeric G-protein complex. BIM-46174 prevents the heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic AMP generation (Galphas), (b) calcium release (Galphaq), and (c) cancer cell invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors (Galphao/i and Galphaq). BIM-46174 inhibits the growth of a large panel of human cancer cell lines, including anticancer drug-resistant cells. Exposure of cancer cells to BIM-46174 leads to caspase-3-dependent apoptosis and poly(ADP-ribose) polymerase cleavage. National Cancer Institute COMPARE analysis for BIM-46174 supports its novel pharmacologic profile compared with 12,000 anticancer agents. The growth rate of human tumor xenografts in athymic mice is significantly reduced after administration of BIM-46174 combined with either cisplatin, farnesyltransferase inhibitor, or topoisomerase inhibitors. Our data validate the feasibility of targeting heterotrimeric G-protein functions downstream the GPCRs to improve anticancer chemotherapy.
Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer
Authors: C. Monnerat, R. Henriksson, T. Le Chevalier, S. Novello, P. Berthaud, S. Faivre, E. Raymond
Journal: Annals of Oncology (2004)
Extraosseous Localized Ewing Tumors: Improved Outcome With Anthracyclines—The French Society of Pediatric Oncology and International Society of Pediatric Oncology
Authors: Marie-Pierre Castex, Hervé Rubie, Michael C.G. Stevens, Carlota Calvo Escribano, Jérôme Sales de Gauzy, Anne Gomez-Brouchet, Annie Rey, Olivier Delattre, Odile Oberlin
Journal: Journal of Clinical Oncology (2007)

Purpose To evaluate the outcome of children with an extraosseous Ewing tumor (EOE) according to treatment. Patients and Methods Children with EOE were treated either with the strategy used for malignant mesenchymal tumors (MMTs) by the International Society of Pediatric Oncology (SIOP) or with the French Society of Pediatric Oncology (SFOP) regimen used for osseous Ewing tumors (OET). The MMT strategy included vincristine/actinomycin for small and resected tumors or ifosfamide/vincristine/actinomycin for unfavorable sites or unresectable tumors. Surgical excision was to be attempted after four courses, followed by local irradiation in case of residue. Osseous Ewing (OE) protocol included three courses of cyclophosphamide/doxorubicin followed either by two similar courses in case of good response or two courses of ifosfamide/etoposide in case of no response. After resection of the primary, treatment included conventional chemotherapy in case of good histologic response and high-dose chemotherapy and radiotherapy for poor response. All diagnosis specimens were reviewed by the panel. Results Between 1989 and 1999, 63 patients were registered. Characteristics of patients treated by both protocols were similar. Five-year overall survival (OS) and event-free survival (EFS) of those treated with the OE protocol are 83% and 75%, respectively, which is significantly better than the OS and EFS of those treated with the MMT strategy (59% and 44%, respectively; P = .04 and .008, respectively). The size of the primary and the type of protocol influenced patients’ EFS. In multivariate analysis, only the regimen had an impact on OS and EFS. Conclusion Our study shows that patients with EOE should be treated with OE regimens, probably because of the use of anthracyclines.