tbuckley/cabot-search huggingface dataset:
Predictors of Cognitive Decline in Older Individuals With Diabetes
Authors: David G. Bruce, Wendy A. Davis, Genevieve P. Casey, Sergio E. Starkstein, Roger M. Clarnette, Osvaldo P. Almeida, Timothy M.E. Davis
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to determine longitudinal predictors of cognitive decline in older individuals with diabetes who did not have dementia. RESEARCH DESIGN AND METHODS—Cognitive assessments were performed in 205 subjects with diabetes (mean age 75.3 years) and repeated a median 1.6 years later. The sample was drawn from an existing cohort study, and data on diabetes, cardiovascular risk factors, and complications were collected 7.6 ± 1.1 years before and at the time of the initial cognitive assessment. Cognitive status was defined using the Clinical Dementia Rating (CDR) scale, and cognitive decline was defined by change in CDR. RESULTS—The sample included 164 subjects with normal cognition (CDR 0) and 41 with cognitive impairment without dementia (CDR 0.5). At follow-up, 33 (16.1%) had experienced cognitive decline (4 new cases of dementia and 29 cognitive impairment without dementia). Only educational attainment predicted cognitive decline from the data collected 7.6 years before cognitive assessment. Univariate predictors of cognitive decline at the time of the first cognitive assessment included age, education, urinary albumin-to-creatinine ratio (ACR), and treatment with either ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). With multiple logistic regression controlling for age and education, cognitive decline was predicted by natural logarithm ACR (odds ratio 1.37 [95% CI 1.05–1.78], P = 0.021), whereas treatment with either ACEIs or ARBs was protective (0.28 [0.12–0.65], P = 0.003). CONCLUSIONS—In this sample of older patients with diabetes, microalbuminuria was a risk factor for cognitive decline, whereas drugs that inhibit the renin-angiotensin system were protective. These observations require confirmation because of their considerable potential clinical implications.
Cisplatin-Induced Antitumor Immunomodulation: A Review of Preclinical and Clinical Evidence
Authors: Andreas R. de Biasi, Jonathan Villena-Vargas, Prasad S. Adusumilli
Journal: Clinical Cancer Research (2014)

Abstract Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (i) MHC class I expression upregulation; (ii) recruitment and proliferation of effector cells; (iii) upregulation of the lytic activity of cytotoxic effectors; and (iv) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy's antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy. Clin Cancer Res; 20(21); 5384–91. ©2014 AACR.
MiR-194 Deregulation Contributes To Colorectal Carcinogenesis via Targeting AKT2 Pathway
Authors: Hui-Jun Zhao, Lin-Lin Ren, Zhen-Hua Wang, Tian-Tian Sun, Ya-Nan Yu, Ying-Chao Wang, Ting-Ting Yan, Weiping Zou, Jie He, Yaou Zhang, Jie Hong, Jing-Yuan Fang
Journal: Theranostics (2014)

Recent studies have increasingly linked microRNAs to colorectal cancer (CRC).MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored.Here we investigated the biological effects, mechanisms and clinical significance of miR-194.Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo.Conversely, block of miR-194 in APC Min/+ mice promoted tumor growth.Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo.Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression.Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases.Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006),lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009).In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC.
Menopausal Status Dependence of Early Mortality Reduction Due to Diagnosis of Smaller Breast Cancers (T1 <i>v</i> T2-T3): Relevance to Screening
Authors: Romano Demicheli, Gianni Bonadonna, William J.M. Hrushesky, Michael W. Retsky, Pinuccia Valagussa
Journal: Journal of Clinical Oncology (2003)

To provide data relevant to the paradoxical mortality excess for women age 40 to 49 years observed during the first 6 to 8 years in the invited group in all mammography screening studies.In 1,173 patients undergoing mastectomy alone as primary treatment, allocated to subsets according to menopausal status and tumor size, hazard rates for death were calculated. The ratios between the hazard rate for T2-T3 patients and the corresponding value for T1 patients were assessed over time.For postmenopausal patients, the ratio appeared to be time-dependent, dropping from the maximum value of approximately 5 at the first year after surgery to a near constant value of approximately 2 after 5 to 6 years. Premenopausal patients, on the contrary, showed a nearly constant ratio of approximately 3. Therefore, although in each T-category the 10-year survival of premenopausal and postmenopausal patients was similar, its time distribution was menopause-dependent. In particular, the difference between cumulative survival of premenopausal and postmenopausal T2-T3 patients attained statistical significance after 3 years.The mortality reduction due to the diagnosis of smaller tumors is significantly higher for postmenopausal women than for premenopausal women during early postsurgery time. According to the hypothesis that primary tumor surgical removal, occurring sooner in the invited group than in the control arm of screening trials, results in some acceleration of metastasis development, a greater number of unfavorable events (recurrence and death) should occur in the invited group. We suggest that for younger women, the early balance between benefit from tumor downsizing and harm from surgery-induced metastasis acceleration results in harm. This disadvantage does not occur in postmenopausal women.
Cholesterol Acyltransferase Gene Mutations Have Accelerated Atherogenesis as Assessed by Carotid 3.0-T Magnetic Resonance Imaging
Authors: Raphaël Duivenvoorden, Adriaan G. Holleboom, Bas van den Bogaard, Aart J. Nederveen, Eric de Groot, Barbara A. Hutten, Alinda W. Schimmel, G. Kees Hovingh, John J.P. Kastelein, Jan Albert Kuivenhoven, Erik S.G. Stroes
Journal: Journal of the American College of Cardiology (2011)
Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population
Authors: David T. Selewski, Timothy T. Cornell, Michael Heung, Jonathan P. Troost, Brett J. Ehrmann, Rebecca M. Lombel, Neal B. Blatt, Kera Luckritz, Sue Hieber, Robert Gajarski, David B. Kershaw, Thomas P. Shanley, Debbie S. Gipson
Journal: Intensive Care Medicine (2014)
Right ventricular ejection fraction and NT-proBNP are both indicators of wall stress in pulmonary hypertension
Authors: A. Vonk Noordegraaf, N. Westerhof
Journal: European Respiratory Journal (2007)

Although many therapeutic options have become available in recent years for the treatment of pulmonary arterial hypertension (PAH), there is still no cure available. The primary cause of death is right ventricular failure. Therefore, monitoring right ventricular function is a way to guide therapeutic decisions and a logical step forward to improve life expectancy in PAH patients. Although magnetic resonance imaging (MRI) is considered the gold standard in measuring right ventricular function, the technique is expensive with limited accessibility; therefore, it is unlikely to be frequently used in PAH centres on a regular basis. Therefore, technically simpler methods are welcomed.

In current issue of the European Respiratory Journal , Blyth et al. 1 report that N-terminal B-type natriuretic peptide (NT-proBNP) might act as a simple and effective alternative to MRI measurement. Thus, the results of Blyth et al. 1 confirm those of earlier studies suggesting a relationship between cardiac function in PAH …
Immunoblot analysis of IgM, IgG, and IgA responses to plasmid encoded released proteins of Yersinia enterocolitica in patients with or without yersinia triggered reactive arthritis.
Authors: T H Stahlberg, J Heesemann, K Granfors, A Toivanen
Journal: Annals of the Rheumatic Diseases (1989)

The IgM, IgG, and IgA antibody responses of patients with Yersinia enterocolitica O:3 infection were studied by immunoblotting with plasmid encoded released proteins of Y enterocolitica as the antigens. The results indicate that antibodies of all three classes are most consistently directed against the proteins of molecular weights 25,000 and 36,000. Less than two months after the onset of infection 18 of the 19 patients with yersinia triggered reactive arthritis had IgA class antibodies against the released protein of mol. wt 36,000, whereas only eight of the 17 patients with non-arthritic yersiniosis had these antibodies. The same difference between the arthritic and non-arthritic patients was observed also 8-12 months after the onset of infection.
Hidden 19S IgM rheumatoid factor in adults with juvenile rheumatoid arthritis onset.
Authors: J C Speiser, T L Moore, T D Weiss, A R Baldassare, S C Ross, T G Osborn, R W Dorner, J Zuckner
Journal: Annals of the Rheumatic Diseases (1985)

Forty-eight adult patients with juvenile rheumatoid arthritis (JRA) (onset before age 16 years) were evaluated at the age of 17 years or more for the presence of hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF that can be detected by the complement-dependent haemolytic assay in the IgM-containing fraction after separation of the serum by acid gel filtration. The average age of the patients was 25.3 years. The mean duration of disease was 16.5 years. Thirty-two of 48 patients (67%) showed the presence of hidden 19S IgM RF in their serum. Disease activity correlated with hidden RF titres in 62% (55/88) of the evaluations. The results indicate that patients with seronegative JRA onset continue to have significant titres of hidden 19S IgM RF in their sera into early adulthood.
Prognostic Implications of Altered Human Epidermal Growth Factor Receptors (HERs) in Gastric Carcinomas: HER2 and HER3 Are Predictors of Poor Outcome
Authors: Maria D. Begnami, Emy Fukuda, José H.T.G. Fregnani, Suely Nonogaki, André L. Montagnini, Wilson L. da Costa, Fernando A. Soares
Journal: Journal of Clinical Oncology (2011)

The human epidermal growth factor receptor (HER) family consists of four members: ErbB-1 (HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). These receptors activate numerous downstream pathways in response to extracellular ligands, regulating diverse processes that include differentiation, migration, proliferation, and survival. Alterations in these genes play a role in the development and progression of many human cancers. In gastric carcinomas (GCs), expression of HER1 and HER2 is thought to be a prognostic factor and target of novel biologic agents. The effect of HER3 or HER4 expression in GC has not been sufficiently studied. In this study, we explored the gene and protein expression of the HER family in GC to establish new potential prognostic factors.Immunohistochemistry and fluorescence in situ hybridization were performed in 221 patients with GC using tissue microarray. Correlation between the expression or amplification of HER genes and the clinicopathologic parameters was statistically analyzed.Alterations of members of the HER family were significantly associated with the parameters involved in tumor progression, including depth of tumor invasion, involved lymph nodes, and tumor stage. In addition, HER2 amplification and HER3 expression were significantly related to worse survival.These results reveal that all members of the HER family are expressed in GC. Furthermore, expression of HER2 and HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER-targeted agents and agents targeting downstream signaling pathways provides new possibilities in the treatment of GC.
A golden rule: Looking first
Authors: M. Turner
Journal: BMJ (2000)

“It's a game, and you have to know the rules,” they said about the membership examination. Tricks of the trade were explained in great detail by ranks of registrars and senior house officers on the other side of this impossibly high fence I had to jump. One consultant, however, simply advised me to “just stop and look before you dive in.”

She was clearly very elderly, sitting there in the chair—that is all I remember thinking on the approach.

“Examine this lady's fundi please.”

I leapt in, introduced myself, and put out my hand—got to look confident, got to look like the registrar. Bilateral optic atrophy. I had never seen it more obviously. Now, causes, causes, got to have the causes. I turned to face the examiner and looked him in the eye.

“This lady has bilateral optic atrophy.” I was on a roll now; picking up the signs—this was “the game” and I had all the aces at the moment.

“What is her acuity?” the examiner asked. The “roll” came to an abrupt halt. There was no Snellen chart to hand, what could he mean? He hadn't asked for that in the original instruction. Where was the catch? I struggled and blurted out the first thing I could think of.

“Well, she fumbled slightly for my hand when I went to shake hers, so I suppose the acuity is reduced, but I would need to test it formally of course.” It sounded lame. He just stared at me.

“Are there any other clues that this lady has poor acuity, doctor?”

Now he had the look, the “smiling death” I had been told about. What had I missed? I turned back to face the patient and allowed myself for the first time to “just stop and look.”

From under her chair, and only visible when I stood back from the patient, her guide dog seemed to be grinning at me.

I didn't fail simply because of that—there were other more fundamental errors to come—but it was a simple lesson that I have tried to apply since—to “just stop and look before diving in.”
Evidence-Based Surgery.
Authors: Gordon Caruana-Dingli
Journal: BMJ (2001)

Eds Toby Gordon, John Cameron 

B C Decker, £99.95, pp 688, with CD ISBN 1 55009 116 6

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I was intrigued when I was asked to review Evidence-Based Surgery because precious little surgery is evidence based. Contrary to the expected short book I was confronted by a 688 page tome from the prestigious Johns Hopkins Hospital. Intended as an introduction, it is not a set of clinical guidelines, …

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The New Bethesda System for Reporting Results of Smears of the Uterine Cervix
Authors: L G Koss
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article The New Bethesda System for Reporting Results of Smears of the Uterine Cervix Get access Leopold G. Koss Leopold G. Koss Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 12, 20 June 1990, Pages 988–991, https://doi.org/10.1093/jnci/82.12.988 Published: 20 June 1990 Article history Received: 01 May 1990 Accepted: 02 May 1990 Published: 20 June 1990
A Direct Test of Potential Roles for β3 and β5 Integrins in Growth and Metastasis of Murine Mammary Carcinomas
Authors: Daniela Taverna, Denise Crowley, Mary Connolly, Roderick T. Bronson, Richard O. Hynes
Journal: Cancer Research (2005)

Abstract αvβ3 or αvβ5 integrins are widely expressed on blood and endothelial cells. Inhibition of the functions of these integrins has been reported to suppress neovascularization and tumor growth, suggesting that they may be critical modulators of angiogenesis. However, mice lacking these integrins exhibit extensive angiogenesis. Tumors arising from s.c. injections of tumor cells into mice lacking one or both integrins show enhanced tumor growth compared with growth in control mice due to both increased angiogenesis and to altered innate immune response. Other data suggest additional roles for these integrins, on either platelets or the tumor cells themselves, in enhancing tumor progression and metastasis. Here, we investigate the involvement of β3 and β5 integrins in the development and progression of mammary carcinomas. We intercrossed mouse mammary tumor virus (MMTV)-c-neu transgenic mice with β3 or β5 or β3β5 integrin-deficient mice and observed that multiple, large mammary tumors developed in 100% of mice on all genetic backgrounds. A statistically significant earlier onset of tumor growth was observed in the MMTV-c-neu/β3β5 integrin-null females compared with control mice. No major differences were observed in tumor size or number, vessel number or vessel structure and lung metastases were observed with similar frequency and size in all strains. MMTV-c-neu/β3β5 integrin-null mice had higher numbers of mammary acini, which may account for the earlier onset of tumors in this strain. These data indicate that αvβ3 or αvβ5 integrins are not essential for tumor growth and progression, although they might play some role in mammary gland development.
IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1
Authors: Stephen J. Jenkins, Dominik Ruckerl, Graham D. Thomas, James P. Hewitson, Sheelagh Duncan, Frank Brombacher, Rick M. Maizels, David A. Hume, Judith E. Allen
Journal: The Journal of Experimental Medicine (2013)

Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment.
Elevated Neuron Number in the Limbic Thalamus in Major Depression
Authors: Keith A. Young, Leigh A. Holcomb, Umar Yazdani, Paul B. Hicks, Dwight C. German
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The mediodorsal and anteroventral/anteromedial nuclei of the thalamus are brain regions of interest in the study of mood disorders because they connect subcortical limbic system structures such as the amygdala with the prefrontal, cingulate, and temporal cortices. Anatomical abnormalities have been observed both in the amygdala and in the aforementioned cortical regions in affective disorder patients. Neuroanatomical studies of the thalamus have rarely been conducted in patients with mood disorders. METHOD: Postmortem tissue from the Stanley Foundation Brain Bank was obtained from subjects diagnosed with major depressive disorder, bipolar disorder, and schizophrenia as well as a nonpsychiatric comparison group (N=10–13 per group). The optical disector stereological procedure was used to count neurons in the mediodorsal and anteroventral/anteromedial nuclei of the thalamus in each brain. RESULTS: There were significantly more neurons in the mediodorsal (37%) and anteroventral/anteromedial (26%) nuclei in subjects with major depressive disorder relative to the nonpsychiatric comparison subjects. Neuron numbers and volumes in these limbic thalamic nuclei were normal in the schizophrenia and bipolar subjects. CONCLUSIONS: The data indicate that there is an elevation in total neuron number in the limbic thalamus that is specific for major depressive disorder. This represents the first report of a neuropsychiatric disorder being associated with an increase in total regional neuron number. The present findings, along with recent data, indicate that significant anatomical and functional abnormalities are present in limbic circuits in major depressive disorder.
Automated external defibrillator in sport: absolutely always available
Authors: Efraim B Kramer
Journal: British Journal of Sports Medicine (2013)

“Pheidippides was a legend in ancient Greece. He ran 250 kms in 2 days to request help from the Spartans when Athens was being invaded. However, after helping defeat the Persians in Marathon, he ran 35 kms to declare victory, collapsed and died. The greatest physical specimen of super-compensated physiology became the first documented case of sudden death in an endurance athlete.”1

The role of regular exercise as a means of preventing, managing and treating disease in all ages is well described.2 ,3 Participating in sport is thus considered to be of benefit to the health of an individual and competitive athletes are often regarded as the healthiest facet of our society: “mens sana in corpore sano—a sound mind in a healthy body.”3 ,4

Sudden cardiac arrest (SCA) in sport was a rare, yet regular event. Recently, with international media coverage5 and committed medical research,6 its rarity has come under scrutiny. Whatever its prevalence, if the end …