tbuckley/cabot-search huggingface dataset:
Long-Term Efficacy of Glibenclamide and Sitagliptin Therapy in Adult Patients With KCNJ11 Permanent Diabetes
Authors: Julia Sastre, Alessandra Luque, Florentino del Val, Angel Aragonés, José López
Journal: Diabetes Care (2014)

Permanent neonatal diabetes (PND) is a rare disease characterized by hyperglycemia diagnosed within the first 6 months of life (1). Activating mutation of the KCNJ11 gene encoding Kir6.2 subunit of the ATP-potassium (KATP) channel has been described as the most frequent cause of PND. Under physiologic circumstances, KATP channel closure plays a central role in glucose-stimulated insulin secretion from pancreatic β-cells. Sulfonylureas (SUs) stimulate insulin secretion by closing KATP channels via an ATP-independent mechanism. Since 2004, SUs are best choice of treatment in PND with such mutations and allow better glycemic control in children and adults than insulin (2).

Some authors report that adult patients are unable to switch successfully from insulin to SU and that the doses required to get the insulin independence are higher (3,4). We present our …
Maintained Sensitivity to EGFR Tyrosine Kinase Inhibitors in <i>EGFR</i>-Mutant Lung Cancer Recurring after Adjuvant Erlotinib or Gefitinib
Authors: Geoffrey R. Oxnard, Yelena Y. Janjigian, Maria E. Arcila, Camelia S. Sima, Samantha L. Kass, Gregory J. Riely, William Pao, Mark G. Kris, Marc Ladanyi, Christopher G. Azzoli, Vincent A. Miller
Journal: Clinical Cancer Research (2011)

Given the unprecedented efficacy of EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutant lung cancer, adjuvant TKI therapy is an appealing strategy. However, there are conflicting findings regarding the potential benefit of adjuvant EGFR-TKI in patients with lung cancer harboring EGFR mutations. To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI.Patients with recurrent EGFR-mutant lung cancer following adjuvant TKI were identified using an Institutional Review Board-approved mechanism. Recurrent cancer specimens were tested for resistance mutations. Sensitivity to retreatment with EGFR-TKI was evaluated.Twenty-two patients with cancers harboring an EGFR sensitizing mutation received adjuvant erlotinib or gefitinib for a median of 17 months (range 1-37 months). T790M was more common in cancers which recurred while receiving TKI than in those which recurred after stopping TKI (67% vs. 0%, P = 0.011). Fourteen patients who developed recurrence after stopping EGFR-TKI were retreated, with a median time to progression of 10 months and radiographic response seen in 8 of 11 patients with evaluable disease (73%).Recurrence of EGFR-mutant lung cancer after stopping adjuvant TKI should not preclude a trial of TKI retreatment; a phase II trial of erlotinib in this setting is underway. Studies of adjuvant EGFR-TKI will underestimate the potential survival benefit of adjuvant TKI for patients with EGFR-mutant lung cancers if retreatment at recurrence is not given.
The Long-Term Clinical Outcomes of Lyme Disease: A Population-Based Retrospective Cohort Study
Authors: Nancy A. Shadick
Journal: Annals of Internal Medicine (1994)

Objective: To ascertain the prevalence of and risk factors for long-term sequelae from acute Lyme disease. Design: Population-based, retrospective cohort study. Setting: A coastal region endemic for Lyme disease. Participants: Patients with a history of Lyme disease who were previously treated with antibiotics were compared with randomly selected controls. Measurements: A standardized physical examination, health status measure (Short Form 36), psychometric test battery, and serologic analysis. Results: Compared with the control group (n = 43), the Lyme group (n = 38; mean duration from disease onset to study evaluation, 6.2 years) had more arthralgias (61% compared with 16%; P < 0.0001); distal paresthesias (16% compared with 2%; P = 0.03); concentration difficulties (16% compared with 2%; P = 0.03); and fatigue (26% compared with 9%; P = 0.04), and they had poorer global health status scores (P = 0.04). The Lyme group also had more abnormal joints (P = 0.02) and more verbal memory deficits (P = 0.01) than did the control group. Overall, 13 patients (34%; 95% CI, 19% to 49%) had long-term sequelae from Lyme disease (arthritis or recurrent arthralgias [n = 6], neurocognitive impairment (n = 4), and neuropathy or myelopathy [n = 3]). Compared with controls, patients who had long-term sequelae had higher IgG antibody titers to the spirochete (P = 0.03) and received treatment later (34.5 months compared with 2.7 months; P < 0.0001). Conclusions: Persons with a history of Lyme disease have more musculoskeletal impairment and a higher prevalence of verbal memory impairment when compared with those without a history of Lyme disease. Our findings suggest that disseminated Lyme disease may be associated with long-term morbidity. *Deceased.
End-tidal CO2 pressure may facilitate differential diagnostics between PH patients with chronic heart or lung disease and CTEPH
Authors: Maria Tscherner, Gabor Kovacs, Vasile Foris, Stefan Scheidl, Alexander Avian, Andrea Olschewski, Horst Olschweski
Journal: European Respiratory Journal (2012)

Background:  End-tidal CO 2  pressure (PETCO 2 ) is a simple parameter, which may be assessed at rest or during exercise during cardiopulmonary exercise testing (CPET). PETCO 2  changes have been described in patients with cardiac failure and acute pulmonary embolism, as well as in pulmonary hypertension (PH), but it is not known if PETCO2 may be helpful in differentiating between PH subgroups.  Patients and Methods:  We retrospectively investigated PETCO 2  data of patients with a meanPAP >25 mmHg at rest, due to chronic left heart (LH-PH), and pulmonary disease (Lu-PH) or CTEPH. PETCO 2  was measured at rest and during maximal exercise. Mean values were compared by ANOVA and multiple comparisons were performed with Scheffe equation as post hoc test.  Results:  N= 46 patients were included (LH-PH: n= 14, mean PAP 40±11 mmHg, PVR 327±188 dyn s cm -5 , PAWP 21±5 mmHg; Lu-PH: n=15, meanPAP 34±8 mmHg, PVR 441±266 dyn s cm -5 , FEV1%pred. 63±27; CTEPH: n=17, meanPAP 46±11mmHg, PVR 732±308 dyn s cm -5 ). PETCO 2  at rest was 4.97±1.04 mmHg, 4.70±1.19 mmHg, and 3.55±0.71 mmHg in LH-PH, Lu-PH and CTEPH patients. The PETCO2 difference between LH-PH and CTEPH was 1.38 (CI 95% 0.48 to 2.29 p=0.001), and between Lu-PH and CTEPH 1.14 (CI 95% 0.24 to 2.04 p=0.007).Comperable similar results were obtained with PETCO 2  during maximal exercise.  Conclusion: PH caused by CTEPH is characterized by lowered PETCO 2  as compared to PH due to chronic heart or lung disease.
Comparison of Isotonic and Hypotonic Intravenous Maintenance Fluids
Authors: Jeremy N. Friedman, Carolyn E. Beck, Julie DeGroot, Denis F. Geary, Daniel J. Sklansky, Stephen B. Freedman
Journal: JAMA Pediatrics (2015)

Use of hypotonic intravenous fluids for maintenance requirements is associated with increased risk of hyponatremia that results in morbidity and mortality in children. Clinical trial data comparing isotonic and hypotonic maintenance fluids in nonsurgical hospitalized pediatric patients outside intensive care units are lacking.To compare isotonic (sodium chloride, 0.9%, and dextrose, 5%) with hypotonic (sodium chloride, 0.45%, and dextrose, 5%) intravenous maintenance fluids in a hospitalized general pediatric population.In this double-blind randomized clinical trial,we recruited 110 children admitted to a general pediatric unit of a tertiary care children's hospital from March 1, 2008, through August 31, 2012 (age range, 1 month to 18 years), with normal baseline serum sodium levels who were anticipated to require intravenous maintenance fluids for 48 hours or longer (intent-to-treat analyses). Children with diagnoses that required specific fluid tonicity and volumes were excluded.Patients were randomized to receive isotonic or hypotonic intravenous fluid at maintenance rates for 48 hours.The primary outcome was mean serum sodium level at 48 hours. The secondary outcomes were mean sodium level at 24 hours, hyponatremia and hypernatremia, weight gain, hypertension, and edema. Confounding variables were included in multiple regression models. Post hoc analyses included change from baseline sodium level at 24 and 48 hours and subgroup analysis of children with primary respiratory diagnosis.Of 110 enrolled patients, 54 received isotonic fluids and 56 received hypotonic fluids. The mean (SD) sodium level at 48 hours was 139.9 (2.7) mEq/L in the isotonic group and 139.6 (2.6) mEq/L in the hypotonic group (95% CI of the difference, -0.94 to 1.74 mEq/L; P = .60). Two patients in the hypotonic group developed hyponatremia, 1 in each group developed hypernatremia, 2 in each group developed hypertension, and 2 in the isotonic group developed edema. Mean (SD) change from baseline to 48-hour sodium level was +1.3 (2.9) vs -0.12 (2.8) mEq/L, respectively (absolute difference, 1.4 mEq/L; 95% CI of the difference, -0.01 to 2.8 mEq/L; P = .05).Our study results support the notion that isotonic maintenance fluid administration is safe in general pediatric patients and may result in fewer cases of hyponatremia.clinicaltrials.gov Identifier: NCT00632775.
Monitoring West Nile virus (WNV) infection in wild birds in Serbia during 2012: first isolation and characterisation of WNV strains from Serbia
Authors: T Petrović, A B Blázquez, D Lupulović, G Lazić, E Escribano-Romero, D Fabijan, M Kapetanov, S Lazić, J C Saiz
Journal: Eurosurveillance (2013)

West Nile virus (WNV), a neurovirulent mosquito-transmissible zoonotic virus, has caused recent outbreaks in Europe, including Serbia from August until October 2012. Although humans can be infected, birds are the main natural WNV reservoir. To assess WNV circulation in northern Serbia, 133 wild birds were investigated. These comprised resident and migratory birds, collected between January and September 2012 in the Vojvodina province. The birds belonged to 45 species within 27 families. Blood sera (n=92) and pooled tissues from respective birds (n=81) were tested by enzyme-linked immunosorbent assay (ELISA), plaque reduction neutralisation test (PRNT) and real-time reverse transcription-polymerase chain reaction (RT-qPCR). WNV antibodies were detected in seven (8%) sera: four from Mute Swans (Cygnus olor), two from White-tailed Eagles (Haliaeetus albicillas), and one from a Common Pheasant (Phasianus colchicus). Five sera neutralised WNV but not Usutu virus. For the first time in Serbia, WNV RNA was detected by RT-qPCR in pooled tissue samples of eight respective birds. WNV RNA was also derived from an additional bird, after a serum sample resulted infective in cell culture. The total nine WNV RNA positive birds included three Northern Goshawks (Accipiter gentilis), two White-tailed Eagles, one Legged Gull (Larus michahelis), one Hooded Crow (Corvus cornix), one Bearded Parrot-bill (Panarus biramicus), and one Common Pheasant. Phylogenetic analysis of partial E region sequences showed the presence of, at least, two lineage 2 Serbian clusters closely related to those responsible for recent human and animal outbreaks in Greece, Hungary and Italy. Full genomic sequence from a goshawk isolate corroborated this data. These results confirm WNV circulation in Serbia and highlight the risk of infection for humans and horses, pointing to the need for implementing WNV surveillance programmes.
Fight over extended hours reaches deadlock
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

The secretary of state for health in England took the unusual step this week of writing to all GPs in the country to try to convince them to accept the latest offer from the government for extending surgery opening hours. The letter goes out a week before a poll of GP members of the BMA on how to proceed over negotiations that have reached deadlock.

In the letter Alan Johnson, the health secretary, reiterated the government’s offer over extended hours, which he has previously said was misrepresented by the BMA.

The deal is for practices to provide 30 minutes of extended opening per week for every 1000 of their registered patients—or three hours for an average sized practice. It will be funded by rerouting £158m (€211m; …
Incidence and determinants of lower extremity running injuries in long distance runners: a systematic review
Authors: R N van Gent, D Siem, M van Middelkoop, A G van Os, S M A Bierma-Zeinstra, B W Koes
Journal: British Journal of Sports Medicine (2007)

The purpose of this study was to present a systematic overview of published reports on the incidence and associated potential risk factors of lower extremity running injuries in long distance runners. An electronic database search was conducted using the PubMed–Medline database. Two observers independently assessed the quality of the studies and a best evidence synthesis was used to summarise the results. The incidence of lower extremity running injuries ranged from 19.4% to 79.3%. The predominant site of these injuries was the knee. There was strong evidence that a long training distance per week in male runners and a history of previous injuries were risk factors for injuries, and that an increase in training distance per week was a protective factor for knee injuries.
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Authors: Glynn Dennis, Brad T Sherman, Douglas A Hosack, Jun Yang, Wei Gao, H Clifford Lane, Richard A Lempicki
Journal: Genome biology (2003)

Functional annotation of differentially expressed genes is a necessary and critical step in the analysis of microarray data. The distributed nature of biological knowledge frequently requires researchers to navigate through numerous web-accessible databases gathering information one gene at a time. A more judicious approach is to provide query-based access to an integrated database that disseminates biologically rich information across large datasets and displays graphic summaries of functional information.Database for Annotation, Visualization, and Integrated Discovery (DAVID; http://www.david.niaid.nih.gov) addresses this need via four web-based analysis modules: 1) Annotation Tool - rapidly appends descriptive data from several public databases to lists of genes; 2) GoCharts - assigns genes to Gene Ontology functional categories based on user selected classifications and term specificity level; 3) KeggCharts - assigns genes to KEGG metabolic processes and enables users to view genes in the context of biochemical pathway maps; and 4) DomainCharts - groups genes according to PFAM conserved protein domains.Analysis results and graphical displays remain dynamically linked to primary data and external data repositories, thereby furnishing in-depth as well as broad-based data coverage. The functionality provided by DAVID accelerates the analysis of genome-scale datasets by facilitating the transition from data collection to biological meaning.
A diarrheal pathogen, enteropathogenic Escherichia coli (EPEC), triggers a flux of inositol phosphates in infected epithelial cells.
Authors: V Foubister, I Rosenshine, B B Finlay
Journal: The Journal of Experimental Medicine (1994)

Enteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that causes diarrhea in infants by adhering to intestinal epithelial cells. EPEC induces host cell protein phosphorylation and increases intracellular calcium levels that may function to initiate cytoskeletal rearrangement. We found that EPEC triggers the release of inositol phosphates (IPs) after adherence of bacteria to cultured epithelial cells. We also demonstrated that the EPEC-induced flux of IPs precedes actin rearrangement and bacterial invasion. EPEC mutants and tyrosine protein kinase inhibitors were used to establish that formation of IPs is dependent on tyrosine phosphorylation of a 90-kD HeLa protein. Collectively these results suggest that EPEC-induced tyrosine phosphorylation of a host cell substrate(s) leads to release of IPs, which may then trigger cytoskeletal rearrangement.
Keystone Symposia 40th Season: MicroRNAs and Noncoding RNAs in Cancer
Authors: Kaja A. Wasik, Clare A. Rebbeck
Journal: Cancer Research (2011)

This year's 40th season of Keystone symposia meetings was held in Banff, Alberta, Canada, on February 11-16 and sponsored by Astellas Pharma and Regulus Therapeutics. The meeting was organized by Gregory Hannon, Curtis Harris, and Martine Roussel and centered on microRNAs (miRNA), noncoding RNAs, and cancer. The meeting was grouped around the following topical areas: miRNA mechanisms, oncogenesis, immune response, angiogenesis and metastasis, cancer biomarkers, stem cells, and therapeutics. This report highlights findings and concepts presented during this meeting.
Relationship between nutritional status and lung function in cystic fibrosis: cross sectional and longitudinal analyses from the German CF quality assurance (CFQA) project
Authors: G Steinkamp
Journal: Thorax (2002)

The German cystic fibrosis (CF) quality assurance (CFQA) project is a patient registry for CF which was founded in 1995. Relevant clinical and laboratory data, respiratory function test results, complications, and CF treatments are entered into the database once a year for each patient. Using the database, a study was undertaken to elucidate the relationship between nutrition and lung function in a large patient cohort by cross sectional and longitudinal analysis.A cohort of 3298 patients above 2 years of age was analysed. Patients were grouped according to the presence or absence of malnutrition (wasting and/or stunting). Cross sectional and longitudinal analyses over 2 and 3 years including mixed model analyses were performed.The prevalence of abnormal weight for height (<90% predicted) increased with age from 19% in children aged <6 years to 38% in adults with CF. Patients with malnutrition had significantly lower mean values of vital capacity, arterial oxygen tension (PO(2)), and forced expiratory volume in 1 second (FEV(1)) and higher serum IgG (p<0.05). Pseudomonas aeruginosa infection was also associated with decreased pulmonary function. Malnourished adolescents aged 12-18 years experienced a serious decline in FEV(1) of about 20% predicted, whereas mean FEV(1) values remained stable at above 80% predicted in adolescents of normal weight. Longitudinal follow up showed that malnourished patients of all ages and those with P aeruginosa infection had significantly worse lung function than their normally nourished counterparts and a greater yearly loss of FEV(1) % predicted. During 1 year of observation adolescents who experienced a >5% predicted decrease in weight for height had a concomitant mean loss of FEV(1) of 16.5% predicted during that year, whereas patients who gained relative weight had a parallel increase in FEV(1) of 2.1% predicted.These data emphasise the close relationship between nutrition, lung function, and clinical course in CF. Normal body weight and absence of P aeruginosa infection was associated with better preservation of lung function.
UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting
Authors: Tapan A Maniar, Miriam Kaplan, George J Wang, Kang Shen, Li Wei, Jocelyn E Shaw, Sandhya P Koushika, Cornelia I Bargmann
Journal: Nature Neuroscience (2011)
Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk
Authors: E. Samoli, A. Lagiou, P. Zourna, A. Barbouni, C. Georgila, A. Tsikkinis, D. Vassilarou, P. Minaki, C. Sfikas, E. Spanos, D. Trichopoulos, P. Lagiou
Journal: Annals of Oncology (2014)
GRP78 is overexpressed in glioblastomas and regulates glioma cell growth and apoptosis
Authors: Hae Kyung Lee, Cunli Xiang, Simona Cazacu, Susan Finniss, Gila Kazimirsky, Nancy Lemke, Norman L. Lehman, Sandra A. Rempel, Tom Mikkelsen, Chaya Brodie
Journal: Neuro-Oncology (2008)

We characterized the expression and function of the endoplasmic reticulum protein GRP78 in glial tumors. GRP78 is highly expressed in glioblastomas but not in oligodendrogliomas, and its expression is inversely correlated with median patient survival. Overexpression of GRP78 in glioma cells decreases caspase 7 activation and renders the cells resistant to etoposide- and cisplatin-induced apoptosis, whereas silencing of GRP78 decreases cell growth and sensitizes glioma cells to etoposide, cisplatin, and gamma-radiation. Thus, GRP78 contributes to the increased apoptosis resistance and growth of glioma cells and may provide a target for enhancing the therapeutic responsiveness of these tumors.
Four-step high-dose sequential chemotherapy with hematopoietic progenitor-cell support as induction treatment for patients with solid tumors
Authors: S. Culine, M. Fabbro, C. Assens, M. Ychou, G. Romieu, A. Kramar, D. Cupissol, F. Pinguet, H. Pujol
Journal: Annals of Oncology (1997)
Phase I Trial of the Proteasome Inhibitor Bortezomib in Patients With Advanced Solid Tumors With Observations in Androgen-Independent Prostate Cancer
Authors: Christos N. Papandreou, Danai D. Daliani, Darrell Nix, Hong Yang, Timothy Madden, Xuemei Wang, Christine S. Pien, Randall E. Millikan, Shi-Ming Tu, Lance Pagliaro, Jeri Kim, Julian Adams, Peter Elliott, Dixie Esseltine, Alexandria Petrusich, Pauline Dieringer, Cherie Perez, Christopher J. Logothetis
Journal: Journal of Clinical Oncology (2004)

To determine the dose-limiting toxicity and maximum-tolerated dose of the proteasome inhibitor bortezomib administered intravenously weekly for 4 every 5 weeks; to determine the bortezomib pharmacokinetics and pharmacodynamics using plasma levels and an assay for 20S proteasome inhibition (PI) in whole blood; to correlate toxicity with bortezomib dose and degree of 20S PI; and to conduct a preliminary determination of the antitumor activity of bortezomib in patients with androgen independent prostate cancer (AIPCa).Fifty-three patients (48 with AIPCa) received 128 cycles of bortezomib in doses ranging from 0.13 to 2.0 mg/m(2)/dose, utilizing a careful escalation scheme with a continuous reassessment method. Pharmacokinetic and pharmacodynamic studies were performed in 24 patients (at 1.45 to 2.0 mg/m(2)).A dose-related 20S PI was seen, with dose-limiting toxicity at 2.0 mg/m(2) (diarrhea, hypotension) occurring at an average 1-hour post-dose of >/= 75% 20S PI. Other side effects were fatigue, hypertension, constipation, nausea, and vomiting. No relationship was seen between body-surface area and bortezomib clearance over the narrow dose range tested. There was evidence of biologic activity (decline in serum prostate-specific antigen and interleukin-6 levels) at >/= 50% 20S PI. Two patients with AIPCa had prostate-specific antigen response and two patients had partial response in lymph nodes.The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib. This agent should be further explored with chemotherapy agents in advanced prostate cancer.