tbuckley/cabot-search huggingface dataset:
An open letter to Simon Stevens, NHS chief executive, and Alistair Burns, national clinical lead for dementia
Authors: Martin Brunet
Journal: BMJ (2014)

We are writing to voice serious concerns regarding the new dementia identification scheme for GPs, whereby English GPs are to be paid £55 (€70; $88) for each additional diagnosis of dementia made before the end of March.

Helping people affected by dementia to achieve a diagnosis is a worthwhile goal, but the means of achieving this must have a sound ethical basis. The …
Where is the evidence base for benefits of sentinel node biopsy in melanoma?
Authors: J. M. Thomas
Journal: BMJ (2013)

Sentinel node biopsy (SNB) has been promoted by claims of a survival advantage after early lymphadenectomy in patients with a positive result. The pivotal paper states that SNB “identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy.”1 An earlier paper by Morton and colleagues states, “Our data suggest a significant therapeutic benefit for immediate …
Nilotinib As Front-Line Treatment for Patients With Chronic Myeloid Leukemia in Early Chronic Phase
Authors: Jorge E. Cortes, Dan Jones, Susan O'Brien, Elias Jabbour, Marina Konopleva, Alessandra Ferrajoli, Tapan Kadia, Gautam Borthakur, Denise Stigliano, Jianqin Shan, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2009)

Purpose Although most patients with chronic myeloid leukemia (CML) in chronic phase respond well to front-line therapy with imatinib, some patients do not achieve the desirable end point, and others may eventually lose response or are intolerant. Patients and Methods Patients with newly diagnosed CML in chronic phase were treated with nilotinib 400 mg twice daily on an empty stomach as initial therapy. Results Among 51 patients in chronic phase observed for at least 3 months, 50 (98%) achieved a complete cytogenetic remission (CCyR), and 39 (76%) achieved a major molecular response (MMR). Responses occurred rapidly, with 96% of patients achieving CCyR by 3 months and 98% achieving CCyR by 6 months. The projected event-free survival at 24 months is 90%, and all patients are alive after a median follow-up time of 17 months. Grade ≥ 3 neutropenia occurred in 12% of patients, and thrombocytopenia in occurred 11%. Nonhematologic toxicity was usually grade 1 to 2 and manageable. The actual median dose at 12 months was 800 mg (range, 200 to 800 mg). Conclusion Nilotinib is an effective option for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR, with most patients reaching these responses early during their therapy.
Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency
Authors: Claudia Wehr, Andrew R. Gennery, Caroline Lindemans, Ansgar Schulz, Manfred Hoenig, Reinhard Marks, Mike Recher, Bernd Gruhn, Andreas Holbro, Ingmar Heijnen, Deborah Meyer, Goetz Grigoleit, Hermann Einsele, Ulrich Baumann, Thorsten Witte, Karl-Walter Sykora, Sigune Goldacker, Lorena Regairaz, Serap Aksoylar, Ömur Ardeniz, Marco Zecca, Przemyslaw Zdziarski, Isabelle Meyts, Susanne Matthes-Martin, Kohsuke Imai, Chikako Kamae, Adele Fielding, Suranjith Seneviratne, Nizar Mahlaoui, Mary A. Slatter, Tayfun Güngör, Peter D. Arkwright, Joris van Montfrans, Kathleen E. Sullivan, Bodo Grimbacher, Andrew Cant, Hans-Hartmut Peter, Juergen Finke, H. Bobby Gaspar, Klaus Warnatz, Marta Rizzi
Journal: Journal of Allergy and Clinical Immunology (2015)
Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report
Authors: Maurizio Fava, A. John Rush, Jonathan E. Alpert, G. K. Balasubramani, Stephen R. Wisniewski, Cheryl N. Carmin, Melanie M. Biggs, Sidney Zisook, Andrew Leuchter, Robert Howland, Diane Warden, Madhukar H. Trivedi
Journal: American Journal of Psychiatry (2008)

About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study.A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression.In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options.Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.
Connect the dots: a rare case of spontaneous haemopneumothorax
Authors: Natalie K Kozij, John Thenganatt
Journal: Thorax (2013)

A 19-year-old woman presented to her local emergency department with acute chest pain and shortness of breath. She denied any cough, haemoptysis, fever or leg swelling.

Her past medical history was significant for premature birth at 28 weeks gestational age. She required surgical correction of a right clubfoot as an infant. In addition, she had intestinal malrotation complicated by caecal volvulus and perforation treated with laparotomy at age 13, and an ovarian cystectomy performed at age 17. There was no family history of pneumothorax or respiratory disease. She was a non-smoker on no medications.

On examination, she was tachycardic, tachypnoeic and had an oxygen saturation in the low 80s. Her respiratory exam demonstrated decreased air entry to bilateral lung bases. A …
Lack of Correlation between p53-Dependent Transcriptional Activity and the Ability to Induce Apoptosis among 179 Mutant p53s
Authors: Yuichi Kakudo, Hiroyuki Shibata, Kazunori Otsuka, Shunsuke Kato, Chikashi Ishioka
Journal: Cancer Research (2005)

Tumor suppressor p53-dependent apoptosis is thought to be one of the most important tumor-suppressive functions in human tumorigenesis. However, whether the major mechanism underlying the p53-dependent apoptosis is transactivation dependent or independent remains unclear. Using 179 mutant p53s with diverse transcriptional activities for distinct p53-binding sequences in yeast, we evaluated both their sequence-specific transcriptional activities on six p53 target genes and their ability to induce apoptosis in Saos-2 cells. These mutant p53s also represented diversity in their ability to both transactivate target genes and induce apoptosis. We identified 17 mutant p53s with superior ability to induce apoptosis than wild-type p53 that tend to cluster at residues 121 or 290 to 292. There was no significant correlation between the two functional properties on any single target gene examined. Furthermore, the 17 mutant p53s were not classified in a specific cluster by hierarchical cluster analysis on their diverse transcriptional activities, indicating that these mutant p53s were not similar in the transcriptional activity of downstream genes. These results suggested that transactivation-dependent apoptosis does not always play a major role in p53-dependent apoptosis, indirectly supporting the importance role of the transactivation-independent mechanism.
Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury
Authors: Yasutada Akiba, Osamu Furukawa, Paul H. Guth, Eli Engel, Igor Nastaskin, Pejvak Sassani, Ramanath Dukkipatis, Alexander Pushkin, Ira Kurtz, Jonathan D. Kaunitz
Journal: Journal of Clinical Investigation (2001)

Secretion of bicarbonate from epithelial cells is considered to be the primary mechanism by which the duodenal mucosa is protected from acid-related injury. Against this view is the finding that patients with cystic fibrosis, who have impaired duodenal bicarbonate secretion, are paradoxically protected from developing duodenal ulcers. Therefore, we hypothesized that epithelial cell intracellular pH regulation, rather than secreted extracellular bicarbonate, was the principal means by which duodenal epithelial cells are protected from acidification and injury. Using a novel in vivo microscopic method, we have measured bicarbonate secretion and epithelial cell intracellular pH (pH(i)), and we have followed cell injury in the presence of the anion transport inhibitor DIDS and the Cl(-) channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). DIDS and NPPB abolished the increase of duodenal bicarbonate secretion following luminal acid perfusion. DIDS decreased basal pH(i), whereas NPPB increased pH(i); DIDS further decreased pH(i) during acid challenge and abolished the pH(i) overshoot over baseline observed after acid challenge, whereas NPPB attenuated the fall of pH(i) and exaggerated the overshoot. Finally, acid-induced epithelial injury was enhanced by DIDS and decreased by NPPB. The results support the role of intracellular bicarbonate in the protection of duodenal epithelial cells from luminal gastric acid.
Competitive selection among age-class ice-hockey players.
Authors: R. J. Shephard, H. Lavallée, G. Larivière
Journal: British Journal of Sports Medicine (1978)

The little-league is an important feature of the North American scene, young boys vying vigorously with one another for places on age-categorized icehockey, football, and baseball teams that compete in municipal, regional and even provincial leagues. The system has been criticized on a number of counts, including the possible psychological risks of premature exposure to intensive competition, the limited knowledge of many of the coaches, and the too frequent insistence upon winning at all costs. The present note examines a further likely hazard of age-class sport competition and even physical collision between small pre-pubertal children and young people of the same chronological age who have reached almost adults' proportions.
Immunohistochemical delineation of the conduction system. I: The sinoatrial node.
Authors: P W Oosthoek, S Virágh, A E Mayen, M J van Kempen, W H Lamers, A F Moorman
Journal: Circulation Research (1993)

We have raised a mouse monoclonal antibody that reacts specifically with the myocytes of the sinoatrial node of the bovine heart. By use of this antibody (445-6E10) and antibodies against the gap junction protein connexin43, the periphery of the sinoatrial node and the distribution of gap junctions in the nodal region were studied. The reaction patterns of 445-6E10 and anti-connexin43 are exactly complementary; ie, connexin43 was not detected in the nodal myocytes but was clearly present in the atrial myocytes. Both reaction patterns demonstrate that nodal myocytes and atrial myocytes can unambiguously be distinguished by their characteristic molecular phenotype. The transitional nodal myocytes at the periphery of the node that have intermediate morphological and electrophysiological characteristics could now clearly be defined as nodal by our immunohistochemical criteria. The center of the node is surrounded by a region of interdigitating nodal and atrial bundles. Nodal bundles, coming from the center of the node, penetrate the atrial myocardium aligned at atrial bundles, forming histological connections between nodal and atrial myocytes at regular distances. This interdigitating arrangement of bundles of connexin43-negative nodal and connexin43-positive atrial myocytes is also found in the human and rat heart. We hypothesize that the architecture of the periphery of the node is important to prevent silencing of the pacemaking nodal myocytes by the atrium while ensuring a sufficient source loading of the nodal myocytes.
Vascular Calcification
Authors: Masahide Mizobuchi, Dwight Towler, Eduardo Slatopolsky
Journal: Journal of the American Society of Nephrology (2009)

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Vascular calcification is a common complication in CKD, and investigators have demonstrated that the extent and histoanatomic type of vascular calcification are predictors of subsequent vascular mortality. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in vascular calcification in patients with kidney disease, many questions remain unanswered. No longer can we accept the concept that vascular calcification in CKD is a passive process resulting from an elevated calcium-phosphate product. Rather, as a result of the metabolic insults of diabetes, dyslipidemia, oxidative stress, uremia, and hyperphosphatemia, "osteoblast-like" cells form in the vessel wall. These mineralizing cells as well as the recruitment of undifferentiated progenitors to the osteochondrocyte lineage play a critical role in the calcification process. Important transcription factors such as Msx 2, osterix, and RUNX2 are crucial in the programming of osteogenesis. Thus, the simultaneous increase in arterial osteochondrocytic programs and reduction in active cellular defense mechanisms creates the "perfect storm" of vascular calcification seen in ESRD. Innovative clinical studies addressing the combined use of inhibitors that work on vascular calcification through distinct molecular mechanisms, such as fetuin-A, osteopontin, and bone morphogenic protein 7, among others, will be necessary to reduce significantly the accrual of vascular calcifications and cardiovascular mortality in kidney disease. In addition, the roles of oxidative stress and inflammation on the fate of smooth muscle vascular cells and their function deserve further translational investigation.
Analysis of Patients Treated with Cisplatin or Carboplatin-Based Doublet Chemotherapy in the European Frame Observational Study
Authors: E.F. Smit, D. Moro-Sibilot, J.Castro De Carpeño, K. Kmak-Lesniewski, J.G. Aerts, R. Villatoro, K. Kraaij, K. Nacerddine, Y. Dyachkova, K. Smith, A. Girvan, C.M. Visseren-Grul, P.A. Schnabel
Journal: Annals of Oncology (2014)
Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD
Authors: Giancarlo Castaman, Stefan Lethagen, Augusto B. Federici, Alberto Tosetto, Anne Goodeve, Ulrich Budde, Javier Batlle, Dominique Meyer, Claudine Mazurier, Edith Fressinaud, Jenny Goudemand, Jeroen Eikenboom, Reinhard Schneppenheim, Jorgen Ingerslev, Zdena Vorlova, David Habart, Lars Holmberg, John Pasi, Frank Hill, Ian Peake, Francesco Rodeghiero
Journal: Blood (2008)
LOWER LIMB FUNCTIONAL ASYMMETRIES IN YOUNG SOCCER PLAYERS: DO DIFFERENCES EXIST BETWEEN DIFFERENT AGE GROUPS?
Authors: I Sannicandro, A Quarto, A Piccinno, G Cofano, RA Rosa
Journal: British Journal of Sports Medicine (2014)

Background Functional asymmetries of the lower limbs(FA) have been recognised as a potential source of injury risk of in soccer players;moreover a difference in strength performance between the lower limbs exceeding 15% is considered an injury risk factor. Preventative strategies should be integrated into young football player training regimes. Table 1. Young soccer players: mean age 9.1±0.1 years. n.athletes&gt;15% Total %&gt;15% % others Hop 25 227 11,2 88,8 Triple 19 227 8,4 91,6 Side 33 227 14,5 85,5 Table 2. Young soccer players: mean age 11.2±0.1 years *p&gt;0.05. n.athletes&gt;15% Total %&gt;15% % others Hop 27 200 13,7 86,3 Triple 16 200 8,3 91,7 Side 37 200 18,5 81,5 Objective To assess the presence of FA in the lower limbs and evaluate whether the percentage of subjects presenting asymmetries exceeding 15% increases with age. Design Cross-sectional studies. Setting Youth sports. Participants 427 young soccer players: 9.1±0.1 years, 36.3±6.5 kg, 137.9±7.1cm (n=227) and 11.2±0.1 yrs, 43.8±9.7 kg, 148.9±9.1 cm (n=200). Risk factor assessment Monopodalic jump ; all three versions were employed: Single (SI), Triple (TR) and Side hop(SE) is considered a valid indicator of FA in the lower limbs. Main outcome measurements Strength in each of the lower limbs was assessed by means of the SI, TR and SE test; the percentage of FA between the lower limbs was calculated using the formula proposed by Yamamoto, 1993: (jump dominant-limb-jump non-dominant limb)/jump dominant-limb*100. Results The percentage valuesare summarised in tables 1 and 2. Conclusions The highest percentage of subjects presenting asymmetries was detected in the 11yr-olds. Comparing the results for the two age groups revealed a statistically significant difference for the SideHop test.
Retinopathy Predicts Coronary Heart Disease Events in NIDDM Patients
Authors: Heikki Miettinen, Steven M Haffner, Seppo Lehto, Tapani Rönnemaa, Kalevi Pyörälà, Markku Laakso
Journal: Diabetes Care (1996)

OBJECTIVE Proliferative retinopathy has been shown to be associated with increased all-cause mortality in diabetic patients. We assessed the relationship between the different degrees of retinopathic changes at baseline and serious coronary heart disease (CHD) events (CHD death or nonfatal myocardial infarction) in a prospective population-based study of NIDDM patients. RESEARCH DESIGN AND METHODS Our study is based on the 7-year follow-up cohort of 1,059 NIDDM patients in east and west Finland. Classification of retinopathic changes was based on clinical examination of fundi, and the findings were classified to three categories according to the status of the worse eye: no retinopathic changes, background retinopathy, and proliferative retinopathy. RESULTS During the 7-year follow-up, 255 (24%) patients developed serious CHD event. In patients with proliferative retinopathy at baseline, the risk of CHD events during the follow-up was statistically significantly higher compared with patients without retinopathic changes (odds ratio [OR] 2.31, 95% CI 1.21–4.40). The association between proliferative retinopathy and CHD events remained significant when other cardiovascular risk factors were controlled for. CONCLUSIONS Proliferative retinopathy in NIDDM patients was associated with CHD events. Our findings suggest that retinopathy and CHD may have similar pathophysiological backgrounds.
Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice.
Authors: K Eichmann, A Coutinho, F Melchers
Journal: The Journal of Experimental Medicine (1977)

The absolute frequencies of B cells-producing A5A idiotype have been determined in vitro by limiting dilution analysis in a culture system in which every LPS-reactive B cell grows into a clone of IgM-secreting cells. Spleen cells from normal A/J mice contain 1 A5A-idiotype-producing B-cell precursor in 2.5 X 10(3) LPS-reactive B cells. Approximately a 10-20-fold increase in frequencies of precursor cells from antigen priming with Strep A-CHO (1 in 2.8 X 10(2)) or from sensitization with IgG1 anti-A5A idiotype (1 in 1.3 X 10(2)). Injection of IgG2 anti-A5A idiotype which has been shown to suppress A5A idiotype in vivo results in only a marginal and maybe insignificant decrease in precursor frequencies (1 in 6.7 X 10(3)). On the other hand, priming does not result in a detectable qualitative difference in the specific precursor cells, since each clone of B cells secretes 30 ng of A5A-bearing Ig within 8 days of culture, regardless of being unprimed or primed. Nearly half of all A5A idiotype-producing clones, both from unprimed as well as from primed mice, show antigen specificity in binding A-CHO. Priming by antigen, therefore, also results in a 10-fold increase in the frequency of idiotype positive B cells without antigen specificity. This result is a prediction of the network hypothesis.
Chylopericardium of neoplastic aetiology
Authors: J. Andrade Santiago, L. Robles, C. Casimiro, V. Casado, A. Ageitos, M. Domine, L. Estevez, J. Vicente, F. Lobo
Journal: Annals of Oncology (1998)

Here we present the case of a 30-year-old man diagnosed with a dysgerminoma with mediastinal involvement, who developed an isolated chylopericardium during treatment. The purpose of this paper is to review the etiology, diagnosis and new approaches to the treatment of chylopericardium.
Epidemiology and Cause-Specific Outcome of Hypertrophic Cardiomyopathy in Children
Authors: Steven D. Colan, Steven E. Lipshultz, April M. Lowe, Lynn A. Sleeper, Jane Messere, Gerald F. Cox, Paul R. Lurie, E. John Orav, Jeffrey A. Towbin
Journal: Circulation (2007)

Background— Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. Methods and Results— The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients &lt;18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. Conclusions— In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults.
Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS)
Authors: Joachim Schofer, Michael Schlüter, Anthony H Gershlick, William Wijns, Eulogio Garcia, Erick Schampaert, Günter Breithardt
Journal: The Lancet (2003)
Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy
Authors: Paul A. van der Zwaag, Ingrid A.W. van Rijsingen, Angeliki Asimaki, Jan D.H. Jongbloed, Dirk J. van Veldhuisen, Ans C.P. Wiesfeld, Moniek G.P.J. Cox, Laura T. van Lochem, Rudolf A. de Boer, Robert M.W. Hofstra, Imke Christiaans, Karin Y. van Spaendonck‐Zwarts, Ronald H. Lekanne dit Deprez, Daniel P. Judge, Hugh Calkins, Albert J.H. Suurmeijer, Richard N.W. Hauer, Jeffrey E. Saffitz, Arthur A.M. Wilde, Maarten P. van den Berg, J. Peter van Tintelen
Journal: European Journal of Heart Failure (2012)