tbuckley/cabot-search huggingface dataset:
Functional respiratory imaging to predict post-operative FEV1 after lobectomy/pneumonectomy
Authors: Wim Vos, Annelies Janssens, Cedric Van Holsbeke, Glenn Leemans, Jan De Backer, Wilfried De Backer, Paul Van Schil, Jan van Meerbeeck
Journal: European Respiratory Journal (2014)

Rationale   Current ACCP guidelines (Chest 2007) recommend usage of segment count and perfusion scintigraphy method for calculating post-operative FEV1 (poFEV1) in patients undergoing lob/pneumonectomy, respectively. In this trial, functional respiratory imaging (FRI) is evaluated for calculating poFEV1.   Methods   23 pts (14 analyzed/9 dropouts) were included. All patients underwent spirometry, perfusion scanning, and HRCT scans at RV and TLC. Post-surgery tests were acquired after recovery and before starting adjuvant therapy. FRI analysis provided regional expansion (EXP) and resistance (iRaw, before and after virtual resection). poFEV1 was predicted using ACCP formulas and (for FRI):   Results    Conclusions   In contrast with ACCP, FRI predicted and measured poFEV1 are not significantly different. RMSE of FRI method is 43% smaller than ACCP, and is lower than the minimally important changes in FEV1 (323 ml, Respiratory Medicine 2013). Also, the slope of the linear fit from the FRI prediction is very close to 1, indicating that the model is very well predicting reality. FRI seems to be a better tool to predict poFEV1 as compared to ACCP.  This study was funded by IWT.
Fixed vs Variable Costs of Hospital Care—Reply
Authors: Rebecca R. Roberts
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 127: Overexpression of neurotrophic tyrosine receptor kinases (NTRKs) as a potential therapeutic target for cancer
Authors: Ge (Gina) Wei, Nicholas Cam, Roopal Patel, Robert Shoemaker, Robert Wild, Gang Li
Journal: Cancer Research (2015)

Abstract Neurotrophic tyrosine receptor kinases (NTRKs), or Tropomyosin receptor kinases (Trks), belong to a family of tyrosine kinases that regulate synaptic strength and plasticity during neural development. Deregulated kinase activity of Trk family members due to chromosomal rearrangements, gene mutations, splice variants and overexpression has been shown to be associated with cancer cell proliferation, survival, invasion and chemo-resistance in a number of cancer types. For example, chromosomal rearrangements involving NTRK1-3 have been reported in lung, colorectal, papillary thyroid, glioblastoma, melanoma and other cancers, and have been demonstrated to function as oncogenic drivers in these tumors. Moreover, overexpression of TrkA, TrkB and/or their corresponding ligands has been observed in a number of solid tumors such as breast, lung, prostate and pancreatic cancers. However, the functional implication of Trk overexpression has not been well defined or fully explored as a potential therapeutic strategy. To characterize the expression, signaling and function of full-length Trks in cancer, a series of stable cell lines with full-length NTRK genes were established. The engineered cell lines were characterized for Trk expression, Trk phosphorylation and their response to ligand stimulation. Moreover, cell proliferation, cell transformation and growth inhibition by RXDX-101, a clinical stage, potent and selective pan-Trk inhibitor, were assessed. Trk downstream effectors, such as PLCγ, AKT and ERK, were also evaluated in the relevant settings. Furthermore, several cancer cell lines with endogenous overexpression of full-length Trks or rearranged Trks were identified and functionally characterized. Our studies highlight the similarities and differences between Trk rearrangement and overexpression as potential oncogenic drivers and support further exploration of RXDX-101 in cancers with Trk overexpression. Citation Format: Ge (Gina) Wei, Nicholas Cam, Roopal Patel, Robert Shoemaker, Robert Wild, Gang Li. Overexpression of neurotrophic tyrosine receptor kinases (NTRKs) as a potential therapeutic target for cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 127. doi:10.1158/1538-7445.AM2015-127
Clinical governance in primary care: Knowledge and information for clinical governance
Authors: A. McColl
Journal: BMJ (2000)

This is the last of five articles 

The new requirements of clinical governance are a challenge for everyone working in the NHS. If the quality of health care is to be improved, existing knowledge about effective clinical and organisational practice must be applied and new information to monitor and evaluate care must be generated and interpreted.

Within individual general practices and primary care teams, all staff will have a role in obtaining and using information for clinical governance—whether for maintaining chronic disease registers, promoting evidence based practice, improving the organisation of services, or reporting on the outcomes of care. In primary care groups and trusts, there is greater emphasis on improving the health of the population. This requires the collection and aggregation of information across practices to assess health needs, reduce inequalities, and monitor the quality of care in comparison to agreed standards.

In this paper, we discuss the additional knowledge that will be needed by all staff working in primary care and the challenges faced by leaders of primary care groups and trusts. We suggest where they can find relevant information. Everyone in primary care needs to be familiar with these sources if clinical governance is to succeed as a way to improve the quality of health care.

#### Summary points

Everyone in primary care needs to be familiar with the requirements of clinical governance if it is to succeed as a way to improve the quality of care

Producing, collecting, and analysing primary care information is difficult, but some practices have already overcome these barriers

Individuals and primary care group and trust leaders can do much to promote clinical governance, but problems remain

Clinical governance has highlighted the need for additional knowledge and information on determinants of population health

Many problems exist with producing, collecting, and analysing the necessary information; we …
Collateral sensitivity to methylmercaptopurine riboside of 6-mercaptopurine and 6-thioguanine resistant human acute T-lymphoblastic leukemia cell lines
Authors: Freidoun Albertioni, Kambiz Fotoohi, Malin Lindqvist, Sayma Rahman, Curt Peterson
Journal: Cancer Research (2004)

2961   6-Mercaptopurine (6-MP), 6-thioguanine (6-TG) and azathioprine are antimetabolites, which interfere with nucleic acid metabolism. They have antiproliferative and immunosuppressive properties and are part of many protocols in the treatment of malignant hematological disorders and after organ transplantation as well as in autoimmune diseases. However, mechanisms of action and resistance to these analogues are not yet clearly established. In order to understand of these mechanisms, we developed two resistant cell lines derived from a human T-lymphocytic leukemic cell line (Molt-4). 6-MP resistant cell line was >20-fold resistance to 6-MP, and in the case of 6-TG-cells the resistance to 6-TG was >30-fold in comparison with parental Molt-4 wild types. Both resistant cell lines showed about 10-fold decreased transport of 6-MP. Decreased accumulation of metabolites of 6-MP after 24h exposure to 6-MP was observed in both resistant cell lines, 20 and 50-fold lower in Molt-4/6-MP and Molt-4/6-TG sub-lines, respectively. Thiopurine methyltransferase (TPMT) catalyzes S-methylation of thiopurines and mRNA levels analyzed by real time quantitative PCR method showed no difference in TPMT expression as compared to the wild type cells. Hypoxanthine-guanine phosphoribosyltransferase activity in both resistant cells was lower, 439±54 and 408±41 pmol/mg protein/min in Molt-4/6-MP and Molt-4/6-TG sub-lines, respectively, compared to 643±65 pmol/mg protein/min of their parental cells. Interestingly, we found a collateral sensitivity to 6-methylmercaptopurine ribose and this was not due to elevated levels in adenosine kinase activity in resistant cell lines. This study indicated some provoked mechanisms of resistance to 6-MP and 6-TG in malignant cells, which can be bypassed by methylated metabolites of 6-MP. Our results also clearly indicate that some methylated metabolites should be considered as potential contributors to the effect of thiopurines.
A retrospective study into the prevalence of herpes simplex virus 1&amp;2 in female patients tested for Chlamydia trachomatis and/or Neisseria gonorrhoeae using vaginal swabs
Authors: A. Vahidnia, I. Op den Buijs, R. Roymans, H. Bliekendaal, J. van de Bovenkamp
Journal: Clinical Microbiology and Infection (2012)
Catharina Hooft With Her Nurse
Authors: M. Therese Southgate
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Diseases Peculiar to Civilized Man: Clinical Management and Surgical Treatment
Authors: George Crile, Amy Rowland
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3473: Down Regulation of Class I Histone Deacetylase in the Deficit of Cardiac Lineage Protein-1 Protects Heart from Ischemia Reperfusion Injury
Authors: Narasimman Gurusamy, Istvan Lekli, Eduardo Mascareno, M.A.Q. Siddiqui, Dipak K Das
Journal: Circulation (2008)

Cardiac lineage protein-1 (CLP-1), the mouse homologue of human Hexim1 protein, exerts inhibitory control over transcriptional elongation factor-b (P-TEFb) of RNA transcript elongation, and this inhibitory control of CLP-1 over P-TEFb is released under hypertrophic stimuli. Histone deacetylases (HDACs) are known to repress the transcription of genes via maintaining compact chromatin structure. Reports have shown that class II HDACs repress the growth of myocytes, whereas, class I HDACs promotes cellular growth. A recent report suggests that inhibition of HDACs can protect the heart from ischemic injury. In the present study, we determined the role of HDACs under the down regulation of CLP-1 in ischemia reperfusion (I/R) injury and in the regulation of cardiac hypertrophy. Our results showed that the nuclear expression of class I HDACs such as HDAC1, HADC2 and HDAC3 were reduced in CLP +/− mice compared to CLP +/+ mice. In contrast to class I HDACs, class II HDACs such as HDAC4, HDAC5 and HDAC7 were not significantly altered between CLP +/− and CLP +/+ mice. When the isolated mice hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion, cardiac functional parameters like aortic flow, left ventricular developed pressure and left ventricular dp/dt were significantly improved in CLP +/− mice compared to CLP +/+ mice. The percentage of myocardial infarct size after I/R injury was significantly less in CLP +/− mice than CLP +/+ mice. The occurrence of cardiac hypertrophy in CLP +/− mice was confirmed by the increased expression of fetal gene expression markers such as β-myosin heavy chain, atrial natriuretic factor and α-skeletal actin. The nuclear expression of HDAC1, HDAC2 and HDAC3 were reduced after I/R injury in CLP +/− mice compared to control CLP +/− mice. However, HDAC4, HDAC5 and HDAC7 were not altered after I/R injury in CLP +/− mice. In conclusion, our results suggest that the down regulation of class I HDACs but not class II HDACs in CLP-1 +/−mice could cause cardioprotection against I/R injury, and may also responsible for the elicitation of cardiac hypertrophy.
Original article: Atopy and asthma in rural Poland: a paradigm for the emergence of childhood respiratory allergies in Europe
Authors: B. Sozanska, S. J. MacNeill, M. Kajderowicz‐Kowalik, H. Danielewicz, M. Wheatley, A. J. Newman Taylor, A. Boznanski, P. Cullinan
Journal: Allergy (2007)

Background: We hypothesized that, in south‐west Poland, a ‘rural’ protective effect on atopy and respiratory allergies would be most pronounced among children but that at all ages would be stronger among those with a rural background. Methods: A cross‐sectional survey of the inhabitants (age &gt;5 years, n = 1657) of Sobotka, a town of 4000 people in south‐west Poland: and seven neighbouring villages. We measured and analysed responses to skin prick tests (atopy) and to a standard questionnaire (asthma and hayfever). Results: Atopy was very uncommon (7%) among villagers at all ages but not among townspeople (20%, P &lt; 0.001); the differences were most marked among those aged under 40 years. Asthma and hayfever were similarly distributed, both being very rare among villagers. The differences appear to be explained by the cohort effect of a communal move away from rural life. This interpretation is supported by an ecological correlation ( ρ = −0.59) between rural populations and childhood wheeze in 22 European countries. Conclusion: The very striking differences in the prevalence of allergy between these two neighbouring communities of central Europe reflect the pan‐continental population movements that may have been responsible for the emergence of childhood allergies in Europe.
Correction of CFTR malfunction and stimulation of Ca<sup>2+</sup> -activated Cl<sup>−</sup> channels restore HCO 3− secretion in cystic fibrosis bile ductular cells
Authors: Ákos Zsembery, Wolfgang Jessner, Gerlinde Sitter, Carlo Spirlí, Mario Strazzabosco, Jürg Graf
Journal: Hepatology (2002)

In view of the occurrence of hepatobiliary disorders in cystic fibrosis (CF) this study addresses the role of the cystic fibrosis transmembrane conductance regulator (CFTR) and of Ca(2+)-activated Cl(-) channels in promoting HCO3- secretion in bile ductular cells. Human cholangiocytes were isolated from control livers and from 1 patient with CF (DeltaF508/G542X mutations). Single channel and whole cell currents were analyzed by patch clamp techniques, and HCO3- secretion was determined by fluorometric analysis of the rate of recovery of intracellular pH following alkaline loading. In control cholangiocytes, both cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) catalytic subunit, activated CFTR Cl(-) channels that exhibited a nonrectifying conductance of 8 pS and appeared in clusters. Activation of Cl(-) current by cAMP was associated with an increase in the rate of HCO3- secretion. The basal rate of HCO3- secretion was lower in CF than in control cholangiocytes. In both control and CF cholangiocytes, raising intracellular Ca(2+) concentrations with ionomycin led to a parallel activation of Cl(-) current and HCO3- secretion. Consistent with reports that premature stop codon mutations (class I; e.g., G542X) can be read over by treatment with aminoglycoside antibiotics, exposure of CF cholangiocytes to gentamicin restored activation by cAMP of Cl(-) current and HCO3- secretion. The observation that activation of Ca(2+)-dependent Cl(-) channels can substitute for cystic fibrosis transmembrane conductance regulator (CFTR) in supporting HCO3- secretion and the efficacy of gentamicin in restoring CFTR function and HCO3- secretion in class I mutations are of potential clinical interest.
Abstract 12967: Efficacy of Combining Assessment of Right Ventricular Function and Right Atrial Remodeling as Prognostic Factor in Patients With Pulmonary Hypertension
Authors: Yuko Fukuda, Hidekazu Tanaka, Yoshiki Motoji, Keiko Ryo, Hiroki Matsuzoe, Keiko Hatazawa, Yutaka Hatani, Kumiko Dokuni, Hiromi Toki, Hiroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Takuma Sawa, Yasuhide Mochizuki, Kazuhiro Tatsumi, Kensuke Matsumoto, Noriaki Emoto, Ken-ichi Hirata
Journal: Circulation (2014)

Background: Since survival of patients with pulmonary hypertension (PH) is closely related to right ventricular (RV) function, assessment of RV function is important for patients with PH. Right atrial (RA) area and/or RA pressure have also been reported to serve as prognostic predictors for adverse outcomes for in PH patient. Accordingly, we tested the hypothesis that the addition of RA remodeling to RV function enhances the capability of the latter to predict long-term outcome for PH patients. Methods: We studied 82 PH patients, all of whom underwent echocardiography and right heart catheterization. RV function was calculated by averaging the three regional peak speckle-tracking longitudinal strains from RV free wall (RV-free). RA remodeling was assessed as the RA area traced planimetrically at end-systole. Pre-defined cutoffs for RV dysfunction and RA remodeling were RV-free≤19.4% and RA area of &gt;18cm2, respectively. Long-term unfavorable outcome events were tracked for 2.0 years. Results: RA area correlated with mean RA pressure (r=0.62, p&lt;0.001), as well as with tricuspid E/E’ (r=0.38, p=0.001). However, RA area with RV restrictive filling was significantly larger than with others (all p&lt;0.05). Kaplan-Meier analysis revealed that patients with RV-free ≤19.4% had worse long-term outcomes than those with RV-free &gt;19.4% (log-rank p=0.01), as did patients with RA area&gt;18cm2 compared with those with RA area ≤18cm2 (log-rank p&lt;0.05). For sequential Cox models, a model based on hemodynamic parameters of RV performance (χ2 =3.11) was improved by addition of brain natriuretic peptide, World Health Organization functional class (χ2 =9.24; p&lt;0.05), and RV-free (χ2 =17.11; p=0.005), and further improved by addition of RA area (χ2 =21.36, p&lt;0.05). Conclusions: The combined assessment of RV function and RA remodeling results in more accurate prediction of long-term outcome, and may well have clinical implications for better management of PH patients.
KANK deficiency leads to podocyte dysfunction and nephrotic syndrome
Authors: Heon Yung Gee, Fujian Zhang, Shazia Ashraf, Stefan Kohl, Carolin E. Sadowski, Virginia Vega-Warner, Weibin Zhou, Svjetlana Lovric, Humphrey Fang, Margaret Nettleton, Jun-yi Zhu, Julia Hoefele, Lutz T. Weber, Ludmila Podracka, Andrej Boor, Henry Fehrenbach, Jeffrey W. Innis, Joseph Washburn, Shawn Levy, Richard P. Lifton, Edgar A. Otto, Zhe Han, Friedhelm Hildebrandt
Journal: Journal of Clinical Investigation (2015)

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive renal function decline and affects millions of people. In a recent study, 30% of SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different genes. Here, using homozygosity mapping and whole-exome sequencing, we identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. In an independent functional genetic screen of Drosophila cardiac nephrocytes, which are equivalents of mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is essential for nephrocyte function. RNAi-mediated knockdown of dKank in nephrocytes disrupted slit diaphragm filtration structures and lacuna channel structures. In rats, KANK1, KANK2, and KANK4 all localized to podocytes in glomeruli, and KANK1 partially colocalized with synaptopodin. Knockdown of kank2 in zebrafish recapitulated a nephrotic syndrome phenotype, resulting in proteinuria and podocyte foot process effacement. In rat glomeruli and cultured human podocytes, KANK2 interacted with ARHGDIA, a known regulator of RHO GTPases in podocytes that is dysfunctional in some types of nephrotic syndrome. Knockdown of KANK2 in cultured podocytes increased active GTP-bound RHOA and decreased migration. Together, these data suggest that KANK family genes play evolutionarily conserved roles in podocyte function, likely through regulating RHO GTPase signaling.