tbuckley/cabot-search huggingface dataset:
Effect of body mass index on outcomes in biliary tract cancer.
Authors: Mark Doherty, Mairead Geraldine McNamara, Priya Aneja, Lisa W Le, Sean P. Cleary, Anne M. Horgan, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2015)

399 Background: Biliary Tract Cancer (BTC) is associated with poor outcomes, and prognostic factors are not well documented. Body Mass Index (BMI) has been shown to correlate with survival in colon, breast, lung and prostate cancer. The effect of BMI on survival in patients with BTC is unclear. Greater understanding of prognostic markers in BTC can help with treatment decisions. Methods: Patients treated for BTC in Princess Margaret Cancer Centre between 06/1987 and 08/2014 were included for analysis. Data were collected on clinicopathologic features, BMI, and survival. Patients were separated into two groups by resectability: definitive surgery (DS) or no definitive surgery (NDS). Multivariable proportional hazards regression was used to investigate the association between variables and overall survival (OS) for DS and NDS groups. Results: 902 patients (461 DS, 441 NDS) were included, with median BMI 25.7 (range 15.5-48.7). Median OS was 48.1 months in DS patients and 11 months in NDS patients. 244 NDS patients received palliative chemotherapy (55%). BMI was prognostic for OS in DS patients. In univariate analysis, DS patients with BMI &lt;25 had poorer outcomes than those with BMI ≥25 [HR 1.40, 95% CI 1.08-1.82, p=0.01]. In multivariable analysis, the effect of BMI in DS patients remained significant: BMI &lt;25 was associated with poorer OS [HR 1.36, 95%CI 1.03-1.81, p=0.03]. No significant differences were found in OS in NDS patients according to BMI by univariate [HR 1.04, 95%CI 0.83-1.29, p=0.74] or multivariable analysis. Prognostic factors by multivariable analysis are summarized in the Table. Conclusions: For patients undergoing definitive surgery for BTC, BMI &lt;25 was a poor prognostic marker independent of other known prognostic variables. Other prognostic variables from our dataset match reported literature. This study is limited by its retrospective nature, however BMI may aid patient risk stratification after DS for BTC. [Table: see text]
Hunt dismisses<i>BMJ</i>editor’s claims that he misused weekend mortality data
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

England’s health secretary, Jeremy Hunt, has dismissed concerns raised by The BMJ ’s editor in chief that he misrepresented research published in the journal to justify his drive to implement seven day NHS services for patients.

Fiona Godlee wrote to Hunt in October about an article in The BMJ that found that 11 000 more people die each year within 30 days of admission to hospital on a Friday, Saturday, Sunday, or Monday than on other days of the week.1 2 She said that Hunt had repeatedly told MPs and the public that these excess deaths were due to poor staffing at weekends, despite the article offering no explanation for the excess mortality.

“This clearly implies that you believe these …
Abstract 15839: Effect of Serotonin Neuron Depletion on Arterial Blood Pressure Regulation in Young Rats
Authors: Jennifer Magnusson, Kevin Cummings
Journal: Circulation (2014)

Infants dying of Sudden Infant Death Syndrome (SIDS) have reduced brainstem serotonin (5-hydroxytryptamine, 5-HT) where some cases die following episodes of severe bradycardia and hypoxemia. The specific role of central 5-HT in resting arterial blood pressure (BP) and on baroreflex sensitivity during neonatal life has not been studied. In adult animals, systemic depletion of 5-HT increases BP with no effect on heart rate (HR) and reduces the sensitivity of the baroreflex. Other studies have also shown that a loss of central 5-HT beginning in embryogenesis reduces resting BP and HR in adulthood. Based on these reports, we hypothesized that loss of brainstem 5-HT neurons in the neonatal period would reduce baseline BP and HR as well as reduce baroreflex gain. To test this, we utilized 3-week old Sprague Dawley rats treated centrally with 5,7-dihydroxytryptamine (5,7-DHT, n=4; ~120 ug in saline, i.c.v.), a chemical that is toxic to serotonergic neurons. Littermate controls were injected with saline (CTRL, n=5, ~3ul, i.c.v.). We measured BP with a femoral artery catheter. HR was derived from BP. Following a recovery period, we measured resting variables for 15 minutes and then injected phenylephrine (PE; 3mg/kg s.c.) followed by sodium nitroprusside (SNP; 2.5mg/kg s.c.), separated by 15 minutes, to induce pressor or depressor responses, respectively. For both responses, baroreflex gain was calculated as the [[Unable to Display Character: &amp;#8710;]]HR at the maximum [[Unable to Display Character: &amp;#8710;]]BP following drug injection. We found that a loss of 5-HT neurons did not alter baseline BP (p&gt;0.05) but did reduce baseline HR when compared to control littermates (p&lt;0.02). 5-HT neuron deficiency tended to reduce baroreflex gain in response to PE (CTRL: -2.756 ± 0.483 beats/mmHg; 5,7-DHT: -1.499 ± 0.348 beats/mmHg; p=0.058), but not SNP (CTRL: -2.408 ± 0.351 beats/mmHg; 5,7-DHT: -3.316 ± 1.214 beats/mmHg; p&gt;0.05). Our data indicate that brainstem 5-HT maintains resting HR, and is involved in baroreflex control of HR in response to hypertensive stimuli. Reduced brainstem 5-HT may predispose an infant to SIDS via altered autonomic control of BP and HR. The role of 5-HT in BP regulation during hypoxic conditions remains to be elucidated.
Extending T-cell transfer therapy to melanoma and oral squamous carcinoma.
Authors: N. Junker, M. H. Andersen, T. Zeeberg, P. thor Straten, I. M. Svane
Journal: Journal of Clinical Oncology (2010)

e13071 Background: T-cell based immune therapy in melanoma has shown markedly objective clinical responses in a single-center study at the NIH. In order to extend the treatment to other centers and investigate application to other histologies, we compare the characteristics of tumor infiltrating lymphocytes (TIL) expanded from two groups of cancer patients: malignant melanoma (MM) and squamous cell carcinoma (SCC) of the oral cavity. Methods: Expanded TIL cultures were examined for T-cell phenotype subsets using FACS and clonality by TCRBV gene segment semi quantification with PCR. Tumor reactivity was assessed by INFγ Elispot, CD107a expression by FACS and Cr51 release assay. To identify possible Tumor Associated Antigen (TAA) specific populations TIL were screened for a panel of epitopes from the known TAA Survivin, Telomerase, Bcl-x, Bcl-2, Ny-ESO 1, MART-1, and IDO. Results: Preclinical part: In both patient cohorts TIL were expanded within 5 weeks in 80% of the patients. Cultures comprised an oligoclonal repertoire of T effector memory cells (TEM). Tumor activity against HLA-A matched cell lines showed varying responses regarding frequency and magnitude; activity directed against autologous tumor cells were characterized by a strikingly high frequency of INFg producing cells and/or distinct CD107a+ populations with tumorlytic capacity. Peptide screening revealed that specific TIL cultures were not correlated with tumor activity although the TAA mRNA were identified in the tumor cell lines. Clinical part: TIL were expanded in 5 of 5 (100%) MM patients included. Kinetics, phenotypes, and preliminary activity data resemble preclinical results. Three patients have completed treatment and two have been evaluated by CT scan (1 SD and 1 PR). Immune monitoring is pending. Conclusions: Results on ex vivo expanding TEM from both MM and SCC show comparable outcome and demonstrates shared activity against several common TAA. A clinical pilot trial is ongoing in MM patients with metastatic disease and a pilot trial in patients with primary SCC stage T3/T4 will start in 2010. No significant financial relationships to disclose.
PTH-075 The effect of storage conditions on the stability of faecal calprotectin
Authors: S Whitehead, M Brookes, J French, C Ford, R Gama
Journal: Gut (2015)

<h3>Introduction</h3> Faecal calprotectin (f-Cp) is a sensitive non-invasive marker of intestinal inflammation used to help distinguish between inflammatory bowel disease (IBD) and functional bowel disorders such as IBS, thereby reducing the number of unnecessary endoscopic and radiological investigations in patients presenting with chronic diarrhoea. It has previously been reported that calprotectin is stable in faeces for up to seven days at room temperature (RT). A nationwide study was undertaken via the UK NEQAS Faecal Markers of Inflammation external quality assessment (EQA) programme in order to further investigate the stability of f-Cp. <h3>Method</h3> Complete 24 h stool collections were provided by three IBD patients. Each stool was homogenised and split into six portions, each of which was stored under different conditions: i) RT (∼20˚C) for seven days; ii) RT for 14 days; 4°C for seven days; 4°C for 14 days and; two portions immediately frozen at –40°C. Following storage, the portions not already in the freezer were frozen at –40°C. Sub-aliquots of each of the six portions from each patient were dispatched to the participants of the UK NEQAS Faecal Markers of Inflammation EQA scheme for analysis. <h3>Results</h3> Forty-four scheme participants returned results. Mean f-Cp concentrations in the baseline specimens were 9.3–95.4 µg/g [patient 1], 204–449 µg/g [patient 2] and 5.5–66.4 µg/g [patient 3]. F-Cp levels decreased over the period of 14 days when the stool samples were stored at RT but to varying degrees depending upon the initial concentration and the assay used for analysis. For the most severely-affected method (Thermo Fisher ELiA) f-Cp levels decreased by ∼50% following storage at RT for 14 days in the specimen from patient 2. No decrease was observed for the same assay at lower f-Cp concentrations [patients 1 and 3] under the same conditions. No effect of storage was observed at either RT or 4°C for the users of the Buhlmann, Immundiagnostik, Calpro (ELISA) and Buhlmann Quantum Blue assays at lower f-Cp concentrations [Patients 1 and 3]. Storage for 14 days at 4°C had no significant effect for the Buhlmann ELISA, Calpro ELISA and Quantum Blue users at higher f-Cp concentrations (Patient 2). A decrease of ∼10% was observed for the Thermo Fisher ELiA and Immundiagnostik ELISA assays stored under the same conditions. <h3>Conclusion</h3> The conditions under which stool samples are transported and stored prior to calprotectin analysis can affect the results obtained in the laboratory depending upon the baseline f-Cp level and the particular assay being used for analysis. Our data also further highlights the between-assay variability that exists amongst f-Cp kits. <h3>Disclosure of interest</h3> None Declared.
Virus of Avian Myeloblastosis. XIX. Protein, Polysaccharide, Lipide, and Nucleic Acid of Myeloblasts and Cytidine Uptake <italic>In Vitro</italic><xref ref-type="fn" rid="fn1">2</xref>
Authors: J R SOMMER, D WEINSTEIN, C BECKER, G S BEAUDREAU, D BEARD, J W BEARD
Journal: JNCI Journal of the National Cancer Institute (1962)
Abstract 262: Knockout of Type VI Collagen Preserves Mitochondrial Structure and Function Following Myocardial Infarction
Authors: J G Meszaros, Daniel J Luther, Patrick T Kang, Yeong-Renn Chen, R Lance Miller, Paolo Bonaldo, William M Chilian, Charles K Thodeti
Journal: Circulation Research (2015)

Cardiac remodeling is a dynamic process that is accelerated after myocardial infarction (MI), and the traditional focus of key extracellular matrix proteins that mediate remodeling has been on the fibrillar types I and III collagen. We have previously reported that knockout mice of the lesser-known, non-fibrillar collagen VI (Col6-/-) are protected from MI injury as evidenced by significantly reduced infarct size, fibrosis and apoptosis leading to preserved long-term cardiac function. Determining the mechanisms underlying this cardioprotection is the goal of this study. Interestingly, the Col6-/- mice are a model for Bethlam Myopathy, a rare skeletal muscular dystrophy that is characterized by mitochondrial dysfunction leading to premature apoptosis of skeletal myocytes. We hypothesized that alterations in mitochondrial structure and function in the myocardium of Col6-/- mice may play key mechanistic roles responses to ischemic injury. Mitochondrial morphology was visualized by transmission electron microscopy to compare pre- and post-MI changes. Mitochondria from uninjured Col6-/- LV tissue had similar morphology as WT, and at 3 days post-MI the mitochondrial morphology was similarly compromised in both WT and Col6-/- mice. However, at 14 days post-MI the Col6-/- mitochondria were less swollen (43 ± 5.1% decrease in overall volume) and displayed improved orientation/organization over WT (continuous strands). We measured basal O2 consumption and 24 hours post-MI in mitochondria isolated from the infarcted zones of both genotypes. The respiratory control index (RCI) of the Col6-/- mitochondria was lower in the basal, uninjured hearts (7.2 ± 0.9 in WT vs. 4.9 ± 0.6 in Col6-/-). However, the RCI of mitochondria in the infarcted region of Col6-/- hearts at 24 hours post-MI declined less than WT (post-MI values of 2.7 ± 0.5 in WT vs. 2.8 ± 0.7 in Col6-/-) . These data indicate that Col6-/- mice have preserved mitochondrial morphology and a smaller decline in respiration following MI, which may represent a novel homeostatic mechanism underlying protection from ischemic injury in the Col6-/- heart.
Bioactive Glass for Large Bone Repair
Authors: Weitao Jia, Grace Y. Lau, Wenhai Huang, Changqing Zhang, Antoni P. Tomsia, Qiang Fu
Journal: Advanced Healthcare Materials (2015)

There has been an ongoing quest for new biomedical materials for the repair and regeneration of large segmental bone defects caused by disease or trauma. Autologous bone graft (ABG) remains the gold standard for bone repair despite their limited supply and donor-site morbidity. The current tissue engineering approach with synthetically derived bone grafts requires a bioactive ceramic or polymeric scaffold loaded with growth factors for osteoinduction and angiogenesis, and bone marrow stromal cells (BMSCs) for osteogenic properties. Unfortunately, this approach has serious drawbacks: the low mechanical strength of scaffolds, the high cost of growth factors, and a lack of optimal strategies for growth-factor delivery. Here, it is shown that, for the first time, a synthetic material alone can repair large bone defects as efficiently as the gold standard ABG. Through the use of strong and resorbable bioactive glass scaffolds, complete bone healing, and defect bridging can be achieved in a rabbit femur segmental defect model without growth factors or BMSCs. New bone and blood vessel formation, in both inner and peripheral scaffolds, demonstrates the excellent osteoinductive and osteogenic properties of these scaffolds similar as ABG.
Adiposity but not severity of obstructive sleep-disordered breathing correlates with morning plasma TNF-α levels in Greek children
Authors: Vasiliki Theologi, Vasiliki Varlami, Georgia Malakasioti, Irene Tsilioni, Konstantinos Chaidas, Emmanouel Alexopoulos, Athanasios Kaditis, Konstantinos Gourgoulianis
Journal: European Respiratory Journal (2012)

Background:  Sleep-disordered breathing (SDB) has been associated with increased frequency of excessive daytime sleepiness (EDS). In adults, increased TNF-α plasma levels probably mediate this association, but conflicting results have been reported in children. We hypothesized that: i) the higher the severity of SDB in childhood, the higher the frequency of EDS and morning TNF-α plasma levels; ii) subjects with high TNF-α levels are more likely to have EDS.  Methods:  Children without and with snoring underwent polysomnography, EDS was determined by parental response to specific questions and TNF-α morning plasma levels were measured.  Results:  Children with moderate-to-severe SDB [n=24; 5.7±2 yo; apnea-hypopnea index (AHI) 6-23.5 episodes/hour), but not participants with mild SDB (n=22; 6±2.5 yo; AHI 1.1-4.7) were at significantly higher risk for EDS compared to controls without snoring (n=26; 6.2±2.3 yo; AHI 0.2-1) [OR (95% CI): 7 (1.6-30.9) and 3 (0.6-13.8), respectively]. The 3 groups did not differ regarding TNF-α levels (0.63±0.2 vs. 0.65±0.2 vs. 0.57±0.13 pg/mL; p>0.05). TNF-α levels were associated significantly with body mass index z-score (p 2  nadir (p>0.05). Subjects with high TNF-α levels (>0.57 pg/mL i.e. median in controls) were not at higher risk for EDS compared to those with low levels [OR (95% CI) adjusted for obesity: 1.9 (0.6-6.4)].  Conclusions:  Increasing severity of SDB is related to increasing frequency of EDS but not with elevated TNF-α plasma concentrations which are positively correlated with the degree of adiposity. Children with high TNF-α levels are not at increased risk for EDS.
Pulmonary nodules in the initial evaluation of pediatric patients with bone and soft-tissue sarcoma
Authors: M. J. Absalon, M. B. McCarville, T. Liu, A. Cain, F. Navid
Journal: Journal of Clinical Oncology (2004)

8549 Background: The radiographic detection of the small pulmonary nodule during the initial metastatic workup of the pediatric oncology patient presents a significant clinical dilemma. The outcome of the decision of whether the nodule is malignant or benign often affects decisions regarding treatment, protocol enrollment, and assessment of prognosis. The incidence of this clinical situation in the era of helical computed tomography (CT) is unknown and practice guidelines pertaining to the pretherapy evaluation of the small pulmonary nodule are lacking. Methods: We performed a retrospective review of initial lung CT reports of 181 consecutive pediatric patients referred to our hospital for the primary treatment of bone or soft-tissue sarcomas from 1999–2003. The frequency, number, size, location and characteristics of nodules were documented. These lung CT findings were correlated with the histologic conclusions from lung biopsy and/or clinical outcome. Results: : Pulmonary nodules were found on CT evaluation in 57 (31%) of patients. In approximately half of these patients, the largest nodule was less than or equal to 10 mm diameter. Twenty-two patients were coded as having pulmonary metastatic disease by the primary oncologist. Four of these patients underwent a lung biopsy to histologically confirm pulmonary metastasis. The remaining 18 patients were determined to have pulmonary metastasis without further intervention. Of the 35 patients who were coded as not having pulmonary metastasis, 12 had lung biopsies showing normal lung or granulomatous disease. Patients with osteosarcoma were more likely to have an invasive procedure (p=0.010), but size, number of nodules, and presence of calcifications were not predicative (p>0.36) of those going to biopsy. Conclusions: Our findings confirm that the finding of a small pulmonary nodule during the initial workup of pediatric patients with sarcoma presents a common clinical scenario and highlights the need for a systematic approach to its evaluation. A proposal to study this problem will be offered. No significant financial relationships to disclose.
Abstract P224: Whole Genome Sequencing of 8 Indian Asians
Authors: John Chambers, Abtehale Al-Hussaini, Tsung Tan, Joban Sehmi, Mark McCarthy, James Scott, Paul Elliott, Jaspal S Kooner
Journal: Circulation (2012)

Background The genetic architecture and variation of Indian Asians, who represent one quarter of the world's population, has not been described. This represents an important obstacle to the identification of the genetic factors contributing to diseases encountered in Indian Asians. Aim To identify and describe the patterns of genetic variation in Indian Asians. Methods We carried out high-depth whole genome sequencing of 8 Indian Asian men, using paired-end and mate-pair libraries, and Illumina GAII x instruments. We used Stampy, with BWA as a pre-mapper, to align reads to Genome Reference Consortium build 37 of the human genome (GRCh37). We used GATK and SAMtools to call SNPs and indels; accepting genetic variants called by both algorithms as confirmed. Results Mean coverage was 28.4x (range 13.9 to 32.5x); 99.8% of the mappable genome was covered by at least one read in each sample. We found 6,602,840 autosomal SNPs (mean 3,318,386 per person) of which 436,823 (6.6%) are novel (not in dbSNP132 or 1000G June 2011). The majority of novel SNPs were singletons (88% vs 20% for known SNPs). There were 50,585 novel SNPs present at least twice (ie MAF&gt;10%), and 2,174 novel SNPs predicted to affect protein coding. Amongst the novel cSNPs that are identified as pathogenic by SIFT or PolyPhen2, 145 are in genes linked by OMIM to human disease, including obesity ( FTO , UCP1 ), diabetes mellitus ( CDKAL1 , GCGR , HNF1B ), lipid metabolism ( APOB ), renal disease ( NPHP4, PKD1 ), hypertension ( NOS2 ), iron and B vitamin metabolism ( CUBN , TCN2, TF ), and susceptibility to malaria and leprosy ( CR1 , FCGR2A , NOS2, TLR1 ). There were 65,613 novel autosomal indels of which 35,097 are present at least twice, and 2,301 novel deletions &gt;100bp. We found that amongst the novel SNPs and indels discovered, &gt;50% are not in high LD (r 2 ≥0.8) with tagSNPs on available high-density microarrays Conclusions Our results reveal 502,436 new genetic variants amongst Indian Asians, including coding SNPs and indels in genes involved in atherosclerosis, carbohydrate and lipid metabolism, immunity and inflammation. The majority of novel variants are in low LD with standard commercial micro-arrays, indicating that these genome-wide arrays do not capture Indian Asian specific genetic variation. Our findings will inform the design of future studies to identify the genetic factors contributing to cardiovascular disease and other disorders that are more common amongst Indian Asians.
Targeted Drug Delivery: Liposome-Loaded Cell Backpacks (Adv. Healthcare Mater. 18/2015)
Authors: Roberta Polak, Rosanna M. Lim, Marisa M. Beppu, Ronaldo N. M. Pitombo, Robert E. Cohen, Michael F. Rubner
Journal: Advanced Healthcare Materials (2015)

Cellular backpacks are circular 7μm-wide polymer patches that can be adhered to the surface of living cells. The image shows backpacks containing liposomes loaded with the anticancer drug doxorubicin (red) attached to the surface of living monocytes. More details are provided on page 2832 by M.F. Rubner and co-workers.