tbuckley/cabot-search huggingface dataset:
P90 Catch - Community Access To Ct Chest
Authors: C. Moorcroft, G. Kamalatharen, S. Elliot, A. Walsham, A. Sharman, S. Taggart
Journal: Thorax (2014)

<h3>Introduction</h3> Rates of lung cancer diagnosis for two week wait (2WW) referrals are low although referrals are increasing. Many 2WW’s are potentially exposed to unnecessary anxiety as the referral requires the G. P. to inform the patient of the possibility of cancer. CATCH (<b>C</b>ommunity <b>A</b>ccess <b>T</b>o CT <b>Ch</b>est) is a new protocol of care that has been developed by the Salford lung cancer team in collaboration with the Salford C. C. G. whereby abnormal "low risk" CXR reports are communicated to G. P.s with instructions for them to request a CT scan, which is then fast tracked allowing rapid performance and reporting of the scan with appropriate advice to the GP. <h3>Methods</h3> A d-base was set up to capture the performance of CATCH from its introduction on 05.02.2014 to 05.07.2014. Demographic details were collected for dates of CXR, CXR report, CT request, CT report, relevant outcomes and 2WW activity for same time (2011–2014). Participating patients were interviewed by telephone using a structured questionnaire (supported by a postal questionnaire for non-responders). <h3>Results</h3> 53 patients underwent an abnormal CXR with advice to enter into the CATCH protocol and of these 7 bypassed CATCH having been referred directly into the 2WW system by their G. P.s. For the 46 patients completing CATCH, seven (15%) urgent 2WW referrals were recommended. In the remaining 39 patients, 28 required no follow up, 9 non-urgent referral to the chest clinic and 2 repeat community CXRs. Timelines for performance of CT scans were acceptable (see Table) and detected cancer in 5/46 (10.9%) and were normal in 8/46 (17.4%). 23–26 patients interviewed to date rated the service overall as either very good or excellent. During same points in 2011, 2012, 2013 and 2014 2WW numbers were 69, 84, 89 and 81 respectively. <h3>Conclusions</h3> Our provisional data support the role of CATCH as a new system of care for managing "low risk "CXR reports that might otherwise be referred into growing 2WW clinics. Thus far, the protocol moves at a rapid pace and has been well received by the patient (although we await the results of the postal survey in due course).
TRANSCRIPTIONAL REGULATION OF OLIGODENDROGLIAL CELL FATE BY DLX HOMEOBOX GENES: POTENTIAL RELEVANCE TO HISTONE H3.3 MUTATIONS IN PEDIATRIC HIGH GRADE GLIOMA
Authors: D. D. Eisenstat, J. Zagozewski, K. Ziegler, S. Japoni, Q. Jiang, D. A. Underhill
Journal: Neuro-Oncology (2014)

BACKGROUND: The discovery of variant histone H3.3 somatic driver mutations in pediatric high grade gliomas (pHGG) has provided important insights into their pathogenesis. The K27M and G34V/R mutants are usually localized to different neuroanatomic compartments (deep midline/brainstem or superficial/cortical, respectively) and have significant differences in their gene expression profiles. For example, there is a marked increase in the expression of the homeobox gene DLX2 and a corresponding decrease in the expression of the myelin transcription factor, MYT1. When neural progenitors that are mutant for both DLX1 and DLX2 are transplanted into a wild-type background in the developing mouse forebrain, they differentiate into cells of the oligodendrocyte lineage, supporting a role for the DLX homeobox genes in neuronal-glial cell fate decisions. METHODS: Bioinformatics approaches were used to identify homeodomain consensus TAAT/ATTA tetranucleotide DNA binding motifs in regulatory regions of genes required for oligodendrocyte differentiation, Modified chromatin immunoprecipitation (ChIP) assays using a DLX2 antibody were followed by qPCR. ChIP-reChIP assays were performed using antibodies that recognize specific histone modifications at active or repressed regulatory regions of chromatin. Electrophoretic mobility shift assays (EMSA) were performed using recombinant DLX2 protein and oligonucleotide probes from ChIP-specified promoter regions. Reporter gene assays provided functional assessment of protein-DNA interactions in vitro. Target gene expression was assessed comparing wild-type (WT) and DLX1/DLX2 mutant forebrain and retina. RESULTS: Homeodomain binding sites were localized to the promoters of several genes, including Olig2, Myt1 and Nkx2.2 in silico. ChIP assays confirmed promoter occupancy by DLX2 in several regions of these gene promoters. ChIPseq experiments are in progress. EMSA studies demonstrated specific DLX2: promoter complexes. Of interest, luciferase assays showed repression of Olig2 and Nkx2.2 reporter gene expression, consistent with co-occupancy of H3K27me3 in WT and increased target gene expression in the DLX1/DLX2 double KO embryonic tissues. CONCLUSIONS: DLX homeobox genes are necessary for tangential migration and differentiation of inhibitory interneurons in the developing CNS. Collectively, our results support a role for these transcription factors in controlling neural progenitor specification by activating GABAergic and inhibiting oligodendroglial cell fates through transcriptional repression of a suite of genes required for oligodendrocyte differentiation. Understanding how pHGG co-opt these neurodevelopmental programs will lead to novel pharmacologic approaches that promote glioma differentiation. SECONDARY CATEGORY: Pediatrics.
The Diagnosis of Posterior Herniation of the Lumbar Intervertebral Disks
Authors: Donald Munro
Journal: New England Journal of Medicine (1945)

IT IS common knowledge that there is considerable difference of opinion in the medical profession concerning the methods and efficiency of the treatment of posterior protrusions of the nucleus pulposus from ruptured lumbar intervertebral disks. Underlying this there is an even greater divergence of views about the criteria that must be met before diagnosing this condition.In a recent group of papers, Magnuson1 points out that a fine differential diagnosis is necessary in low-back cases and that the recent neurosurgical approach to this diagnostic problem, which has been made "mainly from this standpoint of root pressure from a ruptured intervertebral . . .
Choosing chemotherapy: who says “yes please”?.
Authors: RK Price, CZ Morgan, T Roe, E Massey, A Chaudry, P Jenkins*, JB Bristol, CH Chan
Journal: Cancer Research (2009)

Abstract Abstract #5091 Introduction:&amp;#x2028; Increasing numbers of patients are being offered adjuvant chemotherapy for early breast cancer. In the United Kingdom, the National Health Service provides cancer treatment free at the point of delivery. So what makes people decide whether to have chemotherapy?&amp;#x2028; Methods:&amp;#x2028; We examined the decision made by patients treated in our centre in 2007. Data were obtained from our prospectively collected database about age, prognosis (Nottingham Prognosis Index/Score - NPI), ER, HER2 status, and residential ZIP code. The UK Government Index of Multiple Deprivation (ID2000, Office for National Statistics) is based on the 2000 national census and provides two measures, the ID 2000 score and the ID2000 Rank (1 to 8414 in England and Wales). We matched ID2000 scores and ranks to ZIP codes. Low ID2000 scores and ranks are seen in affluent areas. Chemotherapy uptake was examined by age, NPI, ER, HER2 status and ID2000 using Stat View 5.0® software (SAS Institute).&amp;#x2028; Results:&amp;#x2028; 282 patients (279 women and 3 men) with invasive breast carcinoma were treated in 2007 at our centre. 135 (47.9%) were offered chemotherapy. 103/135 (76.3%) decided to have chemotherapy and 32/135 (23.7%) declined.&amp;#x2028; Chemotherapy was more commonly accepted by patients of young age (Mann Whitney U, p=0.0003), high NPI (Mann Whitney U, p=0.0012) and with HER2 positive tumours (Chi2 test, p=0.05). ER status (Chi2 test, p=0.27) and deprivation (Mann Whitney U, ID2000 score p=0.46, ID2000 rank p=0.46) had no effect on whether patients chose to have chemotherapy.&amp;#x2028; Conclusion:&amp;#x2028; Significant numbers of patients are now being offered adjuvant chemotherapy. Most patients accept chemotherapy when this is offered, although a significant minority (23.7%) decline the offer. Younger patients and those with poorer prognosis are more likely to accept this. Social deprivation, however, is not an influence in patient choice, when the patient has care 'free at the point of delivery'. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5091.
AB0179 Hypermethylation of HDAC6 Promoter in Systemic Lupus Erythematosus
Authors: J.-H. Yen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Genes and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE). DNA methylation and histone modification affect the binding of transcription factors, and alter the expression of eukaryotic genes. HDAC6 is involved in cell migration, immune synapse formation, interfering HIV infection, and degradation of misfolded protein. Methylation of <i>HDAC6</i> promoter region may affect the protein expression of HDAC6, and then influence the immunological function of HDAC6 and acetylation status of HDAC6-targeted gene. <h3>Objectives</h3> To investigate the role of methylation in HDAC6 promoter and HDAC6 mRNA expression in the pathogenesis of SLE. <h3>Methods</h3> Direct bisulfite-polymerase chain reaction (PCR) sequencing was performed to detect the HDAC6 promoter methylation in 33 patients with SLE and 35 controls healthy controls. The HDAC6 mRNA expression was measured in 93 SLE patients and 84 healthy controls by using the method of quantitative real-time PCR. <h3>Results</h3> The methylation rates at HDAC6 -1293, -1273, and -1271, which were the binding sites of transcription factors, were significantly increased in the SLE patients compared with the healthy controls (p=0.041, 0.034, and 0.029, respectively). The SLE patients also have lower HDAC6 mRNA expression than the controls (p=0.031). However, there was no significant difference in HDAC6 mRNA expression between active and inactive SLE patients. <h3>Conclusions</h3> The SLE patients have higher methylation in HDAC6 promoter and lower HDAC6 mRNA expression than the controls. These changes may be related to the susceptibility of SLE. However, they are not associated with the disease activity of SLE. <h3>References</h3> Valenzuela-Fernandez, A., J. R. Cabrero, et al. HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 2008; 18: 291-297. Liu CC, Ou TT, Wu CC, et al. Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus. Lupus 2011; 20; 131-6 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2641
PREDICTORS OF PLAQUE RUPTURE WITHIN FIBROATHEROMAS IN PATIENTS WITH ACUTE CORONARY SYNDROMES: THE PROSPECT STUDY
Authors: Bo Zheng, Gary Mintz, John McPherson, Bernard De Bruyne, Naim Farhat, Steven Marso, Ke Xu, Patrick Serruys, Gregg Stone, Akiko Maehara
Journal: Journal of the American College of Cardiology (2015)
Case 41-2009
Authors: Robert L. Sheridan, Mark A. Goldstein, Frederick J. Stoddard, T. Gregory Walker
Journal: New England Journal of Medicine (2009)

A 16-year-old boy was admitted to the hospital after being found unconscious in a snowbank at 6 a.m., approximately 7 hours after leaving a party at which alcohol was being served. He was partially undressed; his limbs were buried in the snow, and a layer of ice surrounded his right foot. On initial examination, he was drowsy and slow to respond but oriented, with spontaneous respirations and no shivering. The rectal temperature was 31.3°C. Both hands and the right foot were cold and hard to palpation; the left foot was cold but soft. A management decision was made.
Abstract LB-150: Influence of CD103-E-cadherin interaction in stimulatory versus cytotoxic immune synapse formed between CTL and specific tumor cell
Authors: Katarzyna Franciszkiewicz, Audrey Le Floc'h, Marie Boutet, Fathia Mami-Chouaib
Journal: Cancer Research (2011)

Abstract We have previously reported that interaction of integrin αE(CD103)β7, often expressed by tumor-infiltrating lymphocytes (TIL), with E-cadherin on epithelial tumor cells is required for polarized exocytosis of cytotoxic granules resulting in target cell lysis. Our results also indicated that binding of CD103 on tumor-specific cytotoxic T lymphocytes (CTL) to a recombinant E-cadherin-Fc molecule is sufficient to induce polarization of cytolytic granules in a phospholipase Cγ-dependent pathway, whereas degranulation also requires co-engagement of the T-cell receptor (TCR). In the present study, we compared the ultrastructure of the immune synapses formed between CD103+ or CD103- CTL and specific lung cancer cells, and analyzed the involvement of adhesion/costimulatory molecules in the activation of cytotoxicity versus stimulatory functions. Our results indicated that stimulatory and lytic synapses display differential activation threshold and intercellular molecular requirements. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-150. doi:10.1158/1538-7445.AM2011-LB-150
Abstract 1729: Mitochondrial necrosis pathway drives tumor progression.
Authors: Melissa K. James, Richard N. Kitsis
Journal: Cancer Research (2013)

Abstract Necrosis is a prominent feature of aggressive and invasive cancers. Previous clinical/epidemiological studies have suggested an association between the extent of tumor necrosis and poor prognosis and survivorship for some cancers. Evasion of apoptosis is widely accepted as a hallmark of cancer. However, whether necrotic cell death plays no role, limits, or drives carcinogenesis has not been studied in any cancer. Recent work suggests that necrosis may be an actively regulated form of cell death. In contrast to apoptosis where permeabilization of the outer mitochondrial membrane is the defining event, the central event in necrosis is the opening of a pore in the inner mitochondrial membrane termed the mitochondrial permeability transition pore (mPTP). Cyclophilin D, a peptidyl prolyl cis-trans isomerase in the mitochondrial matrix, encoded by the gene ppif, is critical for opening of the mPTP. Stable expression of ppif shRNA was used to deplete cyclophilin D in Met-1 cells, a metastatic breast cancer cell line. We first confirmed that knockdown of ppif in Met-1 cells abrogated necrosis, but not apoptosis. When these cells were transplanted into the mammary glands of wildtype FVB mice, tumors resulting from cells that express ppif shRNA were markedly smaller, with decreased volume and mass, than those derived from cells expressing control shRNA. Reconstitution of ppif knockdown cells with wild type cyclophilin D, but not an enzymatically inactive mutant, rescued tumor volume and mass. As expected, tumors arising from ppif knockdown cells exhibited less necrosis, while rates of apoptosis were unchanged. Moreover, rates of BrdU incorporation were significantly decreased in these tumors. Necrotic cell death is characterized by loss of plasma membrane integrity resulting in a marked inflammatory response. Neutrophils and macrophages recruited to tumors often secrete growth/survival/angiogenic factors that promote tumor growth and metastasis. Consistent with this model, both macrophage and neutrophil recruitment were reduced in tumors derived from ppif knockdown cells. In addition, rates of spontaneous pulmonary metastasis were markedly decreased in mice harboring tumors derived from ppif knockdown cells compared with controls. Our data suggest that, in contrast to apoptotic cell death which limits carcinogenesis, necrotic cell death actually drives disease progression by altering the tumor microenvironment. These findings may have therapeutic implications in that they suggest that inhibition - rather than promotion - of necrotic cell death may provide a novel treatment paradigm for some cancers. Citation Format: Melissa K. James, Richard N. Kitsis. Mitochondrial necrosis pathway drives tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1729. doi:10.1158/1538-7445.AM2013-1729
AB0796 Efficiency of customized foot insoles in patients with early rheumatoid arthritis
Authors: A. Surnov, D. Karateev, E. Orlova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The prevalence of foot lesions in rheumatoid arthritis (RA) patients is extremely high [1]. The defeat of the joints of the foot is often observed at the stage of diagnosis. In many patients, joint damage symptoms persist even at the stage of remission [2]. <h3>Objectives</h3> To evaluate the effectiveness of the customized foot insoles in patients with early RA. <h3>Methods</h3> 17 patients with early RA of the study group used customized foot insoles. The recommended mode of insole using was a constant wearing. The control group consisted of 12 patients. Patients of the both groups underwent drug therapy, physical exercises, occupational therapy. Foot pain on 100-mm VAS, DAS4, HAQ, RAPID3 scores and march test were evaluated at baseline and at 3,0±0,5 months. <h3>Results</h3> In the study group RAPID3 decreased by 30,1% (3,2±0,2, p&lt;0,01), pain on VAS – by 52,1% (p&lt;0,01), DAS4 – by 0,89±0,42 points (p&lt;0,01). Also, the time of overcoming patient distance of 20 m (walking test) reduced from 13,5±1,2 sec to 11,2±0,9 sec (p&lt;0,05). At the end of the observation, the statistically significant differences between the study group and the control group were observed by the RAPID3 score (7,5±5,8 and 9,9±6,1, respectively) (p&lt;0,05), foot pain on VAS (15,2±9,1 and 24,5±10,2, respectively) (p&lt;0,05) and walking test (11,2±0,9 sec and 12,9±2,4 sec, respectively) (p&lt;0,05). Most patients of the study group (94%) reported that they preferred to wear the customized foot insoles in daily living and physical activities. 90% of patients complied recommendations about the regime of insole wearing. <h3>Conclusions</h3> The wearing of the customized foot insoles reduces foot pain, improves functional status and quality of life in patients with early RA. There is a high adherence to using the foot insoles. <h3>References</h3> Mjaavatten MD, et al. J Rheumatol 2009;36:1401–6. Landewé R, et al. Ann Rheum Dis 2006;65:637–41. <h3>Disclosure of Interest</h3> None Declared
ACUTE PROXIMAL LEFT ANTERIOR DESCENDING ARTERY THROMBOSIS PRESENTING WITH INFEROLATERAL ST ELEVATION AND SYMPTOMS CONSISTENT WITH PERICARDITIS
Authors: Prabhakaran Gopalakrishnan, Sharan Rufus Ponniah, Digant Bhatt, Pradeepto Ghosh, Muhammad Chaudhry, Nagapradeep Nagajothi
Journal: Journal of the American College of Cardiology (2016)
The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): A phase II, randomized controlled trial
Authors: Tjinta Brinkhuizen, Kiki J.A. Frencken, Patty J. Nelemans, Marlou L.S. Hoff, Nicole W.J. Kelleners-Smeets, Axel zur Hausen, Michiel P.J. van der Horst, Dorit Rennspiess, Véronique J.L. Winnepenninckx, Maurice A.M. van Steensel, Klara Mosterd
Journal: Journal of the American Academy of Dermatology (2016)
Duodenal Crohn’s disease successfully treated with adalimumab
Authors: A Tursi
Journal: Endoscopy (2011)

Upper gastrointestinal involvement in Crohn’s disease is considered to be relatively infrequent (0.4 – 3 %) [1], and treatment mainly relies on the use of high doses of proton pump inhibitors, mesalazine (mesalamine), and steroids [2].
O06 * TARGETING FOXM1 AS A NOVEL THERAPEUTIC STRATEGY FOR THE TREATMENT OF MSH6 DEFICIENT TEMOZOLOMIDE-RESISTANT GLIOBLASTOMA
Authors: D. J. Brierley, M. Locke, A. Merve, S. Marino, S. A. Martin
Journal: Neuro-Oncology (2014)

INTRODUCTION: Mutations in the DNA mismatch repair gene MSH6 can arise in glioblastoma cells during Temozolomide treatment and can mediate drug resistance. Recently, exploiting the concept of synthetic lethality has been proposed as a therapeutic strategy. METHOD & RESULTS: Based on this approach we have identified the thiazole antibiotic Thiostrepton as synthetically lethal with MSH6 deficiency in the presence of Temozolomide, in vitro and in vivo. Our data suggest that in the absence of MSH6, FOXM1, a target of Thiostrepton, is upregulated due to reduced FOXO1/FOXO3a transcriptional repression. This regulation is through an interaction of MSH6 with the TGF beta-transcriptional complex containing phosphorylated-SMAD2 and SMAD3, with their co-SMAD, SMAD4. CONCLUSION: We suggest a novel role for MSH6 in the regulation of FOXM1 levels via the TGF beta-FOXO signaling pathway, which can mediate resistance to Temozolomide. Inhibition of FOXM1 in MSH6-deficient tumours provides a novel therapeutic strategy for the treatment of Temozolomide-resistant disease.
Comparison of a β<sub>2</sub>-Agonist, Terbutaline, with an Inhaled Corticosteroid, Budesonide, in Newly Detected Asthma
Authors: Tari Haahtela, Markku Järvinen, Tuomo Kava, Kirsti Kiviranta, Sirkka Koskinen, Kaarina Lehtonen, Kurt Nikander, Tore Persson, Kaija Reinikainen, Olof Selroos, Anssi Sovijärvi, Brita Stenius-Aarniala, Thore Svahn, Ritva Tammivaara, Lauri A. Laitinen
Journal: New England Journal of Medicine (1991)

The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy. We compared the effect of an inhaled corticosteroid, budesonide, with that of an inhaled β2-agonist, terbutaline, in the long-term treatment of newly detected asthma.
Unsuspected Uterine Metastasis of Breast Carcinoma Diagnosed by 18F-FDG PET/CT
Authors: Jose Muñoz-Iglesias, Jon Uña-Gorospe, Ana Allende-Riera, Marta De Sequera-Rahola, Carlos Cárdenas-Negro
Journal: Clinical Nuclear Medicine (2013)

A 50-year-old woman with a history of bilateral lobular carcinoma of the breast in 1995 and 2001 was treated with mastectomy, axillary lymphadenectomy, chemotherapy, and hormone therapy which achieved a complete response. In 2009, the patient developed a progressive elevation of tumor markers. A CT scan was performed showing no suspicious malignant lesions. She was referred for (18)F-FDG PET/CT and the images revealed highly increased tracer uptake in the uterus suggestive of malignancy. The patient underwent hysterectomy with bilateral double adnexectomy and a histopathological diagnosis of massive carcinomatous infiltration of breast lobular carcinoma was done.
Cotton wool-like plaques due to Candida in ulcerative colitis
Authors: Yasuteru Fujino, Yoshifumi Takaoka, Naoki Muguruma, Miwako Kagawa, Toshiya Okahisa, Mika Sakaki, Tetsuji Takayama
Journal: Endoscopy (2015)

A 62-year-old man with a long history of ulcerative colitis and who was taking 2250 mg of mesalazine and 50 mg of azathioprine daily, developed intermittent abdominal pain and prolonged diarrhea. He was referred to our hospital with a suspicion of exacerbated ulcerative colitis. A physical examination revealed a man in acute distress with mild tenderness to palpation in the mid abdomen. Oral prednisolone was prescribed at a dose that was to be gradually decreased from 80 mg. After 5 weeks, when the dose of prednisolone had decreased to 30 mg, he developed high fever and abdominal colic pain. In his stool examination, Pseudomonas aeruginosa, Clostridium difficile, and some Candida species were present. Serum cytomegalovirus (CMV) antigen was also positive. Colonoscopy revealed multiple ulcers, marked granular change, and edema throughout the colon. White plaques as well as cotton wool-like plaques on a background of inflamed mucosa were seen in the transverse colon ([Fig. 1 a]). The lesions seemed to be an aggregation of filaments when magnified ([Fig. 1 b]). Samples were collected which led to the diagnosis of candidiasis ([Fig. 2]). Intravenous antifungal medication was administered, and the whitish plaques and inflammation disappeared within 2 months.