tbuckley/cabot-search huggingface dataset:
Development of Novel Small Hairpin RNAs That do not Require Processing by Dicer or AGO2
Authors: Shin-ichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mikie Kashiwazako, Hikaru Okuyama, Katsuyoshi Kumagai, Masakatsu Takanashi, Katsuko Sudo, Norihiko Ikeda, Masahiko Kuroda
Journal: Molecular Therapy (2016)

The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single-strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghR caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents. Systemic and local injection of ghR-form miR-34a (ghR-34a) suppressed tumor growth in a mouse model of RAS-induced lung cancer. Furthermore, Dicer and AGO2 are not required for ghR-34a function. This novel RNA interference (RNAi) technology may provide a novel, safe, and effective nucleic acid drug platform that will increase the clinical usefulness of nucleic acid therapy. The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single-strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghR caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents. Systemic and local injection of ghR-form miR-34a (ghR-34a) suppressed tumor growth in a mouse model of RAS-induced lung cancer. Furthermore, Dicer and AGO2 are not required for ghR-34a function. This novel RNA interference (RNAi) technology may provide a novel, safe, and effective nucleic acid drug platform that will increase the clinical usefulness of nucleic acid therapy.
Case 31-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Charles B. Carpenter, Nancy Harris
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 50-year-old woman was admitted to the hospital because of a seizure, fever, and acidosis.There was a history of hypertension, with the more recent development of end-stage renal disease that was believed to be nephrosclerosis. Two months before entry a cadaveric renal transplantation was performed; the postoperative course was uncomplicated. Immunosuppression consisted of cyclosporine, 700 mg daily, and adrenocorticoid therapy that began with methylprednisolone, 200 mg on the day of operation, and was tapered to prednisone, 20 mg daily, by the fifth postoperative day. She was discharged on cyclosporine, 350 mg twice daily, and prednisone, 20 . . .
Clinical activity of rituximab with either CHOP or CVP in MALT lymphoma
Authors: D. Aguiar Bujanda, U. Bohn Sarmiento, S. Saura Grau, C. Rodriguez Franco, J. Aguiar Morales
Journal: Journal of Clinical Oncology (2009)

e19530 Background: Optimal management of MALT lymphoma remains undeffined. Rituximab has been proven to be an active agent in the treatment of MALT lymphoma. Several reports suggest that the activity of rituximab can be improved when added to chemotherapy. We aimed to evaluate safety and activity of rituximab combined with chemotherapy (CHOP or CVP) in first-line therapy for MALT lymphoma. Methods: Retrospective review of patients with MALT lymphoma treated in first-line with R-CHOP or R-CVP. Patients with gastric MALT lymphoma were included if resistant to or not eligible for anti-Helicobacter pylori therapy. Results: There were 22 patients (8 male, 14 female) with a median age 60 years (range 34 to 77 years). Primary origin: 14 stomach (64%), 3 skin, and 5 others (nodal, parotid gland, orbital, colon, and lung). Stage of disease wa I in 13 patients (59%), II in 2 patients (9%), and IV in 7 patients (32%). Bone marrow infiltration was present in 5 patients (23%). Chemo-immunotherapy was R-CVP in 13 patients and R-CHOP in 9 patients. The median number of cycles for patient was 6. The treatment was well tolerated with mild toxicity. Patients with gastric lymphoma did not have bleeding or perforation during therapy. One patient had to stop rituximab after second cycle because severe infusion reaction. In three patients the vincristine was reduced or removed because sensitive neuropathy. The overall response rate (ORR) in 21 evaluable patients was 95% (CR 81%, PR 14%). None of the patients progressed during therapy. Patients with gastric lymphoma (n=14) showed an ORR of 93% (CR 86%, PR 7%, SD 7%). Radiation therapy was given as consolidation after chemotherapy to 3 patients with extra-gastric origin. With a median follow-up of 28 months, two patients (gastric lymphoma) have relapsed at 4 and 12 months respectively. All patients are alive and 19 (86%) in complete response. Conclusions: Combination of rituximab with either CHOP or CVP is very active with acceptable toxicity in the treatment of MALT lymphoma. Further studies are needed to elucidate the optimal combination of rituximab and chemotherapy in this patient population. No significant financial relationships to disclose.
Transgastric endoscopic vacuum therapy with a new open-pore film drainage device in a case of infective pancreatic necrosis
Authors: Gunnar Loske, Tobias Schorsch, Olaf Gobrecht, Eckhard Martens, Frank Rucktäschel
Journal: Endoscopy (2016)

Infected pancreatic necrosis needs to be drained; nowadays this is mostly done by endoscopic means. As yet, few cases of transgastric endoscopic vacuum therapy (EVT) have been reported [1] [2] [3]. This is the first case to be reported in which a new open-pore film drainage (OFD) device was used.
Case 21-1996
Authors: Alan C. Aisenberg, Metin Ozdemirli
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 52-year-old man was admitted to the hospital because of severe back pain.The patient had been well until 13 months earlier, when he had low back pain after lifting a 45-kg object. Three months later, he returned to work. Four months before admission, the back pain recurred when he turned abruptly, and he began to have intermittent low-grade fever and sweats.Thirteen weeks before admission, a radionuclide bone scan (Figure 1), obtained at another hospital, revealed on delayed images focal increased activity in the first and third lumbar spinous processes, a midthoracic vertebral body, the left . . .
CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq
Authors: Tamar Hashimshony, Naftalie Senderovich, Gal Avital, Agnes Klochendler, Yaron de Leeuw, Leon Anavy, Dave Gennert, Shuqiang Li, Kenneth J. Livak, Orit Rozenblatt-Rosen, Yuval Dor, Aviv Regev, Itai Yanai
Journal: Genome biology (2016)

Single-cell transcriptomics requires a method that is sensitive, accurate, and reproducible. Here, we present CEL-Seq2, a modified version of our CEL-Seq method, with threefold higher sensitivity, lower costs, and less hands-on time. We implemented CEL-Seq2 on Fluidigm's C1 system, providing its first single-cell, on-chip barcoding method, and we detected gene expression changes accompanying the progression through the cell cycle in mouse fibroblast cells. We also compare with Smart-Seq to demonstrate CEL-Seq2's increased sensitivity relative to other available methods. Collectively, the improvements make CEL-Seq2 uniquely suited to single-cell RNA-Seq analysis in terms of economics, resolution, and ease of use.
NHS England provides a major boost for general practice
Authors: Sam Everington, Martin Roland
Journal: BMJ (2016)

The next step is to transform the rest of the healthcare system with the same vision

“There is arguably no more important job in modern Britain than that of the family doctor.” So says Simon Stevens, chief executive of NHS England, in his introduction to the General Practice Forward View ,1 a new strategic plan that recognises the mistake of expanding hospital funding at the expense of primary care over the past decade. Maureen Baker, president of the Royal College of General Practitioners, calls it “the most significant announcement for general practice since the 1960s.”2

The proposals are extensive—£2.4bn (€3bn; $3.5bn) extra funding to increase general practice’s share of the NHS budget in England from under 8.5% in 2014-15 to over 10% by 2020. There will be 5000 more general practitioners, 3000 new mental health therapists in primary care, 1500 pharmacists working in general practices, 1000 physician associates, £900m ($1.3bn) for new premises, reductions in bureaucracy, and a wide range of other proposals. The plans are largely in line with recommendations from the Primary Care Workforce Commission3 and the House of Commons …
Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro
Authors: Anastasia Rakow, Janosch Schoon, Anke Dienelt, Thilo John, Martin Textor, Georg Duda, Carsten Perka, Frank Schulze, Andrea Ode
Journal: Biomaterials (2016)
Ifosfamide, Methotrexate, Etoposide, and Prednisolone (IMEP) Plus L-Asparaginase As a First-Line Therapy Improves Outcomes In Stage III/IV NK/T-Cell Lymphoma, Nasal Type (NTCL)
Authors: Miso Kim, Ki Hwan Kim, Bhumsuk Keam, Se-Hoon Lee, Dong-Wan Kim, Jong Seok Lee, Dae Seog Heo, Tae Min Kim
Journal: Blood (2013)
Radiofrequency ablation of lymphoma
Authors: D. Sudheendra, M. Barth, U. Hegde, W. Wilson, S. Libutti, B. Wood
Journal: Journal of Clinical Oncology (2005)

6710 Background: The role of radiofrequency ablation (RFA) for the treatment of lymphoma is undocumented. We present three patients in whom RFA was used, for three different indications, to treat residual lymphomatous lesions unresponsive to conventional treatment. Methods: Three patients with isolated lymphoma masses were treated with percutaneous image-guided RFA. The first patient had a residual hepatic mass after EPOCH and rituximab chemotherapy for polymorphic post-transplant lymphoproliferative disorder. The second patient had a progressively enlarging follicular lymphoma adjacent to the bladder wall following prior maximum radiation therapy and CHOP chemotherapy and was treated with RFA for pain palliation. In the third case, the patient had a rapidly enlarging B-cell lymphoma of the right neck causing impending airway compromise. The water-cooled Radionics generator ablation system was used with a cluster needle probe in all cases. Impedence, temperature, power, current, and time were monitored closely. Patients were followed both clinically and with CT, MRI, or PET to evaluate for treatment response and/or recurrence of their lesions. Results: Following RFA, the first patient had complete radiological resolution of the hepatic masses and remains disease free at four years post-treatment. The second patient achieved a partial response to the pelvic mass, requiring a second ablation treatment for recurrent urinary symptoms. He remained with improved symptoms at most recent follow-up. Although the third patient had short-term relief of his neck pain and respiratory compromise post-ablation, he expired five weeks later from his lymphoma. Conclusions: These cases of chemoresistance, pain palliation, and pending airway compromise illustrate settings in which RFA may be a preferable treatment to radiation or surgery, producing potentially less morbidity than standard treatments. Previous studies have shown that RFA produces a robust inflammatory response and could lead to a boost in the immune response against lymphoma, especially when performed with costimulatory agents like vaccines or other immunostimulation. This study exemplifies ways in which RFA may help manage patients with lymphoma and few alternative therapies. No significant financial relationships to disclose.
TCTAP C-219 Staged-approach with Different Vascular Access Sites May Be Alternative Strategy for Patients with Extensive Peripheral Artery Disease in Lower Extremities
Authors: Choongki Kim, Dong-Ho Shin, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Myeong-Ki Hong, Yang Soo Jang, Dong Hoon Choi
Journal: Journal of the American College of Cardiology (2016)
NIMG-15EMPLOYING PRE-CLINICAL GLIOBLASTOMA MODEL AND MRI DERIVED TEXTURE FEATURES FOR FUNCTIONAL VALIDATION OF RADIOGENOMICS
Authors: Pascal Zinn, Markus Luedi, Sanjay Singh, Masumeh Hatami, Aikaterini Kotrotsou, Islam Hassan, Faramak Zandi, Joy Gumin, Eric Sulman, Frederick Lang, Rivka Colen
Journal: Neuro-Oncology (2015)

A precise clinically relevant characterization of glioblastoma (GBM) heterogeneity and underlying genomic variability is urgently needed. To evaluate the true potential of radiogenomics, an emerging field for GBM research, we have tested its scope in a pre-clinical setting. First, glioblastoma stem cells (GSCs) are altered to express decreased levels of Periostin (POSTN), previously identified in a radiogenomic screen as a key pro-invasive gene. Second, orthotopic tumors arising from these GSCs, were scanned and analyzed to identify gene specific MRI texture feature (MRTF) signatures, which can simultaneously predict POSTN status in GBM patients. Doxycycline inducible short hairpin RNA mediated knockdown of POSTN in GSC lines were established. 5X10^6 cells were stereotactically implanted in nude mice frontal cortex and randomized into POSTN knockdown and control groups. Monitored tumor growth longitudinally by MRI (n = 3-4 per group). Region of interest (ROI) methods were applied to the rigid registration images based on axial T1-weighted imaging and corresponding fluid-attenuated inversion recovery sequences. After pre-processing, gray level co-occurrence matrices (GLCMs) were generated in 4 angular directions and 3 invariant measures (mean, range and angular variance) of each texture feature is calculated. A matrix of 3x20 invariant features is generated for each gray level. Mean values of normalized MRTFs from edema T1 post and T2, subgroup tumors arising from independent GSCs (p <0.009- < 0.039) whereas, a distinct set of MRTFs correctly subgroup tumors arising from GSCs with POSTN knockdown and Control (p < 0.01- < 0.047). Additionally, these features are highly conserved in their respective groups between mouse and human MRI scans. In conclusion, our results provide one of the first pre-clinical validation for the field of radiogenomics, where a specific gene status can be recognized by a specific set of MRI texture features, which in turn can predict gene status in an individual GBM patient.
Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial
Authors: Sally Wenzel, Mario Castro, Jonathan Corren, Jorge Maspero, Lin Wang, Bingzhi Zhang, Gianluca Pirozzi, E Rand Sutherland, Robert R Evans, Vijay N Joish, Laurent Eckert, Neil M H Graham, Neil Stahl, George D Yancopoulos, Mariana Louis-Tisserand, Ariel Teper
Journal: The Lancet (2016)
Case 16-1975
Authors: Alan H. Goodman, Walter G. J. Putschar
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 53-year-old woman was admitted to the hospital because of a lytic lesion of the right femur.She was well until 13 years previously, when she noticed a painless mass in the right thigh, which did not change in size subsequently. Ten years later she came to this hospital, where examination disclosed a firm, slightly movable soft-tissue mass, 15 by 7.5 cm, in the anterior region of the right thigh. The protein was 6.5 g (the albumin 4.1 g, and the globulin 2.4 g) per 100 ml. The alkaline phosphatase was 3.5 Bodansky U. X-ray examination of . . .
PTH-268 The malignant colorectal polyp – how useful is the ACPGBI risk stratification score?
Authors: NS Malik, JG Williams
Journal: Gut (2015)

<h3>Introduction</h3> Colonic polyps containing a focus of invasive malignancy are increasing in frequency with the wider adoption of colonoscopic screening. Decision making as to the next course of action following endoscopic removal of a malignant polyp can be challenging. The ACPGBI position statement on malignant polyps outlines a scoring system to help predict the likelihood of lymph node metastasis and predicate surgical resection of the affected intestine and regional lymph nodes. The aim of this study was to analyse the benefit of this scoring system in predicting the presence of residual disease in patients with a malignant polyp. <h3>Method</h3> Colorectal MDT decision making and outcomes of a consecutive series of malignant polyps treated between 2008 and 2014 was studied. Each polyp was assigned an ACPGBI score retrospectively to assess how well this predicted the presence of residual disease. <h3>Results</h3> 70 patients (47 male) were identified as having a malignant polyp. Median follow-up was 27 months (range 0–58). Median age was 69 years (range 42–87). 36 (51%) polyps were detected during bowel cancer screening colonoscopy, 30 polyps were detected in symptomatic patients. 31 (45%) polyps were located in the rectum, 35 (51%) in the left colon and 3 (4%) in the right colon. 18 polyps were scored as low risk (ACPGBI score &lt;2, chance of residual disease &lt;5%). 15 patients were managed with endoscopic polypectomy only, all were recurrence-free during follow up. 3 patients underwent surgery, two after MDT recommendation and one as a result of perforation following polypectomy. None of these patients had residual disease in the specimen. 52 patients were deemed to have a moderate or high risk polyp (ACPGBI score 3 or more, &gt;10% risk residual disease). 2 patients were deemed unfit for surgery and 2 patients declined surgery. 48 patients underwent surgery: residual (lymph node) disease was found in 3 patients (ACPGBI Scores 4,4 &amp;5) and a further 1 patient (ACPGBI score 6), had a specimen clear of tumour but went on to develop metastatic disease giving an overall risk of residual disease of 8.3%. One patient is alive with metastatic disease and 3 patients have died post operatively, 1 (2.8%) of postoperative complications. The remaining patients are alive and recurrence-free. <h3>Conclusion</h3> Low-risk malignant polyps are readily identified using a composite score and do not require surgical resection of the affected colon or rectum. Criteria used to identify moderate risk polyps are not specific enough as most patients undergoing surgery do not harbour residual disease. Piecemeal removal of polyps makes accurate risk assessment difficult. Accumulation of data such as this will allow fine-tuning of criteria used to identify patients at greatest risk of residual cancer after endoscopic resection of a malignant polyp. <h3>Disclosure of interest</h3> None Declared.
Mitotic Indices of Human Bone Marrow Cells. II. The Use of Mitotic Indices for Estimation of Time Parameters of Proliferation in Serially Connected Multiplicative Cellular Compartments
Authors: SVEN-ÅGE KILLMANN, EUGENE P. CRONKITE, T. M. FLIEDNER, VICTOR P. BOND, GEORGE BRECHER
Journal: Blood (1963)
Initiation of immune tolerance–controlled HIV gp41 neutralizing B cell lineages
Authors: Ruijun Zhang, Laurent Verkoczy, Kevin Wiehe, S. Munir Alam, Nathan I. Nicely, Sampa Santra, Todd Bradley, Charles W. Pemble, Jinsong Zhang, Feng Gao, David C. Montefiori, Hilary Bouton-Verville, Garnett Kelsoe, Kevin Larimore, Phillip D. Greenberg, Robert Parks, Andrew Foulger, Jessica N. Peel, Kan Luo, Xiaozhi Lu, Ashley M. Trama, Nathan Vandergrift, Georgia D. Tomaras, Thomas B. Kepler, M. Anthony Moody, Hua-Xin Liao, Barton F. Haynes
Journal: Science Translational Medicine (2016)

Immune tolerance mechanisms limit gp41 neutralizing antibody lineage maturation to broadly neutralizing antibodies.
Searching for the happy medium in the therapeutic approach to childhood sleep disordered breathing
Authors: Francisco Campos-Rodriguez, Miguel A. Martínez-García
Journal: European Respiratory Journal (2016)

The natural history of a disease is the course it takes in an individual, without medical intervention, from its pathological onset until its eventual resolution or death. Knowledge of this natural history is essential for understanding the disease and designing the most effective strategies for its prevention and control. Is the optimum approach to childhood sleep disordered breathing prompt surgical intervention or watchful waiting? <http://ow.ly/Xypal>
Describing Differences in Survival Curves
Authors: Rick Chappell, Xiaotian Zhu
Journal: JAMA Oncology (2016)

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Cytokine loops involving interferon-gamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma? [see comments]
Authors: AH Sarris, T Esgleyes-Ribot, M Crow, HE Broxmeyer, N Karasavvas, W Pugh, D Grossman, A Deisseroth, M Duvic
Journal: Blood (1995)
TCTAP C-055 The Application of Bioabsorbable Stent in a Balloon - Unexpandable Calcified CTO Lesion in a Stage 5 CKD Patient
Authors: Wei-Chun Huang, Chin-Chang Cheng, Cheng-Hung Chiang, Cheng Chung Hung, Feng Yu Kuo, Guang-Yuan Mar, Chun-Peng Liu
Journal: Journal of the American College of Cardiology (2016)