tbuckley/cabot-search huggingface dataset:
Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts
Authors: Elena Garreta, Lorena de Oñate, M. Eugenia Fernández-Santos, Roger Oria, Carolina Tarantino, Andreu M. Climent, Andrés Marco, Mireia Samitier, Elena Martínez, Maria Valls-Margarit, Rafael Matesanz, Doris A. Taylor, Francisco Fernández-Avilés, Juan Carlos Izpisua Belmonte, Nuria Montserrat
Journal: Biomaterials (2016)

Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.
PWE-396 Diagnostic laparoscopy and the outcome of macroscopically normal appendicectomy in female patients with right iliac fossa pain
Authors: A Ghosh, A Addison, A Agrawal
Journal: Gut (2015)

<h3>Introduction</h3> Right iliac fossa pain (RIF) pain, caused by suspected acute appendicitis continues to prove diagnostically challenging with 15–30% of appendices removed being macroscopically normal. Diagnostic laparoscopy (DL) is being used as both diagnostic and therapeutic procedure particularly in female patients. The aim of this study was to assess the rate of macroscopically negative appendicectomies (MNA) and complications in a cohort of female patients who had DL for suspected appendicitis. Furthermore to follow up the re-admissions rates in those who did not have appendicectomy in the absence of positive findings. <h3>Method</h3> A retrospective study of consecutive female patients admitted with acute abdominal pain that underwent DL for suspected acute appendicitis with an 18-month follow-up. An electronic structured proforma was used to collect data related to white cell count (WCC), C-reactive protein (CRP), ultrasonography (US), operative findings, histology, morbidity and mortality were collated. <h3>Results</h3> In total of the 159 patients were included in the study (mean age 30; 16–76). On admission 118 patients (74%) had a raised WCC (&gt;11), of which 84% (91/119) had a raised CRP (&gt;10). 48 patients underwent US, with 26 having a radiological diagnosis of appendicitis prior to laparoscopy. 146 patients underwent laparoscopic appendicectomy. At laparoscopy 120 patients had a macroscopic diagnosis of acute appendicitis, while 26 of the patients that underwent appendicectomy had MNA, although there was a decision to proceed to appendicectomy. Therefore 13 patients only had a DL. There were no complications in the MNA group of appendicetomies, although complications in the appendicitis group included ileus (1.6%, 2/120) and drainage of pelvic abscess (0.8%, 1/120). Histopathological diagnosis of appendicitis was confirmed in 99% of appendectomies (145/146). One patient had a macroscopically inflamed appendix removed that was normal. One patient who only had diagnostic laparoscopy was later diagnosed with inflammatory bowel disease. While 4 patients who underwent laparoscopy where re-admitted at least twice, and one patient four times during the follow-up period. However none underwent further laparoscopy. <h3>Conclusion</h3> Although there has been some consensus that laparoscopic appendicectomy should be undertaken for the MNA, there has also been suggestion that this maybe associated with increased morbidity. We have shown that often at laparoscopy a macroscopically normal appendix histologically is acute appendicitis. There is no increase complication rate in this group. Furthermore future readmissions may be avoided in this group of female patients with RIF pain. <h3>Disclosure of interest</h3> None Declared.
THE MILK SUPPLY OF CITIES.
Journal: JAMA (1896)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
EPID-13CONCOMITANT GLIOBLASTOMA MULTIFORME IN PATIENTS DIAGNOSED WITH MULTIPLE SCLEROSIS: A REPORT OF TWO CASES
Authors: Corazon Lauren Delumpa, Flavia Nelson, Jay-Jiguang Zhu
Journal: Neuro-Oncology (2015)

Multiple sclerosis (MS) and glioblastoma multiforme (GBM) are two neuropathologies at the opposite ends of the immune spectrum. The incidence of MS with concomitant GBM is rare and only a number of case reports have been described in the literature. MS is an immune-mediated disease characterized by inflammation, demyelination, gliosis and neuronal loss while GBM is a primary malignant brain neoplasm that arises either from cancer stem cells or dysregulated astrocytes that result in uncontrolled tumor growth that escaped immune surveillance. We describe two cases that illustrate the challenges of timely diagnosis and management of GBM in patients with pre-existing MS. The first case is a 59-year-old female with an 18-year history of MS, who is JC virus positive and previously received Rebif and Tysabri. She presented to the emergency department with headache and altered mental status; MRI revealed a hemorrhagic left temporal lesion. She underwent hematoma evacuation and a second craniotomy for tumor debulking and received a diagnosis of anaplastic oligodendroglioma. She received standard of care Temozolomide and radiation therapy. Six months later, the patient had tumor recurrence which required a third resection, pathology was read as GBM. Second-line therapy with Bevacizumab and Irinotecan were added due to temozolomide intolerance and clinical progression. The second case is a 48-year-old female with a 24-year history of mild MS on Copaxone, who presented with improving left sided numbness and tingling of 2 months duration. She was treated with oral steroids and an MRI of the brain was done to evaluate disease activity and showed a large, acute ring-enhancing lesion atypical for MS. She underwent a biopsy that was consistent with GBM and proceeded with oncologic treatment at another facility. Although rare, these two cases illustrate the diagnostic and treatment challenges of primary brain tumors in patients with pre-existing neurological disease.
Mutational load by targeted next generation sequencing (NGS) panels as potential biomarker of response to checkpoint inhibitors
Authors: J. Martin-Liberal, M. Ochoa de Olza, C. Hierro, C. Cruz, C. Rodriguez, I. Brana, A. Vivancos, R. Dienstmann, J. Rodon, J. Tabernero
Journal: Annals of Oncology (2015)
Hospital and Payer Costs Associated With Surgical Complications
Authors: Mark A. Healy, Andrew J. Mullard, Darrell A. Campbell, Justin B. Dimick
Journal: JAMA Surgery (2016)

<h3>Importance</h3> Increased costs of surgical complications have been borne mostly by third-party payers. However, numerous policy changes aimed at incentivizing high-quality care shift more of this burden to hospitals. The potential effect of these policies on hospitals and payers is poorly understood. <h3>Objective</h3> To evaluate costs associated with surgical quality and the relative financial burden on hospitals and payers. <h3>Design, Setting, and Participants</h3> We performed an observational study merging complication data from the Michigan Surgical Quality Collaborative and internal cost accounting data from the University of Michigan Health System from January 2, 2008, through April 16, 2015; the merged files from these data were created between June 5, 2015, and July 22, 2015. A total of 5120 episodes of surgical care for 24 surgical procedure groups (17 general surgical, 6 vascular, and 1 gynecologic) were examined. We report unadjusted and log-transformed risk-adjusted costs. <h3>Main Outcomes and Measures</h3> We compared hospital costs, third-party reimbursement (ie, payer costs), and hospital profit margin for cases with and without complications. <h3>Results</h3> The mean (SD) age of the 5120 patients was 56.0 (16.4) years, and 2883 (56.3) were female. The overall complication rate was 14.5% (744 of 5120) for all procedures, 14.7% (580 of 3956) for general surgery, 15.5% (128 of 828) for vascular surgery, and 10.7% (36 of 336) for gynecologic surgery. For all studied procedures, mean hospital costs were $19 626 (119%) higher for patients with complications ($36 060) compared with those without complications ($16 434). Mean third-party reimbursement was $18 497 (106%) higher for patients with complications ($35 870) compared with those without complications ($17 373). Consequently, with risk adjustment, overall profit margin decreased from 5.8% for patients without complications to 0.1% for patients with complications. <h3>Conclusions and Relevance</h3> Hospitals and third-party payers experience increased costs with surgical complications, with hospitals experiencing a reduction in profit margin. Both hospitals and payers appear to currently have financial incentives to promote surgical quality improvement.
The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2
Authors: Charlotte L. Scott, Bieke Soen, Liesbet Martens, Nicolas Skrypek, Wouter Saelens, Joachim Taminau, Gillian Blancke, Gert Van Isterdael, Danny Huylebroeck, Jody Haigh, Yvan Saeys, Martin Guilliams, Bart N. Lambrecht, Geert Berx
Journal: The Journal of Experimental Medicine (2016)

Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box–binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c+ cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c+ cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knockout mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.
Cephalic Tetanus
Authors: L. Bagratuni
Journal: BMJ (1952)

CONGESTIVE AND SIMPLE GLAUCOMA MEDIATJSHRNA 461 (8) Patients with congestive glaucoma are usually nervous and worrying individuals.This tendency is less marked in simple glaucoma.(9) A plea is made that practitioners should suspect the disease in all patients over 40 years with eye symptoms, especially if haloes have been seen or if there *s a unilateral disturbance of vision.This analysis touches very briefly upon the work of Mr. G. D. Elphick on visual fields, Mr. H.E. Hobbs on gonioscopy, and Mr. D. A. Langley on the phasic variations in simple glaucoma, carried out at the Glaucoma Clinic under the direction of Sir Stewart Duke-Elder.The social histories were taken by Misses Abbey,
Functional role of cation-independent mannose 6-phosphate/insulin-like growth factor II receptor in cell adhesion and proliferation of a human myeloma cell line OPM-2
Authors: T Nishiura, T Karasuno, H Yoshida, H Nakao, M Ogawa, Y Horikawa, M Yoshimura, Y Okajima, Y Kanakura, Y Kanayama, Y Matsuzawa
Journal: Blood (1996)
HER-2 central confirmatory testing using ASCO/CAP guidelines for trastuzumab/lapatinib trial MCCR RC0639
Authors: A. McCullough, A. Dueck, B. Chen, M. Reinholz, A. Wiktor, W. Lingle, R. Jenkins, E. Perez
Journal: Journal of Clinical Oncology (2009)

e11527 Background: 118 Her2 positive invasive carcinomas were retested centrally at the Mayo Clinic for Her2 status confirmation prior to inclusion in Mayo Clinic Cancer Research Consortium study RC0639 phase II study of cardiac safety and tolerability of adjuvant chemotherapy plus trastuzumab with lapatinib for resected Her2+ breast cancer (MCCRC RC0639). Methods: Central confirmatory methods were immunohistochemical (IHC) Dako HercepTest on a Dako Autostainer using the manufacturer's recommendations and HercepTest kit epitrope retrieval kit and fluorescent in situ hybridization (FISH) using Vysis PathVysion probe kit. Test results are interpreted using ASCO/CAP guidelines (IHC &gt;30%, Her2:CEP 17 ratio &gt;2.2). Results: There is local and central test 3+ IHC concordance in 48 of 53 tumors (agreement 90.6%) and FISH amplification in 29 of 33 tumors (agreement 87.9%), improved or similar results using identical methods to results in NCCTG N9831 adjuvant trial (n=1063, 81.6% IHC; n=813, 88.1% FISH). Of 92 centrally tested 3+ IHC positive tumors, 88 (95.7%) were FISH amplified. 5 centrally tested patients interpreted as Her2 positive by pre-ASCO/CAP guidelines (IHC &gt;10%; HER2:CEP17 ratio &gt;2) are Her2 ineligible using ASCO/CAP guidelines. IHC not confirmed centrally was reviewed by a second pathologist in 16 of 118 specimens. IHC concordance between two central pathologists was 10/16 (62.5%) in negative or equivocal (≤30% IHC staining) specimens; 7/10 (70%) with two reader agreement were FISH amplified and 4/6 (66%) with disagreement were FISH amplified. Conclusions: Concordance in IHC and FISH results between local and central labs is similar or improved since N9831. New ASCO/CAP Her2 testing guidelines change eligibility based on Her2 status in 4.2 % of patients. Equivocal IHC results falling between pre- and post- ASCO/CAP IHC positive thresholds (&gt;10% and &lt;30% IHC strong staining) are only partially resolved by repeat IHC review and/or FISH testing. No significant financial relationships to disclose.
Postgastrectomy Syndromes.
Journal: Annals of Internal Medicine (1977)

Nowadays, there are a significant number of patients who have in their personal history a gastrectomy, a very common procedure in the past decades in the treatment of peptic ulcer. In addition, there is also another group of patients who are long-term survivors after gastrectomy made for gastric cancer. The awareness regarding the late complications after gastric resections must be raised not only for surgeons but also for gastroenterologists and general practitioners. This article describes the postgastrectomy syndromes elaborating on the symptoms, the pathophysiological mechanisms involved and the possible treatment.
Contraceptive effectiveness may be being sacrificed for safety
Authors: J. Murty, S. Firth
Journal: BMJ (1996)

EDITOR,—The Committee on Safety of Medicines recently published a statement about the increased risk of breast cancer associated with oral contraceptives.1 Have the effects of previous alerts about the contraceptive pill been assessed to show their impact on choices in contraception? Research shows that women primarily choose a contraceptive for its effectiveness and lack of side effects.2

Recently, the Marie Stopes Centre in Leeds reported a rise in …
PWE-397 What is the correct prophylactic dose of tinzaparin in general surgical patients?
Authors: C El-Sayed, J Francombe
Journal: Gut (2015)

<h3>Introduction</h3> Thrombophylaxis should be prescribed in accordance with risk of thrombosis. The manufacturers of Tinzaparin recommend 3500 units for prophylaxis of DVT in all general surgical patients. Orthopaedic patients are classified as high risk and should receive a weight based calculated dose of 50 IU/kg body or 4500 units. Currently there is no consideration of tinzaparin dose for general surgical patients who are at high risk of thrombosis i.e. cancer patients or emergency surgery patients. Furthermore, there is no guidance for patients who are under or overweight. <h3>Method</h3> A prospective audit was conducted over 8 weeks on one ward. All emergency and elective surgical patients were considered. Data collected included patients’ demographics, weight and tinzaparin dose. This was compared to a theoretical weight calculated dose (TWCD). <h3>Results</h3> 100 general surgical patients were included. Median age 69 years (25–95). Median weight 74 Kg (41–100). 30% of patients underwent surgery and were considered high risk of DVT. 70% were managed conservatively and considered low risk. 13% of patients received 3500 units. 87% received 4500 units. 57% of general surgical patients received too high a dose of tinzaparin on risk criteria alone by 1000 units. Median TWCD 3650 units (2095 -6487). All high risk patients received the recommended 4500 units. Median TWCD 3640 units (2750- 4800). Considering TWCD; 71.2% patients were over anti-coagulated by median 1109 units. 20.7% of overweight patients were under anti-coagulated by median 1560 units. Four patients bled significantly post surgery. They received 4500 units. According to weight based calculations they were over anti-coagulated by a median of 638 units. <h3>Conclusion</h3> The correct dose of tinzaparin needs clarification in general surgical patients. We recommend consideration of a weight calculated dose of tinzaparin. <h3>Disclosure of interest</h3> None Declared.
Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group
Authors: Jason P. Lott, Joann G. Elmore, Ge A. Zhao, Stevan R. Knezevich, Paul D. Frederick, Lisa M. Reisch, Emily Y. Chu, Martin G. Cook, Lyn M. Duncan, Rosalie Elenitsas, Pedram Gerami, Gilles Landman, Lori Lowe, Jane L. Messina, Martin C. Mihm, Joost J. van den Oord, Michael S. Rabkin, Birgitta Schmidt, Christopher R. Shea, Sook Jung Yun, George X. Xu, Michael W. Piepkorn, David E. Elder, Raymond L. Barnhill
Journal: Journal of the American Academy of Dermatology (2016)
Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation
Authors: Khadija M Alawi, Fiona A Russell, Aisah A Aubdool, Salil Srivastava, Yanira Riffo-Vasquez, Lineu Baldissera, Pratish Thakore, Nurjahan Saleque, Elizabeth S Fernandes, David A Walsh, Susan D Brain
Journal: Annals of the Rheumatic Diseases (2016)

Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis. Male wild-type and TRPC5 knockout (KO) mice were used in a complete Freund's adjuvant (CFA)-induced unilateral arthritis model, assessed over 14 days. Arthritis was determined by measurement of knee joint diameter, hindlimb weightbearing asymmetry and pain behaviour. Separate studies involved chronic pharmacological antagonism of TRPC5 channels. Synovium from human postmortem control and inflammatory arthritis samples were investigated for TRPC5 gene expression. At baseline, no differences were observed. CFA-induced arthritis resulted in increased synovitis in TRPC5 KO mice assessed by histology. Additionally, TRPC5 KO mice demonstrated reduced ispilateral weightbearing and nociceptive thresholds (thermal and mechanical) following CFA-induced arthritis. This was associated with increased mRNA expression of inflammatory mediators in the ipsilateral synovium and increased concentration of cytokines in synovial lavage fluid. Chronic treatment with ML204, a TRPC5 antagonist, augmented weightbearing asymmetry, secondary hyperalgesia and cytokine concentrations in the synovial lavage fluid. Synovia from human inflammatory arthritis demonstrated a reduction in TRPC5 mRNA expression. Genetic deletion or pharmacological blockade of TRPC5 results in an enhancement in joint inflammation and hyperalgesia. Our results suggest that activation of TRPC5 may be associated with an endogenous anti-inflammatory/analgesic pathway in inflammatory joint conditions.
Two new blood tests will help doctors rule out pre-eclampsia, says NICE
Authors: Jacqui Wise
Journal: BMJ (2016)

The National Institute for Health and Care Excellence (NICE) has recommended two new blood tests to help doctors rule out pre-eclampsia in women between the 20th and 35th week of pregnancy.1

At the moment women with suspected pre-eclampsia often have to be admitted to hospital for 24 to 36 hours so that a diagnosis can be made. These new tests may help to avoid admission to hospital.

Pre-eclampsia and associated eclampsia are the second leading cause of direct maternal deaths in the United Kingdom. About a third of women with pre-eclampsia have it diagnosed before the 35th week of pregnancy.

The …
The phase III study INTERCEPTOR in locally advanced head and neck cancer (LA-HNC). Preliminary safety report
Authors: M.C. Merlano, S. Vecchio, A. Bacigalupo, E.G. Russi, N. Denaro, O. Ostellino, M. Rampino, M. Benasso, M. Boitano, G. Numico, M. D'Amico, A. Grimaldi, F. Blengio, L. Licitra, C. Pinto, M. Aieta, S. Bui, R. Mattioli, F. Bertolini, G. Gasparini, C. Boni
Journal: Annals of Oncology (2015)
Controversies and research agenda in nephropathic cystinosis: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference
Authors: Craig B. Langman, Bruce A. Barshop, Georges Deschênes, Francesco Emma, Paul Goodyer, Graham Lipkin, Julian P. Midgley, Chris Ottolenghi, Aude Servais, Neveen A. Soliman, Jess G. Thoene, Elena N. Levtchenko, Oliver Amon, Gema Ariceta, Maryan Basurto, Leticia Belmont-Martínez, Aurélia Bertholet-Thomas, Marjolein Bos, Thomas Brown, Stephanie Cherqui, Elisabeth A.M. Cornelissen, Monte Del Monte, Jie Ding, Ranjan Dohil, Maya Doyle, Ewa Elenberg, William A. Gahl, Victor Gomez, Marcella Greco, Christy Greeley, Larry A. Greenbaum, Paul Grimm, Katharina Hohenfellner, Teresa Holm, Valerie Hotz, Mirian C. Janssen, Frederick Kaskel, Rita Magriço, Galina Nesterova, Philip Newsholme, Patrick Niaudet, Patrice Rioux, Minnie M. Sarwal, Jerry Schneider, Rezan Topaloglu, Doris A. Trauner, Maria Helena Vaisbich, Lambertus P. van den Heuvel, William Van't Hoff
Journal: Kidney International (2016)