tbuckley/cabot-search huggingface dataset:
Aberrant TGF-β activation in bone tendon insertion induces enthesopathy-like disease
Authors: Xiao Wang, Liang Xie, Janet Crane, Gehua Zhen, Fengfeng Li, Ping Yang, Manman Gao, Ruoxian Deng, Yiguo Wang, Xiaohua Jia, Cunyi Fan, Mei Wan, Xu Cao
Journal: Journal of Clinical Investigation (2018)

Enthesopathy is a disorder of bone, tendon, or ligament insertion. It represents one-fourth of all tendon-ligament diseases and is one of the most difficult tendon-ligament disorders to treat. Despite its high prevalence, the exact pathogenesis of this condition remains unknown. Here, we show that TGF-β was activated in both a semi-Achilles tendon transection (SMTS) mouse model and in a dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations of active TGF-β recruited mesenchymal stromal stem cells (MSCs) and led to excessive vessel formation, bone deterioration, and fibrocartilage calcification. Transgenic expression of active TGF-β1 in bone also induced enthesopathy with a phenotype similar to that observed in SMTS and DI mice. Systemic inhibition of TGF-β activity by injection of 1D11, a TGF-β–neutralizing antibody, but not a vehicle antibody, attenuated the excessive vessel formation and restored uncoupled bone remodeling in SMTS mice. 1D11-treated SMTS fibrocartilage had increased proteoglycan and decreased collagen X and matrix metalloproteinase 13 expression relative to control antibody treatment. Notably, inducible knockout of the TGF-β type II receptor in mouse MSCs preserved the bone microarchitecture and fibrocartilage composition after SMTS relative to the WT littermate controls. Thus, elevated levels of active TGF-β in the enthesis bone marrow induce the initial pathological changes of enthesopathy, indicating that TGF-β inhibition could be a potential therapeutic strategy.
Tracking digital ulcers in systemic sclerosis: a feasibility study assessing lesion area in patient-recorded smartphone photographs
Authors: Graham Dinsdale, Tonia L Moore, Joanne B Manning, Andrea K Murray, Ross Atkinson, Karen Ousey, Mark R Dickinson, Christopher Taylor, Ariane L Herrick
Journal: Annals of the Rheumatic Diseases (2018)

Systemic sclerosis (SSc)-related digital ulcers (DUs) are painful and disabling,1–3 and DU burden is often the primary outcome measure in clinical trials of SSc-related digital vasculopathy.4 This is despite several studies showing a lack of agreement between rheumatologists as to what constitutes a DU.5–8

Objective outcome measures of SSc-related DUs for tracking change over time are therefore urgently required for clinical practice and research studies. The application of digital planimetry to clinical DU photographs has shown the possibility of fine-grained measurement of DU characteristics (area).9 Our aims were to (1) demonstrate the feasibility of patients with SSc-related DUs/digital lesions photographing their lesions using smartphone cameras, and (2) use digital planimetry-style software analysis on images collected from patients to measure and track lesion area as a marker of healing or progression.

Patients with SSc-related digital lesions (judged to be ulcers by an experienced clinician) were asked to photograph …
Phenotype Does Not Always Equal Function: HDAC Inhibitors and UM171, but Not SR1, Lead to Rapid Upregulation of CD90 on Non-Engrafting CD34+CD90-Negative Human Cells
Authors: Kevin A. Goncalves, Megan D. Hoban, Jennifer L. Proctor, Hillary L. Adams, Sharon L. Hyzy, Anthony E. Boitano, Michael P. Cooke
Journal: Blood (2017)
What is it to remember?
Authors: Johannes B. Mahr, Gergely Csibra
Journal: Behavioral and Brain Sciences (2018)

Abstract In response to the commentaries, we clarify and defend our characterization of both the nature and function of episodic memory. Regarding the nature of episodic memory, we extend the distinction between event and episodic memory and discuss the relational role of episodic memory. We also address arguments against our characterization of autonoesis and argue that, while self-referential, it needs to be distinguished from an agentive notion of self. Regarding the function of episodic memory, we review arguments about the relation between future mental time travel and memory veridicality; clarify the relation between autonoesis, veridicality, and confidence; and finally discuss the role of episodic memory in diachronic commitments.
Fixed and Reproducible Orthostatic Proteinuria
Authors: ALFRED L. THOMPSON
Journal: Annals of Internal Medicine (1970)

Follow-up evaluation was carried out on 43 of 64 young men in whom a diagnosis of "fixed" orthostatic proteinuria had been established 10 years earlier. Forty-nine percent of the patients still had some type of clinical proteinura. Clinical or laboratory evidence of progressive renal disease was not found in a single patient. The 10-year prognosis of patients with this disorder is excellent, although the long-term outlook of those patients with continuing proteinura must still be regarded with some reservation. The final clinical expression of "fixed" orthostatic proteinuria has not yet been established in all patients.
Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer
Authors: Willemien J. van Driel, Simone N. Koole, Karolina Sikorska, Jules H. Schagen van Leeuwen, Henk W.R. Schreuder, Ralph H.M. Hermans, Ignace H.J.T. de Hingh, Jacobus van der Velden, Henriëtte J. Arts, Leon F.A.G. Massuger, Arend G.J. Aalbers, Victor J. Verwaal, Jacobien M. Kieffer, Koen K. Van de Vijver, Harm van Tinteren, Neil K. Aaronson, Gabe S. Sonke
Journal: New England Journal of Medicine (2018)

Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer.In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points.In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76).Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .).
Features of the Immunophenotype of Tumor Plasmocytes in the Bone Marrow and Peripheral Blood for Multiple Myeloma Complicated By Plasmacytomas
Authors: Kirill Belousov, Anatoly Golenkov, Tatiana Mitina, Yulia Chuksina, Elena Trifonova, Elena Kataeva, Lyudmila Vysotskaya, Yulia Chernykh, Sergei Zakharov, Aleksandr Mitin, Sergei Shevelev, Yulia Sverkunova, Elena Klinushkina
Journal: Blood (2017)
Molecular Responses after Switching from a Standard-Dose Twice-Daily Nilotinib Regimen to a Reduced-Dose Once-Daily Schedule in Patients with Chronic Myeloid Leukemia: A Real Life Observational Study (NILO-RED)
Authors: Delphine Rea, Jean-Michel Cayuela, Stephanie Dulucq, Gabriel Etienne
Journal: Blood (2017)
Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease
Authors: Adolfo Ramirez-Zamora, Jill L. Ostrem
Journal: JAMA Neurology (2018)

Selection of the best deep brain stimulation (DBS) target-subthalamic nucleus (STN) or globus pallidus interna (GPi)-for treatment of motor complications in Parkinson disease remains a matter of debate.Increasing evidence from randomized clinical trials indicates that motor benefit is similar between both targets, including an effect on dyskinesia and improvement in quality of life. Deep brain stimulation of the STN offers consistently greater dopaminergic medication reduction, possible mild benefit in nonmotor domains, and potential economic advantage. Deep brain stimulation of the GPi provides a probable advantage in dyskinesia suppression, management of symptoms with unilateral leads, and flexibility in medications and programming adjustments. Overall, STN DBS is at potentially higher or equal risk for neuropsychiatric changes compared with GPi DBS.Both GPi and STN DBS provide similar, consistent, marked motor benefits, but subtle target differences exist. Target selection should be tailored to each patient's clinical presentation, neuropsychiatric profile, and goals of surgery, allowing customization of this therapy and improved individual outcomes.
Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
Authors: Maria J Perugorria, Aitor Esparza-Baquer, Fiona Oakley, Ibone Labiano, Ana Korosec, Alexander Jais, Jelena Mann, Dina Tiniakos, Alvaro Santos-Laso, Ander Arbelaiz, Riem Gawish, Ana Sampedro, Antonio Fontanellas, Elizabeth Hijona, Raul Jimenez-Agüero, Harald Esterbauer, Dagmar Stoiber, Luis Bujanda, Jesus María Banales, Sylvia Knapp, Omar Sharif, Derek A Mann
Journal: Gut (2018)

Objective Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. Design TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and Trem-2 -/- mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments. Results TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in Trem-2 -/- mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses. Conclusion Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.
Overcoming paclitaxel resistance with new fatty acid conjugates of second generation taxoids
Authors: Ralph J. Bernacki, Jean Veith, Larisa V. Kuznetsova, Xinyuan Wu, Jin Chen, Antonella Pepe, Liang Sun, Iwao Ojima
Journal: Cancer Research (2004)

5423  Based on the reported (Bradley et al., Clin. Cancer Res. 7: 3229-3238, 2001) increased efficacy and decreased toxicity of Taxoprexin [docosahexanoic acid conjugated to paclitaxel, DHA-paclitaxel] as compared to paclitaxel in mice implanted with Madison 109 s.c. lung tumor, we synthesized and evaluated a series of paclitaxel analogues conjugated to natural fatty acids including DHA, docosanoic acid (DO), linolenic acid (LNA) and linoleic acid (LNA) for their antitumor efficacy in SCID mice implanted with a human tumor xenograft. Initial experiments using the A121 human ovarian tumor xenograft implanted s.c. in SCID mice confirmed the studies of Bradley et al. demonstrating greater than a two-fold increase in tumor growth delay for DHA-paclitaxel as compared to paclitaxel with complete regressions in 2 of 5 treated mice. In addition, one of the new conjugates, DHA-SBT-1213, administered i.v. on days 5, 8 and 11 at 30mg/kg, caused complete regression (CR) of tumor in all surviving mice (4 of 5), with one animal apparently succumbing to drug toxicity. Using the paclitaxel resistant, Pgp positive DLD1 human colon tumor xenograft implanted s.c. in SCID mice, paclitaxel and DHA-paclitaxel were virtually ineffective causing tumor growth delays of 8 and 4 days, respectively. DHA-SBT-1213 on the other hand, induced a statistically significant 54- day delay in DLD1 tumor growth and treatment with DHA-SBT-1214, another new taxane conjugate, resulted in CR in 5 of 5 mice, with all mice being tumor free 120 days after tumor implantation. Preclinical efficacy studies of these taxanes conjugated to other fatty acids are currently underway. Initial findings indicate conjugated fatty acids other than DHA are equally as effective in increasing the preclinical therapeutic activities of various taxanes. These findings indicate that certain second generation taxoids, previously selected for their ability to overcome Pgp mediated multidrug resistance, can be conjugated to natural fatty acids resulting in compounds that are well tolerated and extremely effective for the treatment of paclitaxel sensitive and more importantly, paclitaxel resistant tumors.
Assessing the feasibility and validity of the Toronto Childhood Cancer Stage Guidelines: a population-based registry study
Authors: Joanne F Aitken, Danny R Youlden, Andrew S Moore, Peter D Baade, Leisa J Ward, Vicky J Thursfield, Patricia C Valery, Adèle C Green, Sumit Gupta, A Lindsay Frazier
Journal: The Lancet Child & Adolescent Health (2018)
Abstract 15643: Early versus Non-Early Administration of Epinephrine After Out-of-Hospital Cardiac Arrest With Non-Shockable Rhythm: A Population-Based Cohort Study
Authors: Tatsuma Fukuda, Anne Grossestreuer, Mathias Holmberg, Ichiro Kukita, Michael Donnino
Journal: Circulation (2017)

Introduction:  There are conflicting studies as to whether prehospital administration of epinephrine is beneficial in out-of-hospital cardiac arrest (OHCA). However, many studies have indicated that if epinephrine is to be administered, it should be given as soon as feasible in cardiac arrest with initial non-shockable rhythm.   Hypothesis:  The effectiveness of epinephrine for OHCA may differ depending on the timing of administration. We sought to assess whether early administration of epinephrine would be associated with an increased chance of survival after adult OHCA with non-shockable rhythm compared with non-early (late or no) administration of epinephrine.   Methods:  This nationwide population-based study of OHCA patients was based on data from the All-Japan Utstein Registry. We included all adult non-shockable OHCA patients who were witnessed and received cardiopulmonary resuscitation (CPR) by bystanders in Japan from 2011 to 2014. Time from bystander witness to the first administration of epinephrine within 20 minutes was defined as early administration. The primary outcome was one-month overall survival.   Results:  A total of 20,673 patients were included; 2,923 (14.1%) received early administration of epinephrine, 17,750 (85.9%) did not. Among these patients, 994 (4.8%) survived one month after OHCA. The odds of one-month overall survival were significantly higher for patients receiving early administration of epinephrine after adjusting for potential confounders: multivariable logistic regression modeling, adjusted OR 1.29 (95%CI 1.09 to 1.52); propensity score (PS) matching, OR 1.30 (95%CI 1.05 to 1.60); PS adjustment (linear), adjusted OR 1.32 (1.12 to 1.56); and PS adjustment (quintiles), adjusted OR 1.31 (95%CI 1.11 to 1.54). Although similar associations were observed for prehospital return of spontaneous circulation, there were no significant differences in one-month neurologically favorable survival between the early and non-early epinephrine groups.   Conclusions:  In adult non-shockable witnessed OHCA with bystander CPR, early administration of epinephrine was associated with an increased chance of one-month overall survival compared with non-early (late or no) administration of epinephrine.
Successful treatment of an impacted lithotripter basket in the common bile duct with intracorporeal electrohydraulic lithotripsy
Authors: Justine Fenner, Michael Croglio, Demetrios Tzimas, Juan Bucobo
Journal: Endoscopy (2018)

A 62-year-old woman with hypothyroidism and hypertension presented to an outside hospital with abdominal pain. She was found on her initial workup to have choledocholithiasis and was transferred to our institution for endoscopic retrograde cholangiopancreatography (ERCP). The cholangiogram demonstrated common bile duct (CBD) dilatation, with right and left hepatic duct dilatation ([Fig. 1 a]). When mechanical lithotripsy to break up the stone was attempted, the stone and basket became impacted in the distal CBD during extraction ([Fig. 1 b]). An emergency lithotripter (Olympus America, Center Valley, Pennsylvania, USA) was used to release the basket from around the stone, but the device broke owing to a mechanical malfunction and the wires of the basket were severed near the handle and sheath. Direct cholangioscopy was then performed with electrohydraulic lithotripsy (EHL) to fragment the stone ([Fig. 2]), although further attempts were unsuccessful.
Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation
Authors: Samar H Ibrahim, Petra Hirsova, Gregory J Gores
Journal: Gut (2018)

A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed non-alcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation.
EARLY INTRODUCTION OF SUBCUTANEOUS (S.C.) HEPATITIS B IMMUNOGLOBULIN (HBIg) PROVIDES LP19 : Early introduction of subcutaneous (S.C.) hepatitis B immunoglobulin (HBIg) provides effective prophylaxis for hepatitis B virus (HBV) reinfection after liver transplantation (TX).
Authors: D Samuel, P De Simone, M Salizzoni, Ad Pinna, U Cillo, F Zamboni, D Mutineer
Journal: Journal of Hepatology (2015)
Abstract 17285: Disruption of A-kinase Anchoring Protein 150 Causes Coronary Spasm Through Enhanced Calcium Sensitization: A Potential Role of Microrna-30b
Authors: Kimitaka Nishizaki, Hirofumi Tomita, Maiko Senoo, Noritomo Narita, Masato Narita, Manabu Yonekura, Hiroaki Ichikawa, Yoshihiro Kimura, Makoto Tanaka, Tomohiro Osanai, Ken Okumura
Journal: Circulation (2016)

Introduction: We previously reported that human variant form of phospholipase C (PLC)-δ1, an amino acid replacement of arginine 257 to histidine (R257H), shows an enhanced PLC activity, leading to ...
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
Authors: Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric H. Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H. Souter, Erik Thunnissen, Ming S. Tsao, Christina B. Ventura, Murry W. Wynes, Yasushi Yatabe
Journal: Journal of Thoracic Oncology (2018)
Is the Time of Revisiting Classification of Thalassemia Syndromes According with the Phenotype Severity?
Authors: Angela Vitrano, Giuseppina Calvaruso, Lorella Pitrolo, Alessia Pepe, Antonella Meloni, Laura Pistoia, Maria Rita Gamberini, Vincenzo Caruso, Aldo Filosa, Paolo Ricchi, Liana Cuccia, Domenico D'Ascola, Francesco Sorrentino, Angelo Peluso, Aurelio Maggio
Journal: Blood (2017)
Emotional memories and how your life may depend upon them
Authors: Tayler Eaton, Adam K Anderson
Journal: Behavioral and Brain Sciences (2018)

Abstract In this commentary, we discuss how one's internal body state and the appraisals an individual utilizes at encoding alter later episodic memory irrespective of social discourse. We suggest that the purpose of episodic memory is originally the preservation of the self, which may have been co-opted to navigating the social world.
Comparison of Pathological Responses (PR) Observed on Colorectal Cancer Metastases (CRCM) Resected After Different Preoperative Treatments
Authors: M. van den Eynde, M. Gizzi, G. Pairet, P. Lefesvre, V. Lannoy, J. Gigot, B. Navez, J. Canon, C. Sempoux, J. Carrasco
Journal: Annals of Oncology (2012)
Considering the Ability of General Surgeons to Add Value to Pediatric Surgery
Authors: Lorraine I. Kelley-Quon, Nam Nguyen, Jeffrey S. Upperman
Journal: JAMA Surgery (2018)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal