tbuckley/cabot-search huggingface dataset:
A novel GTPCH deficiency mouse model exhibiting tetrahydrobiopterin-related metabolic disturbance and infancy-onset motor impairments
Authors: Xiaoling Jiang, Huazhen Liu, Yongxian Shao, Mingzhi Peng, Wen Zhang, Duan Li, Xiuzhen Li, Yanna Cai, Ting Tan, Xinshuo Lu, Jianan Xu, Xueying Su, Yunting Lin, Zongcai Liu, Yonglan Huang, Chunhua Zeng, Ya-ping Tang, Li Liu
Journal: Metabolism (2019)
Spatial Distribution of Motor Endplates and its Adaptive Change in Skeletal Muscle
Authors: Xiaofeng Yin, Tingting Yu, Bo Chen, Jianyi Xu, Wentao Chen, Yisong Qi, Peixun Zhang, Yusha Li, Yuhui Kou, Yilin Ma, Na Han, Peng Wan, Qingming Luo, Dan Zhu, Baoguo Jiang
Journal: Theranostics (2019)

Motor endplates (MEPs) are the important interfaces between peripheral nerves and muscle fibers. Investigation of the spatial distribution of MEPs could help us better understand neuromuscular functional activities and improve the diagnosis and therapy of related diseases. Methods: Fluorescent α-bungarotoxin was injected to label the motor endplates in whole-mount skeletal muscles, and tissue optical clearing combined with light-sheet microscopy was used to investigate the spatial distribution of MEPs and in-muscle nerve branches in different skeletal muscles in wild-type and transgenic fluorescent mice. Electrophysiology was used to determine the relationship between the spatial distribution of MEPs and muscle function. Results: The exact three-dimensional distribution of MEPs in whole skeletal muscles was first obtained. We found that the MEPs in the muscle were distributed in an organized pattern of lamella clusters, with no MEPs outside the lamella zone. Each MEP lamella was innervated by one independent in-muscle nerve branch and mediated an independent muscle subgroup contraction. Additionally, the MEPs changed along the lamella clusters after denervation and regained the initial pattern after reinnervation. The integrity and spatial distribution of MEPs could reflect the functional state of muscles. The signal absence of a certain MEP lamella could suggest a problem in certain part of the muscle. Conclusions: The MEP lamella clusters might be the basis of neuromuscular function, and the spatial distribution of MEPs could serve as a testbed for evaluating the functional status of muscle and the therapeutic targeting map related to MEPs.
Impact of new chemotherapy regimens on the treatment landscape and survival of advanced pancreatic cancer (PAC) patients (pts).
Authors: Markus Kieler, Matthias Unseld, Daniela Bianconi, Werner Scheithauer, Gerald W. Prager
Journal: Journal of Clinical Oncology (2019)

403 Background: The clinical phase III first-line trials MPACT and PRODIGE4/ACCORD11 in metastatic PAC pts have changed the treatment paradigm. We aimed to analyse the impact of these regimens on the treatment landscape and survival of advanced PAC pts. Methods: In this single institutional retrospective cohort analysis patient characteristics and overall survival (OS) from all pts with advanced PAC treated between 01/2011-12/2017 were analysed. Survival analyses were performed by Kaplan-Meier method. Results: A total of 301 pts started a systemic treatment in the observation period. Concerning the first-line treatment, there was a clear shift from four different main regimens (gemcitabine/nab-paclitaxel (G+nab-P), FOLFIRINOX, gemcitabine/oxaliplatin +/- erlotinib, gemcitabine mono) to only two (G+Nab-P, FOLFIRINOX), that made up more than 80% of the administered first-line treatments in each of the groups (2011-2013 vs. 2014-2017). The rate for first-line FOLFIRINOX treatment was balanced between the two groups (19% and 15%). G+nab-P treated pts had a median age of 66 years, 41.3% had an ECOG 1-2, the FOLFIRINOX treated pts were younger and fitter (57 years and 24.5 % ECOG 1, 0% ECOG 2). 60.7% of pts treated with G+nab-P received a second-line and 30.7% pts received a third-line treatment, while for the FOLFIRINOX pts these rates were 69.8% and 41.5%. Median OS of pts that started first-line treatment between 2011 and 2013 was 8.77 months (95% CI 6.98-10.57) and for those that started first-line treatment between 2014 and 2017 median OS was 11.07 months (95% CI 8.94 13.20) (p = 0.038, Log-Rank-Test). Conclusions: There is a clear impact of new chemotherapy regimens on the treatment landscape. Furthermore, we provide real-world evidence that since the introduction of these new treatment options, the survival of pts with advanced PAC has significantly improved.
Cost and Outcomes Information Should Be Part of Shared Decision Making
Authors: William B. Weeks, James N. Weinstein
Journal: JAMA Surgery (2019)

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
The strategy of zero-mortality due to postoperative VTE in patients with colorectal cancer.
Authors: Shoko Iwahashi, Masaaki Nishi, Ikemoto Tetsuya, Kozo Yoshikawa, Jun Higashijima, Tomohiko Miyatani, Takuya Tokunaga, Chie Takasu, Hideya Kashihara, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2019)

511 Background: The best method of venous thromboembolism (VTE) prevention after surgery for colorectal cancer remains unclear. It is reported that about 20-40% of high-risk patients were diagnosed as DVT and 2-4% was diagnosed as PE and its mortality rate is 0.5-1.0%. The aim of this study is to evaluate the incidence of postoperative VTE patients with colorectal adenocarcinoma and to evaluate the efficacy of VTE preventive strategy. Methods: A total of 264 patients who had undergone curative surgical resection for colorectal cancer at Tokushima University Hospital were included in this study (n = 264 colon: rectum = 1:0.57). All patients were measured D-dimer preoperatively. When D-dimer was ≥ 1.1, lower extremities ultrasonography (US) was performed. All patients were treated with Heparin (10,000U/24h) continuously intravenous injection from the day of surgery, and administered Enoxaparin (2,000U/24h) subcutaneous injection after 24h of the operation. Results: In all 264 patients, 74 (28%) were D-dimer ≥ 1.1 and 16 (6%) diagnosed VTE in US (proximal:distal type n = 6:1). 239 (91%) were treated with postoperative anticoagulant therapy. 2 developed perioperative VTE (symptomatic: asymptomatic = 1:1) and after discharge 12 developed postoperative VTE and mortality rate of VTE was 0%. Univariate analysis indicated that obesity (BMI ≥ 25), hyperlipidemia and preoperative PE were risk factors for deep venous thrombosis (DVT) (p &lt; 0.0001, 0.014, 0.0135, respectively) and multivariate analysis revealed that obesity was an independent risk factor for postoperative DVT (p &lt; 0.0001). Conclusions: Obesity (BMI ≥ 25) was independent risk factor for postoperative VTE. Our preventive protocol including screening using D-dimer and lower extremities US and treatment with Enoxaparin is considered as effective for prevention of postoperative VTE.
Baseline and Early Changes in Serum B-Cell Maturation Antigen Levels Predict Progression Free Survival and Response Status for Multiple Myeloma Patients in a Phase 1 Trial Evaluating Ruxolitinib, Lenalidomide and Methylprednisolone
Authors: Sean Bujarski, Camilia Soof, Mingjie Li, Cathy S. Wang, Eric Sanchez, Marsiye Emamy-Sadr, Regina Swift, Kian Rahbari, Saurabh Patil, Tanya M. Spektor, Haiming Chen, James R. Berenson
Journal: Blood (2018)
Food-Protein Induced Allergic Proctocolitis is Prospectively Associated with IgE-Mediated Milk and Egg Allergies by Age 3
Authors: Neelam A. Phadke, Yamini V. Virkud, Victoria Martin, Hannah L. Seay, Corinne Keet, Qian Yuan, Wayne G. Shreffler
Journal: Journal of Allergy and Clinical Immunology (2019)
Late ulceration of residual abortive infantile haemangioma: a rare complication
Authors: A. Welfringer‐Morin, S. Fraitag, X. Balguerie, C. Laaengh‐Massoni, S. Leclerc‐Mercier, S. Hadj‐Rabia, C. Bodemer, O. Boccara
Journal: British Journal of Dermatology (2019)
Identification of genomic alterations differentiating lobular and ductal subtypes of breast cancer
Authors: Lenora W. M. Loo, Carl C. Ton, Douglas I. Grove, Jamie E. Guenthoer, Erin M. Flynn, Kathleen E. Malone, Christopher I. Li, Li Hsu, Peggy L. Porter
Journal: Cancer Research (2006)

2594  The two major histological breast cancer subtypes, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in clinical presentation, morphology, and molecular characteristics. ILC is less common than IDC, but the incidence of ILC has increased over the past 10 years, with no significant increase in the incidence of IDC. This increase has been shown to associate with use of combined hormone replacement therapy in post-menopausal women. To identify molecular alterations that might account for differences between the subtypes, we used Affymetrix GeneChip Mapping 10K Array®, which contains over 11K single nucleotide polymorphisms (SNPs), to assess loss of heterozygosity (LOH) and gene copy number gain or loss in IDC and ILC tumors. Ninety five (53 IDC and 42 ILC) estrogen receptor (ER) positive, stage I or II breast tumors, collected as part of a large epidemiological study, were evaluated using the Map 10K array. Allele calls were compared between constitutive normal genomic blood lymphocyte DNA and genomic DNA from formalin-fixed paraffin-embedded (FFPE) tumor cells enriched by flow cytometric sorting prior to analysis. We calculated fractional allelic loss (FAL) (number of tumors with LOH over the number informative at that site) for each SNP and identified 158 SNPs that showed significantly higher LOH (p-value ≤0.05, Fisher’s exact test) in one histologic subtype over the other. One hundred seventeen SNPs showed a significantly higher frequency of LOH in IDC over ILC, whereas only 41 SNPs showed a significantly higher frequency of LOH in ILC over IDC. SNPs with more frequent LOH in IDC occurred in multiple chromosomal regions. However, 50 of the 117 (43%) SNPs with higher LOH in IDC were located in chromosome arm 8p. SNPs with a higher frequency of LOH in ILC also showed a unique cluster in chromosome arm 6q (20 of the 41 (49%)). SNPs that showed differential LOH between subtypes were located within, or near, genes that have been implicated in tumor cell functions such as DNA repair, cell signaling, adhesion, angiogenesis, apoptosis, and tumor suppression. Evaluation of LOH of specific genes is being done using targeted single tandem repeat (STR) analyses. We used the Affymetrix Chromosome Copy Number Analysis Tool and aCGH to compare gene copy number (loss or gain) and LOH between IDC and ILC. While there were remarkable concordances between regions of LOH and gene copy number alterations, there were also differences, suggesting the complexity of events leading to LOH and/or gene copy number changes. These results support the approach of a genome-wide analysis assessing allelic loss and gene copy number changes for identifying molecular events that have a role in breast cancer subtype characterization.
Abstract 16525: Left Ventricular Unloading Before, Not After, Reperfusion Limits Infarct Size and Improves Survival in Acute Myocardial Infarction: A Bench to Bedside Study
Authors: Navin K Kapur, Vikram Paruchuri, Xiaoying Qiao, Kevin Morine, Lyanne Buiten, Noam Josephy, Mariah Hout, Richard H Karas
Journal: Circulation (2015)

Ischemia-reperfusion injury (IRI) is a major determinant of myocardial damage in acute myocardial infarction (AMI). We explored the hypothesis that reducing left ventricular wall stress (LV unloading) with an axial flow catheter (Impella) before, not after, coronary reperfusion reduces infarct size and improves survival. Methods: We first employed a model of AMI. After 90 minutes of LAD occlusion, adult, male swine (n=4/group) were randomized to: 1) 120 minutes of reperfusion alone (IRI), 2) 30 minutes of LV unloading before 120 minutes of reperfusion (Impella to Balloon Group; ITB) or 3) 30 minutes of reperfusion followed by LV unloading and an additional 120 minutes of reperfusion (Balloon to Impella Group; BTI). Infarct size, myocardial kinase activity, and mitochondrial integrity were quantified. To explore the clinical utility of LV unloading before reperfusion we retrospectively studied all patients in the USPella registry presenting with ST-segmentc elevation AMI and cardiogenic shock who received an Impella within 120 minutes before (n=41; STEMI-ITB) or within 120 minutes after (n=76; STEMI-BTI) percutaneous reperfusion between 2009 and 2014. Results: Compared to IRI alone, infarct size was reduced in the ITB group, not the BTI group (62±2% vs 33±6% vs 58±15%, IRI vs ITB vs BTI, p&lt;0.01 for IRI vs ITB; p&lt;0.05 for ITB vs BTI). Levels of phosphorylated Akt, Erk-1/2, and GSK3b were increased within the infarct zone in the ITB, not BTI group. Mitochondrial numbers and markers of integrity were higher within the infarct zone in the ITB, compared to IRI or BTI. In the registry, in-hospital (51% vs 28%, p=0.02) and 30-day survival (42% vs 20%, p=0.03) were higher in the STEMI-ITB than the STEMI-BTI group. A STEMI-ITB time of less than 60 minutes (n=38) was associated with higher in-hospital survival than a STEMI-BTI time of less than 60 minutes (n=40) (50% vs 25%, p=0.02). Conclusion: Primary LV unloading before, not after, coronary reperfusion reduces infarct size, increases cardioprotective signaling, and improves mitochondrial integrity. These findings are supported by improved survival among patients treated with an Impella before, not after reperfusion in AMI. Future studies are required to explore the clinical utility of primary LV unloading in AMI.
Mohs Appropriate Use Criteria for Superficial Basal Cell Carcinoma—Reply
Authors: Howard K. Steinman, Anthony Dixon, Christopher B. Zachary
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Nasal polyposis is a risk factor for having positive lysine-aspirin nasal challenges in aspirin-exacerbated respiratory disease
Authors: Inmaculada Doña, Natalia Pérez-Sánchez, Paloma Campo, Maria Salas, Testera-Monte Almudena, Jesus Verge, Teresa Espino, Jose A. Cornejo-Garcia, Cristobalina Mayorga, M.J. Torres
Journal: Journal of Allergy and Clinical Immunology (2019)
Quality and Safety in Health Care, Part XLV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Burnout not only is a serious problem for physicians, but it also adversely affects the quality and safety of health care for the patients they care for. A doctor with burnout may commit more errors, exhibit unprofessional behavior and a callous attitude to others, have diminished productivity, and cause other problems for the health care system. Furthermore, the percentage of doctors who experience at least 1 symptom of burnout is increasing.
Racial effect of early stage colorectal cancer outcomes in a comprehensive cancer center.
Authors: Benjamin D Fangman, Muhammad Shaalan Beg, Aravind Sanjeevaiah, Farshid Araghizadeh, Shannon Scielzo, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2019)

710 Background: Oncologic treatment at National Cancer Institute (NCI) designated comprehensive cancer centers improves outcomes in a variety of malignancies. Racial disparity plays an important role in cancer outcomes and prognosis. Racial outcomes were compared in early stage colorectal cancer patients that presented to a comprehensive cancer center. Methods: This is a retrospective analysis on patients diagnosed with AJCC stage II or stage III colorectal cancer and underwent surgery or adjuvant chemotherapy within the University of Texas Southwestern and Simmons Comprehensive Cancer Center. Pertinent data points were abstracted from EMR including demographic data and dates of initial diagnosis, surgery, adjuvant chemotherapy, progression, and death. Results: Between 4/2011 and 11/2015, 203 patients were identified and 167 patients had complete follow up data available. Median age of cohort was 62 (range 21-90) and most of the patients were men (52.7%). Stage II comprised 44.3% of patients while 55.7% were diagnosed at stage III. One hundred and twenty patients (71.9%) were white, while 34 patients (20.4%) identified as black and the rest belonged to other races. Hispanic ethnicity was identified in 10.4% of patients. There was no significant difference between white and black cohorts between variables age (median 62 vs. 64.5 years; p = 0.44), gender (p = 0.43), and stage (p = 0.99) of colorectal cancer. Similarly there was no significant difference between white and black race in regards to days to surgery (median 17 vs 32 days; p = 0.53), first medical oncology appointment (30 vs. 34 days; p = 0.23) and days to adjuvant chemotherapy (42 vs 52 days; p = 0.24). The rate of recurrence (10.9% vs. 26%; p = 0.09), rate of death (14.1% vs 14.7%; p = 1.0), median relapse free survival (41.7 vs. 36.2 months; p = 0.173) and median overall survival (42 vs. 38.5 months; p = 0.491) from colorectal cancer were also not significantly different between white and black races. Conclusions: Oncologic treatment at NCI designated comprehensive cancer centers may lead to racial parity in colorectal cancer outcomes. Further research should be completed to compare these results to those seen at safety net hospitals.
Improving Cardiac Arrest Outcomes: Fine-tuning or Paradigm Shift?
Authors: Petter Andreas Steen
Journal: Circulation (2011)

In the 1970-80ies we studied barbiturates, moderately severe hypothermia, free radical scavengers and calcium blockers without impacting outcome after cerebral ischemia. In fact cardiac arrest outcome in general did not improve much until 2005. We underestimated the impact of CPR quality. Long pauses in inadequate depth chest compressions, particularly before, during and after series of defibrillation attempts were documented and found detrimental. We and others have shown that quality can be improved, but as with quality work also outside the health care industry, it requires continuous focus, local champions and continuous feedback both on performance and results. This is true both pre-and in-hospital, both during CPR and in the post-arrest period. The controversy of CPR or defibrillation first is solved, at least for the moment. The place of drugs during CPR is questionable, without solid clinical evidence for improved long term outcome for any drug. Although not universally achieved, significant improvements in cardiac arrest outcome have been reported by some pre- and in-hospital services over the last 5-6 years due to fine-tuning of the treatment process including much focus on the post-arrest period with temperature control/hypothermia and coronary interventions. There are more fine-tuning challenges ahead, and better implementation of known science is required, but what about paradigm shifts? We tend to forget that globally cardiac arrest of non-cardiac origin is a much larger challenge and opportunity that cardiac arrest of cardiac origin, both as potential lives saved, and even more as life-years saved.
Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma
Authors: Vineesh Indira Chandran, Charlotte Welinder, Ann-Sofie Månsson, Svenja Offer, Eva Freyhult, Maria Pernemalm, Sigrid M. Lund, Shona Pedersen, Janne Lehtiö, Gyorgy Marko-Varga, Maria C. Johansson, Elisabet Englund, Pia C. Sundgren, Mattias Belting
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma. Experimental Design: PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay–based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82). Results: Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery. Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.
Comprehensive Minimal Residual Disease (MRD) Analysis of the Fondazione Italiana Linfomi (FIL) MCL0208 Clinical Trial for Younger Patients with Mantle Cell Lymphoma: A Kinetic Model Ensures a More Refined Risk Stratification
Authors: Simone Ferrero, Barbero Daniela, Mariella Lo Schirico, Andrea Evangelista, Annalisa Cifaratti, Daniela Drandi, Elisa Genuardi, Daniele Grimaldi, Luigia Monitillo, Gian Maria Zaccaria, Pietro Maria Stefani, Fabio Benedetti, Ivana Casaroli, Manuela Zanni, Claudia Castellino, Vincenzo Pavone, Mario Petrini, Francesca Re, Stefan Hohaus, Gerardo Musuraca, Nicola Cascavilla, Angela Giovanna Congiu, Anna Marina Liberati, Giovannino Ciccone, Umberto Vitolo, Sergio Cortelazzo, Marco Ladetto
Journal: Blood (2018)