tbuckley/cabot-search huggingface dataset:
Revisit linear regression-based deconvolution methods for tumor gene expression data
Authors: Bo Li, Jun S. Liu, X. Shirley Liu
Journal: Genome biology (2017)

We have recently published a statistical deconvolution method to study infiltrating immune cells using tumor RNA-seq data [1].One of the goals in that work was to understand how proportions of different cell types covary across different cancer tissues.To this end, we estimated the abundance of six cell types over 9000 tumor samples across 23 cancer types, and then assessed the correlations of these estimated proportions across the different samples within a cancer type.In particular we compared our method (TIMER) with CIBERSORT [2], a previously published deconvolution approach, for their ability to assess such correlations.To our surprise, we found many non-biological negative correlations between CIBERSORT estimates, and we believed that this artifact was, to a large extent, due to the incorporation of highly similar features in the linear model, or statistical collinearity.Newman et al., the authors of CIBER-SORT, have raised concerns that these correlations were due to data normalization, instead of collinearity [3].While we agree with Newman and coauthors that the forced normalization indeed introduces unwanted negative correlations, we will show in this response that the inclusion of highly similar features contributes as significantly as normalization, if not more, to the observed artificial negative correlations among the estimates obtained by CIBERSORT.Highly correlated features (covariates) in linear regression models can lead to many technical difficulties, such as high estimation variances, non-robustness, and nonidentifiability.Furthermore, it is often misleading to
Impact of Socio-Economic Deprivation on Mortality Rates after Upper GI Cancer Surgery
Authors: Y Leigh, J Seagroatt, S Cole, M Goldacre, P McCulloch
Journal: Endoscopy (2006)

Aims: Mortality after oesophagectomy and gastrectomy for cancer varies widely between UK centres. We hypothesized that deprivation adversely affects mortality following upper GI cancer surgery.
Association of Hospital Costs With Complications Following Total Gastrectomy for Gastric Adenocarcinoma
Authors: Luke V. Selby, Renee L. Gennarelli, Geoffrey C. Schnorr, Stephen B. Solomon, Mark A. Schattner, Elena B. Elkin, Peter B. Bach, Vivian E. Strong
Journal: JAMA Surgery (2017)

Postoperative complications are associated with increased hospital costs following major surgery, but the mechanism by which they increase cost and the categories of care that drive this increase are poorly described.To describe the association of postoperative complications with hospital costs following total gastrectomy for gastric adenocarcinoma.This retrospective analysis of a prospectively collected gastric cancer surgery database at a single National Cancer Institute-designated comprehensive cancer center included all patients undergoing curative-intent total gastrectomy for gastric adenocarcinoma between January 2009 and December 2012 and was conducted in 2015 and 2016.Ninety-day normalized postoperative costs. Hospital accounting system costs were normalized to reflect Medicare reimbursement levels using the ratio of hospital costs to Medicare reimbursement and categorized into major cost categories. Differences between costs in Medicare proportional dollars (MP $) can be interpreted as the amount that would be reimbursed to an average hospital by Medicare if it paid differentially based on types and extent of postoperative complications.In total, 120 patients underwent curative-intent total gastrectomy for stage I through III gastric adenocarcinoma between 2009 and 2012. Of these, 79 patients (65.8%) were men, and the median (interquartile range) age was 64 (52-70) years. The 51 patients (42.5%) who underwent an uncomplicated total gastrectomy had a mean (SD) normalized cost of MP $12 330 (MP $2500), predominantly owing to the cost of surgical care (mean [SD] cost, MP $6830 [MP $1600]). The 34 patients (28.3%) who had a major complication had a mean (SD) normalized cost of MP $37 700 (MP $28 090). Surgical care was more expensive in these patients (mean [SD] cost, MP $8970 [MP $2750]) but was a smaller contributor to total cost (24%) owing to increased costs from room and board (mean [SD] cost, MP $11 940 [MP $8820]), consultations (mean [SD] cost, MP $3530 [MP $2410]), and intensive care unit care (mean [SD] cost, MP $7770 [MP $14 310]).Major complications were associated with tripled normalized costs following curative-intent total gastrectomy. Most of the excess costs were related to the treatment of complications. Interventions that decrease the number or severity of postoperative complications could result in substantial cost savings.
Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial.
Authors: Lajos Pusztai, Andrea Silber, Erin Wysong Hofstatter, Gina G. Chung, Nina Ruth Horowitz, Donald R. Lannin, Brigid K. Killelea, Anees B. Chagpar, Borbala Szekely, Courtney Frederick, Lawrence Rispoli, Michael DiGiovanna
Journal: Journal of Clinical Oncology (2017)

572 Background: Pathologic complete response (pCR) rates to neoadjuvant chemotherapy in TNBC plateaued at 40% with existing regimens, the co-administration of an immune checkpoint inhibitor might increase pCR rate. The objective of the Phase I portion of this trial was to assess the safety of administering MEDI4736 concomitant with sequential taxane and anthracycline chemotherapy. Methods: The Phase I part followed the 3+3 design exploring two dose levels of MEDI4736 (3 and 10 mg/kg iv q2wk) in combination with weekly nab-paclitaxel (100 mg/m2) x 12 followed by ddAC x 4. Dose limiting toxicities (DLT) were evaluated during the entire 20 weeks of therapy and were defined as (1) gr 4 immune related adverse event (irAE), (2) gr 3 irAE that did not resolve to gr 2 within 3 days or to ≤ gr 1 within 14 days, (3) &gt; gr 3 colitis or pneumonitis, (4) ≥ gr 3 non-irAE causally related to MEDI4736. Results: 3 patients completed therapy at the 3 mg/kg dose without any DLT, 1 additional patient refused further study medication because of recurrent gr 2 fatigue after 7 weeks of therapy. At the 10 mg/kg dose level, all 3 patients completed the nab-paclitaxel+MEDI4736 treatment without any DLT and 2 patients also completed 3 of the 4 planned treatments with ddAC without DLT. Among all 7 patients who started therapy, 1 at the 3 mg/kg group experienced gr 3 dehydration and dyspnea without chest X ray abnormalities which resolved within 48 hours with hydration. There were no other gr 3 AEs. Among the 3 patients who have completed therapy as per protocol (not including the patient who withdraw consent), 1 achieved pCR, 1 had minimal, and 1 had extensive residual cancer. No surgical AE were seen. All patients at the 10 mg/kg dose level will complete surgery by March 2017 and final Phase I toxicity and efficacy results will be presented. Conclusions: Concomitant administration of MEDI4736 10 mg/kg with weekly nab-paclitaxel and subsequently with ddAC neoadjuvant chemotherapy appears safe. The Phase II portion of the trial is open and will accrue a maximum of 50 patients to assess the efficacy of the combination. Clinical trial information: NCT02489448.
Prognostic markers of tumour recurrence and survival of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and radical surgery: A retrospective study
Authors: Michael Abdalmassih, Zachary Raizman, Gokulan Sivananthan, Daniel Kroeker, Pascal Lambert, Debrah Wirtzfeld, Robert Wightman, Maged Nashed
Journal: Annals of Oncology (2017)
Time to move from prognostication to diagnosis and treatment of heart disease in acute exacerbation of COPD
Authors: Sara Roversi, Nathaniel M. Hawkins
Journal: European Respiratory Journal (2017)

In this edition of the journal, Laribi et al . [1] report the incremental value of biomarkers relative to the CURB-65 score for predicting 30-day mortality in acute exacerbations of chronic obstructive pulmonary disease (COPD). The derivation cohort of 356 elderly patients combined four single centre studies of consecutive emergency department attendees, 12% being subsequently admitted to the intensive care unit (ICU). Cardiovascular comorbidity was common (41% hypertension, 20% heart failure). The primary end-point of 30-day mortality occurred in 27 patients (7.6%), congruent with existing literature reporting variable rates of 4.6–12% short-term mortality [2, 3]. The authors focus on the performance of myocardial injury markers, recognising that cardiac disease is a common cause of death in patients with COPD [4]. The link between copeptin, troponin and mortality indicates a strong need for examining cardiac mechanisms in AECOPD <http://ow.ly/iehc30cxZB0>
Subgroup analysis by prior non-liposomal irinotecan therapy in NAPOLI-1: A phase 3 study of nal-IRI±5-fluorouracil/leucovorin in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy
Authors: Jean-Frédéric Blanc, Richard Hubner, Chung-Pin Li, Andrea Wang-Gillam, Gyorgy Bodoky, Andrew Dean, Yan-Shen Shan, Gayle Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Chang-Fang Chiu, Gilberto Schwartsmann, Fadi Braiteh, Daniel Von Hoff, Li-Tzong Chen, Khalid Mamlouk, Parul Bhargava, Floris de Jong, Jens Siveke
Journal: Annals of Oncology (2017)
An older man with memory impairment and convulsions
Authors: Xiu-he Zhao, Yi-ming Liu, Xue Yang, Shu-zhen Wang, Sheng-jun Wang
Journal: BMJ (2017)

A 62 year old man was admitted to hospital with a one month history of convulsions and confusion without fever. He had seizures, memory impairment, and changes in behaviour, sometimes becoming irritated and aggressive. He had no history of alcohol or drug misuse.

Neurological examination showed impairment to memory and cognition, orientation, calculation, and attention abilities. The patient’s Glasgow coma scale score was 13.

Blood tests including full blood count, glucose, serum electrolytes, ammonia, lactate, renal function, and liver function were normal. Tests for infectious and autoimmune conditions were requested.

Analysis of the patient’s cerebrospinal fluid showed normal cytology, with a slightly increased protein level. An electroencephalography exam showed low amplitude slow waves in the temporal lobes. Magnetic resonance imaging (MRI) of the brain showed abnormalities in the bilateral medial temporal lobes (fig 1, A⇓). Based on the imaging findings, blood tests were requested. The patient’s serum anti-thyroid peroxidase level was raised, and the gamma-aminobutyric acid receptor B (GABABR) antibody was positive, both in the serum and cerebrospinal fluid. Tests for anti-onconeural antibodies, including antineuronal nuclear autoantibody type 1 (anti-Hu), antineuronal nuclear autoantibody type 1 (anti-Ri), and Purkinje cell cytoplasmic autoantibody type 1 (anti-Yo), were negative. In addition, thorax computed tomography (CT) showed a nodule in the left lung with lymph …
Dual Isotope SPECT Study With Epilepsy Patients Using Semiconductor SPECT System
Authors: Tohru Shiga, Atsuro Suzuki, Kotarou Sakurai, Tsugiko Kurita, Wataru Takeuchi, Takuya Toyonaga, Kenji Hirata, Keiji Kobashi, Chietsugu Katoh, Naoki Kubo, Nagara Tamaki
Journal: Clinical Nuclear Medicine (2017)

We developed a prototype CdTe SPECT system with 4-pixel matched collimator for brain study. This system provides high-energy-resolution (6.6%), high-sensitivity (220 cps/MBq/head), and high-spatial-resolution images. The aim of this study was to evaluate dual-isotope study of CBF and central benzodiazepine receptor (BZR) images using Tc-ECD and I-IMZ with the new SPECT system in patients with epilepsy comparing with single-isotope study using the conventional scintillation gamma camera.This study included 13 patients with partial epilepsy. The BZR images were acquired at 3 hours after I-IMZ injection for 20 minutes. The images of IMZ were acquired with a conventional 3-head scintillation gamma camera. After BZR image acquisition with the conventional camera, Tc-ECD was injected, and CBF and BZR images were acquired simultaneously 5 minutes after ECD injection with the new SPECT system. The CBF images were also acquired with the conventional camera on separate days. The findings were visually analyzed, and 3D-SSP maximum Z scores of lesions were compared between the 2 studies.There were 47 abnormal lesions on BZR images and 60 abnormal lesions on CBF images in the single-isotope study with the conventional camera. Dual-isotope study with the new system showed concordant abnormal findings of 46 of 47 lesions on BZR and 54 of 60 lesions on CBF images with the single-isotope study with the conventional camera. There was high agreement between the 2 studies in both BZR and CBF findings (Cohen κ values = 0.96 for BZR and 0.78 for CBF). In semiquantitative analysis, maximum Z scores of dual-isotope study with the new system strongly correlated with those of single-isotope study with the conventional camera (BZR: r = 0.82, P < 0.05, CBF: r = 0.87, P < 0.05).Our new SPECT system permits dual-isotope study for pixel-by-pixel analysis of CBF and BZR information with the same pathophysiological condition in patients with epilepsy.
Comparison on the efficacy between partially covered self-expandable metal stent with enlarged head versus uncovered self-expandable metal stent for palliation of gastric outlet obstruction
Authors: Wan Choe Jung, Jin Hyun Jong, Dong-won Lee, Young Kim Seung, Woo Jung Sung, Kul Jung Young, Seol Koo Ja, Joon Yim Hyung, Woo Lee Sang
Journal: Annals of Oncology (2017)
UK lags far behind Europe on diagnosis of dementia with Lewy bodies
Authors: Joseph Freer
Journal: BMJ (2017)

Around half of UK patients who have dementia with Lewy bodies (DLB)—about 60 000 people—have it misdiagnosed, usually as the far more common Alzheimer’s disease, says the DLB Consortium in updated recommendations on diagnosing and managing DLB.

The recommendations update the expert group’s 2005 recommendations and are published in Neurology this month,1 including new consensus criteria for diagnosing DLB that give increased weight to neuroimaging and cardiac imaging alongside clinical criteria. Use of these imaging methods will …
Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation—a position paper
Authors: L. Sarmati, M. Andreoni, G. Antonelli, W. Arcese, R. Bruno, N. Coppola, G.B. Gaeta, M. Galli, C. Girmenia, M. Mikulska, F. Pane, C.F. Perno, M. Picardi, M. Puoti, A. Rambaldi, V. Svicher, G. Taliani, G. Gentile
Journal: Clinical Microbiology and Infection (2017)
Efficacy and safety of lorlatinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) with one or more prior ALK tyrosine kinase inhibitor (TKI): A phase I/II study.
Authors: Alice Tsang Shaw, Sai-Hong Ignatius Ou, Enriqueta Felip, Todd Michael Bauer, Benjamin Besse, Shirish M. Gadgeel, D. Ross Camidge, Chia-Chi Lin, Takashi Seto, Ross A. Soo, Rita Chiari, Leonard P. James, Jill S. Clancy, Jean-Francois Martini, Antonello Abbattista, Yazdi K. Pithavala, Benjamin J. Solomon
Journal: Journal of Clinical Oncology (2017)

9006 Background: Lorlatinib is a selective, potent, brain-penetrant, next generation ALK/ROS1 TKI active against most known resistance mutations. In Ph I of this Ph I/II study, lorlatinib showed robust clinical activity in ALK+ or ROS1+ advanced NSCLC pts, most of whom had CNS metastases (mets) and were heavily pre-treated. In Ph II of this study, efficacy was explored based on prior ALK TKI tx as well as safety across all patients treated at the recommended Ph II dose. Methods: In this ongoing Ph II study (NCT01970865), pts with ALK+ or ROS1+ NSCLC, ± asymptomatic untreated or treated CNS mets, were enrolled into 6 expansion cohorts (EXP) based on prior tx (EXP 1-5, ALK+) and rearrangement status (EXP 6, ROS1+). Pts received lorlatinib 100mg QD. Primary objective was ORR and intracranial ORR (IC-ORR) by independent central review (ICR). Results: Efficacy (ALK+ pts with prior tx): At data cut-off (15 Aug 2016), 82 ALK+ pts were enrolled in cohorts EXP 2-5, received C1 no later than 31 Mar 2016 and were evaluated for ORR (ITT population); 52 were evaluated for IC-ORR and 35 were evaluated for IC-ORR response based on target lesions only (≥5mm; no prior radiotherapy or progression post prior radiotherapy). Confirmed response rates by ICR are reported in the table below. Safety (all pts): 116 ALK/ROS1+ pts were evaluated for safety at data cut-off. Most common tx-related AEs (TRAEs) and grade 3/4 TRAEs were hypercholesterolemia (90%, 17%) and hypertriglyceridemia (72%, 17%). Dose interruptions and reductions due to TRAEs were reported in 29% and 20% of pts, respectively. 14% of pts had tx-related SAEs. 5 pts (4%) discontinued tx due to TRAEs and there were no tx-related deaths. 74/116 pts (64%) remain on tx. Conclusions: Lorlatinib showed compelling clinical activity, with substantial IC activity, in ALK+ pts who received ≥1 prior ALK TKI, many of whom were heavily pre-treated. Clinical trial information: NCT01970865. [Table: see text]
Gamma Glutamyl Transferase Activity in Gilbert's Disease
Authors: RA Raja Ali, FM Stevens, H Grimes
Journal: Endoscopy (2006)

Gilbert's disease (GD), an isolated non-haemolytic unconjugated hyperbilirubinaemia occuring in 8% of the population, is diagnosed by estimating serum unconjugated bilirubin level. GD is under diagnosed leading to inappropriate expensive and invasive Investigation. A patient with congenital hyperbilirubinaemia was noted to have low gamma glutamyl transferase (gGT) activity. A prospective study has been undertaken to determine if low gGT is a marker for unconjugated hyperbilirubinaemia. The gGT and bilirubin results of random blood samples sent for liver function tests to the Clinical Biochemistry Department were abstracted and entered into a database.
Human Papillomavirus Vaccination and Keratinocyte Carcinomas—Reply
Authors: Anna J. Nichols, Robert S. Kirsner, Tim Ioannides
Journal: JAMA Dermatology (2017)

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
A Phase Ib/II Study of Ibrutinib in Combination with Obinutuzumab-Gazyva As First-Line Treatment for Patients with Chronic Lymphocytic Leukemia &gt; 65 Years Old or with Coexisting Conditions
Authors: Carlos I. Amaya-Chanaga, Michael Y. Choi, Natalie Nguyen, Elizabeth DeVore, Colin MacCarthy, Jacqueline Hilger-Rolfe, Thomas J. Kipps, Januario E. Castro
Journal: Blood (2016)
IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis
Authors: Sebastian Theurich, Eva Tsaousidou, Ruth Hanssen, Adelheid M. Lempradl, Jan Mauer, Katharina Timper, Katharina Schilbach, Kat Folz-Donahue, Christian Heilinger, Veronika Sexl, John Andrew Pospisilik, F. Thomas Wunderlich, Jens C. Brüning
Journal: Cell Metabolism (2017)
Bispecific Antibody Therapy in Hemophilia
Authors: David Lillicrap
Journal: New England Journal of Medicine (2017)

Hemophilia A is the most common severe inherited bleeding disorder in humans. Bleeding occurs as a result of a deficiency or dysfunction of the procoagulant cofactor protein, factor VIII. For the past 50 years, the treatment and prevention of bleeding in hemophilia A has involved the intravenous infusion of plasma-derived or recombinant factor VIII protein replacement.1 With an average half-life of 12 hours, these infusions have to be repeated several times each week to maintain protective levels of factor VIII in the blood, and although recent bioengineering innovations have produced factor VIII molecules with an average half-life of approximately 18 . . .
Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation
Authors: Kate J. Newberry, Keyur Patel, Lucia Masarova, Rajyalakshmi Luthra, Taghi Manshouri, Elias Jabbour, Prithviraj Bose, Naval Daver, Jorge Cortes, Hagop Kantarjian, Srdan Verstovsek
Journal: Blood (2017)
Characterization of the Genomic Landscape of BCR-ABL1 Kinase-Independent Mechanisms of Resistance to ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Christopher A. Eide, Daniel Bottomly, Samantha L. Savage, Libbey White, Beth Wilmot, Anna M. Reister Schultz, Kimberly A. Uchida, Anupriya Agarwal, Elie Traer, Lan Beppu, Olga Sala-Torra, Jerald P. Radich, Garrett Eickelberg, Richard D. Press, Marc M. Loriaux, Srinivas K. Tantravahi, Anthony D. Pomicter, Matthew S. Zabriskie, Michael W. Deininger, Thomas O'Hare, Jeffrey W. Tyner, Shannon K. McWeeney, Cristina E. Tognon, Brian J. Druker
Journal: Blood (2016)
Fibrosis scoring has significant impact on the outcome of antiviral therapy for chronic hepatitis C
Authors: A Qasim, A Grogan, B Hynes, H Irish, D Kevans, A Zaheer, N Mahmud, G McDonald, S Norris, S McKiernan
Journal: Endoscopy (2006)

Background: Hepatic fibrosis reflects architectural alterations of chronic hepatitis and remains most reliable way of determining disease progression in hepatitis C.
The Endoscopist, the Referring Physician and the Patient: Who is Responsible for a Final Decision?
Authors: K Triantafyllou, N Misailidis, SD Ladas
Journal: Endoscopy (2006)

Case: An otherwise healthy 26-year-old male patient is referred by his general practitioner for gastroscopy to an open-access gastroenterology unit because of episodes of abdominal pain not related with meals for the last 6 months. Clinical examination is normal, the patient is not taking NSAIDs and he is H. pylori negative by serology. He had a weekly course of PPI that failed to relieve his symptoms. Upon discussion with the endoscopist during the informed consent process, the patient revealed that his pain is often relieved by defecation and it is worse when under stress. The gastroenterologist (endosopist) made the clinical diagnosis of IBS and he has the ethical dilemma to perform the scheduled gastroscopy or for the patient's best interest, to discuss with him alternative tests and treatment.
Ultra‐short‐course booster is effective in recurrent grass pollen‐induced allergic rhinoconjunctivitis
Authors: O. Pfaar, S. Lang, U. Pieper‐Fürst, A. Astvatsatourov, F. Gerich, L. Klimek, M. F. Kramer, Y. Reydelet, K. Shah‐Hosseini, R. Mösges
Journal: Allergy (2017)

A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters.