tbuckley/cabot-search huggingface dataset:
Unmasking PD-1 Resistance by Next-Generation Sequencing
Authors: Carlo B. Bifulco, Walter J. Urba
Journal: New England Journal of Medicine (2016)

Monoclonal antibodies that inhibit the programmed death 1 (PD-1)–programmed death ligand 1 (PD-L1) pathway are clinically active against a broad range of tumors; however, even the most susceptible tumors (e.g., melanoma) respond less than half the time because of innate resistance. In this issue of the Journal, Zaretsky et al.1 describe the use of whole-exome sequencing to identify mechanisms of acquired immune resistance in tumors from patients with melanoma who had a relapse after more than 6 months of tumor response to treatment with pembrolizumab. Tumor regression after PD-1–PD-L1 blockade is presumed to be mediated by the activation of tumor-infiltrating . . .
Designed Stem Cell Aggregates: Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles (Adv. Healthcare Mater. 15/2016)
Authors: Yan Zhang, Hongli Mao, Chao Gao, Suhua Li, Qizhi Shuai, Jianbin Xu, Ke Xu, Lei Cao, Ren Lang, Zhongwei Gu, Toshihiro Akaike, Jun Yang
Journal: Advanced Healthcare Materials (2016)

E-cadherin-modified poly(lactic-co-glycolic acid) (hE-cad-PLGA) microparticles were fabricated and then mediated the 3D cell aggregates of human mesenchymal stem cells (MSCs) on page 1949 by Jun Yang and co-workers. The hE-cad-Fc matrix and the PLGA microparticles synergistically regulate the proliferation and bioactive factors secretions of MSCs by activating EGFR, AKT and ERK1/2 signaling pathways. The hE-cad-PLGA microparticles offer a novel route to expand multipotent stem cell-based clinical applications.
"A New Operation for Hemorrhoids"
Authors: S. Iglick
Journal: JAMA (1913)

secretary of the state of Coahuila, who held them quite a while without replying to my numerous letters regarding them.At last they were returned with the statement that a new law had been passed the day before which made all of my certifi- cates void, and that it would be necessary for me to obtain new ones, notwithstanding the fact
Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)
Authors: I.Y.K. Iskandar, D.M. Ashcroft, R.B. Warren, I. Evans, K. McElhone, C.M. Owen, A.D. Burden, C.H. Smith, N.J. Reynolds, C.E.M. Griffiths
Journal: British Journal of Dermatology (2016)

Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined.To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR).The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined.In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic.More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.
P0998 : Evaluation of circulating progenitor cells levels and functional capacity in patients with Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: E. Elsheikh, Z. Younoszai, M. Otgonsuren, T. Jeffers, H. Allawi, B. Marsiglia, D. Chapman, S.L. Hunt, B.P. Lam, Z. Younossi
Journal: Journal of Hepatology (2015)
Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis
Authors: Yin Ting Cheung, Noah D Sabin, Wilburn E Reddick, Deepa Bhojwani, Wei Liu, Tara M Brinkman, John O Glass, Scott N Hwang, Deokumar Srivastava, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Kevin R Krull
Journal: The Lancet Haematology (2016)
Treatment of Adult Depression in the United States
Authors: Mark Olfson, Carlos Blanco, Steven C. Marcus
Journal: JAMA Internal Medicine (2016)

Despite recent increased use of antidepressants in the United States, concerns persist that many adults with depression do not receive treatment, whereas others receive treatments that do not match their level of illness severity.To characterize the treatment of adult depression in the United States.Analysis of screen-positive depression, psychological distress, and depression treatment data from 46 417 responses to the Medical Expenditure Panel Surveys taken in US households by participants aged 18 years or older in 2012 and 2013.Percentages of adults with screen-positive depression (Patient Health Questionnaire-2 score of ≥ 3) and adjusted odds ratios (AORs) of the effects of sociodemographic characteristics on odds of screen-positive depression; percentages with treatment for screen-positive depression and AORs; percentages with any treatment of depression and AORs stratified by presence of serious psychological distress (Kessler 6 scale score of ≥13); and percentages with depression treatment by health care professional group (psychiatrists, other health care professionals, and general medical providers); and type of depression treatment (antidepressants, psychotherapy, and both) all stratified by distress level.Approximately 8.4% (95% CI, 7.9-8.8) of adults screened positive for depression, of which 28.7% received any depression treatment. Conversely, among all adults treated for depression, 29.9% had screen-positive depression and 21.8% had serious psychological distress. Adults with serious compared with less serious psychological distress who were treated for depression were more likely to receive care from psychiatrists (33.4% vs 17.3%, P < .001) or other mental health specialists (16.2% vs 9.6%, P < .001), and less likely to receive depression care exclusively from general medical professionals (59.0% vs 74.4%, P < .001). They were also more likely to receive psychotherapy (32.5% vs 20.6%, P < .001), though not antidepressant medications (81.1% vs 88.6%, P < .001).Most US adults who screen positive for depression did not receive treatment for depression, whereas most who were treated did not screen positive. In light of these findings, it is important to strengthen efforts to align depression care with each patient's clinical needs.
A candidate transacting modulator of fetal hemoglobin gene expression in the Arab—Indian haplotype of sickle cell anemia
Authors: Vinod Vathipadiekal, John J. Farrell, Shuai Wang, Heather L. Edward, Heather Shappell, A.M. Al‐Rubaish, Fahad Al‐Muhanna, Z. Naserullah, A. Alsuliman, Hatem Othman Qutub, Irene Simkin, Lindsay A. Farrer, Zhihua Jiang, Hong‐Yuan Luo, Shengwen Huang, Gustavo Mostoslavsky, George J. Murphy, Pradeep K. Patra, David H.K. Chui, Abdulrahman Alsultan, Amein K. Al‐Ali, Paola Sebastiani, Martin H. Steinberg
Journal: American Journal of Hematology (2016)

Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) β-globin gene haplotype of sickle cell anemia compared with African-origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes-seven selected for low HbF (8.2% ± 1.3%) and seven selected for high HbF (23.5% ± 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax toxin receptor (chromosome 2p13), was associated with HbF. These results were replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients, but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI haplotype patients of Indian origin, suggesting that this association is effective only in the Saudi AI haplotype background. ANTXR1 variants explained 10% of the HbF variability compared with 8% for BCL11A. These two genes had independent, additive effects on HbF and together explained about 15% of HbF variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA and protein levels in erythroid progenitors derived from induced pluripotent stem cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased ANTXR1 expression increased; as iPSCs differentiated and their HbF increased, ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1 contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and is the first gene in trans to HBB that is associated with HbF only in carriers of the Saudi AI haplotype. Am. J. Hematol. 91:1118-1122, 2016. © 2016 Wiley Periodicals, Inc.
Cold autoimmune hemolytic anemia secondary to atypical pneumonia
Authors: Maria Atta, Eimear T. Brannigan, Barbara J. Bain
Journal: American Journal of Hematology (2016)

Her blood count on admission showed a raised white cell count of 16 × 109/L and platelet count of 494 × 109/L. She was anemic with a hemoglobin concentration of 84 g/L, an MCV of 77 fL, and a reticulocyte count of 176 × 109/L. Renal and liver function (including total bilirubin) were normal, with a raised C-reactive protein of 34 mg/L (normal range <6) and a high lactate dehydrogenase of 639 iu/L (125–243). An automated differential count suggested monocytosis but a manual differential count showed neutrophils 8.3 × 109/L, lymphocytes 6.1 × 109/L, and monocytes 0.6 × 109/L. Her blood film showed red cell agglutinates, polychromatic macrocytes, nucleated red blood cells, and atypical lymphocytes. Some of the lymphocytes were large with increased cytoplasmic basophilia (left Image). Others had plasmacytoid features with an eccentric nucleus and a Golgi zone (right Image). There were occasional examples of erythrophagocytosis. A direct antiglobulin test was positive for C3d. On the basis of the clinical and the hematological findings, cold-antibody-induced hemolytic anemia secondary to Mycoplasma pneumoniae infection was suspected. This was confirmed by demonstration of both immunoglobulin (Ig) G and IgM antibodies, indicative of a recent infection. Polymerase chain reaction (PCR) for Epstein–Barr virus (EBV) was negative, as were laboratory tests for multiple other organisms. A computed tomography (CT) scan showed "tree in bud" airspace consolidation and associated mediastinal lymphadenopathy. The patient made a rapid recovery with intravenous co-amoxiclav and oral clarithromycin. Subsequent imaging showed complete resolution of radiographic abnormalities. The combination of cold autoimmune hemolytic anemia and atypical lymphocytes suggests either EBV or mycoplasma infection. As in this patient, consideration of the clinical as well as hematological features can indicate the correct diagnosis.
Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres
Authors: Amy C. Doty, Keiji Hirota, Karl F. Olsen, Naoya Sakamoto, Rose Ackermann, Meihua R. Feng, Yan Wang, Stephanie Choi, Wen Qu, Anna Schwendeman, Steven P. Schwendeman
Journal: Biomaterials (2016)
Markers of anaerobic glycolysis as predictive factor in neoadjuvant chemoradiotherapy of rectal cancer.
Authors: D. Sun, B. Shim, J. Jung, K. Lee, H. Kim, S. Hong, S. Kim, H. Cho
Journal: Journal of Clinical Oncology (2010)

10573 Background: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to resistance of radiotherapy and chemotherapy. We investigate the relationship between biomarkers related to anaerobic glycolytic metabolism (glucose transporter-1 [GLUT-1], lactate dehydrogenase [LDH]-5 and pyruvate dehydrogenase kinase [PDK]-1) and prognosis. Methods: GLUT-1, LDH-5, PDK-1 expression determined by immunohistochemistry were assessed in 109 patients with rectal cancer treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. Results: This study included 74 male and 35 female patients with a median age of 63 (range 53-70 years). Stage I, II and III accounted for 7.3%, 43.1% and 49.5%. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (425 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33 and surgery was done on 7 to 10 weeks after completion of all therapies. The down staging rate of this neoadjuvant therapy was 53% and pathologic complete response rate is 18.3%. High expression of GLUT-1, LDH-5, PDK-1 was observed in 34 (31.2%), 62 (56.9%) and 45 (41.3%) patients, respectively. A negative GLUT-1 was associated with a significantly higher rate of pathologic complete response compared to positive GLUT-1 (25.3% vs. 0.02%, p = 0.006). LDH-5, PDK-1 was not correlated with down staging and complete response of chemoradiotherapy. Conclusions: The GLUT-1 expression is the predictive factor of pathologic complete response in rectal cancer patients treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy. No significant financial relationships to disclose.
Procoagulant Phospholipid Activity, Whole Blood Thromboelastography and Thrombin Generation Assay to Detect Hypercoagulability in Thalassemic Children
Authors: Burcak Tatli Gunes, Meral Turker, Salih Gozmen, Yesim Oymak, Yilmaz Ay, Dilek Ince, Gulcihan Ozek, Tuba Hilkay Karapinar, Berna Atabay, Canan Vergin
Journal: Blood (2014)
Pharmacodynamic (PD) Analyses of Asparagine (Asn) Deamination and Asn Input (Imax) in Serum of Pediatric Patients with Standard Risk Acute Lymphoblastic Leukemia (SR ALL) Receiving Native or Pegylated E. Coli Asparaginases (ASNase) (CCG-1962).
Authors: Vassilios I. Avramis, Eduard H. Panosyan, Cecilia H. Fu, Linda C. Stork, Paul S. Gaynon
Journal: Blood (2004)
Effect of Tryptophan and Nicotinamide Loads on Urinary Excretion of RNA Metabolites by Bladder Cancer Patients: Brief Communication23
Authors: Henrik Rist Nielsen, Hans Wolf, Raymond R. Brown
Journal: JNCI Journal of the National Cancer Institute (1977)

In a comparative study of tryptophan metabolism and urinary excretion of nucleic acid derivatives (including beta-aminoisobutyric acid, 7-methylguanine, pseudouridine, and urate) in 12 male bladder cancer patients, the excretion of pseudouridine and 7-methylguanine decreased significantly after an oral dose of 2 g L-tryptophan. A similar decrease occurred after an oral nicotinamide load of 50 mg four times a day, which indicated a possible common mode of action of tryptophan and nicotinamide. No definite resolution could be made as to the causal mechanism for the observed descrase in RNA turnover.
Optimal step doses for drug provocation tests to prove beta-lactam hypersensitivity
Authors: A.-M. Chiriac, T. Rerkpattanapipat, P.-J. Bousquet, N. Molinari, P. Demoly
Journal: Allergy (2016)

Drug provocation tests (DPT) are commonly performed as part of β-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects).The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT.During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h.This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.
14 million people in central Africa to be vaccinated to try to halt yellow fever outbreak
Authors: Anne Gulland
Journal: BMJ (2016)

One of the largest mass vaccination campaigns ever undertaken will begin in Angola and the Democratic Republic of Congo (DRC) this week as health agencies attempt to halt a yellow fever outbreak.

The World Health Organization (WHO), alongside ministries of health in the two countries and other partners, will try to vaccinate around 14 million people in the DRC capital of Kinshasa and along the country’s 2646 km long border with Angola. Kinshasa has a population of around 10 million people, only 2 million of whom have so far been vaccinated against the disease.

WHO hopes the campaign will be over by the time the rainy season begins in …
Paludisme et tourisme : analyse rétrospective de cas de paludisme importés de la République Dominicaine en Allemagne
Authors: J Richter, A Sagir, A. Schöneberg, K Alpers, D Häussinger
Journal: Eurosurveillance (2001)

Cet article recense des cas de paludisme importes par des touristes allemands lors de sejours touristiques dans une zone reputee non endemique en Republique Dominicaine, entre juillet 1999 et mars 2000. Le paludisme a Plasmodium falciparum est endemique dans les provinces occidentales et a l’intereur de la Republique Dominicaine. En revanche, dans les principaux complexes touristiques de l’est du pays, le risque de contracter le paludisme etait considere si faible que la prophylaxie antipaludeenne n’y etait pas recommandee (1).
AMERICAN ASSOCIATION FOR CANCER RESEARCH
Journal: JAMA (1913)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
The complex role of transglutaminase 2 in glioblastoma proliferation
Authors: Soner Gundemir, Alina Monteagudo, Abdullah Akbar, Jeffrey W. Keillor, Gail V.W. Johnson
Journal: Neuro-Oncology (2016)

Glioblastomas (GBMs) are a heterogeneous group of primary brain tumors. These tumors are resistant to therapeutic interventions and invariably recur after surgical resection. The multifunctional protein transglutaminase 2 (TG2) has been shown to promote cell survival in a number of different tumors. There is also evidence that TG2 may be a pro-survival factor in GBMs. However, the roles that TG2 plays in facilitating GBM survival and proliferation have not yet been clearly delineated . The functions of TG2 are often cell- and context-specific. Therefore, in this study we examined the ability of TG2 to facilitate GBM proliferation using colony formation assays and 5-ethynyl-2ʹ-deoxyuridine (EdU) incorporation in several different GBM cell lines as well as neurospheres derived from patient tumors representing the 3 major subtypes of GBM tumors (mesenchymal, proneural, and classical) and maintained in the absence of serum. TG2 knockdown or selective TG2 inhibitors were used to modulate TG2 expression and activity. We show that TG2 plays differential roles in the proliferative process depending on the cell type. In most, but not all, GBM models TG2 plays a crucial role in the proliferative process, and some but not all TG2 inhibitors were highly effective at reducing proliferation in a large subset of the GBM models. Our results show that TG2 plays an important–but notoriously context-specific–role in GBM cell biology. Nonetheless, as future studies unravel the genetic "fingerprints" that make TG2 inhibitors effective, this information could be exploited to develop TG2 inhibitors into personalized GBM therapies.