tbuckley/cabot-search huggingface dataset:
HHLA2, a New Immune Checkpoint Member of the B7 Family, Is Widely Expressed in Human Lung Cancer and Associated with EGFR Mutational Status
Authors: Haiying Cheng, Murali Janakiram, Alain Borczuk, Juan Lin, Wanglong Qiu, Huijie Liu, Jordan M. Chinai, Balazs Halmos, Roman Perez-Soler, Xingxing Zang
Journal: Clinical Cancer Research (2016)

Immunotherapy with antibodies against B7/CD28 family members, including PD-1, PD-L1, and CTLA-4 has shifted the treatment paradigm for non-small cell lung carcinoma (NSCLC) with improved clinical outcome. HHLA2 is a newly discovered member of the family. By regulating T-cell function, HHLA2 could contribute to tumor immune suppression and thus be a novel target for cancer immunotherapy. There is limited information and critical need to characterize its expression profile and clinical significance in NSCLC.We performed IHC with an HHLA2-specific antibody (clone 566.1) using tissue microarrays constructed from 679 NSCLC tumor tissues, including 392 cases in the discovery set and 287 cases in the validation cohort. We also studied clinicopathologic characteristics of these patients.Overall, HHLA2 was not detected in most of normal lung tissue but expressed in 66% of NSCLC across different subtypes. In particular, EGFR-mutated NSCLC was significantly associated with higher tumor HHLA2 expression in both discovery (EGFR vs. WT: 76% vs. 53%, P = 0.01) and validation cohorts (89% vs. 69%, P = 0.01). In one of the two cohorts, HHLA2 expression was higher in lung adenocarcinoma as compared with squamous and large cell histology, non-Hispanic White versus Hispanics, and tumors with high tumor-infiltrating lymphocyte (TIL) density. In the multivariate analysis, EGFR mutation status and high TIL intensity were independently associated with HHLA2 expression in lung adenocarcinoma.HHLA2 is widely expressed in NSCLC and is associated with EGFR mutation and high TILs in lung adenocarcinoma. It is potentially a novel target for lung cancer immunotherapy. Clin Cancer Res; 23(3); 825-32. ©2016 AACR.
Adverse Effects of Incretin Therapy for Type 2 Diabetes—Reply
Authors: Anastassios G. Pittas, Renee E. Amori, Joseph Lau
Journal: JAMA (2007)

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
Характеристика функціонального стану жовчного міхура та структурних змін печінки при неалкогольній жировій хворобі печінки в дітей
Authors: N.Yu. Zavgorodnya, O.Yu. Lukianenko, V.B. Yagmur, I.S. Konenko
Journal: GASTROENTEROLOGY (2016)

Протягом останнього десятиліття поширеність неалкогольної жирової хвороби печінки досягла масштабів епідемії, вона стала одним з найбільш поширених хронічних захворювань печінки в дитячій популяції. Мета: вивчити взаємозв’язок функціонального стану жовчного міхура зі структурними змінами печінки в дітей з неалкогольною жировою хворобою печінки. Матеріали й методи. Обстежені 34 дитини віком від 8 до 17 років. Визначення стеатозу печінки проводили з використанням апарата FibroScan® 502 touch з визначенням контрольованого параметра ультразвукового затухання (CAP). За даними еластометрії й УЗД органів черевної порожнини з дослідженням функції жовчного міхура пацієнти були розподілені на 4 групи: 1-ша група складалася з 7 пацієнтів зі стеатозом і гіпофункцією жовчного міхура (20,5 %), 2-га група — 6 пацієнтів зі стеатозом і нормокінезією жовчного міхура (17,65 %), 3-тя група — 11 пацієнтів без стеатозу печінки з гіпофункцією жовчного міхура (32,35 %), 4-та група — 10 пацієнтів без стеатозу печінки з нормофункцією жовчного міхура (29,4 %). Результати. Результати сонологічного обстеження продемонстрували, що в дітей 1-ї групи (стеатоз із гіпокінезією жовчного міхура) визначалися значно більші розміри часток печінки порівняно з 4-ю групою (діти без стеатозу з нормофункцією жовчного міхура). Крім того, показники жорсткості паренхіми печінки були максимальні у хворих зі стеатозом печінки й гіпокінезією жовчного міхура. Обговорення. Поєднання стеатозу печінки та гіпокінезії жовчного міхура в дітей супроводжується значним збільшенням розмірів печінки, підвищенням жорсткості паренхіми печінки зі збільшенням ступеня стеатозу. Отримані дані вказують на взаємозв’язок функції жовчного міхура та структурних змін печінки.
HERPES ZOSTER AND CHICKENPOX
Authors: A. G. Hough
Journal: JAMA (1918)

<h3>To the Editor:</h3> —The report of cases showing the relation between herpes zoster and chickenpox made by Drs: Goldberg and Francis in the April 13 number ofThe Journalrecalled to my mind an experience I recently had which showed such a relation. On Feb. 15, 1918, a young lady came to my office with a typical case of herpes zoster following the course of the superficial nerves of the cervical plexus. March 3, I was called to see the patient's younger brother and found a well developed case of chickenpox. During February there were only fourteen cases of chickenpox reported in the city. Thirteen of these were in the extreme other end of town and one was about four blocks distant from my patient, and the child in that case went to another school. I am not able to find that my patient was ever exposed to chickenpox.
Case 58-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case A seventy-seven-year-old male musician entered the hospital because of hematuria. The patient experienced increasing nocturia, urgency and terminal dribbling on urination for approximately eight years before admission. One year previously there was an episode of hematuria of three days' duration. Four weeks before entry the urine became bright red throughout urination, and this condition persisted, occurring almost daily, to the time of admission. At the age of twenty-seven years an empyema of the left side of the chest was treated by removal of ribs. He reported one episode of gonorrhea during the same year; there was no . . .
Bernard Nchewa Nwulu
Authors: Ugochi Nwulu
Journal: BMJ (2016)

Bernard Nchewa Nwulu was born in Umuode Nsulu, Nigeria, and won a scholarship to study medicine at the University of Lovanium in Zaire. After qualifying, he stayed in Zaire, worked as a district medical officer for a Belgian railway company, and was the sole general practitioner for more than 150 000 people in the region. He made a pragmatic choice to specialise in psychiatry when he returned to Nigeria three years later. He moved to Scotland in 1978 to study at the University of Edinburgh and wrote …
The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells
Authors: Xiaoshu Chen, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2016)

Ohno proposed that the expression levels of X-linked genes have been doubled to compensate the degeneration of Y-linked homologs during the evolution of mammalian sex chromosomes, but RNA sequencing in human somatic tissues showed no such upregulation for the vast majority of X-linked genes. Here we report that the X to autosome expression ratio equals ∼1 in haploid human parthenogenetic embryonic stem (pES) cells and ∼0.5 in diploidized pES cells, both with one active X chromosome. Although we confirmed the upregulation of ∼5% of X-linked genes encoding members of large protein complexes in diploids, these genes are also upregulated in haploids, breaking the otherwise balanced dosage. These findings argue against Ohno's hypothesis for both haploid and diploid cells and demonstrate that, at least in humans, precise gene regulation for dosage balance, even for members of large protein complexes, is much less critical than is commonly thought.
Fertility Recovery Following Allogeneic Bone Marrow Transplantation in Aplastic Anemia; A Study of 157 Patients
Authors: Feras Alfraih, Shad Ahmed, Dennis Dong Hwan Kim, Walid Rasheed, Ghuzayel Aldawsari, Fahad Alsharif, Said Y Mohamed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Naeem A. Chaudhri, Fahad Al Mohareb, Mahmoud Al-Jurf, Hazza A Alzahrani
Journal: Blood (2015)
Associations between Extending Access to Primary Care and Emergency Department Visits: A Difference-In-Differences Analysis
Authors: William Whittaker, Laura Anselmi, Søren Rud Kristensen, Yiu-Shing Lau, Simon Bailey, Peter Bower, Katherine Checkland, Rebecca Elvey, Katy Rothwell, Jonathan Stokes, Damian Hodgson
Journal: PLoS Medicine (2016)

Health services across the world increasingly face pressures on the use of expensive hospital services. Better organisation and delivery of primary care has the potential to manage demand and reduce costs for hospital services, but routine primary care services are not open during evenings and weekends. Extended access (evening and weekend opening) is hypothesized to reduce pressure on hospital services from emergency department visits. However, the existing evidence-base is weak, largely focused on emergency out-of-hours services, and analysed using a before-and after-methodology without effective comparators.Throughout 2014, 56 primary care practices (346,024 patients) in Greater Manchester, England, offered 7-day extended access, compared with 469 primary care practices (2,596,330 patients) providing routine access. Extended access included evening and weekend opening and served both urgent and routine appointments. To assess the effects of extended primary care access on hospital services, we apply a difference-in-differences analysis using hospital administrative data from 2011 to 2014. Propensity score matching techniques were used to match practices without extended access to practices with extended access. Differences in the change in "minor" patient-initiated emergency department visits per 1,000 population were compared between practices with and without extended access. Populations registered to primary care practices with extended access demonstrated a 26.4% relative reduction (compared to practices without extended access) in patient-initiated emergency department visits for "minor" problems (95% CI -38.6% to -14.2%, absolute difference: -10,933 per year, 95% CI -15,995 to -5,866), and a 26.6% (95% CI -39.2% to -14.1%) relative reduction in costs of patient-initiated visits to emergency departments for minor problems (absolute difference: -£767,976, -£1,130,767 to -£405,184). There was an insignificant relative reduction of 3.1% in total emergency department visits (95% CI -6.4% to 0.2%). Our results were robust to several sensitivity checks. A lack of detailed cost reporting of the running costs of extended access and an inability to capture health outcomes and other health service impacts constrain the study from assessing the full cost-effectiveness of extended access to primary care.The study found that extending access was associated with a reduction in emergency department visits in the first 12 months. The results of the research have already informed the decision by National Health Service England to extend primary care access across Greater Manchester from 2016. However, further evidence is needed to understand whether extending primary care access is cost-effective and sustainable.
Preliminary data on precision of QuantiFERON-TB Plus performance
Authors: David Gallagher, Davide Manissero, Christopher Stocking, Chris Pyne
Journal: European Respiratory Journal (2016)

We welcome the findings by Barcellini et al. [1] in their recent publication on the first independent evaluation of QuantiFERON-TB Plus (QFT-Plus; QIAGEN GmbH, Hilden, Germany). The authors conclude that the addition of novel peptides, aimed at stimulating a CD8+ T-cell response, resulted in a diagnostic sensitivity for culture-confirmed tuberculosis of 88% suggesting that the QFT-Plus might offer improved sensitivity when compared with the most recent meta-analysis for QuantiFERON-TB Gold In-Tube (QFT-GIT) [2]. The findings also reinforce recent evidence supporting the theory that CD8+ T-cells have a major role in host defence by stimulating the production of interferon-γ and other soluble factors, activating macrophages which in turn suppress the growth of Mycobacterium tuberculosis (MTB) [3]. We agree with the statement of Barcellini et al. [1] on the need to corroborate such findings and assess sensitivity in CD4+ T-cell depleted patient populations, as in HIV-infected patients where it has been shown that CD8+ T-cells associate with active tuberculosis (TB) [4]. QFT Plus variability of 9.6% vs 18.25% in QFT Gold: this could reduce TB reversion/conversion in low-risk individuals <http://ow.ly/W97W300mUtZ>
Notch activation drives adipocyte dedifferentiation and tumorigenic transformation in mice
Authors: Pengpeng Bi, Feng Yue, Anju Karki, Beatriz Castro, Sara E. Wirbisky, Chao Wang, Abigail Durkes, Bennett D. Elzey, Ourania M. Andrisani, Christopher A. Bidwell, Jennifer L. Freeman, Stephen F. Konieczny, Shihuan Kuang
Journal: The Journal of Experimental Medicine (2016)

Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of the lack of animal models, the cellular origin and molecular regulation of LPS remain unclear. Here, we report that mice with adipocyte-specific activation of Notch signaling (Ad/N1ICD) develop LPS with complete penetrance. Lineage tracing confirms the adipocyte origin of Ad/N1ICD LPS. The Ad/N1ICD LPS resembles human dedifferentiated LPS in histological appearance, anatomical localization, and gene expression signature. Before transformation, Ad/N1ICD adipocytes undergo dedifferentiation that leads to lipodystrophy and metabolic dysfunction. Although concomitant Pten deletion normalizes the glucose metabolism of Ad/N1ICD mice, it dramatically accelerates the LPS prognosis and malignancy. Transcriptomes and lipidomics analyses indicate that Notch activation suppresses lipid metabolism pathways that supply ligands to Pparγ, the master regulator of adipocyte homeostasis. Accordingly, synthetic Pparγ ligand supplementation induces redifferentiation of Ad/N1ICD adipocytes and tumor cells, and prevents LPS development in Ad/N1ICD mice. Importantly, the Notch target HES1 is abundantly expressed in human LPS, and Notch inhibition suppresses the growth of human dedifferentiated LPS xenografts. Collectively, ectopic Notch activation is sufficient to induce dedifferentiation and tumorigenic transformation of mature adipocytes in mouse.
Association of surgeons in training 40th anniversary conference: Liverpool #ASiT2016
Authors: Rhiannon L. Harries, Adam P. Williams, Philip J. McElnay, Vimal J. Gokani
Journal: International Journal of Surgery (2016)

The Association of Surgeons in Training (ASiT) is a professional body and registered charity working to promote excellence in surgical training for the benefit of junior doctors and patient alike. ASiT is independent of the National Health Service (NHS), Surgical Royal Colleges and specialty associations, and represents trainees in all ten surgical specialities. We were delighted to be celebrating our 40th Anniversary Conference in the fantastic city of Liverpool with over 700 delegates in attendance and in the company of many ASiT Past Presidents. The conference programme focused on how to overcome threats to training in light of the recent turbulent events associated with the junior doctor contract dispute with inspiring talks from Professor Sir Bruce Keogh, NHS Medical Director and Rt Hon Heidi Alexander MP, Shadow Health Secretary. The other central topic to the conference was 'celebrating excellence in surgical training' and we were thankful to many other high profile speakers who attended to help in this celebration. In addition, over £4000 was distributed between more than 30 prizes and was awarded by the incoming President, Mr Adam Williams, to delegates who presented the highest scoring academic work from over 1200 submitted abstracts.
Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis
Authors: Ary Serpa Neto, Matthieu Schmidt, Luciano C. P. Azevedo, Thomas Bein, Laurent Brochard, Gernot Beutel, Alain Combes, Eduardo L. V. Costa, Carol Hodgson, Christian Lindskov, Matthias Lubnow, Catherina Lueck, Andrew J. Michaels, Jose-Artur Paiva, Marcelo Park, Antonio Pesenti, Tài Pham, Michael Quintel, V. Marco Ranieri, Michael Ried, Roberto Roncon-Albuquerque, Arthur S. Slutsky, Shinhiro Takeda, Pier Paolo Terragni, Marie Vejen, Steffen Weber-Carstens, Tobias Welte, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J. Schultz
Journal: Intensive Care Medicine (2016)
Cell-Intrinsic Determinants of Ibrutinib-Induced Apoptosis in Chronic Lymphocytic Leukemia
Authors: Nisar A. Amin, Sriram Balasubramanian, Kamlai Saiya-Cork, Kerby Shedden, Nan Hu, Sami N. Malek
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, is approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) and CLL with del17p. Mechanistically, ibrutinib interferes with B-cell receptor (BCR) signaling as well as multiple CLL cell-to-microenvironment interactions. Given the importance of ibrutinib in the management of CLL, a deeper understanding of factors governing sensitivity and resistance is warranted. Experimental Design: We studied 48 longitudinally sampled paired CLL samples, 42 of which were procured before and after standard CLL chemotherapies, and characterized them for well-studied CLL molecular traits as well as by whole-exome sequencing and SNP 6.0 array profiling. We exposed these samples to 0.25 to 5 μmol/L of ibrutinib ex vivo and measured apoptosis fractions as well as BCR signaling by immunoblotting. We disrupted TP53 in HG3, PGA1, and PG-EBV cell lines and measured BCR signaling and ibrutinib responses. Results: CLL samples demonstrated a surprisingly wide range of ex vivo sensitivities to ibrutinib, with IC50 values ranging from 0.4 to 9.7 μmol/L. Unmutated IGVH status, elevated ZAP70 expression, and trisomy 12 were associated with heightened sensitivity to ibrutinib treatment. Five CLL samples were substantially more resistant to ibrutinib following relapse from chemotherapy; of these, three had acquired a del17p/TP53-mutated status. A validation sample of 15 CLL carrying TP53 mutations, of which 13 carried both del17p and a TP53 mutation, confirmed substantially less sensitivity to ibrutinib-induced apoptosis. Conclusions: This study identifies that CLL harboring del17p/TP53-mutated cells are substantially less sensitive to ibrutinib-induced apoptosis than del17p/TP53 wild-type cells. Clin Cancer Res; 23(4); 1049–59. ©2016 AACR.
Phase II trial of neratinib for HER2 mutated, non-amplified metastatic breast cancer (HER2<sup>mut</sup> MBC).
Authors: Cynthia X. Ma, Ron Bose, Feng Gao, Rachel A. Freedman, Mark D. Pegram, Kimberly Blackwell, Philippe L. Bedard, Daniel F. Hayes, Matthew P. Goetz, Polly Ann Niravath, Christy Ann Russell, Debu Tripathy, Melody A. Cobleigh, Andres Forero, Timothy J. Pluard, Carey K. Anders, Caroline Bumb, Michael Naughton, Hussam Al-Kateb, Matthew James Ellis
Journal: Journal of Clinical Oncology (2016)

516 Background: HER2 mutation occurs in ~2% of breast cancer (BC). Preclinical models suggested neratinib, an irreversible HER2/EGFR tyrosine kinase inhibitor, could be an effective treatment. This trial was conducted to assess the clinical benefit rate (CBR), defined as complete response (CR), partial response (PR) or stable disease (SD) ≥ 6 months (mo.), for neratinib in patients (pts) with HER2mutMBC (NCT01670877). Methods: This single arm phase II trial employed the Simon's Optimal 2-stage design (1st stage: n=10, 2nd stage: n=19) to detect CBR of 20% versus the null hypothesis of 5% (80% power, 1-sided alpha 0.05). The primary endpoint is met if ≥ 4 CB is observed. Eligibility required the presence of somatic HER2mut and absent HER2 amplification. Activating HER2mut by in vitro study was required in the 2nd stage. Pts received neratinib 240 mg PO daily (28-day cycle) with prophylactic loperamide. Response was assessed every 2 cycles by RECIST 1.1. Enrollment was stopped early due to a protocol amendment to add fulvestrant to neratinib for ER+ disease. Results: Between May 2013 and Aug. 2015, 16 pts (n=14 with known activating HER2mut, n=2 with HER2mut unknown significance (UNK)), a median age of 58 (range 31-74) years and 3 (range 2-10) prior regimens for MBC, enrolled to the study. 15 pts (95%) had ER+ and 5 (31%) had lobular BC. Mutations in CDH1 (5/11), TP53 (4/11), and PIK3CA (4/11) were common. 14 pts came off study due to PD (n=13) or adverse event (AE) (n=1). 2 pts continue to receive study drug as of Jan 30, 2016. Among the 14 pts with activating HER2mut, 5 (36%, 90% CI: 15-61%) achieved CB, including 1 CR, 1 PR, and 3 SD ≥ 6 mo. (Table 1). Median progression free survival was 5 mo. (90% CI: 2-8). The 2 pts with HER2mut UNK had PD as best response. Common AEs included diarrhea (G2 31%, G3 19%) and anorexia (G2 44%). Conclusions: This phase II trial of neratinib for HER2 mutated, non-amplified MBC met its primary endpoint, with CBR of 36% in a heavily pretreated pt population. Since almost all pts were ER+ a combination with fulvestrant is a logical next step, currently under study. Clinical trial information: NCT01670877.HER2mut N Best Response CR PR SD PD ≥ 6 mo. 4 mo. 2 mo. Exon 20 ins. 4 1 1# 1 1 (ER-) D769H 1 1 L755S 6 1 1 4 L869R 1 1# S310F 2 1 1 Total 14 1 1 3 1 2 6 CBR 36% (90% CI: 15-61%), #ongoing
Bacteriuria increases the risk of edematous attacks in hereditary angioedema with C1‐inhibitor deficiency
Authors: Z. Zotter, N. Veszeli, K. V. Kőhalmi, L. Varga, É. Imreh, G. Kovács, M. Nallbani, H. Farkas
Journal: Allergy (2016)

Urinary tract infections are considered among the most common infectious disorders in humans. Various infections may have a role in inducing HAE attacks. Our study intended to evaluate bacteriuria in the urinalysis of patients with C1-INH-HAE. Urine specimens contributed by 139 patients with C1-INH-HAE at the annual control visits were studied retrospectively for microorganisms. We analyzed the presence of bacteriuria in relation to the clinical symptoms. Taking into account three randomly selected urine specimens, we found that the cumulative number of edematous attacks was higher in patients with bacteriuria than in those without (P = 0.019, P = 0.022, P = 0.014). Considering the same patients, attack number was significantly higher (14.51 vs 8.63) in patients with bacteriuria than in those without (P < 0.0001). In patients with bacteriuria, we found a higher incidence of edema formation during the year before evaluation, which may suggest the triggering role of bacteriuria in the occurrence of edematous episodes.
Is the risk of neoplastic recurrence increased after prescribing direct-acting antivirals for HCV patients whose HCC was previously cured?
Authors: Claudio Zavaglia, Stefano Okolicsanyi, Lucia Cesarini, Chiara Mazzarelli, Valerio Pontecorvi, Antonio Ciaccio, Mario Strazzabosco, Luca Saverio Belli
Journal: Journal of Hepatology (2016)