tbuckley/cabot-search huggingface dataset:
Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury
Authors: Masahiro Omoto, Kunal Suri, Afsaneh Amouzegar, Mingshun Li, Kishore R. Katikireddy, Sharad K. Mittal, Sunil K. Chauhan
Journal: Molecular Therapy (2017)

Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.
A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin–Specific Immune Responses and Tuberculosis
Authors: Javeed A. Shah, Munyaradzi Musvosvi, Muki Shey, David J. Horne, Richard D. Wells, Glenna J. Peterson, Jeffery S. Cox, Michelle Daya, Eileen G. Hoal, Lin Lin, Raphael Gottardo, Willem A. Hanekom, Thomas J. Scriba, Mark Hatherill, Thomas R. Hawn
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood.Objectives: To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis.Methods: We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis–induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection.Measurements and Main Results: We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2+ CD4+ T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection.Conclusions: TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG vaccination.
Diabetic retinopathy after two years of intensified insulin treatment. Follow-up of the Kroc Collaborative Study
Authors: R. M. Bergenstal, P. Morse, A. H. Rubenstein, J. J. Bending, R. W. Bilous, H. Keen, J. C. Pickup, G. C. Viberti, G. Gosh, E. M. Kohner, P. M. Lawson, R. A. Rizza, J. C. Trautmann, C. C B Canny, M. C. Champion, J. Dupre, N. W. Rodger, J. E. Puklin
Journal: JAMA (1988)
Targeted mRNA sequencing of small formalin-fixed and paraffin-embedded breast cancer samples for the quantification of immune and cancer-related genes
Authors: B.V. Sinn, S. Loibl, R. Kronenwett, J. Furlanetto, K. Krappmann, T. Karn, B. Kerns, K. Weber, M. Schmidt, C. Denkert
Journal: Annals of Oncology (2017)
Clinical outcomes of adolescent and young adults (AYA) with colorectal cancer (CRC), a multi-institutional retrospective review (MIRR).
Authors: Young soo Rho, Marine Gilabert, Niamh Coleman, Megan Greally, Vera Georgieva Megdanova, Zhasmina Mihaylova Milanova, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2015)

e14692 Background: Contrary to the general population, incidence of CRC in AYA is on the rise. However, their clinical outcomes and treatment (tx) efficacy remains somewhat abstruse. A MIRR was performed to capture real world outcomes of AYA patients (AYAp) with CRC. Methods: Three tertiary institutions participated in the MIRR: Segal Cancer Centre Canada, St.Vincent's University Hospital Ireland and Military Medical Academy Bulgaria. Data of AYAp (18-44) diagnosed with CRC from June 2007 to June 2014 were retrieved, and their demographics, tumor site, tx and outcomes were pooled for analysis. Survival estimates were performed using Kaplan Meier methodology. Results: 67 CRC adenocarcinoma (stage II n = 14, stage III n = 14, stage IV n = 39) AYAp were identified. Median age (years) at diagnosis was 40 (26-44) and 34 were male. Primary site was 35 colon (52.3%), 7 rectosigmoid (10.4%), 25 rectum (37.3%). Most common presentations were abdominal pain (n = 36, 53.7%) and rectal bleeding (n = 22, 32.8%). Mutation analysis found no mutations in KRAS 28/39 (71.8%), in NRAS 8/10 (80%), and in BRAF 11/12 (91.7%) patients. At the time of diagnosis, 39 (58.2%) were stage IV, majority having liver (n = 18, 46.2%) or multi-organ (n = 21, 53.8%) metastasis. Metastatic 1st-line chemotherapy included CAPOX/FOLFOX (n = 28), FOLFIRI (n = 6), FLOX (n = 4), FOLFIRINOX (n = 1); 25 (64.1%) received concurrent bevacizumab (n = 22), cetuximab (n = 2), or panitumumab (n = 1). 55 (82.1%) underwent surgical intervention (palliative surgery n = 47). With a median follow up 20.6 months (1.3-62.9), stage IV progression free survival and overall survival (OS) was 10 and 42.0 months respectively. Stage II and III data did not reach OS but collectively had disease free survival of 69.9 months. Conclusions: Despite the small cohort size of unselected population, our study suggests AYAp may have a more aggressive disease (multi-organ metastasis, unfavorable mutation profile) compare to the general patient population (GPp). However, clinical outcomes were similar to GPp possibly as majority were able to undergo surgery and more aggressive tx. Further studies, including biomarker driven research specifically for AYAp should be sought out.
대한간학회 제 8 차 춘계학술대회 초록집 : 복수를 동반한 간경변증 환자에 있어서의 첫 자발성 세균성 복막염의 발생 위험 요인
Authors: 한광협, 전재윤, 문영명, 정재연, 박영수, 이관식, 김용수, 이현웅, 문병수
Journal: Clinical and Molecular Hepatology (2002)
Circuits and Mechanisms for Surround Modulation in Visual Cortex
Authors: Alessandra Angelucci, Maryam Bijanzadeh, Lauri Nurminen, Frederick Federer, Sam Merlin, Paul C. Bressloff
Journal: Annual Review of Neuroscience (2017)

Surround modulation (SM) is a fundamental property of sensory neurons in many species and sensory modalities. SM is the ability of stimuli in the surround of a neuron's receptive field (RF) to modulate (typically suppress) the neuron's response to stimuli simultaneously presented inside the RF, a property thought to underlie optimal coding of sensory information and important perceptual functions. Understanding the circuit and mechanisms for SM can reveal fundamental principles of computations in sensory cortices, from mouse to human. Current debate is centered over whether feedforward or intracortical circuits generate SM, and whether this results from increased inhibition or reduced excitation. Here we present a working hypothesis, based on theoretical and experimental evidence, that SM results from feedforward, horizontal, and feedback interactions with local recurrent connections, via synaptic mechanisms involving both increased inhibition and reduced recurrent excitation. In particular, strong and balanced recurrent excitatory and inhibitory circuits play a crucial role in the computation of SM.
Clinical significance of <i>ERas</i> oncogene on cancer
Authors: K. Yasuda, M. Yashiro, T. Sawada, M. Ohira, K. Hirakawa
Journal: Journal of Clinical Oncology (2007)

15083 Background: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. When ES cells are subcutaneously injected into immunodeficient or isogenic mice, a teratoma is formed within a few weeks. This tumor is composed of all three germ layers in a disorganized fashion. Thus there could be some common molecular mechanisms shared by ES cells and somatic cancer cells. The ERas oncogene is a recently identified gene that supports the tumorigenic growth of ES cells by producing a constitutively active Ras protein. There have been no report about expression of ERas oncogene on cancer cells until now. The aim of this study is to investigate expression and clinical significance of ERas oncogene on cancer cell lines and clinical cancer tissues. Methods: A panel of 35 human cancer cell lines, 5 normal cell lines, and 20 patiants with gastric cancer tissues were used in this study. ERas mRNA expression was examined by reverse transcription-polymerase chain reaction. The effect of the DNA methyl transferase inhibitor, 5-aza-2’- deoxycitydine on the ERas expression was analyzed. Methylation of CpG islands of ERas promoter lesion was investigated using bisulfate-directsequence analysis. Results: Expression of ERas mRNA was not found in any normal cells. In contrast, ERas mRNA was found in 15 of 35 cancer cell lines, including 8 of 15 gastric cancers, 4 of 7 colorectal cancers, 2 of 6 pancreas cancers, 1 of 3 breast cancers and none of esophageal cancers. Eras mRNA was found in all gastric cancer tissues, but not normal tissues. 5-aza-2’-deoxycytidine treatment at 2, 5, and 10μM for 24 h resulted in ERas expression in 10 of 20 cancer cell lines with respect to the silencing of ERas, including 7 of 7 gastric cancers, 1 of 3 colorectal cancers and 2 of 3 breast cancers. Methylation of CpG island were found in the cancer cell lines without ERas expression, but not in these with ERas expression. Conclusions: ERas oncogene is associated with the carcinogenesis pathway in human cancer. Eras might be useful marker for cancer diagnosis. No significant financial relationships to disclose.
Effect of cilastatin on cisplatin-induced nephrotoxicity and on antitumoral activity.
Authors: Montserrat Blanco-Codesido, Blanca Humanes, Alberto Lazaro, Sonia Camaño, Juan Carlos Jado, Alberto Tejedor
Journal: Journal of Clinical Oncology (2013)

e13535 Background: Cisplatin (CDDP) is a very effective and common treatment in solid malignancies used mostly in breast, ovarian, bladder, esophageal, gastric, head and neck cancer and germ cell tumors. One of the most important side effects of CDDP is the nephrotoxicity, a limitating side effect, especially with high CDDP doses, affecting as much as 30% of the patients. Cilastatin (Cls) is a specific inhibitor of renal dedydrodipeptidase I which prevents hydrolysis of imipenem and its accumulation in the proximal tubule. In this work we show that Cls acts as a nephroprotector against CDDP-induced damage without compromising its antitumor activity. Methods: Primary cultures of proximal tubular cells (PTCs) and cell lines of different malignancies (colon, breast, ovarian, bladder) were cultured with CDDP (1, 10 and 30 μM) in the presence or absence of Cls. Cell viability was assessed with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) assay. Wistar rats were treated with 5 mg/Kg of CDDP (single dose) and 75 mg/Kg/12 hours of Cls. We measured body weight, serum albumin, ALT, AST, creatinine, BUN, serum iones and GAP anion as well as urinary creatinine, osmolality, potassium, sodium and urea. Results: Concomitant treatment with Cls reduced CDDP-induced changes in PCTs. Several tumoral cell lines were tested with CDDP and Cls together. Cls did not increase or decreased tumor growth alone or in combination with CDDP. CDDP sensitivity was not affected by Cls. Wistar rats treated with CDDP alone showed loss of weight and significant worsening in renal function tests. Wistar rats experienced less loss of weight and a significant reduction in renal function worsening when treated simultaneously with CDDP and Cls. Liver function tests were not altered by the addition of Cls to the treatment. Conclusions: Our findings suggest that Cls administration might represent a novel strategy in the prevention of CDDP-induced acute renal injury without compromising its antitumor activity. Cls treatment could potentially increase the number of patients undergoing CDDP treatment or maintaining treatment. Further clinical trials for renal function preservation in cancer patients are on development.
Low tumor-infiltrating lymphocytes (TILs) to predict and refine risk in patients not achieving a pathological complete response (pCR) in HER2-positive breast cancers.
Authors: Naoki Hayashi, Giampaolo Bianchini, Michiko Murai, Koyu Suzuki, Mieko Uno, Shiro Uchida, Hiroshi Yagata, Atsushi Yoshida, Takayuki Iwamoto, Naoki Niikura, Seigo Nakamura, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2015)

e11612 Background: Higher tumor-infiltrating lymphocytes (TILs) in HER2+ early breast cancers have been associated with higher pCR rate and better outcome, with the major attention at the group with the highest TILs (lymphocyte predominant breast cancer, LPBC). We aimed to assess the prognostic and predictive value of tumors with the opposite feature of the lowest TILs in the neoadjuvant setting. Methods: We identified 96 HER2+ patients who received a neoadjuvant treatment between 2001 and 2008 in a single institution (St. Luke’s International Hospital), with chemotherapy (CT, n = 68) or in combination with trastuzumab (CT/H, n = 28). Stromal-TILs were assessed on pre-treatment biopsies and surgical specimens. Associations among TILs, pCR, and distant metastasis-free survival (DMFS) were evaluated. TILs were defined as Low; 0-10%, Int; 11-59% and High (LPBC); ≥ 60%, respectively. Results: The median follow-up was 91.2 months with an overall pCR rate of 43.7%. At baseline, 53,1% and 46.9% had LowTILs and Int/HighTILs, respectively (including 13.5% LPBC). The pCR rates were 27.4% (14/51) and 62.2% (28/45) in the LowTILs and Int/HighTILs groups, respectively (p = 0.0006), without significant difference for patients receiving CT or CT/H. Despite the small number of distant events (n = 10), a non-significant trend for worst DMFS was observed for the LowTILs group (HR 3.87 CI 0.82-18.3; p = 0.087). Considering only patients without pCR, at 10 years there was no recurrence in the Int/HighTILs, while the LowTILs group had 19.9% (CI 6%-32%) of distant recurrences (log rank p = 0.06). In patients with residual disease (RD), post-treatment TILs were significantly lower than pre-treatment (p = 0.0005), with 35.3% (6/17) changing from Int/HighTILs to LowTILs. Post-treatment LowTILs group was slightly less prognostic than the corresponding pre-treatment group. Conclusions: In HER2+ tumors, the group with the lowest baseline TILs had lower pCR rate after treatment with or without trastuzumab, and might be identified at the highest risk of recurrences in patients not achieving a pCR. This group should be prioritized for investigating new treatment strategies.
Give patients access to their medical records
Authors: Fiona Godlee
Journal: BMJ (2017)

Last week nearly 3000 healthcare providers and users attended the International Forum for Quality and Safety in London.Hosted by The BMJ and the Institute for Healthcare Improvement, it's always an inspiring event.You can watch recorded sessions (http://internationalforum.bmj.com/london), and I encourage you to sign up for the Asia Forum in Kuala Lumpur in August and for next year's International Forum in Amsterdam (http://bit.ly/2pTIi6P).This time delegates got even more than they bargained for, thanks to the patients who joined the steering and programme committees and led plenary and parallel sessions.They contributed not only as patient representatives but as leaders of system redesign and as innovators in improving their own care.Among others we heard from Margaret Murphy, who, after her son Kevin died as a result of medical error, took up the cause of patient safety and now chairs WHO's Patients for Patient Safety.We also heard Tim Omer and Sara Riggare explain, from their experience of living with, respectively, type 1 diabetes and early onset Parkinson's disease, why they are not waiting for health professionals or the industry to deliver the improvements they need (#wearenotwaiting).Their closing challenge echoed through the rest of the conference: how will you care for the empowered patient?
Vitamin D deficiency, incidence, and response to oral supplementation among various gastrointestinal malignancies
Authors: C. Gilmore, J. James, B. Zubal, D. Thomas, B. Tan
Journal: Journal of Clinical Oncology (2009)

9586 Background: Vitamin (vit) D dficiency is prevalent amongst patients (pts) with colorectal and pancreatic cancers. Data for other GI malignancies are limited and the impact of short-course vit D supplementation is unclear. Methods: An IRB-approved retrospective review of 202 pts with GI cancers from 12/2007 to 9/2008 was done to evaluate the incidence of vitamin D deficiency defined as serum 25-OH vit D levels of ≤ 30 ng/ml (severe=&lt;10 ng/ml; moderate=10–20 ng/ml; mild=21–30 ng/ml) and incidence of ‘low-normal' (31–50 ng/ml) and normal (&gt;50 ng/ml) vit D levels. Oral supplementation with vit D at 50,000 ‘u' weekly x 8–12 weeks were done and serum levels were redrawn at 2–3 months for pts with low normal and deficient vit D, respectively. Results: 87.6% of all 202 pts is vit D deficient (61% severe to moderate). (see Table ). 92 pts were re-evaluated after 2–3 months of oral vit D supplementation. Among this cohort, the incidence of pts with vitamin deficiency decreased from 91.3% to 57.6% after first re- evaluation. Severe/moderate deficiency rates also decreased from 71.7% to 13%. There were no significant difference in response between males/females, age &lt; or ≥ 65, caucasian or non-caucasian or tumor type. Conclusions: Vitamin D levels should routinely be evaluated for patients with GI maligancies. Oral supplementation decreases the rate 'any' vit D deficiency from 91% to 57%, and of 'severe to moderate' deficiency from 72% to 13%. Prospective studies on the impact of vit D deficiency and supplementation on various clinical outcomes among patients with GI cancers would improve supportive care management of these patients. [Table: see text] No significant financial relationships to disclose.
Mycobacterium ulcerans infection (Buruli ulcer) in French Guiana, South America, 1969–2013: an epidemiological study
Authors: Maylis Douine, Rodolphe Gozlan, Mathieu Nacher, Julie Dufour, Yann Reynaud, Eric Elguero, Marine Combe, Camilla J Velvin, Christine Chevillon, Alain Berlioz-Arthaud, Sylvain Labbé, Dominique Sainte-Marie, Jean-François Guégan, Roger Pradinaud, Pierre Couppié
Journal: The Lancet Planetary Health (2017)

BackgroundMycobacterium ulcerans infection is the third most common mycobacterial disease in the world after tuberculosis and leprosy. To date, transmission pathways from its environmental reservoir to humans are still unknown. In South America, French Guiana has the highest reported number of M ulcerans infections across the continent. This empirical study aimed to characterise the epidemiology of M ulcerans infection in French Guiana between 1969 and 2013.MethodsData were collected prospectively mainly by two dermatologists at Cayenne Hospital's dermatology department between Jan 1, 1969, and Dec 31, 2013, for age, date of diagnosis, sex, residence, location of the lesion, type of lesion, associated symptoms, and diagnostic method (smear, culture, PCR, or histology) for all confirmed and suspected cases of M ulcerans. We obtained population data from censuses. We calculated mean M ulcerans infection incidences, presented as the number of cases per 100 000 person-years.Findings245 patients with M ulcerans infections were reported at Cayenne Hospital's dermatology department during the study period. M ulcerans infection incidence decreased over time, from 6·07 infections per 100 000 person-years (95% CI 4·46–7·67) in 1969–83 to 4·77 infections per 100 000 person-years (3·75–5·79) in 1984–98 and to 3·49 infections per 100 000 person-years (2·83–4·16) in 1999–2013. The proportion of children with infections also declined with time, from 42 (76%) of 55 patients in 1969–83 to 26 (31%) of 84 in 1984–98 and to 22 (21%) of 106 in 1999–2013. Most cases occurred in coastal areas surrounded by marshy savannah (incidence of 21·08 per 100 000 person-years in Sinnamary and 21·18 per 100 000 person-years in Mana). Lesions mainly affected limbs (lower limbs 161 [66%] patients; upper limbs 60 [24%] patients). We diagnosed no bone infections.InterpretationThe decrease of M ulcerans infection incidence and the proportion of children with infections over a 45 year period in this ultra-peripheral French territory might have been mostly driven by improving living conditions, prophylactic recommendations, and access to health care.FundingAgence Nationale de la Recherche.
Obstacles to the Adoption of Biosimilars for Chronic Diseases
Authors: Aaron Hakim, Joseph S. Ross
Journal: JAMA (2017)

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Do patients have worse outcomes in heart failure than in cancer? A primary care‐based cohort study with 10‐year follow‐up in Scotland
Authors: Mamas A. Mamas, Matthew Sperrin, Margaret C. Watson, Alasdair Coutts, Katie Wilde, Christopher Burton, Umesh T. Kadam, Chun Shing Kwok, Allan B. Clark, Peter Murchie, Iain Buchan, Philip C. Hannaford, Phyo K. Myint
Journal: European Journal of Heart Failure (2017)
Linear and Logistic Regression Models of Patient-Reported Outcomes and Patient Characteristics in US Adults with Hemophilia from the Pain, Functional Impairment, and Quality of Life (P-FiQ) Study
Authors: Katharine Batt, Michael Recht, Michael Wang, Doris V. Quon, Lisa N Boggio, Craig M. Kessler, Tyler W. Buckner, Anne T. Neff, Neeraj N Iyer, David L Cooper, Christine L Kempton
Journal: Blood (2016)