tbuckley/cabot-search huggingface dataset:
Toward More Accurate Understanding of Lymph Node Metastasis Risk in Early Gastric Cancer
Authors: Jashodeep Datta, Vivian E. Strong
Journal: JAMA Surgery (2019)

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Australian MPs visit Southport GP to learn about low carb diet for type 2 diabetes
Authors: Jane Feinmann
Journal: BMJ (2019)

A delegation of Australian MPs travelled to the UK earlier this month to meet Southport GP and low carb proponent David Unwin as part of an ongoing inquiry into the role of diet in the prevention and management of type 2 diabetes.

The team of four MPs and a scientific officer, all members Western Australia’s Education and Health Standing Committee, spent 24 hours at the Southport practice. They viewed presentations and met patients before sitting down to a low carb dinner (chicken liver pate followed by braised beef and celeriac Dauphinoise) with the practice team and a patient expert. …
Risk of Histological Transformation in Patients with Primary Refractory Follicular Lymphoma
Authors: Sara Alonso, Martina Manni, Clementine Sarkozy, Marielle Wondergem, Attilio Guarini, Laura Magnano, Miguel Alcoceba, Martine E.D. Chamuleau, Sara Galimberti, Maria Gomes da Silva, Harald Holte, Emanuele Zucca, Silvia Montoto, Sandra Lockmer, Igor Aurer, Luigi Marcheselli, Dolores Caballero, Gilles Salles, Massimo Federico
Journal: Blood (2018)
Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method
Authors: Agustina Bessa, Steven Maclennan, Deborah Enting, Richard Bryan, Debra Josephs, Simon Hughes, Suzanne Amery, Muhammad Shamim Khan, Sachin Malde, Rajesh Nair, Fidelma Cahill, Harriet Wylie, Ramesh Thurairaja, Kathryn Chatterton, Netty Kinsella, Christel Häggström, Mieke Van Hemelrijck
Journal: European Urology (2019)
Preoperative Sinonasal Symptom Scores Predict Post-Surgery, Post-Aspirin Desensitization Disease Status in Aspirin Exacerbated Respiratory Disease
Authors: Edward C. Kuan, William P. Kennedy, Neil N. Patel, Michael A. Kohanski, Charles C. Tong, David W. Kennedy, James Palmer, Nithin D. Adappa, John V. Bosso
Journal: Journal of Allergy and Clinical Immunology (2019)
Fcγ Receptors I and III on Splenic Macrophages Mediate GPIIb/IIIa Autoantibody-Dependent Phagocytosis of Platelets in Human Immune Thrombocytopenia
Authors: Peter A. A. Norris, George B. Segel, Ulrich J Sachs, Behnaz Bayat, Gestur Vidarsson, Rick Kapur, Christine M. Cserti-Gazdewich, Jeannie Callum, Yulia Lin, Richard Burack, John W Semple, Alan H Lazarus
Journal: Blood (2018)
T-Type Cav3.1 Channels Mediate Progression and Chemotherapeutic Resistance in Glioblastoma
Authors: Anna Visa, Marta C. Sallán, Oscar Maiques, Lía Alza, Elisabet Talavera, Ricard López-Ortega, Maria Santacana, Judit Herreros, Carles Cantí
Journal: Cancer Research (2019)

Abstract T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacologic blockers have limited selectivity for TTCC and are unable to distinguish between TTCC isoforms. Here we analyzed the expression of TTCC transcripts in human GBM cells and show a prevalence of Cacna1g/Cav3.1 mRNAs. Infection of GBM cells with lentiviral particles carrying short hairpin RNA against Cav3.1 resulted in GBM cell death by apoptosis. We generated a murine GBM xenograft via subcutaneous injection of U87-MG GBM cells and found that tumor size was reduced when Cav3.1 expression was silenced. Furthermore, we developed an in vitro model of temozolomide-resistant GBM that showed increased expression of Cav3.1 accompanied by the activation of macroautophagy. We confirmed a positive correlation between Cav3.1 and autophagic markers in both GBM cultures and biopsies. Of note, Cav3.1 knockdown resulted in transcriptional downregulation of p62/SQSTM1 and deficient autophagy. Together, these data identify Cav3.1 channels as potential targets for slowing GBM progression and recurrence based on their role in regulating autophagy. Significance: These findings identify Cav3.1 calcium channels as a molecular target to regulate autophagy and prevent progression and chemotherapeutic resistance in glioblastoma.
Outcomes of younger patients diagnosed with locally advanced rectal cancer.
Authors: Rosemary Habib, Val Gebski, James Toh, Nimalan Pathma-Nathan, Toufic El Khoury, Grahame Ctercteko, Jayasingham Jayamohan, Ka Yeung Mark Wong, Nicholas Wilcken, Adnan Nagrial
Journal: Journal of Clinical Oncology (2019)

500 Background: The incidence of rectal cancer is higher in the older population. In developed nations there has been a rise in incidence in young onset rectal cancer (yRC). We evaluated and compared the presentation and survival outcomes of treatments for locally advanced rectal cancer in yRC patients to that of older patients. Methods: All cases of rectal cancers referred to a large tertiary referral cancer centre in Western Sydney between 2009-2016 were examined. Patient demographics, presenting symptoms, treatment, clinico-pathological characteristics, progression free survival (PFS) and overall survival (OS) were obtained. Under 50 years old was used as the cut-off age for defining yRC. Results: One hundred sixty-two patients were identified, 33 in the yRC and 129 in the older patient group. The median age at diagnosis was 62 (24 – 92). Median follow-up was 40 months. There was no difference in presenting symptoms between the two groups, with per rectal bleeding being the most common symptom at presentation. 17.5% of yRC presented with stage IV disease, compared with 22.1% of older patients. yRC were more likely to complete neoadjuvant therapy (97% vs 81%; P=0.02). yRC were more likely to proceed to surgery (91% vs 72%, P=0.02). There were no significant differences in surgical outcomes, including complications and postoperative TNM staging. yRC were more likely to have microsatellite high tumours (18% vs 4%; P=0.01). No statistical differences were seen in survival outcomes (PFS 57.1 vs 62.9 months, P=0.26; OS 85.1 Vs 92.8 months, P=0.57) between older and yRC patients. Eight progressions (eight deaths) were observed in the yRC group and 40 progressions (36 deaths) were observed in the older patient group. Conclusions: 20% of rectal cancers were considered yRC. These patients were more likely to complete neoadjuvant therapy and proceed to surgery. In this cohort, median PFS and OS were longer compared to the older patient group, although this was not statistically significant. yRC were more likely to have MMR deficiency. Patients under 50 years with alarm symptoms including per rectal bleeding require vigilance in investigations to allow for earlier detection and appropriate management of rectal cancer.
Variability of allergens in commercial fish extracts for skin prick testing
Authors: Thimo Ruethers, Aya C. Taki, Roni Nugraha, Trúc T. Cao, Martina Koeberl, Sandip D. Kamath, Nicholas A. Williamson, Sean O'Callaghan, Shuai Nie, Sam S. Mehr, Dianne E. Campbell, Andreas L. Lopata
Journal: Allergy (2019)

Abstract Background Commercial allergen extracts for allergy skin prick testing ( SPT ) are widely used for diagnosing fish allergy. However, there is currently no regulatory requirement for standardization of protein and allergen content, potentially impacting the diagnostic reliability of SPT s. We therefore sought to analyse commercial fish extracts for the presence and concentration of fish proteins and in vitro IgE reactivity using serum from fish‐allergic patients. Methods Twenty‐six commercial fish extracts from five different manufacturers were examined. The protein concentrations were determined, protein compositions analysed by mass spectrometry, followed by SDS ‐ PAGE and subsequent immunoblotting with antibodies detecting 4 fish allergens (parvalbumin, tropomyosin, aldolase and collagen). IgE‐reactive proteins were identified using serum from 16 children with confirmed IgE‐mediated fish allergy, with focus on cod, tuna and salmon extracts. Results The total protein, allergen concentration and IgE reactivity of the commercial extracts varied over 10‐fold between different manufacturers and fish species. The major fish allergen parvalbumin was not detected by immunoblotting in 6/26 extracts. In 7/12 extracts, five known fish allergens were detected by mass spectrometry. For cod and tuna, almost 70% of patients demonstrated the strongest IgE reactivity to collagen, tropomyosin, aldolase A or β‐enolase but not parvalbumin. Conclusions Commercial fish extracts often contain insufficient amounts of important allergens including parvalbumin and collagen, resulting in low IgE reactivity. A comprehensive proteomic approach for the evaluation of SPT extracts for their utility in allergy diagnostics is presented. There is an urgent need for standardized allergen extracts, which will improve the diagnosis and management of fish allergy.
Germline pharmacogenomics of thymidylate synthase gene in patients with gastrointestinal malignancies treated with fluoropyrimidines-based chemotherapy regimens.
Authors: Saad Awan, Girijesh K. Patel, Anu Singh Maharjan, Gwendolyn A. McMillin, William R. Taylor, Sachin Pai, Arthur E. Frankel, Clayton Smith, Leander Grimm, Paul Rider, John Hunter, Spencer Liles, Cindy Nelson, Bin Wang, Peter Joel Hosein, Ajay Singh, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2019)

545 Background: Fluoropyrimidines are antimetabolites that target the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS) enzyme, thus preventing DNA synthesis and ultimately cell death. While controversy exists in the literature, polymorphism in the promoter region of thymidylate synthase gene (TYMS) that decrease TS expression has been associated with increased fluoropyrimidines-associated toxicities. This study explored the association between polymorphism in the promoter region of TYMS gene and fluoropyrimidines-associated toxicities in patients with gastrointestinal malignancies with mixed racial background. Methods: Between 2011 and 2018, 126 patients were genotyped for TYMS. Patients with known high-risk dihydropyrimidine dehydrogenase gene variants were excluded. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institiute Common Terminology Criteria for Adverse Events (v 5.0). Fisher’s exact test was used for statistical analysis. Results: TYMS genotypes that predict increased TS expression (3RG/3RG, 3RG/3RC, 2R/3RG, 2R/4R, 3R/4R, 4R/3RG) were identified in 55 patients (44%). TYMS genotypes that predict decreased TS expression (2R/2R, 2R/3RC, 3RC/3RC) were seen in 71 patients (56%). Among patients with genotypes that predict increased TS expression (N = 55), 12 patients had grade 3-4 toxicity (22%) while among patients with genotypes that predict decreased TS expression, 30 patients had grade 3-4 toxicities (42%) (P = 0.0219). Compared to patients with genotypes predicting increased TS expression, 17 out of 31 patients (55%) with 2R/2R TYMS genotype had grade 3-4 toxicity (P = 0.0039) and 15 out 40 patients (38%) with 2R/3RC and 3RC/3RC TYMS genotype had grade 3-4 toxicity (P = 0.1108). Among patients with 2R/2R TYMS, Caucasians represented 61% and African Americans represented 39%. Females represented 65% of the patients. Conclusions: Polymorphism in the promoter region of TYMS gene that predict decreased TS expression due to 2R/2R variant was associated with grade 3-4 fluoropyrimidines-associated toxicities.
Seasonal Variations in the Achievement of Guideline Targets for HbA1c, Blood Pressure, and Cholesterol Among Patients With Type 2 Diabetes: A Nationwide Population-Based Study (ABC Study: JDDM49)
Authors: Masaya Sakamoto, Daisuke Matsutani, Soichiro Minato, Yuki Tsujimoto, Yosuke Kayama, Norihiko Takeda, Seiichi Ichikawa, Ryuzo Horiuchi, Kazunori Utsunomiya, Masako Nishikawa
Journal: Diabetes Care (2019)

Precise monthly achievement rates for reaching guideline targets for HbA1c, blood pressure (BP), and lipid levels remain unknown. We evaluated achievement rates on a monthly basis in persons with type 2 diabetes mellitus (T2DM) and explored related factors.This retrospective study initially analyzed data on 104,601 persons with T2DM throughout Japan. Patients whose HbA1c, BP, and LDL cholesterol were measured ≥12 times during a 24-month period were included. We evaluated monthly achievement rates. Achieved targets were defined as HbA1c <7%, BP <130/80 mmHg, and LDL cholesterol <100 mg/dL. Achievement of all targets was expressed as the "all ABC achievement."A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA1c, BP, and LDL cholesterol were lowest in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA1c, 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL cholesterol, 50.8%, 47.2%). In winter, age ≥65 years (odds ratio 0.47 [95% CI 0.34-0.63]) was independently related to decreased achievement rates for SBP, BMI ≥25 kg/m2 (BMI 25-30 kg/m2, 0.45 [0.29-0.70]; BMI ≥30 kg/m2, 0.35 [0.22-0.57]), and diabetes duration ≥10 years (0.53 [0.37-0.76]) were independently related to lower achievement rates for HbA1c. Insulin use and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter.The all ABC achievement rate for guideline targets changed on a monthly basis. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices.
Blomia tropicalis And Component Resolved Diagnosis: Performance Outcomes In Moderate-Severe Allergic Rhinitis
Authors: Ruperto Gonzalez-Perez, Fernando Pineda, Paloma Poza-Guedes, Miriam Castillo Fernandez, Maria Inmaculada Sanchez-Machin, Cristina Alava, Victor M. Matheu
Journal: Journal of Allergy and Clinical Immunology (2019)
Sweeteners are added to modify consumer behaviour
Authors: Sven E Jordt, Sairam Jabba
Journal: BMJ (2019)

The meta-analysis by Toews and colleagues indicates that artificial sweeteners are safe to consume, but their uses go beyond sugar substitution and calorie reduction.12 Artificial sweeteners allow the cheaper and more efficient production of highly processed foods with long shelf lives and enable the formulation of new sweet products. 

Sweeteners such as sucralose or aspartame are 200-600 times sweeter than sugar. Novel candy products and beverages often contain sugar and artificial …
Balloon enteroscopy-assisted radial incision and cutting method for refractory hepaticojejunostomy anastomotic strictures
Authors: Tadahisa Inoue, Mayu Ibusuki, Rena Kitano, Yuji Kobayashi, Tomohiko Ohashi, Yukiomi Nakade, Yoshio Sumida, Kiyoaki Ito, Haruhisa Nakao, Masashi Yoneda
Journal: Endoscopy (2019)

Abstract Background Balloon enteroscopy-assisted balloon dilation and temporary biliary stent placement are effective for hepaticojejunostomy anastomotic strictures (HJAS), but the re-stenosis rates are relatively high. We examined the feasibility and efficacy of a novel treatment technique for refractory HJAS, called balloon enteroscopy-assisted radial incision and cutting (BE-RIC). Methods Between January 2016 and June 2018, 11 patients with refractory HJAS that recurred after balloon dilation and/or stent placement, underwent BE-RIC. We evaluated the technical success, clinical success, adverse events, and re-stenosis rates associated with BE-RIC. Results The technical success rate of BE-RIC was 91 % (10/11). Clinical success was achieved in all patients who underwent technically successful procedures. The procedure-related adverse event rate was 9 % (1/11). No re-stenosis was observed during the follow-up period; 9 patients were followed up for more than 6 months, and of these, 5, 4, and 2 patients were followed up for more than 12, 18, and 24 months, respectively, without re-stenosis. Conclusions BE-RIC for refractory HJAS showed favorable results. BE-RIC might be a useful option for treating refractory HJAS.
AB0134 Sulphasalazine (salazopyrine en) in treatment of reactive arthritis (efficacy, safety and tolerability)
Authors: Z Gnjidic, M Gnjidic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Evaluation of the efficacy and tolerance of sulphasalazine (SALAZOPYRIN EN-tabs) in the management of Reactive arthritis (ReA) triggered by a urogenital infection. <h3>Methods</h3> We conducted an open randomised trial on 2 parallel groups of patients, 30 patients each during 12 months (30 treated with SALAZOPYRIN EN 1–2 g/day, versus 30 treated with NSAID or analgesics). Tolerability and safety were assessed with whole blood picture test for liver and renal function, gastro-intestinal (G-I) adverse effects, and other side effects. Every month the efficiency of treatment was checked by clinical and laboratory methods. <h3>Results</h3> There were no significant differences in demographic, clinical and laboratory parameters among the two groups at the study entry. By the end of the study, there was evidence of significant improvement shown by pain score, ability of movement, and reduction in the acute phase response in sulphasalazine (SALAZOPYRINE EN) group. Adverse reactions in the sulphasalazine (SALAZOPYRINE EN) group (12% of patients) occurred mainly in the first ten weeks of treatment and were mild, reversible and did not require termination of therapy. In 1% of patients these were severe enough to stop treatment. The NSAID group encountered adverse reactions in 27% of patients and 4% required termination of therapy. <h3>Conclusion</h3> Sulphasalazine (SALAZOPYRINE EN) proved to be a good first choice as a second-line of a disease modifying antirheumatic drug because of its early efficacy (8 weeks), persistent efficacy and its good tolerance.
IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-Dependent Anti-inflammatory Properties
Authors: Liming Du, Liangyu Lin, Qing Li, Keli Liu, Yin Huang, Xuefeng Wang, Kai Cao, Xiaodong Chen, Wei Cao, Fengying Li, Changshun Shao, Ying Wang, Yufang Shi
Journal: Cell Metabolism (2019)
Subsequent anticancer medication following first-line lenvatinib: A posthoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma.
Authors: Angel Alsina, Masatoshi Kudo, Arndt Vogel, Ann-Lii Cheng, Won Young Tak, Baek-Yeol Ryoo, T.R. Jeffry Evans, Carlos López-López, Bruno Daniele, Soamnauth Misir, Min Ren, Namiki Izumi, Shukui Qin, Richard S. Finn
Journal: Journal of Clinical Oncology (2019)

371 Background: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79–1.06). LEN was superior vs SOR for secondary endpoints including objective response rate (ORR) per mRECIST: 24.1% vs 9.2% by investigator and 40.6% vs 12.4% by independent review (Kudo M et al. Lancet 2018). We report a posthoc responder analysis of patients (pts) who received first-line LEN in REFLECT and subsequent anticancer medication during survival follow up. Methods: In REFLECT, pts with unresectable hepatocellular carcinoma were randomized 1:1 to receive first-line LEN or SOR. Objective response was defined as complete or partial response by mRECIST per investigator. Pts with disease progression and who discontinued treatment were followed for survival every 12 weeks; subsequent anticancer medication during survival follow up were recorded until time of death. Data cutoff: Nov 13, 2016. mOS was calculated using Kaplan-Meier estimates with 2-sided 95% CIs. Results: In REFLECT, one third of the overall study population (156/478 pts randomized to LEN and 184/476 to SOR) received subsequent anticancer medication, most commonly SOR (25% in LEN arm). ECOG performance status and laboratory assessments, including liver function tests, were comparable between arms prior to subsequent treatments. Among these pts, mOS was 21 vs 17 mo and ORR was 27.6% vs 8.7% for LEN vs SOR arms, respectively. In a subset analysis of LEN responders who received any subsequent anticancer medication (n = 43), mOS was 26 mo (95% CI 18.5–34.6). For SOR responders who received any subsequent anticancer medication (n = 16), mOS was 22 mo (95% CI, 14.6–NE). For LEN responders who subsequently received SOR (n = 35), mOS was 26 mo (95% CI 18.2–34.6). Conclusions: In REFLECT, one third of pts randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory, posthoc analysis of pts who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo. Clinical trial information: NCT01761266.
Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01
Authors: Guillem Pascual-Pasto, Miriam Bazan-Peregrino, Nagore G. Olaciregui, Camilo A. Restrepo-Perdomo, Ana Mato-Berciano, Daniela Ottaviani, Klaus Weber, Genoveva Correa, Sonia Paco, Monica Vila-Ubach, Maria Cuadrado-Vilanova, Helena Castillo-Ecija, Gaia Botteri, Laura Garcia-Gerique, Helena Moreno-Gilabert, Marta Gimenez-Alejandre, Patricia Alonso-Lopez, Marti Farrera-Sal, Silvia Torres-Manjon, Dolores Ramos-Lozano, Rafael Moreno, Isabelle Aerts, François Doz, Nathalie Cassoux, Elodie Chapeaublanc, Montserrat Torrebadell, Monica Roldan, Andrés König, Mariona Suñol, Joana Claverol, Cinzia Lavarino, Torres Carmen de, Ligia Fu, François Radvanyi, Francis L. Munier, Jaume Catalá-Mora, Jaume Mora, Ramón Alemany, Manel Cascalló, Guillermo L. Chantada, Angel M. Carcaboso
Journal: Science Translational Medicine (2019)

Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.