tbuckley/cabot-search huggingface dataset:
OC-080 Stat2 is a key mediator of acute pancreatitis
Authors: H Heath, G Renney, M Ward, P Cutillas, H Kudu, R Goldin, R Hutchins, GR Foster, K Brohi, W Alazawi
Journal: Gut (2017)

Introduction  Acute pancreatitis is a major cause of morbidity and mortality. It can be caused by a range of insults such as alcohol and gallstones which result in inappropriate activation of digestive enzymes, cellular injury, and local inflammation. The disease spectrum ranges from mild self-limiting illness through to systemic inflammation, organ dysfunction and death. Current predictive tools are crude, mostly due to a lack of understanding of the molecular mechanisms driving inflammation. For the same reasons, there are no specific therapies for acute pancreatitis and treatment is supportive. We have previously shown that the Stat2 protein is a pivotal mediator of TLR-mediated inflammation. Therefore, we tested the hypothesis that Stat2 mediates inflammation in mouse models and in patients with acute pancreatitis.  Method  Wild type (WT) and Stat2-/- mice were injected intraperitoneally with 2 µg or 1 µg cerulein hourly for 4 or 7 hours respectively; or 4 g/kg l-arginine. Pancreata and blood were harvested 1 hour and 24 hour after the final dose of cerulein, and 24 hour, 48 hour, 72 hour and 96 hour after l-arginine treatment. Blood was taken from patients with acute pancreatitis on the day of admission. PBMCs from patients and healthy controls were analysed by phos-flow following ex-vivo stimulation with interferon-α.  Results  Stat2-/- mice are protected in both cerulein and l-arginine models compared to WT, as evidenced by histology, significantly lower levels of serum amylase, inflammatory gene and protein expression and plasma leakage. Global protein expression analysis using label-free mass spectrometry identified 187 proteins whose expression was altered in cerulein-treated WT mice compared to control, 172 of which were differentially expressed in Stat2-/- mice. Among these were major blood clotting pathways and we used rotational thromboelastometry to show that clotting abnormalities seen in WT cerulein-treated mice were more severe than in the protected Stat2-/-. Phosphoproteome analysis revealed differences in MAPK pathway proteins phosphorylation. Western blotting confirmed reduced NF-kB and phosphorylated p38MAPK in pancreatic nuclear extracts from Stat2-/-compared to WT mice. In patients with acute pancreatitis, levels of activated STAT2 but not STAT1 were increased in PBMCs compared to healthy controls.  Conclusion  Stat2 is a mediator of acute pancreatitis and required for MAPK and NF-kB function. Stat2 or associated factors identified in this study are potential biomarkers for pancreatic inflammation and/or therapeutic targets.  Disclosure of Interest  None Declared
Screening for pancreatic cancer in a high-risk cohort: A 7-year experience.
Authors: W. Al-Sukhni, A. Borgida, H. Rothenmund, S. Holter, S. Wilson, M. J. Moore, S. Narod, K. Jhaveri, M. A. Haider, S. Gallinger
Journal: Journal of Clinical Oncology (2011)

4045 Background: Pancreatic cancer is the fourth leading cause of cancer death, and most cases are detected at an advanced stage. Successfully identifying and resecting early invasive or pre-invasive pancreatic lesions can significantly improve outcome. Individuals with predisposing genetic mutations or families which cluster pancreatic cancer are ideal targets for screening. Here we describe the largest pancreatic cancer screening study to date. Methods: This prospective cohort study was undertaken between 2003-2010 at a tertiary care centre in Toronto, Canada. Two hundred and fifty-nine high-risk subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected (i.e., pancreatic mass; cystic lesions; pancreatic duct dilation). Evidence of malignancy or significant change in cystic lesions prompted referral for surgery. Results: Average length of follow-up was 3.2 years, during which 2/259 subjects developed invasive pancreatic adenocarcinoma. One asymptomatic subject underwent total pancreatectomy for a 1.5cm T1N1M0 tumor, but she had recurrence with metastasis leading to death three years later. A second subject had main duct dilation over a six-month interval, prompting referral for further investigation; however, he had metastases four months later and died soon after. Fifteen subjects had radiologic evidence of small branch-duct intraductal papillary mucinous neoplasms, most of which have remained stable under surveillance. Two subjects with branch-duct intraductal papillary mucinous neoplasms underwent surgical resection; resected specimens contained low- to moderate-grade dysplasia with no invasive cancer. Conclusions: Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, although improvement in sensitivity is needed to allow intervention at an earlier stage. The majority of branch-duct intraductal papillary mucinous neoplasms appear to have low malignant potential, and a better understanding of their natural history is required to guide management.
Who are “we” and why are we cooperating? Insights from social psychology
Authors: Margaret S. Clark, Brian D. Earp, Molly J. Crockett
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello argues in the target article that a sense of moral obligation emerges from the creation of a collaborative “we” motivating us to fulfill our cooperative duties. We suggest that “we” takes many forms, entailing different obligations, depending on the type (and underlying functions) of the relationship(s) in question. We sketch a framework of such types, functions, and obligations to guide future research in our commentary.
Nuclear Medicine Imaging Techniques in Melanoma
Authors: Ismaheel O. Lawal, Mike M. Sathekge
Journal: Clinical Nuclear Medicine (2020)

Melanoma is a malignant tumor of the skin that arises from melanocytes located in the dermo-epidermal junction of the skin. Sun exposure is a strong predisposing factor to melanoma of the skin. The Breslow thickness of the skin lesion predicts the presence of metastasis and is a strong prognostic indicator. Melanoma commonly metastases first to lymph nodes and then to visceral organs. Sentinel lymph node biopsy is an essential procedure in the determination of the presence of early metastasis in lymph nodes. It is required for accurate staging and prognostication of the disease. 18F-FDG PET/CT is useful for the accurate staging of thick melanoma. Its use may lead to upstaging of disease due to detection of previously unknown site of metastasis, and this may lead to a significant change in patient management. The introduction of immune modulators and therapies targeting mutational changes in melanoma has increased the utility of 18F-FDG PET for therapy response assessment. This has, however, come with many challenges due to the high rate of immune-related complications associated with immune modulation therapy. This challenge has created a need for clinical application of tracers capable of direct targeting of melanoma cells which may be very specific for therapy response assessment. Melanin is produced in high levels by some melanomas, and melanocortin 1 receptor which is overexpressed on melanoma cells is a common target for specific melanoma imaging.
circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer
Authors: Yao Kong, Yuting Li, Yuming Luo, Jiang Zhu, Hanhao Zheng, Bowen Gao, Xiaofeng Guo, Zhihua Li, Rufu Chen, Changhao Chen
Journal: Molecular Cancer (2020)

Abstract Background Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown. Methods Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p. Results In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC. Conclusions Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC. Graphical abstract
Publisher Correction: ASPI: a public–private partnership to develop treatments for autism
Authors: Seth Ness, Gahan Pandina, Shyla Jagannatha, Kyle Wathen, Abigail Bangerter, Nikolay V. Manyakov, Robert Hendren, Bennett Leventhal, Declan Murphy, Geraldine Dawson, Wayne C. Drevets, Husseini K. Manji
Journal: Nature Reviews Drug Discovery (2020)
Systemic Immune Response and Cancer Risk: Filling the Missing Piece of Immuno-Oncology
Authors: Mingyang Song, Shelley S. Tworoger
Journal: Cancer Research (2020)

Abstract While immuno-oncology has made significant advances in activating local tumor immune responses, leading to improved outcomes, the role of systemic immunity in cancer incidence remains poorly understood. Le Cornet and colleagues prospectively studied circulating immune cells quantified by DNA methylation markers in relation to incidence of breast, colorectal, lung, and prostate cancer among initially healthy individuals. A positive association with cancer risk was observed for higher FOXP3+ T-cell–mediated immune tolerance and lower CD8+ T-cell–mediated cytotoxicity. Further studies of systemic immunity in cancer development are crucial to identify novel prediction markers and interventional targets for cancer immunoprevention. See related article by Le Cornet et al., p. 1885
Returning to work after treatment for breast cancer.
Authors: E. M. Stroppa, L. Cavanna, M. Ambroggi, C. di Nunzio, L. Dallanegra, M. Monfredo
Journal: Journal of Clinical Oncology (2011)

e11572 Background: Relatively few studies have assessed the association of cancer survivorship with unemployment, and return to work (RTW) after the diagnosis of breast cancer remind still a problem. Methods: In the present study the treating physician or psychoncologist recruited patients before the start of initial treatment, in the period from August 2007 to January 2008 at our institution. 76 of 112 consecutive patients with early breast cancer admitted to our outpatient medical oncology accepted to participate this study and to complete the interviews; all patients were interviewed at diagnosis and after 1, 3, 6, 9, 18 and 24 months. Clinical and psychological data including diagnosis, stage, age, anxiety, depression, treatment planned, job at diagnosis were recorded for each patient. Results: After 1 month from diagnosis, 45% of patients stopped work and after 3 to 9 months 55.3% of patients stopped work. In our group of patients, 77.9% of them had full RTW after a median delay of 10.3 months; anxiety and depression seem affect employment by decreasing work hours, and increasing absence. Age > 55 years, chemotherapy, physical and psychological status were the major factors affecting the return to work, while type of surgery, sentinel lymphnode biopsy or axillary dissection, radiation therapy and hormonal therapy did not negatively influence the return to work. Conclusions: People treated for cancer have reported a variety of problems at work. Also the importance of social support from the workplace in relation to sickness absence in general is well documented and more recently the importance of social support from the employer and coworkers for the return to work, was demonstred. Work is important for individual’s identity and provides also a social connection, however the experience of continuing or returning to work following cancer and related treatment is a largely unknown area of cancer research.
A molecular mechanism explaining albuminuria in kidney disease
Authors: Linus Butt, David Unnersjö-Jess, Martin Höhne, Aurelie Edwards, Julia Binz-Lotter, Dervla Reilly, Robert Hahnfeldt, Vera Ziegler, Katharina Fremter, Markus M. Rinschen, Martin Helmstädter, Lena K. Ebert, Hayo Castrop, Matthias J. Hackl, Gerd Walz, Paul T. Brinkkoetter, Max C. Liebau, Kálmán Tory, Peter F. Hoyer, Bodo B. Beck, Hjalmar Brismar, Hans Blom, Bernhard Schermer, Thomas Benzing
Journal: Nature Metabolism (2020)
Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is required for CHK1 activation
Authors: Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y. Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H. Young, Wei Wang, Yong Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC. Methods We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse xenograft tumorigenesis. We analyzed human CRC specimens by immunohistochemistry. Results TRAF4 catalyzed the ubiquitination of CHK1 in multiple CRC cell lines. Following DNA damage, ubiquitination of CHK1 at K132 by TRAF4 is required for CHK1 phosphorylation and activation mediated by ATR. Notably, TRAF4 was highly expressed in chemotherapy-resistant CRC specimens and positively correlated with phosphorylated CHK1. Furthermore, depletion of TRAF4 impaired CHK1 activity and sensitized CRC cells to fluorouracil and other chemotherapeutic agents in vitro and in vivo. Conclusions These data reveal two novel steps required for CHK1 activation in which TRAF4 serves as a critical intermediary and suggest that inhibition of the ATR–TRAF4–CHK1 signaling may overcome CRC chemoresistance.
Abstract 18702: Closed-loop Servo-regulatory Neuromodulation (Bionic Baroreflex System) Instantly Resolves Pulmonary Congestion Without Imposing Excessive Hypotension in a Rat Model of Acute Heart Failure
Authors: Keita Saku, Takeshi Tohyama, Kazuya Hosokawa, Kazuhiro Kamada, Hiroshi Mannoji, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2017)

Background: Acute heart failure (AHF) excessively activates sympathetic nerve activity (SNA), markedly increases stressed volume and thereby left ventricular end-diastolic pressure (LVEDP), and oft...
A Trial of Lopinavir–Ritonavir in Covid-19
Authors: Bin Cao, Dingyu Zhang, Chen Wang
Journal: New England Journal of Medicine (2020)

19To the Editor: After a review of the findings of Cao et al. (published in the Journal online on March 18), 1 many clinicians are abandoning the use of lopinavir-ritonavir for the treatment of Covid-19.We consider this action to be premature.It is crucial to realize that although this trial did not show that the time until clinical improvement was meaningfully better than standard care among patients with severe Covid-19 who received lopinavir-ritonavir, the trial was statistically underpowered to show this outcome.In addition, the analyses of secondary outcomes (which still require confirmation) suggested that lopinavir-ritonavir may be associated with substantial lowering of overall mortality (19% in patients in the lopinavir-ritonavir group vs. 25% in the standard-care group), the risk of severe adverse events (20% vs. 32%), and the risk of respiratory failure or acute respiratory distress syndrome (13% vs. 27%).Lopinavir-ritonavir has shown activity against SARS-CoV-1 2,3 and is available for immediate clinical use in many countries.Because there currently are no approved treatments for Covid-19, 4 and because the pandemic diffusion of SARS-CoV-2 is causing shortages of alternative drugs, we should not yet abandon lopinavir-ritonavir.We therefore advocate that therapeutic guidelines retain lopinavir-ritonavir as a treatment option against Covid-19, pending completion of the World Health Organization SOLIDARITY trial. 5
Николай Кудрицкий: от земского врача — до профессора
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2020)

В статье представлены трагический жизненный путь, врачебная, научная, педагогическая и общественная деятельность профессора-гигиениста Николая Антоновича Кудрицкого. Отражен его вклад в развитие украинской гигиенической школы, создание направления «школьная гигиена». Особое внимание уделено началу профессиональной деятельности ученого в местечке Петриковка Екатеринославской губернии — нынешней Днепропетровщины-Сичеславщины.
Abstract MP038: Soft Drink Consumption Increases the Risk of Hypertension in Korean Adults: A Prospective Cohort Study
Authors: Garam Jo, SoYoung Kwak, Yoonsu Cho, Min-Jeong Shin
Journal: Circulation (2017)

Introduction: Several previous studies have reported that consumption of soft drink is associated with increased risk of hypertension (HTN) in Western societies. However, epidemiological information on such associations is very limited in Koreans. Hypothesis: We tested the hypothesis whether an increase in soft drink consumption is related to higher risk of HTN among Korean middle aged adults from Korean community based Cohort (Ansan-Ansung cohort). Methods: Data from Ansan-Ansung cohort from 2001 to 2010 in the Korean genome and epidemiology study (KoGES) were used for statistical analyses. Among the participants, we selected 5,296 subjects (2,475 men and 2,821 women, aged 39-64 yrs) who were free from presence of HTN, diabetes, cardiovascular disease and cancer at baseline and those who completely followed up for 10.4 years. Participants who completed a semi-quantitative food frequency questionnaire for dietary assessment and questionnaire for baseline health status in 2001-2002 were included in analyses. Subjects were categorized as quartile based on their soft drink consumption. Soft drink consumption was calculated as frequency per week summed up by consumption frequency of soda (such as Coke and Sprite) and other beverages (including sweet rice drink and Citrus tea). To assess the relationship between soft drink consumption and HTN, we estimated multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) using cox regression analysis. In addition, stratified analysis by body mass index (BMI) was conducted. Results: During the follow-up period of 10.4 years, we ascertained 1,035 incident cases (19.5% of study population) of HTN. Total soft drink consumption showed significant association with increased risk for HTN after adjusting for potential confounders (age, sex, total energy intake, BMI, and socio-economic factors). The adjusted HR of HTN for the highest quartile of soft drink consumption was 1.24 (95% CIs: 1.02-1.51) compared to the lowest quartile. Furthermore, we found that higher consumption of soft drink was significantly associated with increased incidence of HTN in subjects with BMI ≥25 (HR: 1.54; 95% CIs: 1.15-2.01), whereas there was no significant association among subjects with BMI &lt;25. Conclusions: In conclusion, this study suggested that soft drink consumption contributes to increased risk of HTN, being prominent in obese participants. Our results support recommendations to reduce the consumption of soft drink to prevent and control HTN, although further large prospective studies or randomized controlled trials are warranted to confirm the observed association.
PTH-075 Long-term outcomes after endoscopic resection of large colorectal superficial neoplastic lesions in an expert centre
Authors: Andrew Emmanuel, Shraddha Gulati, Anil Ghosh, Christo Lapa, Margaret Burt, Bu Haji, Amyn Haji
Journal: Endoscopy (2018)

<h3>Introduction</h3> There are very few western data describing the long term outcomes of endoscopic resection of large colorectal superficial neoplastic lesions (CSNL) beyond 12–18 months. The best available data suggests most recurrence occurs early whereas late recurrence (after 3–6 months) is rare and not a significant problem. Given the widespread and increasing use of advanced endoscopic resection techniques, it is important to define the long term outcomes beyond the first year of surveillance. <h3>Methods</h3> We analysed endoscopic resections (ER) of large (≥2 cm) CSNL performed at a tertiary referral centre. Surveillance is conducted according to a standardised protocol involving magnification chromoendoscopy and NBI performed at 3–6 months and 12 months, followed by standard adenoma surveillance again at 3 years. Recurrence rates at &lt;6 months, 12–23 months, 24–35 months and ≥36 months follow up were calculated. Recurrence rates at each interval were only calculated for patients in whom no prior recurrence had been detected at an earlier interval. χ<sup>2</sup> test was used to determine factors significantly associated with early recurrence (&lt;12 months) and late recurrence (≥12 months). <h3>Results</h3> 588 ER of large CSNL were performed (mean size 52.5 mm). After relevant exclusions, 425 patients had undergone at least the first surveillance endoscopy, of which 259 had undergone 12 month follow up, 90 had undergone ≥24 months follow up and 51≥36 months follow up. Recurrence at &lt;6 months occurred in 34 (8%). 15/235 (6.4%) patients had recurrence at 12 month surveillance. 7/70 (10%) had recurrence from 24–35 months follow up and 4/35 (11.4%) developed recurrence after ≥36 months follow up. Factors significantly associated with recurrence were similar for both early and late recurrence (size &gt;40 mm, piecemeal resection, EMR vs ESD, prior heavy manipulation, use of APC). However, of patients followed up ≥36 months (n=51), 93% had successful ER (including treatment of recurrence) and have remained free from recurrence at last follow up. <h3>Conclusions</h3> These data demonstrate that recurrence after apparent successful ER of large CSNL continues to occur after 2 and even 3 years of follow up, despite subsequent normal initial surveillance. Although recurrence at 12 months was similar to large published series, significant proportions of patients continue to develop recurrence with longer term follow up. Nevertheless, ER in an expert centre is safe and highly effective for the vast majority.
Prevalence of Special Health Care Needs Among Foster Youth in a Nationally Representative Survey
Authors: Lucy A. Bilaver, Judy Havlicek, Matthew M. Davis
Journal: JAMA Pediatrics (2020)

MHI; specify that Dr Thompson's affiliation is called "Peds AI" and not "Peds AI Clinic"; and add 2 missing notations denoting significance to the graphs for cigar and cocaine