tbuckley/cabot-search huggingface dataset:
Letter to the editor: Pending challenges in passenger contact tracing in air transport – a German perspective
Authors: Juliane Seidel, Dorothea Matysiak-Klose, Matthias Jeglitza, , Nadine Litzba
Journal: Eurosurveillance (2019)

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Resolving attacker-defender conflicts through intergroup negotiation
Authors: Nir Halevy
Journal: Behavioral and Brain Sciences (2019)

Abstract The target article focuses on how attacker-defender conflicts are fought . This commentary complements it by considering how attacker-defender conflicts may be resolved at the bargaining table. I highlight multiple linkages between asymmetric intergroup conflict as modeled with the attacker-defender game and negotiation research and illustrate how the proposed model of attacker-defender conflicts can inspire new research on intergroup negotiation.
Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi
Authors: Virginia E. Pitzer, Aisleen Bennett, Naor Bar-Zeev, Khuzwayo C. Jere, Benjamin A. Lopman, Joseph A. Lewnard, Umesh D. Parashar, Nigel A. Cunliffe
Journal: Science Translational Medicine (2019)

Administering an additional dose of rotavirus vaccine at 9 months of age in Malawi is predicted to lead to only modest improvements in vaccine impact.
Diversity of genetic alterations of primary central nervous system lymphoma in Hispanic versus non-Hispanic population.
Authors: Mohamad Barakat, Maher Albitar, Robin L. Whitney, Calvin Chen, Yu-Hung Kuo, William Silveira, Mohammed SANI Bukari, Subramanyeswara Rao Arekapudi, Karamjit Dhaliwal-Binning, Haifaa Abdulhaq
Journal: Journal of Clinical Oncology (2019)

7535 Background: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma, distinguished by poor prognosis. Previous studies have identified MYD88, CD79b and PIM1 as the most common genetic mutations in PCNSL. However, the extent to which mutations vary by ethnicity is unknown. The purpose of this study was to describe differences in genetic mutations and survival by Hispanic ethnicity in PCNSL. Methods: We retrospectively reviewed records of 30 patients with PCNSL diagnosed between January 2007- December 2017. We examined mutations in 275 genes by DNA analysis and 1382 genes by RNA analysis utilizing next generation sequencing. Results: Among the thirty patients, median age was 60 years, 60% were male, and 60% were Hispanic. Twenty-four patients had activated B-cell (ABC) and 5 patients had germinal center (GC) type per Hans criteria. Among 29 patients with complete mutation data, 125 different mutated genes were detected. Missense mutations were the most common (75%) followed by frame shift mutations (25%). The most commonly affected genes were: MYD88 (44%), CARD11 (21%), CD79b (17%), PIM1 (17%), KMT2D (17%) and ETV6 (14%). CD79b mutation was more common in GC type vs. ABC type (60% vs. 8%, P=.01). MYD88 mutation was less frequent in Hispanic patients (27% vs 66%, P=.02), while there were no statistically significant differences in CARD11 (22% vs 18%, P=.79), KMT2D (22% vs 9%, P=.36), CD79B (16% vs 19%, P=.92) and PIM1 (16% vs 19%, P=.92). There were more Hispanic patients with &gt;3 mutated genes (89% vs 55 %. P=.03). Two-year progression-free survival (PFS) and overall survival (OS) were 46% and 50%, respectively. Both outcomes were superior among Hispanic vs. non-Hispanic patients (2-yr PFS 60% vs 27%, P=.09), (2-yr OS 60% vs 36%, P=.23), but this was not statistically significant. MYD88, CARD11, PIM1, and KMT2D were not associated with significant differences in 2-year OS or PFS. However, patients with CD79b mutations had superior 2-yr PFS (P=.04). Conclusions: We identified highly recurrent genetic alterations in PCNSL. Our data suggest that some heterogeneity in the most frequent mutations in PCNSL may be related to ethnicity. However, the superiority in 2-yr PFS and OS did not reach statistical significance in our Hispanic patients. Further studies on a larger patient population may further help to describe the differences in incidence, tumor biology, and outcomes in Hispanic patients.
A New Prognostic Scoring System to Predict Disease Progression and Mortality in Patients with Newly Diagnosed Primary CNS Lymphoma
Authors: Chia-Jen Liu, Chia-Hsin Lin, Ying-Chung Hong, Ching-Fen Yang, Huai-Che Yang, Li-Yu Fay, Chiu-Mei Yeh, Jyh-Pyng Gau, Yuan-Bin Yu, Tzeon-Jye Chiou, Jin-Hwang Liu, Yao-Chung Liu, Chung-Jen Teng
Journal: Blood (2017)
Surgical resection and peri-operative chemotherapy for colorectal cancer (CRC) liver metastases in routine clinical practice: A population-based outcomes study.
Authors: Christopher M. Booth, Gavin Li, James Joseph Biagi, Monika K. Krzyzanowska, William J. Mackillop, Sulaiman Nanji
Journal: Journal of Clinical Oncology (2012)

3632 Background: Resection of liver metastases combined with peri-operative chemotherapy is an important treatment option for patients with advanced CRC. Most of the literature describes outcomes achieved in highly selected patients treated at a few high volume institutions. Here we report the results of a population-based study of the management and outcome of all patients who underwent resection of CRC liver metastases in Ontario, Canada. Methods: All cases of CRC in Ontario who underwent surgical resection of liver metastases in 1994-2009 were identified using the population-based Ontario Cancer Registry (OCR). The OCR captures diagnostic and demographic information on ~98% of all incident cancer cases in Ontario. We linked electronic records of treatment to the OCR to identify surgery, neoadjuvant (NACT) and adjuvant chemotherapy (ACT). We describe time trends in treatment and survival using 3 study periods: 1994-1999, 2000-2004, 2005-2009. Results: During 1994-2009, 2717 patients underwent resection of CRC liver metastases in Ontario; mean age was 65 years and 61% were male. From 1994-2009 there was a 103% increase in the number of patients undergoing resection of liver metastases (117/year to 237/year) while incident cases of CRC during this time increased by 31% (5285/year to 6956/year). Use of NACT increased over the study period: 94-99, 11% (78/700); 00-04, 15% (124/830); 05-09, 36%; (424/1187), (p&lt;0.001). Use of ACT also increased: 94-99, 38% (263/700); 00-04, 40% (335/830); 05-09, 45% (532/1187), (p=0.006). In 2005-2009 there was substantial variation across geographic regions in use of NACT (range 19% to 46%, p=0.029) and ACT (range 31% to 56%, p=0.015). Five year overall survival during the 3 study periods was 36% (95%CI 32-39%), 40% (95%CI 36-43%), and 47% (95%CI 43-51%) (p&lt;0.001). Conclusions: Resection of CRC liver metastases in routine practice in the general population of Ontario is associated with survival outcomes that are comparable to those reported in case series from leading comprehensive cancer centres. Survival improved over the study period despite a greater proportion of patients with CRC undergoing liver resection.
Influence of different dates of sowing and spacings on growth and yield of scented rice cv. pusa sugandh-3 under temperate conditions of Kashmir
Authors: Asma Fayaz, Purshotam Singh, Sameera Qayoom, Latief Ahmad, Bilal Lone, Lal Singh, Kanwal Nain Singh
Journal: Journal of Clinical Oncology (2015)

A field experiment was conducted during kharif seasons of 2013 and 2014 to determine the effect of different dates of sowing and spacing on growth and yield of scented rice (Pusa sugandh -3) under temperate condition of Kashmir. The soil of the experimental field was silty clay loam in texture with neutral pH, low in available nitrogen and medium in available phosphorus and potassium. The experiment comprised of 9 treatments, viz D1S1 (15th meteorological week (10th April) + (20 cm x 20 cm), D1S2 (15th meteorological week (10th April) + ( 20 cm x 15 cm), D1S3 (15th meteorological week (10th April + (15 cm x15 cm), D2S1 (16th meteorological week (20th April ) + (20 cm x 20 cm), ), D2S2 (16th meteorological week (20th April) + ( 20 cm x 15 cm), D2S3 (16th meteorological week (20th April + (15 cm x 15 cm), D3S1 (18th meteorological week (30th April) + (20 cm x 20 cm),D3S2 (18th meteorological week (30th April) + (20 cm x 15 cm), D3S3 (18th meteorological week (30th April + (15 cm x 15 cm) were laid out in a split plot design with 3 replications on plot size of 10 m2. The growth parameters such as plant height, number of tillers hill-1, SPAD and dry matter production was also observed significantly high in D1S2 with average. Grain yield (48.01 q ha-1), straw yield (77.26 q ha1) were seen significantly higher in D1S2 (15th meteorological week 10th April and 20 cm x 15 cm) compared to other treatments. The yield attributes like number of panicles m-2, number of grains panicle-1, 1000-grain weight (g) and harvest index (%) was seen significantly higher in D1S2. The economic analysis showed that treatment D1S2 showed maximum benefit cost ratio (3.32) followed by D1S1 respectively.

	 

	Key words: Pusa Sugandh-3, growth, yield, spacing, sowing dates.
Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation
Authors: Ning Ma, Jie Zhang, Russel J. Reiter, Xi Ma
Journal: Medicinal Research Reviews (2019)

Nowadays, melatonin, previously considered only as a pharmaceutical product for rhythm regulation and sleep aiding, has shown its potential as a co-adjuvant treatment in intestinal diseases, however, its mechanism is still not very clear. A firm connection between melatonin at a physiologically relevant concentration and the gut microbiota and inflammation has recently established. Herein, we summarize their crosstalk and focus on four novelties. First, how melatonin is synthesized and degraded in the gut and exerts potentially diverse phenotypic effects through its diverse metabolites. Second, how melatonin mediates the activation and proliferation of intestinal mucosal immune cells with paracrine and autocrine properties. By modulating T/B cells, mast cells, macrophages and dendritic cells, melatonin immunomodulatory involved in regulating T-cell differentiation, intervening T/B cell interaction and attenuating the production of pro-inflammatory factors, achieving its antioxidant action via specific receptors. Third, how melatonin exerts antimicrobial action and modulates microbial components, such as lipopolysaccharide, amyloid-β peptides via nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) or signal transducers and activators of transcription (STAT1) pathway to modulate intestinal immune function in immune-pineal axis. The last, how melatonin mediates the effect of intestinal bacterial activity signals on the body rhythm system through the NF-κB pathway and influences the mucosal epithelium oscillation via clock gene expression. These processes are achieved at mitochondrial and nuclear levels to control the host immune cell development. Considering unclear mechanisms and undiscovered actions of melatonin in gut-microbiome-immune axis, it's time to reveal them and provide new insight for the outlook of melatonin as a potential therapeutic target in the treatment and management of intestinal diseases.
Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest via suppression of NF-\#312;B pathway in human colon cancer HCT116 cells
Authors: Jung-Mi Yun, Farrukh Afaq, Naghma Khan, Hasan Mukhtar
Journal: Cancer Research (2007)

4195  Colon cancer is the third most common cancer in men and women and accounts for 10% of all cancers related deaths in the United States. Because of unsatisfactory treatment options for colon cancer, there is a need to develop novel treatment approaches for this malignancy. One such strategy is through chemoprevention by the use of non-toxic dietary substances and botanical products. Delphinidin is the most abundant and major anthocyanidin present in pigmented fruits (pomegranate, berries and dark grapes) and vegetables (egg plant, tomato, carrot, purple sweet potatoes, red cabbage and red onion) and possesses strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effect of delphinidin on the growth and proliferation of human colon cancer HCT116 cells. As assessed by MTT assay, treatment of cells with delphinidin (30-240 µM; 48 hrs) caused dose-dependent growth inhibitory effects. TUNEL (terminal deoxynucleotide transferase dUTP nick-end labeling) assay indicated that delphinidin treatment (120, 180 and 240 μM; 48 hrs) dose-dependently induced apoptosis by 18%, 35% and 38% respectively. In dephinidin treated cells suppression in the protein expression of poly (ADP-ribose) polymerase (116 kDa) and procaspase-3 was observed. Furthermore, cell cycle analysis using flow cytometry showed that delphinidin treatment (120, 180 and 240μM; 48 hrs) resulted in a G2/M arrest by 34% 39% and 30% respectively. NF-κB provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of both pre-neoplastic and malignant cells to resist apoptosis-based tumor surveillance mechanisms. We therefore, explored NF-κB signaling pathway. The immunoblot analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKα, (ii) NF-κB/p65 and (iii) degradation and phosphorylation of IκBα. Immunoblot analysis also indicated that delphinidin treatment of cells resulted in inhibition of translocation of NF-κB/p65. These data were further confirmed by performing electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. We found that treatment of cells with delphinidin inhibited NF-κB DNA-binding activity. Our results suggest that delphinidin treatment of HCT116 cells suppresses NF-κB pathway, resulting in G2/M phase arrest and apoptosis. We suggest that delphinidin could be a potent inhibitor of NF-κB signaling in human HCT116 cells and suggests its potential use as a cancer therapeutic agent against colon cancer.
Treatment response and drug retention rates in 24 195 biologic-naïve patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration
Authors: Lykke Midtbøll Ørnbjerg, Cecilie Heegaard Brahe, Johan Askling, Adrian Ciurea, Herman Mann, Fatos Onen, Eirik Klami Kristianslund, Dan Nordström, Maria Jose Santos, Catalin Codreanu, Juan Gómez-Reino, Ziga Rotar, Bjorn Gudbjornsson, Daniela Di Giuseppe, Michael J Nissen, Karel Pavelka, Merih Birlik, Tore Kvien, Kari Kalervo Eklund, Anabela Barcelos, Ruxandra Ionescu, Carlos Sanchez-Piedra, Matija Tomsic, Árni Jón Geirsson, Anne Gitte Loft, Irene van der Horst-Bruinsma, Gareth Jones, Florenzo Iannone, Lise Hyldstrup, Niels Steen Krogh, Merete Lund Hetland, Mikkel Østergaard
Journal: Annals of the Rheumatic Diseases (2019)

Objective To study drug retention and response rates in patients with axial spondyloarthritis (axSpA) initiating a first tumour necrosis factor inhibitor (TNFi). Methods Data from 12 European registries, prospectively collected in routine care, were pooled. TNFi retention rates (Kaplan-Meier statistics), Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive disease (&lt;1.3), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) &lt;40 mm and Assessment of SpondyloArthritis International Society responses (ASAS 20/40) were assessed at 6, 12 and 24 months. Results A first TNFi was initiated in 24 195 axSpA patients. Heterogeneity of baseline characteristics between registries was observed. Twelve-month retention was 80% (95% CI 79% to 80%), ranging from 71% to 94% across registries. At 6 months, ASDAS Inactive disease/BASDAI&lt;40 rates were 33%/72% (LUNDEX-adjusted: 27%/59%), ASAS 20/40 response rates 64%/49% (LUNDEX-adjusted 52%/40%). In patients initiating first TNFi after 2009, 6097 patients was registered to fulfil ASAS criteria for axSpA, 2935 was registered to fulfil modified New York Criteria for Ankylosing Spondylitis and 1178 patients was registered as having non-radiographic axSpA. In nr-axSpA patients, we observed lower 12-month retention rates (73% (70%–76%)) and lower 6-month LUNDEX adjusted response rates (ASDAS Inactive disease/BASDAI40 20%/50%, ASAS 20/40 45%/33%). For patients initiating first TNFi after 2014, 12-month retention rate, but not 6-month response rate, was numerically higher compared with patients initiating TNFi in 2009–2014. Conclusion A large European database of patients with axSpA initiating a first TNFi treatment in routine care, demonstrated that 27% of patients achieved ASDAS inactive disease after 6 months, while 59% achieved BASDAI &lt;40. Four of five patients continued treatment after 1 year.
Human cancer cell lines resistant to EGFR inhibitors acquire an altered expression of VEGFR-1/Flt-1 and become sensitive to ZD6474
Authors: R Bianco, G Daniele, T Gelardi, C Tuccillo, A J Ryan, A R Bianco, S De Placido, F Ciardiello, G Tortora
Journal: Cancer Research (2006)

3776  The mammalian target of rapamycin (mTOR) is a key regulator of growth and proliferation, regulating the binding of capped mRNAs to eIF4E. In some RCC cell lines and primary tumors, eIF4E is overexpressed. Epidermal growth factor receptor (EGFR) and tumor growth factor alpha (TGFalpha) are frequently upregulated in RCC. Extracellular signal-regulated kinases (ERK1/2) represent an important downstream target of EGFR and other growth factor receptors known to be active in RCC. We have previously shown that the combination of mTOR and EGFR inhibitors synergistically inhibits growth in RCC cell lines. Interestingly, we observed that phospho-ERK1/2 inhibition by gefitinib was greater in cells with wt-VHL. We have expanded our analysis to include more cell lines and to isolate the biochemical effect of EGF. Pre-incubation of cells with gefitinib inhibited AKT phosphorylation following EGF stimulation in a VHL-independent manner. In contrast, ERK1/2 phosphorylation was less efficiently inhibited in VHL mutant cell lines. Using cell growth assays, the MEK1/2 inhibitors U0126 and PD184352 blocked growth in all RCC lines with no apparent relationship to VHL. This effect was enhanced with the addition of rapamycin. Similarly, the combination of gefitinib (or erlotinib) and rapamycin was greater than the effect of each drug alone. At the cell cycle level, these agents were associated with a G1 arrest. Interestingly, although eIF4E overexpresssion has been suggested to make cells resistant to rapamycin, we observed marked growth inhibition with rapamycin as a single agent in SKRC39, which has marked overexpresssion of eIF4E. In summary, combined mTOR and other upstream inhibitors has strong potential in the treatment of RCC.
Use of fumarate and nitrate reduction regulator-responsive DNA promoter elements in Salmonella typhimurium to target gene therapy to hypoxic areas of solid tumors.
Authors: Rachel Ryan, Jeffery Green, Claire Lewis
Journal: Cancer Research (2004)

2343  The delivery of drugs to their site of action is a fundamental barrier to the full exploitation of post-genomics in cancer treatment. Oxygen microelectrodes have demonstrated the presence of many areas of hypoxia and anoxia in human tumors. Tumor cells are non-proliferating, and therefore relatively refractory to radiotherapy and chemotherapy, in hypoxic areas. This has prompted the development of alternative approaches to target therapeutic genes specifically to these hypoxic tumor areas, including the use of bacteria. Many bacteria selectively replicate and accumulate within the tumor microenvironment including Salmonella, Clostridia and Bifidobacterium. Attenuated strains of S. typhimurium have been used as effective cellular vectors for systemic anti-cancer gene therapy. However expression of therapeutic genes in normal (normoxic) tissue is a major problem, which can be overcome if an additional level of targeting is included. This can be achieved by placing a therapeutic gene under the control of a hypoxia-inducible transcription factor such as the S. typhimurium transcription factor, Fumarate and Nitrate reduction Regulator (FNR). This oxygen-responsive transcription factor activates genes in severe hypoxia and anoxia. Here, we show that an FNR-regulated promoter (FFpmelR) can activate expression of the reporter gene (lacZ) under anoxic conditions in an attenuated S. typhimurium strain in vitro. Reporter gene expression from this plasmid was 52-fold higher in anoxia than normoxia. Specific mutations made to the –10 element (TATAAC) in the FNR promoter improved anoxic induction of the lacZ reporter gene from 52- to 625-fold. More importantly, it markedly decreased expression under normoxic conditions. This mutant FFpmelR:lacZ construct in S. typhimurium was used to infect a human breast cancer cell line (T47D). The reporter gene was expressed when these infected cells were exposed to hypoxia (0.5% oxygen) but not normoxia (20.9% oxygen) for 16h in vitro. This engineered S. typhimurium mutant was utilized to infiltrate multicellular tumor spheroids grown from T47D cells. The migration of the S. typhimurium and expression of the lacZ gene were monitored using immunohistochemical methods. The bacteria rapidly migrated throughout the spheroid and reporter activity was restricted to the hypoxic, inner areas of spheroids. We conclude that it may be possible to target therapeutic genes to hypoxic areas of tumors using FNR-dependent promoters in an attenuated strain of S. typhimurium.
Rectal prognostic index (RPI) to predict outcome of patients with locally advanced rectal cancer (LARC) treated with preoperative chemo-radiation (preop-CRT)
Authors: M. Piperdi, V. Velagapudi, G. Ayata, J. Simons, J. F. Tseng, B. Piperdi
Journal: Journal of Clinical Oncology (2009)

e15139 Background: Preop-CRT followed by surgical resection is the standard for LARC. LARC patients (pts) treated with preop-CRT have 60–70% 5-year survival. Several pathologic features including T stage (yT), lymph node (N) ratio (# of positive N (Np) / # of N examined (Ne)) and tumor regression grade (TRG) have been shown to be independent prognostic markers. We developed a prognostic score to determine pts with low risk of recurrence after preop-CRT. Methods: Our sample set consists of 20 pts treated on in house trial of preop-CRT with paclitaxel. All pts had R0 resections and received 4 months of 5-FU based adjuvant chemotherapy. All pathology slides were independently reviewed by GI pathologist. RPI scale of -4 to 14 was developed based on the formula: RPI = T (1–4) + (Np/Ne x 10) - TRG (0–4). The low, intermediate and high risk for recurrence were predefined as RPI (≤1), (&gt;1 and &lt;5), (≥5). Results: Between 1999–2003, 20 pts were treated on the trial and had R0 resection. The data is summarized in table 1 . The 5yr disease-free (DFS) and overall survival (OS) rate of all pts were 62 and 77%. Two pts (10%) achieved complete pathological response. Low, intermediate and high risk RPI was noted in 50, 35, and 15 % of pts. The 5yr DFS and OS for low, intermediate and high risk groups were 75, 42, 33 % and 86, 71 and 33% respectively.Conclusions: RPI can accurately predict a subset of pts with low risk of recurrence after preop-CRT. Majority of pts in this cohort have low risk RPI and have a favorable outcome (5yr survival rate of 86%). RPI could be very helpful in designing future trials tailoring adjuvant chemotherapy based on risk of recurrence. We are validating this data with a larger, independent group of LARC patients from our cancer registry (N=30) and this data will be available for presentation. Since RPI only requires the final pathology after CRT, it should be readily reproducible in future prospective studies across different institutions. [Table: see text] No significant financial relationships to disclose.