tbuckley/cabot-search huggingface dataset:
<i>MGMT</i> methylation status as a prognostic factor in anaplastic astrocytomas
Authors: A. Tosoni, E. Franceschi, M. Ermani, A. Bacci, L. Volpin, L. Lombardo, G. Ravenna, G. Pinna, R. Poggi, A. A. Brandes
Journal: Journal of Clinical Oncology (2009)

2052 Background: MGMT methylation status has been found to be an important prognostic factor in glioblastoma patients (pts). However, further data on the epigenetic feature are needed before its role in rare diseases such as anaplastic astrocytomas (AA) can be established. Methods: A retrospective analysis was made on a database of 139 AA pts followed prospectively from January 1995 and August 2008. We evaluated only pts who met the following inclusion criteria: age &gt;18 years; PS 0–2; histological diagnosis of AA; postoperative radiotherapy (RT) and chemotherapy (CT). MGMT status was determined with methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in AA. The log-rank test was employed to evaluate the significance of the prognostic variables. Results: 80 pts (m/f: 46/34, median age: 41 years, range: 18–71 years) were enrolled. MGMT was assessable in 71 of 80 pts (88.8%), being methylated in 30 (42.9%), and unmethylated in 41 (57.7%) pts. Median PFS was 48.6 months (95% CI: 33.7 - 63.5), being 96 months (95% CI: 29–163) and 38 months (95%CI: 18.9–57.2) in MGMT methylated and unmethylated pts, respectively (p = 0.09). At univariate analysis, complete resection (p = 0.02), age (p = 0.002), and KPS (p = 0.003) were significantly correlated with PFS. At multivariate analysis only age remains correlated with PFS (p = 0.01). Median survival (OS) was 93.7 months (95% CI: 63.5–123.8), being not reached and 77 months (95% CI: 20–134.2), in MGMT methylated and unmethylated pts, respectively (p = 0.03). MGMT methylation (p = 0.03), age (p = 0.0003), and KPS (p = 0.03) were significantly correlated with OS at univariate analysis. At multivariate analysis, age (p = 0.0002) and MGMT methylation (p = 0.01) were correlated with a better OS. Conclusions: MGMT methylation status is an independent prognostic factor together with age in AA. This datum should provide the background to improve the therapeutic index with temozolomide concurrent with and adjuvant to RT in AA. No significant financial relationships to disclose.
Prospective randomized trial evaluating weekly paclitaxel (WP) versus docetaxel in combination with capecitabine (DC) in operable breast cancer
Authors: A. U. Buzdar, M. C. Green, K. R. Broglio, C. D. Carter, V. Valero, N. K. Ibrahim, K. K. Hunt, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2009)

542 Background: Paclitaxel has scheduled-dependant efficacy, and WP is associated with better therapeutic index (J Clin Oncol. 2005;23:5983–5992). The DC combination had higher response rate, longer control of disease, and improved survival in metastatic disease (J Clin Oncol. 2002;20:2812–2823). This randomized study compared the efficacy and safety of WP to DC in patients (pts) with operable breast cancer. Methods: Pts were randomized 1:1 and stratified by the timing of therapy (preoperative vs adjuvant). The primary endpoint was disease-free survival (DFS), and the secondary endpoint in pts receiving preoperative therapy was complete pathologic response (pCR). WP arm was paclitaxel 80 mg/m 2 weekly for 12 weeks, followed by 4 cycles of FEC. DC arm included docetaxel 75 mg/m 2 day 1, and capecitabine 1500mg/m 2 daily for 14 days of each 3 week cycle for a planned 4 cycles of DC followed by 4 cycles of FEC. The study was designed to include 930 pts to have 80% power to detect a difference in 4 year DFS from 85% on the WP arm to 92% on the DC arm, based on a two-sided test at the 0.05 significance level. Results: 601 pts were randomized, 304 on WP arm and 297 on DC arm. 37% of pts on each arm received therapy in the preoperative setting. Pts characteristics were balanced between the two arms. Median follow-up was 38 months. 4-year DFS on DC arm was 91.0% (95% confidence interval [CI], 84.8- 94.1) and the 4-year DFS on the WP arm was 89.3% (95% CI, 84.8- 94.1) (p = 0.957). A total of 107 pts have been treated with DC and 109 have been treated with WP in the preoperative setting and are evaluable for pCR. The pCR rates were 18.7% and 17.4% on each arm respectively (p = 0.81). The DC arm had higher incidence of hand foot syndrome, and myelosuppression, and WP treatment was associated with higher neurotoxicity. Interim data was presented June 2008 to the institutional data monitoring committee and the study was closed due to futility. If the trial had continued as planned, the predictive probability of concluding in favor of the DC arm for DFS and pCR were 0.005 and 0.001, respectively. Conclusions: WP and DC as utilized in this study had similar efficacy in pts with early stage breast cancer. WP was a better tolerated therapy, associated with little myelotoxicity. [Table: see text]
Current understanding of periodontal disease pathogenesis and targets for host‐modulation therapy
Authors: George Hajishengallis, Triantafyllos Chavakis, John D. Lambris
Journal: Periodontology 2000 (2020)

Abstract Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self‐sustained feed‐forward loop that perpetuates the disease. These considerations provide a strong rationale for developing adjunctive host‐modulation therapies for the treatment of periodontitis. Such host‐modulation approaches aim to inhibit harmful inflammation and promote its resolution or to interfere directly with downstream effectors of connective tissue and bone destruction. This paper reviews diverse strategies targeted to modulate the host periodontal response and discusses their mechanisms of action, perceived safety, and potential for clinical application.
Cryptobiosis-inspired assembly of “AND” logic gate platform for potential tumor-specific drug delivery
Authors: Hu Zhou, Gang He, Yanbin Sun, Jingguo Wang, Haitao Wu, Ping Jin, Zhengbao Zha
Journal: Acta Pharmaceutica Sinica B (2020)

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and FeIII ([email protected]III NPs) were successfully developed as an "AND" logic gate platform for tumor-targeted DOX delivery. Moreover, benefiting from the well-reported photothermal conversion ability of TA-FeIII complex, a synergistic tumor inhibition effect was confirmed by treating 4T1 tumor-bearing mice with [email protected]III NPs and localized near-infrared (NIR) laser irradiation. As a proof of concept study, this work present a simple strategy for developing "AND" logic gate platforms by coating enzyme-degradable drug conjugates with detachable polyphenol‒metal shells.
VEGF transcripts expression in relation to erythropoietin-induced reduction of tumor hypoxia
Authors: Sophie Pinel, Muriel Barberi-Heyob, Jean-Louis Merlin, Pascal Chastagner
Journal: Cancer Research (2004)

4137  Our study investigated the influence of recombinant human erythropoietin (rHuEPO) treatment on intratumor oxygenation before and after 5 fractions of ionizing radiation. As hypoxia is the most important stimulus for up-regulation of vascular endothelial growth factor (VEGF), we assessed the relationships between tumor hypoxia modulation and VEGF mRNA expression. Experiments were performed on two human malignant gliomas (GBM Nan1 and U87) grafted in nude mice. Xenograft-bearing animals were randomly assigned into 4 groups: Control (Ctrl), rHuEPO, radiotherapy (RT), and RT + rHuEPO. RHuEPO was delivered s.c. (0.3 IU/g, once a day, 5 days/week) as soon as a micro-tumor was observed. Fractionated irradiation (5 fractions of 2 Gy, once a day) was started when tumors reached a volume of 250 ± 50 mm3 (T1), i.e. after exposure to rHuEPO for three to four weeks. Before the first fraction (T1) and 24h after the last fraction of radiation (T6), hemoglobin concentrations were measured using the cyanmethemoglobin method, and intratumor oxygen tension (pO2) measurements were performed using the pO2-Histograph, Eppendorf™. The primary oxygen parameter was the hypoxic fraction (HF), defined as the percentage of pO2 values
High risk of systemic lupus erythematosus development in patients with ITP: antiphospholipid syndrome is also a concern
Authors: Murat İnanç, Bahar Artim-Esen, Reyhan Diz-Küçükkaya
Journal: Annals of the Rheumatic Diseases (2020)

Zhu et al in their elegant population-based cohort study investigated the development of systemic lupus erythematosus (SLE) in patients with idiopathic (immune) thrombocytopenic purpura (ITP) and demonstrated the significantly higher risk compared with the control population.1 They rightfully used sensitivity analysis and treatment data to improve the accuracy of clinical diagnosis. Despite this effort, the difficulty remains to compare epidemiological studies using self-reported diagnosis, health records or using classification criteria.2 In clinical practice, lack of a generally acknowledged diagnostic criteria might lead to SLE diagnosis of cases like undifferentiated connective tissue disease that …
Prognostic significance of tumor size in patients with stage III non-small cell lung cancer: A SEER database survey
Authors: S. N. Waqar, F. Gao, R. Govindan, D. Morgensztern
Journal: Journal of Clinical Oncology (2009)

7529 Background: Although tumor size is a known predictor of stage I and II non-small cell lung cancer (NSCLC) treated with surgery or radiotherapy, there is limited information regarding its prognostic significance in patients with mediastinal lymph node involvement. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with unresected NSCLC stage III, without malignant pleural effusion, aged 21 or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1–3 cm), S2 (3.1–5 cm), S3 (5.1–7 cm) and S4 (7.1–20 cm). Demographic variables included age, gender, race and histology. The Kaplan-Meier method was used to estimate the overall survival (OS) and disease-specific survival (DSS), and the Cox proportional hazard model to evaluate whether tumor size remained an independent risk factor after adjusting for stage and other demographic variables. Results: A total of 12,205 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were male (58.8%) and white (81.3%). Tumor size was a statistically significant predictor for both overall survival (p&lt;0.0001) and disease-specific survival (p&lt;0.0001) on multivariate analysis. Selected groups of patients with smaller stage IIIB disease had better OS compared to patients with stage IIIA, including; IIIBS1 vs. IIIAS3 (p=0.0005) or IIIA S4 (p&lt;0.0001) and IIIBS2 vs. IIIAS4 (p=0.0001). Conclusions: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC and should be considered in the stratification of patients treated in this setting. [Table: see text] No significant financial relationships to disclose.
A Patient With Back Pain and Morning Stiffness
Authors: Sameet Sangha, Petar Lenert, Bharat Kumar
Journal: JAMA (2020)

A 44-year-old White man had symptoms and radiographic signs of diffuse osteoarthritis, negative inflammatory markers and HLA-B27, and a brother with osteoarthritis, hypogonadism, and type 2 diabetes. What is the diagnosis and what would you do next?
Improved reference genome of the arboviral vector Aedes albopictus
Authors: Umberto Palatini, Reem A. Masri, Luciano V. Cosme, Sergey Koren, Françoise Thibaud-Nissen, James K. Biedler, Flavia Krsticevic, J. Spencer Johnston, Rebecca Halbach, Jacob E. Crawford, Igor Antoshechkin, Anna-Bella Failloux, Elisa Pischedda, Michele Marconcini, Jay Ghurye, Arang Rhie, Atashi Sharma, Dmitry A. Karagodin, Jeremy Jenrette, Stephanie Gamez, Pascal Miesen, Patrick Masterson, Adalgisa Caccone, Maria V. Sharakhova, Zhijian Tu, Philippos A. Papathanos, Ronald P. Van Rij, Omar S. Akbari, Jeffrey Powell, Adam M. Phillippy, Mariangela Bonizzoni
Journal: Genome biology (2020)

Abstract Background The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary approach to prevent mosquito-borne diseases. A reliable and accurate DNA sequence of the Ae. albopictus genome is essential to develop new approaches that involve genetic manipulation of mosquitoes. Results We use long-read sequencing methods and modern scaffolding techniques (PacBio, 10X, and Hi-C) to produce AalbF2, a dramatically improved assembly of the Ae. albopictus genome. AalbF2 reveals widespread viral insertions, novel microRNAs and piRNA clusters, the sex-determining locus, and new immunity genes, and enables genome-wide studies of geographically diverse Ae. albopictus populations and analyses of the developmental and stage-dependent network of expression data. Additionally, we build the first physical map for this species with 75% of the assembled genome anchored to the chromosomes. Conclusion The AalbF2 genome assembly represents the most up-to-date collective knowledge of the Ae. albopictus genome. These resources represent a foundation to improve understanding of the adaptation potential and the epidemiological relevance of this species and foster the development of innovative control measures.
Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction
Authors: Yu Horiuchi, Nicholas Wettersten, Mitul P. Patel, Christian Mueller, Sean-Xavier Neath, Robert H. Christenson, Nils G. Morgenthaler, James McCord, Richard M. Nowak, Gary M. Vilke, Lori B. Daniels, Judd E. Hollander, Fred S. Apple, Chad M. Cannon, John T. Nagurney, Donald Schreiber, Christopher deFilippi, Christopher Hogan, Deborah B. Diercks, Gary Headden, Alexander T. Limkakeng, Inder Anand, Alan H.B. Wu, Stefan Ebmeyer, Allan S. Jaffe, W. Frank Peacock, Alan Maisel
Journal: Circulation (2020)

The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers.Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated.Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI.Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.
β-catenin represses miR455-3p to stimulate m6A modification of HSF1 mRNA and promote its translation in colorectal cancer
Authors: Ping Song, Lifeng Feng, Jiaqiu Li, Dongjun Dai, Liyuan Zhu, Chaoqun Wang, Jingyi Li, Ling Li, Qiyin Zhou, Rongkai Shi, Xian Wang, Hongchuan Jin
Journal: Molecular Cancer (2020)

Abstract Background Heat shock transcription factor1 (HSF1) was overexpressed to promote glutaminolysis and activate mTOR in colorectal cancer (CRC). Here, we investigated the mechanism for cancer-specific overexpression of HSF1. Methods HSF1 expression was analyzed by chromatin immunoprecipitation, qRT-PCR, immunohistochemistry staining and immunoblotting. HSF1 translation was explored by polysome profiling and nascent protein analysis. Biotin pulldown and m6A RNA immunoprecipitation were applied to investigate RNA/RNA interaction and m6A modification. The relevance of HSF1 to CRC was analyzed in APC min/+ and APC min/+ HSF1 +/− mice. Results HSF1 expression and activity were reduced after the inhibition of WNT/β-catenin signaling by pyrvinium or β-catenin knockdown, but elevated upon its activation by lithium chloride (LiCl) or β-catenin overexpression. There are much less upregulated genes in HSF1-KO MEF treated with LiCl when compared with LiCl-treated WT MEF. HSF1 protein expression was positively correlated with β-catenin expression in cell lines and primary tissues. After β-catenin depletion, HSF1 mRNA translation was impaired, accompanied by the reduction of its m6A modification and the upregulation of miR455-3p, which can interact with 3′-UTR of HSF1 mRNA to repress its translation. Interestingly, inhibition of miR455-3p rescued β-catenin depletion-induced reduction of HSF1 m6A modification and METTL3 interaction. Both the size and number of tumors were significantly reduced in APC min/+ mice when HSF1 was genetically knocked-out or chemically inhibited. Conclusions β-catenin suppresses miR455-3p generation to stimulate m6A modification and subsequent translation of HSF1 mRNA. HSF1 is important for β-catenin to promote CRC development. Targeting HSF1 could be a potential strategy for the intervention of β-catenin-driven cancers.
Interpreting the Need for Implantable Loop Recorder Monitoring in Pregnant Women at High Risk of Arrhythmias—Reply
Authors: Charle Viljoen, Karen Sliwa, Ashley Chin
Journal: JAMA Cardiology (2020)

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Predicting risk of late age-related macular degeneration using deep learning
Authors: Yifan Peng, Tiarnan D. Keenan, Qingyu Chen, Elvira Agrón, Alexis Allot, Wai T. Wong, Emily Y. Chew, Zhiyong Lu
Journal: npj Digital Medicine (2020)

By 2040, age-related macular degeneration (AMD) will affect ~288 million people worldwide. Identifying individuals at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Although deep learning has shown promise in diagnosing/screening AMD using color fundus photographs, it remains difficult to predict individuals' risks of late AMD accurately. For both tasks, these initial deep learning attempts have remained largely unvalidated in independent cohorts. Here, we demonstrate how deep learning and survival analysis can predict the probability of progression to late AMD using 3298 participants (over 80,000 images) from the Age-Related Eye Disease Studies AREDS and AREDS2, the largest longitudinal clinical trials in AMD. When validated against an independent test data set of 601 participants, our model achieved high prognostic accuracy (5-year
The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic–epigenetic reprogramming and resolves inflammatory injury
Authors: Bisheng Zhou, Lissette Magana, Zhigang Hong, Long Shuang Huang, Sreeparna Chakraborty, Yoshikazu Tsukasaki, Cary Huang, Li Wang, Anke Di, Balaji Ganesh, Xiaopei Gao, Jalees Rehman, Asrar B. Malik
Journal: Nature Immunology (2020)
19 Barrett’s oesophagus in childhood: a population-based case series analysis
Authors: L Twohig-Bennett, HG Coleman, LJ Murray, DT McManus, AT Gavin, S Bhat, BT Johnston
Journal: Gut (2017)

Background  Adults detected with Barrett’s oesophagus (BO) are often entered into surveillance for oesophageal adenocarcinoma (OAC), although cancer risk is relatively low. More rarely, BO can be detected in children. Little is known about the epidemiology of paediatric BO, and it is unclear what the optimal surveillance regimes are in these children.  Aim  To evaluate the demographic and clinical characteristics, and future neoplastic progression risk in all paediatric BO patients diagnosed in Northern Ireland between 1993 and 2010.  Method  Data was collected using the Northern Ireland BO register and matched to the Northern Ireland Cancer Registry for OAC outcomes until end 2013. Age-adjusted incidence of paediatric BO was calculated, and chi-squared tests performed to compare characteristics between paediatric and adult BO patients.  Results  Over 18 years, 42 paediatric BO patients were identified, equivalent to an age-adjusted incidence of   Conclusions  This is the largest series of paediatric BO ever to be reported. It demonstrates that paediatric BO is a rare disease. The male preponderance of this condition is even more apparent in childhood compared with adult cases. No children developed HGD/OAC during follow-up, suggesting that regular surveillance is not required, at least until early adulthood.