tbuckley/cabot-search huggingface dataset:
Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?
Authors: Matias Emanuel Valsecchi, Susan Joy Littman, Thomas Holdbrook, Benjamin Leiby, Edith P. Mitchell, Charles Yeo, Jonathan Robert Brody, Agnieszka Witkiewicz
Journal: Journal of Clinical Oncology (2012)

246 Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce. Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS). Results: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, either in univariate or multivariate analyses, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively) (Table 1). Similar results were obtained for DFS. Conclusions: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes. [Table: see text]
The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: A systematic review
Authors: T.H. Dierikx, D.H. Visser, M.A. Benninga, A.H.L.C. van Kaam, N.K.H. de Boer, R. de Vries, J. van Limbergen, T.G.J. de Meij
Journal: Journal of Infection (2020)

The intestinal microbiota develops in early infancy and is essential for health status early and later in life. In this review we focus on the effect of prenatal and intrapartum maternally administered antibiotics on the infant intestinal microbiota.A systematic literature search was conducted in PubMed and EMBASE. All studies reporting effect on diversity or microbiota profiles were included.A total of 4.030 records were encountered. A total of 24 articles were included in the final analysis. Infants from mothers exposed to antibiotics during delivery showed a decreased microbial diversity compared to non-exposed infants. The microbiota of infants exposed to antibiotics was characterised by a decreased abundance of Bacteriodetes and Bifidobacteria, with a concurrent increase of Proteobacteria. These effects were most pronounced in term vaginally born infants.Maternal administration of antibiotics seems to have profound effects on the infant gut microbiota colonisation. Interpretation of microbiota aberrations in specific populations, such as preterm and caesarean born infants, is complicated by multiple confounding factors and by lack of high quality studies and high heterogeneity in study design. Further research is needed to investigate the potential short- and long-term clinical consequences of these microbial alterations.
Unrelated Cord Blood Transplantation and Post-Transplant Cyclophosphamide (PT-CY)
Authors: Patrizia Chiusolo, Andrea Bacigalupo, Simona Sica, Sabrina Giammarco, Elisabetta Metafuni, Federica Sora, Luca Laurenti, Francesco Autore, Idanna Innocenti, Silvia Bellesi, Gina Zini, Maria Bianchi, Caterina Giovanna Valentini, Luciana Teofili
Journal: Blood (2019)
Covid-19: Deprived areas have the highest death rates in England and Wales
Authors: Gareth Iacobucci
Journal: BMJ (2020)

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ADWE-01 The prediction of diminutive/small polyp histology using didactic vs computer based training in gastroenterology trainees
Authors: Graham Baker, Samuel Smith, Marietta Iacucci, John Saltzman, Uday Shivaji, Brendan Lethebe, Ayman Bannaga, Aditi Kumar, Adam McCulloch, Beata Polewiczowska, Daniel Geh, Faraz Tahir, Harriet Fowler, Joanne O’Rourke, Maria Qurashi, Monika Widlak, Philip Harvey, Paul Lim, Sheeba Khan, Tarun Gupta, Subrata Ghosh
Journal: Endoscopy (2018)

<h3>Introduction</h3> Experts are able to predict and differentiate between neoplastic and non-neoplastic colonic polyps with high accuracy and meet the PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) thresholds. However, this has not been replicated in non-experts and cannot be currently recommended in clinical practice. The aim of this randomised trial was to establish the optimum method of training to increase the diagnostic accuracy of diminutive/small colonic polyp histological prediction by trainee gastroenterologists. <h3>Methods</h3> Gastroenterology trainees from the Midlands, UK, reviewed 78 videos (48 i-Scan-OE+30 NBI) of diminutive/small polyps. Participants were randomised to computer-based learning or didactic training. The 78 videos (randomised order) were re-assessed. The NICE (NBI International Colorectal Endoscopic) classification and SIMPLE (Simplified Identification Method for Polyp Labelling during Endoscopy) classification systems were used to classify diminutive/small polyps (figure 1). <h3>Results</h3> 16 trainees (12 gastroenterology trainees and 4 naïve endoscopists) were randomised to receive either self-training (n=8) or didactic training (n=8). A higher proportion of high confidence predictions of polyps were made by the self-training group vs didactic group when using the SIMPLE classification 77.1% vs. 69.9% (p&lt;0.005) and using the NICE classification 77% vs. 69.8% (p=0.006). When using NICE classification, the sensitivity of the self-training group was 72% vs. 83% p&lt;0.0005, and the accuracy 66.1% vs. 69.1%. When using SIMPLE classification the sensitivity was 78% vs. 83% (NS) and accuracy 65.7% vs. 69% (table 1). <h3>Conclusions</h3> Self-learning for the prediction of diminutive/small polyp histology is a method of training that can achieve results similar to the more labour intensive and expensive didactic training. The availability of adequate self-learning teaching modules that teach how to differentiate neoplastic vs non-neoplastic colonic polyps with high accuracy could enable more widespread implementation of optical diagnosis in clinical practice.
Phylogenetic Supertrees: Combining Information to Reveal the Tree of Life, Olaf R.P. Bininda-Emonds (Ed.). Kluwer Academic Publishers (2004), £111.00/£25.00 hbk/pbk (550 pages), ISBN: 1 4020 2328 6/1 4020 2329 4
Authors: Christopher J. Creevey
Journal: Trends in Ecology & Evolution (2005)
Prospective evaluation of candidate SNPs of <i>VEGF/VEGFR</i> pathway in metastatic colorectal cancer (mCRC) patients (pts) treated with first-line FOLFIRI plus bevacizumab (BV).
Authors: Chiara Cremolini, Fotios Loupakis, Dongyun Yang, Lisa Salvatore, Wu Zhang, Takeru Wakatsuki, Marta Schirripa, Sara Lonardi, Carlotta Antoniotti, Giuseppe Aprile, Gianluca Masi, Francesco Graziano, Annamaria Ruzzo, Sara Lucchesi, Monica Ronzoni, Martin Karl Herbert Maus, Guido Bocci, Giuseppe Tonini, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

3518 Background: Despite several attempts, no predictors of benefit from BV have been so far identified. We reported the association of VEGF rs833061 T/T to a worse outcome in mCRC pts treated with first-line FOLFIRI+BV, but not in a historical cohort treated with FOLFIRI. Recent post-hoc analyses on randomized trials suggested the potential prognostic and/or predictive role of other VEGF and VEGFR1/2 SNPs. Methods: Moving from our retrospective finding, we designed a prospective validation trial in mCRC pts treated with first-line FOLFIRI+ BV to detect a HR for PFS of 1.7 for VEGF rs833061 T/T compared to C- variants. With two-sided a=0.05 and b=0.20, 199 events were required. Accrual was faster than expected and in the meanwhile promising results about other SNPs were reported and we therefore included a confirmatory analysis of VEGF rs699946 A/G, VEGFR1 rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and rs2305948 C/T and EPAS rs4145836 A/G SNPs. Germ-line DNA was extracted from peripheral blood. SNPs were analyzed by PCR and sequencing. Results: Four-hundred-twenty-four pts were included. At a median follow up of 24 months, median PFS was 10.5 months. At the univariate analysis, no differences in PFS according to VEGF rs833061 C/T variants were observed (p=0.38). Among analyzed SNPs, only VEGFR2 rs12505758 C- variants (n=118) were associated to shorter PFS compared to TT (n=306) (HR: 1.40 [95%CI: 1.07-1.84], p=0.015). In the multivariate model, this association retained significance (HR: 1.402 [95%CI:1.079-1.822], p=0.012), that was lost by applying multiple testing correction. Conclusions: This prospective experience failed to validate the hypothesized predictive impact of VEGF rs833061 variants. Also other previous retrospective findings on different candidate SNPs were not confirmed. Only VEGFR2 rs12505758 variants, whose prognostic rather than predictive impact was previously reported, correlated with PFS. We suggest that future studies on biomarkers of benefit from BV should look at the complexity of tumoral angiogenesis at different levels and not only from the genetic perspective.
Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures
Authors: Kenrie P Y Hui, Man-Chun Cheung, Ranawaka A P M Perera, Ka-Chun Ng, Christine H T Bui, John C W Ho, Mandy M T Ng, Denise I T Kuok, Kendrick C Shih, Sai-Wah Tsao, Leo L M Poon, Malik Peiris, John M Nicholls, Michael C W Chan
Journal: The Lancet Respiratory Medicine (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
TCT-349 Drug-Eluting Stents for the Treatment of Small Coronary Artery with Diabetes Mellitus: A Comparison with Sirolimus, Paclitaxel, Zotarolimus (Endeavor Resolute), BiolimusA9, EPC Capture and Everolimus-Eluting Stent: Multicenter Registry in Asia
Authors: Sunao Nakamura, Shotoro Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2012)
PTH-071 Outcomes of endoscopic resection of large colorectal lesions in very elderly (≥85 years) patients
Authors: Andrew Emmanuel, Shraddha Gulati, Margaret Burt, Bu Hayee, Amyn Haji
Journal: Endoscopy (2018)

<h3>Background</h3> Endoscopic resection (ER) provides organ conserving treatment for large colorectal superficial neoplastic lesions (CSNL), allowing many patients to avoid surgery. Although ER is widely practised, little is known about outcomes in very elderly patients who may benefit the most from avoiding major surgery. The few studies examining outcomes in the elderly originate from eastern expert centres using ESD or use a relatively young definition of elderly. We aimed to compare outcomes of ER in very elderly compared to younger patients. <h3>Methods</h3> Colorectal ERs of large (≥2 cm) CSNL performed at a tertiary institution were included. ER was performed for all lesions without overt invasive cancer regardless of size or location. Surveillance colonoscopy was performed at 3 months (SC1) and 12 months (SC2). Very elderly was defined as age ≥85 years. Outcomes were compared between patients aged ≥85 years and those &lt;85 years. <h3>Results</h3> 570 ERs of lesions≥2 cm were included. Very elderly patients (n=57) had a mean age of 88 years <i>vs</i> 70 years for younger patients. There were no significant differences in mean lesion size (61 mm <i>vs</i> 52 mm, p=0.19) or location (p=0.74). The proportion of ERs using ESD/Hybrid ESD was similar (25% <i>versus</i> 26%, p=0.81). More patients≥85 years had covert invasive adenocarcinoma, although this was not significant (12% <i>vs</i> 7%, p=0.13). More patients≥85 years experienced post procedure bleeding (8% <i>vs</i> 1%, p&lt;0.001), but there was no difference in perforation rates (3% <i>vs</i> 3%, p=0.83) and no patients≥85 years required surgery for a complication. Recurrence was similar (15% <i>vs</i> 13%, p=0.79). Similar proportions underwent surgery for covert invasive adenocarcinoma (3.5% <i>vs</i> 2.9%, p=0.79) and for recurrence (2.4% <i>vs</i> 1.3%, p=0.55). Although they were equally likely to complete SC1 (p=0.42), patients≥85 years were significantly less likely to complete SC2 (OR 0.43, p=0.013), probably because of a lack of medical fitness or unwillingness to undergo further surveillance (OR 24.3, p&lt;0.001) but not necessarily due to death (OR 1.13, p=0.87). <h3>Conclusions</h3> ER for large CSNL is safe and effective in very elderly patients, who can be treated using similar techniques to younger patients with similar short term recurrence. Serious complications are rare. If surgery is indicated for covert adenocarcinoma or recurrence, it appears very elderly patients are equally likely to undergo surgery. However, significantly fewer very elderly patients are eligible for long-term follow up and therefore treatment should be tailored according to each patient's specific lesion characteristics, symptoms and physiological fitness.
Frailty after lung transplantation is associated with impaired health-related quality of life and mortality
Authors: Aida Venado, Nicholas A Kolaitis, Chiung-Yu Huang, Ying Gao, David V Glidden, Allison Soong, Nicole Sutter, Patricia P Katz, John R Greenland, Daniel R Calabrese, Steven R Hays, Jeffrey A Golden, Rupal J Shah, Lorriana E Leard, Jasleen Kukreja, Tobias Deuse, Paul J Wolters, Kenneth Covinsky, Paul D Blanc, Jonathan P Singer
Journal: Thorax (2020)

Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown.Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes.Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant.Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.
Factors predictive of maternal-fetal transmission of HIV-1. Preliminary analysis of zidovudine given during pregnancy and/or delivery
Authors: P. J. Boyer
Journal: JAMA (1994)

<h3>Objective.</h3> —To assess maternal risk factors potentially influencing vertical transmission of human immunodeficiency virus, type 1 (HIV-1), including maternal CD4 cell count; presence of immune complex dissociated (ICD) p24 antigen; maternal zidovudine therapy during pregnancy and/or delivery; complications of pregnancy, such as preterm labor and birth; and obstetric events during labor and delivery, such as duration of labor, mode of delivery, chorioamnionitis, and maternal blood exposure. <h3>Design and Setting.</h3> —A nonrandomized prospective cohort study at a university medical center and two general hospital affiliates. <h3>Patients.</h3> —Sixty-three HIV-1—seropositive pregnant women and their 68 infants. <h3>Intervention.</h3> —Twenty-six mothers received zidovudine therapy during pregnancy and/or during labor and delivery. <h3>Main Outcome Measure.</h3> —HIV-1 infection status of the infant. <h3>Results.</h3> —Thirteen of the 68 infants were vertically infected with HIV-1. Mothers with events involving fetal exposure to maternal blood were more likely to transmit infection (four [31%] of 13 vs three [5%] of 55,<i>P</i>=.02), as were women with plasma ICD p24 antigenemia at delivery (six [67%] of nine vs 11 [25%] of 44,<i>P</i>=.02). Zidovudine treatment was associated with a significant reduction in vertical transmission (one [4%] of 26 mothers treated with zidovudine vs 12 [29%] of 42 mothers not treated with zidovudine,<i>P</i>=.01). There was a significant protective effect of zidovudine treatment despite lower mean absolute CD4 cell counts (0.37×10<sup>9</sup>/L) in the 24 zidovudine-treated nontransmitters and in the nine non—zidovudine-treated transmitters (0.37×10<sup>9</sup>/L) than in the 24 non—zidovudine-treated nontransmitters (0.62×10<sup>9</sup>/L) (<i>P</i>=.008). <h3>Conclusion.</h3> —Maternal-fetal HIV-1 transmission is multifactorial, with increased risk associated both with ICD p24 antigenemia at term and with intrapartum events that increase fetal exposure to maternal blood. Zidovudine therapy given during pregnancy and/or labor and delivery was associated with a significant reduction in vertical transmission. These data suggest that the beneficial effects of zidovudine therapy in reducing maternal-fetal HIV-1 transmission recently found in protocol 076 of the placebo-controlled Acquired Immunodeficiency Syndrome Clinical Trials Group Study may extend to women with lower CD4 cell counts and suggest that prolonged treatment of infants may not be necessary. (<i>JAMA</i>. 1994;271:1925-1930)
The Diagnosis of Stupor and Coma.
Authors: Fred Plum, Jerome B Posner
Journal: Annals of Internal Medicine (1973)

Advances in the knowledge and understanding of stupor and coma, aided by the considerable impact of CT scanning on neurological diagnosis, are reflected in this substantially revised edition. The authors have included new references and illustrations, but the third edition retains its approach to that art of diagnosis based on the understanding of pathophysiology and pathobiochemistry.
Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study
Authors: X. Pivot, S. Verma, L. Fallowfield, V. Müller, M. Lichinitser, A. Sñnchez Muñoz, Z. Machackova, S. Osborne, J. Gligorov
Journal: Annals of Oncology (2016)
Exit strategy to control covid-19 and relaunch the economy
Authors: Cam Bowie, Tony Hill
Journal: BMJ (2020)

In a fast expanding epidemic, after the surge is contained by physical distancing, the public health option of choice is to control the contact of new cases.1 This has worked in the past and with covid-19 in parts of Asia and in New Zealand with physical distancing234 and in other Asian countries without physical distancing or recourse to lockdown.567 Elimination, not suppression, is the goal. Public health staff …
Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology
Authors: Paul J. McKiernan, Orla Cunningham, Noel G. McElvaney, Sally Ann Cryan, Catherine M. Greene
Journal: European Respiratory Journal (2012)

Cystic Fibrosis (CF) is characterised by chronic pulmonary inflammation. microRNAs (miRs) are regulatory RNAs which inhibit gene expression. miR-126, a regulator of TOM1, is decreased in CF bronchial brushings; TOM1 is reciprocally increased. Polymeric nanoparticles of Polyethylenimine (PEI) and Chitosan-TPP can be used to deliver nucleic acids into bronchial epithelial cells. Here a proof-of-concept study was performed testing their efficacy at delivery of premiR-126 into non-CF and CF bronchial epithelial cells lines. PremiR-126-nanoparticles were prepared and characterized using a Zetasizer and used to transfect CFBE41o- and 16HBE14o- cell lines. RNA extraction was carried out 24h post transfection, cDNA was prepared and miR-126 and TOM1 expression was assessed using qRT-PCR. Toxicity was measured by high content analysis (HCA). Over-expression of miR-126 resulted in down-regulation of TOM1 in both cell types. The use of polymeric, cationic nanoparticles was shown to efficiently deliver premiR-126 into cells in order to achieve this knockdown. PremiR-126 encapsulated in PEI at a nanoparticle/premiR (N/P) ratio of 1:1 resulted in knockdown of TOM1 in CFBE41o- cells, with a reduction of ∼47% in TOM1 expression in comparison to a scrambled negative control complexed with commercial transfection reagent (p≤0.05). HCA showed no significant difference in cell counts between untreated cells and cells treated with PEI- and chitosan-TPP-premiR-126 nanoparticles, suggesting they are relatively non-toxic. miRs are potential novel targets for respiratory gene therapy and could be targeted to CF bronchial epithelial cells in the lungs using PEI nanoparticles.  Funding:SFI and HRB PhD/2007/11.