tbuckley/cabot-search huggingface dataset:
Association of Gestational Age at Birth With Risk of Perinatal Mortality and Special Educational Need Among Twins
Authors: Sarah Murray, Daniel MacKay, Sarah Stock, Jill Pell, Jane Norman
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Twin pregnancies account for 3% of live births but experience substantially more perinatal morbidity and mortality than singleton pregnancies. Optimizing the timing of birth is a key strategy in improving twin pregnancy outcomes. Current UK and US policies are based on observational studies of perinatal mortality and not on longer-term effects. The association of timing of birth with long-term childhood outcomes among twins is uncertain. <h3>Objective</h3> To identify the optimal gestation week for birth of twin infants by calculating the week of birth associated with the lowest risk of short-term and long-term adverse outcomes (perinatal mortality and special educational need [SEN] at school). <h3>Design, Setting, and Participants</h3> This population-based, data-linkage cohort study included 43 133 twin infants born at a gestational age of 34 weeks onward between January 1, 1980, and December 31, 2015, in Scotland. The data were analyzed from June 1, 2017, to March 1, 2019. <h3>Exposures</h3> Gestational age (in weeks) at the time of birth. <h3>Main Outcomes and Measures</h3> The primary outcomes were extended perinatal mortality and a record of SEN (≥1 of intellectual disabilities, dyslexia, physical or motor impairment, language or speech disorder, autistic spectrum disorder, and social, emotional, or behavioral difficulties) at school (children aged 4-18 years). To infer the consequence of the gestational age at birth, clinical outcomes of twin infants born at each week of gestation from 34 weeks onward were compared with those of twin infants remaining in utero thereafter. <h3>Results</h3> Of the total 43 133 twin infants included in the study, 21 696 (50.3%) were females. Although maternity records were available for all infants, 9519 sex-discordant twin children were linked to their educational data, of whom 1069 (13.8%) had a record of SEN. Compared with twins remaining in utero (n = 26 172), birth at any gestational age from 34 to 37 weeks was associated with increased odds of perinatal death (ie, adjusted odds ratio [AOR], 1.99; 95% CI, 1.53-2.69 at 36 weeks [n = 8056]) and increased risk of SEN at school (AOR, 1.39; 95% CI, 1.11-1.74, for birth at 36 weeks compared with 37 weeks). In a competing risk analysis, the risks of stillbirth and neonatal death were balanced at 37 weeks (risk difference, 2.05; 95% CI, 0.8-3.3). <h3>Conclusions and Relevance</h3> The findings of this study suggest that, in the absence of a medical complication, twins should not be routinely delivered before 37 completed weeks of gestation. These findings may help optimize shared decision-making around the timing of twin birth.
Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application
Authors: Le Zhang, Xiaonan Xu, Xiulan Su
Journal: Molecular Cancer (2020)

Abstract It is well acknowledged that immune system is deeply involved in cancer initiation and progression, and can exert both pro-tumorigenic and anti-tumorigenic effects, depending on specific microenvironment. With the better understanding of cancer-associated immune cells, especially T cells, immunotherapy was developed and applied in multiple cancers and exhibits remarkable efficacy. However, currently only a subset of patients have responses to immunotherapy, suggesting that a boarder view of cancer immunity is required. Non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are identified as critical regulators in both cancer cells and immune cells, thus show great potential to serve as new therapeutic targets to improve the response of immunotherapy. In this review, we summarize the functions and regulatory mechanisms of ncRNAs in cancer immunity, and highlight the potential of ncRNAs as novel targets for immunotherapy.
Platelet-derived growth factor receptor alpha (PDGFRA) and C-Kit immunohistochemistry (IHC) in gastrointestinal stromal tumours (GISTs)
Authors: D. Skarlos, E. Kyrodimou, N. Papakonstantinou, G. Klouvas, C. Christodoulou, G. Papadimas, H. Koutselini
Journal: Journal of Clinical Oncology (2007)

15156 Background: The vast majority of GISTs show activating mutations of the genes coding for c-kit (CD 117) and PDGFRA, two receptor tyrosine kinases (RTKs). The exact role of PDGFRA as this expressed immunohistochemically (IHC), has not been fully elucidated in the diagnosis and treatment of GISTs. The aim of this study was (1) to try to correlate the pathological features of patients (pts) with GISTs, with c-kit and PDGFRA as these expressed by IHC and 2) to correlate the c-kit and PDGFRA with the clinical outcome of the pts. We report here the first part of the study. Materials and Methods: Twenty one (21) pts with GISTs were studied 14 located in the stomach, 3 in small bowel, 3 in colon and 1 in the mesenterium. Criteria for positivity of c-kit were strong membranus, cytoplasmic and paranuclear staining and for PDGFRA dot-like or Golgi pattern of staining. Median age was 61 years while there was a male predominance. Results: C-kit was detected in 95% of cases while PDGFRA in 90.5%. All the GISTs that were positive for PDGFRA were also positive for c-kit. Conclusions: Preliminary results of the first part of the study show that an accurate diagnosis of GISTs can be achieved based on the conventional histological and IHC criteria without the need for mutational analysis. No significant financial relationships to disclose.
Abstract P1-04-02: Multicellular spheroids to dissect the interplay between human immune system and cancer
Authors: Elaheh Ahmadzadeh, Jan Martinek, Florentina Marches, Gabby Aucello, Chun I Yu, Karolina Palucka
Journal: Cancer Research (2020)

Abstract The interaction between various components in the tumor environment plays a pivotal role in tumor development, migration and metastasis. While the 2-dimensional (2D) in vitro culture methods fail to assimilate the complexity of tumor microenvironment, the 3D multicellular tumor spheroids support co-culture conditions and allow a more physiologically relevant environment. We are working to establish such 3D model to investigate the molecular mechanisms regulating the interactions between human cancer cells such as melanoma or breast cancer, myeloid cells and T cells. Spheroids were developed using hanging drop technique with multiple cancer cell lines, dermal fibroblasts and immune cells. Preliminary experiments were carried out to determine the optimum conditions for spheroid formation. Spheroid formation occurred within 72 hours and their integrity was maintained throughout the experiments. Immunofluorescence analysis of spheroid cryosections showed a homogeneous distribution of fibroblasts in spheroids. Addition of purified blood CD14+ blood monocytes to the mixture of cancer cells and dermal fibroblasts enabled monocyte integration into spheroids. Adding melanoma specific CD8+ T cells to tumor spheroids formed by melanoma cell line (Me275), dermal fibroblasts and monocytes resulted in homogeneous infiltration and increased number of cell death. Addition of PBMCs to the mix of breast cancer cells and fibroblasts enabled the discrimination of spheroids into two groups, tumor spheroids with immune cells at the margin preferentially located at tumor margin and tumor spheroids with infiltrating immune cells. These preliminary observations resemble those from our in vivo models of humanized mice, where different tumor xenografts show different level of immune cell infiltration. Thus, our 3D model might allow the classification of tumor cells based on immune cell infiltration and could potentially be used to assess the distribution of immune infiltrates and the interaction of cancer cells with immune compartments. Citation Format: Elaheh Ahmadzadeh, Jan Martinek, Florentina Marches, Gabby Aucello, Chun I Yu, Karolina Palucka. Multicellular spheroids to dissect the interplay between human immune system and cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-04-02.
SARS-CoV-2 Infection among Travelers Returning from Wuhan, China
Authors: Oon-Tek Ng, Kalisvar Marimuthu, Po-Ying Chia, Vanessa Koh, Calvin J. Chiew, Liang De Wang, Barnaby E. Young, Monica Chan, Shawn Vasoo, Li-Min Ling, David C. Lye, Kai-qian Kam, Koh-Cheng Thoon, Lalitha Kurupatham, Zubaidah Said, Ethan Goh, Constance Low, Soon-Kok Lim, Pream Raj, Olivia Oh, Valerie T.J. Koh, Cuiqin Poh, Tze-Minn Mak, Lin Cui, Alex R. Cook, Raymond T.P. Lin, Yee-Sin Leo, Vernon J.M. Lee
Journal: New England Journal of Medicine (2020)

SARS-CoV-2 Infection in Travelers Returning from Wuhan Data on travelers returning from areas with many cases of Covid-19 may be useful in estimating incidence. The authors report follow-up data on...
Abstract P260: Determinants of Statin Response: A Secondary Analysis of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)
Authors: Oluremi N Ajala, Olga Demler, Yanyan Liu, Paul Ridker, Robert J Glynn, Daniel Chasman, Samia Mora
Journal: Circulation (2020)

Introduction: Wide variability in LDLC change is observed with statins, yet determinants of statin response are uncertain. Hypotheses: Some markers of inflammation are associated with decreased statin response. Components of metabolic syndrome and older age are associated with better response. Methods: JUPITER (NCT00239681) randomized participants with LDLC&lt;130 mg/dL and hs-CRP≥2 mg/L to rosuvastatin 20 mg/d or placebo. Baseline and 1-year levels of LDLC and a panel of 20 other biomarkers were measured. We defined optimal statin response as ≥50% LDLC reduction; suboptimal response as &lt;50% reduction; and non-response as no change or increase in LDLC. χ 2 , t-tests and ANOVA were used to compare variables across optimal (N=3,801), suboptimal (N=3,235) and non-responders (N=868). Multinomial regression models evaluated associations of determinants of statin response after adjusting for risk factors including compliance. Backward selection identified variables that associated with response. t-distributed Stochastic Neighbor Embedding (t-SNE) suggested predictor clusters for statin response. Results: Compliance was the strongest determinant of statin response (Table). On multivariable analyses, blacks and Hispanics were at higher risk for suboptimal/non-response compared with whites as were greater alcohol use and HbA1c. Higher baseline levels of lipids [lipoprotein(a), apolipoprotein (apo) AI and B], inflammatory biomarkers, and lower branched-chain amino acids associated with decreased statin response (Table). By contrast, determinants of better response included older age, female sex, and higher waist circumference and baseline levels of LDLC, triglycerides, and blood pressure. We observed systematic patterns in t-SNE clustering for statin response by LDLC, LDL particle number, and apo B. Conclusions: This study identified determinants for high-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.
HER2 expression and efficacy of preoperative paclitaxel and 5-fluorouracil, cyclophosphamide, doxorubicin chemotherapy in breast cancer
Authors: L. Pusztai, F. Andre, C. Mazouni, C. Liedtke, S. Kau, D. Frye, M. Green, A. M. Gonzalez-Angulo, W. F. Symmans, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2007)

548 Purpose: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in stage II-III breast cancer. Patients and Methods: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from a subset of 132 patients and were used to examine the co-expression of HER2 and topoisomerase II a (TOP2A) and microtubule associated protein tau (MAP-Tau). Results: Of the 534 patients, 105 (20%) had HER2 overexpressing (HER2+) breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P&lt;0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). In multivariate analysis ER-negative status (OR 3.1, 95% CI 1.7–5.5, P &lt; 0.001), high nuclear grade (OR 6.7, 95% CI 3.1–14.2, P &lt; 0.001), weekly paclitaxel regimen (OR 2.6, 95% CI 1.5–4.5, P &lt;0.001), and HER2 overexpression (OR 2.4, 95% CI 1.3–4.2, P = 0.003) were significant predictors of pCR. Among ER- cancers, the pCR rates were 50% (95%CI: 36–64%) in HER2+ (n=24/48) and 30% (95%CI: 23–37%) in HER2- disease (n=48/159), P = 0.02. Among ER+ cancers, the pCR rate was 19% (95% CI: 9–29%) in HER2+ (n=11/57) and 6% (95% CI: 3–9%) in HER2- disease (n=17/270), P = 0.003. In the gene expression data, HER2 overexpression was associated with lower expression of MAP-tau (mean 303 vs 500, p=0.001) and higher expression of TOP2A mRNAs (mean 398 vs 274, p=0.048) in patients with ER+ disease. All ER- cancers had low MAP-Tau expression (compared to ER+ cancers) regardless of HER2 status. Conclusion: HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy in both ER- and ER+ cancers. HER2 overexpression correlates with increased TOP2A and decreased MAP-Tau expression in ER+ cancers which could explain increased anthracycline and taxane sensitivity of these tumors. No significant financial relationships to disclose.
Abstract P391: The Effects of Obstructive Sleep Apnea on Cardiac Arrhythmia Risk
Authors: Emily Biben, Lauren Burgess, Julie Allen, Noah Jouett, John Burk, Michael Smith
Journal: Circulation (2020)

Background: Over 20 million people in the United States suffer from Obstructive Sleep Apnea (OSA). Compared to the general population, OSA patients are 2.6 times more likely to experience sudden cardiac death (SCD), and it is suspected that this is due, in part, to QT prolongation leading to fatal dysrhythmias. OSA events have previously been shown to cause prolonged QT intervals compared to the post-apnea hyperventilation period, and studies have also observed increased QT dispersion in patients without cardiac disease. However, those with cardiac disease may be at the greatest risk for SCD, and it is not known what role QT prolongation plays and what factors influence these responses. Thus, the purpose of this study is to evaluate the factors that affect QT interval during periods of sleep apnea including OSA severity, time of night, and quantity of obstructive apneic events during sleep. Methods: We determined QTc intervals from the electrocardiograms of 36 patients undergoing polysomnography for diagnosis of OSA. Patients that were selected had an apnea hypopnea index &gt;20/Hr and had no prior myocardial infarction or heart failure. Each patient’s ECG during their sleep study was analyzed to assess QT interval throughout the night. Baseline QT intervals were compared to QT intervals during obstructive apneas during the first 2 hours of sleep (Early) and last 2 hours of sleep (Late). In addition, apneas &gt;40 seconds were analyzed in 11 patients for changes in QTc as the apnea progressed. Statistical comparisons were made with paired t tests and a one-way ANOVA analysis with repeated measures. Results: Early analyses of data showed QTc intervals in Early and Late apneas were significantly prolonged compared to awake baseline (p=0.04 and p=0.006 respectively). For patients with apneas &gt;40 seconds, significant differences in QTc interval were observed at increasing time points during the apnea compared to the QTc immediately preceding the apnea (p&lt;0.001). Furthermore, patients with longer apneas tend to have longer baseline QTc (p=0.07). Conclusions: Sleep apneic events are associated with periods of mild QTc prolongation despite some cardiac cycle shortening. The prolongation tends to become enhanced later in the night, implying that there is a cumulative effect of numerous prior apneas. Furthermore, prolongation tends to increase as the apnea duration progresses. Early data analyses also suggest that baseline QTc tends to be longer in patients who have more severe/longer apneic events throughout the night. Future studies will focus on QTc changes in OSA patients with prior heart disease, as these are the patients at greatest risk for serious arrhythmias during the night.
Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM)
Authors: R. Stupp, R. Goldbrunner, B. Neyns, U. Schlegel, P. Clement, G. G. Grabenbauer, M. E. Hegi, J. Nippgen, M. Picard, M. Weller
Journal: Journal of Clinical Oncology (2007)

2000 Background: To evaluate safety, toxicity, and efficacy of the combination of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, in addition to standard temozolomide (TMZ) and radiotherapy (RT). Methods: 52 pts (PS 0–1: 92%, 2: 8%; median age 57 yrs) after tumor resection (n=43/83%) or biopsy (n= 9/17%) were treated with standard TMZ/RT (Stupp et al. NEJM 2005). In addition cilengitide (500 mg i.v., 2x/week) was started one week before TMZ/RT and given throughout for the duration of chemotherapy or until progression. The primary endpoint was progression free survival rate at 6 months (target: 65%). Pts were followed with MRI every 2 months. Histopathologic diagnosis and MRI imaging were independently reviewed, O 6 -Methylguanine- DNA methyltransferase (MGMT) promotor methylation status was assessed in 45 (86.5%) pts. Results: 46 pts (92%) completed RT, = 90% of concomitant TMZ was received by 42 pts and cilengitide by 45 pts. 20 pts (3 ongoing) completed 6 cycles of maintenance TMZ and cilengitide. Observed hematological grade 3 and 4 toxicities were: lymphopenia (28/52, 53.8%), thrombocytopenia (7/52 pt. 13.4%) and neutropenia (5/52, 9.6%). Treatment related non-hematologic grade 3/4 toxicities were reported for n=3/52 (5.7%) patients: constitutional symptoms (asthenia, fatigue, anorexia, n=3); elevated liver function tests (n=1), deep venous thrombosis and pulmonary embolism (n=1). One patient with a history of sigmoid diverticulosis experienced sigmoid perforation (grade 2). In total, 34/52 (65.4% [95% CI, 50.9–78.0%]) of the pts were progression free at 6 months. Pts with MGMT gene-promotor methylation in the tumor were more likely to reach 6 months PFS endpoint. Conclusions: The study reached its primary endpoint. The combination of the integrin inhibitor RGD peptide Cilengitide and TMZ/RT was well tolerated, PFS at 6 months is encouraging. MGMT gene promoter methylation correlates with outcome. At the time of ASCO, updated results and survival estimates after a minimum follow-up of at least 1 year will be available. [Table: see text]
Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery versus upfront surgery followed by chemotherapy (CT) in advanced epithelial ovarian carcinoma (EOC): A prospective randomized study—Interim results
Authors: L. Kumar Prof, R. Hariprasad, S. Kumar, N. Bhatla, S. Thulkar, M. Vijayaraghavan, S. Deo, N. Shukla, R. Singh
Journal: Journal of Clinical Oncology (2007)

5531 Background: To determine the impact of NACT on surgical debulking rate, overall and disease-free survival and quality of life (QOL) in patients with advanced EOC. Methods: Between Oct 2001 and Dec 2006, 128 previously untreated EOC patients (median age- 50 years, range 30 to 65) with FIGO stage III C &amp; IV (pleural effusion only) have been randomized into - Arm A (n=65) upfront debulking Surgery followed by 6 cycles of Paclitaxel &amp; carboplatin (PC) and Arm B (n=63): NACT with 3 cycles of PC followed by debulking Surgery then 3 more cycles. Eligibility criteria include - age 18 to 65 years, biopsy / cytological proven EOC, adequate hematological, renal, liver &amp; cardiac functions, normal upper &amp; lower GI endoscopy &amp; CEA levels. Both groups were compared for debulking rate, duration of surgery, blood loss, intra &amp; postoperative morbidity &amp; mortality, overall response to treatment and QOL (FACT- O questionnaire). Results: 100 of 128 patients have completed treatment (arm A- 56, B-44). 7 patients were not evaluable; (Germ cell tumor-1, mixed Mullerian tumor-2, dual primary-1 and krukenburg-3). 93 patients are evaluable. Patients’ characteristics are similar in both arms. Grade III-IV - GIT (3% vs. 4%) &amp; bone marrow (9% Vs 7%, p=ns) toxicity was similar in arm A &amp; B, among 463 CT cycles administered. Patients in NACT arm had higher optimum debulking rate, p&lt;. 0001, decreased blood loss during surgery (mean vol 520 vs 373 ml p&lt;0.003) and reduced postoperative infections 14.8 % vs. 2.5%, p&lt;0.04. Mean operative time (110 vs 95 minutes, p=0.12) and hospital stay (12 Vs 9.4 days, p=0.1) were similar in arm A &amp; B. The median overall survival (arm A &amp; B: 42 vs 29 months, p=0.07) and disease free survival (20 vs 25 months, p=0.11) is not different at a median follow up of 41 months. QOL score was significantly better in NACT arm at the end of treatment. (93 vs 114, p&lt;. 001). Conclusions: Neoadjuvant chemotherapy in advanced epithelial ovarian cancer is associated with higher optimum debulking rate with reduced postoperative morbidity and improved quality of life. No significant financial relationships to disclose.
Revitalising audit and feedback to improve patient care
Authors: Robbie Foy, Mirek Skrypak, Sarah Alderson, Noah Michael Ivers, Bren McInerney, Jill Stoddart, Jane Ingham, Danny Keenan
Journal: BMJ (2020)

Audit and feedback are widely used in quality improvement. <b>Robbie Foy and colleagues</b> argue that their full potential to improve patient care could be realised through a more evidence based and imaginative approach
Glucose transporter 4 (GLUT4) distribution on metabolic healthy obese (MHO) vs metabolic unhealthy obese (MUO)
Authors: K. De La Vega-Moreno, C.B. Romero-Hernández, D.G. Ruíz-Dangú, E. Vera-Gómez, A. Hernández-Patricio, G.A. Domínguez-Pérez, J.A. Gutiérrez-Buendía, R. Pérez-Cabeza De Vaca, O.F. Gaytán-Fuentes, J. Montoya-Ramírez, M. Salamanca-García, P. Mondragón-Terán, K.G. Carvajal-Aguilera, L.C. Camacho-Castillo, J.A. Suárez-Cuenca
Journal: Metabolism (2020)