tbuckley/cabot-search huggingface dataset:
What is the role of serum and skin testing in children with a parent reported beta-lactam allergy?
Authors: M. Lucas, Regli B. S. Von Ungern-Sternberg, A. Arnold, M. Trevenen, A. Sommefield, Y. Jeelall, L. Slevin, D. Sommerfield, K. Murray, K. Rueter
Journal: Allergy (2019)
OS3.6 Prediagnostic symptoms and signs of adult glioma: the patients’ view
Authors: M C M Peeters, L Dirven, J A F Koekkoek, E G Gortmaker, L Fritz, M J Vos, M J B Taphoorn
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Little is known about the symptoms and signs glioma patients experience in the year before diagnosis, either or not resulting in health care usage. The objective of this study was to determine the incidence of several symptoms and signs glioma patients experienced in the year prior to diagnosis, as well as visits to a general practitioner (GP) related to these issues. MATERIAL AND METHODS This was a cross-sectional study, including adults diagnosed with a glioma &lt;12 months ago. Patients were asked to complete a 30-item study-specific questionnaire, if possible with input of a proxy, focusing on symptoms and signs they experienced in the 12 months before diagnosis. For each indicated symptom/sign, patients were asked whether they consulted the GP for this issue. In addition, the presence of comorbidity and other chronic complaints were assessed, as well as consulted health care professionals (HCPs) in the year prior to diagnosis. The statistical analyses were corrected for multiple testing. RESULTS Between July 2016 and March 2019, 58 patients completed the questionnaires, 54 (93%) with input of a proxy. Forty-one (72%) patients were men, with a median age of 60 years (range 43–78), and the median time since diagnosis was 4 months (range 1–12). Forty (69%) patients had a comorbidity or chronic complaint, and the median number of consulted HCPs was 2 (range 0–8). The median number of symptoms/signs experienced in the year before diagnosis was 8 (range 2–19) in low-grade and 5 (range 0–24) in high-grade glioma (p=0.258). The five most frequently mentioned problems were fatigue (34/58, 59%), mental tiredness (28/58, 48%), sleeping disorder (23/58, 40%), headache (22/58, 38%) and stress (20/58, 34%), with no differences between low- and high grade glioma. Twenty-five (43%) patients had visited the GP with at least one issue. We found that patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p=0.002), paralysis in for example a hand or leg (10 vs 3, p=0.006), or a change in consciousness (9 vs 3, p=0.013) compared to those that did not consult the GP. However, they did not differ with respect to the number of symptoms (median 7 vs 5), comorbidities and chronic complaints (median 1 vs 1), or overall health care usage (median 3 vs 2). CONCLUSION Glioma patients experience a range of problems in the year prior to diagnosis, but patients who consult the GP report significantly more often neurological problems.
Sharing terms and concepts under the selectionist umbrella: Difficult but worthwhile
Authors: Philip N. Hineline
Journal: Behavioral and Brain Sciences (2001)

Comparing and sharing selectionist terms and concepts from disparate domains can aid understanding in each domain. But constraints of interpretive language will make this difficult – such as the bipolar constraint of interpretive language when addressed to intrinsically tripolar phenomena. Hull et al. acknowledge that some key terms in their account remain problematic; the term, “information,” probably needs to be replaced.
Abstract 67: Polycystin-1 is Required for Normal Cardiomyocyte Excitability and Heart Function
Authors: Francisco J Altamirano, Gabriele G Schiattarella, Sergiy Kyrychenko, Jay W Schneider, Sergio Lavandero, Thomas G Gillette, Joseph A Hill
Journal: Circulation Research (2017)

Mutations in the gene ( Pkd1 ) encoding Polycystin-1 (PC-1) leads to autosomal dominant polycystic kidney disease (ADPKD). Although renal failure is the leading cause of death, cardiovascular alterations are described in ADPKD patients. Our lab has previously demonstrated that PC-1 is involved in cardiac L-type Ca 2+ channel (LTCC) protein stability, which is required for hypertrophic growth during mechanical stretch. PC-1 is expressed in cardiomyocytes and its gene ablation in mice decreases basal cardiac function. Here, we hypothesized that PC-1 regulates excitation-contraction coupling in cardiomyocytes. To test this hypothesis, we studied mice harboring floxed Pkd1 alleles and a Cre transgene (α-MHC promoter) to engineer cardiomyocyte-specific PC-1 KO (F/F αMHC Cre, PC-1 cKO) mice. Human-derived cardiomyocytes were differentiated from embryonic stem cells (H9), and PC-1 was depleted using specific siRNA constructs. Fractional shortening measured by echocardiography was significantly reduced under basal conditions in PC-1 cKO mice compared with controls. Likewise, adult ventricular cardiomyocytes isolated from PC-1 cKO mice manifested decreased contractility (measured by Ionoptix) and a reduced Ca 2+ transients (measured using Fluo-8AM and line scan) during pacing (0.5 Hz). Unexpectedly, assessment of both Ca 2+ stores (caffeine-evoked Ca 2+ transients) and Ca 2+ entry (LTCC currents, whole-cell voltage clamp) showed no differences between PC-1 cKO and control cardiomyocytes. Remarkably, Ca 2+ transients evoked by high K + depolarization were similar across genotypes, suggesting an alteration in excitability. Indeed, action potential duration (measured by current clamp or FluoVolt) was shorter in cardiomyocytes lacking PC-1 (mouse adult cardiomyocytes and hESC-derived cardiomyocytes). Moreover, PC-1 cKO mice manifested shorter QT intervals on ECG, and a pharmacological intervention with quinidine improved cardiac function and cardiomyocyte contractility to near-normal levels. Our findings uncover a novel role for PC-1 as an important regulator of cardiac function, required to fine-tune both excitability and contraction in ventricular myocytes.
Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection
Authors: Adeline Gasser, Yu-Wen Chen, Anais Audebrand, Ayhan Daglayan, Marine Charavin, Brigitte Escoubet, Pavel Karpov, Igor Tetko, Michael W.Y. Chan, Daniela Cardinale, Laurent Désaubry, Canan G. Nebigil
Journal: JACC CardioOncology (2019)

This study investigated how different concentrations of doxorubicin (DOX) can affect the function of cardiac cells. This study also examined whether activation of prokineticin receptor (PKR)-1 by a nonpeptide agonist, IS20, prevents DOX-induced cardiovascular toxicity in mouse models.High prevalence of heart failure during and following cancer treatments remains a subject of intense research and therapeutic interest.This study used cultured cardiomyocytes, endothelial cells (ECs), and epicardium-derived progenitor cells (EDPCs) for in vitro assays, tumor-bearing models, and acute and chronic toxicity mouse models for in vivo assays.Brief exposure to cardiomyocytes with high-dose DOX increased the accumulation of reactive oxygen species (ROS) by inhibiting a detoxification mechanism via stabilization of cytoplasmic nuclear factor, erythroid 2. Prolonged exposure to medium-dose DOX induced apoptosis in cardiomyocytes, ECs, and EDPCs. However, low-dose DOX promoted functional defects without inducing apoptosis in EDPCs and ECs. IS20 alleviated detrimental effects of DOX in cardiac cells by activating the serin threonin protein kinase B (Akt) or mitogen-activated protein kinase pathways. Genetic or pharmacological inactivation of PKR1 subdues these effects of IS20. In a chronic mouse model of DOX cardiotoxicity, IS20 normalized an elevated serum marker of cardiotoxicity and vascular and EDPC deficits, attenuated apoptosis and fibrosis, and improved the survival rate and cardiac function. IS20 did not interfere with the cytotoxicity or antitumor effects of DOX in breast cancer lines or in a mouse model of breast cancer, but it did attenuate the decreases in left ventricular diastolic volume induced by acute DOX treatment.This study identified the molecular and cellular signature of dose-dependent, DOX-mediated cardiotoxicity and provided evidence that PKR-1 is a promising target to combat cardiotoxicity of cancer treatments.
Docetaxel, oxaliplatin, and capecitabine (DOX) combination chemotherapy for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Luigi Di Lauro, Domenico Sergi, Franca Belli, Silvia Ileana Fattoruso, Maria Grazia Arena, Laura Pizzuti, Patrizia Vici
Journal: Journal of Clinical Oncology (2013)

e15065 Background: So far, the prognosis of advanced gastric cancer is dismal. Combination chemotherapy of docetaxel (D), cisplatin (C) and fluorouracil (F) showed activity in metastatic gastric cancer, but this regimen was complicated by a high incidence of myelotoxicity. We performed a multicenter phase II trial substituting C with oxaliplatin (O) and F with capecitabine (X) in chemotherapy-naive patients (pts) with gastric or GEJ adenocarcinoma. Methods: Pts with measurable distant metastases received D 60 mg/mq iv, O 100 mg/mq iv on day 1 and X 500 mg/mq orally twice daily continuously, with cycles repeated every 3 weeks for a maximum of 8. G-CSF was used only as secondary prophylaxis. The primary endpoint was overall response rate (RR) according to RECIST. Toxicity was reported according to NCI-CTC v 3.0. Optimal Simon's two-stage design was employed with 6/15 responses required in the first stage to allow continuation to 46 pts. Results: 46 pts were enrolled: M/F 28/18; median age 66 years (32-75); median ECOG PS 1 (0-2); primary tumor resected/ unresected 16/30; disease location was gastric in 34 and GEJ in 12 pts; sites of disease were liver in 27, nodes in 25, peritoneum in 20, lung in 8 and bone in 5 pts. At the time of analysis all pts were evaluable for response and toxicity. In 46 pts, 3 CR and 21 PR were observed, for an overall RR of 52.1% (95% CI, 37.7%-66.5%). Responses were obtained in 15/27 pts (55%) with liver metastases. Disease remained stable in 14 pts (30.5 %). Median TTP was 6.8 months and median OS was 12.6 months. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 41%, 4% and 9% of the pts, respectively. Febrile neutropenia was observed in 2 pts (4%). Other grade 3 toxicities included mucositis in 2 pts (4%), vomiting in 3 pts (6.5%) and diarrhea in 2 pt (4%). There were no severe neurotoxicity, nor treatment-related deaths. Conclusions: The DOX combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomized trials and, hopefully, in neoadjuvant setting.
Epidermal growth factor receptor mutation (EGFRMUT) in non-small cell lung cancer (NSCLC) in the Middle East.
Authors: Abdul Rahman Jazieh, Hassan Nadim Jaafar, Rasha Mustafa, Kakil Rasul, Jamal Zekri, Rabab Mohamed Gaafar, Hamed Homoud Al Husaini, Hamdy A. Azim, Hanaa Bamefleh, Ahmed Gasmelseed
Journal: Journal of Clinical Oncology (2013)

e19035 Background: EGFR mutation is an important therapeutic marker for the management of NSCLC with known ethnic variations. Our study aims at determining the prevalence of the mutation in the Middle East and its correlation with demographic and clinical features. Methods: A multisite retrospective study was conducted including institutions from Saudi Arabia, UAE, Qatar and Egypt. All consecutive patients (pts) with NSCLC tested for EGFRMUT were eligible. Data were obtained on demographic and disease characteristics, and EGFR test results. Institutional Review Board approval was obtained from all participating sites. Results: Data on 201 patients were obtained. Median age was 61 years (51 - 69), 140 (69.65%) were males and 174 pts were Arab (86.57%) Tumor histology subtypes were adenocarcinoma in 175 patients (87.07%), squamous cell carcinoma in 15 pts (7.46%) and others in 11 pts (5.48%). EGFRMUT was detected in 66 pts, with (36.50%) prevalence in adenocarcinoma. No squamous cell carcinoma harbored EGFRMUT. The most frequent abnormality detected was in exon 19 in 39 pts (57.36%), abnormalities in exon 21 in 22 pts (32.35%) and in exon 18 in 7 pts (10.29%). Two pts had dual mutations on exons 19 and 21. Univariate and multivariate analyses revealed significant predictors for having EGFRMUT to be: female gender (42.42 % vs. 27.7% in males, p= 0.0096), non-smoking status (81.82% vs. 16.21% in smokers, p=0.0001) and adenocarcinoma subtypes (36.25 % vs. 15.38% in others, p=0.035). There was no difference between Arabs and non-Arabs. Conclusions: This is the first study from our region to report the prevalence of EGFRMUT in ME population which seems to be similar to Far East population with similar clinical predictors. Studies about the impact of targeted therapy in our patient’s population are underway.
Multiple Myeloma and Renal Impairment: Analysis of Induction Therapy Strategies and Outcome after Autologous Stem Cell Transplantation
Authors: Thomas Reiter, Marlies Antlanger, Alexandra Böhm, Wolfgang Lamm, Max Gornicec, Ella Willenbacher, David Nachbauer, Werner Rabitsch, Daniel Lechner, Hildegard Greinix, Felix Keil, Heinz Gisslinger, Hermine Agis, Maria-Theresa Krauth
Journal: Blood (2017)
Evaluating Chemicals for Thyroid Disruption: Opportunities and Challenges with <i>in Vitro</i> Testing and Adverse Outcome Pathway Approaches
Authors: Pamela D. Noyes, Katie Paul Friedman, Patience Browne, Jonathan T. Haselman, Mary E. Gilbert, Michael W. Hornung, Stan Barone, Kevin M. Crofton, Susan C. Laws, Tammy E. Stoker, Steven O. Simmons, Joseph E. Tietge, Sigmund J. Degitz
Journal: Environmental Health Perspectives (2019)

Extensive clinical and experimental research documents the potential for chemical disruption of thyroid hormone (TH) signaling through multiple molecular targets. Perturbation of TH signaling can lead to abnormal brain development, cognitive impairments, and other adverse outcomes in humans and wildlife. To increase chemical safety screening efficiency and reduce vertebrate animal testing, in vitro assays that identify chemical interactions with molecular targets of the thyroid system have been developed and implemented.We present an adverse outcome pathway (AOP) network to link data derived from in vitro assays that measure chemical interactions with thyroid molecular targets to downstream events and adverse outcomes traditionally derived from in vivo testing. We examine the role of new in vitro technologies, in the context of the AOP network, in facilitating consideration of several important regulatory and biological challenges in characterizing chemicals that exert effects through a thyroid mechanism.There is a substantial body of knowledge describing chemical effects on molecular and physiological regulation of TH signaling and associated adverse outcomes. Until recently, few alternative nonanimal assays were available to interrogate chemical effects on TH signaling. With the development of these new tools, screening large libraries of chemicals for interactions with molecular targets of the thyroid is now possible. Measuring early chemical interactions with targets in the thyroid pathway provides a means of linking adverse outcomes, which may be influenced by many biological processes, to a thyroid mechanism. However, the use of in vitro assays beyond chemical screening is complicated by continuing limits in our knowledge of TH signaling in important life stages and tissues, such as during fetal brain development. Nonetheless, the thyroid AOP network provides an ideal tool for defining causal linkages of a chemical exerting thyroid-dependent effects and identifying research needs to quantify these effects in support of regulatory decision making. https://doi.org/10.1289/EHP5297.
Toward clinical digital phenotyping: a timely opportunity to consider purpose, quality, and safety
Authors: Kit Huckvale, Svetha Venkatesh, Helen Christensen
Journal: npj Digital Medicine (2019)

The use of data generated passively by personal electronic devices, such as smartphones, to measure human function in health and disease has generated significant research interest. Particularly in psychiatry, objective, continuous quantitation using patients' own devices may result in clinically useful markers that can be used to refine diagnostic processes, tailor treatment choices, improve condition monitoring for actionable outcomes, such as early signs of relapse, and develop new intervention models. If a principal goal for digital phenotyping is clinical improvement, research needs to attend now to factors that will help or hinder future clinical adoption. We identify four opportunities for research directed toward this goal: exploring intermediate outcomes and underlying disease mechanisms; focusing on purposes that are likely to be used in clinical practice; anticipating quality and safety barriers to adoption; and exploring the potential for digital personalized medicine arising from the integration of digital phenotyping and digital interventions. Clinical relevance also means explicitly addressing consumer needs, preferences, and acceptability as the ultimate users of digital phenotyping interventions. There is a risk that, without such considerations, the potential benefits of digital phenotyping are delayed or not realized because approaches that are feasible for application in healthcare, and the evidence required to support clinical commissioning, are not developed. Practical steps to accelerate this research agenda include the further development of digital phenotyping technology platforms focusing on scalability and equity, establishing shared data repositories and common data standards, and fostering multidisciplinary collaborations between clinical stakeholders (including patients), computer scientists, and researchers.
The prescreening tool for gastric cancer in China
Authors: Kecheng Liu, Mengbin Qin, Jiean Huang
Journal: Gut (2019)

We read with interest the work by Cai et al 1 presenting a precise and cost-effective initial mass-prescreening tool for improving the detection of gastric cancer (GC), including early GC. However, we have several comments on the design and results of this study, hoping to improve the transferability and cost-effectiveness of this prescreening tool to other cohorts.

The first point is about the strategy of handling missing data. This study prevented all participants with any missing data from the analysis without reporting the percentage of those participants in the total cohort, which …
Myelodysplastic Syndromes with Isolated 20q Deletion: A New Clinical-Biological Entity?
Authors: Daniela De Benedittis, Luana Fianchi, Pasquale Niscola, Annalina Piccioni, Ambra Di Veroli, Alessia Campagna, Stefano Mancini, Nicoletta Villivà, Sara Mohamed, Ida Carmosino, Marianna Criscuolo, Susanna Fenu, Maria Antonietta Aloe Spiriti, Francesco Buccisano, Massimo Breccia, Marco Mancini, Roberto Latagliata
Journal: Blood (2018)
P14.20 Anxiety level in a prospective cohort of newly diagnosed glioblastoma patients: preliminary results from the IMAGE study
Authors: D Maillet, P Narme, V Menard, M Larrieu, K Sahel, C Belin, A Carpentier
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Quality of life (QoL) is an important area of clinical neuro-oncology, especially in glioblastoma patients. Although previous studies showed an association between QoL and anxiety, few studies have focused on the anxiety level throughout the disease progression (Bunevicius et al., 2017; Kilbride et al., 2007). Underestimating anxiety may have several consequences: a low treatment compliance, exacerbation of somatic symptoms or side effects of treatment, difficulties with understanding medical information and lower cooperation with the medical staff (Spencer, 2010). In the present study, we aimed assessing the current state of anxiety in a prospective cohort of patients treated for glioblastoma. We also investigated potential correlations with other clinical and psychological variables to better understand determinants of anxiety in this population. MATERIAL AND METHODS At the beginning of their cycle of temozolomide cure and after radio-chemotherapy, 30 patients with glioblastoma were included. Inclusion criteria were: Karnofsky index (IK) ≥ 70% and absence of cognitive disorder that could interfere with the completion of questionnaires. The characteristics of patients were as follows: mean age of 56.6 years ± 12.5 (70% were more than 50 years old); 20% were women; 50% had a university degree and IK of 87% ± 5. Anxiety level was assessed using the State-Trait Anxiety Inventory. This scale consists of 40 items on a self-report basis measuring how patients feel right now (“state”) and how they generally feel (“trait”). We also assessed (i) QoL using the Cancer Quality of Life Questionnaire 30 and the Brain Cancer Module-20; (ii) the presence of depressive symptoms using the Hospital Anxiety and Depression Scale; (iii) the self-esteem using the Rosenberg self-esteem scale and (iv) memory complains using the Prospective and Retrospective Memory Questionnaire. RESULTS The preliminary results showed that - at baseline - 21% of our sample reported high levels of anxiety. Correlation analyses showed that state anxiety was correlated with trait anxiety (rho=0.799, p&lt; .001), QoL (rho=0.678, p&lt; .001), level of self-esteem (rho=-0.514, p=0.004) and memory complains (rho=0.618, p&lt; .001). Any correlation was found with age, education level, lesional lateralization or depressive symptoms. Women had higher state anxiety scores than men (t(27)=-2.4, p=0.02). CONCLUSION These preliminary results suggest that higher current state of anxiety is associated with lower QoL and lower self-esteem, regardless the presence of depressive symptoms, age, education level or lesional lateralization. Anxiety level at the follow-up (4 and 6 months after the baseline) and determinants of its progression will also be presented and might help health professionals to understand patients’ experience and better meet their needs.
P14.119 Clinical-radiological description of a retrospective series of patients diagnosed with stroke due to hypercoagulability associated with cancer
Authors: I Esparragosa, R Valenti-Azcarate, D Moreno-Ajona, C Toledano-Illan, P Irimia Sieira, E Martinez-Vila, J Gallego Perez de Larraya
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES To describe the clinical-radiological characteristics of a monocentric series of patients with stroke due to a state of hypercoagulability associated with cancer. MATERIAL AND METHODS We retrospectively reviewed the clinical, radiological and laboratory data of 32 patients diagnosed of ischemic stroke secondary to a state of hypercoagulability associated with cancer between 2007 and 2017. RESULTS 15/32 were women. The median age was 65 years (range: 48–82). In 4/32 patients, stroke led to the diagnosis of advanced stage cancer, and in 15/32 it occurred in the context of uncontrolled cancer progression. 24/32 patients had at least an additional vascular risk factor. Complementary tests were performed (blood analysis, carotid echo-Doppler, ECG-monitoring, echocardiogram) to rule out other aetiologies. 25/32 patients had acute ischemic lesions in 3 to 5 cerebrovascular territories. 23/32 had multiorgan infarctions in body CT. The D-Dimer was analysed in 14/32 patients, being elevated in 13/14 patients. Half of patients (16/32) suffered a recurrence of stroke in the first 4 weeks. Most frequently detected tumours were lung adenocarcinoma (11/32) and pancreatic adenocarcinoma (8/32). The median survival after the stroke was 1 month (range: 0.2–25 months). CONCLUSIONS Uncontrolled cancer may lead to a prothrombotic state that facilitates the development of strokes in multiple cerebrovascular territories. Recurrences are frequent despite anticoagulant therapy, and prognosis is poor because of the underlying cancer and stroke-related neurological deterioration.