tbuckley/cabot-search huggingface dataset:
Developing a prediction model for benefit from fulvestrant in heavily pretreated metastatic breast cancer (MBC) patients
Authors: E. Amir, O. C. Freedman, G. Dranitsaris, J. Napolskikh, S. Chia, T. Petrella, S. Dent, R. Kumar, M. Fralick, M. Clemons
Journal: Journal of Clinical Oncology (2009)

1041 Background: Fulvestrant use in heavily pretreated patients with MBC is associated with highly variable responses. This study aimed to characterize the benefit of fulvestrant therapy and develop a prediction model for clinical benefit in this setting. Methods: A nationwide, retrospective chart review of patients enrolled in a Canadian compassionate use program was performed. This program mandated prior therapy with tamoxifen and both steroidal and non-steroidal aromatase inhibitors. Charts from the seven highest accruing centers were reviewed. Sample size was based on the derivation of a model to predict the probability of a patient remaining on fulvestrant and free from chemotherapy for at least 3 months. Results: 305 women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Of these, 48 (23%) required chemotherapy at 3 months, 113 (55%) at 6 months, and 170 (82%) by 12 months. Median duration of fulvestrant treatment was 126 days (range 23–1920). Median overall survival from start of fulvestrant was 698 days (25 th percentile 316 days-75 th percentile 1,359 days). The preliminary prediction model showed that older age (OR 0.96, 95% CI 0.93–0.99) and having received no adjuvant hormonal therapy (OR 0.5, 95% CI 0.2–1.25) predicted a greater chance of remaining chemotherapy-free at 3 months. Presence of lung (OR 2.55, 95% CI 1.1–5.9) or brain metastases (OR12.8, 95% CI 4.1–55.4) predicted a lower chance of remaining chemotherapy-free at 3 months. Conclusions: Older age and having received no prior adjuvant hormonal therapy predicted a greater chance of remaining chemotherapy free at 3 months, while lung and brain metastases predicted a lower chance. These factors will be validated in an international data set, and may be considered when prescribing fulvestrant. A 6-month prediction model is currently under development. [Table: see text]
Abstract 14066: Repeat Coronary Reactivity Testing in Women With Ischemia and No Obstructive Coronary Artery Disease
Authors: Nissi Suppogu, Janet Wei, Jenna Maughan, Sandy Joung, Odayme Quesada, Chrisandra Shufelt, Bruce Samuels, Babak Azarbal, Noel Bairey-Merz
Journal: Circulation (2019)

Background: Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) determined invasively by coronary reactivity tes...
SAT0183 Bone mineral density in women with rheumatoid arthritis
Authors: AN Dimic, V Radenkovic, S Milenkovic, Z Markovic, A Stankovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) has a significant influence on bone loss in both periph­eral (juxtaarticular osteoporosis) and axial skeleton. Glucocorticoids (GC) are often used in the therapy of RA and contribute significantly to favourable disease outcome but have been accused to cause a bone loss in these patients. <h3>Objectives</h3> To assess the influence of GC on the occurrence of osteoporosis in RA patients. <h3>Methods</h3> Hundred and seven women with RA were evaluated. They were divided in two age-groups: 40–49 and 50–59. The assessment of bone mineral density was performed by dual energy x-ray absorptiometry (DEXA), using Lunar DPX densitometer. Anterior-posterior spine scan of lumbar vertebrae L1-L4 was performed. <h3>Results</h3> The following average values of bone mineral density (BMD) were found: 1.116 g/cm<sup>2</sup> for age-group of 40–49 and 0.942 g/cm<sup>2</sup> for 50–59 years old patients. In comparison with control group (300 healthy women of the same age-groups) we found significantly lower BMD in RA patients (p &lt; 0.05 for the age group of 40–49 and p &lt; 0.001 for age-group of 50–59). Annual rate of bone loss in both control and group of RA patients was also evaluated. In the control group annual loss was 0.57%, and in group of RA patients 1.45% (p &lt; 0.001). In RA patients treated with GC significantly lower BMD in comparison with RA patients not taking these drug was found. <h3>Conclusion</h3> Osteopenia defined as BMD below one standard deviation from the corresponding young adult normal value was found in 26% of RA patients aged 40–49 and in 45% RA patients aged 50–59. In conclusion this study has confirmed that the disease itself, therapy with glucocorticoids and oestrogen deficiency during menopause influence bone loss in RA patients.
The fibrotic response of primary liver spheroids recapitulates in vivo hepatic stellate cell activation
Authors: Inge Mannaerts, Nathalie Eysackers, Elise Anne van Os, Stefaan Verhulst, Tiffany Roosens, Ayla Smout, Andreas Hierlemann, Olivier Frey, Sofia Batista Leite, Leo A. van Grunsven
Journal: Biomaterials (2020)
Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer
Authors: Mitsuro Kanda, Dai Shimizu, Koichi Sawaki, Shunsuke Nakamura, Shinichi Umeda, Takashi Miwa, Haruyoshi Tanaka, Chie Tanaka, Masamichi Hayashi, Yohei Iguchi, Suguru Yamada, Masahisa Katsuno, Yasuhiro Kodera
Journal: Molecular Cancer (2020)

Abstract Background Controlling metastasis is essential for improving the prognosis of patients with gastric cancer (GC). Here, we aimed to identify a molecule required for GC metastasis and to investigate its potential utility as a target for the development of therapeutic antibodies (Abs). Methods Transcriptome and bioinformatics analyses of human GC cell lines identified the neuronal pentraxin receptor ( NPTXR ) as a candidate molecule. NPTXR function was probed by modulating its expression in GC cells and assessing the effects on intracellular signaling and malignant behaviors in vitro and in mouse xenograft models. We also generated anti-NPTXR Abs and Nptxr −/− mice, and assessed the clinical significance of NPTXR expression in GC specimens. Results NPTXR mRNA expression in clinical specimens was associated with disease progression and was significantly higher in tissues from GC patients with distant metastasis compared with those without. NPTXR regulated expression of genes involved in metastatic behaviors as well as activation of the PI3K–AKT–mTOR, FAK–JNK, and YAP signaling pathways. NPTXR silencing promoted caspase-mediated apoptosis and attenuated GC cell proliferation, cell cycle progression, migration, invasion, adhesion, stem cell-like properties, and resistance to 5-fluorouracil in vitro, and also inhibited the tumorigenicity of GC cells in vivo. Anti- NPTXR Abs inhibited GC peritoneal metastasis in mice. Nptxr −/− mice showed no abnormalities in reproduction, development, metabolism, or motor function. Conclusions NPTXR plays an essential role in controlling the malignant behavior of GC cells in vitro and in vivo. NPTXR -targeting Abs may thus have utility as novel diagnostic tools and/or treatment modalities for GC.
Evidence for stress-induced myocardial stunning as assessed by gated single-photon emission computed tomography
Authors: H Tanaka, Taishiro Chikamori, Satoshi Hida, Yuko Igarashi, Manabu Miyagi, Yasuhiro Usui, Tsuguhisa Hatano, Kenichi Hirose, Chie Shiba, Yuka Ohtaki, Akira Yamashina
Journal: Circulation (2008)
Diabetes as a Risk Factor for Poor Early Outcomes in Patients Hospitalized With COVID-19
Authors: Jacqueline Seiglie, Jesse Platt, Sara Jane Cromer, Bridget Bunda, Andrea S. Foulkes, Ingrid V. Bassett, John Hsu, James B. Meigs, Aaron Leong, Melissa S. Putman, Virginia A. Triant, Deborah J. Wexler, Jennifer Manne-Goehler
Journal: Diabetes Care (2020)

Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19.
Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment
Authors: Xiaojie Chen, Jiafeng Zou, Ke Zhang, Jingjing Zhu, Yue Zhang, Zhihong Zhu, Hongyue Zheng, Fanzhu Li, Ji-Gang Piao
Journal: Acta Pharmaceutica Sinica B (2020)

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving "on-demand" drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed in vitro experiments, it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic. Consequently, GNP-DOX/ICG could efficiently suppress the growth of 4T1 tumor in vivo. In conclusion, this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.
Response to: ‘Exaggerated neutrophil extracellular trap formation in Kawasaki disease: a key phenomenon behind the outbreak in western countries?’ by Yamashita<i>et al</i>
Authors: Marie Pouletty, Glory Dingulu, Naim Ouldali, Olivier Corseri, Camille Ducrocq, Ulrich Meinzer, Albert Faye, Caroline Galeotti, Isabelle Melki
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the correspondence from Mizugishi et al .1 The pathophysiology of Kawasaki disease (KD) and more recently Kawasaki-like paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) or Kawa-COVID-19 remains largely unknown, even if the infectious trigger by SARS-CoV-2 in the prior weeks seems to be a key feature.2 Furthermore, it is still uncertain whether Kawasaki-like PIMS-TS can be considered as the same entity as KD or if it should be individualised as a novel distinct condition, as it may have been suggested with several significant clinical and biological differences between classical KD and Kawa-COVID-19.3

Mizugishi et al 1 speculate that KD and Kawa-COVID-19 share a common pathophysiology through excessive neutrophil extracellular trap (NET) formation. Similar to Yoshida et al ,4 Mizugishi et al 1 showed increased NET formation in KD patients sera. Through a KD mouse model, the authors describe that severe vasculitis (in the aorta and coronary arteries) was associated with infiltrative neutrophils. Those neutrophils were primed to produce NETs through the PAD4 pathway and seemed to produce a specific type of NET formation (enriched in citrullinated histones). Excessive NET formation was also described in sera of adult COVID-19 patients with endothelial injuries. Kawa-COVID-19 could represent a severe form of KD triggered by an exaggerated NET formation induced by SARS-CoV-2.

NETs are an important first-line defence mechanism against bacterial, viral, fungal and parasitic infections, but they have been also suspected to play a role in autoimmune diseases such as systemic lupus erythematosus (SLE) or antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) for example.5 Van Dam et al 5 showed that NET formation is involved in the pathophysiology of two clinically and pathologically distinct forms …
Is it too early to condemn early sport specialisation?
Authors: Joseph Baker, Alexandra Mosher, Jessica Fraser-Thomas
Journal: British Journal of Sports Medicine (2020)

There has been a rapid and substantial increase in scholarly and public discourse regarding the perceived consequences of single sport specialisation during periods of early development. Since 2017, there have been three systematic reviews and 10 narrative reviews/editorials about the negative implications of specialisation in sport. A 2009 review in this area asked ‘what do we know about early sport specialisation’ and concluded ‘not much’.1 In this editorial, we argue things have not changed much in the intervening decade, despite the considerable increase in rhetoric around this subject.

Much of the discussion in this area positions specialisation as binary, either you are specialising or you are not, despite clear evidence that the patterns of early engagement in youth sport are more diverse.2 Usually, discussions focus on ‘engagement in a single sport to the exclusion of all others’ without acknowledging the limits of this simple distinction. For instance, if there is a dose–response relationship between the quantity and/or type of exposure and likelihood of positive outcomes, does the number …
Basildon hospital: “Dysfunctional” working between staff in maternity care led to safety risks
Authors: Clare Dyer
Journal: BMJ (2020)

Basildon University Hospital has been rated inadequate for its maternity services and given a formal warning after an anonymous whistleblower alerted the Care Quality Commission (CQC) to six serious incidents.1

The CQC carried out a surprise inspection after learning of the cluster of six cases in March and April 2020 in which babies were born in poor condition and transferred out for cooling therapy. The procedure is given to newborn babies with brain injury caused by oxygen shortage during birth.

The inspection in June found that concerns raised by the last inspection in February 2019, after the …
Abstract 13914: Artificial Intelligence Finds Myocardial Infaction in ECG More Accurately Than Cardiologists
Authors: Hisaki Makimoto, Moritz Hoeckmann, Shqipe Gerguri, Lukas Clasen, Jan Schmidt, Athena Assadi-Schmidt, Alexandru Bejinariu, Patrick Mueller, David Gloeckner, Stephan Angendohr, Christoph Brinkmeyer, Malte Kelm
Journal: Circulation (2019)

Introduction: Artificial intelligence (AI) based on neural networks (NN) is remarkably developing also in medical field. It has developed particularly in the image analysis in radiology, and still ...
Hydrogen sulfide-modified extracellular vesicles from mesenchymal stem cells for treatment of hypoxic-ischemic brain injury
Authors: Xili Chu, Dexiang Liu, Tingting Li, HongFei Ke, Danqing Xin, Shuhan Wang, Ying Cao, Hao Xue, Zhen Wang
Journal: Journal of Controlled Release (2020)
Can we distinguishing HHV-6B encephalitis/myelitis in the early phase of cord blood transplantation by next-generation sequencing of peripheral blood?
Authors: Ping Qiang, Kaidi Song, Baoling Tang, Lan Shi, Xiaoyu Zhu, Wen Yao, Lei Zhang, Weibo Zhu, Liangquan Geng, Xingbing Wang, Xin Liu, Huilan Liu, Zimin Sun, Xiaoling Ma
Journal: Journal of Infection (2020)
Abstract 6662: Effects of tumor treating fields (TTFields) on dendritic cells functionality
Authors: Tali Voloshin, Shiri Davidi, Noa Kaynan, Rosa Schneiderman, Alexandra Volodin, Moshe Giladi, Uri Weinberg, Yoram Palti
Journal: Cancer Research (2020)

Abstract Introduction Tumor Treating Fields (TTFields) are a clinically applied anti-neoplastic treatment modality delivered via noninvasive application of low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields. In this study we evaluated the effects of in vitro TTFields application on dendritic cell (DC) properties that include maturation, phagocytosis, and migration. Methods Bone marrow cells were flushed from the femurs and tibias of 5-7 week old C57BL/6 mice to generate bone marrow-derived DCs. For the DC maturation assay, TTFields treated cancer cells were added at a ratio of 1:1 for 24 h. DC maturation was analyzed using flow cytometry to assess surface expression of major histocompatibility complex class II (MHC II), CD40, and CD80 activation markers. For the phagocytosis assay, CellTrackerTM Deep Red Dye, pre-stained TTFields treated cancer cells were added at a ratio of 1:1 for 2h and phagocytosis by DCs was evaluated using flow cytometry. DC migration assays were performed using a modified Matrigel coated Boyden chamber either with or without C-C Motif Chemokine Ligand 19 (CCL19), utilized as a chemoattractant. Results TTFields treated cancer cells were effectively phagocytosed by DCs, while untreated control cells did not show similar outcomes. In addition, activation markers were found to be upregulated in DCs that were co-cultured with TTFields treated cells. This up-regulation was observed for all the costimulatory molecules analyzed. DC migration assays, showed no significant difference in migration rates between untreated and TTFields treated DCs, with or without the chemoattractant CCL19. Conclusions These in vitro results indicate that TTFields treated cancer cells promote DC elicited phagocytosis and DC maturation. Moreover, in contrast to previous studies reporting that TTFields show an inhibitory effect on cancer cell migration, we demonstrate that TTFields do not impair the migratory properties of DCs. Citation Format: Tali Voloshin, Shiri Davidi, Noa Kaynan, Rosa Schneiderman, Alexandra Volodin, Moshe Giladi, Uri Weinberg, Yoram Palti. Effects of tumor treating fields (TTFields) on dendritic cells functionality [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6662.
Young Male With Incessantly Alternating Tachyarrhythmias
Authors: Ping-Huang Tsai, Yuan Hung, Pauling Chu
Journal: Circulation (2020)

ECG CHALLENGEA 19-year-old male patient with history of depression presented to the emergency department with unconsciousness and seizure-like activity after a suicide attempt involving ingestion of 40 g anhydrous caffeine powder.He did not have arrhythmia, syncope, epilepsy-like symptoms, aborted cardiac arrest, or sudden cardiac death before this event.None of his relatives had syncope or sudden cardiac death.Physical examination at presentation revealed extreme tachycardia of 193 beats per minute, blood pressure of 152/72 mm Hg, temperature of 35.8°C (96.44°F), and respiration of 35 breaths per minute.Laboratory testing revealed a serum potassium level of 2.3 mmol/L, creatine kinase level of 1655 U/L, serum lactate level of 7.2 mmol/L, and a serum pH of 7.182.Serum free calcium and magnesium levels were normal.No pericardial effusion or collapse of the left and right atria in end diastole was revealed by transthoracic echocardiography.A 12-lead ECG was recorded (Figure 1).What is the arrhythmia displayed in Figure 1, and how should the patient be managed?Please turn the page to read the diagnosis.
Abstract 17163: Rise in Primary Non-cardiac Diagnoses Among Cardiac Intensive Care Unit Patients Over Time in the United States
Authors: Shashank S Sinha, Michael W Sjoding, Devraj Sukul, Hallie C Prescott, Theodore J Iwashyna, Hitinder S Gurm, Colin R Cooke, Brahmajee K Nallamothu
Journal: Circulation (2016)

Introduction: Reports suggest an increasing prevalence of patients with primary non-cardiac diagnoses in the cardiac intensive care unit (CICU). However, national data on the characteristics of CIC...
The relationship between the responses to prior systemic therapies and the efficacy of subsequent pemetrexed (Pem) therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: J. Sun, D. Oh, S. Lee, D. Kim, S. Im, T. Kim, J. Lee, Y. Kim, D. S. Heo, Y. Bang
Journal: Journal of Clinical Oncology (2009)

8061 Background: Pem has been used for pts with previously treated advanced NSCLC. We tried to examine whether the response to prior systemic therapy regimen could predict the efficacy of subsequent Pem therapy. Methods: The medical record of clinical stage IIIB or IV NSCLC pts who received Pem as the second-line or further-line treatment were analyzed retrospectively. Prior systemic therapies were divided into 4 types [gemcitabine based (G), paclitaxel based (P), docetaxel based (D), and EGFR tyrosine kinase inhibitors (I)]. Along with that, patients were classified into two response groups, either responders (partial responses or stable disease for 4 months or more) or non-responders to each type of the prior therapy. Response rate (RR) and progression free survival (PFS) for Pem therapy were analyzed according to the response groups for each type of prior therapies. Results: A total of 247 pts received Pem therapy, and their median PFS was 2.3 months. The number of pts who previously received G, P, D and I, was 159, 120, 110, and 139, respectively. The RR for Pem was higher in responders to G therapy than in non-responders to G (15.0% vs 4.3%, p = 0.02). In addition, median PFS after Pem therapy was longer in responders to G therapy than in non-responders (3.0 vs 1.7 months, p = 0.007). However, the responses to prior P, D, I therapies had no impact on the efficacy of subsequent Pem therapy. By univariate analyses, the variables of the responders to G therapy, female, never-smoker, ECOG performance status 0–1 were good predictive factors for Pem therapy in terms of PFS. By multivariate analysis, only the responders to G therapy had a statistical significance (Hazard ratio = 0.55; 95% CI, 0.37–0.82). Conclusions: The response to the prior gemcitabine based therapy was a predictive factor for subsequent pemetrexed therapy for advanced NSCLC. No significant financial relationships to disclose.
Coronavirus disease outbreak: a simple infection prevention measure using a surgical mask during endoscopy
Authors: Hirotsugu Maruyama, Akira Higashimori, Kei Yamamoto, Akinobu Nakata, Yuki Ishikawa-Kakiya, Masafumi Yamamura, Yasuhiro Fujiwara
Journal: Endoscopy (2020)

Coronavirus disease (COVID-19) transmission occurs primarily through direct contact or air droplets [1] [2], and endoscopic procedures are high risk. In this era of "with COVID-19," establishing simple infection prevention measures within an endoscopy department to protect both patients and personnel is strongly recommended. Hence, we proposed a simple method using a modified surgical mask. We made a hole (10 mm diameter) in the center of a surgical mask ([Fig. 1]). Next, simulated endoscopy was performed with and without the modified surgical mask using a mannequin with the mouthpiece in place ([Video 1]).