tbuckley/cabot-search huggingface dataset:
Dynamic genomic instability modulation by neoadjuvant therapy in early breast cancer (GEICAM/2006-03_2006-14).
Authors: Emilio Alba, Oscar M Rueda, Ana Lluch, Joan Albanell, Suet-Feung Chin, Jose Ignacio Chacon, Lourdes Calvo, Juan De La Haba, Begona Bermejo, Nuria Ribelles, Pedro Sanchez Rovira, Arrate Plazaola, Agusti Barnadas, Eva Maria Carrasco, Jesus Herranz, Massimo Chiesa, Rosalia Caballero, Angela Santonja Climent, Federico Rojo, Carlos Caldas
Journal: Journal of Clinical Oncology (2018)

592 Background: Genomic instability (GI) drives tumor development, generates selective clonal competence and enhances cancer aggressiveness. Copy Number Alterations (CNAs) data from a cohort of pre- and post-treatment (ttm) breast cancer (BC) tumors from patients (pts) in neoadjuvant trials GEICAM/2006-03 (NCT00432172) and GEICAM/2006-14 (NCT00841828) were used to obtain a GI Index for each sample. We analyzed the variation of GI index induced by therapy and their associations with tumor phenotype. Methods: GEICAM/2006-03 HER2-negative pts were selectively treated according to clinical subtypes: triple negative (TN) pts were treated with standard taxane/anthracycline-based chemotherapy (TA-CT) +/- carboplatin, while luminal patients were randomized to TA-CT vs. hormonotherapy; GEICAM/2006-14 HER2+ pts received TA-CT plus anti-HER2 therapy. Shallow-whole genome Illumina sequencing DNA data from 204 paraffin-BC (100 pre- and 104 post-ttm tumors) were segmented to obtain CNAs. The area under the segmentation curve (sum of segmented mean normalized by CNAs number) was calculated for each sample as index of GI. Differences between GI indexes in pre- and post-ttm samples were analyzed using Wilcoxon test. Results: A significant reduction in GI index was observed after ttm compared to pre-therapy samples (p = 5.1e-07), which was confirmed in a subset of pre/post-therapy paired tumors (N = 39, p = 0.0034). Luminal (61%) tumors revealed a significant decrease in GI index, both in overall population (median GI index: 0.141 pre-ttm vs 0.068 post-ttm, p = 1e-09) and in paired samples (0.126 vs 0.072, p = 0.00013). Similarly, HER2+ (9%) tumors showed a trend towards GI reduction (0.143 vs 0.079, p = 0.085). In contrast, TN (30%) cases presented an increasing trend in GI index in the residual tumor (0.132 pre- vs 0.17 post-ttm, p = 0.68). Conclusions: Our data suggest that GI could be a direct target of neoadjuvant therapy in BC. Treatment seems selectively eliminate tumor cells with higher genomic aberrations in luminal and HER2+ BC, resulting in a reduction of GI index in the residuals tumors. In contrast, according to previous publications, we suggest that GI could be a mechanism of adaptative CT resistance in TNBC. Clinical trial information: GEICAM/2006-03 NCT00432172. GEICAM/2006-14 NCT00841828.
Stretchable Optomechanical Fiber Sensors for Pressure Determination in Compressive Medical Textiles
Authors: Joseph D. Sandt, Marie Moudio, J. Kenji Clark, James Hardin, Christian Argenti, Matthew Carty, Jennifer A. Lewis, Mathias Kolle
Journal: Advanced Healthcare Materials (2018)

Medical textiles are widely used to exert pressure on human tissues during treatment of post-surgical hematoma, burn-related wounds, chronic venous ulceration, and other maladies. However, the inability to dynamically sense and adjust the applied pressure often leads to suboptimal pressure application, prolonging treatment or resulting in poor patient outcomes. Here, a simple strategy for measuring sub-bandage pressure by integrating stretchable optomechanical fibers into elastic bandages is demonstrated. Specifically, these fibers possess an elastomeric photonic multilayer cladding that surrounds an extruded stretchable core filament. They can sustain repetitive strains of over 100%, and respond to deformation with a predictable and reversible color variation. Integrated into elastic textiles, which apply pressure as a function of their strain, these fibers can provide instantaneous and localized pressure feedback. These colorimetric fiber sensors are well suited for medical textiles, athletic apparel, and other smart wearable technologies, especially when repetitive, large deformations are required.
Effectiveness and safety of 0·5% colchicine cream vs. photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratosis and skin field cancerization of the forearms: a randomized controlled trial
Authors: A.C. Miola, E.R. Ferreira, T.R.R. Lima, J.V. Schmitt, L.P.F. Abbade, H.A. Miot
Journal: British Journal of Dermatology (2018)

Skin field cancerization (SFC) is a process that occurs in areas of the skin that have undergone genomic alterations induced by ultraviolet radiation. Actinic keratosis (AK) is a sign of its activity.To evaluate the effectiveness and safety of 0·5% colchicine (COL) cream vs. methyl aminolaevulinate photodynamic therapy (MAL-PDT) in the treatment of AK and SFC.We conducted a randomized, open, intrasubject controlled trial. A total of 36 participants with 3-10 AKs on each forearm were treated with either COL cream (twice daily for 10 days) or a single session of MAL-PDT and were reassessed after 60 days. The clinical evaluation was performed using AK count, forearm photoageing scale (PAS) and AK degree (AKD). Patients underwent central forearm biopsies and histopathological evaluation by keratinocyte intraepithelial neoplasia (KIN) assessment, epithelial atrophy and immunohistochemistry (p53/Ki67).Overall, 50% of patients were male. The mean age was 70·9 years (SD 8·6) and phototypes I and II were predominant (89%). Total clearance was observed in six (17%) forearms treated with COL and seven (19%) forearms treated with MAL-PDT (P = 0·76); partial clearance was observed in 44% of forearms in the COL group and 67% of forearms in the MAL-PDT group (P = 0·07). In both COL and MAL-PDT groups, reductions in PAS (-6% vs. -6%) and AKD (-45% vs. -40%) were observed. KIN normalized in 28% of patients treated with MAL-PDT and 20% of those treated with COL. Epithelial atrophy reduced after treatment (P < 0·01). Expression levels of Ki67 and p53 were also assessed. Mild or moderate adverse effects were similar for both groups.COL 0·5% cream and MAL-PDT are safe and effective for treating SFC.
Overall survival (OS) update of the double-blind placebo (PBO)-controlled randomized phase 2 LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for locally advanced/metastatic triple-negative breast cancer (mTNBC).
Authors: Rebecca Dent, Seock-Ah Im, Marc Espie, Sibel Blau, Antoinette R. Tan, Steven J. Isakoff, Mafalda Oliveira, Cristina Saura, Matthew Wongchenko, Amy V. Kapp, Wai Y. Chan, Stina M. Singel, Daniel J. Maslyar, Jose Baselga, Sung-Bae Kim
Journal: Journal of Clinical Oncology (2018)

1008 Background: In LOTUS (NCT02162719), adding the oral AKT inhibitor IPAT to first-line PAC for mTNBC improved progression-free survival (PFS; primary endpoint) [Kim, Lancet Oncol 2017]. The stratified PFS hazard ratio (HR) in the intent-to-treat (ITT) population (n = 124) was 0.60 (95% CI 0.37–0.98; p = 0.037; median PFS 6.2 vs 4.9 months with IPAT vs PBO, respectively). In prespecified analyses of patients (pts) with PIK3CA/AKT1/PTEN-altered tumors, the unstratified PFS HR was 0.44 (95% CI 0.20–0.99; median 9.0 vs 4.9 months). We now report updated OS results in the ITT population after OS events in ~50% of pts. OS results in the PIK3CA/AKT1/PTEN-altered subgroup are immature. Methods: Eligible pts had measurable inoperable mTNBC previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval (6–12 months vs > 12 months vs not applicable) and tumor IHC PTEN status, and randomized 1:1 to PAC 80 mg/m2 (d1, 8, & 15) with either IPAT 400 mg or PBO (d1–21) q28d until progression or unacceptable toxicity. OS was a prespecified secondary endpoint. Results: The table shows results after 23 months' follow-up (data cutoff 26 July, 2017). No new safety signals were seen. Conclusions: The previously observed PFS improvement with IPAT was followed by a trend toward improved OS (~5-month difference in the medians) at the updated OS analysis. Post-progression therapy was similar. These findings support further evaluation of first-line IPAT + PAC for mTNBC in the ongoing IPATunity130 (NCT03337724) randomized phase 3 trial. Final OS results from LOTUS are expected in 2019. Clinical trial information: NCT02162719.Parameter IPAT + PAC (n = 62) PBO + PAC (n = 62) OS events, n (%) 33 (53) 35 (56) Median OS, months (95% CI) 23.1 (18.6–28.1) 18.4 (15.1–29.1) OS hazard ratio (95% CI) Stratified: 0.62 (0.37–1.05) Unstratified: 0.77 (0.48–1.25) 1-year OS rate, % (95% CI) 83 (73–93) 70 (58–81) Post-progression systemic anti-cancer therapy, n (%) 47 (76) 55 (89) Immunotherapy 7 (11) 7 (11) Adverse event leading to treatment discontinuation, n (%)a IPAT/PBO 4 (7) 1 (2) PAC 7 (11) 6 (10) an = 61 in IPAT + PAC arm
Abstract 12554: Circulating Eosinophil Count is Associated With Thoracic Aortic Wall Thickness Evaluated by Computed Tomography
Authors: Yoshihiro Takeda, Shu-ichi Fujita, Hideaki Morita, Koichi Sohmiya, Masaaki Hoshiga, Nobukazu Ishizaka
Journal: Circulation (2016)

Background and Purpose: Eosinophil count is known to be increased in various forms of arteritis/aortitis that may potentially lead to vascular wall thickening. We investigated whether circulating eosinophil count is associated with aortic wall thickness. Methods: Subjects who underwent 320 detector-row computer tomography (Toshiba Medical Systems, Tokyo, Japan) to evaluate the coronary artery were enrolled in the study. Aortic wall thickness was measured perpendicularly to the center of the aorta in the axial image. The protruding atheroma was defined as the maximum aortic wall thickness of ≥4 mm with irregular surface. Results: This study included 405 patients (255 men) with mean age 67.6 +/- 10.5 years old. Those patients with aortic wall thickness of ≤2 mm (n=109), 2-2.9 mm (n=179), 3-3.9 mm (n=70), and ≥4 mm (n=47) had eosinophil count (cells/μL) of 120.0, 130.3, 133.2 and 222.4, respectively. Eosinophil count was positively associated with aortic wall thickness (R 2 =0.034, P&lt;0.001), meanwhile, neutrophil, monocyte, basophil and lymphocyte count were not. By multiple regression analysis using eosinophil count and other potential confounders including sex, age, BMI, systolic blood pressure, lipid and glucose profile, and renal function as independent variables, eosinophil count was selected as a factor that had significant association with aortic wall thickness with correlation coefficient of 0.172 (95% confidence interval 0.001-0.003, p&lt;0.0001). In addition, multiple logistic regression analysis using eosinophil count tertile and other atherosclerotic risk factors as independent variables showed that the 2 nd and 3 rd eosinophil count tertile were independently associated with protruding atheroma with an odds ratio of 2.82 (95% confidence interval 1.16-6.80, P=0.022) and 5.75 (95% confidence interval 1.79-18.52, P=0.003). Conclusions: Eosinophil count was associated with thoracic aortic wall thickness. Considering that circulating eosinophil is increased in various immuno-inflammatory aortic disease, histopathologic analyses should be performed to investigate whether there is any causal and resultant relationship underlying this observed link between eosinophil and aortic wall thickening.
Culturally Competent Science
Authors: David C. Chang, Diego B. López, George Molina
Journal: JAMA Surgery (2018)

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Effect of MMP-13 degraded SPARC on type I collagen and its biomarker potential in colorectal cancer.
Authors: Stephanie Nina Kehlet, Henrik Harling, Lars N Jørgensen, Morten A Karsdal, Nicholas Willumsen
Journal: Journal of Clinical Oncology (2018)

717 Background: Increased collagen deposition and remodeling of the extracellular matrix has been shown to play a role in the pathology of gastrointestinal cancer (GC). The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) binds collagens and hereby regulates collagen fibrillogenesis. Matrix metalloproteinase (MMP) mediated cleavage of SPARC, increases the affinity for collagens up to 20-fold. SPARC has been shown to be overexpressed in GC patients and associated with GC cell invasion and metastasis. Increased expression and cleavage of SPARC might therefore be implicated in GC pathology by increasing collagen deposition. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific MMP-13 generated fragment of SPARC - a cleavage site involved in increased collagen affinity. The biomarker potential of this fragment was examined in serum from colorectal cancer (CRC) patients and healthy controls. Moreover, we evaluated the ability of cleaved SPARC to prevent type I collagen degradation in vitro. Methods: A monoclonal antibody was raised against a MMP-13-generated neo-epitope of SPARC and a competitive ELISA assay (SPARC-M) was developed and technically validated. Serum levels were assessed in CRC patients (n=50) and healthy controls (n=30). The ability of cleaved SPARC to prevent collagen degradation was investigated using an ELISA assay measuring type I collagen degradation by MMP-9. Results: SPARC-M was technically robust and specific for SPARC cleaved by MMP-13. The fragment was elevated in CRC patients when compared to healthy controls (p=0.0097). When MMP-13 degraded SPARC was incubated with type I collagen and MMP-9, type I collagen degradation was completely inhibited suggesting that SPARC increases collagen deposition by preventing collagen degradation. Conclusions: SPARC-M was significantly elevated in CRC patients compared to healthy controls suggesting biomarker potential. Biologically, cleaved SPARC may prevent type I collagen degradation hereby leading to a pro-tumorigenic environment. Larger clinical studies are needed to validate the clinical use of this biomarker in GC.
Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy
Authors: Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Journal: Molecular Cancer (2018)

Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease. Clinical studies on some neoplasms, such as glioblastoma, ovarian cancer, and cholangiocarcinoma, have achieved desirable outcome. This review describes the history and evolution of CAR-T, generalizes the structure and preparation of CAR-T, and summarizes the latest advances on CAR-T cell therapy in different tumor types. The last section presents the current challenges and prospects of CAR-T application to provide guidance for subsequent research.
Adherence to aromatase inhibitors (AIs) in Hispanic patients with early stage breast cancer.
Authors: Alexander Philipovskiy, Aleli Campbell, Rosalinda Heydarian, Krysta Lin, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2018)

70 Background: Adherence to Aromatase Inhibitors (AIs) is essential for the effective prevention of breast cancer recurrence. We sought to evaluate adherence to AIs as well as possible factors behind non-adherence in a large American-Mexican border city with predominantly Hispanic population. Methods: After IRB approval, women with Stages I-III breast cancer treated at the Texas Tech breast care center in El Paso, TX were included if they were receiving adjuvant AI therapy. We utilized the validated Morisky Medication Adherence Scale (MMAS-8) to determine AI compliance. In addition, a question to indicate reasons for noncompliance was added. Results: 87 patients were enrolled, median age was 61 years; 78 (90%) were identified as Hispanic. The majority of participants were women of low socioeconomic status 53 (61%) with an annual income of &lt; $15,000. MMAS-8 results showed 35 (40%) patients admitted to forgetting to take their AI pill. Additionally, 71 (82%) of the patients denied forgetting to take the AI pill within the past two weeks. 11 (13%) patients admitted to sometimes having difficulty remembering to take their AI medication, and 74 (85%) stated never or rarely having difficulty remembering to take their AI medication. 50 (57.5%) patients provided a reason why they did not take their AI pill, 35 (40%) cited forgetfulness, 14 (17%) cited other reasons including cost, limited insurance coverage, lack of transportation involved in obtaining the medication and timely prescription refills, and only 1(1%) due to side effects. Conclusions: Non-adherence to AI appears to be prevalent among Hispanic patients with breast cancer. Main causes of noncompliance are forgetfulness and financial reasons. Healthcare providers could reinforce educating patients about the importance of compliance. Financial assistance may also be helpful in improving AI compliance. Clinical trial information: NCT03144037.
Safe staffing legislation will be introduced in Scotland
Authors: Bryan Christie
Journal: BMJ (2018)

The health service in Scotland will be required by law to ensure that safe staffing levels are in force wherever care is provided.

The Scottish government has published the Health and Care (Staffing) Scotland Bill, which will place a legal requirement on NHS boards and care services to ensure that appropriate numbers of suitably trained staff are in place at all times.

It follows the lead set in 2016 by Wales, which became the first country in Europe to introduce safe staffing levels for nurses. The Scottish bill applies to all NHS staff and will increase pressure on the rest of the UK …
Identification of galectin-3 as an autoantigen in patients with IgG4-related disease
Authors: Cory A. Perugino, Sultan B. AlSalem, Hamid Mattoo, Emanuel Della-Torre, Vinay Mahajan, Gayathri Ganesh, Hugues Allard-Chamard, Zachary Wallace, Sydney B. Montesi, Johannes Kreuzer, Wilhelm Haas, John H. Stone, Shiv Pillai
Journal: Journal of Allergy and Clinical Immunology (2018)
New tests, new tools: mobile and connected technologies in advancing psychiatric diagnosis
Authors: Laura Weiss Roberts, Steven Chan, John Torous
Journal: npj Digital Medicine (2017)

Mental health is an area of growing interest in the digital health space. Mobile and connected technologies offer new tools that can potentially aid in both the diagnostic and interventional aspects of psychiatric care. To understand the potential of these digital tools in psychiatry, this paper offers an overview of the development, current research, clinical use cases, and next steps necessary to realize the potential of digital health in mental health. Focusing on smartphones' and wearable sensors' ability to advance clinical data collection via multiple domains: self-report, behavioral, and physiological, we explore opportunities and challenges in translating these technologies into clinical care tools that can advance how we understand and approach mental illness.
Decitabine demonstrates antileukemic activity in B cell precursor acute lymphoblastic leukemia with MLL rearrangements
Authors: C. Roolf, A. Richter, C. Konkolefski, G. Knuebel, A. Sekora, S. Krohn, J. Stenzel, B. J. Krause, B. Vollmar, H. Murua Escobar, C. Junghanss
Journal: Journal of Hematology & Oncology (2018)

Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias.Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL. Further, efficacy of HMA and concomitant application of cytostatic drugs (cytarabine and doxorubicin) were evaluated on established SEM and RS4;11 cell lines. In addition, promising approaches were studied on BCP-ALL cell line- and patient-derived xenograft models.In general, DEC effects were stronger compared to AZA on MLL-positive BCP-ALL cells. DEC significantly reduced proliferation by induction of cell cycle arrest in G0/G1 phase and apoptosis. Most sensitive to HMA were SEM cells which are characterized by a fast cell doubling time. The combination of low-dose HMA and conventional cytostatic agents revealed a heterogeneous response pattern. The strongest antiproliferative effects were observed when ALL cells were simultaneously exposed to HMA and cytostatic drugs. Most potent synergistic effects of HMA were induced with cytarabine. Finally, the therapeutic potential of DEC was evaluated on BCP-ALL xenograft models. DEC significantly delayed leukemic proliferation in xenograft models as demonstrated longitudinally by non-invasive bioluminescence as well as 18F-FDG-PET/CT imaging. Unexpectedly, in vivo concomitant application of DEC and cytarabine did not enhance the antiproliferative effect compared to DEC monotherapy.Our data reveal that DEC is active in MLL-positive BCP-ALL and warrant clinical evaluation.