tbuckley/cabot-search huggingface dataset:
Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification
Authors: Jie Shen, Bo Chen, Xinyun Zhai, Wei Qiao, Shuilin Wu, Xuanyong Liu, Ying Zhao, Changshun Ruan, Haobo Pan, Paul K. Chu, Kenneth M.C. Cheung, Kelvin W.K. Yeung
Journal: Bioactive Materials (2020)

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg2+) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg2+ content niche (~4.11 mM) led to superior bone regeneration, while Mg2+-free and strong Mg2+ content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg2+ cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.
Efficacy of VDT PACE-like Regimens in Treatment of Relapsed/Refractory Multiple Myeloma—a Single Center Experience
Authors: Arjun Lakshman, Preet Paul Singh, S. Vincent Rajkumar, Martha Q Lacy, Morie A. Gertz, Francis K Buadi, David Dingli, Angela Dispenzieri, Lisa Hwa, Amie Fonder, Miriam Hobbs, Steven Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Ronald S. Go, Yi Lin, Wilson I Gonsalves, Prashant Kapoor, Taxiarchis Kourelis, Rahma Warsame, Robert A Kyle, Shaji K Kumar
Journal: Blood (2017)
鉄欠乏性貧血における静脈内フェルモキシトール対第二鉄カルボキシマルトの比較安全性:無作為化試験【JST・京大機械翻訳】 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Adkinson N. Franklin, E Strauss William, C Macdougall Iain, E Bernard Kristine, Auerbach Michael, F Kaper Robert, M Chertow Glenn, S Krop Julie
Journal: American Journal of Hematology (2018)
Corrigendum to “Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics” [Biomaterials 192 (2019) 551–559]
Authors: Svenja Siemer, Dana Westmeier, Matthias Barz, Jonas Eckrich, Désirée Wünsch, Christof Seckert, Christian Thyssen, Oliver Schilling, Mike Hasenberg, Chengfang Pang, Dominic Docter, Shirley K. Knauer, Roland H. Stauber, Sebastian Strieth
Journal: Biomaterials (2020)
Cyclin K interacts with β-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer
Authors: Guojun Yao, Jing Tang, Xijie Yang, Ye Zhao, Rui Zhou, Rui Meng, Sheng Zhang, Xiaorong Dong, Tao Zhang, Kunyu Yang, Gang Wu, Shuangbing Xu
Journal: Theranostics (2020)

Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance. Methods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. Protein-protein interaction was assessed by immunoprecipitation and GST pull-down assays. Results: We report that Cyclin K is frequently overexpressed and correlates with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion results in reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and promotes the stabilization of β-catenin protein, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector that mediates the biological functions of Cyclin K in lung cancer. Conclusions: These findings suggest that Cyclin K positively modulates the β-catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating that Cyclin K may represent a novel attractive biomarker for lung cancer radiotherapy.
Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas
Authors: Elizabeth Lenkiewicz, Smriti Malasi, Tara L. Hogenson, Luis F. Flores, Whitney Barham, William J. Phillips, Alexander S. Roesler, Kendall R. Chambers, Nirakar Rajbhandari, Akimasa Hayashi, Corina E. Antal, Michael Downes, Paul M. Grandgenett, Michael A. Hollingsworth, Derek Cridebring, Yuning Xiong, Jeong-Heon Lee, Zhenqing Ye, Huihuang Yan, Matthew C. Hernandez, Jennifer L. Leiting, Ronald M. Evans, Tamas Ordog, Mark J. Truty, Mitesh J. Borad, Tannishtha Reya, Daniel D. Von Hoff, Martin E. Fernandez-Zapico, Michael T. Barrett
Journal: Cancer Research (2020)

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in
Abstract #3867: Degradation of the anti-apoptotic protein Mcl-1 correlates with mitotic cell death in response to the novel KSP inhibitor ARRY-520.
Authors: Brian Tunquist, Duncan Walker
Journal: Cancer Research (2009)

Mitotic kinesin inhibitors are promising cancer drug candidates. Inhibition of the mitotic kinesin KSP/Eg5 prevents the formation of a bipolar spindle and causes a prolonged arrest of the cell cycle in M phase of both normal and cancer cells. Cells respond to mitotic arrest in several ways. Firstly, apoptotic cell death can be triggered while the cell is arrested in mitosis. Alternatively, the mitotic checkpoint can fail (mitotic slippage) and the cell can enter an interphase state. In some cases, the cell can survive mitotic slippage, while in others this leads to cell death. We have studied the fate of four multiple myeloma cell lines (RPMI8226, JJN3, U266 and H929) in response to the novel KSP inhibitor ARRY-520. Upon continuous treatment with ARRY-520, the majority (3/4) of cell lines undergo a sustained mitotic arrest, with the resulting onset of apoptosis (as measured by caspase 3/7 activation and PARP cleavage) occurring within 24-30h while the cell remains in M-phase. The remaining cell line (H929) is temporally refractory to ARRY-520 treatment, initiating mitotic slippage and subsequently showing a peak in apoptotic markers after 72-80h of treatment, while the majority of cells are in interphase. Biochemical analysis of these lines suggests that the loss of the key anti-apoptotic protein MCL-1 correlates with apoptosis in mitotic cells. MCL-1 is a typically short-lived member of the BCL-2 family of anti-apoptotic proteins, and is a key survival protein in hematological malignancies and normal hematopoietic cells. Of interest in H929 cells, MCL-1 remains stable during the mitotic arrest and cells subsequently slip and enter interphase, consistent with the failure of these cells to trigger cell death in mitosis. These data suggest that the loss of survival signaling in mitosis is consistent with the onset of apoptosis during mitosis, and persistent anti-apoptotic signals during mitosis enables the cell to survive until mitotic slippage and entry into interphase. These results indicate that variation in sensitivity to KSP inhibition is governed by a delicate balance between anti-apoptotic proteins and spindle checkpoint activity. Cells that rely on short-lived anti-apoptotic proteins for survival during mitotic arrest are more likely to undergo a rapid onset of apoptosis in response to novel mitotic inhibitors such as KSP inhibitors. These data would suggest that hematological malignancies, which frequently rely on MCL-1, are good candidates for treatment with KSP inhibitors. ARRY-520 is currently in clinical trials in both AML and multiple myeloma.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3867.
Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study
Authors: Li Zhang, Li Meng, Bingcheng Liu, Yanli Zhang, Huanling Zhu, Jiuwei Cui, Aining Sun, Yu Hu, Jie Jin, Hao Jiang, Xi Zhang, Yan Li, Li Liu, Wanggang Zhang, Xiaoli Liu, Jian Gu, Jianhui Qiao, Guifang Ouyang, Xin Liu, Jianmin Luo, Ming Jiang, Xiaobao Xie, Jianyong Li, Chunting Zhao, Mei Zhang, Tonghua Yang, Jianxiang Wang
Journal: Clinical Cancer Research (2020)

Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP).In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups.The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm.Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644.See related commentary by Müller, p. 3.
Extensive Tumor Thrombosis of Portal Venous System Demonstrated on 68Ga-DOTATATE and 68Ga-NODAGA-LM3 PET/CT in a Patient With Well-Differentiated Neuroendocrine Tumor
Authors: Wenjia Zhu, Yuejuan Cheng, Ning Ding, Li Huo
Journal: Clinical Nuclear Medicine (2020)

We present a case with a pancreatic neuroendocrine tumor and extensive tumor thrombosis in portal venous system. The tumor was first identified on contrast-enhanced CT and later confirmed using Ga-DOTATATE and Ga-NODAGA-LM3 PET/CT. Both tracers demonstrated similar pattern with higher tumor affinity and tumor-to-background ratio using Ga-NODAGA-LM3.
'The virtual consultation': A COVID-19 necessity, but how does it work in practice?
Authors: M. Verma, R. Barlow, A. Maguire, D. Choi, Q. Minh Chu, M. Gilaberte, S. Rajpopat, A. Ekeowa-Anderson
Journal: British Journal of Dermatology (2020)

As a result of the COVID-19 pandemic, routine dermatology appointments in our trust were suspended from March 2020  In response, we later introduced virtual telephone and video consultations using accuRx for new routine dermatology referrals  Although supported by guidance from the British Association of Dermatologists, there is a relative lack of evidence for use of the virtual consultation (VC) in routine dermatology  We therefore sought to assess its practicality and effectiveness, and reflect on the experience  We undertook a review of 200 consecutive routine new patient VCs by an experienced general practitioner (GP) associate specialist during lockdown  Patients were allocated a specific time for the consultation  The outcomes, diagnosis, type of dermatology presentation and the use of video were recorded  This was compared with 200 routine new patients seen face to face (F2F) by the same GP associate specialist in 2019  Both groups showed similar demographics (57% females, 43% males, mean age 52 1 years)  Owing to the COVID-19 pandemic, average waiting times were significantly longer for VCs (33 6 weeks vs  15 5 weeks;P < 0 001)  Did not attend/answer rates were very similar (VC 9 5%, F2F 10 5%)  AccuRx video was used successfully for 32 5% of the patients in the VC group  Of the remaining VC patients, 30 5% did not require video, 23 5% said it was not possible (no mobile phone, lack of technical experience, inappropriate location, patient refusal) and 3 5% failed  The 'not possible' group were older, with a mean age of 69 2 years (P < 0 001)  Dermatological presentations were similar in both groups (49% lesions, 27% inflammatory rashes, 11% other rashes, 13% miscellaneous)  Fewer patients were discharged from VC after the first consultation (VC 15%, F2F 26%) and fewer referred for minor surgery (VC 22%, F2FC 27%)  More VC patients were referred for routine follow-up (VC 37%, F2FC 16%)  More lesions were followed-up routinely after VC (VC 39%, F2F 7%)  Additionally, fewer patients with lesions were discharged after VC (VC 7%, F2F 37%)  VC may have a role in the management of the long referral waiting times generated by COVID-19 in the future  We conclude that VC is a satisfactory method of assessing some new routine patient referrals but does create more routine follow-up work particularly for patients with lesions  VC requires a committed and organized practitioner, has advantages for the patient, a potential triage role and possible cost savings for the National Health Service  We recommend seeking patient feedback concerning the VC process and analysing final diagnosis outcomes in both groups
Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial
Authors: Leah M. Wilson, Peter G. Jacobs, Katrina L. Ramsey, Navid Resalat, Ravi Reddy, Deborah Branigan, Joseph Leitschuh, Virginia Gabo, Florian Guillot, Brian Senf, Joseph El Youssef, Isabelle Isa Kristin Steineck, Nichole S. Tyler, Jessica R. Castle
Journal: Diabetes Care (2020)

OBJECTIVE To assess the efficacy and feasibility of a dual-hormone (DH) closed-loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed-loop system and a predictive low glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: 1) dual-hormone (DH) closed-loop control, 2) insulin-only single-hormone (SH) closed-loop control, and 3) PLGS system. The primary end point was percentage time in hypoglycemia (&amp;lt;70 mg/dL) from the start of in-clinic aerobic exercise (45 min at 60% VO2max) to 4 h after. RESULTS DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [interquartile range 0.0–4.2], SH 8.3% [0.0–12.5], P = 0.025). There was an increased time in hyperglycemia (&amp;gt;180 mg/dL) during and after exercise for DH versus SH (20.8% DH vs. 6.3% SH, P = 0.038). Mean glucose during the entire study duration was DH, 159.2; SH, 151.6; and PLGS, 163.6 mg/dL. Across the entire study duration, DH resulted in 7.5% more time in target range (70–180 mg/dL) compared with the PLGS system (71.0% vs. 63.4%, P = 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P = 0.044) and 34.7% for PLGS (P = 0.140). Four participants experienced nausea related to glucagon, leading three to withdraw from the study. CONCLUSIONS The glucagon formulation demonstrated feasibility in a closed-loop system. The DH system reduced hypoglycemia during and after exercise, with some increase in hyperglycemia.
Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Richard J. Massey, Phoi P. Diep, Ellen Ruud, Marta M. Burman, Anette B. Kvaslerud, Lorentz Brinch, Svend Aakhus, Lars L. Gullestad, Jan O. Beitnes
Journal: JACC CardioOncology (2020)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a potentially curative therapy for malignant and nonmalignant diseases, is being increasingly used in younger patients. Although allo-HSCT survivors have an established increased risk of cardiovascular disease, there is limited knowledge of the long-term effects on cardiac function in survivors.The purpose of this study was to describe left ventricular (LV) systolic function in long-term allo-HSCT survivors treated in childhood, adolescence, or early adulthood.Our cross-sectional cohort study included 104 patients (56% women), age 18 ± 10 years at time allo-HSCT with 17 ± 6 years of follow-up. Echocardiography included 2-dimensional (2D) and 3-dimensional (3D) analyses and speckle tracking imaging. In total, 55 healthy control subjects with a similar age, sex, and body mass index were used for comparison. Left ventricular systolic dysfunction (LVSD) was defined as reduced 2D left ventricular ejection fraction (LVEF) of <52% in men and <54% in women, and/or a reduced global longitudinal strain (GLS) of ≥-17%. Multivariable linear regression was used to determine independent predictors of 2D-LVEF and GLS.Allo-HSCT survivors had significantly reduced LV systolic function compared with control subjects: 2D-LVEF (55.2 ± 5.8% vs. 59.0 ± 2.9%; p < 0.001), 3D LVEF (54.0 ± 5.1% vs. 57.6 ± 2.7%; p < 0.001), and GLS (-17.5 ± 2.2% vs. -19.8 ± 1.4%; p < 0.001). LVSD was found in 44.2%, of whom 28.3% were symptomatic. Clinical factors independently associated with 2D-LVEF and/or GLS included age, anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension. In the 45% of survivors pre-treated with anthracyclines, the effect of anthracyclines on 2D-LVEF and GLS was dose-dependent.LVSD is common in long-term survivors of allo-HSCT treated in their youth. Pre-HSCT therapies with anthracyclines, age, heart rate, hypertension, and graft versus host disease are associated with measures of LV function.
From intestinal dysbiosis to alcohol-associated liver disease
Authors: Beatriz Garcia Mendes, Bernd Schnabl
Journal: Clinical and Molecular Hepatology (2020)

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.
Bone marrow stromal cell-mediated degradation of CD20 leads to primary rituximab resistance in mantle cell lymphoma
Authors: Yoshiaki Kuroda, Akiko Yashima-Abo, Daisuke Koyama, Jiro Kikuchi, Shigehisa Mori, Shigeki Ito, Yusuke Furukawa
Journal: Leukemia (2020)
Comparison of the long-term efficacy between tenofovir and entecavir in chronic hepatitis B patients
Authors: Kecheng Liu, Peng Peng, Fuqing Cai, Jiean Huang
Journal: Gut (2020)

We read with interest the work by Su et al concerning whether entecavir and tenofovir are equally effective for chronic hepatitis B patients.1 They concluded that there was no significant difference between tenofovir and entecavir in reducing the risk of death/liver transplant or hepatocellular carcinoma (HCC). Their findings have significant clinical implications, but we believe that the study design and results should be discussed in more detail.

In the research of Su et al , Cox proportional hazards (PH) model was conducted to identify the relationship between antiviral regimen and clinical outcomes. After correcting for baseline imbalance by an inverse probability weighting method, no difference in reducing HCC or death/liver transplant risks between the two drugs was found, with …
Policies Among US Pediatricians for Dismissing Patients for Delaying or Refusing Vaccination
Authors: Sean T. O’Leary, Jessica R. Cataldi, Megan C. Lindley, Brenda L. Beaty, Laura P. Hurley, Lori A. Crane, Allison Kempe
Journal: JAMA (2020)

This survey study assesses US pediatrician practices and office policies in response to parents who either refuse primary vaccinations or request to spread out individual vaccines in the primary series.