tbuckley/cabot-search huggingface dataset:
AB0899 TREATMENT STATUS OF PATIENTS WITH GLUCOCORTICOID-INDUCED OSTEOPOROSIS IN THE AKITA ORTHOPEDIC GROUP ON RHEUMATOID ARTHRITIS REGISTRY
Authors: T. Kawano, T. Kashiwagura, M. Kobayashi, Y. Sugimura, H. Sato, N. Miyakoshi, Y. Shimada
Journal: Annals of the Rheumatic Diseases (2020)

Background: Glucocorticoids (GC) have potent anti-inflammatory and immunosuppressive effects and are used to treat a variety of diseases. However, GC are associated with several adverse effects. Glucocorticoid-induced osteoporosis (GIO), a bone metabolism disorder, accounts for 25% of the side effects associated with GC, and long-term use of these agents leads to fragility fractures in 30 to 50% of patients [1]. GC are frequently used to treat rheumatoid arthritis (RA). No report on the current treatment status for glucocorticoid-induced osteoporosis (GIO) has been published following the publication of the new guidelines for the management and treatment of GIO issued by the Japanese Society for Bone Mineral Research provided in 2014 (Figure 1) [2]. Objectives: The present study aimed to investigate the current treatment status of GIO patients in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA) registry. Methods: This retrospective, multicenter study included 683 patients (138 men, 545 women) with fracture risk factor scores ≥3 based on the new guidelines who were in the AORA registry. We examined patient characteristics, differences in patient backgrounds between treated and non-treated groups. Results: There were no significant differences in mean GC dose between men and women (4.0 ± 2.3 mg/day vs 3.6 ± 1.8 mg/day, p = 0.08). The mean disease duration of RA in women was significantly longer than in men (180.2 ± 140.2 months vs 143.8 ± 129.6 months, Untreated GIO patients were significantly more likely to be men and younger. The univariate analysis showed that clinic visits, male sex, younger age, and longer disease duration were significant risk factors for lack of therapeutic intervention for GIO. Multivariate analysis showed that being treated in a clinic, male sex, and younger age were significant risk factors for lack of therapeutic intervention for GIO. Conclusion: Our results emphasize the importance of considering the prevention and treatment of GIO in all patients with RA, including younger and male patients, who have lower intervention rates. References: [1]Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. New Engl J Med. 2011; 365(1): 62-70. [2]Suzuki Y, Nawata H, Soen S, Fujiwara S, Nakayama H, Tanaka I, et al. Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research: 2014 update. J Bone Miner Metab. 2014; 32(4): 337-350. Disclosure of Interests: None declared
Dissolving Microneedles with Spatiotemporally controlled pulsatile release Nanosystem for Synergistic Chemo-photothermal Therapy of Melanoma
Authors: Wanbing Qin, Guilan Quan, Ying Sun, Minglong Chen, Peipei Yang, Disang Feng, Ting Wen, Xinyu Hu, Xin Pan, Chuanbin Wu
Journal: Theranostics (2020)

High aggressiveness and recurrence of melanoma tumors require multiple systemic drug administrations, causing discomfort and severe side effects to the patients. Topical treatment strategies that provide repetitively controllable and precise drug administrations will greatly improve treatment effects. Methods: In this study, a spatiotemporally controlled pulsatile release system, which combined dissolving microneedles (DMNs) and thermal-sensitive solid lipid nanoparticles (SLNs), was constructed to realize multiple doses of dual-modal chemo-photothermal therapy in a single administration. Paclitaxel (PTX) and photothermal agent IR-780 were encapsulated into SLNs and were concentrated in the tips of DMNs (PTX/IR-780 SLNs @DMNs). Equipped with several needles, the DMN patch could be directly inserted into the tumor site and provide a stable "Zone accumulation" to constrain the PTX/IR-780 SLNs at the tumor site with uniform distribution. Results:In vitro experiments showed that after irradiation with near-infrared light, the PTX/IR-780 SLNs gradually underwent phase transition, thereby accelerating the release of PTX. When irradiation was switched off, the PTX/IR-780 SLNs cooled to re-solidify with limited drug release. Compared with intravenous and intratumoral injections, very few SLNs from PTX/IR-780 SLNs @DMNs were distributed into other organs, resulting in enhanced bioavailability at the tumor site and good safety. In vivo analysis revealed that PTX/IR-780 SLNs @DMNs exhibited significant anti-tumor efficacy. In particular, the primary tumor was completely eradicated with a curable rate of 100% in 30 days and the highest survival rate of 66.67% after 100 days of treatment. Conclusion: Herein, we developed a DMN system with a unique spatiotemporally controlled pulsatile release feature that provides a user-friendly and low-toxicity treatment route for patients who need long-term and repeat treatments.
Outcomes of donor-derived superinfection screening in HIV-positive to HIV-positive kidney and liver transplantation: a multicentre, prospective, observational study
Authors: Tania S Bonny, Charles Kirby, Craig Martens, Rebecca Rose, Niraj Desai, Michael Seisa, Christos Petropoulos, Sander Florman, Rachel J Friedman-Moraco, Nicole A Turgeon, Diane Brown, Dorry L Segev, Christine M Durand, Aaron A R Tobian, Andrew D Redd
Journal: The Lancet HIV (2020)
Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics
Authors: Kwangbom Choi, Yang Chen, Daniel A. Skelly, Gary A. Churchill
Journal: Genome biology (2020)

Abstract Background Single-cell RNA sequencing is a powerful tool for characterizing cellular heterogeneity in gene expression. However, high variability and a large number of zero counts present challenges for analysis and interpretation. There is substantial controversy over the origins and proper treatment of zeros and no consensus on whether zero-inflated count distributions are necessary or even useful. While some studies assume the existence of zero inflation due to technical artifacts and attempt to impute the missing information, other recent studies argue that there is no zero inflation in scRNA-seq data. Results We apply a Bayesian model selection approach to unambiguously demonstrate zero inflation in multiple biologically realistic scRNA-seq datasets. We show that the primary causes of zero inflation are not technical but rather biological in nature. We also demonstrate that parameter estimates from the zero-inflated negative binomial distribution are an unreliable indicator of zero inflation. Conclusions Despite the existence of zero inflation in scRNA-seq counts, we recommend the generalized linear model with negative binomial count distribution, not zero-inflated, as a suitable reference model for scRNA-seq analysis.
HIV incidence in US first-time blood donors and transfusion risk with a 12-month deferral for men who have sex with men
Authors: Eduard Grebe, Michael P. Busch, Edward P. Notari, Roberta Bruhn, Claire Quiner, Daniel Hindes, Mars Stone, Sonia Bakkour, Hong Yang, Phillip Williamson, Debra Kessler, Rita Reik, Susan L. Stramer, Simone A. Glynn, Steven A. Anderson, Alan E. Williams, Brian Custer
Journal: Blood (2020)
Hepatic Arterial Infusion Chemotherapy versus Sorafenib in Patients with Advanced Hepatocellular Carcinoma
Authors: Kazuomi Ueshima, Sadahisa Ogasawara, Masafumi Ikeda, Yutaka Yasui, Takeshi Terashima, Tatsuya Yamashita, Shuntaro Obi, Shinpei Sato, Hiroshi Aikata, Takumi Ohmura, Hidekatsu Kuroda, Takamasa Ohki, Kengo Nagashima, Yoshihiko Ooka, Masahiro Takita, Masayuki Kurosaki, Kazuaki Chayama, Shuichi Kaneko, Namiki Izumi, Naoya Kato, Masatoshi Kudo, Masao Omata
Journal: Liver Cancer (2020)

Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM).The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM.Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475-0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699-2.155; p = 0.475).HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.
To Procure or Not to Procure: Hospitals Face Significant Ethical Dilemmas Regarding Organ Donation During the COVID-19 Pandemic
Authors: Jordan Potter, Jessica Ginsberg, Jason Lesandrini, Amy Andrelchik
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Pyrvinium Pamoate Induces Death of Triple-Negative Breast Cancer Stem–Like Cells and Reduces Metastases through Effects on Lipid Anabolism
Authors: Rosanna Dattilo, Carla Mottini, Emanuela Camera, Alessia Lamolinara, Noam Auslander, Ginevra Doglioni, Michela Muscolini, Wei Tang, Melanie Planque, Cristiana Ercolani, Simonetta Buglioni, Isabella Manni, Daniela Trisciuoglio, Alessandra Boe, Sveva Grande, Anna Maria Luciani, Manuela Iezzi, Gennaro Ciliberto, Stefan Ambs, Ruggero De Maria, Sarah-Maria Fendt, Eytan Ruppin, Luca Cardone
Journal: Cancer Research (2020)

Cancer stem-like cells (CSC) induce aggressive tumor phenotypes such as metastasis formation, which is associated with poor prognosis in triple-negative breast cancer (TNBC). Repurposing of FDA-approved drugs that can eradicate the CSC subcompartment in primary tumors may prevent metastatic disease, thus representing an effective strategy to improve the prognosis of TNBC. Here, we investigated spheroid-forming cells in a metastatic TNBC model. This strategy enabled us to specifically study a population of long-lived tumor cells enriched in CSCs, which show stem-like characteristics and induce metastases. To repurpose FDA-approved drugs potentially toxic for CSCs, we focused on pyrvinium pamoate (PP), an anthelmintic drug with documented anticancer activity in preclinical models. PP induced cytotoxic effects in CSCs and prevented metastasis formation. Mechanistically, the cell killing effects of PP were a result of inhibition of lipid anabolism and, more specifically, the impairment of anabolic flux from glucose to cholesterol and fatty acids. CSCs were strongly dependent upon activation of lipid biosynthetic pathways; activation of these pathways exhibited an unfavorable prognostic value in a cohort of breast cancer patients, where it predicted high probability of metastatic dissemination and tumor relapse. Overall, this work describes a new approach to target aggressive CSCs that may substantially improve clinical outcomes for patients with TNBC, who currently lack effective targeted therapeutic options. SIGNIFICANCE: These findings provide preclinical evidence that a drug repurposing approach to prevent metastatic disease in TNBC exploits lipid anabolism as a metabolic vulnerability against CSCs in primary tumors.
What Caging Force Cells Feel in 3D Hydrogels: A Rheological Perspective
Authors: Giuseppe Ciccone, Oana Dobre, Graham M. Gibson, Jose Manuel Rey, Cristina Gonzalez–Garcia, Massimo Vassalli, Manuel Salmeron–Sanchez, Manlio Tassieri
Journal: Advanced Healthcare Materials (2020)

It is established that the mechanical properties of hydrogels control the fate of (stem) cells. However, despite its importance, a one-to-one correspondence between gels' stiffness and cell behaviour is still missing from literature. In this work, the viscoelastic properties of Poly(ethylene-glycol) (PEG)-based hydrogels - broadly used in 3D cell cultures and whose mechanical properties can be tuned to resemble those of different biological tissues - are investigated by means of rheological measurements performed at different length scales. When compared with literature values, the outcomes of this work reveal that conventional bulk rheology measurements may overestimate the stiffness of hydrogels by up to an order of magnitude. It is demonstrated that this apparent stiffening is caused by an induced 'tensional state' of the gel network, due to the application of a compressional normal force during measurements. Moreover, it is shown that the actual stiffness of the hydrogels is instead accurately determined by means of passive-video-particle-tracking (PVPT) microrheology measurements, which are inherently performed at cells length scales and in absence of any externally applied force. These results underpin a methodology for measuring the linear viscoelastic properties of hydrogels that are representative of the mechanical constraints felt by cells in 3D hydrogel cultures.
Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up
Authors: Judith Trotman, Stephen Opat, David Gottlieb, David Simpson, Paula Marlton, Gavin Cull, Javier Munoz, Alessandra Tedeschi, Andrew W. Roberts, John F. Seymour, Siminder Kaur Atwal, Yiling Yu, William Novotny, Eric Holmgren, Ziwen Tan, James D. Hilger, Jane Huang, Constantine S. Tam
Journal: Blood (2020)
Reduced Morbidity and Mortality in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
Authors: Stephanie B. Dixon, Yan Chen, Yutaka Yasui, Ching-Hon Pui, Stephen P. Hunger, Lewis B. Silverman, Kirsten K. Ness, Daniel M. Green, Rebecca M. Howell, Wendy M. Leisenring, Nina S. Kadan-Lottick, Kevin R. Krull, Kevin C. Oeffinger, Joseph P. Neglia, Ann C. Mertens, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong, Paul C. Nathan
Journal: Journal of Clinical Oncology (2020)

Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its impact on long-term toxicity remains unknown.We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population.Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio [95% CI]: 90sSR, 0.2 [0.1 to 0.4]; 90sHR, 0.3 [0.1 to 0.7]), comparable to the US population (standardized mortality ratio [95% CI]: 90sSR, 1.3 [0.8 to 2.0]; 90sHR, 1.7 [0.7 to 3.5]). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio [95% CI], 0.3 [0.1 to 0.6]) that was not different from that of the US population (standardized incidence ratio [95% CI], 1.0 [0.6 to 1.6]). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence [95% CI], 11.0% [9.7% to 12.3%] v 22.5% [19.4% to 25.5%]) and a lower prevalence of impaired memory (prevalence ratio [95% CI], 0.7 [0.6 to 0.9]) and task efficiency (0.5 [0.4 to 0.7]).Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.
cDC1 dysregulation in cancer: An opportunity for intervention
Authors: Thomas F. Gajewski, Kyle R. Cron
Journal: The Journal of Experimental Medicine (2020)

Conventional dendritic cells driven by the transcription factor Batf3 (cDC1 cells) are critical for the activation and maintenance of tumor-specific CD8+ T cells. In this issue of JEM, Lin et al. (https://doi.org/10.1084/jem.20190673) demonstrate systemic dysfunction of cDC1 cells in pancreatic cancer, which offers potential treatment strategies to expand the benefit of checkpoint blockade immunotherapy.
m<sup>6</sup>A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer
Authors: Qijie Zhao, Yueshui Zhao, Wei Hu, Yan Zhang, Xu Wu, Jianwei Lu, Mingxing Li, Wei Li, Weiqing Wu, Jianhong Wang, Fukuan Du, Huijiao Ji, Xiao Yang, Zhenyu Xu, Lin Wan, Qinglian Wen, Xiang Li, Chi Hin Cho, Chang Zou, Jing Shen, Zhangang Xiao
Journal: Theranostics (2020)

Rationale: Methylation at the N6 position of adenosine (m6A) is the most prevalent RNA modification within protein-coding mRNAs in mammals, and it is a reversible modification with various important biological functions. The formation and function of m6A are regulated by methyltransferases (writers), demethylases (erasers), and special binding proteins (readers) as key factors. However, the underlying modification mechanisms of m6A in gastrointestinal (GI) cancer remain unclear. Here, we performed comprehensive molecular profiling of the nine known m6A writer, eraser, and reader proteins in GI cancer. Methods: Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used. Gene alteration and pathway analysis were done in cBioportal. The protein network of m6A regulators and its related pathway members was analyzed in STRING online platform. Phylogenetic tree was constructed in MEGA7. m6A modification sites were predicted by SRAMP. m6A related SNPs were analyzed by m6ASNP. The modulation of m6A on its related pathway members was validated by m6A-seq, real-time PCR and phosphor-MAPK array. Results: We found that m6A regulators were mostly upregulated in GI cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m6A modification in most human cancers, including GI cancer, which was further verified by m6A-Seq and phospho-MAPK array. Conclusions: Our findings suggest that m6A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.
Host-Pathogen Interactions after Lung Transplant: Are Cystic Fibrosis Patients Unique?
Authors: Eric D. Morrell, Erika D. Lease
Journal: Cell Reports Medicine (2020)

The impact of Pseudomonas aeruginosa airway colonization on lung allografts is not entirely clear. In this issue of Cell Reports Medicine, Dugger et al.1 identify distinct clinical outcomes and lung allograft biology in recipients with and without cystic fibrosis.
Functional CT Contrast Nanoagents for the Tumor Microenvironment
Authors: Xianfu Meng, Yelin Wu, Wenbo Bu
Journal: Advanced Healthcare Materials (2020)

Abstract Understanding the detailed tumor microenvironment (TME) is essential to achieve effective treatment of tumor, because TME has an extremely profound influence on the occurrence, development, invasion, and metastasis of tumor. It is of great significance to realize accurate diagnosis of the TME by using functional computed tomography (CT) contrast nanoagents (FCTNAs). Here, an overview of FCTNAs that respond to the overexpressed receptors, acidic microenvironment, overexpressed glutathione and enzymes, and hypoxia in tumor is provided, and also prospects the advance of novel spectral CT technique to detect the TME precisely. Utilizing FCTNAs is expected to achieve accurate monitoring of the TME and further provide guidance for the effective personalized tumor treatment in clinic.
Genomic and Clinicopathologic Characterization of<i>ATM</i>-deficient Prostate Cancer
Authors: Harsimar Kaur, Daniela C. Salles, Sanjana Murali, Jessica L. Hicks, Minh Nguyen, Colin C. Pritchard, Angelo M. De Marzo, Jerry S. Lanchbury, Bruce J. Trock, William B. Isaacs, Kirsten M. Timms, Emmanuel S. Antonarakis, Tamara L. Lotan
Journal: Clinical Cancer Research (2020)

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Stem cell programs in cancer initiation, progression, and therapy resistance
Authors: Tianzhi Huang, Xiao Song, Dandan Xu, Deanna Tiek, Anshika Goenka, Bingli Wu, Namratha Sastry, Bo Hu, Shi-Yuan Cheng
Journal: Theranostics (2020)

Over the past few decades, substantial evidence has convincingly revealed the existence of cancer stem cells (CSCs) as a minor subpopulation in cancers, contributing to an aberrantly high degree of cellular heterogeneity within the tumor. CSCs are functionally defined by their abilities of self-renewal and differentiation, often in response to cues from their microenvironment. Biological phenotypes of CSCs are regulated by the integrated transcriptional, post-transcriptional, metabolic, and epigenetic regulatory networks. CSCs contribute to tumor progression, therapeutic resistance, and disease recurrence through their sustained proliferation, invasion into normal tissue, promotion of angiogenesis, evasion of the immune system, and resistance to conventional anticancer therapies. Therefore, elucidation of the molecular mechanisms that drive cancer stem cell maintenance, plasticity, and therapeutic resistance will enhance our ability to improve the effectiveness of targeted therapies for CSCs. In this review, we highlight the key features and mechanisms that regulate CSC function in tumor initiation, progression, and therapy resistance. We discuss factors for CSC therapeutic resistance, such as quiescence, induction of epithelial-to-mesenchymal transition (EMT), and resistance to DNA damage-induced cell death. We evaluate therapeutic approaches for eliminating therapy-resistant CSC subpopulations, including anticancer drugs that target key CSC signaling pathways and cell surface markers, viral therapies, the awakening of quiescent CSCs, and immunotherapy. We also assess the impact of new technologies, such as single-cell sequencing and CRISPR-Cas9 screening, on the investigation of the biological properties of CSCs. Moreover, challenges remain to be addressed in the coming years, including experimental approaches for investigating CSCs and obstacles in therapeutic targeting of CSCs.