tbuckley/cabot-search huggingface dataset:
Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study
Authors: Ling-Zhi Ma, Lan Tan, Yan-Lin Bi, Xue-Ning Shen, Wei Xu, Ya-Hui Ma, Hong-Qi Li, Qiang Dong, Jin-Tai Yu
Journal: Molecular Neurodegeneration (2020)

Abstract Background Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear. Methods According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ 1–42 , T-tau and P-tau), stage 1 (low Aβ 1–42 , normal T-tau and P-tau), stage 2 (low Aβ 1–42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ 1–42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology. Results The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 ( P &lt; 0.001), and then increased in the stage 2 ( P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P &lt; 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ 1–42 (β = 0.192, P &lt; 0.001), T-tau (β = 0.215, P &lt; 0.001) and P-tau (β = 0.123, P &lt; 0.001). Conclusion CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.
Myocardium-targeted transplantation of PHD2 shRNA-modified bone mesenchymal stem cells through ultrasound-targeted microbubble destruction protects the heart from acute myocardial infarction
Authors: Zhenxing Sun, Yuji Xie, Robert J. Lee, Yihan Chen, Qiaofeng Jin, Qing Lv, Jing Wang, Yali Yang, Yuman Li, Yu Cai, Rui Wang, Zhengyang Han, Li Zhang, Mingxing Xie
Journal: Theranostics (2020)

Ultrasound-targeted microbubble destruction (UTMD) is a promising approach to facilitate the precise delivery of bone marrow stem cells (BMSCs) to the ischemic myocardium. However, stem cell therapy for ischemic myocardium is challenging due to the poor survival of transplanted stem cells under severe ischemic conditions. In this study, we investigated whether myocardium-targeted transplantation of prolyl hydroxylase domain protein 2 (PHD2) shRNA-modified BMSCs by UTMD increases the viability of grafted cells, and enhances their cardioprotective effects in acute myocardial infarction. Methods: BMSCs were transduced with lentiviral PHD2 shRNA, and a novel microbubble formulation was prepared by a thin-film hydration method. In rats, BMSCs with or without PHD2 shRNA modification were transplanted by UTMD after inducing acute myocardium infarction. Effects of PHD2 shRNA on BMSC survival, myocardial apoptosis, angiogenesis, and cardiac function were evaluated. In vitro, anti-apoptotic effects and its mechanisms of PHD2 silencing on BMSC and BMSC-conditioned medium on H9C2 cell were detected. Results: PHD2 shRNA-modified BMSC transplantation by UTMD resulted in increased BMSC survival, reduced myocardial apoptosis, reduced infarct size, increased vascular density, and improved cardiac function compared to the control vector-modified BMSC transplantation by UTMD. PHD2 silencing increased BMSC survival through a HIF-1α-dependent mechanism. The decrease in cardiomyocyte apoptosis by conditioned medium from PHD2 shRNA-treated BMSCs was due to an increase in the expression of insulin-like growth factor (IGF)-1. Conclusions: The delivery of PHD2 shRNA-modified BMSCs by UTMD promoted grafted cell homing and activity, and increased myocardial angiogenesis in the infarcted heart, leading to improved cardiac function. This combination may provide a promising strategy for enhancing the effectiveness of stem cell therapy after acute myocardial infarction.
Sodium‐Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes
Authors: Iaarah Montalvo‐Gordon, Luis Alberto Chi‐Cervera, Guadalupe García‐Tsao
Journal: Hepatology (2020)

Montalvo‐Gordon, Iaarah M.D.; Chi‐Cervera, Luis Alberto; García‐Tsao, Guadalupe Author Information
Treg sensitivity to FasL and relative IL-2 deprivation drive idiopathic aplastic anemia immune dysfunction
Authors: Shok Ping Lim, Benedetta Costantini, Syed A. Mian, Pilar Perez Abellan, Shreyans Gandhi, Marc Martinez Llordella, Juan Jose Lozano, Rita Antunes dos Reis, Giovanni A. M. Povoleri, Thanos P. Mourikis, Ander Abarrategi, Linda Ariza-McNaughton, Susanne Heck, Jonathan M. Irish, Giovanna Lombardi, Judith C. W. Marsh, Dominique Bonnet, Shahram Kordasti, Ghulam J. Mufti
Journal: Blood (2020)
Esophageal, gastric and colorectal cancers: Looking beyond classical serological biomarkers towards glycoproteomics-assisted precision oncology
Authors: Elisabete Fernandes, Janine Sores, Sofia Cotton, Andreia Peixoto, Dylan Ferreira, Rui Freitas, Celso A. Reis, Lúcio Lara Santos, José Alexandre Ferreira
Journal: Theranostics (2020)

Esophageal (OC), gastric (GC) and colorectal (CRC) cancers are amongst the digestive track tumors with higher incidence and mortality due to significant molecular heterogeneity. This constitutes a major challenge for patients' management at different levels, including non-invasive detection of the disease, prognostication, therapy selection, patient's follow-up and the introduction of improved and safer therapeutics. Nevertheless, important milestones have been accomplished pursuing the goal of molecular-based precision oncology. Over the past five years, high-throughput technologies have been used to interrogate tumors of distinct clinicopathological natures, generating large-scale biological datasets (e.g. genomics, transcriptomics, and proteomics). As a result, GC and CRC molecular subtypes have been established to assist patient stratification in the clinical settings. However, such molecular panels still require refinement and are yet to provide targetable biomarkers. In parallel, outstanding advances have been made regarding targeted therapeutics and immunotherapy, paving the way for improved patient care; nevertheless, important milestones towards treatment personalization and reduced off-target effects are also to be accomplished. Exploiting the cancer glycoproteome for unique molecular fingerprints generated by dramatic alterations in protein glycosylation may provide the necessary molecular rationale towards this end. Therefore, this review presents functional and clinical evidences supporting a reinvestigation of classical serological glycan biomarkers such as sialyl-Tn (STn) and sialyl-Lewis A (SLeA) antigens from a tumor glycoproteomics perspective. We anticipate that these glycobiomarkers that have so far been employed in non-invasive cancer prognostication may hold unexplored value for patients' management in precision oncology settings.
Coronavirus Disease 2019 in the Perioperative Period of Lung Resection: A Brief Report From a Single Thoracic Surgery Department in Wuhan, People’s Republic of China
Authors: Yixin Cai, Zhipeng Hao, Yi Gao, Wei Ping, Qi Wang, Shu Peng, Bo Zhao, Wei Sun, Min Zhu, Kaiyan Li, Ying Han, Dong Kuang, Qian Chu, Xiangning Fu, Ni Zhang
Journal: Journal of Thoracic Oncology (2020)
Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden
Authors: Alicia Nevriana, Matthias Pierce, Christina Dalman, Susanne Wicks, Marie Hasselberg, Holly Hope, Kathryn M Abel, Kyriaki Kosidou
Journal: BMJ (2020)

Abstract Objective To determine the association between parental mental illness and the risk of injuries among offspring. Design Retrospective cohort study. Setting Swedish population based registers. Participants 1 542 000 children born in 1996-2011 linked to 893 334 mothers and 873 935 fathers. Exposures Maternal or paternal mental illness (non-affective psychosis, affective psychosis, alcohol or drug misuse, mood disorders, anxiety and stress related disorders, eating disorders, personality disorders) identified through linkage to inpatient or outpatient healthcare registers. Main outcome measures Risk of injuries (transport injury, fall, burn, drowning and suffocation, poisoning, violence) at ages 0-1, 2-5, 6-9, 10-12, and 13-17 years, comparing children of parents with mental illness and children of parents without mental illness, calculated as the rate difference and rate ratio adjusted for confounders. Results Children with parental mental illness contributed to 201 670.5 person years of follow-up, while children without parental mental illness contributed to 2 434 161.5 person years. Children of parents with mental illness had higher rates of injuries than children of parents without mental illness (for any injury at age 0-1, these children had an additional 2088 injuries per 100 000 person years; number of injuries for children with and without parental mental illness was 10 235 and 72 723, respectively). At age 0-1, the rate differences ranged from 18 additional transport injuries to 1716 additional fall injuries per 100 000 person years among children with parental mental illness compared with children without parental mental illness. A higher adjusted rate ratio for injuries was observed from birth through adolescence and the risk was highest during the first year of life (adjusted rate ratio at age 0-1 for the overall association between any parental mental illness that has been recorded in the registers and injuries 1.30, 95% confidence interval 1.26 to 1.33). Adjusted rate ratios at age 0-1 ranged from 1.28 (1.24 to 1.32) for fall injuries to 3.54 (2.28 to 5.48) for violence related injuries. Common and serious maternal and paternal mental illness was associated with increased risk of injuries in children, and estimates were slightly higher for common mental disorders. Conclusions Parental mental illness is associated with increased risk of injuries among offspring, particularly during the first years of the child’s life. Efforts to increase access to parental support for parents with mental illness, and to recognise and treat perinatal mental morbidity in parents in secondary care might prevent child injury.
Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome?
Authors: John S. Tsang, Carlota Dobaño, Pierre VanDamme, Gemma Moncunill, Arnaud Marchant, Rym Ben Othman, Manish Sadarangani, Wayne C. Koff, Tobias R. Kollmann
Journal: Trends in Immunology (2020)
Entecavir prophylaxis for hepatitis B virus reactivation in patients with CAR T-cell therapy
Authors: Wenyue Cao, Jia Wei, Na Wang, Hao Xu, Min Xiao, Lifang Huang, Yang Cao, Chunrui Li, Yi Xiao, Chaojiang Gu, Shangkun Zhang, Dengju Li, Yichen Zhang, Tongcun Zhang, Jianfeng Zhou, Liang Huang
Journal: Blood (2020)
Novel nicastrin mutation in hidradenitis suppurativa–Dowling–Degos disease clinical phenotype: more than just clinical overlap?
Authors: S. Garcovich, P.M. Tricarico, C. Nait‐Meddour, G. Giovanardi, K. Peris, S. Crovella, M. Boniotto
Journal: British Journal of Dermatology (2020)
Abstract 12986: Intravenous Injection of Adult Human Bone Marrow Mesenchymal Stromal Cells Attenuates Spinal Cord Ischemia Reperfusion Injury in a Mouse Aortic Arch Cross Clamping Model
Authors: Yasuyuki Fujita, Hidekazu Nakai, Satoru Masuda, Yasuko Gotake, Miki Komatsu, Ayumi Tani, Yutaka Okita, Atsuhiko Kawamoto
Journal: Circulation (2018)

Background: Paraplegia induced by spinal cord ischemia reperfusion injury (SCIR) remains a devastating complication following thoracic and thoracoabdominal aortic open surgery / endovascular aortic...
Abstract 12611: A Bedside Medication Delivery Service Program Reduces 30 Day Readmissions in Patients With Cardiac Disease
Authors: David Cordwin, Kristin R Daniel, Donald G Klepser, Paul P Dobesh
Journal: Circulation (2018)

Introduction: Hospital readmission within 30 days of discharge is an important quality of care metric, as well as having significant cost implications. Patients with cardiac disease are among the l...
A dual-functional Embolization-Visualization System for Fluorescence image-guided Tumor Resection
Authors: M. Martin Jensen, Zachary B. Barber, Nitish Khurana, Kyle J. Isaacson, Douglas Steinhauff, Bryant Green, Joseph Cappello, Abigail Pulsipher, Hamidreza Ghandehari, Jeremiah A. Alt
Journal: Theranostics (2020)

Rationale: Intraoperative bleeding impairs physicians' ability to visualize the surgical field, leading to increased risk of surgical complications and reduced outcomes. Bleeding is particularly challenging during endoscopic-assisted surgical resection of hypervascular tumors in the head and neck. A tool that controls bleeding while marking tumor margins has the potential to improve gross tumor resection, reduce surgical morbidity, decrease blood loss, shorten procedure time, prevent damage to surrounding tissues, and limit postoperative pain. Herein, we develop and characterize a new system that combines pre-surgical embolization with improved visualization for endoscopic fluorescence image-guided tumor resection. Methods: Silk-elastinlike protein (SELP) polymers were employed as liquid embolic vehicles for delivery of a clinically used near-infrared dye, indocyanine green (ICG). The biophysical properties of SELP, including gelation kinetics, modulus of elasticity, and viscosity, in response to ICG incorporation using rheology, were characterized. ICG release from embolic SELP was modeled in tissue phantoms and via fluorescence imaging. The embolic capability of the SELP-ICG system was then tested in a microfluidic model of tumor vasculature. Lastly, the cytotoxicity of the SELP-ICG system in L-929 fibroblasts and human umbilical vein endothelial cells (HUVEC) was assessed. Results: ICG incorporation into SELP accelerated gelation and increased its modulus of elasticity. The SELP embolic system released 83 ± 8% of the total ICG within 24 hours, matching clinical practice for pre-surgical embolization procedures. Adding ICG to SELP did not reduce injectability, but did improve the gelation kinetics. After simulated embolization, ICG released from SELP in tissue phantoms diffused a sufficient distance to deliver dye throughout a tumor. ICG-loaded SELP was injectable through a clinical 2.3 Fr microcatheter and demonstrated deep penetration into 50-µm microfluidic-simulated blood vessels with durable occlusion. Incorporation of ICG into SELP improved biocompatibility with HUVECs, but had no effect on L-929 cell viability. Principle Conclusions: We report the development and characterization of a new, dual-functional embolization-visualization system for improving fluorescence-imaged endoscopic surgical resection of hypervascular tumors.
Osteoblastic and anti-osteoclastic activities of strontium-substituted silicocarnotite ceramics: In vitro and in vivo studies
Authors: Junkai Zeng, Jingshu Guo, Zhenyu Sun, Fanyan Deng, Congqin Ning, Youzhuan Xie
Journal: Bioactive Materials (2020)

Osteoporosis bone defect is a refractory orthopaedic disease which characterized by impaired bone quality and bone regeneration capacity. Current therapies, including antiosteoporosis drugs and artificial bone grafts, are not always satisfactory. Herein, a strontium-substituted calcium phosphate silicate bioactive ceramic (Sr-CPS) was fabricated. In the present study, the extracts of Sr-CPS were prepared for in vitro study and Sr-CPS scaffolds were used for in vivo study. The cytocompatibility, osteogenic and osteoclastogenic properties of Sr-CPS extracts were characterized in comparison to CPS. Molecular mechanisms were also evaluated by Western blot. Sr-CPS extracts were found to promote osteogenesis by upregulating Wnt/β-catenin signal pathways and inhibit osteoclastogenesis through downregulating NF-κB signal pathway. In vivo, micro-CT, histological and histomorphometric observation were conducted after 8 weeks of implantation to evaluate the bone formation using calvarial defects model in ovariectomized rats. Compared with CPS, Sr-CPS significantly promoted critical sized ovariectomy (OVX) calvarial defects healing. Among all the samples, Sr-10 showed the best performance due to a perfect match of bone formation and scaffold degradation rates. Overall, the present study demonstrated that Sr-CPS ceramic can dually modulate both bone formation and resorption, which might be a promising candidate for the reconstruction of osteoporotic bone defect.
Next-generation RNA Sequencing–based Biomarker Characterization of Chromophobe Renal Cell Carcinoma and Related Oncocytic Neoplasms
Authors: Stephanie L. Skala, Xiaoming Wang, Yuping Zhang, Rahul Mannan, Lisha Wang, Sathiya P. Narayanan, Pankaj Vats, Fengyun Su, Jin Chen, Xuhong Cao, Javed Siddiqui, Pedram Argani, Marcin P. Cieślik, Thomas J. Giordano, Arul M. Chinnaiyan, Saravana M. Dhanasekaran, Rohit Mehra
Journal: European Urology (2020)
Correction to: Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit
Authors: Jianlei Cao, Xiaorong Hu, Wenlin Cheng, Lei Yu, Wen-Jun Tu, Qiang Liu
Journal: Intensive Care Medicine (2020)

The original version of this article unfortunately contained a mistake. There was an error in Xiaorong Hu's name. The original article has been corrected. The authors apologize for the mistake.
Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naïve and Solvent-Front–Mutant ROS1-Rearranged Non–Small Cell Lung Cancer
Authors: Mi Ran Yun, Dong Hwi Kim, Seok-Young Kim, Hyeong-Seok Joo, You Won Lee, Hun Mi Choi, Chae Won Park, Seong Gu Heo, Han Na Kang, Sung Sook Lee, Adam J. Schoenfeld, Alexander Drilon, Seok-Gu Kang, Hyo Sup Shim, Min Hee Hong, J. Jean Cui, Hye Ryun Kim, Byoung Chul Cho
Journal: Clinical Cancer Research (2020)

Although first-line crizotinib treatment leads to clinical benefit in ROS1+ lung cancer, high prevalence of crizotinib-resistant ROS1-G2032R (ROS1G2032R) mutation and progression in the central nervous system (CNS) represents a therapeutic challenge. Here, we investigated the antitumor activity of repotrectinib, a novel next-generation ROS1/TRK/ALK-tyrosine kinase inhibitor (TKI) in ROS1+ patient-derived preclinical models.Antitumor activity of repotrectinib was evaluated in ROS1+ patient-derived preclinical models including treatment-naïve and ROS1G2032R models and was further demonstrated in patients enrolled in an on-going phase I/II clinical trial (NCT03093116). Intracranial antitumor activity of repotrectinib was evaluated in a brain-metastasis mouse model.Repotrectinib potently inhibited in vitro and in vivo tumor growth and ROS1 downstream signal in treatment-naïve YU1078 compared with clinically available crizotinib, ceritinib, and entrectinib. Despite comparable tumor regression between repotrectinib and lorlatinib in YU1078-derived xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. Moreover, repotrectinib induced profound antitumor activity in the CNS with efficient blood-brain barrier penetrating properties. Notably, repotrectinib showed selective and potent in vitro and in vivo activity against ROS1G2032R. These findings were supported by systemic and intracranial activity of repotrectinib observed in patients enrolled in the on-going clinical trial.Repotrectinib is a novel next-generation ROS1-TKI with improved potency and selectivity against treatment-naïve and ROS1G2032R with efficient CNS penetration. Our findings suggest that repotrectinib can be effective both as first-line and after progression to prior ROS1-TKI.
Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation
Authors: Peng Chen, Xuejie Li, Ruonan Zhang, Shuiping Liu, Yu Xiang, Mingming Zhang, Xiaying Chen, Ting Pan, Lili Yan, Jiao Feng, Ting Duan, Da Wang, Bi Chen, Ting Jin, Wengang Wang, Liuxi Chen, Xingxing Huang, Wenzheng Zhang, Yitian Sun, Guohua Li, Lingpan Kong, Xiaohui Chen, Yongqiang Li, Zuyi Yang, Qin Zhang, Lvjia Zhuo, Xinbing Sui, Tian Xie
Journal: Theranostics (2020)

Background and Purpose: RAS mutations limit the effectiveness of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in combination with chemotherapy for metastatic colorectal cancer (mCRC) patients. Therefore, new cell death forms have focused on identifying indirect targets to inhibit Ras-induced oncogenesis. Recently, emerging evidence has shown the potential of triggering ferroptosis for cancer therapy, particularly for eradicating aggressive malignancies that are resistant to traditional therapies. Methods: KRAS mutant CRC cell HCT116 and Lovo were treated with cetuximab and β-elemene, a bioactive compound isolated from Chinese herb Curcumae Rhizoma. Ferroptosis and epithelial-mesenchymal transformation (EMT) were detected in vitro and in vivo. Orthotopic CRC animal model were established and the tumor growth was monitored by IVIS bioluminescence imaging. Tumor tissues were collected to determine ferroptosis effect and the expression of EMT markers after the treatment. Results: CCK-8 assay showed that synergetic effect was obtained when 125 µg/ml β-elemene was combined with 25 µg/ml cetuximab in KRAS mutant CRC cells. AV/PI staining suggested a non-apoptotic mode of cell death after the treatment with β-elemene and cetuximab. In vitro, β-elemene in combination with cetuximab was shown to induce iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of HO-1 and transferrin, and downregulation of negative regulatory proteins for ferroptosis (GPX4, SLC7A11, FTH1, glutaminase, and SLC40A1) in KRAS mutant CRC cells. Meanwhile, combinative treatment of β-elemene and cetuximab inhibited cell migration and decreased the expression of mesenchymal markers (Vimentin, N-cadherin, Slug, Snail and MMP-9), but promoted the expression of epithelial marker E-cadherin. Moreover, ferroptosis inhibitors but not other cell death suppressors abrogated the effect of β-elemene in combination with cetuximab on KRAS mutant CRC cells. In vivo, co-treatment with β-elemene and cetuximab inhibited KRAS mutant tumor growth and lymph nodes metastases. Conclusions: Our data for the first time suggest that the natural product β-elemene is a new ferroptosis inducer and combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant CRC cells by inducing ferroptosis and inhibiting EMT, which will hopefully provide a prospective strategy for CRC patients with RAS mutations.
Heroes of our own story: Self-image and rationalizing in thought experiments
Authors: Tomer David Ullman
Journal: Behavioral and Brain Sciences (2020)

Abstract Cushman's rationalization account can be extended to cover another part of his portrayal of representational exchange: thought experiments that lead to conclusions about the self. While Cushman's argument is compelling, a full account of rationalization as adaptive will need to account for the divergence in rationalizing one's actions compared to the actions of others.