tbuckley/cabot-search huggingface dataset:
Retinoic acid promotes metabolic maturation of human Embryonic Stem Cell-derived Cardiomyocytes
Authors: Shumei Miao, Dandan Zhao, Xiaoxiao Wang, Xuan Ni, Xing Fang, Miao Yu, Lingqun Ye, Jingsi Yang, Hongchun Wu, Xinglong Han, Lina Qu, Lei Li, Feng Lan, Zhenya Shen, Wei Lei, Zhen-Ao Zhao, Shijun Hu
Journal: Theranostics (2020)

Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development. However, the effects of RA on cardiomyocyte differentiation efficiency and maturation are still unknown. Methods: RA was added at different time intervals to identify the best treatment windows for cardiomyocyte differentiation and maturation. The efficiency of cardiomyocyte differentiation was detected by quantitative real-time PCR and flow cytometry. Cardiomyocytes maturation was detected by immunofluorescence staining, metabolic assays and patch clamp to verify structural, metabolic and electrophysiological maturation, respectively. RNA sequencing was used for splicing analysis. Results: We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number. RNA sequencing revealed RA promoted RNA isoform switch to the maturation-related form. Meanwhile, RA promoted electrophysiological maturation and calcium handling of hESC-CMs. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. Conclusion: Our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.
Supraglottic Lung Microbiome Taxa Are Associated with Pulmonary Abnormalities in an HIV Longitudinal Cohort
Authors: Jin J. Zhou, Jing Zhai, Hua Zhou, Yin Chen, Stefano Guerra, Ian Robey, George M. Weinstock, Erica Weinstock, Qunfeng Dong, Kenneth S. Knox, Homer L. Twigg
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Outcomes Associated With Use of a Kinin B2 Receptor Antagonist Among Patients With COVID-19
Authors: Frank L. van de Veerdonk, Ilse J. E. Kouijzer, Aline H. de Nooijer, Hans G. van der Hoeven, Coen Maas, Mihai G. Netea, Roger J. M. Brüggemann
Journal: JAMA Network Open (2020)

matched controls, only 3 (17%) showed a spontaneous reduction in oxygen supplementation of 3 L/min or greater within 24 hours.We noted that in 3 patients treated with icatibant there was a resurgence in the need for oxygen supplementation.Icatibant treatment was well tolerated in all 10 patients who received the drug.There were no severe adverse events.There was no clear association with D-dimer concentrations and fever. DiscussionThis study found evidence of an association between receipt of icatibant and improved oxygenation, suggesting that targeting the kallikrein-kinin system in patients with COVID-19, especially in the early stages of disease when patients are hypoxic and are admitted to the hospital, might be beneficial.An important limitation of the current study is that it is exploratory and not a randomized clinical trial.The observed resurgence of oxygen need in some patients after icatibant may be due to icatibant's short half life of about 2 hours. 3We propose that treatment strategies targeting the kallikrein-kinin system should be investigated in randomized trials for patients with COVID-19.
The crow in the room: New Caledonian crows offer insight into the necessary and sufficient conditions for cumulative cultural evolution
Authors: Alex H. Taylor, Sarah Jelbert
Journal: Behavioral and Brain Sciences (2020)

Abstract New Caledonian (NC) crow populations have developed complex tools that show suggestive evidence of cumulative change. These tool designs, therefore, appear to be the product of cumulative technological culture (CTC). We suggest that tool-using NC crows offer highly useful data for current debates over the necessary and sufficient conditions for the emergence of CTC.
Radiomics‐based model for accurately distinguishing between severe acute respiratory syndrome associated coronavirus 2 (SARS‐CoV‐2) and influenza A infected pneumonia
Authors: Qi‐Qiang Zeng, Kenneth I. Zheng, Jun Chen, Zheng‐Hao Jiang, Tian Tian, Xiao‐Bo Wang, Hong‐Lei Ma, Ke‐Hua Pan, Yun‐Jun Yang, Yong‐Ping Chen, Ming‐Hua Zheng
Journal: MedComm (2020)

Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine-learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty-one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real-time RT-PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77-0.93). The nomogram also showed excellent calibration with Hosmer-Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS-CoV-2 pneumonia.
Bone health in cancer: ESMO Clinical Practice Guidelines
Authors: R. Coleman, P. Hadji, J.-J. Body, D. Santini, E. Chow, E. Terpos, S. Oudard, Ø. Bruland, P. Flamen, A. Kurth, C. Van Poznak, M. Aapro, K. Jordan
Journal: Annals of Oncology (2020)

•The clinical course of advanced cancer for many patients with bone metastases can be transformed through optimum multidisciplinary management.•Bone-targeted agents significantly reduce skeletal morbidity in patients with bone metastases across tumour types and should be part of standard treatment.•Treatment-induced bone loss increases fracture risk and may require use of a bone-targeted agent in addition to lifestyle modifications.•The addition of a bisphosphonate to standard adjuvant therapies for postmenopausal early breast cancer reduces bone recurrence and improves survival.
IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma
Authors: Rebekka Weber, Zeno Riester, Laura Hüser, Carsten Sticht, Alina Siebenmorgen, Christopher Groth, Xiaoying Hu, Peter Altevogt, Jochen S Utikal, Viktor Umansky
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Myeloid-derived suppressor cells (MDSC) play a major role in the immunosuppressive melanoma microenvironment. They are generated under chronic inflammatory conditions characterized by the constant production of inflammatory cytokines, chemokines and growth factors, including IL-6. Recruitment of MDSC to the tumor is mediated by the interaction between chemokines and chemokine receptors, in particular C–C chemokine receptor (CCR)5. Here, we studied the mechanisms of CCR5 upregulation and increased immunosuppressive function of CCR5 + MDSC. Methods The immortalized myeloid suppressor cell line MSC-2, primary immature myeloid cells and in vitro differentiated MDSC were used to determine factors and molecular mechanisms regulating CCR5 expression and immunosuppressive markers at the mRNA and protein levels. The relevance of the identified pathways was validated on the RET transgenic mouse melanoma model, which was also used to target the identified pathways in vivo. Results IL-6 upregulated the expression of CCR5 and arginase 1 in MDSC by a STAT3-dependent mechanism. MDSC differentiated in the presence of IL-6 strongly inhibited CD8 + T cell functions compared with MDSC differentiated without IL-6. A correlation between IL-6 levels, phosphorylated STAT3 and CCR5 expression in tumor-infiltrating MDSC was demonstrated in the RET transgenic melanoma mouse model. Surprisingly, IL-6 overexpressing tumors grew significantly slower in mice accompanied by CD8 + T cell activation. Moreover, transgenic melanoma-bearing mice treated with IL-6 blocking antibodies showed significantly accelerated tumor development. Conclusion Our in vitro and ex vivo findings demonstrated that IL-6 induced CCR5 expression and a strong immunosuppressive activity of MDSC, highlighting this cytokine as a promising target for melanoma immunotherapy. However, IL-6 blocking therapy did not prove to be effective in RET transgenic melanoma-bearing mice but rather aggravated tumor progression. Further studies are needed to identify particular combination therapies, cancer entities or patient subsets to benefit from the anti-IL-6 treatment.
Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy
Authors: Yu Liu, Jiacheng Du, Peng Peng, Ruoyu Cheng, Jiayi Lin, Congxin Xu, Huilin Yang, Wenguo Cui, Haiqing Mao, Yuling Li, Dechun Geng
Journal: Bioactive Materials (2020)

Surgery is the final choice for most patients with intervertebral disc degeneration (IDD). Operation-caused trauma will cause inflammation in the intervertebral disc. Serious inflammation will cause tissue defects and induce tissue degeneration, IDD recurrence and the occurrence of other diseases. Therefore, we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin (ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation. ASP-liposomes (ASP-Lips) were incorporated into a photocrosslinkable gelatin-methacryloyl (GelMA) via mixing. This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm. We further assessed the expression of inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and degeneration-related factors, such as type II collagen (COL-2), Aggrecan, matrix metallopeptidases-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 in rat nucleus pulpous cells. The level of IDD was analyzed through H&E, safranin-O staining and immunohistochemistry in rabbit samples. In vitro, we found that [email protected] treatment significantly decreased inflammatory cytokines, MMP-3 and -13, and ADAMTS-4 and -5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus. In vivo, [email protected] can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects. This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.
Extracorporeal shockwave therapy improves pain and function in subjects with knee osteoarthritis: A systematic review and meta-analysis of randomized clinical trials
Authors: Juan Avendaño-Coy, Natalia Comino-Suárez, Jesús Grande-Muñoz, Carlos Avendaño-López, Julio Gómez-Soriano
Journal: International Journal of Surgery (2020)
Cryogenic 3D printing of dual-delivery scaffolds for improved bone regeneration with enhanced vascularization
Authors: Chong Wang, Jiahui Lai, Kai Li, Shaokui Zhu, Bingheng Lu, Jia Liu, Yujin Tang, Yen Wei
Journal: Bioactive Materials (2020)

Three-dimensional (3D) printing has been increasingly employed to produce advanced bone tissue engineering scaffolds with biomimetic structures and matched mechanical strengths, in order to induce improved bone regeneration in defects with a critical size. Given that the successful bone regeneration requires both excellent osteogenesis and vascularization, endowing scaffolds with both strong bone forming ability and favorable angiogenic potential would be highly desirable to induce improved bone regeneration with required vascularization. In this investigation, customized bone tissue engineering scaffolds with balanced osteoconductivity/osteoinductivity were produced via cryogenic 3D printing of β-tricalcium phosphate and osteogenic peptide (OP) containing water/poly(lactic-co-glycolic acid)/dichloromethane emulsion inks. The fabricated scaffolds had a hierarchically porous structure and were mechanically comparable to human cancellous bone. Angiogenic peptide (AP) containing collagen I hydrogel was then coated on scaffold surface to further provide scaffolds with angiogenic capability. A sequential release with a quick AP release and a slow but sustained OP release was obtained for the scaffolds. Both rat endothelial cells (ECs) and rat bone marrow derived mesenchymal stem cells (MSCs) showed high viability on scaffolds. Improved in vitro migration and angiogenesis of ECs were obtained for scaffolds delivered with AP while enhanced osteogenic differentiation was observed in scaffolds containing OP. The in vivo results showed that, toward scaffolds containing both AP and OP, the quick release of AP induced obvious angiogenesis in vivo, while the sustained OP release significantly improved the new bone formation. This study provides a facile method to produce dual-delivery scaffolds to achieve multiple functions.
A Review of Bioresorbable Implantable Medical Devices: Materials, Fabrication, and Implementation
Authors: Rahul Singh, Mohammad Javad Bathaei, Emin Istif, Levent Beker
Journal: Advanced Healthcare Materials (2020)

Implantable medical devices (IMDs) are designed to sense specific parameters or stimulate organs and have been actively used for treatment and diagnosis of various diseases. IMDs are used for long-term disease screening or treatments and cannot be considered for short-term applications since patients need to go through a surgery for retrieval of the IMD. Advances in bioresorbable materials has led to the development of transient IMDs that can be resorbed by bodily fluids and disappear after a certain period. These devices are designed to be implanted in the adjacent of the targeted tissue for predetermined times with the aim of measurement of pressure, strain, or temperature, while the bioelectronic devices stimulate certain tissues. They enable opportunities for monitoring and treatment of acute diseases. To realize such transient and miniaturized devices, researchers utilize a variety of materials, novel fabrication methods, and device design strategies. This review discusses potential bioresorbable materials for each component in an IMD followed by programmable degradation and safety standards. Then, common fabrication methods for bioresorbable materials are introduced, along with challenges. The final section provides representative examples of bioresorbable IMDs for various applications with an emphasis on materials, device functionality, and fabrication methods.
Association between the intake of soy foods and risk of breast cancer in Korean women
Authors: Myung-Hee Shin, Seok-Jin Nam, Jung-Hyun Yang
Journal: Cancer Research (2008)

3085  High intake of soy foods has been suggested to reduce the risk of breast cancer especially among Asian women. However, experimental data show mild estrogenic effect of soy constituents and epidemiologic evidences are also not consistent. We investigated the association between the intake of soy foods and the risk of breast cancer among Korean women in a case-control study.  Newly diagnosed breast cancer cases were recruited between 1998 and 2004 from a university hospital in Seoul. Non-cancer controls were selected from 7 different clinical departments during the same time period from the same hospital. Detailed interview on the various life-style factors was conducted. A total of 1399 cases and 938 controls were interviewed for dietary intake using food-frequency questionnaire. Multivariate odds ratios (mOR) and 95% confidence intervals (CI) of the daily intakes of soy bean, tofu, and soy bean paste for breast cancer risk were estimated by unconditional logistic regression.  When adjusted for known risk factors, such as, age, educational attainment, family history of breast cancer, history of benign breast diseases, smoking, alcohol intake, height, body mass index, number of full term delivery, age at menarche, menopausal status, and hormone replacement therapy, women in the highest quintile (q5) of soy bean intake had the lower odds of having the breast cancer (mOR = 0.70, 95% CI = 0.54-0.89) compared to those in the lowest quintile (q1). High intake of tofu also showed inverse association with breast cancer risk (q5 vs. q1; mOR = 0.67, 95%CI = 0.51-0.89). High intake of soy bean paste showed non significant association with breast cancer (q5 vs. q1; mOR = 0.85, 95%CI = 0.63-1.14). The association between soy bean intake and breast cancer risk was stronger in postmenopausal women (mOR = 0.60, 95%CI = 0.39-0.91) than premenopausal women (mOR = 0.76, 95%CI = 0.56-1.04). The association between tofu intake and breast cancer risk was stronger in premenopausal women (mOR = 0.62, 95%CI=0.44-0.87) than postmenopausal women (mOR = 0.78, 95%CI = 0.45-1.26) . Our result suggests that high intakes of soy bean and tofu, but not of soy bean paste, had inverse associations with risk of breast cancer.
An overview of filtration efficiency through the masks: Mechanisms of the aerosols penetration
Authors: A. Tcharkhtchi, N. Abbasnezhad, M. Zarbini Seydani, N. Zirak, S. Farzaneh, M. Shirinbayan
Journal: Bioactive Materials (2020)

The masks have always been mentioned as an effective tool against environmental threats. They are considered as protective equipment to preserve the respiratory system against the non-desirable air droplets and aerosols such as the viral or pollution particles. The aerosols can be pollution existence in the air, or the infectious airborne viruses initiated from the sneezing, coughing of the infected people. The filtration efficiency of the different masks against these aerosols are not the same, as the particles have different sizes, shapes, and properties. Therefore, the challenge is to fabricate the filtration masks with higher efficiency to decrease the penetration percentage at the nastiest conditions. To achieve this concept, knowledge about the mechanisms of the penetration of the aerosols through the masks at different effective environmental conditions is necessary. In this paper, the literature about the different kinds of face masks and respiratory masks, common cases of their application, and the advantages and disadvantages of them in this regard have been reviewed. Moreover, the related mechanisms of the penetration of the aerosols through the masks are discussed. The environmental conditions affecting the penetration as well as the quality of the fabrication are studied. Finally, special attention was given to the numerical simulation related to the different existing mechanisms.
Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes
Authors: Asaf Poran, Dewi Harjanto, Matthew Malloy, Christina M. Arieta, Daniel A. Rothenberg, Divya Lenkala, Marit M. van Buuren, Terri A. Addona, Michael S. Rooney, Lakshmi Srinivasan, Richard B. Gaynor
Journal: Genome Medicine (2020)

Abstract Background The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports identify protective roles for both humoral and cell-mediated immunity for SARS-CoV-2. Methods We leveraged our bioinformatics binding prediction tools for human leukocyte antigen (HLA)-I and HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I and HLA-II alleles to predict peptide binding to diverse allele sets. We applied these binding predictors to viral genomes from the Coronaviridae family and specifically focused on T cell epitopes from SARS-CoV-2 proteins. We assayed a subset of these epitopes in a T cell induction assay for their ability to elicit CD8 + T cell responses. Results We first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then utilized our HLA-I and HLA-II predictors to identify 11,897 HLA-I and 8046 HLA-II candidate peptides which were highly ranked for binding across 13 open reading frames (ORFs) of SARS-CoV-2. These peptides are predicted to provide over 99% allele coverage for the US, European, and Asian populations. From our SARS-CoV-2-predicted peptide-HLA-I allele pairs, 374 pairs identically matched what was previously reported in the ViPR database, originating from other coronaviruses with identical sequences. Of these pairs, 333 (89%) had a positive HLA binding assay result, reinforcing the validity of our predictions. We then demonstrated that a subset of these highly predicted epitopes were immunogenic based on their recognition by specific CD8 + T cells in healthy human donor peripheral blood mononuclear cells (PBMCs). Finally, we characterized the expression of SARS-CoV-2 proteins in virally infected cells to prioritize those which could be potential targets for T cell immunity. Conclusions Using our bioinformatics platform, we identify multiple putative epitopes that are potential targets for CD4 + and CD8 + T cells, whose HLA binding properties cover nearly the entire population. We also confirm that our binding predictors can predict epitopes eliciting CD8 + T cell responses from multiple SARS-CoV-2 proteins. Protein expression and population HLA allele coverage, combined with the ability to identify T cell epitopes, should be considered in SARS-CoV-2 vaccine design strategies and immune monitoring.