tbuckley/cabot-search huggingface dataset:
Formation of 3D Self‐Organized Neuron‐Glial Interface Derived from Neural Stem Cells via Mechano‐Electrical Stimulation
Authors: Youyi Tai, Gerardo Ico, Karen Low, Junze Liu, Tanvi Jariwala, David Garcia‐Viramontes, Kyu Hwan Lee, Nosang V. Myung, B. Hyle Park, Jin Nam
Journal: Advanced Healthcare Materials (2021)

Abstract Due to dissimilarities in genetics and metabolism, current animal models cannot accurately depict human neurological diseases. To develop patient‐specific in vitro neural models, a functional material‐based technology that offers multi‐potent stimuli for enhanced neural tissue development is devised. An electrospun piezoelectric poly(vinylidene fluoride‐trifluoroethylene) (P(VDF‐TrFE)) nanofibrous scaffold is systematically optimized to maximize its piezoelectric properties while accommodating the cellular behaviors of neural stem cells. Hydro‐acoustic actuation is elegantly utilized to remotely activate the piezoelectric effect of P(VDF‐TrFE) scaffolds in a physiologically‐safe manner for the generation of cell‐relevant electric potentials. This mechano‐electrical stimulation, which arose from the deflection of the scaffold and its consequent generation of electric charges on the scaffold surface under hydro‐acoustic actuation, induces the multi‐phenotypic differentiation of neural stem cells simultaneously toward neuronal, oligodendrocytic, and astrocytic phenotypes. As compared to the traditional biochemically‐mediated differentiation, the 3D neuron‐glial interface induced by the mechano‐electrical stimulation results in enhanced interactions among cellular components, leading to superior neural connectivity and functionality. These results demonstrate the potential of piezoelectric material‐based technology for developing functional neural tissues in vitro via effective neural stem cell modulation with multi‐faceted regenerative stimuli.
Control imaging after blunt renal trauma in the adult patient - A single level 1 trauma center experience
Authors: C. Deininger, T. Freude, F. Wichlas, L.K. Kriechbaumer, S.H.M. Deininger, P. Törzsök, L. Lusuardi, M. Pallauf, A. Kanovsky, S. Deininger
Journal: European Urology (2021)
<i>ZBTB33</i> Is Mutated in Clonal Hematopoiesis and Myelodysplastic Syndromes and Impacts RNA Splicing
Authors: Ellen M Beauchamp, Matthew Leventhal, Elsa Bernard, Emma R Hoppe, Gabriele Todisco, Maria Creignou, Anna Gallì, Cecilia A Castellano, Marie McConkey, Akansha Tarun, Waihay Wong, Monica Schenone, Caroline Stanclift, Benjamin Tanenbaum, Edyta Malolepsza, Björn Nilsson, Alexander G Bick, Joshua S Weinstock, Mendy Miller, Abhishek Niroula, Andrew Dunford, Amaro Taylor-Weiner, Timothy Wood, Alex Barbera, Shankara Anand, Bruce M Psaty, Pinkal Desai, Michael H Cho, Andrew D Johnson, Ruth Loos, Daniel G MacArthur, Monkol Lek, Donna S Neuberg, Kasper Lage, Steven A Carr, Eva Hellstrom-Lindberg, Luca Malcovati, Elli Papaemmanuil, Chip Stewart, Gad Getz, Robert K Bradley, Siddhartha Jaiswal, Benjamin L Ebert
Journal: Blood Cancer Discovery (2021)

Clonal hematopoiesis results from somatic mutations in cancer driver genes in hematopoietic stem cells. We sought to identify novel drivers of clonal expansion using an unbiased analysis of sequencing data from 84,683 persons and identified common mutations in the 5-methylcytosine reader,
A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model
Authors: Manoj Kumar, Burak Toprakhisar, Matthias Van Haele, Asier Antoranz, Ruben Boon, Francois Chesnais, Jonathan De Smedt, Tine Tricot, Teresa Izuel Idoype, Marco Canella, Pierre Tilliole, Jolan De Boeck, Manmohan Bajaj, Adrian Ranga, Francesca Maria Bosisio, Tania Roskams, Leo A. van Grunsven, Catherine M. Verfaillie
Journal: Biomaterials (2021)

Chronic liver injury, as observed in non-alcoholic steatohepatitis (NASH), progressive fibrosis, and cirrhosis, remains poorly treatable. Steatohepatitis causes hepatocyte loss in part by a direct lipotoxic insult, which is amplified by derangements in the non-parenchymal cellular (NPC) interactive network wherein hepatocytes reside, including, hepatic stellate cells, liver sinusoidal endothelial cells and liver macrophages. To create an in vitro culture model encompassing all these cells, that allows studying liver steatosis, inflammation and fibrosis caused by NASH, we here developed a fully defined hydrogel microenvironment, termed hepatocyte maturation (HepMat) gel, that supports maturation and maintenance of pluripotent stem cell (PSC) derived hepatocyte- and NPC-like cells for at least one month. The HepMat-based co-culture system modeled key molecular and functional features of TGFβ-induced liver fibrosis and fatty-acid induced inflammation and fibrosis better than monocultures of its constituent cell populations. The novel co-culture system should open new avenues for studying mechanisms underlying liver steatosis, inflammation and fibrosis as well as for assessing drugs counteracting these effects.
Haplotype-resolved genome assembly provides insights into evolutionary history of the tea plant Camellia sinensis
Authors: Xingtan Zhang, Shuai Chen, Longqing Shi, Daping Gong, Shengcheng Zhang, Qian Zhao, Dongliang Zhan, Liette Vasseur, Yibin Wang, Jiaxin Yu, Zhenyang Liao, Xindan Xu, Rui Qi, Wenling Wang, Yunran Ma, Pengjie Wang, Naixing Ye, Dongna Ma, Yan Shi, Haifeng Wang, Xiaokai Ma, Xiangrui Kong, Jing Lin, Liufeng Wei, Yaying Ma, Ruoyu Li, Guiping Hu, Haifang He, Lin Zhang, Ray Ming, Gang Wang, Haibao Tang, Minsheng You
Journal: Nature Genetics (2021)

Abstract Tea is an important global beverage crop and is largely clonally propagated. Despite previous studies on the species, its genetic and evolutionary history deserves further research. Here, we present a haplotype-resolved assembly of an Oolong tea cultivar, Tieguanyin. Analysis of allele-specific expression suggests a potential mechanism in response to mutation load during long-term clonal propagation. Population genomic analysis using 190 Camellia accessions uncovered independent evolutionary histories and parallel domestication in two widely cultivated varieties, var. sinensis and var. assamica . It also revealed extensive intra- and interspecific introgressions contributing to genetic diversity in modern cultivars. Strong signatures of selection were associated with biosynthetic and metabolic pathways that contribute to flavor characteristics as well as genes likely involved in the Green Revolution in the tea industry. Our results offer genetic and molecular insights into the evolutionary history of Camellia sinensis and provide genomic resources to further facilitate gene editing to enhance desirable traits in tea crops.
Abstract 959: C/EBPβ antagonist peptide, ST101, as a therapeutic approach in breast cancer
Authors: Jim A. Rotolo, Mark Koester, Ricardo Ramirez, Lila Ghamsari, Siok Leong, Erin Gallagher, Gene Merutka, Barry J. Kappel
Journal: Cancer Research (2021)

Abstract Breast cancer (BC) is the most common invasive cancer in women, with more than 2.1 million cases and over 626,000 deaths occurring worldwide annually. Although age-adjusted mortality from BC has been declining since 1990, the median survival for patients with metastatic disease remains at 2-3 years, and 5-year survival approximates 25%. Thus, the medical need for more effective agents in this clinical setting remains very high. CCAAT/Enhancer Binding Protein Beta (C/EBPβ) is a transcription factor overexpressed in many cancers that regulates expression of factors that promote tumor survival, proliferation and inhibit differentiation. C/EBPβ dimers, such as with Jun/Fos and CREB/ATF family members, form via basic leucine zipper (bZIP)-driven coiled-coil interactions and are necessary for its association with DNA and transcriptional activity. Due in part to the difficulty in therapeutically targeting transcription factors, no effective C/EBPβ inhibitors are clinically available. ST101 is a novel peptide antagonist of C/EBPβ currently being evaluated in a Phase 1/2 clinical study in patients with advanced unresectable and metastatic solid tumors. ST101 was designed to bind the C/EBPβ bZIP domain, thereby preventing dimer formation and inhibiting its transcriptional activity. Here we describe ST101 non-clinical anti-tumor activity to support further development as a therapeutic approach in BC. In vitro studies in 4T1-luc triple-negative breast cancer (TNBC) and MCF7 HRPOS breast adenocarcinoma cells demonstrate ST101 dose-dependent impact of cell viability (EC50 of 4.8 and 2.1 µM, respectively), accompanied by significant impact on C/EBPβ-mediated gene expression as determined by qPCR analysis. In contrast, normal human mammary epithelial cells were not sensitive to ST101 (EC50 &amp;gt;100 µM). In vivo experiments indicate dose-dependent tumor growth inhibition in an orthotopic 4T1-luc model following ST101 exposure, with significant tumor growth delays observed following 25 mg/kg ST101 (p&amp;lt;0.05 vs. controls). Mice treated with 25 mg/kg ST101 via subcutaneous injection demonstrated significant tumor growth delay and decrease in tumor volume vs. controls. These data emphasize the potential of ST101 as a potent peptide therapeutic for HRPOS and TN BC. Citation Format: Jim A. Rotolo, Mark Koester, Ricardo Ramirez, Lila Ghamsari, Siok Leong, Erin Gallagher, Gene Merutka, Barry J. Kappel. C/EBPβ antagonist peptide, ST101, as a therapeutic approach in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 959.
Abstract 796: Investigating incidence and survival patterns of cutaneous malignant melanoma in the United States from 2006-2017
Authors: Yae Kye, Luis Alvarado, Alok Dwivedi, Jessica Chacon
Journal: Cancer Research (2021)

Abstract Introduction: Skin cancers are one of the most common cancers in the United States with melanoma being the fifth leading cause of cancer. Despite its increasing incidence, there are limited studies on how skin cancer affects different races and ethnicities. Here, we conduct a population-based registry study to derive incidence and survival patterns of cutaneous malignant melanoma (CMM) in the US from 2006-2017. 17 population-based cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. A total of 58,666 cases with histologically confirmed cases of cutaneous malignant melanoma were evaluated. Surprisingly, the CMM subtype that was predominantly found in the non-Hispanic whites (56%) and Hispanic whites (45%) was acral lentiginous melanoma, while “other” melanomas were predominant in the Asian (54%) and Black (77%) populations. Superficial spreading and lentigo maligna melanomas presented more commonly in men (69% and 63%). In addition, nodular and lentigo maligna melanomas had the poorest survival rates and had a median survival of 26 and 21 months. Methods: The Surveillance, Epidemiology, and End Results Program (SEER) of the National Cancer Institute was used to calculate the incidence, proportion, and survival data. 58,66 histologically confirmed CMM cases reported by the 17 cancer registries from 2006-2017 were used. The 17 registries include 14 states (Alaska, greater and California, Connecticut, Georgia, Hawaii, Idaho, Iowa, Kentucky, Louisiana, Massachusetts, New Mexico, New York, Utah, Washington) and 4 standard metropolitan areas (Los Angeles, San Francisco-Oakland, and San Jose-Monterey, California; and Seattle-Puget Sound, Washington). Cases of the 4 major CMM subtypes as well as the “other” subtypes were identified using the World Health Organization's International Classification of Diseases for Oncology (ICD-0-3) morphology code. Conclusion and future direction: CMM has been steadily increasing in incidence within the US. Moreover, the incidence rate of CMM in the Hispanic population has been rising. It is important that we continue to assess the epidemiological characteristics and trends of CMM subtypes in the US and increase awareness of skin cancer and its preventative measures in the Hispanic population. In addition, future studies should analyze the genetic and environmental factors that may be contributing to observed incidence rates in the Hispanic population. Citation Format: Yae Kye, Luis Alvarado, Alok Dwivedi, Jessica Chacon. Investigating incidence and survival patterns of cutaneous malignant melanoma in the United States from 2006-2017 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 796.
Potential of Plasmatic Biomarkers to Predict Acute Gvhd Severity: A Validation Study in a Prospective Cohort of 177 Patients
Authors: Marie Robin, Raphael Porcher, Laetitia Taurines, Bastien Oriano, Regis Peffault De Latour, Flore Sicre De Fontbrune, David Michonneau, Nathalie Dhedin, Christine Chomienne, Gérard Socié, Marie-Hélène Schlageter
Journal: Blood (2017)
History of urological malignancies before kidney transplantation, oncological outcome on the long term
Authors: R. Boissier, R.H Hidalgo, O. Rodriguez-Faba, A. Territo, J.D. Subiela, J. Huguet, A. Sanchez-Puy, A. Galliolia, D. Vanacore, A. Mercade, C. Martinez, J. Palou, L. Guirado, A. Breda
Journal: European Urology (2021)
Abstract 14856: Adipocyte-Specific Deletion of Ager Mice With Established Obesity Induces Weight Loss and Induces Adaptive Thermogenesis in Adipose Tissue
Authors: Lakshmi Arivazhagan, Henry H Ruiz, Jay Pendse, Laura Frye, Kaamashri Mangar, Ann Marie Schmidt
Journal: Circulation (2019)

Introduction: Obesity is an epidemic, with over one third of adults in the US alone classified as overweight or obese. It often leads to insulin resistance (IR), type 2 diabetes and its complicatio...
Induction of Interferon‐γ and Tissue Inflammation by Overexpression of Eosinophil Cationic Protein in T Cells and Exosomes
Authors: Huai‐Chia Chuang, Ming‐Han Chen, Yi‐Ming Chen, Yi‐Ru Ciou, Chia‐Hsin Hsueh, Ching‐Yi Tsai, Tse‐Hua Tan
Journal: Arthritis & Rheumatology (2021)

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Serum-derived exosomes are increased in SLE patients and are correlated with disease severity. This study was undertaken to investigate whether T cell-derived exosomal proteins play a role in SLE pathogenesis.We characterized proteins in T cell-derived exosomes from SLE patients and healthy controls by MACSPlex exosome analysis and proteomics. To study the potential pathogenic functions of the exosomal protein identified, we generated and characterized T cell-specific transgenic mice that overexpressed that protein in T cells.We identified eosinophil cationic protein (ECP, also called human RNase III) as overexpressed in SLE T cell-derived exosomes. T cell-specific ECP-transgenic mice (n = 5 per group) displayed early induction of serum interferon-γ (IFNγ) levels (P = 0.062) and inflammation of multiple tissue types. Older T cell-specific ECP-transgenic mice (n = 3 per group) also displayed an increase in follicular helper T cell and plasma B cell numbers, and in autoantibody levels (P < 0.01). Single-cell RNA sequencing showed the induction of IFNγ messenger RNA (P = 2.2 × 10-13 ) and inflammatory pathways in ECP-transgenic mouse T cells. Notably, adoptively transferred ECP-containing exosomes stimulated serum autoantibody levels (P < 0.01) and tissue IFNγ levels in the recipient mice (n = 3 per group). The transferred exosomes infiltrated into multiple tissues of the recipient mice, resulting in hepatitis, nephritis, and arthritis.Our findings indicate that ECP overexpression in T cells or T cell-derived exosomes may be a biomarker and pathogenic factor for nephritis, hepatitis, and arthritis associated with SLE.
Abstract 1861: Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse
Authors: Li Hui, Hui Lu, Yabo Zhang, Shuwen Huang, Ping Zhang, Huizhen Zhao, Ruifang Chang, Bing Yang, Fengqian Zhang, Wendong Yang, Fang Yang, Hao Yang, Jiawei Yao, Lei Chen, Qingcong Lin
Journal: Cancer Research (2021)

Abstract The common challenges of bispecific therapeutic antibody discovery are immunogenicity and chain mispairing issues. Biocytogen's RenLiteTM immunoglobulin humanized mouse is designed not only to overcome these two issues, but also to provide a full human heavy chain repertoire diversity. RenLiteTM mouse carries full human heavy chain VDJ loci and a fixed common human light chain VJ gene. The derived antibodies share the same light chain with different heavy chain variable domain. This technology dramatically simplifies the following heavy and light chain pairing process. Antibodies generated by RenLiteTM mice underwent natural selection, differentiation, and affinity maturation in vivo utilizing a human heavy chain repertoire, the potential of immunogenicity is minimized. RenLiteTM mice show robust immune response comparable to wild type mice and RenLiteTM mice derived antibodies have high binding affinity at subnanomolar range. RenLiteTM antibodies also showed strong in vivo efficacy against tumor growth in xenograft mouse models. In summary, RenLiteTM mouse is a powerful tool for advancing current bispecific or multispecific antibody discovery. Citation Format: Li Hui, Hui Lu, Yabo Zhang, Shuwen Huang, Ping Zhang, Huizhen Zhao, Ruifang Chang, Bing Yang, Fengqian Zhang, Wendong Yang, Fang Yang, Hao Yang, Jiawei Yao, Lei Chen, Qingcong Lin. Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1861.
Abstract 2052: TRIP13 amplification confers PARP inhibitor resistance and polymerase theta inhibitor sensitivity
Authors: Jeffrey Patterson-Fortin, Jia Zhou, Alan D'Andrea
Journal: Cancer Research (2021)

Abstract Genome integrity is critical for cellular survival and is maintained by DNA repair pathways collectively known as the DNA damage response (DDR). Double-stranded breaks (DSBs) are the most deleterious form of DNA damage and can be repaired through homologous recombination (HR), non-homologous end-joining (NHEJ), and microhomology-mediated end-joining (MMEJ). The first step in both HR and MMEJ is resection of the DNA DSB termini to create single-stranded DNA 3' overhangs. In contrast, the 53BP1-Shieldin complex limits DNA end-resection and promotes NHEJ. Defects in HR repair can be present in cancer cells secondary to germline or somatic mutations in BRCA1, BRCA2, or other genes in the HR pathway, and such defects confer sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP). Resistance to PARP inhibitors can occur if there is loss of the 53BP1-Shieldin complex or amplification of TRIP13, a negative regulator of the 53BP1-Shieldin complex (Clairmont, et al. NCB 22:87, 2020). Here, we show that cells with TRIP13 amplification have increased DNA end-resection and increased expression of polymerase theta (POLQ), the critical enzyme for MMEJ. The resulting increase in POLQ activity limits DNA end-resection and increases MMEJ-mediated DSB repair. In these cells, inhibition of POLQ by a POLQ inhibitor, novobiocin (Zhou, et al. bioRxiv, 2020), resulted in excessive DNA end-resection, replication stress, activation of the ataxia-telangiectasia and Rad3 related (ATR) DNA damage response, and ultimately cell death. Conversely, knockdown of TRIP13 promotes PARP inhibitor sensitivity and POLQ inhibitor resistance. Thus, TRIP13 amplification may function as a biomarker for resistance to PARP inhibitors and sensitivity to a POLQ inhibitor. In summary, these results reveal a mechanism of PARP inhibitor resistance and POLQ inhibitor sensitivity in HR-deficient cells, provide a rationale for using TRIP13 as a biomarker for PARP inhibitor or POLQ inhibitor sensitivity, and may offer novel therapeutic strategies for PARP inhibitor resistant cancers. Citation Format: Jeffrey Patterson-Fortin, Jia Zhou, Alan D'Andrea. TRIP13 amplification confers PARP inhibitor resistance and polymerase theta inhibitor sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2052.
Prevalence of negative child disciplinary practices and its associated factors as reported by mothers in the West Bank: a cross-sectional study
Authors: Bashaer Al-Natsheh, Rawan Al-Sharif, Rawnaq Khdour, Shireen Othman, Wala Durgham, Aya Shamasneh, Aiasha Houshiah, Rula Ghandour, Shiraz Nasr, Rita Giacaman
Journal: The Lancet (2021)
Abstract 831: State of medical and surgical oncology training in India: An infrastructural challenge to delivering high-quality cancer care
Authors: Ahmad Ozair, Faique Rahman, Kaushal K. Singh
Journal: Cancer Research (2021)

Abstract Introduction: Cancer care delivery in low- and middle-income countries (LMICs) is significantly influenced by the number and distribution of oncologists, which are products of the state of oncology training in those LMICs. In LMICs like India, where the number of trained oncologists is low, cancer care is often delivered by generalists, resulting in poorer outcomes. India, with a population of 1.38 billion people, was projected to have needed over 5000 oncologists in 2020. But, the Global Survey of Clinical Oncology Workforce reported only 1500 clinical oncologists here in 2018. Therefore, we sought to systematically determine and describe the current state of accredited oncology training in India. Methods: We searched, in October 2020, the databases of two major accrediting bodies, the National Medical Council (NMC) and the National Board of Examinations (NBE) to determine the total number of programs and the positions therein for the fields of medical, surgical, and gynecological oncology. We correlated our search with the current regulations from NMC and NBE. Results: Both the NMC and NBE currently offer training for 3-year specialty oncology training after 3-years of medical or surgical residency. We found India currently has a total of 166, 139, and 22 training positions for surgical, medical, and gynecological oncology respectively (Table 1). Significant variation in the number of positions exists, with a few institutions providing training to over 10 fellows, leading to concerns about the volume of training and exposure to cases. There is a clustering of training programs in major metropolitan cities. Discussion: India is currently training a highly insufficient number of clinical oncologists for its increasing cancer burden. Clustering of training programs in metropolitan cities results in a greater likelihood of trained physicians practicing in the same location. Both of these may cause greater disparities in cancer care delivery. Table 1.State of accredited oncology training programs and positions in India.SubspecialtyMCI-accredited trainingNBE-accredited trainingNumber of training programsTotal number of positionsMedian (IQR) number of positions per programNumber of training programsTotal number of positionsMean number of positions per programSurgical oncology23983 (2.5)36682Medical Oncology18762 (4)30632Gynecologic Oncology8152 (0.5)472 Citation Format: Ahmad Ozair, Faique Rahman, Kaushal K. Singh. State of medical and surgical oncology training in India: An infrastructural challenge to delivering high-quality cancer care [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 831.
A 2-arm pseudo-randomized multicenter (MR PROPER) trial: MRI-directed pathway outperforms TRUS-directed pathway in prostate cancer diagnosis following upfront risk stratification
Authors: I.M. Wagensveld, D.F. Osses, P.M. Groenendijk, F.M. Zijta, C.H. Bangma, J.P.M. Sedelaar, J.O. Barentsz, B. Arbeel, G.P. Krestin, M.J. Roobol, I.G. Schoots
Journal: European Urology (2021)