tbuckley/cabot-search huggingface dataset:
AB0370 SAFETY OF CS20AT04, A HAPLOIDENTICAL ALLOGENEIC BONE MARROW-DERIVED MESENCHYMAL STEM CELLS, IN A PHASE 1 STUDY IN LUPUS NEPHRITIS
Authors: C. B. Choi, T. Y. Lee, K. S. Kim, S. C. Bae
Journal: Annals of the Rheumatic Diseases (2020)

Background: Mesenchymal stem cells are known to have immunomodulatory properties and may potentially have therapeutic effect in lupus nephritis. Mesenchymal stem cells form a haploidentical donor are an attractive cell source Objectives: CS20AT04, a haploidentical allogeneic bone marrow-derived mesenchymal stem cell, was evaluated in patients with lupus nephritis for safety and tolerability. Methods: This was a single-arm phase 1 dose-escalation trial of CS20AT04 in adult patients with lupus nephritis ( NCT03174587 ). A 3 + 3 design was used for dose escalation. The starting dose was 2.0 x 106 cells/kg and was escalated to 3.0 x 106 cells/kg if there no dose-limiting toxicity. The primary objective was to determine the maximum tolerated dose and evaluate the safety and tolerability at 28 days after the infusion. Results: Seven patients were enrolled in the study. Patients received CS20AT04 through intravenous infusion. The initial dose of 2.0 x 106 cells/kg was administered for the first 3 patients without any dose limiting toxicity. There was 1 patient who were not administered the full 2.0 x 106 cells/kg dose due to technical error during infusion. The patient did not show dose limiting toxicity, but 1 additional patient was enrolled to have 3 patients who received the full 2.0 x 106 cells/kg dose before escalating to the next level dose. The dose of 3.0 x 106 cells/kg was administered for the next 3 patients without any dose limiting toxicity. Three adverse events were reported (1 diarrhea, 1 toothache, and 1 arthralgia) and they were all NCI-CTC grade I events. Conclusion: CS20AT04 was well tolerated in single dose up to 3.0 x 106 cells/kg in patients with lupus nephritis. Acknowledgments: This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea (grant number: HI15C0778). Disclosure of Interests: Chan-Bum Choi: None declared, Tae Yong Lee Shareholder of: Corestem Inc, Employee of: Corestem Inc, Kyung Suk Kim Shareholder of: Corestem Inc, Employee of: Corestem Inc, Sang-Cheol Bae: None declared
Relationship of Altmetric Attention Score to Overall Citations and Downloads for Papers Published in JACC
Authors: Purvi Parwani, Glen P. Martin, Mohamed O. Mohamed, Amer Hajeer, Maureen Nwaokoro, Akhil Narang, Andrew D. Choi, Juan Lopez-Mattei, Andrew M. Freeman, Mamas A. Mamas
Journal: Journal of the American College of Cardiology (2020)
The role of dermatology in Kaposi sarcoma diagnosis across 3 regions in sub-Saharan Africa
Authors: Divya Seth, Victoria L. Williams, Devon E. McMahon, Susan Regan, Naftali Busakhala, Kara Wools-Kaloustian, Karen Mosojane, Tlotlo B. Ralefala, Mukendi Kayembe, Kenneth Iregbu, Vivian Kwaghe, Elima Jedy-Agba, Linda Oyesiku, Toby Maurer, Antoine Jaquet, Ingrid V. Bassett, Jeff Martin, Surbhi Grover, Esther E. Freeman
Journal: Journal of the American Academy of Dermatology (2020)
Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up
Authors: Joost H van den Berg, Bianca Heemskerk, Nienke van Rooij, Raquel Gomez-Eerland, Samira Michels, Maaike van Zon, Renate de Boer, Noor A M Bakker, Annelies Jorritsma-Smit, Marit M van Buuren, Pia Kvistborg, Hergen Spits, Remko Schotte, Henk Mallo, Matthias Karger, Joris A van der Hage, Michel W J M Wouters, Loes M Pronk, Marnix H Geukes Foppen, Christian U Blank, Jos H Beijnen, Bastiaan Nuijen, Ton N Schumacher, John B A G Haanen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses. Purpose Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial. Experimental Ten patients were treated with TIL therapy. Infusion products and peripheral blood samples were phenotypically characterized and neoantigen reactivity was assessed. Here, we present long-term clinical outcome and translational data on neoantigen reactivity of the T cell products. Results Five out of 10 patients, who were all anti-PD-1 naïve at time of treatment, showed an objective clinical response, including two patients with a complete response that are both ongoing for more than 7 years. Immune monitoring demonstrated that neoantigen-specific T cells were detectable in TIL infusion products from three out of three patients analyzed. For six out of the nine neoantigen-specific T cell responses detected in these TIL products, T cell response magnitude increased significantly in the peripheral blood compartment after therapy, and neoantigen-specific T cells were detectable for up to 3 years after TIL infusion. Conclusion The clinical results from this study confirm the robustness of TIL therapy in metastatic melanoma and the potential role of neoantigen-specific T cell reactivity. In addition, the data from this study supported the rationale to initiate an ongoing multicenter phase III TIL trial.
FRI0395 PROGNOSIS OF TREATMENT OUTCOMES IN PATIENTS WITH ANKLE JOINT OSTEOCHONDRAL LESIONS AND DEFECTS
Authors: O. Burianov, L. Khimion, T. Omelchenko, V. Lyanskorynsky, E. Levitskyi
Journal: Annals of the Rheumatic Diseases (2020)

Background: in most cases osteochondral lesions and defects (OHLD) in the ankle joint are the consequences of trauma, and the results of their treatment depend on a number of factors. Some factors are directly related to the area of damage (depth, localization, size), others are connected to the patients age, presence of degenerative changes in the affected joint, comorbidities, body mass index (BMI), etc. Objectives: to develop an effective system for predicting long-term outcomes in patients with ankle joint OHLD. Methods: 24 prognostic factors (age, gender, severity of injury, Charlson comorbidity index, BMI, OA stage, size of defect, localization of injury, degree of osteoporosis, contracture, instability, etc.) influence on the long-term (36 ± 4.5 months) treatment outcomes was analyzed by Bayesian probability analysis in 223 patients after ankle joint OHLD. The prognostic coefficient (PC) was calculated by Wald sequential analysis for each prognostic factor and prognostic system was developed for prediction of high, medium or low probability of positive treatment result, which was determined as a functional joint outcome in AOFAS 75 - 100 points. Results: the greatest predictive value for the positive result of OHLD treatment had the following factors: age&lt; 40 years (PC = 8.5); BMI &lt; 25 kg/m 2 (PC=7.0), time from trauma &lt; 1 year (PC = 4,1); OA stage &lt; II (PC = 7.2); size of OHLD &lt;1.0 cm 2 ; volume &lt;1.5 cm 3 (PC = 8.0). The prognostic system is based on the calculating of total factors values for individual patients case in points (Σ PC). If Σ PC is less (-20) the probability of achieving a positive joint-saving result is absent; at Σ PC from (-20) to (+40) the probability is medium; and at Σ PC above (+40) probability is high. The accuracy of the prognostic assessment was retrospectively tested with a 95% confidence interval, the accuaracy of predicitive method – 84,17% (76,59-89,62)%. Conclusion: the size and volume of osteochondral damage, BMI, age and time from trauma has the greatest predictive value for the determination of the long-term results of treatment in patients with ankle joint OHLD; use of the developed prognostic method can be used as a basis for the clinical decision making in choosing different approaches in treatment. Disclosure of Interests: None declared
Hypoxia-inducible factors and innate immunity in liver cancer
Authors: Vincent Wai-Hin Yuen, Carmen Chak-Lui Wong
Journal: Journal of Clinical Investigation (2020)

The liver has strong innate immunity to counteract pathogens from the gastrointestinal tract. During the development of liver cancer, which is typically driven by chronic inflammation, the composition and biological roles of the innate immune cells are extensively altered. Hypoxia is a common finding in all stages of liver cancer development. Hypoxia drives the stabilization of hypoxia-inducible factors (HIFs), which act as central regulators to dampen the innate immunity of liver cancer. HIF signaling in innate immune cells and liver cancer cells together favors the recruitment and maintenance of pro-tumorigenic immune cells and the inhibition of anti-tumorigenic immune cells, promoting immune evasion. HIFs represent attractive therapeutic targets to inhibit the formation of an immunosuppressive microenvironment and growth of liver cancer.
Four in 10 dementia cases could be prevented or delayed by targeting risk factors, report says
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Around 40% of dementia cases worldwide could have potentially been delayed or prevented if 12 risk factors had been targeted, the Lancet commission on dementia has said.1

The 28 dementia experts on the commission have added three modifiable risk factors to the nine they advised on in 2017: excessive alcohol consumption, traumatic brain injury, and air pollution.

The nine factors they previously highlighted were less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, and low social contact.

“Together the 12 modifiable risk factors account for around 40% of worldwide dementias, which consequently could theoretically be prevented or delayed. The potential for prevention is high and might be higher in low-income and middle-income countries where more dementias occur,” the report said.

Around 50 million of the world’s people have dementia, and this number …
A Move to Demarginalize the Liver Donor Allograft
Authors: Austin D. Schenk, W. Kenneth Washburn
Journal: JAMA Surgery (2020)

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Increased prediction value of biomarker combinations for the conversion of mild cognitive impairment to Alzheimer’s dementia
Authors: Aonan Zhao, Yuanyuan Li, Yi Yan, Yinghui Qiu, Binyin Li, Wei Xu, Ying Wang, Jun Liu, Yulei Deng
Journal: Translational Neurodegeneration (2020)

Progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia can be predicted by clinical features and a combination of biomarkers may increase the predictive power. In the present study, we investigated whether the combination of olfactory function and plasma neuronal-derived exosome (NDE) Aβ1-42 can best predict progression to AD dementia.87 MCI patients were enrolled and received the cognitive assessment at 2-year and 3-year follow-up to reevaluate cognition. In the meanwhile, 80 healthy controls and 88 AD dementia patients were enrolled at baseline as well to evaluate the diagnose value in cross-section. Olfactory function was evaluated with the sniffin sticks (SS-16) and Aβ1-42 levels in NDEs were determined by ELISA. Logistic regression was performed to evaluate the risk factors for cognitive decline in MCI at 2-year and 3-year revisits.In the cross cohort, lower SS-16 scores and higher Aβ1-42 levels in NDEs were found in MCI and AD dementia compared to healthy controls. For the longitudinal set, 8 MCI individuals developed AD dementia within 2 years, and 16 MCI individuals developed AD dementia within 3 years. The two parameter-combination of SS-16 scores and Aβ1-42 level in NDEs showed better prediction in the conversion of MCI to AD dementia at 2-year and 3-year revisit. Moreover, after a 3-year follow-up, SS-16 scores also significantly predicted the conversion to AD dementia, where lower scores were associated with a 10-fold increased risk of developing AD dementia (p = 0.006). Similarly, higher Aβ1-42 levels in NDEs in patients with MCI increased the risk of developing AD dementia by 8.5-fold (p = 0.002).A combination of two biomarkers of NDEs (Aβ1-42) and SS-16 predicted the conversion of MCI to AD dementia more accurately in combination. These findings have critical implications for understanding the pathophysiology of AD dementia and for developing preventative treatments for cognitive decline.
複数のアジア人集団におけるHER2遺伝子増幅を示す進行乳癌に対する二次治療としてのラパチニブ+パクリタキセルとパクリタキセル単剤療法との比較: TyTAN-A無作為化第III相研究
Authors: Satoh Taroh, XU Rui-Hua, Chung Hyun Cheol, Sun Guo-Ping, Doi Toshihiko, XU Jian-Ming, Tsuji Akihito, Omuro Yasushi, Li Jin, Wang Jin-Wan, Miwa Hiroto, Qin Shu-Kui, Chung Ik-Joo, Yeh Kun-Huei, Feng Ji-Feng, Mukaiyama Akihira, Kobayashi Mikiro, Ohtsu Atsushi, Bang Yung-Jue
Journal: Journal of Clinical Oncology (2014)
Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis
Authors: Matteo Ghisa, Giorgio Laserra, Elisa Marabotto, Sebastiano Ziola, Salvatore Tolone, Nicola de Bortoli, Marzio Frazzoni, Aurelio Mauro, Roberto Penagini, Vincenzo Savarino, Brigida Barberio, Edoardo Giovanni Giannini, Patrizia Zentilin, C. Prakash Gyawali, Edoardo Savarino
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract A62: A cerebral organoid model of pediatric glioma
Authors: Amin Ismail, Demis Balamatsias
Journal: Cancer Research (2020)

Abstract Glioblastoma is the most devastating brain cancer with dismal prognosis both in adults and children and accounts for 16% of primary brain tumors. Despite aggressive therapeutic approaches, the majority of patients die within one year after diagnosis. Current in vivo modeling of glioblastoma involves xenografts either of cultured cell lines or human biopsies transplanted into mice. These models do not faithfully recapitulate the complex biology/pathogenesis of cancer. Here we used human pluripotent embryonic stem cells (or young children fibroblast-driven induced pluripotent stem cells) to create 3D structures with histology reminiscent of human fetal brain (the so-called cerebral organoids). Cerebral organoids combine the accurate multilineage differentiation and physiology of a developing brain with the easiness of manipulation of an in vitro system. We engineered these mini-brains to develop tumors by forced expression of combinations of epigenetic and genetic hits that have previously been shown to drive pediatric glioblastoma multiform (GMB). These include the expression of a mutant histone H3 variant H3F3A (mutated at K27M or G34R) or a gain of function of a mutant form of isocitrate dehydrogenase (IDH1R132H) in combination with the loss of ATRX histone remodeling factor and/or p53 tumor suppressor. Lentiviral transfection was used to express combination of these genetic and epigenetic hits into cerebral organoids. The mutated organoids exhibited tumorigenic growth that was histologically characterized. For example, the expression of H3K27M in combination with loss of both p53 and ATRX showed a remarkable dysplasia reminiscent of primary glioblastoma. Moreover, these organoids exhibited tumor rosette structures resembling those found in ependymoma. In contrast, organoids expressing K27M alone did not show such structures. Interestingly, IDH1R132H combined with p53 and ATRX loss resulted in different tumor morphology, suggestive of a possibility to model oncogenic dependence in pediatric GBM. Cerebral organoids could also be used as a model to study tumor invasion starting with glioma stem-like cells (GSCs, which are believed to be the tumor-initiating cells in GBM). Interestingly, the GSC cell line 923 (which does not invade mouse brain in vivo) invaded and formed a focal lesion in a cocultured organoid. The organoid-based cancer model presented here carries a promising potential to uncover the initiation and pathogenesis of pediatric tumors early in the developing brain. Note: This abstract was not presented at the conference. Citation Format: Amin Ismail, Demis Balamatsias. A cerebral organoid model of pediatric glioma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A62.
Pathogenesis of COVID-19-induced ARDS: implications for an ageing population
Authors: Manuel A. Torres Acosta, Benjamin D. Singer
Journal: European Respiratory Journal (2020)

The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.
Association Between <i>ABCB1</i> Genetic Variants and Persistent Chemotherapy-Induced Alopecia in Women With Breast Cancer
Authors: Rocío Núñez-Torres, Miguel Martín, Jose Ángel García-Sáenz, María Rodrigo-Faus, María del Monte-Millán, Hugo Tejera-Pérez, Guillermo Pita, Julio C. de la Torre-Montero, Karen Pinilla, Belén Herraez, Lorena Peiró-Chova, Begoña Bermejo, Anna Lluch, Anna González-Neira
Journal: JAMA Dermatology (2020)

Persistent chemotherapy-induced alopecia (pCIA) has been recently described in patients with breast cancer and in its most severe form occurs in up to 10% of these patients. Genetic risk factors associated with pCIA have not been adequately explored.To identify genetic variants associated with pCIA.In this genetic association study, 215 women with breast cancer treated with docetaxel-based chemotherapy with a follow-up of 1.5 to 10 years after the end of the treatment were recruited retrospectively through 3 hospital oncology units across Spain between 2005 and 2018. Severe pCIA was defined as lack of scalp hair recovery (Common Terminology Criteria for Adverse Events, version 3.0, grade 2) 18 months or more after the end of treatment. Patients with grade 2 pCIA were selected as cases, and those with no sign of residual alopecia 12 months after the end of docetaxel treatment were selected as controls. A genome-wide association study in a discovery phase was conducted, and logistic regression was used to identify variants associated with the risk to develop this adverse effect. The validity of the association was addressed through a replication phase.Docetaxel-based chemotherapy.Genotypes of single-nucleotide variants associated with pCIA.In total, 215 women with breast cancer (median age, 51.6 years; interquartile range, 44-60 years) were recruited (173 patients for the discovery phase and 42 patients for the replication phase). In the discovery phase, ABCB1 genetic variants were associated with risk to develop pCIA. In particular, single-nucleotide variation rs1202179, a regulatory variant located in an enhancer element that interacts with the ABCB1 promoter, was associated with the occurrence of pCIA. This finding was validated in the replication cohort (combined odds ratio, 4.05; 95% CI, 2.46-6.67; P = 3.946 × 10-8). This variant is associated with ABCB1 mRNA expression, and the risk allele was associated with decreased ABCB1 expression levels (P = 1.64 × 10-20).This is the first study, to our knowledge, that identifies an association between a regulatory variant in the ABCB1 gene and the occurrence of pCIA in patients with breast cancer who were treated with docetaxel-based therapies. This finding suggests an important insight into the biological mechanisms underlying pCIA and opens the opportunity to explore personalized treatment of these patients.
Phenotypic and Prognostic Relevance of the Who Diagnostic Distinction between Polycythemia Vera and JAK2 -Mutated Essential Thrombocythemia: Combined Analysis of 785 Informative Cases
Authors: Silvia Betti, Daniela Barraco, Mythri Mudireddy, Curtis A. Hanson, Rhett P. Ketterling, Animesh D. Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: Blood (2017)