tbuckley/cabot-search huggingface dataset:
Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps
Authors: Aiko I. Klingler, Whitney W. Stevens, Bruce K. Tan, Anju T. Peters, Julie A. Poposki, Leslie C. Grammer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Robert C. Kern, Robert P. Schleimer, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2020)
Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank
Authors: Jie V. Zhao, C. Mary Schooling
Journal: Journal of the American Society of Nephrology (2020)

Kidney function declines faster in men. Testosterone levels may mediate the sex disparity. Correspondingly, levels of sex hormone binding globulin (SHBG), which modulates sex hormones, might also be relevant to the lower kidney function in men. The sex-specific role of SHBG is unclear.A sex-specific, Mendelian randomization (MR) study provided unconfounded estimates of SHBG levels among the United Kingdom Biobank population. Univariable MR applied 357 single nucleotide polymorphisms (SNPs) in men and 359 SNPs in women. These published SNPs strongly (P<5×10-8) predict SHBG level. They were profiled in 179,916 white British men (6016 patients with CKD) and 212,079 white British women (5958 patients with CKD), to obtain the effect of SHBG on CKD, albuminuria, and eGFR. Multivariable MR controlling for testosterone was used to assess the effect of SHBG on CKD and kidney function independent of testosterone in men.Genetically predicted higher SHBG was associated with a lower risk of CKD in men (odds ratio [OR], 0.78 per SD; 95% confidence interval [95% CI], 0.65 to 0.93) but had no benefit in women. The effect in men remained in multivariable MR, allowing for testosterone (OR, 0.61; 95% CI, 0.45 to 0.82).Genetically predicted higher SHBG was associated with a lower risk of CKD and better kidney function in men, but not in women, suggesting that SHBG may play a role in CKD specifically in men. Identifying drivers of SHBG and the underlying pathways could provide new insights into CKD prevention and treatment.
Outcomes in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Chemotherapy Followed by (Chemo)radiotherapy in the BC2001 Trial
Authors: Syed A. Hussain, Nuria Porta, Emma Hall, Abdulazeez Salawu, Rebecca Lewis, Thiagarajan Sreenivasan, Jan Wallace, Malcolm Crundwell, Peter Jenkins, Jean Tremlett, Robert Huddart, Nicholas D. James
Journal: European Urology (2020)
Optic nerve head anatomy in myopia and glaucoma, including parapapillary zones alpha, beta, gamma and delta: Histology and clinical features
Authors: Ya Xing Wang, Songhomitra Panda-Jonas, Jost B. Jonas
Journal: Progress in Retinal and Eye Research (2020)

The optic nerve head can morphologically be differentiated into the optic disc with the lamina cribrosa as its basis, and the parapapillary region with zones alpha (irregular pigmentation due to irregularities of the retinal pigment epithelium (RPE) and peripheral location), beta zone (complete RPE loss while Bruch's membrane (BM) is present), gamma zone (absence of BM), and delta zone (elongated and thinned peripapillary scleral flange) within gamma zone and located at the peripapillary ring. Alpha zone is present in almost all eyes. Beta zone is associated with glaucoma and may develop due to a IOP rise-dependent parapapillary up-piling of RPE. Gamma zone may develop due to a shift of the non-enlarged BM opening (BMO) in moderate myopia, while in highly myopic eyes, the BMO enlarges and a circular gamma zone and delta zone develop. The ophthalmoscopic shape and size of the optic disc is markedly influenced by a myopic shift of BMO, usually into the temporal direction, leading to a BM overhanging into the intrapapillary compartment at the nasal disc border, a secondary lack of BM in the temporal parapapillary region (leading to gamma zone in non-highly myopic eyes), and an ocular optic nerve canal running obliquely from centrally posteriorly to nasally anteriorly. In highly myopic eyes (cut-off for high myopia at approximately −8 diopters or an axial length of 26.5 mm), the optic disc area enlarges, the lamina cribrosa thus enlarges in area and decreases in thickness, and the BMO increases, leading to a circular gamma zone and delta zone in highly myopic eyes.
Integrated genomic profiling and modelling for risk stratification in patients with advanced oesophagogastric adenocarcinoma
Authors: Dapeng Hao, Siyuan He, Kazuto Harada, Melissa Pool Pizzi, Yang Lu, Pujun Guan, Lu Chen, Ruiping Wang, Shaojun Zhang, Matheus Sewastjanow-Silva, Ahmed Abdelhakeem, Namita Shanbhag, Manoop Bhutani, Guangchun Han, Jeffrey H Lee, Shuangtao Zhao, Brian Weston, Mariela Blum Murphy, Rebecca Waters, Jeannelyn Santiano Estrella, Sinchita Roy-Chowdhuri, Qiong Gan, Ju-Seog Lee, Guang Peng, Samir M Hanash, George Adrian Calin, Xingzhi Song, Jianhua Zhang, Shumei Song, Linghua Wang, Jaffer A Ajani
Journal: Gut (2020)

Prognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes.We profiled 40 untreated mEGACs (20 shorter survivors <13 months and 20 longer survivors >36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts.KMT2C alterations were exclusively observed in shorter survivors together with high level of intratumour heterogeneity and complex clonal architectures, whereas the APOBEC mutational signatures were significantly enriched in longer survivors. Notably, the loss of heterozygosity in chromosome 4 (Chr4) was associated with shorter survival and 'cold' immune phenotype characterised by decreased B, CD8, natural killer cells and interferon-gamma responses. Unsupervised transcriptomic clustering revealed a shorter survivor subtype with distinct expression features (eg, upregulated druggable targets JAK2, MAP3K13 and MECOM). An integrated model was then built based on clinical variables and the identified molecular determinants, which significantly segregated shorter and longer survivors. All the above features and the integrated model have been validated independently in multiple TCGA cohorts.This study discovered novel molecular features prognosticating overall survival in patients with mEGAC and identified potential novel targets in shorter survivors.
Coronary Vasospasm and Coronary Atherosclerosis: Do We Have to Choose?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Mario Marzilli, Alda Huqi
Journal: Journal of the American College of Cardiology (2012)
Direct Pharmacological Inhibition of the Transcription Factor PU.1 in Acute Myeloid Leukemia
Authors: Ileana Antony-Debre, Ananya Paul, Joana Leite, Kelly Mitchell, Hye Mi Kim, Luis A. Carvajal, Tihomira Tidorova, Samuel Taylor, Kenneth Huang, Arvind Kumar, Abdelbasset A Farahat, Boris Bartholdy, Swathi-Rao Narayanagari, Jiahao Chen, Alberto Ambesi-Impiombato, Adolfo A. Ferrando, Ioannis Mantzaris, Evripidis Gavathiotis, Amit Verma, Britta Will, David W Boykin, W David Wilson, Gregory MK Poon, Ulrich G. Steidl
Journal: Blood (2017)
Racism and Bioethics: The Myth of Color Blindness
Authors: Clarence H. Braddock
Journal: The American Journal of Bioethics (2020)

Like many fields, bioethics has been constrained to thinking to race in terms of colorblindness, the idea that ideal deliberation would ignore race and hence prevent bias. There are practical and ethically significant problems with colorblind approaches to ethical deliberation, and important reasons why race is ethically relevant. Future discourse needs to understand how and why race is relevant in bioethics.
STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway
Authors: Chengfei Zhang, Xiaoming Wang, Dan Fang, Ping Xu, Xiao Mo, Chao Hu, Alaa Abdelatty, Mei Wang, Haojun Xu, Qi Sun, Guoren Zhou, Junjun She, Jinglin Xia, Kam Man Hui, Hongping Xia
Journal: Theranostics (2020)

Rationale: Protein kinases are critical therapeutic targets for curing hepatocellular carcinoma (HCC). As a serine/threonine kinase, the potential roles of serine/threonine kinase 39 (STK39) in HCC remain to be explored. Methods: The expression of STK39 was examined by RT-qPCR, western blotting and immunohistochemistry. Cell proliferation and apoptosis were detected by CCK8 and TUNEL kit. Cell migration and invasion assays were performed using a transwell system with or without Matrigel. RNA-seq, mass spectrometry and luciferase reporter assays were used to identify STK39 binding proteins. Results: Here, we firstly report that STK39 was highly overexpressed in clinical HCC tissues compared with adjacent tissues, high expression of STK39 was induced by transcription factor SP1 and correlated with poor patient survival. Gain and loss of function assays revealed that overexpression of STK39 promoted HCC cell proliferation, migration and invasion. In contrast, the depletion of STK39 attenuated the growth and metastasis of HCC cells. Moreover, knockdown of STK39 induced the HCC cell cycle arrested in the G2/M phase and promoted apoptosis. In mechanistic studies, RNA-seq revealed that STK39 positively regulated the ERK signaling pathway. Mass spectrometry identified that STK39 bound to PLK1 and STK39 promoted HCC progression and activated ERK signaling pathway dependent on PLK1. Conclusions: Thus, our study uncovers a novel role of STK39/PLK1/ERK signaling axis in the progress of HCC and suggests STK39 as an indicator for prognosis and a potential drug target of HCC.
TMOD-07. HUMAN DIFFUSE MIDLINE GLIOMA AVATARS AS A PLATFORM TO SEARCH FOR NOVEL THERAPEUTIC TARGETS
Authors: Tomoyuki Koga, Shunichiro Miki, Kasey R Skinner, Sriram Venneti, Denise Malicki, Robert Wechsler-Reya, Robert Gruener, R Stephanie Huang, Clark Chen, C Ryan Miller, Frank Furnari
Journal: Neuro-Oncology (2020)

Abstract Diffuse midline glioma is the leading cause of brain tumor death among the pediatric population. Drugs that show notable promise in preclinical models inevitably fail to demonstrate efficacy in clinical trials, likely due to the inadequacy of preclinical models. We have recently proposed glioblastoma models derived from human induced pluripotent stem cells (hiPSCs) genetically engineered with different combinations of glioblastoma-associated genetic alterations as a platform to search for therapeutic targets. These glioblastoma avatars authentically recapitulated the different pathobiology of glioblastoma subtypes, depending on what genetic alterations to be introduced. To investigate the biology and to develop novel therapeutics for diffuse midline glioma with H3K27M mutation, we have established a novel model by introducing H3.3 K27M mutation together with one of the most common concurrent genetic alterations, TP53 R248Q mutation, into hiPSCs through CRISPR/Cas9 genome engineering. Orthotopic engraftment of the neural progenitor cells derived from these edited hiPSCs formed diffusely invasive brainstem tumors with histological features of the diffuse midline glioma. These tumor avatars presented a global reduction in H3K27me3 accompanied by the expression of H3K27M. Transcriptome analyses of these models revealed that these avatars with H3K27M cluster apart from the pediatric glioma samples without this particular mutation, and that they present signatures of oligodendroglial progenitor differentiation as discovered in patient samples with this mutation. Using these models faithfully recapitulating histology and pathobiology of the patient tumors, we have performed drug screening and confirmed that their sensitivity to known drugs, including an EZH2 inhibitor and histone deacetylase inhibitors. On these faithful human avatars of diffuse midline glioma with H3K27M, we have applied bioinformatics algorithms of drug sensitivity prediction aiming at developing novel therapeutics for this devastating pediatric glioma.
QOLP-17. GROUP MEDICAL PLAY EFFECTIVELY IMPROVES HOSPITALIZATIONADAPTABILITY OF PEDIATRIC PATIENTS WITH NEUROTUMOR
Authors: Xing Zhang, Fuqiang Zhang, Mingyao Lai, Juan Li, Yangqiong Zhang, Cheng Zhou, Changguo Shan, Linbo Cai
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To explore the effect of group medical games on the hospitalization adaptability of pediatric patients with neuro tumor. METHODS pediatric patients with neuro tumor (age:6 to 13 years) who were treated in hospital from June to December 2019 and were hospitalized for 1 month to 2 months. 29 pediatric patients(mean age:9y) were selected as the control group and treated as usual; 26 pediatric patients(meanage:8y) were selected as the experimental group for group therapeutic play intervention. Interventions last Monday, Wednesday and Friday of each week, with an average duration of one hour. Group medical play include: medical picture book education, medical preview game, emotional games, social table games. Two groups completed self-made questionnaires at the time of admission and two weeks after admission, including: diet, sleep, compliance, and social status, hospital adaptation and other related issues, two groups completed a satisfaction questionnaire after two weeks of admission, recorded analysis and compared the difference of questionnaire data and satisfaction of the two groups of pediatric patients. RESULTS There was no statistical difference in age and sex between the two groups, and there was no significant difference in baseline RESULTS: The re-test results showed that the experimental group was significantly better than the control group in terms of social status, hospital adaptation, compliance and family satisfaction(p＜0.05). CONCLUSION Group medical games can effectively improve the adaptability, compliance and family satisfaction of pediatric with neuro tumor.
Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C)
Authors: Ming-Lung Yu, Chung-Feng Huang, Yu-Ju Wei, Wen-Yi Lin, Yi-Hung Lin, Po-Yao Hsu, Cheng-Ting Hsu, Ta Wei Liu, Jia-Jung Lee, Sheng-Wen Niu, Jiun-Chi Huang, Tzu-Sui Hung, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Ming-Yen Hsieh, Szu-Chia Chen, Jee-Fu Huang, Jer-Ming Chang, Yi-Wen Chiu, Chia-Yen Dai, Shang-Jyh Hwang, Wan-Long Chuang
Journal: Gut (2020)

Objective HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. Design The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (&gt;80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and ‘No-C HD’ (no HCV-viremic subjects at the end of follow-up). Results At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and ‘No-C HD’ were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. Conclusion Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. ClinicalTrials.gov identifier NCT03803410 and NCT03891550
LBA1 First-line nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) for the treatment of unresectable malignant pleural mesothelioma (MPM): Patient-reported outcomes (PROs) from CheckMate 743
Authors: A. Scherpereel, S. Antonia, Y. Bautista, F. Grossi, D. Kowalski, G. Zalcman, A. Nowak, N. Fujimoto, S. Peters, A. Tsao, A. Mansfield, S. Popat, X. Sun, B. Padilla, P. Aanur, M. Daumont, B. Bennett, M. McKenna, P. Baas
Journal: Annals of Oncology (2020)
LINC-10. SIOP PODC ADAPTED TREATMENT GUIDELINES FOR CRANIOPHARYNGIOMA IN LOW- AND MIDDLE-INCOME SETTINGS
Authors: Nisreen amayiri, Ariane Spitaels, Mohamed Zaghloul, Anthony Figaji, Sergio Cavalheiro, Hermann L Muller, Moawia Elhassan, Jeannette Parkes, Naureen Mushtaq, Mohamed El Beltagy, Yacoub Yousef, Natia Esiashvili, Michael Sullivan, Marcos Devanir da Costa, Patricia Dastoli, Fatima Mubarak, Ute Bartels, Omar Chamdine, Alan Davidson, Awni Musharbash, Patricia Alcasabas, Eric Bouffet, Simon Bailey
Journal: Neuro-Oncology (2020)

Abstract Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage and behavioral changes are amongst the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries (LMICs) where resources are variable. We provide a risk-stratified management guideline for children diagnosed with craniopharyngioma in a resource limited setting based on the service levels describing the facilities and personnel required for management as previously specified by the Pediatric Oncology in Developing Countries (PODC) committee of The International Society of Pediatric Oncology (SIOP). A multi-disciplinary group of neurosurgeons, radiation and pediatric oncologists, radiologists, pediatric endocrinologists and an ophthalmologist with experience in managing children with craniopharyngioma in LMIC setting was formed and carried online meetings to form a consensus guideline. The clinical characteristics (including the visual and endocrine presentations), suggestive radiological features as well as potential treatment options including surgery, radiotherapy and intra-cystic therapies were discussed in depth and in relation to available resources. In addition, hormonal management, pre- and post-operative PICU care and expected future complications related to craniopharyngioma and to follow up these children were discussed and documented in the guideline. We believe this guideline is a useful reference for health care providers in LMIC.
HGG-31. UNIQUE BIOLOGICAL CHARACTERISTICS OF RADIATION-INDUCED GLIOMAS
Authors: Kateřina Váňová, Aleš Vícha, Lenka Krsková, Josef Zámečník, Běla Malinová, David Sumerauer, Adéla Mišove, Petr Libý, Michal Zápotocký
Journal: Neuro-Oncology (2020)

Abstract Radiation-induced gliomas (RIGs) are the most common secondary solid tumours with very unfavourable prognosis. We aimed to describe different clinical and molecular biological characteristic of RIGs from primary gliomas. We reviewed clinical data of ten patients with RIGs. In patients with available samples, we used the whole genome methylation array and performed targeted sequencing for specific mutations. Between 2000–2018, we diagnosed RIG in 10 patients (M/F 2/8) aged 5–12 years at primary diagnosis of different solid tumours and acute leukaemia. These patients developed RIG with a median 9.5 years (ranging 3–31) after primary diagnosis. Eight patients died within 1 year after diagnosis of RIG and 2 patients are still alive more than 4 years from this diagnosis. According to Heidelberg DNA methylation-based classification, most RIGs belong to the IDH-wild type glioblastoma subclass midline which biologically corresponds to diffuse midline glioma (DMG). However, compared to primary DMGs they do not carry the characteristic H3K27M mutation. One patient developed anaplastic ganglioglioma with BRAF-V600E mutation and methylation profile identical to pleomorphic xanthoastrocytoma (alive for 4 years after diagnosis of RIG). In half of the patients from the group DMGs IDH wild type, examined by methylation array, PDGFRA amplification was found. Our data shows that most RIGs are midline IDH-wild type glioblastomas with poor prognosis that are biologically different from primary DMGs. PDGFRA amplifications are potentially targetable by kinase inhibitors in order to order to prognosis of these patients.
Risk assessment and seroprevalence of SARS-CoV-2 infection in healthcare workers of COVID-19 and non-COVID-19 hospitals in Southern Switzerland
Authors: Luca Piccoli, Paolo Ferrari, Giovanni Piumatti, Sandra Jovic, Blanca Fernandez Rodriguez, Federico Mele, Isabella Giacchetto-Sasselli, Tatiana Terrot, Chiara Silacci-Fregni, Elisabetta Cameroni, Stefano Jaconi, Nicole Sprugasci, Istvan Bartha, Davide Corti, Mariagrazia Uguccioni, Antonio Lanzavecchia, Christian Garzoni, Olivier Giannini, Enos Bernasconi, Luigia Elzi, Emiliano Albanese, Federica Sallusto, Alessandro Ceschi
Journal: The Lancet Regional Health - Europe (2020)
EPEN-14. GENERATION OF A C11orf95-RELA FUSION TARGETING ANTIBODY AS A DIAGNOSTIC TOOL FOR SUPRATENTORIAL EPENDYMOMA
Authors: Lisa Ruff, Denice Y Chan, Lesley Jenkinson, Stuart Haynes, Mark Austin, Sarah Holt, Maria Groves, Richard J Gilbertson
Journal: Neuro-Oncology (2020)

Abstract Ependymomas account for 10% of paediatric brain tumours and arise in the ventricular walls of the central nervous system. Ependymomas were previously classified as one tumour type and all patients received similar treatment. However, recent genomic studies have identified nine different molecular subgroups of the disease, including one supratentorial subtype characterized by a novel fusion gene C11ORF95-RELA. When introduced into neural stem cells, this fusion is a potent driver of tumorigenesis and its presence in patient samples has previously also been shown to negatively correlate with overall survival. Accurate diagnosis of this subgroup is currently limited to sophisticated approaches such as break-apart FISH or RNA sequencing. Here, we report the generation of a C11ORF95-RELA Fusion-specific antibody that can be used for routine immunohistochemistry (IHC). Candidate antibodies were first selected using phage display and favourable leads were subjected to affinity maturation using ribosome display after a screening process involving immunoblotting and IHC. Further IHC-based screening of affinity-matured candidates using fusion-positive and -negative mouse tissue as well as human fusion-negative ependymoma tumour tissue produced one lead antibody. The antibody detects fusion-specific nuclear staining pattern on fusion-positive tissue and does not react with fusion-negative tissues. This candidate antibody is currently being tested on human fusion-positive ependymoma tissue. This accurate diagnostic tool holds great promise to transform the management of patients with supratentorial ependymoma.