tbuckley/cabot-search huggingface dataset:
Anosmia as a predictor for post-COVID-19 fatigue syndrome
Authors: Peter Wostyn
Journal: The Lancet Regional Health - Europe (2021)

I read with great interest the excellent prospective cohort study by Augustin et al. [1Augustin M Schommers P Stecher M et al.Post-COVID syndrome in non-hospitalized patients with COVID-19: a longitudinal prospective cohort study.Lancet Reg Health Eur. 2021; (published online May 18)https://doi.org/10.1016/j.lanepe.2021.100122Summary Full Text Full Text PDF PubMed Scopus (395) Google Scholar]. In this study of non-hospitalized patients with mild COVID-19, the authors described symptoms and predictors for post-COVID syndrome (PCS). Most common symptoms at disease onset were cough (64.4%), ageusia (59.1%), anosmia (54.3%), body aches (53.2%), headache (53.1%), and fever (44.6%). Most common symptoms after a median follow-up of four months were anosmia (12.4%), ageusia (11.1%), fatigue (9.7%), and shortness of breath (8.6%). A lower baseline level of SARS-CoV-2 IgG, anosmia, and diarrhea during acute COVID-19 were predictors for a PCS after seven months. As discussed below, I believe these findings could shed light on a possible mechanism underlying post-COVID-19 fatigue syndrome. Anosmia usually shows spontaneous improvement over a 2–3 week period [2Altundag A Saatci O Sanli DET et al.The temporal course of COVID-19 anosmia and relation to other clinical symptoms.Eur Arch Otorhinolaryngol. 2021; 278: 1891-1897Crossref PubMed Scopus (23) Google Scholar]. However, some COVID-19 patients remain anosmic for longer time periods [2Altundag A Saatci O Sanli DET et al.The temporal course of COVID-19 anosmia and relation to other clinical symptoms.Eur Arch Otorhinolaryngol. 2021; 278: 1891-1897Crossref PubMed Scopus (23) Google Scholar]. The most likely explanation is that in those cases, a larger area of the olfactory epithelium is affected, possibly with a more profound destruction of the epithelium that included death of a larger number of olfactory receptor neurons [3Butowt R von Bartheld CS. Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection.Neuroscientist. 2020; (published online Sep 11)https://doi.org/10.1177/1073858420956905Crossref PubMed Scopus (196) Google Scholar]. I recently proposed that post-COVID-19 fatigue syndrome may result from damage to olfactory sensory neurons, causing an increased resistance to cerebrospinal fluid outflow through the cribriform plate, and further leading to congestion of the glymphatic system with subsequent toxic build-up within the brain [4Wostyn P. COVID-19 and chronic fatigue syndrome: is the worst yet to come?.Med Hypotheses. 2021; 146110469Crossref PubMed Scopus (117) Google Scholar]. From this point of view, it can be anticipated that the COVID-19 patients with persistent anosmia and persistent fatigue at month four (or month seven) are largely the same, and I wonder if the authors have such data for review. No funding to declare.
Impact of early release of apical adenoma during Holmium Laser Enucleation of the Prostate (HoLEP) on early postoperative functional outcome
Authors: M. Deuker, M.N. Welte, L.A. Kluth, P. Mandel, F.C. Roos, F.K.H. Chun, A. Becker
Journal: European Urology (2021)
Abstract LB018: Cloud-based biological domain knowledge derived gene expression classifier to predict the cancer clinical outcome
Authors: Rao V. Papineni, Seema Gupta, Aravindan Natarajan, Ram Papineni, Chandra Kasinathan
Journal: Cancer Research (2021)

Abstract We report the advances of a cloud-based software utilizing advanced algorithms to identify the molecular cancer drivers and its signal transduction. To test, a classifier based on the NFκB signaling pathway gene expression profiles that predicts the clinical therapeutic response to chemo-radiation therapy of Squamous Cell Carcinomas of the Head and Neck (SCCHN) patients are described here. Expression of HPV16, p16 and 84 NFκB signaling pathway genes were determined using real time RT PCR in SCCHN patient samples and SCCHN cell lines. Gene expression was correlated to chemo-radiation response in cell lines and the model was blindly tested in SCCHN patients to predict their clinical outcome to chemo-radiation. This tool intends to fuse biological domain knowledge by way of integrating disease targets, cell line experiments towards creating a gene expression classifier for clinical outcome. The gene expression-based predicted clinical outcome compared with patients actual observed clinical outcome correctly identified the clinical response in 73% of the cases. Such work will allow design of tailored individualized clinical treatment strategies to target NFκB inhibition using biological modifying agents with or without chemo/radiation therapy. This will help to develop several targets to directly inhibit the NFκB activity or inhibit the downstream pivotal targets. The significance of the classifier would be the ability to use the biologic attributes of a tumor to tailor specific treatment protocols for each individual patient. This would not only spare the chemo-radiation resistant patients the ill effects of the therapy but will also decrease the delay in effective treatment among the resistant patients. The long-term objective is to use such pro-survival driver genes in other cancers; SMAD, TGFβ in pancreatic cancer, and AR in prostate cancer. This tool (MeghaOncomine) intends to fuse biological domain knowledge by way of integrating cancer targets, cell line experiments towards creating a gene expression classifier for clinical outcome. Citation Format: Rao V. Papineni, Seema Gupta, Aravindan Natarajan, Ram Papineni, Chandra Kasinathan. Cloud-based biological domain knowledge derived gene expression classifier to predict the cancer clinical outcome [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 LB018.
Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection
Authors: Ismail Cem Yilmaz, Emre Mert Ipekoglu, Artun Bulbul, Nilsu Turay, Muzaffer Yildirim, Irem Evcili, Naz Surucu Yilmaz, Nese Guvencli, Yagmur Aydin, Bilgi Gungor, Berfu Saraydar, Asli Gulce Bartan, Bilgehan Ibibik, Tugce Bildik, İlayda Baydemir, Hatice Asena Sanli, Basak Kayaoglu, Yasemin Ceylan, Tugce Yildirim, Irem Abras, Ihsan Cihan Ayanoglu, Sefa Burak Cam, Eda Ciftci Dede, Merve Gizer, Osman Erganis, Fahriye Sarac, Serdar Uzar, Hakan Enul, Cumhur Adiay, Gamze Aykut, Hivda Polat, Ismail Selim Yildirim, Saban Tekin, Gulay Korukluoglu, Hasan Ersin Zeytin, Petek Korkusuz, Ihsan Gursel, Mayda Gursel
Journal: Allergy (2021)

Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2.VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine.Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals.These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.
Rodin’s Thinker: An Alternative Position in Awake Patients with COVID-19
Authors: Anna Coppo, Dario Winterton, Annalisa Benini, Anna Monzani, Gabriele Aletti, Barbara Cadore, Stefano Isgrò, Jonata Pizzagalli, Giacomo Bellani, Giuseppe Foti
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Abstract 2364: MicroRNA-1205 directly targets ONECUT2 in neuroendocrine prostate cancer cells
Authors: Bachelard Dieujuste, Michelle Naidoo, Olorunseun Ogunwobi
Journal: Cancer Research (2021)

Abstract One of six deaths globally is due to cancer. In 2018, prostate cancer (PCa) represented 1.28 million cases worldwide, the second most frequent cancer diagnosis and fifth leading cause of death in men. Currently, the mortality rate of PCa has experienced a steady increase due to the progression of metastatic castration-resistant prostate cancer (mCRPC). As an androgen driven disease, androgen deprivation therapies (ADTs) have been employed for treatment. However, despite ADTs, mCRPC develops by maintaining AR signaling, which can eventually lead to progression of AR-independent neuroendocrine PCa (NEPC). NEPC is observable in 1 in 5 men with mCRPC and associated with poor outcome. Therefore, further understanding the mechanisms of progression to mCRPC and NEPC is required. The 8q24 human chromosomal region associated with Increased PCa incidence and aggressiveness contains the PVT1 (Plasmocytoma Variant Translocation 1) locus. The PVT1 locus encodes six microRNAs, including microRNA-1205 (miR-1205) in PCa. Our laboratory previously confirmed that miR-1205 is underexpressed in PCa tissue in comparison to normal prostatic tissue and in CRPC cells in comparison to non-CRPC cells. To understand the molecular mechanism of miR-1205, we performed RNA pull down and RNA sequencing analysis to identify miR-1205 molecular targets in non-tumorigenic RWPE-1 prostate epithelial cells and PCa cells (MDA PCa 2b (metastatic PCa), PC-3 (NEPC), and C4-2B (CRPC)). We identified one cut homeobox 2 (ONECUT2 or OC2) as a direct molecular target of miR-1205. ONECUT2 is a master regulator of transcriptional factors that drives NEPC by through regulating hypoxia signaling or inducing neuroendocrine markers. ONECUT2 enrichment was approximately 3-fold higher in RWPE-1 (P=0.26), 2-fold in PC-3 (P=0.06), 1-fold in C4-2B (P=0.05) and MDA PCa 2b (P=0.02) cells. The significant binding of miR-1205 to ONECUT-2 in the PC-3 NEPC cell line suggests that miR-1205 regulation of ONECUT2 may be an important molecular mechanism in NEPC. Consequently, further study of miR-1205 and ONECUT2 in NEPC is required. Citation Format: Bachelard Dieujuste, Michelle Naidoo, Olorunseun Ogunwobi. MicroRNA-1205 directly targets ONECUT2 in neuroendocrine prostate cancer cells [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 2364.
長鎖脂肪族アシルCoAエステルはAMPKβ1イソ型のアロステリック制御を介して代謝を調節する【JST・京大機械翻訳】
Authors: L Pinkosky Stephen, W Scott John, M Desjardins Eric, K Smith Brennan, A Day Emily, J Ford Rebecca, G Langendorf Christopher, X Y Ling Naomi, L Nero Tracy, Loh Kim, Galic Sandra, Hoque Ashfaqul, J Smiles William, R W Ngoei Kevin, W Parker Michael, Yan Yan, Melcher Karsten, E Kemp Bruce, S Oakhill Jonathan, R Steinberg Gregory
Journal: Nature Metabolism (2020)
Abstract 1149: Nuclear receptor 4A1 (NR4A1) antagonists target PD-L1 in colon cancer
Authors: Kumaravel Mohankumar, Keshav Karki, Stephen Safe, Maen Abdelrahim
Journal: Cancer Research (2021)

Abstract The nuclear orphan receptor 4A1 (NR4A1, Nur77, TR3) is overexpressed in multiple solid tumors including colorectal tumors and is a negative prognostic factor for patient survival. NR4A1 is expressed in colon cancer cells and exhibit pro-oncogenic activity and results of examination of several colon cancer cell lines show that PD-L1 expression is limited and NR4A1 and PD-L1 are co-expressed in SW480 and RKO colon cancer cell lines. Previous studies in breast cancer cells showed that PD-L1 was regulated by NR4A1 which activates transcription factor Sp1 bound to the PD-L1 gene promoter. Knockdown of NR4A1 or Sp1 by RNA interference or treatment with mithramycin an inhibitor of Sp-mediated transcription decreased expression of PD-L1 in RKO and SW480 colon cancer cell lines. These data coupled with ongoing gene expression and PD-L1 promoter studies demonstrate that PD-L1 expression is regulated by NR4A1/Sp1 in colon cancer cells. Bis-indole derived NR4A1 ligand that act as receptor antagonists have been developed in this laboratory and these compounds block pro-oncogenic NR4A1-regulated genes/pathways. Treatment of RKO and SW480 colon cancer cell lines with a series of potent 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl) analogs decreased expression of PD-L1. These results show that bis-indole derived NR4A1 antagonists act as small molecule mimics of immunotherapeutics that target PD-L1. In vivo applications of NR4A1 ligands that target PD-L1 and their effects on tumor growth and immune surveillance are currently being investigated. Citation Format: Kumaravel Mohankumar, Keshav Karki, Stephen Safe, Maen Abdelrahim. Nuclear receptor 4A1 (NR4A1) antagonists target PD-L1 in colon 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 1149.
The Association of Fried Meat Consumption With the Gut Microbiota and Fecal Metabolites and Its Impact on Glucose Homoeostasis, Intestinal Endotoxin Levels, and Systemic Inflammation: A Randomized Controlled-Feeding Trial
Authors: Jian Gao, Xiaoyu Guo, Wei Wei, Ran Li, Ke Hu, Xin Liu, Wenbo Jiang, Siyao Liu, Weiqi Wang, Hu Sun, Huanyu Wu, Yuntao Zhang, Wenbo Gu, Ying Li, Changhao Sun, Tianshu Han
Journal: Diabetes Care (2021)

This randomized controlled-feeding trial aimed to determine the impact of fried meat intake on the gut microbiota and fecal cometabolites and whether such impacts influenced host glucose homoeostasis, intestinal endotoxin levels, and systemic inflammation.A total of 117 overweight adults were randomized into two groups. Fifty-nine participants were provided fried meat four times per week, and 58 participants were restricted from fried meat intake, while holding food group and nutrient compositions constant, for 4 weeks. The gut microbiota was analyzed by 16S rRNA sequencing. Glucose and insulin concentrations at 0, 30, 60, and 120 min of an oral glucose tolerance test, fecal microbiota-host cometabolite levels, and intestinal endotoxin and inflammation serum biomarker levels were measured. The area under the curve (AUC) for insulin, insulinogenic index (IGI), and muscle insulin resistance index (MIRI) were calculated.The participants who consumed fried meat had lower IGI values than the control subjects, but they had higher MIRI and AUC values of insulin and lipopolysaccharide (LPS), TNF-α, IL-10, and IL-1β levels (P < 0.05). Fried meat intake lowered microbial community richness and decreased Lachnospiraceae and Flavonifractor abundances while increasing Dialister, Dorea, and Veillonella abundances (P FDR <0.05), provoking a significant shift in the fecal cometabolite profile, with lower 3-indolepropionic acid, valeric acid, and butyric acid concentrations and higher carnitine and methylglutaric acid concentrations (P FDR <0.05). Changes in these cometabolite levels were significantly associated with changes in IGI and MIRI values and LPS, FGF21, TNF-α, IL-1β, and IL-10 levels (P < 0.05).Fried meat intake impaired glucose homoeostasis and increased intestinal endotoxin and systemic inflammation levels by influencing the gut microbiota and microbial-host cometabolites.
Abstract 2430: HOXC6 promotes tumorigenesis of right-sided colon cancer
Authors: Xin li, Jinhong Xia, Dengbo Ji, Jin Gu
Journal: Cancer Research (2021)

Abstract Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, with high heterogeneity. The significant difference in prognosis and therapeutic response of left and right colon cancer is a hot spot in the field of colorectal cancer (CRC) in recent years. The prognosis and drug response of right-sided colon cancer were significantly worse than that of the left-sided colon cancer. Clinical trials have proved that MSI-H colon cancer is mainly seen in the right-sided colon cancer, and the prognosis is better than that of MSS. Because MSS and MSI-H patients have different molecular characteristics and prognosis, we searched for key genes of RCC and LCC in MSS and MSI-H groups respectively. The difference between the prognosis and the curative effect of the left and right-sided colon cancer is essentially the difference between the molecular pathology and the immune environment. Therefore, the aim of this study is to explore the molecular mechanism related to the prognosis of left and right-sided colon cancer in order to provide a molecular target for accurate treatment of left and right-sided colon cancer. First of all, bioinformatics methods were used to screen the right and left-sided CRC differentially expressed genes in MSS and MSI-H. The expression levels of these key genes in clinical samples and cell lines were detected by RT-qPCR and IHC, and their correlation with survival prognosis was analyzed. Homeobox C6(HOXC6)were selected. First, HOXC6 stable overexpressed and knockout colorectal cancer cell lines were established and its biological function was preliminarily studied, including transwell, wound-healing assay and CCK-8 tests. Finally, the ChIP-seq data were used to analyze the carcinogenic mechanism of HOXC6. Bioinformatics methods were used to screen 30 differentially expressed genes in MSS right and left CRC, of which HOXC6 in the right colon cancer was significantly higher than that in the left-sided colon cancer, which was positively correlated with TNM staging and lymph node metastasis. Kaplan-Meier survival analysis showed that the expression of HOXC6 was negatively correlated with the total survival of CRC patients (p=0.002). RT-qPCR and IHC showed that the expression of HOXC6 in the right-sided colon cancer was higher than that in the left, P&amp;lt;0.05. Functional experiments showed that Hoxc6 promoted the growth, invasion and migration. ChIP-seq data and real-time PCR results showed that SPOCD1 and S100A1 were the target genes of HOXC6. Citation Format: Xin li, Jinhong Xia, Dengbo Ji, Jin Gu. HOXC6 promotes tumorigenesis of right-sided colon 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 2430.
The obesity paradox in metastatic castration resistant prostate cancer
Authors: G.O. Cirulli, A. Martini, J.P. Sfakianos, G. Gandaglia, N. Fossati, A. Stabile, V. Cucchiara, E. Mazzone, A. Necchi, P.I. Karakiewicz, A. Briganti, F. Montorsi, W.K. Oh, E.D. Gallagher, M.D. Galsky
Journal: European Urology (2021)
Abstract 1751: Decoding the immune system response to leptomeningeal metastasis
Authors: Jan Remsik, Xinran Tong, Ugur Sener, Min Jun Li, Jessica Wilcox, Danielle Isakov, Camille Derderian, Kiana Chabot, Andrea Schietinger, Adrienne Boire
Journal: Cancer Research (2021)

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle' state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient's own immune system into an active weapon against pathogens and cancer. Citation Format: Jan Remsik, Xinran Tong, Ugur Sener, Min Jun Li, Jessica Wilcox, Danielle Isakov, Camille Derderian, Kiana Chabot, Andrea Schietinger, Adrienne Boire. Decoding the immune system response to leptomeningeal metastasis [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 1751.
Early phago-/endosomal escape of platinum drugs via ROS-responsive micelles for dual cancer chemo/immunotherapy
Authors: Pei-Wei Shueng, Lu-Yi Yu, Hsin-Cheng Chiu, Hui-Ching Chang, Yen-Ling Chiu, Tzu-Yu Kuo, Yu-Wei Yen, Chun-Liang Lo
Journal: Biomaterials (2021)
Minimally Invasive Surgery (MIS) in simple nephrectomy – differences in perioperative outcomes based on infectious or noninfectious aetiology
Authors: A. Papadopoulou, N. Campain, Y. Abu-Ghanem, F. Mumtaz, R. Barod, M. Tran, A. Bex, P. Patki
Journal: European Urology (2021)