tbuckley/cabot-search huggingface dataset:
The rectal mucosal but not fecal microbiota detects subclinical ulcerative colitis
Authors: Yu-Fei Lin, Chang Mu Sung, Huei-Mien Ke, Chia-Jung Kuo, Wei-an Liu, Wen-Sy Tsai, Cheng-Yu Lin, Hao-Tsai Cheng, Meiyeh J Lu, Isheng. J. Tsai, Sen-Yung Hsieh
Journal: Gut Microbes (2021)

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, is characterized by repetitive remission and relapse. Gut microbiome is critically involved in pathogenesis of UC. The shifts in microbiome profile during disease remission remain under-investigated. Recent studies revealed that UC pathogenesis is likely to originate in the mucosal barrier. Therefore, we investigated the effectiveness of mucosal tissue microbiomes to differentiate patients with subclinical UC from healthy individuals. The microbiomes of cecal and rectal biopsies and feces were characterized from 13 healthy individuals and 45 patients with subclinical UC. Total genomic DNA was extracted from the samples, and their microbial communities determined using next-generation sequencing. We found that changes in relative abundance of subclinical UC were marked by a decrease in Proteobacteria and an increase in Bacteroidetes phyla in microbiome derived from rectal tissues but not cecal tissue nor feces. Only in the microbiome of rectal tissue had significantly higher community richness and evenness in subclinical UC patients than controls. Twenty-seven operational taxonomic units were enriched in subclinical UC cohort with majority of the taxa from the Firmicutes phylum. Inference of putative microbial functional pathways from rectal biopsy microbiome suggested a differential increase in interleukin-17 signaling and T-helper cell differentiation pathways. Rectal biopsy tissue was suggested to be more suitable than fecal samples for microbiome assays to distinguish patients with subclinical UC from healthy adults. Assessment of the rectal biopsy microbiome may offer clinical insight into UC disease progression and predict relapse of the diseases.
Effect of inclisiran, the siRNA against PCSK9, on platelets, immune cells and immunological biomarkers - a pre-specified analysis from ORION-1.
Authors: U Landmesser, A Haghikia, LA Leiter, RS Wright, D Kallend, P Wijngaard, R Stoekenbroek, Jjp Kastelein, KK Ray
Journal: Cardiovascular Research (2020)
Corrigendum to “Entrectinib in patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC) or NTRK fusion-positive solid tumours: Analysis of response by line of therapy”
Authors: S.V. Liu, F. De Braud, A. Drilon, R.C. Doebele, M.R. Patel, B.C. Cho, M.J. Ahn, C.H. Chiu, A.F. Farago, K. Goto, J. Lee, Y. Ohe, S.H.I. Ou, P. Cassier, D.S.W. Tan, G.A. Otterson, L. Veronese, S. Osborne, B. Simmons, S. Siena
Journal: Annals of Oncology (2021)
Re: Ivo G. Schoots, Jelle O. Barentsz, Leonardo K. Bittencourt, et al. PI-RADS Committee Position on MRI Without Contrast Medium in Biopsy-naive Men with Suspected Prostate Cancer: Narrative Review. Am J Roentgenol 2021;216:3–19
Authors: Michele Scialpi, Pietro Scialpi, Alfredo D’Andrea, Aldo Di Blasi
Journal: European Urology (2021)
Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Renée L Mulder, Anna Font-Gonzalez, Daniel M Green, Erik A H Loeffen, Melissa M Hudson, Jacqueline Loonen, Richard Yu, Jill P Ginsberg, Rod T Mitchell, Julianne Byrne, Roderick Skinner, Antoinette Anazodo, Louis S Constine, Andrica de Vries, Kirsi Jahnukainen, Armando Lorenzo, Andreas Meissner, Leena Nahata, Marij Dinkelman-Smit, Herman Tournaye, Riccardo Haupt, Marry M van den Heuvel-Eibrink, Hanneke M van Santen, Ans M M van Pelt, Uta Dirksen, Jaap den Hartogh, Eline van Dulmen-den Broeder, W Hamish Wallace, Jennifer Levine, Wim J E Tissing, Leontien C M Kremer, Lisa B Kenney, Marianne D van de Wetering, Claire Berger, Tamara Diesch, Aleksander Giwercman, Desiree Grabow, Clarisa Gracia, Sarah E Hunter, Julia Inthorn, Peter Kaatsch, Joanne F Kelvin, James L Klosky, Joop S E Laven, Barbara A Lockart, Sebastian JCMM Neggers, Norbert W Paul, Michelle Peate, Bob Phillips, Gwendolyn P Quinn, Damon R Reed, Eva Maria E Tinner, Marleen van den Berg, Chris Verhaak
Journal: The Lancet Oncology (2021)
Association of fibrosis in the bulge portion with hair follicle miniaturization in androgenetic alopecia
Authors: Kaitao Li, Fang Liu, Yang Sun, Yuyang Gan, Decong Zhu, Hailin Wang, Qian Qu, Jin Wang, Ruosi Chen, Zhexiang Fan, Bingcheng Liu, Danlan Fu, Yong Miao, Zhiqi Hu
Journal: Journal of the American Academy of Dermatology (2021)
Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy
Authors: Song Xue, Xiaojun Zhou, Weilin Sang, Cong Wang, Haiming Lu, Yiming Xu, Yiming Zhong, Libo Zhu, Chuanglong He, Jinzhong Ma
Journal: Bioactive Materials (2021)

Cartilage-targeting delivery of therapeutic agents is still an effective strategy for osteoarthritis (OA) therapy. Recently, scavenging for reactive oxygen species (ROS) and activating autophagy have been increasingly reported to treat OA effectively. In this study, we designed, for the first time, a dual-drug delivery system based on metal organic framework (MOF)-decorated mesoporous polydopamine (MPDA) which composed of rapamycin (Rap) loaded into the mesopores and bilirubin (Br) loaded onto the shell of MOF. The collagen II-targeting peptide (WYRGRL) was then conjugated on the surface of above nanocarrier to develop a cartilage-targeting dual-drug delivery nanoplatform (RB@MPMW). Our results indicated the sequential release of two agents from RB@MPMW could be achieved via near-infrared (NIR) laser irritation. Briefly, the rapid release of Br from the MOF shell exhibited excellent ROS scavenging ability and anti-apoptosis effects, however responsively reduced autophagy activity, to a certain extent. Meanwhile, following the NIR irradiation, Rap was rapidly released from MPDA core and further enhanced autophagy activation and chondrocyte protection. RB@MPMW continuously phosphorylated AMPK and further rescued mitochondrial energy metabolism of chondrocytes following IL-1β stimulation via activating SIRT1-PGC-1α signaling pathway. Additionally, the cartilage-targeting property of peptide-modified nanocarrier could be monitored via Magnetic Resonance (MR) and IVIS imaging. More significantly, RB@MPMW effectively delayed cartilage degeneration in ACLT rat model. Overall, our findings indicated that the as-prepared dual-drug delivery nanoplatform exerted potent anti-inflammation and anti-apoptotic effects, rescued energy metabolism of chondrocytes in vitro and prevented cartilage degeneration in vivo, which thereby showed positive performance for OA therapy.
Abstract 412: Global Phosphopeptide Analyses Identifies a Profile that Distinguishes Advanced Heart Failure Patients Capable of Cardiac Recovery Following Left Ventricular Assist Device Unloading
Authors: Christopher M Tracy, Aman Makaju, Sutip Navankasattusas, Lauren McCreath, Nikolaos Diakos, Craig Selzman, Stavros Drakos, Sarah Franklin
Journal: Circulation Research (2016)

The classical view of the human heart characterizes it as an organ with limited ability to recover and restore itself. Consequently, left ventricular assist devices (LVAD), which provide mechanical circulatory support and profound ventricular unloading, have been used as both a destination therapy as well as a bridge to transplantation in heart failure patients. However, evidence from many prospective studies indicates that a subset of patients with LVAD implants can significantly improve the structure and function of their heart (i.e. “responders”) and undergo LVAD explantation. This intriguing phenomenon provides great promise for heart failure patients, although the underlying mechanisms driving this recovery are largely unknown. To identify global changes in signaling pathways operative in the normal and failing human heart and to distinguish patients who respond to LVAD therapy from non-responders we performed phosphopeptide profiling and label-free quantitation of 38 patients. Our analysis utilized cardiac tissue from 10 donor controls, 6 recovered heart failure patients (responder), and 22 patients that did not respond to LVAD therapy (non-responders). Phosphopeptide enrichment and mass spectrometry-based analyses identified 15,816 unique phosphopeptides, 2,017 of which were shared between all samples. Label-free quantitation and bioinformatic analysis further classified 288 peptides [≥ 2 fold change (p&lt;0.01)] within this dataset that distinguish control tissue from those in heart failure. Most intriguing however, was our assessment of the phosphopeptide profile of heart failure patients at the time of LVAD implantation which, using a signature of 67 peptides [≥ 2 fold change (p&lt;0.01)], allowed complete separation of responder and non-responder samples via statistical analysis. Thus, this panel of 67 phosphopeptides enabled us to determine which patients would experience cardiac recovery following ventricular unloading prior to LVAD implantation. Overall this study characterizes unique changes in phosphoproteins and signaling pathways between the normal and failing human heart and specifies those which define hearts capable of cardiac recovery which may guide strategies to improving current heart failure therapies.
SARS-CoV-2 transmission among children and staff in daycare centres during a nationwide lockdown in France: a cross-sectional, multicentre, seroprevalence study
Authors: Eric Lachassinne, Loïc de Pontual, Marion Caseris, Mathie Lorrot, Carole Guilluy, Aurélie Naud, Marie-Aliette Dommergues, Didier Pinquier, Evelyne Wannepain, Elisabeth Hausherr, Camille Jung, Vincent Gajdos, Robert Cohen, Jean-Ralph Zahar, Ségolène Brichler, Romain Basmaci, Pierre-Yves Boelle, Coralie Bloch-Queyrat, Camille Aupiais, Lorelei Charbonnier, Anais Chosidow, Véronique Hentgen, Oscar Lescano, Nathalie Mestre, Gaelle Pinto Cardoso, Roselyne Masson, Bahia Rabehi, Anne-Sophie Romain, François Vié le Sage, Xavier Vuillaume
Journal: The Lancet Child & Adolescent Health (2021)
Illustration of the Added Value of 18F-DOPA PET to Multimodal MRI to Distinguish Low- and High-Grade Gliomas
Authors: Nicolas Louarn, Paul Kauv, Laurent Capelle, Karima Mokhtari, Emmanuel Itti
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F-DOPA PET-MRI was performed on a 38-year-old man referred for complementary imaging after a brain tumor was discovered, according to EANM/RANO recommendations. We performed a simultaneous PET with 3-T brain MRI, which revealed 2 high 18 F-DOPA uptakes, with no multimodal MRI sign of aggressiveness. An awake surgery was performed and found a grade III anaplastic astrocytoma IDH1-R132L mutant, according to the 2016 WHO classification. This was probably the aggressive transition of a grade II diffuse astrocytoma. This case illustrates the added value of 18 F-DOPA PET to multimodal MRI to distinguish low- and high-grade gliomas.
Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms
Authors: Hanna Tukachinsky, Russell W. Madison, Jon H. Chung, Ole V. Gjoerup, Eric A. Severson, Lucas Dennis, Bernard J. Fendler, Samantha Morley, Lei Zhong, Ryon P. Graf, Jeffrey S. Ross, Brian M. Alexander, Wassim Abida, Simon Chowdhury, Charles J. Ryan, Karim Fizazi, Tony Golsorkhi, Simon P. Watkins, Andrew Simmons, Andrea Loehr, Jeffrey M. Venstrom, Geoffrey R. Oxnard
Journal: Clinical Cancer Research (2021)

Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC). mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain. We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that inform clinical care.Using plasma from 3,334 patients with mCRPC (including 1,674 screening samples from TRITON2/3), we evaluated the landscape of GAs detected in ctDNA and assessed concordance with tissue-based CGP.A total of 3,129 patients (94%) had detectable ctDNA with a median ctDNA fraction of 7.5%; BRCA1/2 was mutated in 295 (8.8%). In concordance analysis, 72 of 837 patients had BRCA1/2 mutations detected in tissue, 67 (93%) of which were also identified using ctDNA, including 100% of predicted germline variants. ctDNA harbored some BRCA1/2 alterations not identified by tissue testing, and ctDNA was enriched in therapy resistance alterations, as well as possible clonal hematopoiesis mutations (e.g., in ATM and CHEK2). Potential androgen receptor resistance alterations were detected in 940 of 2,213 patients (42%), including amplifications, polyclonal and compound mutations, rearrangements, and novel deletions in exon 8.Genomic analysis of ctDNA from patients with mCRPC recapitulates the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 mutations, but more acquired resistance alterations detected in ctDNA. CGP of ctDNA is a compelling clinical complement to tissue CGP, with reflex to tissue CGP if negative for actionable variants.See related commentary by Hawkey and Armstrong, p. 2961.
Increased bactericidal activity but dose-limiting intolerability at 50 mg·kg<sup>−1</sup> rifampicin
Authors: Lindsey H.M. te Brake, Veronique de Jager, Kim Narunsky, Naadira Vanker, Elin M. Svensson, Patrick P.J. Phillips, Stephen H. Gillespie, Norbert Heinrich, Michael Hoelscher, Rodney Dawson, Andreas H. Diacon, Rob E. Aarnoutse, Martin J. Boeree
Journal: European Respiratory Journal (2021)

Background Accumulating data indicate that higher rifampicin doses are more effective and shorten tuberculosis (TB) treatment duration. This study evaluated the safety, tolerability, pharmacokinetics, and 7- and 14-day early bactericidal activity (EBA) of increasing doses of rifampicin. Here we report the results of the final cohorts of PanACEA HIGHRIF1, a dose escalation study in treatment-naive adult smear-positive patients with TB. Methods Patients received, in consecutive cohorts, 40 or 50 mg·kg −1 rifampicin once daily in monotherapy (day 1–7), supplemented with standard dose isoniazid, pyrazinamide and ethambutol between days 8 and 14. Results In the 40 mg·kg −1 cohort (n=15), 13 patients experienced a total of 36 adverse events during monotherapy, resulting in one treatment discontinuation. In the 50 mg·kg −1 cohort (n=17), all patients experienced adverse events during monotherapy, 93 in total; 11 patients withdrew or stopped study medication. Adverse events were mostly mild/moderate and tolerability rather than safety related, i.e. gastrointestinal disorders, pruritis, hyperbilirubinaemia and jaundice. There was a more than proportional increase in the rifampicin geometric mean area under the plasma concentration–time curve from time 0 to 12 h (AUC 0–24 h ) for 50 mg·kg −1 compared with 40 mg·kg −1 ; 571 (range 320–995) versus 387 (range 201–847) mg·L −1 ·h, while peak exposures saw proportional increases. Protein-unbound exposure after 50 mg·kg −1 (11% (range 8–17%)) was comparable with lower rifampicin doses. Rifampicin exposures and bilirubin concentrations were correlated (Spearman's ρ=0.670 on day 3, p&lt;0.001). EBA increased considerably with dose, with the highest seen after 50 mg·kg −1 : 14-day EBA −0.427 (95% CI −0.500– −0.355) log 10 CFU·mL −1 ·day −1 . Conclusion Although associated with an increased bactericidal effect, the 50 mg·kg −1 dose was not well tolerated. Rifampicin at 40 mg·kg −1 was well tolerated and therefore selected for evaluation in a phase IIc treatment-shortening trial.
Assisted mobilisation in critical patients with COVID-19
Authors: M. Polastri, F. Daniele, F. Tagariello
Journal: Pulmonology (2021)

The therapeutic value of early physiotherapeutic treatment in critical respiratory settings has already been clearly outlined in the last fifteen years by several authors. However, there is still a controversial perception of mobilisation by healthcare professions. In-bed cycling has attracted increasing attention having been demonstrated as a feasible and safe intervention in critical settings. Patients with respiratory diseases are typically prone to fatigue and exertional dyspnoea, as we observe in COVID-19 pandemic; in fact, these patients manifest respiratory and motor damage that can even be associated with cognitive and mental limitations. COVID-19 is at risk of becoming a chronic disease if the clinical sequelae such as pulmonary fibrosis are confirmed as permanent outcomes by further analysis, particularly in those cases with overlapping pre-existent pulmonary alterations. In the present article, we propose a practical analysis of the effects of in-bed cycling, and further discuss its potential advantages if used in critical patients with COVID-19 in intensive care settings.
Abstract PO042: ROR2 is epigenetically regulated in endometrial cancer
Authors: Dongli Liu, Luis Enriquez, Benjamin Daniels, Tracy O'Mara, Katrina Tang, Caroline Ford
Journal: Clinical Cancer Research (2021)

Abstract BACKGROUND: The Wnt signalling receptor ROR2 has been identified as a potential target in numerous cancers, however its exact role remains controversial. ROR2 has been shown to play distinct roles in regards to tumorigenesis in different tumour types. Our previous study suggested a potential tumour suppressor role for ROR2 in endometrial cancer (EC), however the mechanism associated with ROR2 repression in EC remains unclear. ROR2 has been found to be epigenetically inactivated in colorectal cancer. OBJECTIVE: The aim of this study was to investigate the role of ROR2 in EC, and to determine if ROR2 expression in EC was regulated epigenetically. METHODS: The correlation between ROR2 mRNA expression levels and clinicopathological parameters, including overall survival (OS) was analysed in The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC, n=546) cohort and GEO datasets (GSE17025, n=91). Immunohistochemistry (IHC) of ROR2 was performed on a large EC patient cohort (Australia-wide population-based Australian EC Study, ANECS, n=499). The correlation between ROR2 staining intensity (0-3) and clinicopathological parameters as well as 5-year progression free survival (PFS) and OS was analysed. Cox regression was also applied to analyse the impact of selected covariates (age, BMI, FIGO stage and grade) on the PFS and OS. Four EC cell lines (KLE, MFE-296, Ishikawa and ARK-1) and eight clinical EC samples were analysed for ROR2 methylation via COmbined Bisulphite Restriction Analysis (COBRA) and bisulphite genomic sequencing (BGS). RESULTS: ROR2 promoter methylation or reduced ROR2 expression were both found to correlate with lower OS, high grade and serous EC in the TCGA-UCEC and GEO dataset at p&amp;lt;0.05 level. In our ANECS cohort, the same trend of correlation was observed of ROR2 expression and grade (p=0.062). No significant correlation was observed for ROR2 expression with OS or PFS in this cohort at univariate or multivariable survival analysis. ROR2 was epigenetically silenced by promoter methylation in KLE and ARK-1 cell lines. There was also a significant correlation between ROR2 expression level and promoter methylation in our patient cohort (r=-0.79, p=0.02). CONCLUSION: ROR2 plays a tumour suppressor role in EC and is epigenetically suppressed with the development of disease. It may therefore be a diagnostic or therapeutic candidate for EC. Citation Format: Dongli Liu, Luis Enriquez, Benjamin Daniels, Tracy O'Mara, Katrina Tang, Caroline Ford. ROR2 is epigenetically regulated in endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO042.
FACEts of mechanical regulation in the morphogenesis of craniofacial structures
Authors: Wei Du, Arshia Bhojwani, Jimmy K. Hu
Journal: International Journal of Oral Science (2021)

Abstract During embryonic development, organs undergo distinct and programmed morphological changes as they develop into their functional forms. While genetics and biochemical signals are well recognized regulators of morphogenesis, mechanical forces and the physical properties of tissues are now emerging as integral parts of this process as well. These physical factors drive coordinated cell movements and reorganizations, shape and size changes, proliferation and differentiation, as well as gene expression changes, and ultimately sculpt any developing structure by guiding correct cellular architectures and compositions. In this review we focus on several craniofacial structures, including the tooth, the mandible, the palate, and the cranium. We discuss the spatiotemporal regulation of different mechanical cues at both the cellular and tissue scales during craniofacial development and examine how tissue mechanics control various aspects of cell biology and signaling to shape a developing craniofacial organ.
Минуле, сучасне та майбутнє хірургічного лікування виразкової хвороби (50-річний досвід інституту)
Authors: B.F. Shevchenko, V.M. Ratchick, A.M. Babii, N.V. Prolom, S.A. Таrabarov
Journal: GASTROENTEROLOGY (2017)

У статті наведені дані літератури та результати власних досліджень авторів щодо розвитку хірургії виразкової хвороби в історичному аспекті. Показано, що еволюція знань про етіопатогенез виразкової хвороби впливала на розвиток методів хірургічних втручань при виразковій хворобі. Виділено основні періоди розвитку хірургії виразкової хвороби: перший період (1842–1881 рр.) — час зародження шлункової хірургії; другий період (80–90-ті роки XIX століття) — час становлення шлункової хірургії як самостійної клінічної дисципліни; третій період (кінець XIX — 20-ті роки XX століття) — час розвитку хірургії виразкової хвороби, коли методом вибору хірургічного лікування була гастроентеростомія; четвертий період (30–60-ті рр. XX століття) — час виникнення патогенетичних принципів хірургії виразкової хвороби, коли методом вибору служила резекція шлунка; п’ятий, останній період (із 70-х років XX століття і до сьогодні) — час підбивання підсумків 150-річної історії хірургії виразкової хвороби, коли лікарі схиляються до консервативного лікування цієї складної патології, а хірургічне втручання при виразковій хворобі направлене тільки на корекцію її ускладнень без руйнування органів травлення. Історичний досвід лікарів, які пройшли тернистим шляхом надій і розчарувань у пошуках оптимального підходу до хірургічного лікування виразкової хвороби, допоможе хірургам, терапевтам, морфологам та фізіологам у майбутньому.