tbuckley/cabot-search huggingface dataset:
Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts
Authors: Jie Wei, Yuqing Zhang, Nicola Dalbeth, Robert Terkeltaub, Tuo Yang, Yilun Wang, Zidan Yang, Jiatian Li, Ziying Wu, Chao Zeng, Guanghua Lei
Journal: Arthritis & Rheumatology (2021)

Objective Hyperuricemia is a precursor to gout and is often present in other metabolic diseases that are promoted by microbiome dysbiosis. We undertook this study to examine the association of gut microbiota with hyperuricemia and serum urate levels in humans. Methods Study participants were derived from a community‐based observational study, the Xiangya Osteoarthritis Study (discovery cohort). Hyperuricemia was defined as the presence of a serum urate level &gt;357 μmoles/liter in women and &gt;416 μmoles/liter in men. Gut microbiota were analyzed using 16S ribosomal RNA sequencing of stool samples. We examined the relationship of microbiota dysbiosis (i.e., richness, diversity, composition, and relative abundance of microbiota taxa) and predicted functional pathways to prevalent hyperuricemia and serum urate levels. We verified the associations in an independent observational study, the Step Study (validation cohort). Results The discovery cohort consisted of 1,392 subjects from rural areas (mean age 61.3 years, 57.4% women, 17.2% with hyperuricemia). Participants with hyperuricemia had decreased richness and diversity, altered composition of microbiota, and lower relative abundances of genus Coprococcus compared to those with normouricemia. Predicted KEGG metabolism pathways including amino acid and nucleotide metabolisms were significantly altered in subjects with hyperuricemia compared to those with normouricemia. Gut microbiota richness, diversity, and low relative abundances of genus Coprococcus were also associated with high levels of serum urate. These findings were replicated in the validation cohort with 480 participants. Conclusion Gut microbiota dysbiosis is associated with elevated serum urate levels. Our study examines the possibility that microbiota dysbiosis may modulate these levels.
Identification of genes leading to cisplatin-resistance in testicular germ cell tumours
Authors: Elodie E. Noel, Jackie Perry, Ningfeng F. Li, Tracy Chaplin, Bryan D. Young, Tim Oliver, Simon P. Joel, Yong-Jie Lu
Journal: Cancer Research (2006)

3742  Testicular germ cell tumour (TGCT) is the commonest cancer in young men, and its incidence has increased in recent years. Around 90% of TGCT patients are cured due to its exquisite sensitivity to cisplatin-based chemotherapy, placing testicular cancer as an ideal model for the study of chemo-resistance that occurs in most human cancers. Our previous study using three pairs of cisplatin-sensitive and their derivative resistant TGCT cell lines revealed consistent expression changes of some chromosomal regions across all three pairs of cell lines, comparing the parental lines against their resistant derivatives. However, no consistent genomic alterations were found. Therefore, we further analysed the expression changes in these three pairs of cell lines using Affymetrix microarray analysis. Expression differences between untreated cells, and after 24-hour exposure to cisplatin at the EC50 concentration of the resistant cell line in each pair, were investigated using the Affymetrix gene expression microarray profiling approach (Human Genome U133 plus 2.0 arrays). Genes potentially involved in the mechanisms of TGCT cisplatin-resistance were identified using GeneSpring v7.2 software. With a 2-fold expression difference as a cut-off value, no consistent gene expression changes were found between the untreated sensitive and resistant lines. However, 7 genes were up-regulated in the resistant lines when a 1.5-fold cut-off value was used. Following cisplatin exposure, consistent 2-fold expression changes were found across all three cell line pairs. Interestingly, 71 of these 2-fold genes, including 32 up-regulated and 39 down-regulated, showed consistent expression changes in the three treated sensitive, but not the resistant cell lines, compared to the untreated cells. We have validated the expression changes of five selected genes in the three pairs of cell lines using quantitative real-time PCR and we are currently also evaluating the significance of these candidate cisplatin resistant genes in clinical samples. This study demonstrates that gene expression changes are associated with cisplatin resistance, and that the immediate response to drug exposure differs between sensitive and resistant cells. These differentially expressed genes have potential to be used both as prognostic markers for stratified treatment and as targets to re-sensitise tumour cells to cisplatin.
Stress and telomere shortening: Insights from cellular mechanisms
Authors: Jue Lin, Elissa Epel
Journal: Ageing Research Reviews (2021)

Short telomeres confer risk of degenerative diseases. Chronic psychological stress can lead to disease through many pathways, and research from in vitro studies to human longitudinal studies has pointed to stress-induced telomere damage as an important pathway. However, there has not been a comprehensive model to describe how changes in stress physiology and neuroendocrine pathways can lead to changes in telomere biology. Critically short telomeres or the collapse of the telomere structure caused by displacement of telomere binding protein complex shelterin elicit a DNA damage response and lead to senescence or apoptosis. In this narrative review, we summarize the key roles glucocorticoids, reactive oxygen species (ROS) and mitochondria, and inflammation play in mediating the relationship between psychological stress and telomere maintenance. We emphasis that these mediators are interconnected and reinforce each other in positive feedback loops. Telomere length has not been studied across the lifespan yet, but the initial setting point at birth appears to be the most influential point, as it sets the lifetime trajectory, and is influenced by stress. We describe two types of intergenerational stress effects on telomeres - prenatal stress effects on telomeres during fetal development, and 'telotype transmission" -the directly inherited transmission of short telomeres from parental germline. It is clear that the initial simplistic view of telomere length as a mitotic clock has evolved into a far more complex picture of both transgenerational telomere influences, and of interconnected molecular and cellular pathways and networks, as hallmarks of aging where telomere maintenance is a key player interacting with mitochondria. Further mechanistic investigations testing this comprehensive model of stress mediators shaping telomere biology and the telomere-mitochondrial nexus will lead to better understanding from cell to human lifespan aging, and could lead to anti-aging interventions.
Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models
Authors: Avik Dutta, Dipmoy Nath, Yue Yang, Bao T. Le, Mohammad Ferdous-Ur Rahman, Patrick Faughnan, Zhenjia Wang, Matthew Stuver, Rongquan He, Wuwei Tan, Robert E. Hutchison, Jason M. Foulks, Steven L. Warner, Chongzhi Zang, Golam Mohi
Journal: Leukemia (2021)
Sphingosine-1-phosphate, a novel TREM2 ligand, promotes microglial phagocytosis to protect against ischemic brain injury
Authors: Tengfei Xue, Juan Ji, Yuqin Sun, Xinxin Huang, Zhenyu Cai, Jin Yang, Wei Guo, Ruobing Guo, Hong Cheng, Xiulan Sun
Journal: Acta Pharmaceutica Sinica B (2021)

The mechanism of sphingosine-1-phosphate (S1P)-mediated phagocytosis remains unknown. Here, we found that S1P or FTY720 (an analog of S1P) promoted microglial phagocytosis in stroke independent of S1PRs. First, we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Next, microscale thermophoresis (MST), surface plasmon resonance (SPR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to reveal that S1P was a novel TREM2 ligand. Then, we confirmed the pro-phagocytosis of S1P targeting in Trem2-Dap12 transfected CHO cells and TREM2 knockdown microglia. Point mutation analysis showed that D104 was the critical binding residue. Trem2-/- mice were used to demonstrate the role of S1P-induced phagocytosis targeting on TREM2 in protecting against ischemic brain injury. Finally, further studies revealed that apolipoprotein E (APOE) loaded with S1P was released by microglia and bound to apoptotic neurons via LDL receptor related protein 1B (LRP1B) and thereby induced microglia to phagocytose apoptotic neurons. Overall, the present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis. Our findings provide a new lead compound for developing immunomodulator targeting on TREM2.
Association of Self-reported High-Risk Allergy History With Allergy Symptoms After COVID-19 Vaccination
Authors: Lily Li, Lacey B. Robinson, Rajesh Patel, Adam B. Landman, Xiaoqing Fu, Erica S. Shenoy, Dean M. Hashimoto, Aleena Banerji, Paige G. Wickner, Upeka Samarakoon, Christian M. Mancini, Yuqing Zhang, Kimberly G. Blumenthal
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Allergic history in individuals with confirmed anaphylaxis to a messenger RNA (mRNA) COVID-19 vaccine is common. However, the risk factors for allergy symptoms after receiving the vaccine are unknown. <h3>Objective</h3> To assess the association between self-reported history of high-risk allergy and self-reported allergic reactions after mRNA COVID-19 vaccination of health care employees. <h3>Design, Setting, and Participants</h3> This cohort study obtained demographic, medical, and vaccine administration data of employees of Mass General Brigham from the institutional electronic health record. Employees who received at least 1 dose of an mRNA COVID-19 vaccine between December 14, 2020, and February 1, 2021, and who completed at least 1 postvaccination symptom survey in the 3 days after vaccination were included. <h3>Exposures</h3> Self-reported history of high-risk allergy, defined as a previous severe allergic reaction to a vaccine, an injectable medication, or other allergen. <h3>Main Outcomes and Measures</h3> The primary outcome was 1 or more self-reported allergic reactions in the first 3 days after dose 1 or dose 2 of an mRNA COVID-19 vaccine. Multivariable log binomial regression was used to assess the association between allergic reactions and high-risk allergy status. <h3>Results</h3> A total of 52 998 health care employees (mean [SD] age, 42 [14] years; 38 167 women [72.0%]) were included in the cohort, of whom 51 706 (97.6%) received 2 doses of an mRNA COVID-19 vaccine and 474 (0.9%) reported a history of high-risk allergy. Individuals with vs without a history of high-risk allergy reported more allergic reactions after receiving dose 1 or 2 of the vaccine (11.6% [n = 55] vs 4.7% [n = 2461]). In the adjusted model, a history of high-risk allergy was associated with an increased risk of allergic reactions (adjusted relative risk [aRR], 2.46; 95% CI, 1.92-3.16), with risk being highest for hives (aRR, 3.81; 95% CI, 2.33-6.22) and angioedema (aRR, 4.36; 95% CI, 2.52-7.54). <h3>Conclusions and Relevance</h3> This cohort study found that self-reported history of high-risk allergy was associated with an increased risk of self-reported allergic reactions within 3 days of mRNA COVID-19 vaccination. However, reported allergy symptoms did not impede the completion of the 2-dose vaccine protocol among a cohort of eligible health care employees, supporting the overall safety of mRNA COVID-19 vaccine.
A comparative study on the measurement properties of Dermatology Life Quality Index (DLQI), DLQI‐Relevant and Skindex‐16*
Authors: Á. Szabó, V. Brodszky, F. Rencz
Journal: British Journal of Dermatology (2021)

Dermatology Life Quality Index (DLQI) and Skindex-16 are among the most commonly used dermatology-specific health-related quality-of-life (HRQoL) instruments. DLQI has two common scoring methods, the original and the DLQI-Relevant (DLQI-R) modification. Head-to-head comparisons of the measurement properties of the DLQI, DLQI-R and Skindex-16 are currently lacking.We aim to compare the measurement properties of the DLQI, DLQI-R and Skindex-16.We analysed data from 618 patients with self-reported physician-diagnosed dermatological conditions from a cross-sectional survey carried out in Hungary in early 2020. DLQI, DLQI-R and Skindex-16 were compared in terms of ceiling and floor effects, informativity, convergent validity and known-group validity.Mean DLQI, DLQI-R and Skindex-16 total scores were 3·76 ± 5·03, 4·11 ± 5·34 and 29·36 ± 26·62, respectively. Among patients with a DLQI/DLQI-R total score of zero, 64% reported problems on Skindex-16. Overall, 23-38% of patients with 'not relevant' responses on DLQI items 3 (shopping/home/gardening), 7 (working/studying), 8 (interpersonal problems) and 9 (sexual difficulties) reported problems on their corresponding Skindex-16 items. Average relative informativity (Shannon's evenness index) was the highest for Skindex-16 (0·85), followed by DLQI-R (0·66) and DLQI (0·54). DLQI, DLQI-R and Skindex-16 demonstrated similar convergent validity. DLQI was able to better discriminate between known groups of patients based on overall skin-related HRQoL impairment, whereas DLQI-R and Skindex-16 performed better with respect to self-perceived health status.Skindex-16 seems to be more sensitive than DLQI/DLQI-R in capturing mild impairment in HRQoL. Our findings help to provide a fuller understanding of the difference between DLQI, DLQI-R and Skindex-16 and support the informed choice of instrument for clinical and research purposes.
Safety and effectiveness of up to 3 years’ bulevirtide monotherapy in patients with HDV-related cirrhosis
Authors: Alessandro Loglio, Peter Ferenci, Sara Colonia Uceda Renteria, Christine Y.L. Tham, Caroline Scholtes, Heidemarie Holzmann, Florian van Bömmel, Marta Borghi, Riccardo Perbellini, Alessandro Rimondi, Elisa Farina, Elena Trombetta, Maria Manunta, Laura Porretti, Daniele Prati, Ferruccio Ceriotti, Fabien Zoulim, Antonio Bertoletti, Pietro Lampertico
Journal: Journal of Hepatology (2021)
Efficacy, safety and feasibility of treatment of chronic HCV infection with directly acting agents in hematopoietic stem cell transplant recipients – Study of infectious diseases working party of EBMT
Authors: Malgorzata Mikulska, Nina Knelange, Laura Ambra Nicolini, Gloria Tridello, Stella Santarone, Paolo Di Bartolomeo, Rafael de la Camara, Clara Cuéllar, Andrea Velardi, Katia Perruccio, Per Ljungman, Jan Zaucha, Agnieszka Piekarska, Grzegorz Basak, Ewa Karakulska-Prystupiuk, Emanuele Angelucci, Fabio Ciceri, Maria Teresa Lupo-Stanghellini, Loic Fouillard, Irene García-Cadenas, Mariacristina Menconi, Igor Wolfgang Blau, Luca Nassi, Simone Cesaro, Jan Styczynski
Journal: Journal of Infection (2021)
Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany
Authors: Hiltraud Kajüter, Ina Wellmann, Laura Khil, Karl-Heinz Jöckel, Can Zhang, Anna-Maria Fink, Michael Hallek, Andreas Stang
Journal: Blood Cancer Journal (2021)

Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults in western countries. Therapy is indicated in symptomatic and advanced stages and has changed fundamentally since 2010 when rituximab, an anti-CD20 antibody, has been approved for treatment of CLL. Until then therapy had been based on chemotherapy drugs. This study investigates whether survival in CLL patients improved at the population level after the introduction of combined chemoimmunotherapy. Data from the cancer registry North-Rhine Westphalia was used to calculate relative survival (RS) by applying period analyses. Age-standardized 5-year RS increased from 79% in 1998-2002 (75% in 2003-2007) to 81% in the calendar period 2008-2012 and 88% in 2013-2016 for men and continuously from 71% in 1998-2002 to 92% in 2013-2016 for women. In CLL patients aged 15-69 years 5-year RS increased from 83% to 90% for men and from 82% to 94% for women after adding an anti-CD20-antibody to chemotherapy while in the older age group of 70-79-year-old CLL patients an increase by 20 percentage points was observed. These findings show marked improvements in the survival of CLL patients at the population level subsequently to the approval of anti-CD 20 antibodies like rituximab, ofatumumab or obinutuzumab for CLL treatment.
Evaluation of Cervical Cancer Screening Uptake and Adherence Among Women Without Human Papillomavirus Vaccination in the US
Authors: Kalyani Sonawane, Ryan Suk, Elizabeth Y. Chiao, Kathleen M. Schmeler, Jane Montealegre, Maria E. Fernandez, Ashish A. Deshmukh
Journal: JAMA Network Open (2021)

a Based on nonmissing National Health Interview Survey data on cervical cancer screening behavior and human papillomavirus vaccination, cervical cancer screening data were missing for 38 patients (15 patients aged 21 to 29 y; 23 patients aged 30 to 39 y), screening adherence data were missing for 85 patients (22 patients aged 21 to 29 y; 63 patients aged 30 to 39 y), and human papillomavirus vaccination information was missing for 281 patients (121 patients aged 21 to 29 y; 160 patients aged 30 to 39 y).b Up-to-date status for women aged 21 to 29 y was established by considering whether they had received a Papanicolaou test within the past 3 years.Up-to-date screening for women aged 30 to 39 y was either having a Papanicolaou test within the past 3 years or having a Papanicolaou test with an HPV cotest within the past 5 years.
Development and Characterization of Gelatin‐Norbornene Bioink to Understand the Interplay between Physical Architecture and Micro‐Capillary Formation in Biofabricated Vascularized Constructs
Authors: Bram G. Soliman, Gretel S. Major, Pau Atienza‐Roca, Caroline A. Murphy, Alessia Longoni, Cesar R. Alcala‐Orozco, Jelena Rnjak‐Kovacina, Debby Gawlitta, Tim B. F. Woodfield, Khoon S. Lim
Journal: Advanced Healthcare Materials (2021)

Abstract The principle challenge for engineering viable, cell‐laden hydrogel constructs of clinically‐relevant size, is rapid vascularization, in order to moderate the finite capacity of passive nutrient diffusion. A multiscale vascular approach, with large open channels and bulk microcapillaries may be an admissible approach to accelerate this process, promoting overall pre‐vascularization for long‐term viability of constructs. However, the limited availability of bioinks that possess suitable characteristics that support both fabrication of complex architectures and formation of microcapillaries, remains a barrier to advancement in this space. In this study, gelatin‐norbornene (Gel‐NOR) is investigated as a vascular bioink with tailorable physico‐mechanical properties, which promoted the self‐assembly of human stromal and endothelial cells into microcapillaries, as well as being compatible with extrusion and lithography‐based biofabrication modalities. Gel‐NOR constructs containing self‐assembled microcapillaries are successfully biofabricated with varying physical architecture (fiber diameter, spacing, and orientation). Both channel sizes and cell types affect the overall structural changes of the printed constructs, where cross‐signaling between both human stromal and endothelial cells may be responsible for the reduction in open channel lumen observed over time. Overall, this work highlights an exciting three‐way interplay between bioink formulation, construct design, and cell‐mediated response that can be exploited towards engineering vascular tissues.
Assessment of Federal Value-Based Incentive Programs and In-Hospital <i>Clostridioides difficile</i> Infection Rates
Authors: Mohammad Alrawashdeh, Chanu Rhee, Heather Hsu, Rui Wang, Kelly Horan, Grace M. Lee
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Health care facility–onset<i>Clostridioides difficile</i>infection (HO-CDI) rates reported to the US Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) became a target quality metric for 2 Centers for Medicare &amp; Medicaid Services (CMS) value-based incentive programs (VBIPs) in October 2016. The association of VBIPs with HO-CDI rates is unknown. <h3>Objective</h3> To examine the association between VBIP implementation and HO-CDI rates. <h3>Design, Setting, and Participants</h3> This interrupted time series study evaluated HO-CDI rates among adults hospitalized from January 2013 to March 2019 at 265 acute-care hospitals. <h3>Interventions</h3> Implementation of VBIPs in October 2016. <h3>Main Outcomes and Measures</h3> Quarterly rates of HO-CDI per 10 000 patient-days, as reported to NHSN by participating hospitals, were evaluated. Generalized estimating equations were used to fit negative binomial regression models to estimate immediate program effect size (ie, level change) and changes in the slope of HO-CDI rates, controlling for each hospital's predominant method of CDI testing (ie, nucleic acid amplification test [NAAT], enzyme immunoassay [EIA] for toxin, or other testing methods). <h3>Results</h3> The study cohort included 24 332 938 admissions, 109 371 136 patient-days, and 74 681 HO-CDI events at 265 hospitals (145 [55%] with 100-399 beds; 205 [77%] not-for-profit hospitals; 185 [70%] teaching hospitals; 229 [86%] in metropolitan areas). Compared with EIA, rates of HO-CDI were higher when detected by NAAT (adjusted incidence rate ratio [aIRR], 1.55; 95% CI, 1.40-1.70;<i>P</i> &lt; .001) and other testing methods (aIRR, 1.47; 95% CI, 1.26-1.71;<i>P</i> &lt; .001). There were no significant changes in testing methods used by hospitals immediately after VBIP implementation. Controlling for CDI testing method, VBIP implementation was associated with a 6% level decline in HO-CDI rates in the immediate postpolicy quarter (aIRR, 0.94; 95% CI, 0.89-0.99;<i>P</i> = .01) and a 4% decline in slope per quarter (aIRR, 0.96; 95% CI, 0.95-0.97;<i>P</i> &lt; .001). Results were similar in a sensitivity analysis using a 1-year roll-in period accounting for the period after the announcement of the HO-CDI VBIP policy and prior to its implementation. <h3>Conclusions and Relevance</h3> In this study, VBIP implementation was associated with improvements in HO-CDI rates, independent of CDI testing method. Given that CMS payment policies have not previously been associated with improvements in other targeted health care–associated infection rates, future research should focus on elucidating the specific processes that contributed to improvement in HO-CDI rates to inform the design of future VBIP interventions.
Intelligent photothermal dendritic cells restart the cancer immunity cycle through enhanced immunogenic cell death
Authors: Zhihong Sun, Guanjun Deng, Xinghua Peng, Xiuli Xu, Lanlan Liu, Jiaofeng Peng, Yifan Ma, Pengfei Zhang, Austin Wen, Yifan Wang, Zhaogang Yang, Ping Gong, Wen Jiang, Lintao Cai
Journal: Biomaterials (2021)
TCT-261 New- vs Old-Generation ACURATE Neo Self-Expanding Valve: A Decrease in Safety Events With an Increase in Post-Procedural Gradients?
Authors: Emanuel Harari, Yaron Almagor, Rami Jubeh, Arik Wolak, Danny Dvir, Hani Karameh
Journal: Journal of the American College of Cardiology (2021)
Blood-thirsty: S1PR5 and TRM
Authors: Victoria M. Hallisey, Susan R. Schwab
Journal: The Journal of Experimental Medicine (2021)

In this elegant study, Evrard et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210116) find that sphingosine 1-phosphate receptor 5 (S1PR5) powerfully impairs tissue-resident memory T cell (TRM) formation, and that tissue-derived TGF-β limits S1pr5 expression by infiltrating T cells.