tbuckley/cabot-search huggingface dataset:
A novel lncRNA ROPM-mediated lipid metabolism governs breast cancer stem cell properties
Authors: Shuiqing Liu, Yan Sun, Yixuan Hou, Liping Yang, Xueying Wan, Yilu Qin, Yongcan Liu, Rui Wang, Pengpeng Zhu, Yong Teng, Manran Liu
Journal: Journal of Hematology & Oncology (2021)

Cancer stem cells (CSCs) are considered as the major cause to tumor initiation, recurrence, metastasis, and drug resistance, driving poor clinical outcomes in patients. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer development and progression. However, limited lncRNAs involved in CSCs have been reported.The novel lncROPM (a regulator of phospholipid metabolism) in breast CSCs (BCSCs) was identified by microarray and validated by qRT-PCR in BCSCs from breast cancer cells and tissues. The clinical significance of lncROPM was evaluated in two breast cancer cohorts and TANRIC database (TCGA-BRCA, RNAseq data). Gain- and loss-of-function assays were performed to examine the role of lncROPM on BCSCs both in vitro and in vivo. The regulatory mechanism of lncROPM was investigated by bioinformatics, RNA FISH, RNA pull-down, luciferase reporter assay, and actinomycin D treatment. PLA2G16-mediated phospholipid metabolism was determined by UHPLC-QTOFMS system. Cells' chemosensitivity was assessed by CCK8 assay.LncROPM is highly expressed in BCSCs. The enhanced lncROPM exists in clinic breast tumors and other solid tumors and positively correlates with malignant grade/stage and poor prognosis in breast cancer patients. Gain- and loss-of-function studies show that lncROPM is required for the maintenance of BCSCs properties both in vitro and in vivo. Mechanistically, lncROPM regulates PLA2G16 expression by directly binding to 3'-UTR of PLA2G16 to increase the mRNA stability. The increased PLA2G16 significantly promotes phospholipid metabolism and the production of free fatty acid, especially arachidonic acid in BCSCs, thereby activating PI3K/AKT, Wnt/β-catenin, and Hippo/YAP signaling, thus eventually involving in the maintenance of BCSCs stemness. Importantly, lncROPM and PLA2G16 notably contribute to BCSCs chemo-resistance. Administration of BCSCs using clinic therapeutic drugs such as doxorubicin, cisplatin, or tamoxifen combined with Giripladib (an inhibitor of cytoplasmic phospholipase A2) can efficiently eliminate BCSCs and tumorigenesis.Our study highlights that lncROPM and its target PLA2G16 play crucial roles in sustaining BCSC properties and may serve as a biomarker for BCSCs or other cancer stem cells. Targeting lncROPM-PLA2G16 signaling axis may be a novel therapeutic strategy for patients with breast cancer.
Lung tissue mechanics and extracellular matrix remodeling in a murine model of chronic asthma
Authors: D. G. Xisto, L. L. Farias, H. C. Ferreira, J. R. Lapa e Silva, D. Amitrano, E. M. Negri, V. L. Capelozzi, D. S. Faffe, W. A. Zin, P. R. M. Rocco
Journal: American Journal of Respiratory and Critical Care Medicine (2004)
Cul4A-DDB1–mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine
Authors: Yajuan Zhang, Hua Yu, Jie Zhang, Hong Gao, Siyao Wang, Shuxian Li, Ping Wei, Ji Liang, Guanzhen Yu, Xiongjun Wang, Xinxiang Li, Dawei Li, Weiwei Yang
Journal: Journal of Clinical Investigation (2021)

Although serine metabolism plays a crucial role in the proliferation and survival of tumor cells, how it supports tumor cell migration remains poorly understood. Phosphoglycerate dehydrogenase (PHGDH) catalyzes the oxidation of 3-phosphoglycerate to 3-phosphonooxypyruvate, the first committed step in de novo serine biosynthesis. Here we show that PHGDH was monoubiquitinated by cullin 4A-based E3 ligase complex at lysine 146 in colorectal cancer (CRC) cells, which enhanced PHGDH activity by recruiting a chaperone protein, DnaJ homolog subfamily A member 1, to promote its tetrameric formation, thereby increasing the levels of serine, glycine, and S-adenosylmethionine (SAM). Increased levels of SAM upregulated the expression of cell adhesion genes (laminin subunit gamma 2 and cysteine rich angiogenic inducer 61) by initiating SET domain containing 1A-mediated trimethylation of histone H3K4, thereby promoting tumor cell migration and CRC metastasis. Intriguingly, SAM levels in tumors or blood samples correlated with the metastatic recurrence of patients with CRC. Our finding not only reveals a potentially new role and mechanism of SAM-promoted tumor metastasis but also demonstrates a regulatory mechanism of PHGDH activity by monoubiquitination.
HIV care continuum interventions for Black men who have sex with men in the USA
Authors: Hilary Goldhammer, Kenneth H Mayer, Linda G Marc, Demetrios Psihopaidas, Nicole S Chavis, Massah Massaquoi, Sean Cahill, Alicia Downes, Kimberly Koester, Sheldon D Fields, Stacy M Cohen, Alex S Keuroghlian
Journal: The Lancet HIV (2021)
Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review
Authors: Tom Jefferson, Elizabeth A. Spencer, Jon Brassey, Igho J. Onakpoya, Elena C. Rosca, Annette Plüddemann, David H. Evans, John M. Conly, Carl J. Heneghan
Journal: Clinical Microbiology and Infection (2021)

BackgroundThe role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown.ObjectivesTo determine infectiousness and probable contribution of asymptomatic persons (at the time of testing) to pandemic SARS-CoV-2 spread.Data sourcesLitCovid, medRxiv, Google Scholar, and WHO Covid-19 databases (to 31 March 2021) and references in included studies.Study eligibility criteriaStudies with a proven or hypothesized transmission chain based either on serial PCR cycle threshold readings and/or viral culture and/or gene sequencing, with adequate follow-up.ParticipantsPeople exposed to SARS-CoV-2 within 2–14 days to index asymptomatic (at time of observation) infected individuals.InterventionsReliability of symptom and signs was assessed within contemporary knowledge; transmission likelihood was assessed using adapted causality criteria.MethodsSystematic review. We contacted all included studies' corresponding authors requesting further details.ResultsWe included 18 studies from a diverse setting with substantial methodological variation (this field lacks standardized methodology). At initial testing, prevalence of asymptomatic cases was 12.5–100%. Of these, 6–100% were later determined to be presymptomatic, this proportion varying according to setting, methods of case ascertainment and population. Nursing/care home facilities reported high rates of presymptomatic: 50–100% (n = 3 studies). Fourteen studies were classified as high risk of, and four studies as at moderate risk of symptom ascertainment bias. High-risk studies may be less likely to distinguish between presymptomatic and asymptomatic cases. Six asymptomatic studies and four presymptomatic studies reported culturing infectious virus; data were too sparse to determine infectiousness duration. Three studies provided evidence of possible and three of probable/likely asymptomatic transmission; five studies provided possible and two probable/likely presymptomatic SARS-CoV-2 transmission.ConclusionHigh-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates.
Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies
Authors: Xiaomeng Huang, Yi Qiao, Samuel W. Brady, Rachel E. Factor, Erinn Downs-Kelly, Andrew Farrell, Jasmine A. McQuerry, Gajendra Shrestha, David Jenkins, W. Evan Johnson, Adam L. Cohen, Andrea H. Bild, Gabor T. Marth
Journal: Genome Medicine (2021)

Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood. Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor's evolution at subclonal resolution. The most unique, previously unreported aspect of the tumor's evolution that we observed in this patient was the presence of "subclone incubators," defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient's metastases for effective clinical intervention. Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.
TCT-305 Cost-Effectiveness of Cerebral Embolic Protection With the SENTINEL Device in Transcatheter Aortic Valve Replacement: A US Medicare Payer Perspective
Authors: Mohamad Alkhouli, Michael Ganz, Katie Mercaldi, Alysha McGovern, Robert Griffiths, Samir Kapadia
Journal: Journal of the American College of Cardiology (2021)
Activation of epigenetic regulator KDM6B by <i>Salmonella</i> Typhimurium enables chronic infections
Authors: Sarika Rana, Sonalika Maurya, Gayatree Mohapatra, Savita Singh, Rohan Babar, Hridya Chandrasekhar, Garima Chamoli, Deepak Rathore, Pallavi Kshetrapal, C. V. Srikanth
Journal: Gut Microbes (2021)

Non-typhoidal Salmonella (NTS) infections result in self limiting gastroenteritis except in rare cases wherein manifestations of chronic infections can occur. Strategies employed by Salmonella to thrive in hostile environments of host during chronic infections are complex and multifaceted. In chronic state, a coordinated action of bacterial effectors allows reprogramming of macrophages to M2 subtype and thereby creating a permissible replicative niche. The mechanistic details of these processes are not fully known. In the current study we identified, histone H3-lysine 27 trimethylation (H3K27me3)-specific demethylase, KDM6B to be upregulated in both cell culture and in murine model of Salmonella infection. KDM6B recruitment upon infection exhibited an associated loss of overall H3K27me3 in host cells and was Salmonella SPI1 effectors coordinated. ChIP-qRT-PCR array analysis revealed several new gene promoter targets of KDM6B demethylase activity including PPARδ, a crucial regulator of fatty acid oxidation pathway and Salmonella-persistent infections. Furthermore, pharmacological inhibition of KDM6B demethylase activity with GSKJ4 in chronic Salmonella infection mice model led to a significant reduction in pathogen load and M2 macrophage polarization in peripheral lymphoid organs. The following work thus reveals Salmonella effector-mediated epigenetic reprogramming of macrophages responsible for its long-term survival and chronic carriage.
Letter to the editor from Pant et al
Authors: Shubham Pant, Justin T Moyers, Aung Naing
Journal: Journal for ImmunoTherapy of Cancer (2021)

Dear Editor: In the previously published work 'Phase 2 study of pembrolizumab in patients with advanced rare cancers', we published in this journal by Naing et al ,[1][1] the checkpoint inhibitor pembrolizumab was evaluated in advanced rare cancers. Herein, we present the extraordinary longer-
The clinical profile of patients attending a large, Australian pediatric gender service: A 10-year review
Authors: Michelle A. Tollit, Tamara May, Tiba Maloof, Michelle M. Telfer, Denise Chew, Melanie Engel, Ken Pang
Journal: International Journal of Transgender Health (2021)

Objectives: To better understand the clinical profile of patients attending a large Australian pediatric gender service. Retrospective clinical audit of patients seen at the Royal Children's Hospital Gender Service (RCHGS) over 10 years (2007-16). Setting: The RCHGS: Australia's largest pediatric gender service. Participants: Patients were eligible for inclusion if they had an appointment with the RCHGS between January 2007 - December 2016, and had either a self-reported gender which differed from what was presumed for them at birth or sought guidance regarding gender identity/expression. Main outcome measures: Demographic/developmental history, clinical presentation including information about gender identity/dysphoria, comorbidities, self-harm, suicidal ideation, gender-affirming treatment, psychosocial functioning. Results: 359 patients were first seen during the study period. Assigned females (54%) slightly outnumbered assigned males (46%), and presented at an older age (14.8 vs 12.4 years. Patients predominantly identified as transgender (87.2%) or non-binary (7.2%). Across the cohort, gender diversity was evident from a young age (median age 3), and symptoms of gender dysphoria were noted earlier in assigned males (median age 4) than assigned females (median age 11). Although 81% of patients met eligibility for GD, rates of hormonal treatment were much lower, with 29% of young people ≥10 years of age receiving puberty blocking treatment and 38% of adolescents ≥ 16 years of age receiving gender-affirming hormones (i.e. testosterone or estrogen). Many patients had mental health difficulties and/or neurodevelopment disorders, including major depressive disorder/low mood (51%), self-harm (25%), suicidal ideation (30%) and autism spectrum disorder (16%). Conclusion: This audit illustrates the complex profile and needs of transgender and gender diverse children and adolescents presenting to specialist gender services. Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1939221 .
Traveling Across Time Zones With Type 1 Diabetes: A Pilot Study Comparing Insulin Degludec With Insulin Glargine U100
Authors: Wendy C. Bevier, Kristin N. Castorino, Ceara Axelrod, Gal Haroush, Christian C. Farfan, Nina Shelton, Kristen Nelson, Lisa A. Spink, Hanqing Liu, David Kerr
Journal: Diabetes Care (2021)

OBJECTIVE For people with type 1 diabetes, there are limited evidence-based resources to support self-management when traveling across multiple time zones. Here, we compared glycemic control on insulin degludec versus glargine U100 as the basal insulin for adults using multiple daily injections (MDI) while traveling across multiple time zones. RESEARCH DESIGN AND METHODS This randomized crossover pilot study compared insulin degludec versus glargine U100 for adults with type 1 diabetes using MDI insulin during long-haul travel to and from Hawaii to New York. Insulin degludec was administered daily at the same time regardless of time zone, and glargine was administered per travel algorithm. Primary end point was the percentage of time in range (TIR) between 70 and 140 mg/dL during the initial 24 h after each direction of travel. Secondary end points included standard continuous glucose monitoring metrics, jet lag, fatigue, and sleep. RESULTS The study enrolled 25 participants (56% women, mean ± SD age of 35 ± 14.5 years, HbA1c of 7.4 ± 1.2% [57 ± 13.1 mmol/mol], and diabetes duration of 20.6 ± 15 years). There was no significant difference in glycemic outcomes between the two arms of the study, including TIR, hypoglycemia, or hyperglycemia. Neither group achieved &amp;gt;70% TIR 70–180 mg/dL during travel. Jet lag was greater on glargine U100 in eastward travel but not westward. Fatigue was greater after westward travel on glargine. Sleep was not significantly different between basal insulins. CONCLUSIONS In adults with type 1 diabetes using MDI of insulin and traveling across multiple time zones, glycemic outcomes were similar comparing insulin degludec and glargine U100.
Abstract P331: Self-Efficacy to Manage Health After Stroke is Related to Quality of Life
Authors: Teresa M Damush, Jason Mackey, Kurian Thomas, Chandon Saha, James Slaven, Flossy Lincoln, JD Fleck, Laura Myers, Christina Ivan, Linda Williams
Journal: Circulation (2017)

Objective: An acute stroke may serve as a major life event that disrupts health-related quality of life. We examined psychosocial and demographic factors related to functioning and well-being after stroke among patients discharged from two health care systems: Veterans Health Administration (VHA) and a Joint Commission Stroke Center. Methods: We enrolled 258 participants into a randomized controlled trial to evaluate a stroke self-management program which targeted functional recovery and risk factor management. All participants completed written consent and a baseline assessment which included demographics, depressive symptoms, self-efficacy, stroke specific, health-related quality of life (SSQoL) and psychosocial factors. We conducted multivariate analyses to evaluate factors related to baseline SSQoL using a social cognitive framework. Results: We enrolled our sample, on average, within 81.5 days after hospital discharge for stroke/TIA. Our sample included 19% women with an average age of 61.7 (10.8) years. The average NIH stroke scale score was 3.0 indicating minor stroke. Across the total and subdomains of SSQoL, self-efficacy to manage stroke health and symptoms was associated with overall better SSQoL (0.16, p&lt;0.0001), social role functioning (0.12, p &lt; 0.01), family role functioning (0.16, p&lt;0.0003), and work role functioning (0.31, p&lt;0.0001). Depressive symptoms were significantly related to poorer SSQoL across all subdomains; however distance walked in a mobility test was not significantly related. Optimism was related to total SSQoL (p&lt;.07) and perceived energy (p&lt;0.02). Demographics were not significantly related to SSQoL in the multivariate models. Conclusions: As social cognitive theory suggests, self-efficacy to manage symptoms and health after stroke and a sense of optimism for recovery are significantly related to greater stroke specific, health-related quality of life shortly after hospital discharge for stroke. Post stroke programs which target building self-efficacy and providing optimism for recovery may enhance SSQoL. Our stroke self-management program targets these concepts and we are currently evaluating our prospective outcomes.
Nano-metal–organic-frameworks for treating H2O2-Secreting bacteria alleviate pulmonary injury and prevent systemic sepsis
Authors: Yi Wu, Wei Jiang, Shaohu Huo, Shuya Li, Youcui Xu, Shenggang Ding, Jing Zhou, Hang Liu, Weifu Lv, Yucai Wang
Journal: Biomaterials (2021)
A clip in the right place: successful endoscopic submucosal dissection of a cecal tumor exhibiting the muscle-retracting sign
Authors: Hisashi Fukuda, Yuka Kowazaki, Itaru Saito, Shinichi Hirooka, Tomohiro Kurokawa, Norio Kanzaki, Anastasios C. Manolakis
Journal: Endoscopy (2021)

Among the challenges encountered during endoscopic submucosal dissection (ESD), firm “retraction” of the muscularis propria towards the tumor (the “muscle-retracting” sign) can lead to non-curative resection, failure to complete ESD, or perforation [1]. Peranal endoscopic myectomy has been introduced as a means for dealing with such lesions, its merit however is currently limited to the lower rectum, where the muscularis propria is thicker compared with the rest of the colon [2]. Based on the above, we decided to illustrate a technical variation of ESD that was used to achieve an R0 resection for a cecal type 0-Is tumor with the muscle-retracting sign ([Fig. 1]; [Video 1]).
Abstract 33: Handgrip Strength is Associated With Insulin Resistance in US Adolescents: Experience in NHANES 2011-2014
Authors: Shengxu Li, Rui Zhang, Liqiang Zheng, Wei Chen
Journal: Circulation (2017)

Background: Handgrip strength is a measure of muscular strength and body fitness. It has been shown that handgrip strength is associated with cardiometabolic risk in adult population. We hypothesized that handgrip strength is associated with insulin resistance measures in children and adolescents. Methods: The sample included 1,023 adolescents (50.4% boys and 49.6% girls) aged 12-19 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2011-2014 and did not take any antidiabetic medications. The sum of the maximum handgrip strength from both hands, standardized to age- and sex-specific z-scores, was used. Fasting plasma glucose, serum insulin, and calculated Homeostatic model assessment of insulin resistance (HOMA-IR) were used as insulin resistance measures. Serum insulin levels and HOMA-IR were log-transformed before further analyses. General linear models were used for data analyses. Results: After adjustment for age, race, sex, and body mass index, handgrip strength was inversely associated with serum insulin levels (P&lt;0.0001) and HOMA-IR (P=0.0002). The associations tended to be stronger in boys than in girls such that the inverse associations of handgrip strength with insulin levels and HOM-IR were significant in boys (P&lt;0.0001 for both) but not in girls (P&gt;0.35), though interaction terms between handgrip strength and sex were not significant (P&gt;0.36). There was no association between handgrip strength and plasma glucose levels (P=0.50). Conclusion: These results suggest that handgrip strength is associated with insulin sensitivity in adolescents, which indicates that increasing muscular strength and body fitness may have beneficial effects in early stage prevention of insulin resistance and type 2 diabetes.