tbuckley/cabot-search huggingface dataset:
RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1
Authors: Zhen Liu, Youqiong Ye, Yizhe Liu, Yanfang Liu, Huifang Chen, Mengting Shen, Zhen Wang, Shenglin Huang, Leng Han, Zhiao Chen, Xianghuo He
Journal: Cancer Research (2022)

Abstract RNA helicases are dysregulated in tumors. Here, we identified DHX37 as one of the top RNA helicase genes with upregulated expression in hepatocellular carcinoma (HCC). DHX37 promoted proliferation of liver cancer cells in vitro and in vivo. Epigenomic profiling of DHX37-knockdown and control HCC cells revealed that DHX37 is associated with superenhancer activity. Mechanistically, DHX37 interacted with pleiotropic regulator 1 (PLRG1) to transcriptionally activate cyclin D1 (CCND1) expression via co-occupation of its promoter and superenhancer elements. DHX37 and PLRG1 promoted liver cancer cell proliferation and contributed to the poor prognosis of patients with HCC. Importantly, CCND1 inhibitors were effective as antiproliferative agents for liver cancer. These results together demonstrate a cooperative mechanistic interaction between DHX37 and PLRG1 that regulates CCND1 expression and promotes liver cancer progression, advancing our understanding of the epigenetic and transcriptional dysregulations mediated by RNA helicases and superenhancers in HCC. Significance: This work characterizes a novel mechanism of superenhancer-driven cyclin D1 upregulation by DHX37 and PLRG1, implicating this pathway as a potential therapeutic target in hepatocellular carcinoma.
AdMSC-derived exosomes alleviate acute lung injury via transferring mitochondrial component to improve homeostasis of alveolar macrophages
Authors: Liangjun Xia, Chunli Zhang, Nianyin Lv, Zihao Liang, Tonghui Ma, Haibo Cheng, Youbing Xia, Liyun Shi
Journal: Theranostics (2022)

Rationale: Aberrant activation of macrophages with mitochondria dismiss was proved to be associated with pathogenesis of ALI (acute lung injury). Exosomes from adipose-derived mesenchymal stem cells (AdMSC-Exos) have been distinguished by their low immunogenicity, lack of tumorigenicity, and high clinical safety, but their role in treating ALI and the mechanism involved need to be defined. In this study, we sought to investigate whether the mitochondrial donation from AdMSC-Exos provides profound protection against LPS-induced ALI in mice, accompanied by improvement of macrophage mitochondrial function. Methods: C57BL/6 mice were orotracheally instilled with LPS (1 mg/kg). AdMSC-Exos were administered via the tail vein 4 h after LPS inhalation. Flow cytometry, H&E, Quantitative Real-Time PCR, immunofluorescence (IF), confocal microscopy imaging was conducted to investigate lung tissue inflammation and macrophage mitochondrial function. And further observe the transfer of exosomes and the effect on mitochondrial function of MH-S cells through in vitro experiments. Results: AdMSC-Exos can transfer the stem cell-derived mitochondria components to alveolar macrophages in a dose-dependent manner. Likely through complementing the damaged mitochondria, AdMSC-Exos exhibited the ability to elevate the level of mtDNA, mitochondrial membrane potential (MMP), OXPHOS activity and ATP generation, while reliving mROS stress in LPS-challenged macrophages. Restoring mitochondrial integrity via AdMSC-Exos treatment enabled macrophages shifting to anti-inflammatory phenotype, as featured with the down-regulation of IL-1β, TNF-α and iNOS secretion and increase in production of anti-inflammatory cytokines IL-10 and Arg-1. As we depleted alveolar macrophages using clodronate liposomes, the protective role for AdMSC-Exos was largely abrogated. Conclusions: AdMSC-Exos can effectively donate mitochondria component improved macrophages mitochondrial integrity and oxidative phosphorylation level, leading to the resumption of metabolic and immune homeostasis of airway macrophages and mitigating lung inflammatory pathology.
Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation
Authors: Joo Myung Lee, Ki Hong Choi, Jin-Oh Choi, Doosup Shin, Yoonjee Park, Juwon Kim, Seung Hun Lee, Darae Kim, Jeong Hoon Yang, Yang Hyun Cho, Kiick Sung, Ji Yeon Choi, Meesoon Park, Jung-Sun Kim, Taek Kyu Park, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Jae K. Oh, Eun-Seok Jeon
Journal: Circulation (2021)

Background: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. Methods: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. Results: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P =0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04–1.34], P =0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR&lt;15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6–65.7], P &lt;0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P &lt;0.001; net reclassification index 1.05, P &lt;0.001; integrated discrimination index 0.20, P &lt;0.001). Conclusions: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02798731.
MultiMAP: dimensionality reduction and integration of multimodal data
Authors: Mika Sarkin Jain, Krzysztof Polanski, Cecilia Dominguez Conde, Xi Chen, Jongeun Park, Lira Mamanova, Andrew Knights, Rachel A. Botting, Emily Stephenson, Muzlifah Haniffa, Austen Lamacraft, Mirjana Efremova, Sarah A. Teichmann
Journal: Genome biology (2021)

Multimodal data is rapidly growing in many fields of science and engineering, including single-cell biology. We introduce MultiMAP, a novel algorithm for dimensionality reduction and integration. MultiMAP can integrate any number of datasets, leverages features not present in all datasets, is not restricted to a linear mapping, allows the user to specify the influence of each dataset, and is extremely scalable to large datasets. We apply MultiMAP to single-cell transcriptomics, chromatin accessibility, methylation, and spatial data and show that it outperforms current approaches. On a new thymus dataset, we use MultiMAP to integrate cells along a temporal trajectory. This enables quantitative comparison of transcription factor expression and binding site accessibility over the course of T cell differentiation, revealing patterns of expression versus binding site opening kinetics.
First-Phase Ejection Fraction Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes
Authors: Haotian Gu, Baldeep S. Sidhu, Lingyun Fang, Jessica Webb, Tom Jackson, Simon Claridge, Eigir Einarsen, Reza Razavi, Nikolaos Papageorgiou, Anthony Chow, Sanjeev Bhattacharyya, Phil Chowienczyk, Christopher A. Rinaldi
Journal: JACC. Cardiovascular imaging (2021)
BioNTech/Pfizer vaccine after Oxford/AZ vaccine increased immune response vs. no second vaccine
Authors: Bruno P. Granwehr
Journal: Annals of Internal Medicine (2021)

Source Citation Borobia AM, Carcas AJ, Perez-Olmeda M, et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet. 2021;398:121-30. 34181880
Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy
Authors: Swayamjeet Satapathy, Amit Sharma, Ashwani Sood, Pooja Maheshwari, Harinder Jit Singh Gill
Journal: Clinical Nuclear Medicine (2022)

177Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of α-emitters such as 225Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy; however, data on long-term toxicity are relatively scarce. In this report, we describe a 76-year-old man with metastatic castration-resistant prostate cancer, who after having an initial excellent response to 2 cycles of 225Ac-PSMA-617 RLT, developed delayed nephrotoxicity in the form of tubulointerstitial nephritis.
In mild acute diverticulitis, outpatient therapy without antibiotics was noninferior to antibiotics
Authors: Meera Jain, Amy Dechet
Journal: Annals of Internal Medicine (2022)

Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, et al. Efficacy and safety of nonantibiotic outpatient treatment in mild acute diverticulitis (DINAMO-study): a multicentre, randomised, open-label, noninferiority trial. Ann Surg. 2021;274:e435-42. 34183510.
Pharyngolaryngeal Hematomas in Hemophilia A
Authors: Wataru Kida, Yuki Yuza
Journal: New England Journal of Medicine (2022)

An 18-year-old man with hemophilia A presented with throat discomfort and a recent neck hematoma. The physical examination showed an anterior neck ecchymosis and multiple pharyngolaryngeal hematomas on laryngoscopy. The patient was treated with recombinant factor VIII, and his symptoms and hematomas resolved.
Surge in SARS-CoV-2 transmission in school-aged children and household contacts, England, August to October 2021
Authors: Dimple Y Chudasama, Elise Tessier, Joe Flannagan, David Leeman, Harriet Webster, Alicia Demirjian, Catherine Falconer, Simon Thelwall, Meaghan Kall, Vanessa Saliba, Mary Ramsay, Gavin Dabrera, Theresa Lamagni
Journal: Eurosurveillance (2021)

Easing of COVID-19 restrictions in England in the summer of 2021 was followed by a sharp rise in cases among school-aged children. Weekly rates of SARS-CoV-2 infection in primary and secondary school children reached 733.3 and 1,664.7/100,000 population, respectively, by week 39 2021. A surge in household clusters with school-aged index cases was noted at the start of the school term, with secondary cases predominantly in children aged 5–15 years and adults aged 30–49 years.
Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma
Authors: Melissa Frizziero, Elaine Kilgour, Kathryn L. Simpson, Dominic G. Rothwell, David A. Moore, Kristopher K. Frese, Melanie Galvin, Angela Lamarca, Richard A. Hubner, Juan W. Valle, Mairéad G. McNamara, Caroline Dive
Journal: Clinical Cancer Research (2022)

Abstract Poorly differentiated neuroendocrine carcinomas (PD-NEC) are rare cancers garnering interest as they become more commonly encountered in the clinic. This is due to improved diagnostic methods and the increasingly observed phenomenon of “NE lineage plasticity,” whereby nonneuroendocrine (non-NE) epithelial cancers transition to aggressive NE phenotypes after targeted treatment. Effective treatment options for patients with PD-NEC are challenging for several reasons. This includes a lack of targetable, recurrent molecular drivers, a paucity of patient-relevant preclinical models to study biology and test novel therapeutics, and the absence of validated biomarkers to guide clinical management. Although advances have been made pertaining to molecular subtyping of small cell lung cancer (SCLC), a PD-NEC of lung origin, extrapulmonary (EP)-PD-NECs remain understudied. This review will address emerging SCLC-like, same-organ non-NE cancer-like and tumor-type–agnostic biological vulnerabilities of EP-PD-NECs, with the potential for therapeutic exploitation. The hypotheses surrounding the origin of these cancers and how “NE lineage plasticity” can be leveraged for therapeutic purposes are discussed. SCLC is herein proposed as a paradigm for supporting progress toward precision medicine in EP-PD-NECs. The aim of this review is to provide a thorough portrait of the current knowledge of EP-PD-NEC biology, with a view to informing new avenues for research and future therapeutic opportunities in these cancers of unmet need.
COVID-19 Vaccination Manifesting as Unilateral Lymphadenopathies Detected by 18F-Choline PET/CT
Authors: Domenico Albano, Giulia Volpi, Francesco Dondi, Raffaele Giubbini, Francesco Bertagna
Journal: Clinical Nuclear Medicine (2021)

A 79-year-old man with a history of prostate adenocarcinoma treated with prostatectomy underwent 18F-FCH PET/CT for restaging purpose, which was negative for relapse but showed the presence of choline-positive lymph nodes in the left axilla. The patient underwent a COVID-19 vaccination in the left arm 6 days prior. Thus, PET/CT findings were considered as inflammatory lymph nodes. With the current drive of global COVID-19 immunization, this case underlines the importance of knowing vaccination history to interpret correctly the findings and to avoid false-positive reports.
Associations between the fast-food environment and diabetes prevalence in the Netherlands: a cross-sectional study
Authors: Anna-Maria Ntarladima, Derek Karssenberg, Maartje Poelman, Diederick E Grobbee, Meng Lu, Oliver Schmitz, Maciej Strak, Nicole Janssen, Gerard Hoek, Ilonca Vaartjes
Journal: The Lancet Planetary Health (2022)

BackgroundDiabetes is a major health concern and is influenced by lifestyle, which can be affected by the neighbourhood environment. Specifically, a fast-food environment can influence eating behaviours and thus diabetes prevalence. Therefore, our aim was to assess the relationship between fast-food environment and diabetes prevalence for urban and rural environments in the Netherlands, using multiple indicators and buffer sizes.MethodsIn this cross-sectional study, data on a nationwide sample of adults older than 19 years in the Netherlands were taken from the 2012 Dutch national health survey (from Public Health Monitor), in which participants were surveyed on topics related to health and lifestyle behaviour. Fast-food outlet exposures were determined within street-network buffers of 100 m, 400 m, 1000 m, and 1500 m around residential addresses. For each of these buffers, three indicators were calculated: presence (yes or no) of fast-food outlets, fast-food outlet density, and ratio. Logistic regression analyses were carried out to assess associations of these indicators with diabetes, adjusting for potential confounders and stratifying into urban and rural areas.Findings387 195 adults were surveyed, 284 793 of whom were included in the study. 22 951 (8%) reported having diabetes. Fast-food outlet exposures were positively associated with diabetes prevalence. We did not observe large differences between urban and rural areas. The effect estimates were small for all indicators. For example, in the 400 m buffer in the urban environment, the odds ratio (OR) for having diabetes among people with a fast-food outlet present compared with those without, was 1·006 (95% CI 1·003–1·009) using the presence indicator. The presence indicator showed higher effect estimates and the most consistent results across buffer sizes (ranging from OR 1·005 [95% CI 1·000–1·010] with the 1000 m buffer to 1·016 [1·005–1·028] with the 1500 m buffer in urban areas and from 1·002 [0·998–1·005] with the 1500 m buffer to 1·009 [1·006–1·018] with the 100 m buffer in rural areas) compared with the density and ratio indicators.InterpretationThe results confirm the evidence that the fast-food outlet environment is a diabetes risk factor. All data included were at the individual level and the variability was ensured by the spatial distribution and number of participants. In this study, we only accounted for residential exposure because we were unable to account for exposure outside the residential environment. The findings of this study encourage local governments to consider the potential adverse effects of fast-food exposures and aim at minimising unhealthy food access.FundingGlobal Geo Health Data Centre, Utrecht University, Netherlands.
Is clinical primary care surveillance for tularaemia a useful addition to laboratory surveillance? An analysis of notification data for Finland, 2013 to 2019
Authors: Charlotte C Hammer, Timothee Dub, Oskari Luomala, Jussi Sane
Journal: Eurosurveillance (2022)

BackgroundIn Finland, surveillance of tularaemia relies on laboratory-confirmed case notifications to the National infectious Diseases Register (NIDR).AimThe aim of the study was to assess the suitability and usefulness of clinical surveillance as an addition to laboratory notification to improve tularaemia surveillance in Finland.MethodsWe retrieved NIDR tularaemia surveillance and primary healthcare data on clinically diagnosed tularaemia cases in Finland between 2013 and 2019. We compared incidences, demographic distributions and seasonal trends between the two data sources.ResultsThe median annual incidence was 0.6 (range: 0.1-12.7) and 0.8 (range: 0.6-7.2) per 100,000 for NIDR notifications and primary healthcare notifications, respectively. Cases reported to NIDR were slightly older than cases reported to primary healthcare (median: 53 years vs 50 years, p = 0.04), but had similar sex distribution. Seasonal peaks differed between systems, both in magnitude and in timing. On average, primary healthcare notifications peaked 3 weeks before NIDR. However, peaks in NIDR were more pronounced, for example in 2017, monthly incidence per 100,000 of NIDR notifications peaked at 12.7 cases in September, while primary healthcare notifications peaked at 7.2 (1.8 ratio) in August.ConclusionsClinically diagnosed cases provide a valuable additional data source for surveillance of tularaemia in Finland. A primary healthcare-based system would allow for earlier detection of increasing incidences and thereby for early warning of outbreaks. This is crucial in order to implement targeted control and prevention measures as early as possible.
Abstract EP48: Long Term Improvement In Cardiorespiratory Fitness Ameliorates Insulin Sensitivity Beyond The Response Of Visceral/Ectopic Fat In Viscerally Obese Men
Authors: Adrien Murphy-Despres, Isabelle Lemieux, Natalie Almeras, Angelo Tremblay, Jean Bergeron, Paul Poirier, Jean-Pierre Despres
Journal: Circulation (2022)

Introduction: The SYNERGIE study has documented the effects on the cardiometabolic risk (CMR) profile of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by an additional 2-year maintenance period in a sample of 144 men with visceral obesity and an atherogenic dyslipidemia. Previously published results, following the 1-year intervention, had reported significant improvements in CMR markers and a decrease in intramuscular lipids assessed by computed tomography (CT) using the area of low attenuation muscle (LAM) as a marker. However, following the 2-year maintenance period, a slight deterioration of CMR markers including visceral adiposity (VAT) was observed, with the exception of circulating insulin levels. Hypothesis: In this secondary analysis, we tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in insulin sensitivity indices. Methods: Anthropometric measurements and an oral glucose tolerance test were performed at 0, 1 and 3 years, as well as a submaximal exercise test to assess CRF. Areas and volume of VAT and areas of LAM at mid-thigh and L4-L5 (psoas and core) were measured by CT. Participants were classified into two groups based on CRF changes observed during the 2-year maintenance period: CRF increased (CRF+) and CRF decreased (CRF-). Results: Complete data were available in a subsample of 72 men (52±8 years). Mean annual PA decreased from 143 min/week during the intervention to 103 min/week after the 2-year maintenance period (p&lt;0.05). CRF changes during the maintenance period were negatively correlated with changes in psoas LAM area (r=-0.31; p&lt;0.01) and core LAM area (r=-0.30; p&lt;0.05). Changes in psoas LAM area (r=0.29; p&lt;0.05) and core LAM area (r=0.35; p&lt;0.01) were also correlated with changes in insulin resistance (HOMA-IR). The CRF+ group showed a greater decrease in HOMA-IR than the CRF- group (p&lt;0.05). CRF was found to limit the deterioration of the CMR profile observed during the 2-year maintenance period (smaller gain in BMI, waist circumference, VAT volume, and LAM at the psoas; p&lt;0.05). Conclusion: Despite some gain in VAT observed during the 2-year maintenance period following the initial 1-year lifestyle intervention, participants who were able to maintain or even increase their CRF during the 2-year maintenance period were those whose insulin sensitivity continued to improve, regardless of the changes in LAM. In conclusion, these results are consistent with the importance of targeting CRF for the long-term management of CMR in men with visceral obesity.
Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer
Authors: Vivek Naranbhai, Kerri J. St. Denis, Evan C. Lam, Onosereme Ofoman, Wilfredo F. Garcia-Beltran, Cristhian B. Mairena, Atul K. Bhan, Justin F. Gainor, Alejandro B. Balazs, A. John Iafrate, Ryan J. Sullivan, Aditya Bardia, Laura M. Spring, Steven J. Isakoff, Jocelyn R. Farmer, Leyre Zubiri, Gabriella S. Hobbs, Joan How, Andrew M. Brunner, Amir T. Fathi, Clarie A. Pernat, A. Gavralidis, Jennifer L. Peterson, Mustafa Sakhi, Grace Hambelton, Elyssa N. Denault, Lindsey J. Mortensen, Lailoo A. Periello, Marissa N. Bruno, M.N. Bruno, Brittany Y. Betraux, Alyssa R. Lawless, Melissa A. Jackson, Elizabeth Niehoff, Claire Barabell, Christain N. Nambu, Erika Nakajima, Thomas Reinecke, Cyndi Bowes, Grace E. Kirkpatrick, Julia C. Thierauf, Kerri Reynolds, Henning Willers, Anand S. Dighe, Rebecca Saff, Kimberley Blumenthal
Journal: Cancer Cell (2022)