tbuckley/cabot-search huggingface dataset:
Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients
Authors: Christian Hinze, Nikos Karaiskos, Anastasiya Boltengagen, Katharina Walentin, Klea Redo, Nina Himmerkus, Markus Bleich, S. Steven Potter, Andrew S. Potter, Kai-Uwe Eckardt, Christine Kocks, Nikolaus Rajewsky, Kai M. Schmidt-Ott
Journal: Journal of the American Society of Nephrology (2020)

Background Single-cell transcriptomes from dissociated tissues provide insights into cell types and their gene expression and may harbor additional information on spatial position and the local microenvironment. The kidney’s cells are embedded into a gradient of increasing tissue osmolality from the cortex to the medulla, which may alter their transcriptomes and provide cues for spatial reconstruction. Methods Single-cell or single-nuclei mRNA sequencing of dissociated mouse kidneys and of dissected cortex, outer, and inner medulla, to represent the corticomedullary axis, was performed. Computational approaches predicted the spatial ordering of cells along the corticomedullary axis and quantitated expression levels of osmo-responsive genes. In situ hybridization validated computational predictions of spatial gene-expression patterns. The strategy was used to compare single-cell transcriptomes from wild-type mice to those of mice with a collecting duct–specific knockout of the transcription factor grainyhead-like 2 (Grhl2 CD−/− ), which display reduced renal medullary osmolality. Results Single-cell transcriptomics from dissociated kidneys provided sufficient information to approximately reconstruct the spatial position of kidney tubule cells and to predict corticomedullary gene expression. Spatial gene expression in the kidney changes gradually and osmo-responsive genes follow the physiologic corticomedullary gradient of tissue osmolality. Single-nuclei transcriptomes from Grhl2 CD−/− mice indicated a flattened expression gradient of osmo-responsive genes compared with control mice, consistent with their physiologic phenotype. Conclusions Single-cell transcriptomics from dissociated kidneys facilitated the prediction of spatial gene expression along the corticomedullary axis and quantitation of osmotically regulated genes, allowing the prediction of a physiologic phenotype.
Covid-19: Government was too slow to respond to ventilator shortages, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2020)

The NHS managed to provide care for all patients affected by covid-19 who needed ventilators earlier this year despite the government being underprepared and slow in responding to hospitals’ needs, MPs have said.

Good luck rather than design helped the NHS to care for patients with covid-19, none of whom were denied access to a ventilator when needed, a report from the parliamentary Public Accounts Committee has concluded.1

The report, published on 25 November, praises the hard work, collaboration, and commitment of workers throughout the public sector and UK industry in responding to the pandemic from March to early August. But it criticises the government for effectively losing a vital month because it was “underprepared and reacted slowly” to the shortage of mechanical ventilators.

From March to early August the Department of Health and Social Care (DHSC) and the …
Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome
Authors: Oren Rom, Yuhao Liu, Zhipeng Liu, Ying Zhao, Jianfeng Wu, Alia Ghrayeb, Luis Villacorta, Yanbo Fan, Lin Chang, Lu Wang, Cai Liu, Dongshan Yang, Jun Song, Jason C. Rech, Yanhong Guo, Huilun Wang, Guizhen Zhao, Wenying Liang, Yui Koike, Haocheng Lu, Tomonari Koike, Tony Hayek, Subramaniam Pennathur, Chuanwu Xi, Bo Wen, Duxin Sun, Minerva T. Garcia-Barrio, Michael Aviram, Eyal Gottlieb, Inbal Mor, Wanqing Liu, Jifeng Zhang, Y. Eugene Chen
Journal: Science Translational Medicine (2020)

A glycine- and leucine-based tripeptide improves symptoms in a mouse model of nonalcoholic fatty liver disease, which lacks approved treatments.
An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy
Authors: Yun Wang, Yan-yu Cai, Tobias Herold, Run-cong Nie, Yu Zhang, Robert Peter Gale, Klaus H. Metzeler, Yun Zeng, Shun-qing Wang, Xue-yi Pan, Tong-hua Yang, Yuan-bin Wu, Qing Zhang, Zhi-jun Wuxiao, Xin Du, Zhi-wei Liang, Yong-zhong Su, Jing-bo Xu, Yong-qing Wang, Ze-lin Liu, Jian-wei Wu, Xiong Zhang, Bing-yi Wu, Ruo-zhi Xiao, San-bin Wang, Jin-yuan Li, Pei-dong Chi, Qian-yi Zhang, Si-liang Chen, Zhe-yuan Qin, Xin-mei Zhang, Na Zhong, Wolfgang Hiddemann, Qi-fa Liu, Bei Zhang, Yang Liang
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. Experimental Design: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. Results: Six flow cytometry–validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P &amp;lt; 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P &amp;lt; 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P &amp;lt; 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. Conclusions: Our immune risk score complements current AML prediction models.
15959 Topically applied lotions containing fatty acids provide nourishment to the skin through maturation of the lipid matrix
Authors: William Lathrop, Galina Yarova, Tony Dadd, Dawn Mihalov, Ana Villa, Li Feng, Stacy S. Hawkins, Sarah Paterson, Kevin D. Hermanson, Brian Dobkowski, Andrew E. Mayes
Journal: Journal of the American Academy of Dermatology (2020)
37 A weighty issue: nutritional screening in the amau
Authors: C Murphy, D Roche, J Carroll, O Crosbie
Journal: Gut (2017)

Background  IrSPEN states that malnutrition affects ~145 000 adults at any time in Ireland, especially in chronic illness with >95% of malnourished being community based. HIQA’s Report “Review of Nutrition and Hydration Care in Public Acute Hospitals” suggests nutritional assessment within 24 hours of hospitalisation to identify high risk or malnourished patients. In 2011, The Acute Medical Assessment Unit (AMAU), CUH reviewed 5560 patients. Nutritional screening is routinely completed on admitted patients however it was unclear what nutrition details were being recorded on day patients.  Aim  To assess if nutritional screening is currently being performed in AMAU day patients.  Method  A chart review of 52 consecutive day patient discharges was undertaken examining recording of nutritional screening and weight loss history.  Results  52 consecutive patient charts (19 males, 33 females) were examined with an average age of 53.4 years with an average of 1.46 co-morbidities. Weight was recorded on 36.5% of patients with 26.9% having a hydration status measured. A weight loss history was taken in 19.2% of patients, 40% of which listed weight loss as their presenting complaint. One patient had a BMI completed. A nursing pro-forma in relation to diet consumed was completed in 55.8% of patients.  Conclusions  Currently full nutritional screening is not being performed on AMAU day patients. An AMAU patient visit could represent a unique opportunity to nutritionally screen and intervene in high risk multimorbid ill community dwelling day patients. Current barriers to implementation of full nutritional screening include staff shortages, staff training and access to dietetics input if found to be at high risk.
17753 Analysis of 24-week response to ruxolitinib cream for the treatment of vitiligo based on patient demographics and clinical characteristics
Authors: Iltefat Hamzavi, John E. Harris, David Rosmarin, Pearl E. Grimes, Amit Pandya, Alice B. Gottlieb, Kathleen A. Butler, Fiona I. Kuo, Incyte, Kang Sun, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2020)
Astrocyte-derived clusterin suppresses amyloid formation in vivo
Authors: Aleksandra M. Wojtas, Jonathon P. Sens, Silvia S. Kang, Kelsey E. Baker, Taylor J. Berry, Aishe Kurti, Lillian Daughrity, Karen R. Jansen-West, Dennis W. Dickson, Leonard Petrucelli, Guojun Bu, Chia-Chen Liu, John D. Fryer
Journal: Molecular Neurodegeneration (2020)

Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer's disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the common non-coding, protective CLU variants associated with increased expression. Although there is strong evidence implicating CLU in amyloid metabolism, the exact mechanism underlying the CLU involvement in AD is not fully understood or whether physiologic alterations of CLU levels in the brain would be protective.
2MO Abemaciclib in high risk early breast cancer
Authors: S. Johnston, N. Harbeck, R. Hegg, M. Toi, M. Martin, Z. Shao, M. Campone, E. Hamilton, J. Sohn, V. Guarneri, J. Cortes, P. Neven, F. Boyle, I. Smith, M. Frenzel, D. Headley, R. Wei, J. Cox, J. O'Shaughnessy, P. Rastogi
Journal: Annals of Oncology (2020)
199O A phase II study investigating neoadjuvant atezolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer: Final analysis
Authors: B.E. Szabados, A. Rodriguez-Vida, I. Duran, S.J. Crabb, M.S. van der Heijden, A. Font Pous, G. Gravis, U. Anido Herranz, A. Protheroe, A. Ravaud, D. Maillet, M.J. Mendez, C. Suarez, M. Linch, A. Prendergast, C. Tyson, K. Mousa, D. Castellano, T.B. Powles
Journal: Annals of Oncology (2020)
18435 Extramammary Paget disease of the eyelid with clivus malignancy
Authors: Juliana Schinzari Palo, Natalia Naomi Suzuki, Bruna Galusni Senna, Maria Leticia Cintra, Thais Helena Buffo, Aparecida Machado de Moraes
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 190: Hybrid Strategy of Damage Control IR (DCIR) and REBOA Would be Feasible for Traumatic Hemorrhagic Shock Patients Suffering From Severe Pelvic Injuries
Authors: Tomohiko Orita, Shokei Matsumoto, Tomohiro Funabiki, Masayuki Shimizu, Yukitoshi Toyoda, Nao Hiroe, Taku Kazamaki, Yoshimi Nakamichi, Keitaro Yajima, Motoyasu Yamazaki, Mitsuhide Kitano
Journal: Circulation (2018)

Introduction: Massive hemorrhage with pelvic injury is sometimes lethal. So, success or failure of hemostatic intervention in the hyperacute phase leads to survival of patients directly. Recently, a hybrid strategy with Operative Management (OM) and Interventional Radiology (IR) and/or Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for torso or pelvic severe trauma has been recognized world-widely. But, awareness of Damage control IR (DCIR) which is conscious of time and coagulopathy as Damage control surgery (DCS) is still not enough. So, we studied the possibility of the hybrid strategy with DCIR and REBOA for traumatic hemorrhagic shock patients with pelvic fracture. Methods: This study included patients who underwent traditional IR or DCIR with REBOA, if it were needed, for a traumatic shock state mainly due to pelvic fracture, at our emergency and trauma center. They were sorted into traditional IR group (group IR) and DCIR group (group DCIR). The primary endpoint was a survival rate in the first 30 days after injured. Secondary endpoints were fluid factors such as total amount of crystalloid infusion and blood transfusion within the first 24 hours, and for the duration of the recovery from shock state. Results: 64 trauma shock patients were sorted into group IR (n=38) and group DCIR (n=26). All REBOA patients (n=18) were in group DCIR. Initial systolic BP (group IR vs DCIR; 75mmHg vs. 54), RTS (5.66 vs. 4.12) and Ps (0.61 vs. 0.39) were significantly lower in group DCIR. ISS (32.8 vs. 41.5) and initial Shock Index (1.9 vs. 2.4) were higher in group DCIR significantly. There were no significant differences in the amount of total crystalloid infusion (7353+/-3152ml vs. 7140+/-5342ml) and blood transfusion (4183+/-3485ml vs. 3972+/-3188ml), and the survival rate (30/38 (79%) vs. 16/28 (62%)). But the required time to recovery from shock state was significantly shorter in group DCIR (65min vs. 43min). Conclusion: The hybrid strategy with DCIR and REBOA did not increase any amount of blood transfusion or crystalloid infusion or the mortality rate. But it could shorten the duration of shock state compared with traditional IR treatment. Thus, this hybrid strategy would be feasible for hemorrhage shock patients suffering from pelvic severe trauma.
Abstract 248: Age-specific Differences in Outcomes Following Isoproterenol-induced Sudden Cardiac Death in Guinea Pigs
Authors: Kathleen C Woulfe, Sarah Chau, Lori A Walker, Christine Tompkins, Carmen C Sucharov, Shelley D Miyamoto, Brian L Stauffer
Journal: Circulation Research (2016)

Background: The pathophysiological mechanisms involved in adult and pediatric heart failure (HF) are unique. One example of clinical differences in these two patient populations is the need for primary prevention implantable defibrillators (ICDs) in adults with HF, whereas pediatric HF patients infrequently have ventricular arrhythmias and rarely require ICDs. To better understand the age-specific molecular mechanisms involved in HF, we are developing a guinea pig model of pediatric HF. We have found age-specific differences in guinea pigs acutely treated with isoproterenol (ISO). Additionally, initial exposure to ISO leads to sudden death in guinea pigs. This sudden death has previously been reported as an interaction with an inhaled volatile anesthesia. We hypothesized that isoproterenol is leading to sustained ventricular arrhythmias in guinea pigs. Methods: Adult (n= 11) and young (n= 50) guinea pigs were treated with vehicle, 16 mg/kg/day or 32 mg/kg/day of ISO by osmotic pump (Alzet) implanted under isoflurane anesthesia. Cardiac rhythm was monitored in a subset via simultaneously implanted Linq recorders (Medtronic, n= 12). Results: Acute exposure to ISO in the presence or absence of isoflurane resulted in sudden death in adult and young guinea pigs. Four of the 6 adult guinea pigs exposed to ISO died even with attempts at resuscitation. In contrast, 61% (22 out of 36) of the young guinea pigs treated with ISO arrested and 60% (13 out of 22) were rescued with chest compressions. Analysis of the heart rhythms demonstrated that the guinea pigs experienced ventricular fibrillation. The arrhythmia was transient in the young guinea pigs, but sustained in the adult. Conclusions: Acute ISO leads to age-dependent differences in arrhythmias and sudden death in guinea pigs. Contrary to prior reports, this response occurs independently of isoflurane. These age-specific differences suggest unique mechanisms in calcium handling, which can lead to arrhythmias. Guinea pigs may be a useful model for the age-related differences in HF arrhythmias seen in humans. A better understanding of these differences may lead to the development of therapies to protect adult HF patients from arrhythmias.
Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation
Authors: Lam T. Khuat, Catherine T. Le, Chien-Chun Steven Pai, Robin R. Shields-Cutler, Shernan G. Holtan, Armin Rashidi, Sarah L. Parker, Dan Knights, Jesus I. Luna, Cordelia Dunai, Ziming Wang, Ian R. Sturgill, Kevin M. Stoffel, Alexander A. Merleev, Shyam K. More, Emanual Maverakis, Helen E. Raybould, Mingyi Chen, Robert J. Canter, Arta M. Monjazeb, Maneesh Dave, James L. M. Ferrara, John E. Levine, Dan L. Longo, Mehrdad Abedi, Bruce R. Blazar, William J. Murphy
Journal: Science Translational Medicine (2020)

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expression of the GVHD marker ST2 (IL-33R) and MHC class II molecules; they also exhibited decreased survival associated with acute severe gut GVHD. This rapid-onset, obesity-associated gut GVHD depended on donor CD4+ T cells and occurred even with a minor MHC mismatch between donor and recipient animals. Retrospective analysis of clinical cohorts receiving allo-HSCT transplants from unrelated donors revealed that recipients with a high body mass index (BMI, >30) had reduced survival and higher serum ST2 concentrations compared with nonobese transplant recipients. Assessment of both DIO mice and allo-HSCT recipients with a high BMI revealed reduced gut microbiota diversity and decreased Clostridiaceae abundance. Prophylactic antibiotic treatment protected DIO mouse recipients from endotoxin translocation across the gut and increased inflammatory cytokine production, as well as gut pathology and mortality, but did not protect against later development of chronic skin GVHD. These results suggest that obesity-induced alterations of the gut microbiota may affect GVHD after allo-HSCT in DIO mice, which could be ameliorated by prophylactic antibiotic treatment.
16188 The burden of skin diseases among US states, 1990-2017
Authors: Mayra B.C. Maymone, Melissa Laughter, Chante Karimkhani Aksut, Parker Hollingsworth, Chandler W. Rundle, Sophia Hu, Sophia Wolfe, Cory A. Dunnick, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2020)
ATM regulates IR-induced p53 acetylation through activation of p300 histone acetyl transferase
Authors: Baskaran Rajasekaran
Journal: Cancer Research (2005)

5489  Exposure to ionizing radiation (IR) results in the formation of double-strand breaks (DSBs) within DNA. These DSBs activate the protein kinase ATM (Ataxia-Telangiectasia, mutated), thus triggering ATM-mediated phosphorylation and stabilization of p53. IR also induces p53 acetylation mediated by the histone acetyl transferase (HAT) activity of the transcriptional co-activator p300/CBP. We have investigated a potential role for ATM in p300-mediated p53 acetylation in response to IR. Our results show that the HAT activity of p300 is upregulated by IR in a time-and dose-dependent manner and that ATM function is required for p300 HAT activation. Cells deficient in ATM function failed to activate p300 HAT activity and showed defective p53 acetylation after IR. Conversely, ectopic expression of recombinant ATM in ATM-deficient cells restored IR-induced p300 HAT activation and p53 acetylation. Using inhibitors of HATs and histone deacetylases (HDACs), we found that p53 acetylation after DNA damage is regulated both by ATM-dependent activation of p300 and by inhibition of HDAC1 deacetylase. Together, the results indicate that ATM, p300 and HDAC1 converge in a common signaling pathway that regulates p53 acetylation after DNA damage.
Probing periodontal microbial dark matter using metataxonomics and metagenomics
Authors: Purnima S. Kumar, Shareef M. Dabdoub, Sukirth M. Ganesan
Journal: Periodontology 2000 (2020)

Abstract Our view of the periodontal microbial community has been shaped by a century or more of cultivation‐based and microscopic investigations. While these studies firmly established the infection‐mediated etiology of periodontal diseases, it was apparent from the very early days that periodontal microbiology suffered from what Staley and Konopka described as the “great plate count anomaly”, in that these culturable bacteria were only a minor part of what was visible under the microscope. For nearly a century, much effort has been devoted to finding the right tools to investigate this uncultivated majority, also known as “microbial dark matter”. The discovery that DNA was an effective tool to “see” microbial dark matter was a significant breakthrough in environmental microbiology, and oral microbiologists were among the earliest to capitalize on these advances. By identifying the order in which nucleotides are arranged in a stretch of DNA (DNA sequencing) and creating a repository of these sequences, sequence databases were created. Computational tools that used probability‐driven analysis of these sequences enabled the discovery of new and unsuspected species and ascribed novel functions to these species. This review will trace the development of DNA sequencing as a quantitative, open‐ended, comprehensive approach to characterize microbial communities in their native environments, and explore how this technology has shifted traditional dogmas on how the oral microbiome promotes health and its role in disease causation and perpetuation.
<i>IDH1</i> mutation contributes to myeloid dysplasia in mice by disturbing heme biosynthesis and erythropoiesis
Authors: Yu Gu, Risheng Yang, Ying Yang, Yuanlin Zhao, Andrew Wakeham, Wanda Y. Li, Alan Tseng, Julie Leca, Thorsten Berger, Mary Saunders, Jerome Fortin, Xing Gao, Yuan Yuan, Liming Xiao, Feng Zhang, Lijun Zhang, Guangxun Gao, Wenjing Zhou, Zhe Wang, Tak W. Mak, Jing Ye
Journal: Blood (2020)
Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat
Authors: Mark J. McVey, Sarah Weidenfeld, Mazharul Maishan, Chris Spring, Michael Kim, Arata Tabuchi, Victoria Srbely, Alisa Takabe-French, Szandor Simmons, Christoph Arenz, John W. Semple, Wolfgang M. Kuebler
Journal: Blood (2020)
57P Therapeutic vulnerability of malignant phyllodes tumour to pazopanib identified through a novel patient-derived xenograft and cell line model
Authors: D.Y.X. Ng, Z. Li, E. Lee, J. Koh, C.C.Y. Ng, A. Lim, L. Wei, S.R. Ng, K.S. Lim, Y. Sim, A.A. Thike, D.B.M.N. Nur, P.H. Tan, B.T. Teh, J.Y. Chan
Journal: Annals of Oncology (2020)