tbuckley/cabot-search huggingface dataset:
Population Mortality and Laws Encouraging Influenza Vaccination for Hospital Workers
Authors: Mariana Carrera, Emily C. Lawler, Corey White
Journal: Annals of Internal Medicine (2021)

Since 1995, 14 states have passed laws encouraging or mandating influenza vaccination for hospital workers. Although the Centers for Disease Control and Prevention recommends vaccinating health care workers to reduce disease transmission and patient risk, the effect of these laws on pneumonia and influenza mortality is unknown.To measure the effect of state-level hospital worker influenza vaccination laws on pneumonia and influenza mortality.Quasi-experimental observational study.United States.Population of all states from 1995 to 2017.State adoption of a law promoting influenza vaccination for hospital workers.Pneumonia and influenza mortality per 100 000 persons by state and by month, both population-wide and separately by age group, obtained from restricted-access National Vital Statistics System files. Linear and log-linear models were used to compare changes in mortality rates for adopting versus nonadopting states.Implementation of state laws requiring hospitals to offer influenza vaccination to their employees was associated with a 2.5% reduction in the monthly pneumonia and influenza mortality rate (-0.16 deaths per 100 000 persons [95% CI, -0.29 to -0.02]; P = 0.022) during the years when the vaccine was well matched to the circulating strains. The largest effects occurred among elderly persons and during peak influenza months.Utilization of large-scale national data precluded analysis of more specific outcomes, such as laboratory-confirmed or hospital-acquired influenza.State laws promoting hospital worker vaccination against influenza may be effective in preventing pneumonia- and influenza-related deaths, particularly among elderly persons. Vaccinating hospital workers may substantially reduce the spread of influenza and protect the most vulnerable populations.None.
Optimism for Interstitial Lung Disease–Associated Pulmonary Hypertension?
Authors: Darren B. Taichman
Journal: New England Journal of Medicine (2021)

Pulmonary hypertension scares us, and for good reason. Pulmonary hypertension may be caused by an intrinsic pulmonary vasculopathy — termed pulmonary arterial hypertension — or it may complicate other, more common problems such as interstitial lung disease, in which it signals the presence of advanced, often end-stage disease.1 Regardless of its cause, without effective therapy, pulmonary hypertension is associated with worsened dyspnea, mobility, quality of life, and short-term survival. Fortunately, remarkable progress in drug development has transformed a diagnosis of pulmonary arterial hypertension from a disease that is uniformly and rapidly fatal into one that in some patients may be . . .
Inhibitory signaling sustains a distinct early memory CD8 <sup>+</sup> T cell precursor that is resistant to DNA damage
Authors: Jonathan B. Johnnidis, Yuki Muroyama, Shin Foong Ngiow, Zeyu Chen, Sasikanth Manne, Zhangying Cai, Shufei Song, Jesse M. Platt, Jason M. Schenkel, Mohamed Abdel-Hakeem, Jean-Christophe Beltra, Allison R. Greenplate, Mohammed-Alkhatim A. Ali, Kito Nzingha, Josephine R. Giles, Christelle Harly, John Attanasio, Kristen E. Pauken, Bertram Bengsch, Michael A. Paley, Vesselin T. Tomov, Makoto Kurachi, Dario A. A. Vignali, Arlene H. Sharpe, Steven L. Reiner, Avinash Bhandoola, F. Bradley Johnson, E. John Wherry
Journal: Science Immunology (2021)

An early memory CD8 + T cell precursor with distinct genome maintenance capacity depends on inhibitory receptor signaling.
In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants
Authors: Zhenshan Liu, Qi Liu, Xiaofei Yang, Yueying Zhang, Matthew Norris, Xiaoxi Chen, Jitender Cheema, Huakun Zhang, Yiliang Ding
Journal: Genome biology (2021)

Abstract Background mRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence content is insufficient for this purpose. Previous studies suggested that RNA structure affects mRNA processing. However, the regulatory role of RNA structure in mRNA processing remains unclear. Results Here, we perform in vivo selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) chemical profiling on Arabidopsis and generate the in vivo nuclear RNA structure landscape. We find that nuclear mRNAs fold differently from cytosolic mRNAs across translation start and stop sites. Notably, we discover a two-nucleotide single-stranded RNA structure feature upstream of 5′ splice sites that is strongly associated with splicing and the selection of alternative 5′ splice sites. The regulatory role of this RNA structure feature is further confirmed by experimental validation. Moreover, we find the single-strandedness of branch sites is also associated with 3′ splice site recognition. We also identify an RNA structure feature comprising two close-by single-stranded regions that is specifically associated with both polyadenylation and alternative polyadenylation events. Conclusions We successfully identify pre-mRNA structure features associated with splicing and polyadenylation at whole-genome scale and validate an RNA structure feature which can regulate splicing. Our study unveils a new RNA structure regulatory mechanism for mRNA processing.
Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy
Authors: Jerome Fortin, Christian Bassi, Parameswaran Ramachandran, Wanda Y. Li, Ruxiao Tian, Ida Zarrabi, Graham Hill, Bryan E. Snow, Jillian Haight, Chantal Tobin, Kelsey Hodgson, Andrew Wakeham, Vuk Stambolic, Tak W. Mak
Journal: Journal of Clinical Investigation (2021)

In order to sustain proficient life-long hematopoiesis, hematopoietic stem cells (HSCs) must possess robust mechanisms to preserve their quiescence and genome integrity. DNA-damaging stress can perturb HSC homeostasis by affecting their survival, self-renewal, and differentiation. Ablation of the kinase ataxia telangiectasia mutated (ATM), a master regulator of the DNA damage response, impairs HSC fitness. Paradoxically, we show here that loss of a single allele of Atm enhances HSC functionality in mice. To explain this observation, we explored a possible link between ATM and the tumor suppressor phosphatase and tensin homolog (PTEN), which also regulates HSC function. We generated and analyzed a knockin mouse line (PtenS398A/S398A), in which PTEN cannot be phosphorylated by ATM. Similar to Atm+/-, PtenS398A/S398A HSCs have enhanced hematopoietic reconstitution ability, accompanied by resistance to apoptosis induced by genotoxic stress. Single-cell transcriptomic analyses and functional assays revealed that dormant PtenS398A/S398A HSCs aberrantly tolerate elevated mitochondrial activity and the accumulation of reactive oxygen species, which are normally associated with HSC priming for self-renewal or differentiation. Our results unveil a molecular connection between ATM and PTEN, which couples the response to genotoxic stress and dormancy in HSCs.
Abstract 14892: Age-associated microRNA Expression in Human Peripheral Blood is Associated With All-cause Mortality and Age-related Traits
Authors: Tianxiao Huan, George Chen, Chunyu Liu, Jian Rong, Kahraman Tanriverdi, Sudha Seshadri, Jane Freedman, Martin Larson, Joanne Murabito, Daniel Levy
Journal: Circulation (2016)

Introduction: Recent evidence supports strong correlations between human aging and molecular signatures of DNA methylation and expression of protein-coding genes. The relations of microRNA (miRNA) ...
Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer
Authors: Xiaoqi Yang, Tao Ye, Haoran Liu, Peng Lv, Chen Duan, Xiaoliang Wu, Kehua Jiang, Hongyan Lu, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang, Zhangqun Ye
Journal: Molecular Cancer (2021)

Abstract Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.
Abstract 11982: Hemodynamic Predictors of Right Heart Failure Requiring Right Ventricular Assist Devices After Continuous-flow Left Ventricular Assist Devices Placement
Authors: Dae Hyun Lee, Zachary Stachura, Deepika Kulkarni, Jason P Feliberti, Ricardo Restrepo-Jaramillo
Journal: Circulation (2019)

Introduction: Right heart failure (RVF) is a severe complication that could require additional mechanical support after implantation of continuous-flow left ventricular assist devices (LVAD). Signi...
Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus
Authors: Li Zhou, Xuemin He, Peihong Cai, Ting Li, Rongdong Peng, Junlong Dang, Yue Li, Haicheng Li, Feng Huang, Guojun Shi, Chichu Xie, Yan Lu, Yanming Chen
Journal: Cellular and Molecular Immunology (2021)
Association of Youth Age at Exposure to Household Dysfunction With Outcomes in Early Adulthood
Authors: Signe Hald Andersen
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The current focus on the association of negative experiences in early childhood with adverse outcomes later in life is based on limited empirical evidence. <h3>Objective</h3> To evaluate whether age at exposure to negative experiences in childhood and adolescence is associated with outcomes in early adulthood. <h3>Design, Setting, and Participants</h3> This cohort study used population data from administrative sources for all Danish individuals born between 1987 and 1995 who were living in Denmark at 19 years of age. Data were analyzed in July 2020. <h3>Exposures</h3> Exposure to 6 household dysfunction items (HDIs) from birth to 17 years of age by age group. Age groups were as follows: 0 to 2 years (early childhood), 3 to 5 years (preschool), 6 to 12 years (mid-childhood), and 13 to 17 years (early adolescence). The 6 items were parents' unemployment, incarceration, mental disorders, death, and divorce and the child's foster care experiences. <h3>Main Outcomes and Measures</h3> Mental disorders, low educational attainment, disconnection from education and the labor market, and criminal charges. A fixed-effects model was used to estimate the dose-response and age-specific associations between HDI exposure and the collated outcome measure. <h3>Results</h3> The study sample included 605 344 individuals observed from birth to 19 years of age (mean [SD] birth year, 1991 [2.56] years; range, 1987-1995; 335 725 [55%] male). Overall, 278 115 individuals (45.94%) were exposed to 1 or more of the 6 HDIs from birth to 17 years of age. Exposure was most prevalent at 1 year of age (exposure rate, 11.3%), and parental unemployment was the most common HDI (15.5% observed in mid-childhood). The risk of experiencing the 4 outcomes was monotonically associated with the number of HDIs. For example, experiencing 1 HDI between birth and 17 years of age was associated with an increased risk of experiencing an adverse outcome by approximately 1.0 percentage point (β = 0.011; 95% CI, 0.010-0.012;<i>P</i> &lt; .001). Similarly, the risk of experiencing adverse outcomes varied significantly in association with age at exposure. Exposure during early adolescence was more strongly associated with adverse outcomes than was exposure during early childhood (increased risk of 5.8 percentage points [β = 0.058; 95% CI, 0.052-0.063;<i>P</i> &lt; .001] vs 1.0 [β = 0.010; 95% CI, 0.004-0.015;<i>P</i> = .001]). <h3>Conclusions and Relevance</h3> In this cohort study, exposure to negative experiences in early adolescence was more strongly associated with later adverse outcomes than was exposure at other points in childhood. Knowledge of age-specific associations is important information for policy makers who need to prioritize resources targeting disadvantaged children and youths.
Cerebral spinal fluid biomarker profiles in CNS infection associated with HSV and VZV mimic patterns in Alzheimer’s disease
Authors: Makiko Shinomoto, Takashi Kasai, Harutsugu Tatebe, Fukiko Kitani-Morii, Takuma Ohmichi, Yuzo Fujino, David Allsop, Toshiki Mizuno, Takahiko Tokuda
Journal: Translational Neurodegeneration (2021)
Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial
Authors: Imre Noth, Vincent Cottin, Nazia Chaudhuri, Tamera J. Corte, Kerri A. Johannson, Marlies Wijsenbeek, Stephane Jouneau, Andreas Michael, Manuel Quaresma, Klaus B. Rohr, Anne-Marie Russell, Susanne Stowasser, Toby M. Maher
Journal: European Respiratory Journal (2021)

Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72-0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.
Drug–Radiotherapy Combination Trial Developments—Letter
Authors: Joseph R. Evans, Kyle C. Cuneo, Theodore S. Lawrence
Journal: Clinical Cancer Research (2021)

We read with great interest the comprehensive review by Chargari and colleagues about the challenges of advancing new radiosensitizing drugs through preclinical models and clinical trials (1). The authors laid out a number of explanations and recommendations for moving forward with more success, and we largely agree with their thoughts. We wish to correct one point used to illustrate the pitfalls of simply adopting chemotherapy agents that have activity when given alone, and the disconnect between preclinical models and eventual clinical results. The authors describe as a cautionary tale the experience with full-dose gemcitabine and large-field radiation producing excess toxicity including fatal events. Thus, the authors suggest that gemcitabine dose reduction is the only viable option.But radiation technique matters too! We wish to draw attention to our long experience at University of Michigan (Ann Arbor, MI) of safely treating borderline and unresectable pancreas cancer with full-dose gemcitabine and radiotherapy. This includes mild hypofractionation (36 Gy in 2.4 Gy/fx; ref. 2), conventional fractionation (our routine clinical practice; ref. 3), in combination with a novel targeted agent (4), and as part of trimodality treatment (5). In our phase II trial, 90% of patients completed gemcitabine-based chemoradiotherapy and there were no deaths (5). We added a Wee1 inhibitor to gemcitabine-based chemoradiotherapy, and saw G3–4 toxicities that were mostly unrelated to radiotherapy (pulmonary embolus, myocardial infarction, febrile neutropenia, etc.). No deaths were due to treatment and all patients completed chemoradiotherapy (4). Summarizing our experience in 180 patients 1999–2012, 7.7% had late gastric or duodenal bleeding (3), which is similar to what others have found for definitive chemoradiation in this setting.We treat only gross disease plus a small margin, and do not include elective nodal irradiation. Among the minority of failures that were local, a majority were in-field and not in regional untreated nodal areas indicating that disease control is not compromised (2). We have been encouraged by our results, with our recent phase II trial after FOLFIRINOX in borderline patients having a 52% resection rate that were all R0 and had a median overall survival (OS) of 37 months (5). And we continue pursuing the combination of gemcitabine and a Wee1 inhibitor along with radiotherapy after our phase I/II study in locally advanced patients resulted in a median OS of 22 months (4).This experience reinforces the authors' overall message about the search for more effective combinations: safe use of full-dose chemotherapy requires careful consideration both in the crafting of radiotherapy technique as well as the systemic therapy dosing.See the Response, p. 356T.S. Lawrence reports grants from NCI during the conduct of the study. No disclosures were reported by the other authors.
Oral sucrosomial iron improves exercise capacity and quality of life in heart failure with reduced ejection fraction and iron deficiency: a non‐randomized, open‐label, proof‐of‐concept study
Authors: Apostolos Karavidas, Efstratios Troganis, George Lazaros, Despina Balta, Ioannis‐Nektarios Karavidas, Eftihia Polyzogopoulou, John Parissis, Dimitrios Farmakis
Journal: European Journal of Heart Failure (2021)
Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis
Authors: Doyeon Hwang, Haneol J. Kim, Seung-Pyo Lee, Seonhee Lim, Bon-Kwon Koo, Yong-Jin Kim, Woong Kook, Daniele Andreini, Mouaz H. Al-Mallah, Matthew J. Budoff, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Edoardo Conte, Hugo Marques, Pedro de Araújo Gonçalves, Ilan Gottlieb, Martin Hadamitzky, Jonathon A. Leipsic, Erica Maffei, Gianluca Pontone, Gilbert L. Raff, Sanghoon Shin, Byoung Kwon Lee, Eun Ju Chun, Ji Min Sung, Sang-Eun Lee, Daniel S. Berman, Fay Y. Lin, Renu Virmani, Habib Samady, Peter H. Stone, Jagat Narula, Jeroen J. Bax, Leslee J. Shaw, James K. Min, Hyuk-Jae Chang
Journal: JACC. Cardiovascular imaging (2021)
Unconjugated bilirubin is associated with protection from early-life wheeze and childhood asthma
Authors: Kedir N. Turi, Christopher McKennan, Tebeb Gebretsadik, Brittney Snyder, Christine M. Seroogy, Robert F. Lemanske, Edward Zoratti, Suzanne Havstad, Carole Ober, Susan Lynch, Kathyrn McCauley, Chang Yu, Daniel J. Jackson, James E. Gern, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2021)

Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood.We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma.We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma.Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress-related metabolites. There were no significant associations between metabolites and allergic sensitization.We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.