tbuckley/cabot-search huggingface dataset:
Intergenic RNA mainly derives from nascent transcripts of known genes
Authors: Federico Agostini, Julian Zagalak, Jan Attig, Jernej Ule, Nicholas M. Luscombe
Journal: Genome biology (2021)

Abstract Background Eukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes almost any genomic context. Currently, the source and function of most RNAs originating from intergenic regions in the human genome remain unclear. Results We hypothesize that many intergenic RNAs can be ascribed to the presence of as-yet unannotated genes or the “fuzzy” transcription of known genes that extends beyond the annotated boundaries. To elucidate the contributions of these two sources, we assemble a dataset of more than 2.5 billion publicly available RNA-seq reads across 5 human cell lines and multiple cellular compartments to annotate transcriptional units in the human genome. About 80% of transcripts from unannotated intergenic regions can be attributed to the fuzzy transcription of existing genes; the remaining transcripts originate mainly from putative long non-coding RNA loci that are rarely spliced. We validate the transcriptional activity of these intergenic RNAs using independent measurements, including transcriptional start sites, chromatin signatures, and genomic occupancies of RNA polymerase II in various phosphorylation states. We also analyze the nuclear localization and sensitivities of intergenic transcripts to nucleases to illustrate that they tend to be rapidly degraded either on-chromatin by XRN2 or off-chromatin by the exosome. Conclusions We provide a curated atlas of intergenic RNAs that distinguishes between alternative processing of well-annotated genes from independent transcriptional units based on the combined analysis of chromatin signatures, nuclear RNA localization, and degradation pathways.
Putting the pieces together: Self-control as a complex interaction of psychological processes
Authors: Fritz Strack, Roland Deutsch, Bleen Abraham
Journal: Behavioral and Brain Sciences (2021)

Abstract Ainslie's account of willpower addresses many important mechanisms (e.g., habit, visceral activation, and implementation intention). We argue that a model of willpower should be grounded in general psychological principles and with a primary focus on their interplay. We discuss the reflective-impulsive model that covers willpower and impulsiveness as special constellations of processes that govern various forms of cognition and behavior.
Prognostic significance of myeloid immune cells and their spatial distribution in the colorectal cancer microenvironment
Authors: Juha P Väyrynen, Koichiro Haruki, Sara A Väyrynen, Mai Chan Lau, Andressa Dias Costa, Jennifer Borowsky, Melissa Zhao, Tomotaka Ugai, Junko Kishikawa, Naohiko Akimoto, Rong Zhong, Shanshan Shi, Tzuu-Wang Chang, Kenji Fujiyoshi, Kota Arima, Tyler S Twombly, Annacarolina Da Silva, Mingyang Song, Kana Wu, Xuehong Zhang, Andrew T Chan, Reiko Nishihara, Charles S Fuchs, Jeffrey A Meyerhardt, Marios Giannakis, Shuji Ogino, Jonathan A Nowak
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Myeloid cells represent an abundant yet heterogeneous cell population in the colorectal cancer microenvironment, and their roles remain poorly understood. Methods We used multiplexed immunofluorescence combined with digital image analysis to identify CD14 + monocytic and CD15 + granulocytic cells and to evaluate their maturity (HLA-DR and CD33), immunosuppressive potential (ARG1) and proximity to cytokeratin (KRT)-positive tumor cells in 913 colorectal carcinomas. Using covariate data of 4465 incident colorectal cancers in two prospective cohort studies, the inverse probability weighting method was used with multivariable-adjusted Cox proportional hazards models to assess cancer-specific mortality according to ordinal quartiles (Q1–Q4) of myeloid cell densities. Immune cell–tumor cell proximity was measured with the nearest neighbor method and the G-cross function, which determines the likelihood of any tumor cell having at least one immune cell of the specified type within a certain radius. Results Higher intraepithelial ( P trend =0.0002; HR for Q4 (vs Q1), 0.48, 95% CI 0.31 to 0.76) and stromal ( P trend &lt;0.0001; HR for Q4 (vs Q1), 0.42, 95% CI 0.29 to 0.63) densities of CD14 + HLA-DR + cells were associated with lower colorectal cancer-specific mortality while, conversely, higher intraepithelial densities of CD14 + HLA-DR − cells were associated with higher colorectal cancer-specific mortality ( P trend =0.0003; HR for Q4 (vs Q1), 1.78, 95% CI 1.25 to 2.55). Spatial analyses indicated that CD15 + cells were located closer to tumor cells than CD14 + cells, and CD14 + HLA-DR + cells were closer to tumor than CD14 + HLA-DR − cells (p&lt;0.0001). The G-cross proximity measurement, evaluating the difference in the likelihood of any tumor cell being colocated with at least one CD14 + HLA-DR + cell versus CD14 + HLA-DR − cell within a 20 µm radius, was associated with lower colorectal cancer-specific mortality ( P trend &lt;0.0001; HR for Q4 (vs Q1), 0.37, 95% CI 0.24 to 0.57). Conclusions Myeloid cell populations occur in spatially distinct distributions and exhibit divergent, subset-specific prognostic significance in colorectal cancer, with mature CD14 + HLA-DR + and immature CD14 + HLA-DR − monocytic phenotypes most notably showing opposite associations. These results highlight the prognostic utility of multimarker evaluation of myeloid cell infiltrates and reveal a previously unrecognized degree of spatial organization for myeloid cells in the immune microenvironment.
Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant — Obesity Associated with Inferior Outcomes
Authors: Andrew Ip, Jeffrey M. Switchenko, Michael Graiser, Jean L. Koff, Vikas A. Gupta, Ajay K. Nooka, Zaid Al-Kadhimi, Mary Jo Lechowicz, Jonathan L. Kaufman, Sagar Lonial, Edmund K. Waller, Amelia Langston, Christopher Flowers, Jonathon B Cohen
Journal: Blood (2017)
Sessile serrated adenoma invading a diverticulum in the right colon: tips and tricks for a safe complete endoscopic resection
Authors: Sophie Geyl, Jérémie Albouys, Romain Legros, Hugo Lepetit, Martin Dahan, Mathieu Pioche, Jérémie Jacques
Journal: Endoscopy (2021)

Large sessile serrated adenomas are at high risk of incomplete resection because of difficulty visualizing their margins [1]. Moreover, cases involving invasion of a diverticulum are technically challenging and carry a high risk of perforation. Here, we report on a 3.5-cm sessile serrated adenoma in the right colon with invasion of the diverticulum ([Fig. 1 a], [Video 1]).
Comparison of COVID-19 Incidence Rates Before and After School Reopening in Israel
Authors: Ido Somekh, Lital Keinan Boker, Tamy Shohat, Massimo Pettoello-Mantovani, Eric A. F. Simões, Eli Somekh
Journal: JAMA Network Open (2021)

This cohort study examines COVID-19 incidence rates in youths aged 0 to 19 before and after reopening schools in Israel.
Covid-19: Early stage cancer diagnoses fell by third in first lockdown
Authors: Matthew Limb
Journal: BMJ (2021)

Covid-19: Early stage cancer diagnoses fell by third in first lockdown Matthew LimbDiagnoses of early stage cancer in England fell by 33% in the first wave of the covid-19 pandemic in 2020, figures show.Experts warned that many people who "missed" a diagnosis could have an early stage cancer but that it might not be identified until later on, potentially affecting their chances of survival.Steven McIntosh, executive director of advocacy and communications for the charity Macmillan Cancer Support, said that although SARS-CoV-2 infection rates were now falling and lockdown was easing the pandemic's knock-on effects on the care of patients with cancer "cannot be overstated."He said, "We are likely to be dealing with covid's long shadow for many years to come, and so we need action now to address the chronic undersupply of cancer staff in the NHS."The charity's analysis of figures from Public Health England's National Cancer Registration and Analysis Service 1 showed that the number of people who had their cancer diagnosed at stage I fell from 18 400 in March to June 2019 to 12 400 in March to June 2020, the first months of the pandemic, a drop of around 1500 people a month.
Economic burden of disease progression among multiple myeloma patients who have received transplant and at least one line of therapy in the US
Authors: Rafael Fonseca, May Hagiwara, Sumeet Panjabi, Emre Yucel, Jacqueline Buchanan, Thomas Delea
Journal: Blood Cancer Journal (2021)

Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) who received their first stem cell transplant (SCT) within 1 year of initial MM diagnosis were estimated using a large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, acute kidney disease, or death within 12 months of LOT initiation. Annual HRU and costs in the first three LOTs (L1-L3) were compared for patients with versus without disease progression using inverse probability of treatment weighting to adjust for differences between groups in baseline characteristics. In all LOTs, mean annual hospitalizations and healthcare costs were greater for patients with versus without progression. Total incremental annual costs among patients with versus without progression in L1-L3 were $18,359, $87,055, and $71,917, respectively, among LOTs initiated between 2006 and 2018. In LOTs initiated between 2013 and 2018, the figures were $46,024, $100,329, and $101,942 in L1-L3, respectively. The economic burden of disease progression is substantial in this population of MM patients who underwent SCT and received systemic anti-myeloma therapy.
OXIDIZED LOW-DENSITY LIPOPROTEIN PROMOTES FORKHEAD BOX P3 GENE METHYLATION OF REGULATORY T CELLS AND ACCELERATE ATHEROSCLEROSIS BY UP-REGULATING DNA METHYLTRANSFERASE 3B
Authors: Ling Zhu, Jing Xu, Qianwei Cui, Yong Zhang, Fuqiang Liu, Gongchang Guan, Zhongwei Liu, Shuo Pan, Junkui Wang
Journal: Journal of the American College of Cardiology (2021)
Straight Curves: Incidental Diagnosis of Pneumothorax on Transesophageal Echocardiography
Authors: Diana Morales Castro, Kalvin Lung, Ghislaine Douflé
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Straight Curves: Incidental Diagnosis of Pneumothorax on Transesophageal Echocardiography." American Journal of Respiratory and Critical Care Medicine, 204(7), pp. e88–e91
COVID-19 and the neonatal microbiome: will the pandemic cost infants their microbes?
Authors: Joann Romano-Keeler, Jilei Zhang, Jun Sun
Journal: Gut Microbes (2021)

Mortality and morbidity from SARS-CoV2 (COVID-19) infections in children remains low, including an exceedingly low rate of horizontal and vertical transmission. However, unforeseen complications to childhood health have emerged secondary to the pandemic. Few studies to date have examined unintended complications of the pandemic in newborns and infants. In this Commentary, we discuss the impact that COVID-19 may have on inheritance of the newborn microbiome and its assembly throughout the first years of life. In the early stages of the pandemic when vertical transmission of COVID-19 was poorly understood, several studies reported increased rates of C-sections in COVID-19 positive women. Initial recommendations discouraged COVID-19 positive mothers from breastfeeding and participating in skin-to-skin care, advising them to isolate during their window of infectivity. These shifts in perinatal care can adversely impact microbial colonization during the first 1000 days of life. While obstetrical and neonatal management have evolved to reflect our current knowledge of perinatal transmission, we are observing other changes in early life exposures of infants, including increased attention to hygiene, fewer social interactions, and decreased global travel, all of which are major drivers of early-life gut colonization. Composition of the gut microbiota in adults directly impacts severity of infection, suggesting a role of microbial communities in modulating immune responses to COVID-19. Conversely, the role of the intestinal microbiome in susceptibility and severity of COVID-19 in newborns and children remains unknown. The onset of adulthood diseases is related to the establishment of a healthy gut microbiome during childhood. As we continue to define COVID-19 biology, further research is necessary to understand how acquisition of the neonatal microbiome is affected by the pandemic. Furthermore, infection control measures must be balanced with strategies that promote microbial diversity to impart optimal health outcomes and potentially modulate susceptibility of children to COVID-19.
SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome
Authors: Piero Pavone, Manuela Ceccarelli, Silvia Marino, Daniela Caruso, Raffaele Falsaperla, Massimiliano Berretta, Emmanuele Venanzi Rullo, Giuseppe Nunnari
Journal: The Lancet Child & Adolescent Health (2021)
"NONTUBERCULOUS MYCOBACTERIA IN BRONCHIECTASIS: PREVALENCE AND PATIENT CHARACTERISTICS". S.J. FOWLER, J. FRENCH, N.J. SCREATON, J. FOWERAKER, A. CONDLIFFE, C.S. HAWORTH, A.R. EXLEY AND D. BILTON. EUR RESPIR J 2006; 28: 1204-1210.
Journal: European Respiratory Journal (2007)
Evaluation of Trials Comparing Single-Enantiomer Drugs to Their Racemic Precursors
Authors: Aaron S. Long, Audrey D. Zhang, Caitlin E. Meyer, Alexander C. Egilman, Joseph S. Ross, Joshua D. Wallach
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Chiral switching, a strategy in which drug manufacturers develop a single-enantiomer formulation of a drug to be substituted for a racemic formulation, allows manufacturers to maintain market exclusivity for drugs losing patent protection, even without demonstrating superior efficacy or safety. <h3>Objective</h3> To identify and characterize all randomized clinical trials (RCTs) directly comparing a Food and Drug Administration (FDA)–approved single-enantiomer drug against a previously approved racemic drug for 1 or more efficacy or safety end points. <h3>Evidence Review</h3> Drugs were identified using the Drugs@FDA database. Randomized clinical trials were identified using Ovid MEDLINE (1949 to October 22, 2019), Ovid Embase (1974 to October 22, 2019), Web of Science Core Collection (all years), ClinicalTrials.gov, and Cochrane Central Registry of Controlled Trials (CENTRAL, Wiley, Issue 8 of 12, October 22, 2019). Trials were characterized as favoring the single-enantiomer or racemic drugs based on whether the primary efficacy, secondary efficacy, and safety end points achieved each study's defined significance level (eg,<i>P</i> &lt; .05). Trials were characterized as favoring neither drug if no statistically significant differences were reported for any end point or if both drugs were found to be superior for 1 or more separate end points. <h3>Findings</h3> Fifteen FDA-approved single-enantiomer drugs were identified with racemic precursors approved in the US or Europe. For 3 single-enantiomer racemic drug pairs, no RCTs directly comparing the drugs were identified. For the remaining 12 pairs, 185 RCTs comparing efficacy or safety of the drug pairs were identified, 124 (67.0%) of which studied 1 pair (levobupivacaine/bupivacaine). There were 179 RCTs directly comparing drug pairs using efficacy end points, of which 23 (12.8%) favored the single enantiomer based on primary efficacy end point results. There were 124 RCTs directly comparing drug pairs using safety end points, of which 17 (13.7%) favored the single-enantiomer drug. For 9 of the 15 single-enantiomer drugs (60.0%), no RCTs were identified providing evidence of improved efficacy, based on primary end point results, or safety as compared with their racemic precursors. <h3>Conclusions and Relevance</h3> The results of this systematic review suggest that most newly marketed FDA-approved single-enantiomer drugs are infrequently directly compared with their racemic precursors, and when compared, they are uncommonly found to provide improved efficacy or safety, despite their greater costs.
Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis
Authors: SeungHyun Park, KangJu Lee, Heekyoung Kang, YeJin Lee, JiYong Lee, Jeong Hun Kim, Hyun Beom Song, WonHyoung Ryu
Journal: Advanced Healthcare Materials (2021)

Abstract Infectious keratitis is mainly treated with topical antibiotics. To achieve and maintain the required therapeutic concentration in the cornea where the tear fluid continuously rinses the surface, the antibiotics must be frequently applied, even while the patient is sleeping, and oral medication is sometimes required. However, the inevitably poor compliance and avascular nature of the cornea decrease drug bioavailability. In this study, a single microneedle (MN) is injected into the cornea to substitute for the repeated application of eyedrops in the treatment of infectious keratitis. After comparing the mechanical integrity and drug release profiles of three different drug‐tips, the drug‐tip with the “high” drug concentration that releases 12.5 ng drug within 3 days is applied to a cornea to evaluate the transferability and in vivo drug release. In the treatment of infectious keratitis with repeated application of eyedrops for six consecutive days, a single MN injection is substituted for the initial 3 days of eyedrop applications. The progression remains similarly attenuated after 3 days without eyedrops, and comparable efficacy is achieved on day 6 when combined with delayed eyedrop treatment from day 3. Thus, the single administration of a biodegradable MN can substitute for the repeated application of eyedrops in the treatment of infectious keratitis.
Willpower through cultural tools: An example from alcoholics anonymous
Authors: Pamela Acquaro, Richard Sosis
Journal: Behavioral and Brain Sciences (2021)

We argue that a closer look at the practices and tools that humans use to support willpower, and the cultural contexts in which they are employed, can broaden the applicability of Ainslie's theory and facilitate the development of more effective self-control techniques. To support our argument, we examine Alcoholics Anonymous's method of temptation resistance known as "playing the tape through" (PTT).
ROUTINE CPY2C19 GENOTYPE ANALYSIS FOLLOWING PERCUTANEOUS CORONARY INTERVENTION: A NOVEL STRATEGY TO GUIDE ANTIPLATELET SELECTION IN THE CARDIAC CATHETERISATION LABORATORY
Authors: Padraig O Drisceoil, Hani Muradagha, Kevin Millar, Rory Gallen, Myles McKittrick, Bing Wei Thaddeus Soh, Samer Arnous, Thomas Kiernan
Journal: Journal of the American College of Cardiology (2021)
Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody
Authors: Zachary A. Schiller, Michael J. Rudolph, Jacqueline R. Toomey, Monir Ejemel, Alan LaRochelle, Simon A. Davis, Havard S. Lambert, Aurélie Kern, Amanda C. Tardo, Colby A. Souders, Eric Peterson, Rebecca D. Cannon, Chandrashekar Ganesa, Frank Fazio, Nicholas J. Mantis, Lisa A. Cavacini, John Sullivan-Bolyai, Linden T. Hu, Monica E. Embers, Mark S. Klempner, Yang Wang
Journal: Journal of Clinical Investigation (2021)

Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B. burgdorferi from infected ticks in animal models. Maintenance of a protective plasma concentration of a human mAb for tick season presents a significant challenge for a preexposure prophylaxis strategy. Here, we describe the optimization of mAb 2217 by amino acid substitutions (2217LS: M428L and N434S) in the Fc domain. The LS mutation led to a 2-fold increase in half-life in cynomolgus monkeys. In a rhesus macaque model, 2217LS protected animals from tick transmission of spirochetes at a dose of 3 mg/kg. Crystallographic analysis of Fab in complex with OspA revealed that 2217 bound an epitope that was highly conserved among the B. burgdorferi, B. garinii, and B. afzelii species. Unlike most vaccines that may require boosters to achieve protection, our work supports the development of 2217LS as an effective preexposure prophylaxis in Lyme-endemic regions, with a single dose at the beginning of tick season offering immediate protection that remains for the duration of exposure risk.
CARDIAC MAGNETIC RESONANCE IMAGING FOR GUIDING DECISION-MAKING ON TREATMENT DURATION: DATA FROM RHAPSODY, A PHASE 3 CLINICAL TRIAL OF RILONACEPT IN RECURRENT PERICARDITIS
Authors: Paul Cremer, David Lin, Alistair Wheeler, Antonio Abbate, Antonio Brucato, Fang Fang, Antonella Insalaco, Martin LeWinter, Basil S. Lewis, Sushil Luis, Stephen J. Nicholls, John Petersen, Allan Klein, Massimo Imazio, John F. Paolini
Journal: Journal of the American College of Cardiology (2021)
GLOBAL LONGITUDINAL STRAIN AT REST IS NOT PREDICTIVE OF SUBSEQUENT INDUCIBLE ISCHEMIA AMONG PATIENTS WITH NON-OBSTRUCTIVE CORONARY ARTERY DISEASE IN THE CIAO-ISCHEMIA STUDY
Authors: Esther Davis, Daniela Crousillat, Michael Picard, Jesus Peteiro, Jose Lopez-Sendon, Roxy Senior, Michael Shapiro, Patricia Pellikka, Todd Miller, Mohammad El-Hajjar, Khaled Alfakih, Khaled Abdul-Nour, Dennis Kunichoff, Rebecca Anthopolos, Jerome Fleg, John Spertus, Judith Hochman, David Maron, Harmony Reynolds
Journal: Journal of the American College of Cardiology (2021)
PREVALENCE AND OUTCOMES OF ARRHYTHMIAS IN TUMOR LYSIS SYNDROME AMONG CHILDREN IN THE UNITED STATES: A POPULATION BASED ANALYSIS
Authors: Krishna Kishore Umapathi, Aravind Thavamani, Harshitha Dhanpalreddy, Aditi Gupta, Sawsan Awad, Hoang Nguyen
Journal: Journal of the American College of Cardiology (2021)
SHOT THROUGH THE HEART : ANGINA LIKE SYMPTOMS DUE TO INFERIOR VENA CAVA FILTER FRACTURE MIGRATING TO INTERCOSTAL SPACE
Authors: Kriti Lnu, Resha Khanal, Isha Shrimanker, Vinod Nookala, Nikhil Theckumparampil
Journal: Journal of the American College of Cardiology (2021)