tbuckley/cabot-search huggingface dataset:
Abstract 16481: Feasibility and Safety of Transcatheter Closure of Patent Ductus Arteriosus in Infants Weighing &lt;700 Grams
Authors: Abhishek Chakraborty, Ranjit Philip, Rush Waller, Ronak Naik, Mimily Harsono, Huma Abdulmajeed, Shyam Sathanandam
Journal: Circulation (2020)

Introduction: Recently, the Amplatzer Piccolo Occluder (APO) was approved for PDA closure for infants weighing &gt; 700 grams. The feasibility and safety of the procedure for anyone below this weight cut-off has not been previously explored. Hypothesis: Transcatheter closure of patent ductus arteriosus (PDA) in premature infants who weigh &lt; 700 grams at the time of the procedure is safe and feasible. Methods: This is a retrospective, single-center, study to explore the outcomes of transcatheter PDA occlusions performed on infants weighing &lt; 700 grams. Results: A total of 18 patients weighing between 540 and 670 grams (mean = 612.8 grams) were identified to have underwent the procedure between the two centers. The gestational age ranged between 22-26 weeks (median 24 weeks), and the average birth weight was 537.5 grams. The mean age at the time of PDA closure was 20 days (range 8-35 days). The implant success rate was 100%. The devices used included the MVP-5Q (N=8), the 3-2 APO (N=5) and the 4-2 APO (N=5). The procedure time was 26 ± 23 minutes and fluoroscopy time was 3.7 ± 3.1 minutes. One patient, weighing 640 grams required chest compressions for resuscitation following the procedure, but recovered and since then has grown normally to hospital discharge. There were no other procedural complications. At the latest follow-up (median 1-year), there have been four non-survivors, all unrelated to the procedure. Conclusions: It is feasible and likely safe to perform transcatheter closure of patent ductus arteriosus (PDA) in premature infants who weigh &lt; 700 grams using currently available technologies. There is a learning curve with these interventions. Extreme care must be taken while performing interventions in such small human beings. Further miniaturization of equipment would facilitate better outcomes.
Guild-based analysis for understanding gut microbiome in human health and diseases
Authors: Guojun Wu, Naisi Zhao, Chenhong Zhang, Yan Y. Lam, Liping Zhao
Journal: Genome Medicine (2021)

To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem's higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same "guild" if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of "guild" to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.
Artificial intelligence identifies and quantifies colonoscopy blind spots
Authors: Sarah K. McGill, Julian Rosenman, Rui Wang, Ruibin Ma, Jan-Michael Frahm, Stephen Pizer
Journal: Endoscopy (2021)

Some mucosal surfaces on folds and within haustra may not be visualized at all during colonoscopy, and thus precancerous lesions are missed. We describe here preliminary results of an artificial intelligence (AI) technology that identifies and quantifies these "blind spots," with the aim, potentially, that endoscopists may be directed to them in real time.
RETRACTED: circTulp4 functions in Alzheimer’s disease pathogenesis by regulating its parental gene, Tulp4
Authors: Nana Ma, Jie Pan, Yi Wen, Qi Wu, Bo Yu, Xi Chen, Jun Wan, Wei Zhang
Journal: Molecular Therapy (2021)

Alzheimer's disease (AD)—one of the most common neurodegenerative diseases worldwide—impairs cognition, memory, and language ability and causes dementia. However, AD pathogenesis remains poorly elucidated. Recently, a potential link between AD and circular RNAs (circRNAs) has been uncovered, but only a few circRNAs that might be involved in AD have been identified. Here, we systematically investigated circRNAs in the APP/PS1 model mouse brain through deep RNA sequencing. We report that circRNAs are markedly enriched in the brain and that several circRNAs exhibit differential expression between wild-type and APP/PS1 mice. We characterized one abundant circRNA, circTulp4, derived from Intron1 of the gene Tulp4. Our results indicate that circTulp4 predominantly localizes in the nucleus and interacts with U1 small nuclear ribonucleoprotein particle (snRNP) and RNA polymerase II to modulate the transcription of its parental gene, Tulp4, and thereby regulate the function of the nervous system, and might participate in the development of AD. Alzheimer's disease (AD)—one of the most common neurodegenerative diseases worldwide—impairs cognition, memory, and language ability and causes dementia. However, AD pathogenesis remains poorly elucidated. Recently, a potential link between AD and circular RNAs (circRNAs) has been uncovered, but only a few circRNAs that might be involved in AD have been identified. Here, we systematically investigated circRNAs in the APP/PS1 model mouse brain through deep RNA sequencing. We report that circRNAs are markedly enriched in the brain and that several circRNAs exhibit differential expression between wild-type and APP/PS1 mice. We characterized one abundant circRNA, circTulp4, derived from Intron1 of the gene Tulp4. Our results indicate that circTulp4 predominantly localizes in the nucleus and interacts with U1 small nuclear ribonucleoprotein particle (snRNP) and RNA polymerase II to modulate the transcription of its parental gene, Tulp4, and thereby regulate the function of the nervous system, and might participate in the development of AD.
Improved Glycemic Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose Suspend in People With Type 1 Diabetes
Authors: Olivia J. Collyns, Renee A. Meier, Zara L. Betts, Denis S.H. Chan, Chris Frampton, Carla M. Frewen, Niranjala M. Hewapathirana, Shirley D. Jones, Anirban Roy, Benyamin Grosman, Natalie Kurtz, John Shin, Robert A. Vigersky, Benjamin J. Wheeler, Martin I. de Bock
Journal: Diabetes Care (2021)

OBJECTIVE To study the MiniMed Advanced Hybrid Closed-Loop (AHCL) system, which includes an algorithm with individualized basal target set points, automated correction bolus function, and improved Auto Mode stability. RESEARCH DESIGN AND METHODS This dual-center, randomized, open-label, two-sequence crossover study in automated-insulin-delivery–naive participants with type 1 diabetes (aged 7–80 years) compared AHCL to sensor-augmented pump therapy with predictive low glucose management (SAP + PLGM). Each study phase was 4 weeks, preceded by a 2- to 4-week run-in and separated by a 2-week washout. RESULTS The study was completed by 59 of 60 people (mean age 23.3 ± 14.4 years). Time in target range (TIR) 3.9–10 mmol/L (70–180 mg/dL) favored AHCL over SAP + PLGM (70.4 ± 8.1% vs. 57.9 ± 11.7%) by 12.5 ± 8.5% (P &amp;lt; 0.001), with greater improvement overnight (18.8 ± 12.9%, P &amp;lt; 0.001). All age-groups (children [7–13 years], adolescents [14–21 years], and adults [&amp;gt;22 years]) demonstrated improvement, with adolescents showing the largest improvement (14.4 ± 8.4%). Mean sensor glucose (SG) at run-in was 9.3 ± 0.9 mmol/L (167 ± 16.2 mg/dL) and improved with AHCL (8.5 ± 0.7 mmol/L [153 ± 12.6 mg/dL], P &amp;lt; 0.001), but deteriorated during PLGM (9.5 ± 1.1 mmol/L [17 ± 19.8 mg/dL], P &amp;lt; 0.001). TIR was optimal when the algorithm set point was 5.6 mmol/L (100 mg/dL) compared with 6.7 mmol/L (120 mg/dL), 72.0 ± 7.9% vs. 64.6 ± 6.9%, respectively, with no additional hypoglycemia. Auto Mode was active 96.4 ± 4.0% of the time. The percentage of hypoglycemia at baseline (&amp;lt;3.9 mmol/L [70 mg/dL] and ≤3.0 mmol/L [54 mg/dL]) was 3.1 ± 2.1% and 0.5 ± 0.6%, respectively. During AHCL, the percentage time at &amp;lt;3.9 mmol/L (70 mg/dL) improved to 2.1 ± 1.4% (P = 0.034) and was statistically but not clinically reduced for ≤3.0 mmol/L (54 mg/dL) (0.5 ± 0.5%; P = 0.025). There was one episode of mild diabetic ketoacidosis attributed to an infusion set failure in combination with an intercurrent illness, which occurred during the SAP + PLGM arm. CONCLUSIONS AHCL with automated correction bolus demonstrated significant improvement in glucose control compared with SAP + PLGM. A lower algorithm SG set point during AHCL resulted in greater TIR, with no increase in hypoglycemia.
From Paternalism to Engagement: Bioethics Needs a Paradigm Shift to Address Racial Injustice During COVID-19
Authors: John Noel Viaña, Sujatha Raman, Marcus Barber
Journal: The American Journal of Bioethics (2021)

COVID-19 has disproportionately affected ethnic minorities and migrants, not only through an increased risk of infection and death (Pan et al. 2020), but also through experiences of harassment, mar...
Clinical and Translational Implications of an Emerging Developmental Substructure for Autism
Authors: John N. Constantino, Tony Charman, Emily J.H. Jones
Journal: Annual Review of Clinical Psychology (2021)

A vast share of the population-attributable risk for autism relates to inherited polygenic risk. A growing number of studies in the past five years have indicated that inherited susceptibility may operate through a finite number of early developmental liabilities that, in various permutations and combinations, jointly predict familial recurrence of the convergent syndrome of social communication disability that defines the condition. Here, we synthesize this body of research to derive evidence for a novel developmental substructure for autism, which has profound implications for ongoing discovery efforts to elucidate its neurobiological causes, and to inform future clinical and biomarker studies, early interventions, and personalized approaches to therapy.
Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats
Authors: Sipin Zhu, Yibo Ying, Yan He, Xingxing Zhong, Jiahui Ye, Zhiyang Huang, Min Chen, Qiuji Wu, Yifan Zhang, Ziyue Xiang, Yurong Tu, Weiyang Ying, Jian Xiao, Xiaokun Li, Qingsong Ye, Zhouguang Wang
Journal: Bioactive Materials (2021)

Cell-based transplantation strategies possess great potential for spinal cord injury (SCI) repair. Basic fibroblast growth factor (bFGF) has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI. Human dental pulp stem cells (DPSCs) are abundant stem cells with low immune rejection, which can be considered for cell replacement therapy. The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements (5HRE) using an adeno-associated virus (AAV-5HRE-bFGF-DPSCs) in SCI repairing model. In this study, DPSCs were revealed to differentiate into CD13+ pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13+ pericytes to vascular endothelial cells. The re-attachment of CD13+ pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance. As a result, increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved. Thus, this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
Selecting Patients for an Implantable Cardioverter-Defibrillator: Can the Genie Be Put Back Into the Bottle?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Suneet Mittal
Journal: Journal of the American College of Cardiology (2008)
Vaccines and allergic reactions: The past, the current COVID‐19 pandemic, and future perspectives
Authors: Vanitha Sampath, Grace Rabinowitz, Mihir Shah, Surabhi Jain, Zuzana Diamant, Milos Jesenak, Ronald Rabin, Stefan Vieths, Ioana Agache, Mübeccel Akdis, Domingo Barber, Heimo Breiteneder, Sharon Chinthrajah, Tomas Chivato, William Collins, Thomas Eiwegger, Katharine Fast, Wytske Fokkens, Robyn E. O'Hehir, Markus Ollert, Liam O'Mahony, Oscar Palomares, Oliver Pfaar, Carmen Riggioni, Mohamed H Shamji, Milena Sokolowska, Maria Jose Torres, Claudia Traidl‐Hoffmann, Menno van Zelm, De Yun Wang, Luo Zhang, Cezmi A. Akdis, Kari C. Nadeau
Journal: Allergy (2021)

Abstract Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID‐19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post‐authorization and post‐marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
Characterization of Prevalent, Post-Endoscopy, and Incident Esophageal Cancer in the United States: A Large Retrospective Cohort Study
Authors: Ravy K. Vajravelu, Jennifer M. Kolb, Shivani U. Thanawala, Frank I. Scott, Samuel Han, Amit G. Singal, Gary W. Falk, David A. Katzka, Sachin Wani
Journal: Clinical Gastroenterology and Hepatology (2021)
Taxonomic Sampling and Rare Genomic Changes Overcome Long-Branch Attraction in the Phylogenetic Placement of Pseudoscorpions
Authors: Andrew Z Ontano, Guilherme Gainett, Shlomi Aharon, Jesús A Ballesteros, Ligia R Benavides, Kevin F Corbett, Efrat Gavish-Regev, Mark S Harvey, Scott Monsma, Carlos E Santibáñez-López, Emily V W Setton, Jakob T Zehms, Jeanne A Zeh, David W Zeh, Prashant P Sharma
Journal: Molecular Biology and Evolution (2021)

Abstract Long-branch attraction is a systematic artifact that results in erroneous groupings of fast-evolving taxa. The combination of short, deep internodes in tandem with long-branch attraction artifacts has produced empirically intractable parts of the Tree of Life. One such group is the arthropod subphylum Chelicerata, whose backbone phylogeny has remained unstable despite improvements in phylogenetic methods and genome-scale data sets. Pseudoscorpion placement is particularly variable across data sets and analytical frameworks, with this group either clustering with other long-branch orders or with Arachnopulmonata (scorpions and tetrapulmonates). To surmount long-branch attraction, we investigated the effect of taxonomic sampling via sequential deletion of basally branching pseudoscorpion superfamilies, as well as varying gene occupancy thresholds in supermatrices. We show that concatenated supermatrices and coalescent-based summary species tree approaches support a sister group relationship of pseudoscorpions and scorpions, when more of the basally branching taxa are sampled. Matrix completeness had demonstrably less influence on tree topology. As an external arbiter of phylogenetic placement, we leveraged the recent discovery of an ancient genome duplication in the common ancestor of Arachnopulmonata as a litmus test for competing hypotheses of pseudoscorpion relationships. We generated a high-quality developmental transcriptome and the first genome for pseudoscorpions to assess the incidence of arachnopulmonate-specific duplications (e.g., homeobox genes and miRNAs). Our results support the inclusion of pseudoscorpions in Arachnopulmonata (new definition), as the sister group of scorpions. Panscorpiones (new name) is proposed for the clade uniting Scorpiones and Pseudoscorpiones.
Success and failure of additional immune modulators in steroid-refractory/resistant pneumonitis related to immune checkpoint blockade
Authors: Jason Beattie, Hira Rizvi, Paige Fuentes, Jia Luo, Adam Schoenfeld, I-Hsin Lin, Michael Postow, Margaret Callahan, Martin H Voss, Neil J Shah, Allison Betof Warner, Mohit Chawla, Matthew D Hellmann
Journal: Journal for ImmunoTherapy of Cancer (2021)

Pneumonitis related to immune checkpoint blockade is uncommon but can be severe, fatal or chronic. Steroids are first-line treatment, however, some patients are refractory or become resistant to steroids. Like many immune-related adverse events, little is known regarding the outcomes and optimal management of patients in whom steroids are ineffective.We performed a single-center retrospective cohort study at a high-volume tertiary cancer center to evaluate the clinical course, management strategies and outcomes of patients treated for immune checkpoint pneumonitis with immune modulatory medications in addition to systemic steroids. Pharmacy records were queried for patients treated with both immune checkpoint blockade and receipt of additional immune modulators. Records were then manually reviewed to identify patients who received the additional immune modulators for immune checkpoint pneumonitis.From 2013 to 2020, we identified 26 patients treated for immune checkpoint pneumonitis with additional immune modulators in addition to steroids. Twelve patients (46%) were steroid-refractory and 14 (54%) were steroid-resistant. Pneumonitis severity included grade 2 (42%) or grade 3-4 (58%). Additional immune modulation consisted of tumor necrosis factor-alpha inhibitor (77%) and/or mycophenolate (23%). Durable improvement in pneumonitis following initiation of additional immune modulators occurred in 10 patients (38%), including three patients (12%) in whom pneumonitis resolved and all immunosuppressants ceased. The rate of 90-day all-cause mortality/hospice referral was 50%. At last follow-up, mortality attributable to pneumonitis was 23%. In addition to mortality from pneumonitis and cancer, 3 patients (12%) died due to infections possibly associated with immunosuppression.Steroid-refractory or -resistant immune checkpoint pneumonitis is uncommon but associated with significant morbidity and mortality. Additional immunomodulators can yield durable improvement, attained in over one third of patients. An improved understanding of the underlying biology of immune-related pneumonitis will be crucial to guide more precise and effective treatment strategies in the future.
Dupilumab Treatment Leads to Clinical Asthma Remission in Patients With Uncontrolled Moderate-to-Severe Asthma With Type 2 Inflammation
Authors: Ian Pavord, William Busse, Elliot Israel, Stanley Szefler, Zhen Chen, Nadia Daizadeh, David Lederer, Leda Mannent, Nikhil Amin, Elizabeth Laws, Marcella Ruddy, Paul Rowe, Yamo Deniz, Asif Khan, Yi Zhang
Journal: Journal of Allergy and Clinical Immunology (2021)
Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Response
Authors: Ping Zhang, Isaac Kitchen-Smith, Lingyun Xiong, Giovanni Stracquadanio, Katherine Brown, Philipp H. Richter, Marsha D. Wallace, Elisabeth Bond, Natasha Sahgal, Samantha Moore, Svanhild Nornes, Sarah De Val, Mirvat Surakhy, David Sims, Xuting Wang, Douglas A. Bell, Jorge Zeron-Medina, Yanyan Jiang, Anderson J. Ryan, Joanna L. Selfe, Janet Shipley, Siddhartha Kar, Paul D. Pharoah, Chey Loveday, Rick Jansen, Lukasz F. Grochola, Claire Palles, Andrew Protheroe, Val Millar, Daniel V. Ebner, Meghana Pagadala, Sarah P. Blagden, Timothy S. Maughan, Enric Domingo, Ian Tomlinson, Clare Turnbull, Hannah Carter, Gareth L. Bond
Journal: Cancer Research (2021)

Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic
<i>SCIRT</i> lncRNA Blocks the Shot of Breast Cancer Cells Self-Renewal Mechanism
Authors: Barbara Pardini, Mihnea P. Dragomir
Journal: Cancer Research (2021)

Abstract The study by Zagorac and colleagues represents an important step forward in the field of breast cancer, explaining a novel molecular mechanism of transition from slowly multiplying tumor-initiating cells (TIC) into their more differentiated version characterized by high proliferation. The mechanism involves the transcription factors SOX2 and EZH2, which directly repress transcription of cell-cycle genes and activate self-renewal genes in breast cancer cells. This mechanism is further controlled by a negative feedback loop mediated by a long noncoding RNA, SCIRT, not described previously, which is upregulated in tumorspheres and inhibits SOX2 and EZH2. SCIRT is an atypical tumor suppressor in breast cancer, being upregulated in cancer cells, but counteracting their aggressive phenotype. At the molecular level, by direct interaction with EZH2, SCIRT inhibits the transcriptional activity of EZH2 and “blocks the shot” of cancer cells' self-renewal. From a translational perspective, activating SCIRT or induction of SCIRT mimetics in breast cancer cells may lead to the dedifferentiation of TICs toward a less protumorigenic phenotype and a therapy-fragile state that could open new therapeutic avenues. See related article by Zagorac et al., p. 580