tbuckley/cabot-search huggingface dataset:
Virus‐Inspired Hollow Mesoporous Gadolinium‐Bismuth Nanotheranostics for Magnetic Resonance Imaging‐Guided Synergistic Photodynamic‐Radiotherapy
Authors: Zongjunlin Liu, Peiyuan Wang, Fang Xie, Jianhao Chen, Meimei Cai, Yang Li, Jianghua Yan, Qin Lin, Fanghong Luo
Journal: Advanced Healthcare Materials (2021)

Abstract The anti‐tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X‐rays. Here, the authors report a biomimetic coronavirus‐inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (termed as HB@VHMBi‐Gd) for magnetic resonance imaging (MRI)‐guided synergistic photodynamic‐RT. HB@VHMBi‐Gd displayed a faster cellular uptake rate than the conventional spherical HMBi‐Gd loaded with HB (HB@SHMBi‐Gd) because of rough surface‐enhanced adhesion. After intravenous injection, HB@VHMBi‐Gd is efficiently delivered to the tumor and rapidly invades the tumor cells by surface spikes. Interestingly, lysosomal acidity can trigger the degradation of VHMBi‐Gd to produce ultrasmall nanoparticles to amplify the X‐ray attenuation ability and enhance MRI contrast and radiosensitization. Under laser and X‐ray irradiation, HB@VHMBi‐Gd significantly enhances 1 O 2 generation from HB to induce activation of caspase 9/3 and inhibition of C‐myc, while enhancing hydroxyl radical generation from Bi 2 O 3 to induce intense DNA breakage. By synergistically inducing cell apoptosis by distinct reactive oxygen species (ROS), HB@VHMBi‐Gd exhibits superior anticancer efficacy with ≈90% tumor inhibition. They envision that biomimetic virus‐inspired hollow hybrid metal nanoparticles can provide a promising strategy for imaging‐guided synergistic photodynamic‐RT.
Childhood adversity: a profound determinant of health
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2021)

On Oct 5, 2021, the Independent Commission on Sexual Abuse in the Catholic Church released its report estimating that, since 1950, more than 216 000 children have been sexually abused by clergy in France. Chilling. Damning. Appalling. Haunting. The report is also a stark reminder of the pervasiveness of childhood trauma more broadly. While a safe and healthy childhood are fundamental to physical, mental, and social development, globally, it is estimated that one out of two children aged 2–17 years suffer some form of violence each year.
Thiamine Supplementation in Patients With Alcohol Use Disorder Presenting With Acute Critical Illness
Authors: Rahul D. Pawar, Lakshman Balaji, Anne V. Grossestreuer, Garrett Thompson, Mathias J. Holmberg, Mahmoud S. Issa, Parth V. Patel, Ryan Kronen, Katherine M. Berg, Ari Moskowitz, Michael W. Donnino
Journal: Annals of Internal Medicine (2021)

Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation.To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States.Retrospective observational study.Cerner Health Facts database.Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017.Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses.The study included 14 998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n = 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n = 3119 [41%]).Specific dosing and duration were not completely captured.Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD.National Institutes of Health.
scGET: Predicting Cell Fate Transition During Early Embryonic Development by Single-Cell Graph Entropy
Authors: Jiayuan Zhong, Chongyin Han, Xuhang Zhang, Pei Chen, Rui Liu
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract During early embryonic development, cell fate commitment represents a critical transition or “tipping point” of embryonic differentiation, at which there is a drastic and qualitative shift of the cell populations. In this study, we presented a computational approach, scGET, to explore the gene–gene associations based on single-cell RNA sequencing (scRNA-seq) data for critical transition prediction. Specifically, by transforming the gene expression data to the local network entropy, the single-cell graph entropy (SGE) value quantitatively characterizes the stability and criticality of gene regulatory networks among cell populations and thus can be employed to detect the critical signal of cell fate or lineage commitment at the single-cell level. Being applied to five scRNA-seq datasets of embryonic differentiation, scGET accurately predicts all the impending cell fate transitions. After identifying the “dark genes” that are non-differentially expressed genes but sensitive to the SGE value, the underlying signaling mechanisms were revealed, suggesting that the synergy of dark genes and their downstream targets may play a key role in various cell development processes. The application in all five datasets demonstrates the effectiveness of scGET in analyzing scRNA-seq data from a network perspective and its potential to track the dynamics of cell differentiation. The source code of scGET is accessible at https://github.com/zhongjiayuna/scGET_Project.
Correction: Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study
Authors: Rema Ramakrishnan, Aiden Doherty, Karl Smith-Byrne, Kazem Rahimi, Derrick Bennett, Mark Woodward, Rosemary Walmsley, Terence Dwyer
Journal: PLoS Medicine (2021)

In subsequent data analyses associated with this article, the authors became aware of a coding error due to which there was an underadjustment for age.As such the following corrections are required.In the Methods and findings subsection of the Abstract the fifth sentence is incorrect.The correct sentence is: Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.79 (0.73, 0.86), 0.70 (0.64, 0.76), and 0.58 (0.53, 0.65); for vigorous-intensity PA: 0.79 (0.72, 0.86), 0.65 (0.59,0.72), and 0.56 (0.50,0.62); and for total volume of PA: 0.79 (0.73, 0.86), 0.72 (0.66, 0.79), and 0.60 (0.54, 0.66).In the Results the third sentence of the second paragraph is incorrect.The correct sentence is: Compared with the lowest category of moderate-intensity PA, the HRs and 95% Cis for increasing quarters were 0.79 (0.73, 0.86), 0.70 (0.64, 0.76), and 0.58 (0.53, 0.65) (Fig 1), and the corresponding values for vigorous activity were: 0.79 (0.72, 0.86), 0.65 (0.59,0.72), and 0.56 (0.50,0.62).In the Subgroup, secondary, and sensitivity analyses subsection of the Results the second sentence of the fourth paragraph is incorrect.The correct sentence is: Furthermore, sensitivity analyses conducted to examine the inclusion of additional covariates (hypertension, self-rated health, BMI, total cholesterol, HDL, LDL, triglycerides, C-reactive protein, HbA1c, red and processed meat, fresh fruit, and cooked vegetables) to the multivariable Cox models utilised in the main analyses attenuated the HRs by just 6.0% to 20.0% (S2-S4 Tables).In the Discussion the second sentence of the first paragraph is incorrect.The correct sentence is: We found broadly similar associations within each subcomponent of CVD, and the associations were comparable for men and women, with the exception of vigorous activity where there was a 14% lower risk for incident CVD among men compared with 27% lower risk among women for the second quarter compared to the first.The following figures are incorrect: Figs 1, 2, 3, 4 and S2.The authors have provided corrected versions here.The following tables are incorrect: S1, S2, S3 and S4 Tables.
The Authors’ Reply
Authors: Francesco Bandera, Raffaele Martone, Liza Chacko, Sharmananthan Ganesananthan, Janet A. Gilbertson, Markella Ponticos, Thirusha Lane, Ana Martinez-Naharro, Carol Whelan, Cristina Quarta, Dorota Rowczenio, Rishi Patel, Yousuf Razvi, Helen Lachmann, Ashutosh Wechelakar, James Brown, Daniel Knight, James Moon, Aviva Petrie, Francesco Cappelli, Marco Guazzi, Luciano Potena, Claudio Rapezzi, Ornella Leone, Philip N. Hawkins, Julian D. Gillmore, Marianna Fontana
Journal: JACC. Cardiovascular imaging (2021)
Abstract 13205: Short and Long-Term Outcomes of OHCA Patients Admitted to Wards From the Emergency Department
Authors: Janet Bray, Stuart Howell, Stephen Bernard, Karen L Smith, Judith Finn, Dion Stub, Peter Cameron
Journal: Circulation (2021)

Introduction: The majority of research has examined out-of-hospital cardiac arrest (OHCA) patients admitted to intensive care units (ICU). Little is known about patients who are admitted to non-ICU wards. Our study aims to describe short and long term outcomes in OHCA patients admitted directly to medical wards from the emergency department. Methods: Data were obtained from the Victorian Ambulance Cardiac Arrest Registry and 12 hospitals for adult, non-traumatic OHCA cases transported to ED between 2014 and 2016. Results: Of 1578 OHCAs, 213 (13.5%) were admitted to medical or cardiac wards -only four were admitted for palliation. The majority were witnessed (38% bystander, 58% paramedic), received bystander CPR (91%, n=81/89), median downtime was 4 minutes (IQR 2-12), 179 (84%) were in a shockable rhythm, and 15 received public access defibrillation. Most had ROSC on arrival at ED (99%) and were conscious in ED (91%). Re-arrest inhospital occurred in 16 cases, the majority had a cardiac aetiology (85%) and underwent angiography (75%, 112/160 proceeded to PCI). The majority were discharged alive (n=194, 91%) and most survivors were discharged home (n=176/194, 84%) with good neurological outcomes (CPC 0-2 =94%, CPC 3= 4%). Survivors from the wards made up 30% of the overall OHCA survivors. Of survivors, 175 were alive at 12 months and 159 completed follow-up. The majority of those working prior were working at 12-months (78/92, 85%), 87% in the same role. The mean EuroQol index score for respondents was 0.77 (SD, 0.15). The mean 12-item short form Mental Component Summary score for patients was 55.0 (SD, 8.1), whereas the mean Physical Component Summary score was 49.1 (SD, 9.1). Conclusion: In our region OHCA patients admitted to wards have favourable arrest characteristics, and have good short- and long-term outcomes which are similar to regular acute coronary syndrome patients.
Twin grasper-assisted endoscopic mucosa-inverting closure for large perforations after endoscopic full-thickness resection: a new endoscopic technique
Authors: Qinbo Cai, Lele Zhang, Wentong Lan, Yuan Lin, Minxuan Shen, Xun Hou, Dongjie Yang
Journal: Endoscopy (2021)

There is no commonly accepted technique for closure of large perforations (diameter > 2 cm) after endoscopic full-thickness resection (EFTR), owing to inevitable limitations of each technique [1]. Gastrointestinal full-thickness defects can be closed by closing the mucosal layer only [2] [3] [4]. Here, we describe a new technique for closing large perforations. This technique uses through-the-scope (TTS) clips, which are widely used in practice, to close the mucosa in an inverted fashion with assistance of a twin grasper, thus overcoming the limitations of TTS clips. This technique may be a better choice for repair of large perforations after EFTR and can be easily adopted in local hospitals.
Cancer Microbiology
Authors: Daniel DiMaio, Brinda Emu, Andrew L Goodman, Walther Mothes, Amy Justice
Journal: JNCI Journal of the National Cancer Institute (2021)

Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.
RADT-11. INCREASED USE OF HYPOFRACTIONATED RADIOTHERAPY IN ELDERLY PATIENTS WITH GLIOBLASTOMA IN THE UNITED STATES FROM 2004-2015
Authors: Matthew Hall, Noah Kalman, Yazmin Odia, Martin Tom, Alexander Mohler, Muni Rubens, Rameen Walters, Sunny Shah, Chase Mallory, Kevin Gates, Katherine Von Werne, Minesh Mehta
Journal: Neuro-Oncology (2021)

Abstract PURPOSE/OBJECTIVES The prognosis for glioblastoma in elderly patients is poor; randomized trials have demonstrated comparable survival following adjuvant radiotherapy (RT) using conventional or hypofractionation. We used the National Cancer Database (NCDB) to measure trends in the use of hypofractionated RT in glioblastoma patients 70 years of age and older. MATERIALS AND METHODS The NCDB was queried for elderly glioblastoma patients treated with a known RT dosing schema from 2004-2015 (n=10,089 patients). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received hypofractionated RT (including 40-45 Gy/15 fractions, 34 Gy/10 fractions, or 25 Gy/5 fractions). Average annual percentage change (AAPC) was compared to determine if a significant change occurred in the use of hypofractionated RT during this period. Multivariable regression was used to determine factors associated with the use of hypofractionated RT. RESULTS Use of hypofractionated RT was stable between 2.5-3.3% from 2004-2008 and then monotonically increased to 22.2% by 2015 (p&amp;lt; 0.001). The AAPC in the use of hypofractionated RT was +29.6% per year (p&amp;lt; 0.001), with a corresponding decline in conventional fractionation over this period. No significant change was observed in palliative dosing schema or the use of stereotactic radiosurgery. On logistic regression, age, treatment at an academic center, Charlson Deyo score ≥2, and treatment year were significantly associated with utilization of hypofractionated RT. In this dataset, 24.8% of patients who received either conventional or hypofractionated RT died within 3 months of beginning RT. CONCLUSIONS During 2008-2015, an increasing number of elderly patients with glioblastoma received hypofractionated RT. Hypofractionated RT should be considered in elderly patients to shorten the time spent receiving medical care during the final months of life. Attention to hospice care is also important, especially in those with brief expected survival who may derive limited benefit from RT.
Therapeutic Effect of <scp>Cyclin‐Dependent</scp> Kinase 4/6 Inhibitor on Dermal Fibrosis in Murine Models of Systemic Sclerosis
Authors: Akio Yamamoto, Tetsuya Saito, Tadashi Hosoya, Kimito Kawahata, Yoshihide Asano, Shinichi Sato, Fumitaka Mizoguchi, Shinsuke Yasuda, Hitoshi Kohsaka
Journal: Arthritis & Rheumatology (2021)

One of the histologic characteristics of systemic sclerosis (SSc) is an increased number of dermal myofibroblasts, and transforming growth factor β (TGFβ) plays a crucial role in the promotion of myofibroblast differentiation from fibroblasts, leading to dermal fibrosis. This study was undertaken to 1) examine whether inhibition of the cell cycle with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor suppresses the proliferation of fibroblasts and their differentiation into myofibroblasts, and 2) assess the therapeutic effects of a CDK4/6 inhibitor, administered as monotherapy or in combination with a TGFβ receptor (TGFβR) inhibitor, on dermal fibrosis in murine models of SSc.Fibroblasts obtained from the skin of patients with SSc were cultured in the presence or absence of TGFβ. The effects of palbociclib, a CDK4/6 inhibitor, on fibroblast proliferation and TGFβ-induced differentiation into myofibroblasts were examined using bromodeoxyuridine uptake assays as well as immunofluorescence and immunoblotting analyses. Murine models of HOCl- and bleomycin-induced dermal fibrosis were used to study the effect of a CDK4/6 inhibitor on dermal fibrosis, with the CDK4/6 inhibitor treatment administered as monotherapy or in combination with galunisertib, a TGFβR inhibitor.Addition of a CDK4/6 inhibitor to the cell cultures suppressed the proliferation of human dermal SSc fibroblasts and their TGFβ-induced differentiation into myofibroblasts, without inhibiting canonical and noncanonical TGFβ signals. In murine models of dermal fibrosis, treatment of mice with a CDK4/6 inhibitor decreased dermal thickness and collagen content, as well as dermal fibroblast proliferation and the numbers of myofibroblasts. Combination therapy with the CDK4/6 inhibitor and TGFβR inhibitor resulted in additive antifibrotic effects. Mechanistically, the CDK4/6 inhibitor suppressed the expression of cellular communication network 2 and cadherin-11, which are proteins that have important roles in the development and progression of fibrosis.Results of this study demonstrate the therapeutic effect of a CDK4/6 inhibitor on dermal fibrosis when administered as monotherapy or in combination with a TGFβR inhibitor. CDK4/6 inhibitors, including palbociclib used in the present study, may represent novel agents for the treatment of SSc, which, if used in combination with a TGFβR inhibitor, might result in increased efficacy.
Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis
Authors: Laurienne Edgar, Naveed Akbar, Adam T. Braithwaite, Thomas Krausgruber, Héctor Gallart-Ayala, Jade Bailey, Alastair L. Corbin, Tariq E. Khoyratty, Joshua T. Chai, Mohammad Alkhalil, André F. Rendeiro, Klemen Ziberna, Ritu Arya, Thomas J. Cahill, Christoph Bock, Jurga Laurencikiene, Mark J. Crabtree, Madeleine E. Lemieux, Niels P. Riksen, Mihai G. Netea, Craig E. Wheelock, Keith M. Channon, Mikael Rydén, Irina A. Udalova, Ricardo Carnicer, Robin P. Choudhury
Journal: Circulation (2021)

Background: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity in macrophages, promoting persistent proatherogenic characteristics. Methods: Bone marrow–derived macrophages from control mice and mice with diabetes were grown in physiological glucose (5 mmol/L) and subjected to RNA sequencing (n=6), assay for transposase accessible chromatin sequencing (n=6), and chromatin immunoprecipitation sequencing (n=6) for determination of hyperglycemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into (normoglycemic) Ldlr −/ − mice was used to assess its functional significance in vivo. Evidence of hyperglycemia-induced trained immunity was sought in human peripheral blood mononuclear cells from patients with diabetes (n=8) compared with control subjects (n=16) and in human atherosclerotic plaque macrophages excised by laser capture microdissection. Results: In macrophages, high extracellular glucose promoted proinflammatory gene expression and proatherogenic functional characteristics through glycolysis-dependent mechanisms. Bone marrow–derived macrophages from diabetic mice retained these characteristics, even when cultured in physiological glucose, indicating hyperglycemia-induced trained immunity. Bone marrow transplantation from diabetic mice into (normoglycemic) Ldlr −/ − mice increased aortic root atherosclerosis, confirming a disease-relevant and persistent form of trained innate immunity. Integrated assay for transposase accessible chromatin, chromatin immunoprecipitation, and RNA sequencing analyses of hematopoietic stem cells and bone marrow–derived macrophages revealed a proinflammatory priming effect in diabetes. The pattern of open chromatin implicated transcription factor Runt-related transcription factor 1 (Runx1). Similarly, transcriptomes of atherosclerotic plaque macrophages and peripheral leukocytes in patients with type 2 diabetes were enriched for Runx1 targets, consistent with a potential role in human disease. Pharmacological inhibition of Runx1 in vitro inhibited the trained phenotype. Conclusions: Hyperglycemia-induced trained immunity may explain why targeting elevated glucose is ineffective in reducing macrovascular risk in diabetes and suggests new targets for disease prevention and therapy.
Correction to: Donor clonal hematopoiesis increases risk of acute graft versus host disease after matched sibling transplantation
Authors: Betül Oran, Richard E. Champlin, Feng Wang, Tomoyuki Tanaka, Rima M. Saliba, Gheath Al-Atrash, Guillermo Garcia-Manero, Hagop Kantarjian, Kai Cao, Elizabeth J. Shpall, Amin M. Alousi, Rohtesh S. Mehta, Uday Popat, Andy Futreal, Koichi Takahashi
Journal: Leukemia (2021)
Amplifying the Call for Anticipatory Governance
Authors: John P. Nelson, Cynthia Selin, Lauren Lambert, David H. Guston
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Response to Open Peer Commentaries on "Developing a Reflexive, Anticipatory, and Deliberative Approach to Unanticipated Discoveries: Ethical Lessons from iBlastoids"