tbuckley/cabot-search huggingface dataset:
Effects of the COVID-19 pandemic on supply and use of blood for transfusion
Authors: Simon J Stanworth, Helen V New, Torunn O Apelseth, Susan Brunskill, Rebecca Cardigan, Carolyn Doree, Marc Germain, Mindy Goldman, Edwin Massey, Daniele Prati, Nadine Shehata, Cynthia So-Osman, Jecko Thachil
Journal: The Lancet Haematology (2020)

The COVID-19 pandemic has major implications for blood transfusion. There are uncertain patterns of demand, and transfusion institutions need to plan for reductions in donations and loss of crucial staff because of sickness and public health restrictions. We systematically searched for relevant studies addressing the transfusion chain—from donor, through collection and processing, to patients—to provide a synthesis of the published literature and guidance during times of potential or actual shortage. A reduction in donor numbers has largely been matched by reductions in demand for transfusion. Contingency planning includes prioritisation policies for patients in the event of predicted shortage. A range of strategies maintain ongoing equitable access to blood for transfusion during the pandemic, in addition to providing new therapies such as convalescent plasma. Sharing experience and developing expert consensus on the basis of evolving publications will help transfusion services and hospitals in countries at different stages in the pandemic.
Circular RNA circSnx5 Controls Immunogenicity of Dendritic Cells through the miR-544/SOCS1 Axis and PU.1 Activity Regulation
Authors: Qi Chen, Ge Mang, Jian Wu, Ping Sun, Tingting Li, Hanlu Zhang, Naixin Wang, Zhonghua Tong, Weiwei Wang, Yang Zheng, Jinwei Tian, Mingyan E, Maomao Zhang, Bo Yu
Journal: Molecular Therapy (2020)

Dendritic cells (DCs) can orchestrate either immunogenic or tolerogenic responses to relay information on the functional state. Emerging studies indicate that circular RNAs (circRNAs) are involved in immunity; however, it remains unclear whether they govern DC development and function at the transcriptional level. In this study, we identified a central role for a novel circRNA, circSnx5, in modulating DC-driven immunity and tolerance. Ectopic circSnx5 suppresses DC activation and promotes the development of tolerogenic functions of DCs, while circSnx5 knockdown promotes their activation and inflammatory phenotype. Mechanistically, circSnx5 can act as a miR-544 sponge to attenuate miRNA-mediated target depression on suppressor of cytokine signaling 1 (SOCS1) and inhibit nuclear translocation of PU.1, regulating DC activation and function. Furthermore, the main splicing factors (SFs) were identified in DCs, of which heterogeneous nuclear ribonucleoprotein (hnRNP) C was essential for circSnx5 generation. Moreover, our data demonstrated that vaccination with circSnx5-conditioned DCs prolonged cardiac allograft survival in mice and alleviated experimental autoimmune myocarditis. Taken together, our results revealed circSnx5 as a key modulator to fine-tune DC function, suggesting that circSnx5 may serve as a potential therapeutic avenue for immune-related diseases. Dendritic cells (DCs) can orchestrate either immunogenic or tolerogenic responses to relay information on the functional state. Emerging studies indicate that circular RNAs (circRNAs) are involved in immunity; however, it remains unclear whether they govern DC development and function at the transcriptional level. In this study, we identified a central role for a novel circRNA, circSnx5, in modulating DC-driven immunity and tolerance. Ectopic circSnx5 suppresses DC activation and promotes the development of tolerogenic functions of DCs, while circSnx5 knockdown promotes their activation and inflammatory phenotype. Mechanistically, circSnx5 can act as a miR-544 sponge to attenuate miRNA-mediated target depression on suppressor of cytokine signaling 1 (SOCS1) and inhibit nuclear translocation of PU.1, regulating DC activation and function. Furthermore, the main splicing factors (SFs) were identified in DCs, of which heterogeneous nuclear ribonucleoprotein (hnRNP) C was essential for circSnx5 generation. Moreover, our data demonstrated that vaccination with circSnx5-conditioned DCs prolonged cardiac allograft survival in mice and alleviated experimental autoimmune myocarditis. Taken together, our results revealed circSnx5 as a key modulator to fine-tune DC function, suggesting that circSnx5 may serve as a potential therapeutic avenue for immune-related diseases.
Salome Maswime: dynamic leader in global surgery
Authors: Richard Lane
Journal: The Lancet (2020)

As Associate Professor and Head of Global Surgery at the University of Cape Town (UCT), South Africa, Salome Maswime is aware of the scale of the job in front of her. "For me the big problem is the disconnect between health systems and clinical care in low and middle income countries, especially concerning surgical care. Outcomes are often poor, there being not enough focus on the quality of surgery, and how it relates to integrated health care and overarching health systems performance", she explains.
Divergence in Timing and Magnitude of Testosterone Levels Between Male and Female Youths
Authors: Jonathon W. Senefeld, Doriane Lambelet Coleman, Patrick W. Johnson, Rickey E. Carter, Andrew J. Clayburn, Michael J. Joyner
Journal: JAMA (2020)

This study uses national survey data to describe testosterone levels by age in youths aged 6 to 20 years and the onset and magnitude of divergence in levels between boys and girls.
Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study
Authors: Xue Bai, De-Hua Wu, Si-Cong Ma, Jian Wang, Xin-Ran Tang, Shuai Kang, Qiang John Fu, Chuan-Hui Cao, He-San Luo, Yu-Han Chen, Hong-Bo Zhu, Hong-Hong Yan, Yi-Long Wu, Zhong-Yi Dong
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Genetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy. Methods In this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study. Tumor samples from the patients were molecularly profiled by MSK-IMPACT or whole exome sequencing. We developed a risk model named GMS based on the MSK training cohort (n=123). The predictive model was first validated in the separate internal MSK cohort (n=82) and then validated in an external cohort containing 111 patients from previously published clinical trials. Results A GMS risk model consisting of eight genes ( TP53 , KRAS , STK11 , EGFR , PTPRD , KMT2C , SMAD4 , and HGF ) was generated to classify patients into high and low GMS groups in the training cohort. Patients with high GMS in the training cohort had longer progression-free survival (hazard ratio (HR) 0.41, 0.28–0.61, p &lt; 0.0001) and overall survival (HR 0.53, 0.32–0.89, p = 0.0275) compared with low GMS. We noted equivalent findings in the internal validation cohort and in the external validation cohort. The GMS was demonstrated as an independent predictive factor for anti-PD-(L)1 therapy comparing with tumor mutational burden. Meanwhile, GMS showed undifferentiated predictive value in patients with different clinicopathological features. Notably, both GMS and PD-L1 were independent predictors and demonstrated poorly correlated; inclusion of PD-L1 with GMS further improved the predictive capacity for PD-1 blockade immunotherapy. Conclusions Our study highlights the potential predictive value of GMS for immunotherapeutic benefit in non-squamous NSCLC. Besides, the combination of GMS and PD-L1 may serve as an optimal partner in guiding treatment decisions for anti-PD-(L)1 based therapy.
Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series
Authors: Eleni Armeni, Umaira Aziz, Sulmaaz Qamar, Sadia Nasir, Chidambaram Nethaji, Rupert Negus, Nicholas Murch, Huw Clarke Beynon, Pierre Bouloux, Miranda Rosenthal, Sidrah Khan, Ahmed Yousseif, Ravi Menon, Efthimia Karra
Journal: The Lancet Diabetes & Endocrinology (2020)
A comparison of mortality-related risk factors of COVID-19, SARS, and MERS: A systematic review and meta-analysis
Authors: Lvliang Lu, Wenyu Zhong, Ziwei Bian, Zhiming Li, Ke Zhang, Boxuan Liang, Yizhou Zhong, Manjiang Hu, Li Lin, Jun Liu, Xi Lin, Yuji Huang, Junying Jiang, Xingfen Yang, Xin Zhang, Zhenlie Huang
Journal: Journal of Infection (2020)

Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment.
99mTc-MDP Bone Scintigraphy in Gaucher Disease
Authors: Selin Kesim, Halil Turgut Turoglu, Engin Tutar, Salih Ozguven, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2020)

Abstract In this case report, we present the bone scintigraphic findings of a 9-year-old boy with Gaucher disease who has a history of fractures to evaluate the extent of his osseous lesions. Gaucher disease is a genetic deficiency of lysosomal enzyme glucocerebrosidase, which results in the accumulation of glucocerebroside in the macrophages in the reticuloendothelial cells of the spleen, liver, and bone marrow. Most patients with type 1 Gaucher disease present a clinical or radiographic evidence of infiltrative bone disease. Lipid-filled macrophages called Gaucher cells infiltrate the bone marrow, leading to medullary expansion, diffuse osteoporosis, ischemic necrosis, and fractures.
Association Between Glycemic Status and the Risk of Parkinson Disease: A Nationwide Population-Based Study
Authors: Sang Youl Rhee, Kyung-Do Han, Hyemi Kwon, Se-Eun Park, Yong-Gyu Park, Yang-Hyun Kim, Soon-Jip Yoo, Eun-Jung Rhee, Won-Young Lee
Journal: Diabetes Care (2020)

OBJECTIVE Previous studies have suggested that diabetes increases the risk of Parkinson disease (PD); however, this has not been conclusively established. We analyzed the risk of PD based on baseline glucose tolerance status in a large-scale cohort representative of the general Korean population. RESEARCH DESIGN AND METHODS This analysis was performed in a cohort of 15,168,021 adults aged ≥40 years who underwent health checkups under the National Health Insurance Service between January 2009 and December 2010. The clinical course of subjects was monitored until December 2016. Subjects were classified into the following groups: no diabetes, impaired fasting glucose (IFG), diabetes duration &amp;lt;5 years, and diabetes duration ≥5 years. We analyzed the adjusted hazard ratio of PD for each group. RESULTS During the observation period of 49,076,148.74 person-years, PD occurred in 31,577 patients. Compared with the nondiabetes group, the adjusted hazard ratio was 1.038 (95% CI, 1.009–1.067) in the IFG group, 1.185 (95% CI, 1.143–1.229) in the diabetes duration &amp;lt;5 years group, and 1.618 (95% CI, 1.566–1.672) in the diabetes duration ≥5 years group. These results were consistent with those of the subgroup analysis, and the presence of diabetes further increased the risk of PD regardless of comorbidities such as cardiovascular, cerebrovascular, and chronic kidney diseases. CONCLUSIONS This population-based cohort study suggests that diabetes is an independent risk factor for PD.
Interleukin-22 acts as a mitochondrial protector
Authors: Seonghwan Hwang, Dechun Feng, Bin Gao
Journal: Theranostics (2020)

Interleukin (IL)-22 has been increasingly recognized as a promising therapeutic option for various types of diseases.This commentary summarizes the novel mechanistic aspects of IL-22 for the treatment of liver diseases including the study by Chen et al. published in the recent issue of the Theranostics that elucidated the novel function of IL-22 as a mitochondrial protector for the adaptive defense against liver injury.
Letter to the Editor: Does c‐Jun N‐Terminal Kinase Regulate Acetaminophen Hepatotoxicity by Modulating Nuclear Factor Erythroid 2–Related Factor 2–Dependent Genes or Mitochondrial Oxidant Stress?
Authors: Hartmut Jaeschke, Anup Ramachandran
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the recent paper by Chen and coworkers, who provided evidence for nuclear factor erythroid 2–related factor 2 (Nrf2) as a target for c‐jun N‐terminal kinase (JNK).(1) Although we agree that JNK activation is a critical part of the signaling mechanism of acetaminophen (APAP) hepatotoxicity,(2) we disagree with the conclusion that phosphorylated JNK phosphorylation of Nrf2, causing down‐regulation of the Nrf2‐dependent antioxidant response element (ARE)–driven genes for reduced nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 and glutathione S‐transferases alpha 3, mu 1, and mu 5, is the critical mechanism by which JNK promotes APAP‐induced cell death.(1) First, although JNK appears to phosphorylate Nrf2 in vivo as early as 3‐6 hours after APAP administration, the effects of the JNK inhibitor SP600125 on expression of these proteins were not observed during the main injury phase (6 hours) but only at 24 hours, i.e., at the end of the injury phase.(1) The authors did not provide any injury data at 6 hours.(1) However, similar experiments demonstrated clearly that even delayed treatment with a potent JNK inhibitor effectively protected against APAP‐induced liver injury at 6 hours.(3) Thus, the effects of Nrf2‐dependent protein expression changes occur too late to affect the mechanisms of cell death.(2) This is reiterated by hepatic glutathione levels, which are a functional readout of ARE activation. Glutathione depletion after 300 mg/kg APAP typically occurs within 30 minutes, and levels start recovering by 6 hours,(2) again indicating that the changes in protein expression described may not be relevant to the injury. Second, the authors show extensive Nrf2 phosphorylation at 6 hours, which, in contrast to the centrilobular necrosis, does not seem to have a zone specificity.(1) This is not consistent with the assumed JNK‐dependent Nrf2 phosphorylation being important for JNK‐dependent cell death. Third, and most importantly, selective inhibition of the mitochondrial oxidant stress by the superoxide dismutase–mimetic Mito‐Tempo(4) or pyruvate dehydrogenase kinase 4 deficiency(5) effectively protected against APAP‐induced liver at 6 hours without preventing JNK activation or phosphorylated JNK translocation to the mitochondria. These data strongly suggest that regulation of the mitochondrial oxidant stress by JNK is the critical downstream event in the pathophysiology,(2) not the delayed modulation of Nrf2‐dependent genes.(1)
Delivery of self-amplifying mRNA vaccines by cationic lipid nanoparticles: The impact of cationic lipid selection
Authors: Gustavo Lou, Giulia Anderluzzi, Signe Tandrup Schmidt, Stuart Woods, Simona Gallorini, Michela Brazzoli, Fabiola Giusti, Ilaria Ferlenghi, Russell N. Johnson, Craig W. Roberts, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie
Journal: Journal of Controlled Release (2020)
Where Did SARS-CoV-2 Come From?
Authors: Thomas Leitner, Sudhir Kumar
Journal: Molecular Biology and Evolution (2020)

Abstract Identifying the origin of SARS-CoV-2, the etiological agent of the current COVID-19 pandemic, may help us to avoid future epidemics of coronavirus and other zoonoses. Several theories about the zoonotic origin of SARS-CoV-2 have recently been proposed. Although Betacoronavirus found in Rhinolophus bats from China have been broadly implicated, their genetic dissimilarity to SARS-CoV-2 is so high that they are highly unlikely to be its direct ancestors. Thus, an intermediary host is suspected to link bat to human coronaviruses. Based on genomic CpG dinucleotide patterns in different coronaviruses from different hosts, it was suggested that SARS-CoV-2 might have evolved in a canid gastrointestinal tract prior to transmission to humans. However, similar CpG patterns are now reported in coronaviruses from other hosts, including bats themselves and pangolins. Therefore, reduced genomic CpG alone is not a highly predictive biomarker, suggesting a need for additional biomarkers to reveal intermediate hosts or tissues. The hunt for the zoonotic origin of SARS-CoV-2 continues.
Single-cell ATAC-seq signal extraction and enhancement with SCATE
Authors: Zhicheng Ji, Weiqiang Zhou, Wenpin Hou, Hongkai Ji
Journal: Genome biology (2020)

Abstract Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells. Single-cell ATAC-seq data are sparse and noisy, and analyzing such data is challenging. Existing computational methods cannot accurately reconstruct activities of individual cis-regulatory elements (CREs) in individual cells or rare cell subpopulations. We present a new statistical framework, SCATE, that adaptively integrates information from co-activated CREs, similar cells, and publicly available regulome data to substantially increase the accuracy for estimating activities of individual CREs. We demonstrate that SCATE can be used to better reconstruct the regulatory landscape of a heterogeneous sample.
Prenatal regenerative fetoscopic interventions for congenital anomalies
Authors: Rodrigo Ruano
Journal: BMJ (2020)

Fetal intervention has progressed in the past two decades from experimental proof-of-concept to practice-adopted, life saving interventions in human fetuses with congenital anomalies. This progress is informed by advances in innovative research, prenatal diagnosis, and fetal surgical techniques. Invasive open hysterotomy, associated with notable maternal-fetal risks, is steadily replaced by less invasive fetoscopic alternatives. A better understanding of the natural history and pathophysiology of congenital diseases has advanced the prenatal regenerative paradigm. By altering the natural course of disease through regrowth or redevelopment of malformed fetal organs, prenatal regenerative medicine has transformed maternal-fetal care. This review discusses the uses of regenerative medicine in the prenatal diagnosis and management of three congenital diseases: congenital diaphragmatic hernia, lower urinary tract obstruction, and spina bifida.
A Reckoning and Research Agenda for Neuroimaging in Psychiatry: Response to Henderson et al.
Authors: Amit Etkin
Journal: American Journal of Psychiatry (2020)

dementia from control subjects, [ 18 F]fluorodeoxyglucose (FDG) PET has a sensitivity of 0.84 and a specificity of 0.74, while perfusion SPECT using multidetector cameras has a sensitivity of 0.93 and a specificity of 0.84 (2, 5).Moreover, both PET and SPECT can differentiate among other forms of dementia with reasonable accuracy (2, 5).Another example is attention deficit hyperactivity disorder (ADHD).Subjects with ADHD can be readily distinguished from control subjects by perfusion SPECT (2,6).Indeed, SPECT can differentiate between patients whose ADHD symptoms are likely to respond to stimulant medication relative to those whose symptoms are not likely to respond (2, 6), a replicated finding.Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are challenging to differentiate clinically.However, TBI and PTSD can be distinguished using SPECT with a sensitivity of 0.92 and a specificity of 0.85, according to a study of 196 veterans (7).These findings were replicated in a study with an N.21,000 (8).In addition, SPECT is widely available, relatively inexpensive, and currently used with clinically beneficial results.Etkin's point of a disconnect between neuroimaging and "real-world clinical care" is well taken ( 1), yet the ISAN and other groups are actively using neuroimaging to guide clinical treatment.The person with ADHD with normal frontal lobe function, but with decreased temporal lobe function, is treated differently than the person with ADHD and decreased frontal lobe function (9, 10).The ISAN is also striving toward a unified data processing algorithm that will be openly available to all clinicians and that will foster a common language for evaluating scan results (9).The ISAN encourages APA to explore the use of brain SPECT and FDG-PET functional neuroimaging in psychiatry with those who are experienced and knowledgeable about their practical applications (9, 10).
COVID-19 Severity Correlates with Weaker T-Cell Immunity, Hypercytokinemia, and Lung Epithelium Injury
Authors: Zhongfang Wang, Xiaoyun Yang, Yumin Zhou, Jing Sun, Xiaoqing Liu, Jing Zhang, Xinyue Mei, Jiaying Zhong, Jincun Zhao, Pixin Ran
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

There are several limitations in the data from this case series.First, as is common with case series, selection bias is possible.Second, there was no control intervention, and the study sample was small.Third, it is uncertain whether these patients would have improved without prone positioning, although the rapid change, within 1 hour, after proning is suggestive of a favorable impact.Fourth, measures of patient dyspnea or comfort after prone positioning were not collected.Fifth, to minimize the documentation burden on nursing-staff workflow, data on patient adherence to the prone-positioning recommendation beyond the first episode of proning were not collected.Given the potential of prone positioning as a low-cost, easily implemented, and scalable intervention, particularly in low-and middle-income countries, expeditious yet thorough testing of prone positioning in patients at risk for intubation is warranted (e.g., W. Al-Hazzani and colleagues, unpublished results