bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liability of Health Care Professionals and Institutions During COVID-19 Pandemic in Italy: Symposium Proceedings and Position Statement
Authors: Oliva Antonio , Caputo Matteo , Grassi Simone , Vetrugno Giuseppe , Marazza Marco , Ponzanelli Giulio , Cauda Roberto , Scambia Giovanni , Forti Gabrio , Bellantone Rocco , Pascali Vincenzo L. 
Published: September 2020

Background
On May 12, 2020, a symposium titled “Liability of healthcare professionals and institutions during COVID-19 pandemic” was held in Italy with the participation of national experts in malpractice law, hospital management, legal medicine, and clinical risk management. The symposium’s rationale was the highly likely inflation of criminal and civil proceedings concerning alleged errors committed by health care professionals and decision makers during the COVID-19 pandemic. Its aim was to identify and discuss the main issues of legal and medicolegal interest and thus to find solid solutions in the spirit of preparedness planning.

Methods
There were 5 main points of discussion: (A) how to judge errors committed during the pandemic because of the application of protocols and therapies based on no or weak evidence of efficacy, (B) whether hospital managers can be considered liable for infected health care professionals who were not given adequate personal protective equipment, (C) whether health care professionals and institutions can be considered liable for cases of infected inpatients who claim that the infection was transmitted in a hospital setting, (D) whether health care institutions and hospital managers can be considered liable for the hotspots in long-term care facilities/care homes, and (E) whether health care institutions and hospital managers can be considered liable for the worsening of chronic diseases.

Results and Conclusion
Limitation of the liability to the cases of gross negligence (with an explicit definition of this term), a no-fault system with statal indemnities for infected cases, and a rigorous methodology for the expert witnesses were proposed as key interventions for successfully facing future proceedings.
Types, Safety, and Efficacy of Limb Distalization for Inadequate Weight Loss After Roux-en-Y Gastric Bypass
Authors: Hamed Hosam , Ali Mahmoud , Elmahdy Youssif 
Published: September 2020

Objective:
Comprehensive classification and evaluation of the outcome of limb distalization (LD) for inadequate weight loss after roux-en-y gastric bypass (RYGB)

Background:
Limb distalization is a revisional malabsorptive procedure for the management of inadequate weight loss after RYGB. Multiple studies with small sample sizes reported the outcome of LD. This meta-analysis aims to reach a higher level of evidence regarding the safety and efficacy of the procedure.

Methods:
A systematic search, including all studies on LD for management of inadequate weight loss after RYGB. The search engines included were PubMed, Embase, Web of Science, Cochrane Library, Scopus, and EBSCOhost.

Results:
Fourteen studies were included. The pooled estimates of the mid-term percentage of excess weight loss (%EWL), diabetic, and hypertension remission were 50.8%, 69.9%, and 59.8%, respectively. The rate of surgical revision for the management of protein-energy malnutrition (PEM) was 17.1%. The %EWL was significantly higher with older age and good response to index surgery (P = 0.01, 0.04, respectively). Less total alimentary limb length was not associated with better %EWL (P = 0.9), but it was significantly associated with severe PEM (P = 0.01).

Conclusions:
LD has an encouraging rate of resolution of comorbidities. A judicious patient selection is essential for better weight loss after LD. Type I LD with total alimentary limb length ≥350 cm was associated with less risk of malnutrition. PEM is a life-threatening complication that may require revisional surgery years after LD. Future studies on LD, adopting standardized surgical practice and terminology, will allow a more conclusive assessment of the outcome of the procedure.
Disparity Between United States Adolescent Class II and III Obesity Trends and Bariatric Surgery Utilization, 2015–2018
Authors: Messiah Sarah E. , Xie Luyu , Atem Folefac , Mathew Matthew S. , Qureshi Faisal G. , Schneider Benjamin E. , Cruz-Muñoz Nestor de la 
Published: September 2020

Objectives:
Class II (120% > body mass index [BMI] < 140% of the 95th percentile for age and sex) and Class III (BMI >140% of the 95th percentile for age and sex) obesity are the fastest growing subcategories of obesity in the United States pediatric population. Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for with class II/III obesity. The primary objectives of this analysis were to determine the (1) current US MBS utilization rates in those with class II/III obesity and (2) utilization rates and 30-day postoperative outcomes.

Background:
The 2015 to 2018 National Health and Nutrition Examination Survey cross-sectional data (N = 19,225) generated US with class II/III obesity prevalence estimates. The 2015 to 2018 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) longitudinal (30 days) cohort data were used to compare adolescent and adult (N = 748,622) postoperative outcomes and to calculate utilization rates.

Methods:
The 2015 to 2018 youth and adult MBS utilization rates were calculated using MBSAQIP data (numerator) and National Health and Nutrition Examination Survey data (denominator). Two-sample tests of proportions were performed to compare the MBS utilization rates by age, ethnicity, and sex and expressed per 1000.

Results:
Mean age of the analytical MBSAQIP sample was 17.9 (1.15) years in youth (n = 3846) and 45.1 (11.5) in adults (N = 744,776), majority female (77.4%, 80.7%, respectively) and non-Hispanic White (68.5%, 59.4%, respectively). The overall 2015 to 2018 MBS utilization rate for youth was 1.81 per 1000 and 5.56 per 1000 for adults (P < 0.001). Adult patients had slightly higher percentage (4.2%) of hospital readmissions compared to youth (3.4%, P = 0.01) but there were no other post-MBS complication differences. From 2015 to 2018 the US prevalence of youth with class II/III obesity increased in Hispanics and non-Hispanic Blacks (P trend < 0.001), but among youth who did complete MBS non-Hispanic Whites had higher rates of utilization (45.8%) compared to Hispanics (22.7%) and non-Hispanic blacks 14.2% (P = 0.006).

Conclusions:
MBS is an underutilized obesity treatment tool for both youth and adults, and among ethnic minority groups in particular.
TransCarotid Revascularization With Dynamic Flow Reversal Versus Carotid Endarterectomy in the Vascular Quality Initiative Surveillance Project
Authors: Malas Mahmoud B. , Dakour-Aridi Hanaa , Kashyap Vikram S. , Eldrup-Jorgensen Jens , Wang Grace J. , Motaganahalli Raghu L. , Cronenwett Jack L. , Schermerhorn Marc L. 
Published: September 2020

Objective:
To compare the outcomes of TCAR with flow reversal to the gold standard CEA using data from the Society for Vascular Surgery Vascular Quality Initiative TCAR Surveillance Project.

Summary of Background Data:
TCAR is a novel minimally invasive procedure for carotid revascularization in high-risk patients that is associated with significantly lower stroke rates compared with carotid artery stenting via the transfemoral approach.

Methods:
Patients in the United States and Canada who underwent TCAR and CEA for carotid artery stenosis (2016-2019) were included. Propensity scores were calculated based on baseline clinical variables and used to match patients in the 2 treatment groups (n = 6384 each). The primary endpoint was the combined outcome of perioperative stroke and/or death.

Results:
No significant differences were observed between TCAR and CEA in terms of in-hospital stroke/death [TCAR, 1.6% vs CEA, 1.6%, RR (95% CI): 1.01 (0.77–1.33), P = 0.945], stroke [1.4% vs 1.4%, RR (95% CI): 1.02 (0.76–1.37), P = 0.881], or death [0.4% vs 0.3%, RR (95% CI): 1.14 (0.64–2.02), P = 0.662]. Compared to CEA, TCAR was associated with lower rates of in-hospital myocardial infarction [0.5% vs 0.9%, RR (95% CI): 0.53 (0.35–0.83), P = 0.005], cranial nerve injury [0.4% vs 2.7%, RR (95% CI): 0.14 (0.08–0.23), P < 0.001], and post-procedural hypertension [13% vs 18.8%, RR (95% CI): 0.69 (0.63–0.76), P < 0.001]. They were also less likely to stay in the hospital for more than 1 day [26.4% vs 30.1%, RR (95% CI): 0.88 (0.82–0.94), P < 0.001]. No significant interaction was observed between procedure and symptomatic status in predicting postoperative outcomes. At 1 year, the incidence of ipsilateral stroke or death was similar between the 2 groups [HR (95% CI): 1.09 (0.87–1.36), P = 0.44].

Conclusions:
This propensity-score matched analysis demonstrated significant reduction in the risk of postoperative myocardial infarction and cranial nerve injury after TCAR compared to CEA, with no differences in the rates of stroke/death.
Holstein Friesian dairy cattle edited for diluted coat color as adaptation to climate change
Authors: Laible G. , Cole S-A. , Brophy B. , Wei J. , Leath S. , Jivanji S. , Littlejohn M.D. , Wells D.N. 
Published: September 2020

AbstractHigh-producing Holstein Friesian dairy cattle have a characteristic black and white coat pattern where black frequently comprises a large proportion of the coat. Compared to a light coat color, black absorbs more solar radiation translating into radiative heat gain which is a contributing factor to heat stress in cattle, negatively impacting on their production levels, fertility and welfare. To better adapt dairy cattle to the rapidly changing climatic conditions with predictions for more frequent and prolonged hot temperature patterns, we aimed to lighten their coat color by genome editing. Using gRNA/Cas9-mediated editing, we introduced a three base pair (bp) deletion in the pre-melanosomal protein 17 gene (PMEL) proposed as the causative variant responsible for the semi-dominant color dilution phenotype seen in Galloway and Highland cattle. Calves generated from cells homozygous for the edited mutation revealed a strong color dilution effect. Instead of the characteristic black and white coat color patterning of control calves generated from unedited parental cells, the edited calves displayed a novel pattern of grey and white markings and absence of any black areas. This, for the first time, verified the causative nature of thePMELmutation for diluting the black coat color in cattle. With these edited animals, it is now possible to dissect the effects of the introgressed edit and other interfering allelic variants that might exist in individual cattle and accurately determine the impact of only the three bp change on important health, welfare and production traits. In addition, our study proved targeted editing as a promising approach for the rapid adaptation of livestock to changing climatic conditions.
Obesity control by SHIP inhibition requires pan-paralog inhibition and an intact eosinophil compartment
Authors: Fernandes Sandra , Srivastava Neetu , Pedicone Chiara , Sudan Raki , Luke Elizabeth A. , Dungan Otto M. , Pacherille Angela , Meyer Shea T. , Dormann Shawn , Chisholm John D. , Kerr William G. 
Published: September 2020

ABSTRACTPreviously a small molecule SHIP inhibitor, K118, was shown to reverse high-fat diet induced obesity and improve blood glucose regulation in obese mice. K118 treatment was also found to increase the frequency and number of IL-4 producing eosinophils in the visceral fat as well two potent immunoregulatory myeloid cell populations: M2-polarized macrophages and myeloid derived suppressor cells (MDSC) suggesting an immune regulatory mechanism. However, the cell(s) or SHIP paralog that should be targeted to improve metabolic regulation was not defined. Here we extend our understanding of how chemical inhibition of SHIP paralogs improves metabolic regulation during excess caloric intake. Here we compare SHIP inhibitors in an obesity prevention model and find that selective inhibitors for SHIP1 or SHIP2 lack the ability to prevent weight gain and body fat accumulation during increased caloric intake. Surprisingly, only pan-SHIP1/2 inhibitors can prevent diet-induced obesity. We confirm that both SHIP1 and SHIP2 must be targeted by showing that dual treatment with the SHIP1 and SHIP2 selective inhibitors can reduced adiposity caused by excess caloric consumption. We also show that pan-SHIP1/2 inhibitors of two different chemical classes can control diet-induced obesity and improve blood glucose regulation. Intriguingly, we find that both classes of pan-SHIP1/2 inhibitors require an intact eosinophil compartment to prevent diet-related fat accumulation demonstrating pan-SHIP1/2 inhibitors act via the VAT innate immune compartment to control adiposity However, improved blood glucose regulation by pan-SHIP1/2 inhibition is not dependent upon eosinophils, indicating a separate mechanism of action for diet-related loss of glucose regulation.
Ebselen, disulfiram, carmofur, PX-12, tideglusib, and shikonin are non-specific promiscuous SARS-CoV-2 main protease inhibitors
Authors: Ma Chunlong , Hu Yanmei , Townsend Julia Alma , Lagarias Panagiotis I. , Marty Michael Thomas , Kolocouris Antonios , Wang Jun 
Published: September 2020

AbstractThere is an urgent need for vaccines and antiviral drugs to combat the COVID-19 pandemic. Encouraging progress has been made in developing antivirals targeting SARS-CoV-2, the etiological agent of COVID-19. Among the drug targets being investigated, the viral main protease (Mpro) is one of the most extensively studied drug targets. Mprois a cysteine protease that hydrolyzes the viral polyprotein at more than 11 sites and it is highly conserved among coronaviruses. In addition, Mprohas a unique substrate preference for glutamine in the P1 position. Taken together, it appears that Mproinhibitors can achieve both broad-spectrum antiviral activity and a high selectivity index. Structurally diverse compounds have been reported as Mproinhibitors, with several of which also showed antiviral activity in cell culture. In this study, we investigated the mechanism of action of six previously reported Mproinhibitors, ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12 using a consortium of techniques including FRET-based enzymatic assay, thermal shift assay, native mass spectrometry, cellular antiviral assays, and molecular dynamics simulations. Collectively, the results showed that the inhibition of Mproby these six compounds is non-specific and the inhibition is abolished or greatly reduced with the addition of reducing reagent DTT. In the absence of DTT, these six compounds not only inhibit Mpro, but also a panel of viral cysteine proteases including SARS-CoV-2 papain-like protease, the 2Aproand 3Cprofrom enterovirus A71 (EV-A71) and EV-D68. However, none of the compounds inhibits the viral replication of EV-A71 or EV-D68, suggesting that the enzymatic inhibition potency IC50values obtained in the absence of DTT cannot be used to faithfully predict their cellular antiviral activity. Overall, we provide compelling evidence suggesting that ebselen, disulfiram, tideglusib, carmofur, shikonin, and PX-12 are non-specific SARS-CoV-2 Mproinhibitors, and urge the scientific community to be stringent with hit validation.
DeLTa-Seq: direct-lysate targeted RNA-Seq from crude tissue lysate
Authors: Kashima Makoto , Kamitani Mari , Nomura Yasuyuki , Hirata Hiromi , Nagano Atsushi J. 
Published: September 2020

AbstractUsing current mRNA quantification methods such as RT-qPCR and RNA-Seq, it is very difficult to examine thousands of tissue samples due to cost and labor of RNA extraction and quantification steps. Here, we developed Direct-RT buffer in which homogenization of tissue samples and direct-lysate reverse transcription can be conducted without RNA purification. We showed that appreciate concentration of DTT prevented RNA degradation but not RT in the lysates of several plants’ tissues, yeast, and zebrafish larvae. Using the buffer, direct reverse transcription on the lysates could produce comparable amount of cDNA with that synthesized from purified RNA. Furthermore, we established DeLTa-Seq (Direct-Lysate reverse transcription andTargeted RNA-Seq) method. DeLTa-Seq is a cost-effective, high-throughput and highly-precise quantification method for the expressions of hundreds of genes. It enables us to conduct large-scale studies using thousands of samples such as chemical screening, field experiments and studies focusing on individual variability.
Characterisation of protease activity during SARS-CoV-2 infection identifies novel viral cleavage sites and cellular targets with therapeutic potential
Authors: Meyer Bjoern , Chiaravalli Jeanne , Gellenoncourt Stacy , Brownridge Philip , Bryne Dominic P. , Daly Leonard A. , Grauslys Arturas , Walter Marius , Agou Fabrice , Chakrabarti Lisa A. , Craik Charles S. , Eyers Claire E. , Eyers Patrick A. , Gambin Yann , Jones Andrew R. , Sierecki Emma , Verdin Eric , Vignuzzi Marco , Emmott Edward 
Published: September 2020

AbstractSARS-CoV-2 is the causative agent behind the COVID-19 pandemic, and responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication, and inhibitors targeting proteases have already shown success at inhibiting SARS-CoV-2 in cell culture models. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigenic proteins S and N, which are the main targets for vaccine and antibody testing efforts. We discovered significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases, validating a subset within vitroassays. We showed that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, showed a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.
Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein
Authors: Roy Sylvie , Ghani Karim , de Campos-Lima Pedro O. , Caruso Manuel 
Published: September 2020

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that started in China at the end of 2019 has rapidly spread to become pandemic. Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies against the SARS-CoV-2 spike (S) protein, however protection and long-term efficacy in humans remain to be demonstrated.We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia virus (MLV) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. First, we showed that a codon optimized version of the S protein could migrate efficiently to the cell membrane. However, efficient production of infectious viral particles was only achieved with stable expression of a shorter version of S in its C-terminal domain (ΔS) in 293 cells that express MLV Gag-Pol (293GP). The incorporation of ΔS was 15-times more efficient into VLPs as compared to the full-length version, and that was not due to steric interference between the S cytoplasmic tail and the MLV capsid. Indeed, a similar result was also observed with extracellular vesicles released from parental 293 and 293GP cells. The amount of ΔS incorporated into VLPs released from producer cells was robust, with an estimated 1.25μg/ml S2 equivalent (S is comprised of S1 and S2). Thus, a scalable platform that has the potential for production of pan-coronavirus VLP vaccines has been established. The resulting nanoparticles could potentially be used alone or as a boost for other immunization strategies for COVID-19.IMPORTANCESeveral candidate COVID-19 vaccines have already been tested in humans, but their protective effect and long-term efficacy are uncertain. Therefore, it is necessary to continue developing new vaccine strategies that could be more potent and/or that would be easier to manufacture in large-scale. Virus-like particle (VLP) vaccines are considered highly immunogenic and have been successfully developed for human papilloma virus as well as hepatitis and influenza viruses. In this study, we report the generation of a robust Moloney murine leukemia virus platform that produces VLPs containing the spike of SARS-CoV-2. This vaccine platform that is compatible with lyophilization could simplify storage and distribution logistics immensely.
Efficient Development of Platform Cell Lines Using CRISPR-Cas9 and Transcriptomics Analysis
Authors: Kwon Andrew Tae-Jun , Mohri Kohta , Takizawa Satoshi , Arakawa Takahiro , Takahashi Maiko , Kaczkowski Bogumil , Furuno Masaaki , Suzuki Harukazu , Tagami Shunsuke , Mukai Hidefumi , Arner Erik 
Published: September 2020

AbstractAntibody-drug conjugates offers many advantages as a drug delivery platform that allows for highly specific targeting of cell types and genes. Ideally, testing the efficacy of these systems requires two cell types to be different only in the gene targeted by the drug, with the rest of the cellular machinery unchanged, in order to minimize other potential differences from obscuring the effects of the drug. In this study, we created multiple variants of U87MG cells with targeted mutation in theTP53gene using the CRISPR-Cas9 system, and determined that their major transcriptional differences stem from the loss of p53 function. Using the transcriptome data, we predicted which mutant clones would have less divergent phenotypes from the wild type and thereby serve as the best candidates to be used as drug delivery testing platforms. Furtherin vitroandin vivoassays of cell morphology, proliferation rate and target antigen-mediated uptake supported our predictions. Based on the combined analysis results, we successfully selected the best qualifying mutant clone. This study serves as proof-of-principle of the approach and paves the way for extending to additional cell types and target genes.
Tumors Negate the Action of ImpL2 by Elevating Wingless
Authors: Lee Jiae , Ng Katelyn G.-L. , Dombek Kenneth M. , Kwon Young V. 
Published: September 2020

SummaryTumors often secrete wasting factors associated with atrophy and degeneration of host tissues. If tumors were affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist and impairing such mechanisms may attenuate tumors. We usedDrosophilamidgut tumor models to show that tumors upregulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (Insulin-like growth factor binding protein (IGFBP)-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination ofImpL2or elevation of Insulin/IGF signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.