bluuebunny/crossref_metadata_2025 huggingface dataset:
Yo el Supremo, dictado y cibernética
Authors: Lupi Juan Pablo
Published: June 2022

Yo el Supremo (1974), la monumental novela de Augusto Roa Bastos (1917-2005), puede entenderse como una dramatización de las relaciones mediales entre poder, historia, tecnología, hegemonía y subalternidad. Este artículo propone que en la novela se plantea una antinomia en la que se entrecruzan dos impulsos: por un lado, una proliferación medial en la que aparecen técnicas que van desde la voz y la escritura manuscrita hasta aparatos anacrónicos o fantásticos como la grabadora o el “portapluma-recuerdo”; por otro lado, el Dictador Supremo como arkhé, cuyo “dictado” (entendido tanto como acto de habla como ejercicio en sí del poder dictatorial) se produce simultáneamente por medio y en contra de dicha multiplicidad. En el marco de esta antinomia se muestra que el Dictador sostiene una concepción de las tecnologías mediales y la fundación del estado que puede caracterizarse como cibernética. La cuestión de la cibernética se ubica en el contexto del interés por esta disciplina en los años 60 y 70 y se muestra en qué sentido el Dictador concibe el mundo en términos cibernéticos y tecnodeterministas. Roa Bastos escribió una obra que no solamente trata de la historia del Paraguay, el republicanismo hispanoamericano y el arquetipo del dictador latinoamericano, sino que también permite intuir el carácter de los modos de dominación global que emergen a partir de los avances tecnológicos de la posguerra.
Pathogen-sugar interactions revealed by universal saturation transfer analysis
Authors: Buchanan Charles J. , Gaunt Ben , Harrison Peter J. , Yang Yun , Liu Jiwei , Khan Aziz , Giltrap Andrew M. , Le Bas Audrey , Ward Philip N. , Gupta Kapil , Dumoux Maud , Tan Tiong Kit , Schimaski Lisa , Daga Sergio , Picchiotti Nicola , Baldassarri Margherita , Benetti Elisa , Fallerini Chiara , Fava Francesca , Giliberti Annarita , Koukos Panagiotis I. , Davy Matthew J. , Lakshminarayanan Abirami , Xue Xiaochao , Papadakis Georgios , Deimel Lachlan P. , Casablancas-Antràs Virgínia , Claridge Timothy D. W. , Bonvin Alexandre M. J. J. , Sattentau Quentin J. , Furini Simone , Gori Marco , Huo Jiandong , Owens Raymond J. , Schaffitzel Christiane , Berger Imre , Renieri Alessandra ,   GEN-COVID Multicenter Study, Naismith James H. , Baldwin Andrew J. , Davis Benjamin G.
Published: June 2022

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis.
Nickel-catalyzed hydrogenative coupling of nitriles and amines for general amine synthesis
Authors: Chandrashekhar Vishwas G. , Baumann Wolfgang , Beller Matthias , Jagadeesh Rajenahally V.
Published: June 2022

Efficient and general methods for the synthesis of amines remain in high demand in the chemical industry. Among the many known processes, catalytic hydrogenation is a cost-effective and industrially proven reaction and currently used to produce a wide array of such compounds. We report a homogeneous nickel catalyst for hydrogenative cross coupling of a range of aromatic, heteroaromatic, and aliphatic nitriles with primary and secondary amines or ammonia. This general hydrogenation protocol is showcased by straightforward and highly selective synthesis of >230 functionalized and structurally diverse amines including pharmaceutically relevant and chiral products, as well as
15
N-isotope labeling applications.
Alphabetized
Inventing the Alphabet
Johanna Drucker
University of Chicago Press, 2022. 384 pp.
Authors: Robinson Andrew
Published: June 2022

The origins of the world’s chief writing system come to life in an illuminating historiography
How ubiquitous is aging in vertebrates?
Authors: Austad Steven N. , Finch Caleb E.
Published: June 2022

Two new studies find little evidence of aging in some turtle species
In Other Journals
Authors: Smith Keith T. , Nusinovich Yevgeniya , Vignieri Sacha , Kelly Priscilla N. , Lavine Marc S. , Ash Caroline , McCartney Melissa
Published: June 2022

Editors’ selections from the current scientific literature
Characterizing SARS-CoV-2 Viral Clearance Kinetics to Improve the Design of Antiviral Pharmacometric Studies
Authors: Watson James A. , Kissler Stephen M. , Day Nicholas P. J. , Grad Yonatan H. , White Nicholas J.
Published: June 2022

A consensus methodology for the pharmacometric assessment of candidate SARS-CoV-2 antiviral drugs would be useful for comparing trial results and improving trial design. The time to viral clearance, assessed by serial qPCR of nasopharyngeal swab samples, has been the most widely reported measure of virological response in clinical trials, but it has not been compared formally with other metrics, notably model-based estimates of the rate of viral clearance.
Colonization of White-Tailed Deer (Odocoileus virginianus) from Urban and Suburban Environments with Cephalosporinase- and Carbapenemase-Producing Enterobacterales
Authors: Ballash Gregory A. , Dennis Patricia M. , Mollenkopf Dixie F. , Albers Amy L. , Robison Terry L. , Adams Rachael J. , Li Cong , Tyson Gregory H. , Wittum Thomas E.
Published: June 2022

The role of wildlife in the spread of antimicrobial resistance is not fully characterized. Some wildlife, including white-tailed deer (WTD), can thrive in suburban and urban environments.
Complete Genome Sequence of
Alkalihalobacillus
sp. Strain LMS39, a Haloalkaliphilic Bacterium Isolated from a Hypersaline Lake
Authors: Kipnyargis Alex , Mwirichia Romano , Pfeiffer Birgit , Daniel Rolf
Published: June 2022

Here, we report the complete genome sequence of a haloalkaliphilic bacterium (
Alkalihalobacillus
sp. strain LMS39) isolated from Lake Magadi, a hypersaline lake in Kenya. The genome comprised 4,850,562 bp with a GC content of 37%.
Differential Binding of Carbapenems with the AdeABC Efflux Pump and Modulation of the Expression of AdeB Linked to Novel Mutations within Two-Component System AdeRS in Carbapenem-Resistant Acinetobacter baumannii
Authors: Roy Subhasree , Junghare Vivek , Dutta Shanta , Hazra Saugata , Basu Sulagna
Published: June 2022

AdeABC is an important efflux pump in
A. baumannii
that plays a role in resistance toward different antibiotics including the “last resort” antibiotic, carbapenem. This pump is regulated by a two-component system, AdeRS.
Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans
Authors: Jung Kwang-Woo , Kwon Sunhak , Jung Jong-Hyun , Bahn Yong-Sun
Published: June 2022

Upon DNA replication or damage stresses, it is critical to provide proper levels of deoxynucleotide triphosphates (dNTPs) and activate DNA repair machinery. Ribonucleotide reductases (RNRs), which are composed of large and small subunits, are required for synthesizing dNTP.
Transcription Start Site Heterogeneity and Preferential Packaging of Specific Full-Length RNA Species Are Conserved Features of Primate Lentiviruses
Authors: Rawson Jonathan M. O. , Nikolaitchik Olga A. , Shakya Saurabh , Keele Brandon F. , Pathak Vinay K. , Hu Wei-Shau
Published: June 2022

Unspliced HIV-1 RNA serves two important roles during viral replication: as the virion genome and as the template for translation of Gag/Gag-Pol. Previous studies of two HIV-1 molecular clones have concluded that the TSS usage affects unspliced HIV-1 RNA structures and functions.
Mafic magma-driven magmatic processes and compositional variation in granitic pluton construction: The Buya intrusion of West Kunlun, Northwestern China
Authors: Wang Chao , Liu Liang , Yang Wen-qiang , Cao Yu-ting , Smithies R. Hugh
Published: June 2022

To investigate the direct evidence for a number of physico-chemical processes related to pluton construction and growth, we examine the Buya pluton of West Kunlun in Northwestern China, which emplaced within the 455–460 Ma time frame. Field observations, geochemical data, and thermodynamic modeling show that mafic dikes of the Buya pluton were conduits for magma chamber replenishment during pluton construction. These mafic inputs, and the enclaves that resulted from them, induced compaction of the semi-consolidated, crystal-rich, felsic mushes below them. The accumulation of highly silicic, fine-grained granite at the top of the Buya pluton is the result of episodic melt segregation events from these mushes. This sequence of events may reflect a common process that promotes compositional variation in granite suites. Combined geochemical and Hf- and Nd-isotopic data suggest that parental magmas of the mafic sheet and enclave are similar to sanukitoid, which is potentially consistent with a mantle peridotitic source metasomatized by slab melts. These mafic magmas intruded the lower crust where the original magma was modified by mafic lower-crust melt. Following emplacement at shallow crustal levels of the mafic inputs (~3.7 kbar, ~5.3 km, constrained by amphibole geobarometry), the felsic mush evolved through the extraction of interstitial melts driven by hybridization with episodic inputs of mafic magmas as well as crystal consequent accumulation and fractional crystallization of plagioclase, hornblende, and accessory phases such as allanite, apatite, and zircon. This fractional crystallization process may also provide an explanation for the apparently high Sr/Y features in some silicic high-K, calc-alkaline magmas.
The evidence base for US joint commission hospital accreditation standards: cross sectional study
Authors: Ibrahim Sarah A , Reynolds Kelly A , Poon Emily , Alam Murad
Published: June 2022

Objective

To evaluate the evidence upon which standards for hospital accreditation by The Joint Commission on Accreditation of Healthcare Organizations (the Joint Commission) are based.

Design

Cross sectional study.

Setting

United States.

Participants

Four Joint Commission R3 (requirement, rationale, and reference) reports released by July 2018 and intended to become effective between 1 July 2018 and 1 July 2019.

Interventions

From each R3 report the associated standard and its specific elements of performance (or actionable standards) were extracted. If an actionable standard enumerated multiple requirements, these were separated into distinct components. Two investigators reviewed full text references, and each actionable standard was classified as either completely supported, partly supported, or not supported; Oxford evidence quality ratings were assigned; and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the strength of recommendations.

Main outcome measure

Strengths of recommendation for actionable standards.

Results

20 actionable standards with 76 distinct components were accompanied by 48 references. Of the 20 actionable standards, six (30%) were completely supported by cited references, six were partly supported (30%), and eight (40%) were not supported. Of the six directly supported actionable standards, one (17%) cited at least one reference of level 1 or 2 evidence, none cited at least one reference of level 3 evidence, and five (83%) cited references of level 4 or 5 evidence. Of the completely supported actionable standards, strength of recommendation in five was deemed GRADE D and in one was GRADE B.

Conclusions

In general, recent actionable standards issued by The Joint Commission are seldom supported by high quality data referenced within the issuing documents. The Joint Commission might consider being more transparent about the quality of evidence and underlying rationale supporting each of its recommendations, including clarifying when and why in certain instances it determines that lower level evidence is sufficient.
Relationship between serum creatinine to cystatin C ratio and subclinical atherosclerosis in patients with type 2 diabetes
Authors: Hashimoto Yoshitaka , Takahashi Fuyuko , Okamura Takuro , Osaka Takafumi , Okada Hiroshi , Senmaru Takafumi , Majima Saori , Ushigome Emi , Nakanishi Naoko , Asano Mai , Hamaguchi Masahide , Yamazaki Masahiro , Fukui Michiaki
Published: June 2022

Introduction

Sarcopenia index (SI), calculated by (serum creatinine/cystatin C)×100, is reported to be associated with sarcopenia. Few studies reported the association between SI and subclinical atherosclerosis. We evaluated the association between SI and subclinical atherosclerosis, assessed by brachial-ankle pulse wave velocity (baPWV).

Research design and methods

One hundred seventy-four patients with type 2 diabetes were included in this cross-sectional study. The relationship between SI and baPWV was assessed by Pearson’s correlation coefficient. To calculate area under the receiver operator characteristic (ROC) curve (AUC) of SI for the presence of subclinical atherosclerosis, which was defined as baPWV >1800 cm/s, ROC analysis was performed. Logistic regression analyses were performed to assess the effect of SI on the prevalence of subclinical atherosclerosis adjusting for covariates.

Results

Mean age, duration of diabetes, baPWV, and SI were 66.9 (10.1) years, 17.7 (11.6) years, 1802 (372) cm/s, and 77.6 (15.8), respectively. There was an association between SI and baPWV (men; r=−0.25, p=0.001, and women; r=−0.37, p=0.015). The optimal cut-off point of SI for the presence of subclinical atherosclerosis was 77.4 (sensitivity=0.72, specificity=0.58, p<0.001, AUC 0.66 (95% CI: 0.57 to 0.74)). In addition, SI was associated with the prevalence of subclinical atherosclerosis (adjusted OR 0.95, 95% CI: 0.91 to 0.99, p=0.015).

Conclusions

SI is associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes.
The effect of hindrance stressors on the emotional exhaustion among front-line healthcare workers in the recuperation period during the COVID-19 epidemic in China: a prospective cross-sectional study
Authors: Wang Huan , Zhou Xinyao , Song Caiping , Yin Pengpeng , Shi Renzhong , Zhang Hua , Dan Yang , Wu Hao , Ye Junying
Published: June 2022

Objectives

This study aimed to examine the influence and conditioning process of hindrance stressors on the emotional exhaustion of the front-line healthcare workers during recuperation, examine the potential mediating process of rumination, and explore the moderating role of organisational and family factors.

Setting

This cross-sectional study was conducted during 12–20 July 2020. Total 418 questionnaires were collected from front-line healthcare workers by random cluster sampling. Hierarchical regression was performed to analyse the mediating effect of affective rumination using SPSS25.0, while PROCESS was used to further investigate the moderating role of servant leadership and family support.

Participants

418 healthcare workers were investigated randomly from front-line medical teams. Inclusion criteria included worked as front-line health workers and participated in the fight against COVID-19 in Hubei; age ≥18 years; normal cognitive and comprehension abilities under physical and mental health; volunteer to participate in this study. Exclusion criteria included recently affected by major events other than COVID-19 or those with a history of neurasthenia and trauma.

Results

Using descriptive analysis of average value and SD measured by a five-item scale (MBI-GS), we found that front-line healthcare workers’ emotional exhaustion score (2.45±0.88) was at the medium level. Hindrance stressors, mediated by affective rumination, had a significant positive predictive effect on emotional exhaustion. Servant leadership negatively moderated the direct effect of hindrance stressors on emotional exhaustion (β=−0.106, p<0.01). Family support positively moderated the impact of hindrance stressors on emotional exhaustion (β=0.082, p<0.05).

Conclusions

During the recuperation period, after successfully controlling COVID-19 at the front line, the first-line healthcare workers should be screened through affective rumination evaluation to gain insight for targeted interventions. We find that servant leadership is beneficial in alleviating emotional exhaustion while family support worsens emotional exhaustion. We suggest that servant leadership should be further promoted in medical organisations, and family support should be applied correctly and cautiously.
Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis
Authors: Krauss Sara Russo , Barbateskovic Marija , Klingenberg Sarah Louise , Djurisic Snezana , Petersen Sesilje Bondo , Kenfelt Mette , Kong De Zhao , Jakobsen Janus C , Gluud Christian
Published: June 2022

Objectives

To assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development.

Design

Systematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Data sources

We searched CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Science Citation Index Expanded and Conference Proceedings Citation Index-Science until 29 June 2021, and Chinese databases until September 2021.

Eligibility criteria

Randomised clinical trials irrespective of type, status and language of publication, with trial participants of any sex, age, ethnicity, diagnosis, comorbidity and country of residence.

Data extraction and synthesis

Two independent reviewers extracted data and assessed risk of bias with Cochrane’s RoB tool 1. Dichotomous data were analysed as risk ratios (RRs) and continuous data as mean differences. We explored both fixed-effect and random-effects models, with 95% CI. Heterogeneity was quantified with I2 statistic. We GRADE assessed the certainty of the evidence.

Results

We included 102 randomised clinical trials (26 457 participants). Aluminium adjuvants versus placebo or no intervention may have no effect on serious adverse events (RR 1.18, 95% CI 0.97 to 1.43; very low certainty) and on all-cause mortality (RR 1.02, 95% CI 0.74 to 1.41; very low certainty). No trial reported on quality of life. Aluminium adjuvants versus placebo or no intervention may increase adverse events (RR 1.13, 95% CI 1.07 to 1.20; very low certainty). We found no or little evidence of a difference between aluminium adjuvants versus placebo or no intervention when assessing serology with geometric mean titres or concentrations or participants’ seroprotection.

Conclusions

Based on evidence at very low certainty, we were unable to identify benefits of aluminium adjuvants, which may be associated with adverse events considered non-serious.
Upstream interventions to promote oral health and reduce socioeconomic oral health inequalities: a scoping review protocol
Authors: Dawson Eleanor R , Stennett Michelle , Daly Blánaid , Macpherson Lorna M D , Cannon Paul , Watt Richard G
Published: June 2022

Introduction

Improving oral health and reducing oral health inequalities is an important global health priority. ‘Upstream interventions’ are a vital part of the collective effort to reduce oral disease burdens, however it is a rather nebulous term. Furthermore, there is little evidence on the effectiveness, impact and sustainability of upstream interventions that have focused on oral health and wider public health measures that impact on oral health. The aim of this scoping review is to systematically map and synthesise evidence on the effectiveness, impact and sustainability of upstream interventions on population oral health and reducing socioeconomic oral health inequalities.

Methods and analysis

This scoping review will be conducted in accordance with the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A detailed search strategy will be used to conduct a comprehensive search of electronic databases: Scopus, Embase and MEDLINE, PsycINFO and CINAHL, ASSIA and Cochrane Database of Systematic Reviews. A search of grey literature will also be completed to identify relevant dissertations, governmental reports and evaluations of implemented policies. Identification and extraction of data will be performed by two pairs of reviewers. Oversight and feedback will be provided by an independent expert advisory group.

Ethics and dissemination

This study will review published and available grey literature and does not require an ethics review. The scoping review protocol has been registered with the Open Science Framework. The final report will be circulated and disseminated through publication and feed into the work of the ongoing Lancet Commission on Oral Health. Due to the policy relevance of this work, discussions will take place with key stakeholders regarding the implications of the findings for future policy development.
A health-education intervention to improve outcomes for children with emotional and behavioural difficulties: protocol for a pilot cluster randomised controlled trial
Authors: Garvey William , Schembri Rachel , Oberklaid Frank , Hiscock Harriet
Published: June 2022

Introduction

One in seven (14%) children aged 4–17 years old meet criteria for a mental illness over a 12-month period. The majority of these children have difficulty accessing clinical assessment and treatment despite evidence demonstrating the importance of early intervention. Schools are increasingly recognised as universal platforms where children with mental health concerns could be identified and supported. However, educators have limited training or access to clinical support in this area.

Methods and analysis

This study is a pilot cluster randomised controlled trial of a co-designed health and education model aiming to improve educator identification and support of children with emotional and behavioural difficulties. Twelve Victorian government primary schools representing a range of socio-educational communities will be recruited from metropolitan and rural regions, with half of the schools being randomly allocated to the intervention. Caregivers and educators of children in grades 1–3 will be invited to participate. The intervention is likely to involved regular case-based discussions and paediatric support.

Ethics and dissemination

Informed consent will be obtained from each participating school, educator and caregiver. Participants are informed of their voluntary participation and ability to withdrawal at any time. Participant confidentiality will be maintained and data will be secured on a password protected, restricted access database on the Murdoch Children’s Research Institute server. Results will be disseminated via peer-reviewed journals and conference presentations. Schools and caregivers will be provided with a report of the study outcomes and implications at the completion of the study.

Trial registration number

ACTRN12621000652875.
Predicting the likelihood of aBRCA1/2pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer
Authors: Morgan Robert D , Burghel George J , Flaum Nicola , Bulman Michael , Smith Philip , Clamp Andrew R , Hasan Jurjees , Mitchell Claire , Salih Zena , Woodward Emma R , Lalloo Fiona , Shaw Joseph , Desai Sudha , Crosbie Emma J , Edmondson Richard J , Schlecht Helene , Wallace Andrew J , Jayson Gordon C , Evans D Gareth R
Published: June 2022

Aims

Clinical guidelines recommend testing both germline and tumour DNA forBRCA1/2pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumourBRCA1/2PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germlineBRCA1/2PVs.

Methods

An observational study that included all tumourBRCA1/2PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumourBRCA1/2PVs were compared with PVs recorded in a prospectively gathered pan-cancer germlineBRCA1/2(gBRCA) testing database for the same geographical region (gBRCA1PVs=910 and gBRCA2PVs=922). TumourBRCA1/2PVs were categorised as common (≥1%), uncommon (<1%) or absent from the germline database.

Results

One hundred and thirteen tumourBRCA1/2PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCAand somaticBRCA1/2(sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test p<0.0001). All sBRCAPVs were detected in non-familial cases. All tumourBRCA1/2PVs with a variant allele frequency (VAF) <35% in non-familial cases were somatic variants. Eighty-one per cent of germline-tumourBRCA1/2PVs were present (common=31, uncommon=25) in the gBRCAtesting database, while 89% of somatic-tumourBRCA1/2PVs were absent (n=39).

Conclusions

We predict the likelihood of a tumourBRCA1/2PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.
Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis
Authors: Guo Weinan , Wu Zhenjie , Chen Jianru , Guo Sen , You Weiming , Wang Sijia , Ma Jinyuan , Wang Huina , Wang Xiangxu , Wang Hao , Ma Jingjing , Yang Yuqi , Tian Yangzi , Shi Qiong , Gao Tianwen , Yi Xiuli , Li Chunying
Published: June 2022

Background

Although anti-programmed cell death protein 1 (PD-1) immunotherapy is greatly effective in melanoma treatment, low response rate and treatment resistance significantly hinder its efficacy. Tumor cell ferroptosis triggered by interferon (IFN)-γ that is derived from tumor-infiltrating CD8+T cells greatly contributes to the effect of immunotherapy. However, the molecular mechanism underlying IFN-γ-mediated ferroptosis and related potentially promising therapeutic strategy warrant further clarification. MicroRNAs (miRNAs) participate in ferroptosis execution and can be delivered systemically by multiple carriers, which have manifested obvious therapeutic effects on cancer.

Methods

MiRNAs expression profile in IFN-γ-driven ferroptosis was obtained by RNA sequencing. Biochemical assays were used to clarify the role of miR-21-3p in IFN-γ-driven ferroptosis and the underlying mechanism. MiR-21-3p-loaded gold nanoparticles were constructed and systemically applied to analyze the role of miR-21-3p in anti-PD-1 immunotherapy in preclinical transplanted tumor model.

Results

MiRNAs expression profile of melanoma cells in IFN-γ-driven ferroptosis was first obtained. Then, upregulated miR-21-3p was proved to facilitate IFN-γ-mediated ferroptosis by potentiating lipid peroxidation. miR-21-3p increased the ferroptosis sensitivity by directly targeting thioredoxin reductase 1 (TXNRD1) to enhance lipid reactive oxygen species (ROS) generation. Furthermore, miR-21-3p overexpression in tumor synergized with anti-PD-1 antibody by promoting tumor cell ferroptosis. More importantly, miR-21-3p-loaded gold nanoparticles were constructed, and the systemic delivery of them increased the efficacy of anti-PD-1 antibody without prominent side effects in preclinical mice model. Ultimately, ATF3 was found to promote miR-21-3p transcription in IFN-γ-driven ferroptosis.

Conclusions

MiR-21–3 p upregulation contributes to IFN-γ-driven ferroptosis and synergizes with anti-PD-1 antibody. Nanoparticle delivery of miR-21–3 p is a promising therapeutic approach to increase immunotherapy efficacy without obvious systemic side effects.
Targeting of Nrf2 improves antitumoral responses by human NK cells, TIL and CAR T cells during oxidative stress
Authors: Renken Stefanie , Nakajima Takahiro , Magalhaes Isabelle , Mattsson Jonas , Lundqvist Andreas , Arnér Elias S J , Kiessling Rolf , Wickström Stina Linnea
Published: June 2022

Background

Adoptive cell therapy using cytotoxic lymphocytes is an efficient immunotherapy against solid and hematological cancers. However, elevated levels of reactive oxygen species (ROS) in the hostile tumor microenvironment can impair NK cell and T cell function. Auranofin, a gold (I)-containing phosphine compound, is a strong activator of the transcription factor Nrf2. Nrf2 controls a wide range of downstream targets important for the cells to obtain increased resistance to ROS. In this study, we present a strategy using auranofin to render human cytotoxic lymphocytes resistant toward oxidative stress.

Methods

Melanoma patient-derived tumor infiltrating lymphocytes (TIL) and healthy donor-derived NK cells and CD19-directed CAR T cells were pretreated with a low dose of auranofin. Their resistance toward oxidative stress was assessed by measuring antitumoral responses (killing-assay, degranulation/CD107a, cytokine production) and intracellular ROS levels (flow cytometry) in conditions of oxidative stress. To confirm that the effects were Nrf2 dependent, the transcription level of Nrf2-driven target genes was analyzed by qPCR.

Results

Pretreatment of human TIL and NK cells ex vivo with a low-dose auranofin significantly lowered their accumulation of intracellular ROS and preserved their antitumoral activity despite high H2O2levels or monocyte-derived ROS. Furthermore, auranofin pretreatment of CD19 CAR-T cells or TIL increased their elimination of CD19 +tumor cells or autologous tumor spheroids, respectively, especially during ROS exposure. Analysis of Nrf2-driven target genes revealed that the increased resistance against ROS was Nrf2 dependent.

Conclusion

These novel findings suggest that Nrf2 activation in human cytotoxic lymphocytes could be used to enhance the efficacy of adoptive cell therapy.
Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor–treated unresectable hepatocellular carcinoma
Authors: Lee Pei-Chang , Wu Chi-Jung , Hung Ya-Wen , Lee Chieh Ju , Chi Chen-Ta , Lee I-Cheng , Yu-Lun Kuo , Chou Shih-Hsuan , Luo Jiing-Chyuan , Hou Ming-Chih , Huang Yi-Hsiang
Published: June 2022

Background

Immune checkpoint inhibitors (ICIs) are promising agents for unresectable hepatocellular carcinoma (uHCC), but lack effective biomarker to predict outcomes. The gut microbiome can modulate tumor response to immunotherapy, but its effect on HCC remains unclear.

Methods

From May 2018 to February 2020, patients receiving ICI treatment for uHCC were prospectively enrolled; their fecal samples were collected before treatment. The fecal microbiota and metabolites were analyzed from 20 patients with radiology-proven objective responses (OR) and 21 randomly selected patients with progressive disease (PD). After March 2020, 33 consecutive Child-Pugh-A patients were recruited as a validation cohort. Additionally, feces from 17 healthy volunteers were collected for comparison of background microbes.

Results

A significant dissimilarity was observed in fecal bacteria between patients with OR and patients with PD before immunotherapy.Prevotella 9was enriched in patients with PD, whereasLachnoclostridium, Lachnospiraceae,andVeillonellawere predominant in patients with OR. Ursodeoxycholic acid and ursocholic acid were significantly enriched in the feces of patients with OR and strongly correlated with the abundance ofLachnoclostridium. The coexistence ofLachnoclostridiumenrichment andPrevotella 9depletion significantly predicted better overall survival (OS). In the validation cohort, better progression-free survival (PFS) and OS were noted in patients who had a preferable microbial signature in comparison with counter-group (PFS: 8.8 months vs 1.8 months; OS: not reached vs 6.5 months, both p<0.001).

Conclusions

Fecal microbiota and bile acids were associated with outcomes of immunotherapy for uHCC. These findings highlight the potential role of gut microbiota and metabolites as biomarkers to predict outcomes of ICI-treated HCC.
Habitual exercise, chronic exposure to fine particulate matter and high-sensitivity C reactive protein in Asian adults
Authors: Zeng Yi Qian , Chan Shin Heng Teresa , Guo Cui , Chang Ly-yun , Bo Yacong , Lin Changqing , Yu Zengli , Lau Alexis K.H. , Tam Tony , Lao Xiang Qian
Published: June 2022

Objectives

Exercise may increase the inhaled amount of air pollutants and exacerbate the adverse health effects. We investigated the combined effects of chronic exposure to fine particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual exercise on C reactive protein (CRP), a sensitive marker of inflammation.

Methods

We selected 40 209 Taiwanese adults who joined a standard medical screening programme between 2001 and 2016. The PM2.5exposure was estimated at each participant’s address using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. Mixed-effects linear regression models were used to investigate the associations of CRP with PM2.5and exercise. An interaction term of PM2.5and exercise was introduced in the models to test the modifying effects.

Results

A greater amount of habitual exercise was associated with a decreased level of CRP, while a higher concentration of PM2.5exposure was associated with an increased level of CRP. The inverse associations of habitual exercise with CRP were not modified by chronic exposure to PM2.5. The participants in the group with a low level of exercise and a high level of PM2.5exposure exhibited a 19.1% higher level of CRP than those in the group with a high level of exercise and a low level of PM2.5exposure (95% CI: 13.7% to 24.8%; p<0.001). The longitudinal and sensitivity analyses yielded similar results.

Conclusions

Increased levels of exercise and reduced exposure levels of PM2.5are associated with a lower CRP level. Habitual exercise reduces CRP level regardless of the levels of chronic PM2.5exposure. Our results support that habitual exercise is a safe approach for reducing systemic inflammation to improve cardiovascular health even for people residing in relatively polluted areas.
Revisiting the challenge: perspectives on Canada’s freshwater fisheries policies three decades after the Pearse Report
Authors: Piczak Morgan L. , Brooks Jill L. , Bard Brittany , Bihun Christian J. , Howarth Andrew , Jeanson Amanda L. , LaRochelle Luc , Bennett Joseph R. , Lapointe Nicolas W. R. , Mandrak Nicholas E. , Cooke Steven J.
Published: June 2022

A seminal report by Peter H. Pearse (1988; Rising to the Challenge: A New Policy for Canada’s Freshwater Fisheries, Canadian Wildlife Federation, Ottawa) outlined 62 policy recommendations focused on the management of Canada’s inland fisheries. Over three decades later, freshwater ecosystems and inland fisheries in Canada are still facing similar challenges with many emerging ones that could not have been foreseen. Here, we reflect on the contemporary relevance of the Pearse Report and propose recommendations that policy makers should consider. Broadly, our recommendations are: (1) manage fishes, fisheries, and habitat using a holistic co-management framework, with clearly defined fishery jurisdictions and partnerships with Indigenous governments; (2) engage in transparent, inclusive, and agile research to support decision-making; (3) facilitate knowledge co-production, involving interdisciplinary projects with diverse groups of actors and sectors including Indigenous Peoples, anglers, policy makers, scientists/researchers, governments, and the public; (4) embrace technological advances to support freshwater fisheries stock assessment and management; and (5) align policy and management activities in Canada with global initiatives related to increasing the sustainability of inland fisheries. We advocate for an updated comprehensive report such as the Pearse Report to ensure that we embrace robust, inclusive, and sustainable management strategies and policies for Canada’s inland fisheries for the next 30 years. It is time to again rise to the challenge.
Equilibrium and nonequilibrium quantum correlations between two detectors in curved spacetime
Authors: Wang He , Wang Jin
Published: June 2022

We investigate the equilibrium and nonequilibrium quantum information correlations encoded in a two-qubit system in curved spacetime near the horizon of a Kerr black hole. We study the impact of mass and the angular momentum and further the local curvature or accelerations on the behaviors of the quantum correlations between the two qubits. We show that the quantum information of the two qubits is encoded in the spacetime structure. Concretely, the quantum correlations in the two-qubit system vary non-monotonically with the mass of the black hole and are amplified by the angular momentum, while the curvature suppresses the quantum correlations in the system. We show that the nonequilibrium can also contribute to the quantum correlations. Remarkably, the nonequilibrium can lead to the increase of quantum correlations in the steady state under the curved spacetime shown in this black hole example.
Renormalizing the vacuum energy in cosmological spacetime: implications for the cosmological constant problem
Authors: Moreno-Pulido Cristian , Solà Peracaula Joan
Published: June 2022

The renormalization of the vacuum energy in quantum field theory (QFT) is usually plagued with theoretical conundrums related not only with the renormalization procedure itself, but also with the fact that the final result leads usually to very large (finite) contributions incompatible with the measured value of$$\Lambda $$Λin cosmology. As a consequence, one is bound to extreme fine-tuning of the parameters and so to sheer unnaturalness of the result and of the entire approach. We may however get over this adversity using a different perspective. Herein, we compute the zero-point energy (ZPE) for a nonminimally coupled (massive) scalar field in FLRW spacetime using the off-shell adiabatic renormalization technique employed in previous work. The on-shell renormalized result first appears at sixth adiabatic order, so the calculation is rather cumbersome. The general off-shell result yields a smooth function$$\rho _{\mathrm{vac}}(H)$$ρvac(H)made out of powers of the Hubble rate and/or of its time derivatives involving different (even) adiabatic orders$$\sim H^N$$∼HN($$N=0, 2,4,6,\ldots )$$N=0,2,4,6,…), i.e. it leads, remarkably enough, to the running vacuum model (RVM) structure. We have verified the same result from the effective action formalism and used it to find the$$\beta $$β-function of the running quantum vacuum. No undesired contributions$$\sim m^4$$∼m4from particle masses appear and hence no fine-tuning of the parameters is needed in$$\rho _{\mathrm{vac}}(H)$$ρvac(H). Furthermore, we find that the higher power$$\sim H^6$$∼H6could naturally drive RVM-inflation in the early universe. Our calculation also elucidates in detail the equation of state of the quantum vacuum: it proves to be not exactly$$-1$$-1and is moderately dynamical. The form of$$\rho _{\mathrm{vac}}(H)$$ρvac(H)at low energies is also characteristic of the RVM and consists of an additive term (the so-called ‘cosmological constant’) together with a small dynamical component$$\sim \nu H^2$$∼νH2($$|\nu |\ll 1$$|ν|≪1). Finally, we predict a slow ($$\sim \ln H$$∼lnH) running of Newton’s gravitational couplingG(H). The physical outcome of our semiclassical QFT calculation is revealing: today’s cosmic vacuum and the gravitational strength should be both mildly dynamical.
Reconfigurable Turbo and Low-Density Parity-Check (LDPC) Decoding Accelerators for Powerline Communications
Authors: Lin Cheng-Hung , Shen Jin-Kun , Lu Cheng-Kai
Published: June 2022

This study presents two reconfigurable turbo/low-density parity-check (LDPC) decoding kernels for the two powerline communication standards, HomePlug and G.hn. Two architectures are presented, both of which use the radix-4 double-binary enhanced max-log maximum a posteriori probability algorithm with next-iteration initialization in turbo decoding. In LDPC decoding, the two architectures employ the normalized min-sum and the layered radix-4 forward and backward algorithms. The two algorithms cause differences in the architecture and throughput rate. Consequently, the proposed decoding kernels have different architectures when combined with the turbo decoding algorithm, and the two proposed decoding kernels each have their own advantages and disadvantages in terms of throughput and area cost. To make the features of two kernels more evident, we have implemented the proposed decoding kernels that lead to significant throughput gains and better area efficiency compared with other studies. The proposed decoding kernels can be operated in all modes specified in the HomePlug and G.hn standards using a 40-nm complementary metal-oxide-semiconductor (CMOS) process. Moreover, the proposed decoding kernels provide different solutions to achieve the expected throughput rates of the G.hn and HomePlug standards.
DRIIS: MapReduce Parameter Optimization of Hadoop Using Genetic Algorithm
Authors: Anusha R. J. , RamaParvathy L.
Published: June 2022

In this era of massive knowledge, Hadoop, jointly of the foremost unremarkably used massive processing platforms, features a variety of parameters that are closely associated with resource utilization, particularly mainframe and memory. Calibration of these parameters through improvement may increase Hadoop’s resource utilization. Manual calibration of those parameters is just about not possible, thanks to the time price. Within the massive knowledge business, there’s a requirement to mechanically set up parameters and thereby maximize resource usage. The previous automatic calibration strategies take an extended time to realize the optimum configuration, reducing the cluster’s overall performance. With the help of a novel perceptive procedure, each genetic programming and a genetic rule are supported with a view to enhancing the performance of a Hadoop MapReduce work, we propose an assistant in nursing the best configuration finder. We have a tendency to use the algorithms on top to search out the simplest values for parameter settings. Experiments were performed on four common applications, WordCount, TeraSort, Index and Grep, and eight virtual machines (VMs) in a very typical Hadoop cluster. Our projected methodology will increase MapReduce job potency by 53.63% for a one GB dataset and by 67.4% for a five GB dataset, in keeping with the findings, and by 73.68% on a 10 GB dataset; additionally, for a TeraSort programmed application, MapReduce job potency will increase by 52.62% for an one GB dataset, 61.2% for a five GB dataset, and 55.17% for a 10[Formula: see text]GB dataset. MapReduce jobs boost the performance of Grep applications by 44.4% for a one GB dataset, 56.25% for a five GB dataset, and 49.44% for a 10 GB dataset.
CNS: Research on Regional Evaluation and Distribution Characteristics of Enterprise Technological Innovation Capability Based on Internet of Things and Big Data
Authors: Bai Yingchao , Song Yu
Published: June 2022

In order to explore the regional evaluation and distribution characteristics of enterprises’ technological innovation capabilities, this paper introduces the Logistic model, a commonly used model in ecology to analyze the law of population growth. Moreover, this paper uses satellite-based symbiosis mode, network-based symbiosis mode, and network-satellite compound symbiosis mode to establish models to solve the stable equilibrium point, and summarize the symbiosis stability conditions of innovation clusters in various modes. In addition to this, this paper combines the Internet of Things and big data technology to study the regional evaluation and distribution characteristics of enterprise technological innovation capabilities, and build an intelligent model based on the Internet of Things and big data. The research results show that the research system of regional evaluation and distribution characteristics of enterprise technological innovation capabilities based on the Internet of Things and big data proposed in this paper has good results. Finally, this paper puts forward relevant suggestions with the support of the model proposed in this paper.
Underwater Video Enhancement Using Manta Ray Foraging Lion Optimization-Based Fusion Convolutional Neural Network
Authors: Honnutagi Pooja , Laitha Y. S. , Mytri V. D.
Published: June 2022

Due to the significance of aquatic robotics and marine engineering, the underwater video enhancement has gained huge attention. Thus, a video enhancement method, namely Manta Ray Foraging Lion Optimization-based fusion Convolutional Neural Network (MRFLO-based fusion CNN) algorithm is developed in this research for enhancing the quality of the underwater videos. The MRFLO is developed by merging the Lion Optimization Algorithm (LOA) and Manta Ray Foraging Optimization (MRFO). The blur in the input video frame is detected and estimated through the Laplacian’s variance method. The fusion CNN classifier is used for deblurring the frame by combining both the input frame and blur matrix. The fusion CNN classifier is tuned by the developed MRFLO algorithm. The pixel of the deblurred frame is enhanced using the Type II Fuzzy system and Cuckoo Search optimization algorithm filter (T2FCS filter). The developed MRFLO-based fusion CNN algorithm uses the metrics, Underwater Image Quality Measure (UIQM), Underwater Color Image Quality Evaluation (UCIQE), Structural Similarity Index Measure (SSIM), Mean Square Error (MSE), and Peak Signal-to-Noise Ratio (PSNR) for the evaluation by varying the blur intensity. The proposed MRFLO-based fusion CNN algorithm acquired a PSNR of 38.9118, SSIM of 0.9593, MSE of 3.2214, UIQM of 3.0041 and UCIQE of 0.7881.
The balance of relative Ext groups defined by semidualizing modules
Authors: Beigi K. Abolfath , Divaani-Aazar K. , Tousi M.
Published: June 2022

Let [Formula: see text] be a commutative Noetherian ring with identity and [Formula: see text] a semidualizing module for [Formula: see text]. Let [Formula: see text] and [Formula: see text] denote, respectively, the classes of [Formula: see text]-projective and [Formula: see text]-injective [Formula: see text]-modules. We show that their induced Ext bifunctors Ext[Formula: see text] and Ext[Formula: see text] coincide for all [Formula: see text] if and only if [Formula: see text] is projective. Also, we provide some other criteria for [Formula: see text] to be projective by using some special cotorsion theories.
Sparse regularization with the ℓ0 norm
Authors: Xu Yuesheng
Published: June 2022

We consider a minimization problem whose objective function is the sum of a fidelity term, not necessarily convex, and a regularization term defined by a positive regularization parameter [Formula: see text] multiple of the [Formula: see text] norm composed with a linear transform. This problem has wide applications in compressed sensing, sparse machine learning and image reconstruction. The goal of this paper is to understand what choices of the regularization parameter can dictate the level of sparsity under the transform for a global minimizer of the resulting regularized objective function. This is a critical issue but it has been left unaddressed. We address it from a geometric viewpoint with which the sparsity partition of the image space of the transform is introduced. Choices of the regularization parameter are specified to ensure that a global minimizer of the corresponding regularized objective function achieves a prescribed level of sparsity under the transform. Results are obtained for the spacial sparsity case in which the transform is the identity map, a case that covers several applications of practical importance, including machine learning, image/signal processing and medical image reconstruction.