bluuebunny/crossref_metadata_2025 huggingface dataset:
Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity
Authors: Chakraborty Saborni , Gonzalez Joseph C. , Sievers Benjamin L. , Mallajosyula Vamsee , Chakraborty Srijoni , Dubey Megha , Ashraf Usama , Cheng Bowie Yik-Ling , Kathale Nimish , Tran Kim Quyen Thi , Scallan Courtney , Sinnott Aanika , Cassidy Arianna , Chen Steven T. , Gelbart Terri , Gao Fei , Golan Yarden , Ji Xuhuai , Kim-Schulze Seunghee , Prahl Mary , Gaw Stephanie L. , Gnjatic Sacha , Marron Thomas U. , Merad Miriam , Arunachalam Prabhu S. , Boyd Scott D. , Davis Mark M. , Holubar Marisa , Khosla Chaitan , Maecker Holden T. , Maldonado Yvonne , Mellins Elizabeth D. , Nadeau Kari C. , Pulendran Bali , Singh Upinder , Subramanian Aruna , Utz Paul J. , Sherwood Robert , Zhang Sheng , Jagannathan Prasanna , Tan Gene S. , Wang Taia T.
Published: January 2022

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG–Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.
Molecular Characterization of Mycobacterium ulcerans DNA Gyrase and Identification of Mutations Reducing Susceptibility to Quinolones
In Vitro
Authors: Kim Hyun , Mori Shigetarou , Kenri Tsuyoshi , Suzuki Yasuhiko
Published: January 2022

Buruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused by
Mycobacterium ulcerans
. Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase.
Factors Associated with Breakthrough Fungemia Caused by
Candida
,
Trichosporon
, or Fusarium Species in Patients with Hematological Disorders
Authors: Kimura Muneyoshi , Asano-Mori Yuki , Sakoh Takashi , Abe Masahiro , Ueno Keigo , Hoshino Yasutaka , Nakamura Shigeki , Umeyama Takashi , Yamagoe Satoshi , Miyazaki Yoshitsugu , Baba Masaru , Okada Chikako , Ogura Sho , Mitsuki Takashi , Yamaguchi Kyosuke , Yuasa Mitsuhiro , Kaji Daisuke , Kageyama Kosei , Nishida Aya , Taya Yuki , Ishiwata Kazuya , Takagi Shinsuke , Yamamoto Hisashi , Yamamoto Go , Uchida Naoyuki , Wake Atsushi , Taniguchi Shuichi , Araoka Hideki
Published: January 2022

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan.
Simulated Intravenous versus Inhaled Tobramycin with or without Intravenous Ceftazidime Evaluated against Hypermutable Pseudomonas aeruginosa via a Dynamic Biofilm Model and Mechanism-Based Modeling
Authors: Bilal Hajira , Tait Jessica R. , Lang Yinzhi , Zhou Jieqiang , Bergen Phillip J. , Peleg Anton Y. , Bulitta Jürgen B. , Oliver Antonio , Nation Roger L. , Landersdorfer Cornelia B.
Published: January 2022

Acute exacerbations of chronic respiratory infections in patients with cystic fibrosis are highly challenging due to hypermutable
Pseudomonas aeruginosa
biofilm formation and resistance emergence. We aimed to systematically evaluate the effects of intravenous versus inhaled tobramycin (TOB) with and without intravenous ceftazidime (CAZ).
Direct Inhibition of RetS Synthesis by RsmA Contributes to Homeostasis of the
Pseudomonas aeruginosa
Gac/Rsm Signaling System
Authors: Corley Jodi M. , Intile Peter , Yahr Timothy L.
Published: January 2022

The
Pseudomonas aeruginosa
Gac/Rsm system controls ∼500 genes and governs a critical lifestyle switch by inversely regulating factors that favor acute or chronic colonization. Control of gene expression by the Gac/Rsm system is mediated through RsmA and RsmF, small RNA-binding proteins that interact with target mRNAs to inhibit or promote protein synthesis and/or mRNA stability.
Expression of the DeaD RNA Helicase Is Regulated at Multiple Levels through Its Long mRNA 5′ Untranslated Region
Authors: Ojha Sandeep , Jain Chaitanya
Published: January 2022

The expression of genes is frequently regulated by determinants with the 5′ UTR. Although many different regulatory mechanisms that operate via the 5′ UTR have been described, the functional relevance of genes with long UTRs is less clear.
A Tool to Advance Inclusive Teaching Efforts: The “Who’s in Class?” Form
Authors: Addy Tracie Marcella , Mitchell Khadijah A. , Dube Derek
Published: January 2022

We developed the "Who's in Class?" form with the major goals of increasing instructors': (1) awareness of their learners' diverse attributes and identities, and (2) implementation of inclusive teaching practices.
Synthetic Control of Metabolic States in Pseudomonas putida by Tuning Polyhydroxyalkanoate Cycle
Authors: Manoli Maria-Tsampika , Nogales Juan , Prieto Auxiliadora
Published: January 2022

Despite large research efforts devoted to understanding the flexible metabolism of
Pseudomonas
beyond the role of key regulatory players, the metabolic basis powering the dynamic control of its biological fitness under disturbance conditions remains largely unknown. Among other metabolic hubs, the so-called PHA cycle, involving simultaneous synthesis and degradation of PHAs, is emerging as a pivotal metabolic trait powering metabolic robustness and resilience in this bacterial group.
lon
Deletion Impairs Persister Cell Resuscitation in Escherichia coli
Authors: Mohiuddin Sayed Golam , Massahi Aslan , Orman Mehmet A.
Published: January 2022

The ATP-dependent Lon protease is one of the most studied bacterial proteases. Although deletion of lon has been frequently shown to reduce fluoroquinolone persistence, the proposed mechanisms underlying this phenomenon are highly controversial.
Dual Effect: High NADH Levels Contribute to Efflux-Mediated Antibiotic Resistance but Drive Lethality Mediated by Reactive Oxygen Species
Authors: Arce-Rodríguez Alejandro , Pankratz Debbie , Preusse Matthias , Nikel Pablo I. , Häussler Susanne
Published: January 2022

The emergence of antibiotic resistance has become one of the major threats to public health. A better understanding of antimicrobial killing mechanisms promises to uncover new ways to resensitize bacteria to commonly used antibiotics.
A Filamentous Bacteriophage Protein Inhibits Type IV Pili To Prevent Superinfection of Pseudomonas aeruginosa
Authors: Schmidt Amelia K. , Fitzpatrick Alexa D. , Schwartzkopf Caleb M. , Faith Dominick R. , Jennings Laura K. , Coluccio Alison , Hunt Devin J. , Michaels Lia A. , Hargil Aviv , Chen Qingquan , Bollyky Paul L. , Dorward David W. , Wachter Jenny , Rosa Patricia A. , Maxwell Karen L. , Secor Patrick R.
Published: January 2022

Pf bacteriophage (phage) are filamentous viruses that infect
Pseudomonas aeruginosa
and enhance its virulence potential. Pf virions can lyse and kill
P. aeruginosa
through superinfection, which occurs when an already infected cell is infected by the same or similar phage.
A Well-Conserved Archaeal B-Family Polymerase Functions as an Extender in Translesion Synthesis
Authors: Feng Xu , Zhang Baochang , Gao Zhe , Xu Ruyi , Liu Xiaotong , Ishino Sonoko , Feng Mingxia , Shen Yulong , Ishino Yoshizumi , She Qunxin
Published: January 2022

In this work, we report that
Sulfolobus islandicus
Dpo2, a B-family DNA polymerase once predicted to be an inactive form, is a bona fide DNA polymerase functioning in translesion synthesis.
S. islandicus
Dpo2 is a member of a large group of B-family DNA polymerases (PolB2) that are present in many archaea and some bacteria, and they carry variations in well-conserved amino acids in the functional domains responsible for polymerization and proofreading. However, we found that this prokaryotic B-family DNA polymerase not only replicates undamaged DNA with high fidelity but also extends mismatch and DNA lesion-containing substrates with high efficiencies.
Human Papillomavirus Type 16 Circular RNA Is Barely Detectable for the Claimed Biological Activity
Authors: Yu Lulu , Zheng Zhi-Ming
Published: January 2022

RNA back-splicing is a rare splicing event accounting for <1% of canonical RNA splicing and, thus, is thought to have little or no biological significance. Recently, circular RNAs (circRNAs) from RNA back-splicing have been found widely in cells and tissues and may have a role in modulating RNA transcription, splicing, and interference and antiviral innate immunity.
Comparative Genomics of Bacteroides fragilis Group Isolates Reveals Species-Dependent Resistance Mechanisms and Validates Clinical Tools for Resistance Prediction
Authors: Wallace Miranda J. , Jean Sophonie , Wallace Meghan A. , Burnham Carey-Ann D. , Dantas Gautam
Published: January 2022

Anaerobic infections present unique challenges in terms of detecting and identifying the etiologic agent and selecting the optimal antimicrobial therapy. Antimicrobial resistance is increasing in anaerobic pathogens, and it is critical to understand the prevalence and mechanisms of resistance to commonly prescribed antimicrobial therapies.
Enabling QTY Server for Designing Water-Soluble α-Helical Transmembrane Proteins
Authors: Tao Fei , Tang Hongzhi , Zhang Shuguang , Li Mengke , Xu Ping
Published: January 2022

Water-soluble expression and purification are of considerable importance for protein identification and characterization. However, there has been a lack of an effective method for water-soluble expression of membrane proteins, which has severely hampered their studies.
Pseudomonas aeruginosa C-Terminal Processing Protease CtpA Assembles into a Hexameric Structure That Requires Activation by a Spiral-Shaped Lipoprotein-Binding Partner
Authors: Hsu Hao-Chi , Wang Michelle , Kovach Amanda , Darwin Andrew J. , Li Huilin
Published: January 2022

Carboxyl-terminal processing proteases (CTPs) are found in all three domains of life. In bacteria, some CTPs have been associated with virulence, raising the possibility that they could be therapeutic targets.
Fine-Scale Reconstruction of the Evolution of FII-33 Multidrug Resistance Plasmids Enables High-Resolution Genomic Surveillance
Authors: Hu Ya , Moran Robert A. , Blackwell Grace A. , McNally Alan , Zong Zhiyong
Published: January 2022

Effective genomic surveillance of antibiotic-resistant bacterial pathogens must consider plasmids, which are frequently implicated in the accumulation and transfer of resistance genes between bacterial strains or species. However, the evolution of plasmids is complex, and simple typing or comparison tools cannot accurately determine whether plasmids belong to the same sublineages.
Elevational Constraints on the Composition and Genomic Attributes of Microbial Communities in Antarctic Soils
Authors: Dragone Nicholas B. , Henley Jessica B. , Holland-Moritz Hannah , Diaz Melisa , Hogg Ian D. , Lyons W. Berry , Wall Diana H. , Adams Byron J. , Fierer Noah
Published: January 2022

Antarctic soils represent an ideal system to study how environmental properties shape the taxonomic and functional diversity of microbial communities given the relatively low diversity of Antarctic soil microbial communities and the pronounced environmental gradients that occur across soils located in reasonable proximity to one another. Moreover, the challenging environmental conditions typical of most Antarctic soils present an opportunity to investigate the traits that allow soil microbes to persist in some of the most inhospitable habitats on Earth.
Supplemental Material: Exhumation of plutons controlled by boundary faults: Insights from the kinematics, microfabric, and geochronology of the Taibai shear zone, Qinling Orogen, China
Authors: Cheng Chao , Sun Shengsi , al. et
Published: January 2022

Table S1: Zircon LA-ICP-MS U-Pb data for samples 18JM01A, 18JM04, 18JM05 and 18JM15 from the Taibai Ductile shear zone.
Prescribing practices for presumptive TB among private general practitioners in South Africa: a cross-sectional, standardised patient study
Authors: Salomon Angela , Boffa Jody , Moyo Sizulu , Chikovore Jeremiah , Sulis Giorgia , Daniels Benjamin , Kwan Ada , Mkhombo Tsatsawani , Wu Sarah , Pai Madhukar , Daftary Amrita
Published: January 2022

Introduction

Medicine prescribing practices are integral to quality of care for leading infectious diseases such as tuberculosis (TB). We describe prescribing practices in South Africa’s private health sector, where an estimated third of people with TB symptoms first seek care.

Methods

Sixteen standardised patients (SPs) presented one of three cases during unannounced visits to private general practitioners (GPs) in Durban and Cape Town: TB symptoms, HIV-positive; TB symptoms, a positive molecular test for TB, HIV-negative; and TB symptoms, history of incomplete TB treatment, HIV-positive. Prescribing practices were recorded in standardised exit interviews and analysed based on their potential to contribute to negative outcomes, including increased healthcare expenditures, antibiotic overuse or misuse, and TB diagnostic delay. Factors associated with antibiotic use were assessed using Poisson regression with a robust variance estimator.

Results

Between August 2018 and July 2019, 511 SP visits were completed with 212 GPs. In 88.5% (95% CI 85.2% to 91.1%) of visits, at least one medicine (median 3) was dispensed or prescribed and most (93%) were directly dispensed. Antibiotics, which can contribute to TB diagnostic delay, were the most common medicine (76.5%, 95% CI 71.7% to 80.7% of all visits). A majority (86.1%, 95% CI 82.9% to 88.5%) belonged to the WHO Access group; fluoroquinolones made up 8.8% (95% CI 6.3% to 12.3%). Factors associated with antibiotic use included if the SP was asked to follow-up if symptoms persisted (RR 1.14, 95% CI 1.04 to 1.25) and if the SP presented as HIV-positive (RR 1.11, 95% CI 1.01 to 1.23). An injection was offered in 31.9% (95% CI 27.0% to 37.2%) of visits; 92% were unexplained. Most (61.8%, 95% CI 60.2% to 63.3%) medicines were not listed on the South African Primary Healthcare Essential Medicines List.

Conclusion

Prescribing practices among private GPs for persons presenting with TB-like symptoms in South Africa raise concern about inappropriate antimicrobial use, private healthcare costs and TB diagnostic delay.
Transforming the once-a-day pill for HIV prevention from medicine to empowering self-care using human-centred design in Zimbabwe
Authors: Harris Emily Lark , Shelley Katharine D , Sisimayi Thenjiwe , Wandie Catherine , Bruns Cal
Published: January 2022

Objective

For adolescent girls and young women (AGYW) in sub-Saharan Africa, oral tenofovir‐based pre‐exposure prophylaxis (commonly referred to as PrEP) provides a user-controlled HIV prevention method, critical to addressing their HIV risk and unmet prevention needs. Addressing the gap between clinical and real-world PrEP efficacy requires new approaches, such as ‘V’. ‘V’ reframes PrEP from medicine to self-care that is as easy to use as a young women’s favourite fashion or beauty brand. This article describes how human-centred design (HCD) was used to adapt the ‘V’ brand and service delivery strategy for implementation in Zimbabwe from its development via formative research in South Africa.

Methods

Following literature review, stakeholder analysis and landscaping, the ‘V’ brand and service delivery strategy were assessed through participatory immersion sessions with 152 participants in four Zimbabwe districts. Insights were synthesised across learning questions: What do AGYW and health workers think about ‘V’?; Which of the ‘V’ materials are most acceptable and relevant for Zimbabwe?; What adaptations are necessary for the selected ‘V’ materials for Zimbabwe?; and How should the selected ‘V’ assets be integrated?

Results

The ‘V’ innovative design principles—delightfully bold branding, a discreet starter kit and user-friendly materials that put young women in control of educating others—remained resonant. Feasible modifications were identified to adapt the ‘V’ brand and service delivery strategy to suit the local context.

Conclusion

‘V’ delivers a ‘delightfully discreet’ approach that puts AGYW in charge of preventing HIV. The resonance of the core ‘V’ design concepts demonstrates how HCD can be applied to reframe PrEP as a product category (ie, from a stigmatising medicine to empowering self-care).
Comparison of safety and usability between peristaltic and pneumatic large-volume intravenous smart pumps during actual clinical use
Authors: Penoyer Daleen , Giuliano Karen , Middleton Aurea
Published: January 2022

Objective

To describe and compare safety and usability between a peristaltic large-volume intravenous smart pump (IVSP) and a novel pneumatic large-volume IVSP during clinical use.

Methods

A prospective, comparative study was conducted in a large, tertiary hospital in the southeastern USA. Safety and usability were measured by observation during medication administration (medication administration error, interruptions, programming time), dose error reduction system (DERS) compliance, end-user surveys and compliance with manufacturer setup requirements. Study implementation began on a small pilot unit for 1 month, followed by data collection on the study unit over 2 months.

Results

For the observed medication administrations (N=158): 79 peristaltic (36 primary; 43 secondary) and 79 pneumatic (42 primary; 37 secondary), use of the peristaltic IVSP was associated with significantly (p<0.05) higher medication administration errors and programming time (11.9 s) and a significantly higher number of interruptions during programming.

DERS compliance was significantly less (p<0.001) with the peristaltic (75.9%) as compared with the pneumatic IVSP (99.8%). Programming workload (National Aeronautics and Space Administration Task Load Index) was significantly (p=0.004) higher with peristaltic versus pneumatic IVSP, and the usability (System Usability Scale) was significantly (p=0.007) lower with peristaltic versus pneumatic IVSP. There was a 0% compliance with peristaltic secondary setup requirements in 43 observed infusions.

Conclusions

Though nurses had a high level of experience with the peristaltic IVSP, results of this study support that the pneumatic IVSP was easier to use and associated with fewer errors and deviations from safe practices as compared with the peristaltic IVSP.
Efficacy of mirror therapy and virtual reality therapy in alleviating phantom limb pain: a meta-analysis and systematic review
Authors: Rajendram Christopher , Ken-Dror G , Han T , Sharma P
Published: January 2022

Introduction

Amputations result from trauma, war, conflict, vascular diseases and cancer. Phantom limb pain (PLP) is a potentially debilitating form of chronic pain affecting around 100 million amputees across the world. Mirror therapy and virtual reality (VR) are two commonly used treatments, and we evaluated their respective success rates.

Methods

A meta-analysis and systematic review was undertaken to investigate mirror therapy and VR in their ability to reduce pain levels. A mean difference (MD) model to compare group pain levels pretreatment and post-treatment via aggregating these results from numerous similar studies was employed. Meta-analysis was conducted using RevMan (V.5.4) and expressed in MD for visual analogue scale (VAS) score.

Results

A total of 15 studies met our search criteria; they consisted of eight mirror therapy with 214 participants and seven VR including 86 participants, totalling 300 participants. Mean age ranged from 36 to 63 years, 77% male, of which 61% were lower body amputees. Both led to a VAS reduction (mirror therapy mean reduction VAS score was 2.54, 95% CI 1.42 to 3.66; p<0.001; VR 2.24, 95% CI 1.28 to 3.20; p<0.001). There was no statistically significant difference in pain alleviation between mirror therapy and VR (p=0.69).

Conclusions

Mirror therapy and VR are both equally efficacious in alleviating PLP, but neither is more effective than the other. However, due to small sample size and limited number of studies, factors such as gender, cause of amputation, site of limb loss or length of time from amputation, which may influence treatment success, could not be explored.
Impact of full personal protective equipment on alertness of healthcare workers: a prospective study
Authors: Wells Helena Jane , Raithatha Meera , Elhag Sabba , Turner James , Osuri Pranav , Kannan Santhana
Published: January 2022

The COVID-19 pandemic has resulted in healthcare workers (HCWs) having to wear full personal protective equipment (FPPE) even for routine patient care. When worn for prolonged periods, FPPE has the potential to adversely affect the ability of HCW to carry out their tasks. This study aimed to assess the impact of FPPE on the alertness levels of HCWs in the intensive care unit.

Fifty HCWs were tested using psychomotor vigilance test (PVT) and serial sevens test (SST) on two occasions during their shift—once without FPPE and once after they had been in FPPE for at least 2 hours. The median time in FPPE was 2.5 hours. FPPE induced a significant increase in the average reaction time and the number of false responses in PVT. Subjects took longer to complete SST in FPPE compared with without it.

This study demonstrates that being in FPPE for as little as 2.5 hours can adversely affect HCW alertness. The findings of this study are relevant in terms of workforce environment considerations as the use of FPPE in certain settings is likely to become a regular feature.
Steampunk Machine Learning
Authors: Kelly Terence
Published: January 2022

Fitting models to data is all the rage nowadays but has long been an essential skill of engineers. Veterans know that real-world systems foil textbook techniques by interleaving routine operating conditions with bouts of overload and failure; to be practical, a method must model the former without distortion by the latter. Surprisingly effective aid comes from an unlikely quarter: a simple and intuitive model-fitting approach that predates the Babbage Engine. The foundation of industrial-strength decision support and anomaly detection for production datacenters, this approach yields accurate yet intelligible models without hand-holding or fuss. It is easy to practice with modern analytics software and is widely applicable to computing systems and beyond.
Clonal Hematopoiesis: Confluence of Malignant and Nonmalignant Diseases
Authors: Lin Amy E. , Rauch Philipp J. , Jaiswal Siddhartha , Ebert Benjamin L.
Published: January 2022

Clonal hematopoiesis of indeterminate potential (CHIP) is a state in which somatic mutations in hematopoietic stem cells lead to clonal expansion of blood cells in individuals without hematologic malignancy. The mutated genes, including TET2, DNMT3A, ASXL1, TP53, JAK2, and SF3B1, are also recurrently mutated in myeloid malignancies. Individuals with CHIP have an increased risk of developing a hematologic cancer. Moreover, individuals with CHIP have an elevated risk of all-cause mortality that is significantly attributable to cardiovascular disease, independent of traditional risk factors. The mechanism for this increased risk is likely linked to increased inflammation driven by mutated macrophages, in part through inflammasome activation. This has broadened our understanding of how chronic diseases are influenced by CHIP and of the mechanistic role of inflammation in these disorders.
Oncohistones: Hijacking the Histone Code
Authors: Sahu Varun , Lu Chao
Published: January 2022

Chromatin dysfunction has been implicated in a growing number of cancers especially in children and young adults. In addition to chromatin-modifying and -remodeling enzymes, mutations in histone genes are linked to human cancers. Since the first reports of hotspot missense mutations affecting key residues at the histone H3 tail, studies have revealed how these so-called oncohistones dominantly (H3K27M and H3K36M) or locally (H3.3G34R/W) inhibit corresponding histone methyltransferases and misregulate epigenome and transcriptome to promote tumorigenesis. More recently, widespread mutations in all four core histones are identified in diverse cancer types. Furthermore, an oncohistone-like protein EZHIP has been implicated in driving childhood ependymomas through a mechanism highly reminiscent of H3K27M mutation. Here we review recent progress in understanding the biochemical, molecular, and biological mechanisms underlying the canonical and novel histone mutations. Importantly, these mechanistic insights have identified therapeutic opportunities for oncohistone-driven tumors.
Cancer Genomic Rearrangements and Copy Number Alterations from Errors in Cell Division
Authors: Zhang Cheng-Zhong , Pellman David
Published: January 2022

Analysis of cancer genomes has shown that a large fraction of chromosomal changes originate from catastrophic events including whole-genome duplication, chromothripsis, breakage-fusion-bridge cycles, and chromoplexy. Through sophisticated computational analysis of cancer genomes and experimental recapitulation of these catastrophic alterations, we have gained significant insights into the origin, mechanism, and evolutionary dynamics of cancer genome complexity. In this review, we summarize this progress and survey the major unresolved questions, with particular emphasis on the relative contributions of chromosome fragmentation and DNA replication errors to complex chromosomal alterations.
Caught in a Web: Emerging Roles of Neutrophil Extracellular Traps in Cancer
Authors: He Xue-Yan , Ng David , Egeblad Mikala
Published: January 2022

Neutrophil extracellular traps (NETs) are meshes of DNA decorated with granular proteins that are extruded from neutrophils during immune responses to pathogens. However, excessive NET formation is negatively associated with many diseases, including cancer. NETs contain, for example, proteases, danger-associated molecular patterns (DAMPs), and DNA. These components can act directly on the cancer cells but also affect the surrounding microenvironment, including altering the extracellular matrix and the immune response to tumors. Here, we discuss the emerging roles of NETs in cancer progression, from their ability to promote primary tumor growth and immune escape to their prometastatic effects. The potential clinical implication of targeting NETs as novel therapeutic strategies in cancer is also discussed.
Editors’ Choice—Review—John Goodenough’s Impact on Electrochemistry in Oxford’s Inorganic Chemistry Laboratory
Authors: Hamnett Andrew
Published: January 2022

This paper covers the period following the appointment of John Goodenough to the Chair of Inorganic Chemistry at Oxford University and the development of the electrochemistry group in the Inorganic Chemistry Laboratory under his leadership. The paper details the studies he initiated into semiconductor electrochemistry and photoelectrochemistry, electrocatalysis, fuel-cell development and battery research, and the way in which these studies complemented each other. A brief account of some of the later developments in electrochemical research at Oxford is given, showing how these developments grew out of Goodenough’s earlier ideas and ambitions.
From the Editor: Going Global
Authors: Rajeshwar Krishnan
Published: January 2022

The information revolution of the nineties is creating strong links among nations, people, and companies, even as the embrace of free markets around the globe is fueling enormous increases in international commerce. Not to be left behind, the science and technology enterprise is forging global links also.
The Impact of Ionic Species on Wet Leakage Current of Conductive Polymer Coated Tantalum Dielectric
Authors: Ning Liancai , Liu Shuang , Liu Yong , Zhong Zhiyong
Published: January 2022

The wet leakage current of anodized anodes and conductive polymer coated anodes are measured in various electrolytes. The anodized anodes are robust to Ag+, Fe2+, and Fe3+. However, conductive polymer coated anodes are highly sensitive to Ag+ and Fe2+, which permanently affected wet leakage current in I-time measurement. I–V curve is plotted in order to understand the conduction mechanism. For 50 V conductive polymer coated anodes, Schottky Effect and Tunneling are the mechanisms between 12 V to 50 V and above 50 V, respectively.
Quasi In Situ XPS on a SiOxFy Layer Deposited on Silicon by a Cryogenic Process
Authors: Antoun G. , Girard A. , Tillocher T. , Lefaucheux P. , Faguet J. , Maekawa K. , Cardinaud C. , Dussart R.
Published: January 2022

A silicon oxyfluoride layer was deposited on a-Si samples using SiF4/O2 plasma at different temperatures between −100°C and −40 °C. In situ X-ray photoelectron spectroscopy measurements were then performed to characterize the deposited layer. The sample was then brought back to room temperature and analyzed again. It has been shown that a temperature below −65 °C is needed to significantly enhance the physisorption of SiFx species. Hence, in this condition, a F-rich oxyfluoride layer, stable at low temperature only, is physisorbed. Above this threshold temperature, the native silicon oxide layer is fluorinated and the proportion of O in the deposited layer is higher and remains stable even when the sample is brought back to room temperature.
(Invited) Surface Engineering of Metal Oxide Photoanodes for Photoelectrochemical Solar Water Splitting
Authors: Park Jong Hyeok
Published: January 2022

The development of new types of energy generation devices is promoted by increasing public awareness that the Earth's oil reserves could run out during this century. As the energy needs of the planet are likely to double within the next 50 years, the stage is set for a major energy shortage, unless renewable energy can cover the substantial deficit left by fossil fuels. Photoelectrochemical (PEC) solar water splitting has become a central research theme for more than four decades, still, their efficiencies remain low. Despite extensive efforts devoted to modifying photoelectrodes through various bandgap and catalysis engineering, the efficient methodologies for charge transfer at electrode/electrolyte interface remain underdeveloped. In this seminar, I will introduce various unique methods to increase light harvesting efficiency to generate hydrogen from solar light by applying disordered engineering to metal oxide materials. Especially, high efficiency TiO2, WO3, and BiVO4 photoanodes with the modification and charge transfer across the electrode/electrolyte interface will be presented.
Associations of Genetic Polymorphisms of mTOR rs2295080 T/G and rs1883965 G/A with Susceptibility of Urinary System Cancers
Authors: Min Zhichao , Mi Yuanyuan , Lv Zhiwei , Sun Yangyang , Tang Bowen , Wu Hao , Zhang Ze , Pan Hong , Zhang Yujuan , Lu Chao , Zuo Li , Zhang Lifeng
Published: January 2022

Background. Genetic polymorphisms in mammalian target of rapamycin (mTOR) signaling axis can influence the susceptibility of cancer. The relationship between mTOR gene variants rs2295080 T/G and rs1883965 G/A and the risk of cancer remains inconsistent. The present study is aimed at comprehensively investigating the association between mTOR polymorphisms and susceptibility to cancer. Methods. We conducted a comprehensive assessment using odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools to evaluate the effect of mTOR variations. Immunohistochemical staining (IHS) and GSEA analysis were used to investigate the expression of mTOR in urinary system cancer. Results. The pooled analysis involved 22 case-control studies including 14,747 cancer patients and 16,399 controls. The rs2295080 T/G polymorphism was associated with the risk of cancer (G-allele versus T-allele,

OR
=
0.89

,

95
%
CI
=
0.80

–0.98,

P
=
0.023

; GT versus TT,

OR
=
0.88

,

95
%
CI
=
0.81

–0.96,

P
=
0.004

; GG+GT versus TT,

OR
=
0.87

,

95
%
CI
=
0.78

–0.96,

P
=
0.008

), especially for cancers of the urinary system, breast, and blood. Variation rs1883965 G/A was associated with cancer susceptibility, especially for digestive cancer. IHS analysis showed that mTOR was upregulated in prostate and bladder cancer. GSEA revealed that the insulin signaling pathway, lysine degradation pathway, and mTOR signaling pathway were enriched in the high mTOR expression group. Conclusions. The mTOR rs2295080 T/G polymorphism may be associated with susceptibility of urinary cancer. The expression of mTOR is positively correlated with tumor malignancy in prostate cancer.
Multiobjective Optimal Dispatching of Smart Grid Based on PSO and SVM
Authors: Bao Man , Zhang Hongqi , Wu Hao , Zhang Chao , Wang Zixu , Zhang Xiaohui
Published: January 2022

The optimization of microgrid is an important part of smart grid. The global energy consumption is seriously greater than the energy it has, and the environmental pollution brought by it should not be underestimated. If we want to reduce their impact, introducing the optimization of microgrid is a good solution. Short-term load forecasting is a very important prerequisite for microgrid optimization, which lays a solid foundation for the realization of the development goal of environmental protection and the improvement of the economic benefits of microgrid. In this paper, a Multi-PSO-SVM forecasting model is proposed to forecast the actual load. By simulating four prediction models with three different samples, we can see that the average predicted value and actual load value of Multi-PSO-SVM algorithm in the three different samples are almost less than 10 MV. Compared with the other three algorithms, Multi-PSO-SVM is superior in accurately predicting the load value at each time point, which provides important conditions for the success of microgrid optimization.
Differences of Circulating CD25hi Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals
Authors: Zhang Jie , Fu Qi , He Yunqiang , Lv Hui , Qian Yu , Zhang YuYue , Chen Heng , Xu Xinyu , Yang Tao , Xu Kuanfeng
Published: January 2022

Circulating CD25hi B cells, a subset of regulatory B cells in humans, are closely related to inflammation and autoimmune diseases. This study is aimed at investigating the alternation of CD25hi Bregs and their correlation with CD4 effector and regulatory T cells in T1D individuals. We included 68 autoantibody-positive T1D and 68 age-matched healthy individuals with peripheral blood mononuclear cells (PBMCs) and assessed them with CD25hi Bregs and CD4 effector or regulatory T cells by flow cytometry. Here, we demonstrate that the frequency of CD25hi Bregs was significantly decreased in T1D subjects (

P
=
0.0016

), but they were not affected by disease status (age at T1D diagnosis or duration) or T1D risk loci (rs2104286 or rs12251307) in IL2RA (all

P
>
0.05

). Moreover, higher IgD (

P
=
0.043

) and lower CD27 (

P
=
0.0003

) expression was observed in CD25hi Bregs of T1D individuals, but not the expression of IgM, CD24, or CD38 (all

P
>
0.05

). Although there was no correlation between CD25hi Bregs and CD4 effector T cell subsets in either T1D or healthy individuals (all

P
>
0.05

), we found a positive correlation between CD25hi Bregs and CD4 Tregs in healthy controls (Sp.

r
=
0.3544

,

P
=
0.0249

), which disappeared in T1D subjects (Sp.

r
=
0.137

,

P
=
0.401

). In conclusion, our results suggest that decreased CD25hi Bregs and alternation of their phenotypes are features of T1D regardless of disease duration and T1D genetic risk loci, and an impaired balance between CD25hi Bregs and CD4 Tregs might contribute to the pathogenesis of T1D.
Usefulness of Macroscopic On-Site Evaluation Using a Stereomicroscope during EUS-FNB for Diagnosing Solid Pancreatic Lesions
Authors: Ishikawa Takuya , Ohno Eizaburo , Mizutani Yasuyuki , Iida Tadashi , Uetsuki Kota , Yashika Jun , Yamada Kenta , Gibo Noriaki , Aoki Toshinori , Kataoka Kunio , Mori Hiroshi , Takada Yoshihisa , Takahashi Hidekazu , Aoi Hironori , Kato Katsuyuki , Yamamura Takeshi , Kakushima Naomi , Furukawa Kazuhiro , Nakamura Masanao , Hirooka Yoshiki , Kawashima Hiroki
Published: January 2022

Background/Aims. The usefulness of macroscopic on-site evaluation (MOSE) during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been reported, but a specific method for MOSE has not been established. We aimed to investigate the usefulness of MOSE using a stereomicroscope (S-MOSE) for the diagnosis of solid pancreatic lesions (SPLs). Methods. We reviewed a total of 60 consecutive patients who underwent both S-MOSE and rapid on-site cytopathological evaluation (ROSE) during EUS-FNB between July 2019 and October 2020, and the usefulness of S-MOSE in comparison with histology was evaluated. A 22-gauge Franseen needle was used to perform EUS-FNB in all patients, and only the specimens obtained by the first pass were evaluated. The final diagnosis was based on the surgical specimen or the clinical course consistent with the EUS-FNB results. Results. The final diagnoses of the 60 patients included 45 patients with pancreatic ductal adenocarcinoma, 6 with autoimmune pancreatitis, 4 with mass-forming pancreatitis, 1 with pancreatic metastasis, 2 with pancreatic neuroendocrine tumor, and 2 with intraductal papillary mucinous carcinoma. The histological diagnostic accuracy of the first pass of EUS-FNB was 83.3% (50/60). The agreement between the S-MOSE and the histological diagnosis was 90% (54/60). The positive predictive value of S-MOSE for histological diagnosis was 90.7%, which can be an indicator of when to stop the EUS-FNB procedure. There were no immediate or delayed adverse events reported after the FNB based on the chart and medical visit history review. Conclusion. In the EUS-FNB of SPLs, S-MOSE can be an alternative to ROSE for specimen evaluation and has the potential to shorten the procedure time.
Prognostic Nomogram and Therapeutic Option of Cancer-Specific Death in the Patients with Metachronous Second Primary Lung Cancer
Authors: Wang Jiahui , Chen Zhen , Xia Daokui , Song Xinyu , Hu Zhigang
Published: January 2022

With the increase of long-term primary lung cancer survivors, studies focused on metachronous second primary lung cancer (SPLC) have become very urgent. This study aimed to develop a prognostic nomogram and determine therapeutic options of cancer-specific death for patients with metachronous SPLC with and without the competing risk of other-specific death. Study population came from the SEER-18 database between 2006 and 2016. According to the clinical practice guideline of SPLC, the interval time of IPLC and metachronous SPLC was set to 4 years. We constructed nomograms with Lasso + Cox regression model and competing risk model to predict the prognosis and identify therapeutic options of metachronous SPLC patients with the assessment of model performance by the C-index, calibration plot, and decision curve analysis. In addition, two subgroup analyses stratified by histology and tumor size were used to better select therapeutic options for a certain population. 1300 patients with metachronous SPLC were incorporated in this study with 50.1% of the 5-year cumulative incidence in cancer-specific death. Compared with Lasso + Cox regression analysis, competing risk analysis harbored a higher C-index (0.811 vs. 0.76) and better net benefit in predicting cancer-specific death of metachronous SPLC. Two statistical analyses suggested that surgery alone was a preferentially therapeutic option of metachronous SPLC, whereas the effect of surgery + radiation in treating metachronous SPLC was similar to radiation alone. Subgroup analyses indicated that patients with metachronous SPLC were considered receiving different therapeutic options in different histology and tumor size but preferred to receive surgical treatment as the first choice. For primary lung cancer survivors, aggressive surgical treatment was the first-line selection of metachronous SPLC, followed by radiation alone, surgery + radiation, and no surgery + radiation.
Multi-GNSS Fast Precise Point Positioning with Multi-Frequency Uncombined Model and Cascading Ambiguity Resolution
Authors: Zhao Qing , Pan Shuguo , Gao Wang , Wu Bo
Published: January 2022

Conventional ambiguity resolution (AR) strategy of directly fixing all raw frequency ambiguities for uncombined precise point positioning (PPP) generally requires a long initial time to ensure fixing reliability. The rich signals from multi-frequency GNSS can provide new opportunities for rapid PPP AR. In this paper, based on a unified multi-frequency uncombined PPP model, the raw frequency ambiguities are linearly transformed to the between-satellite-single-differenced extra-wide-lane (EWL), wide-lane (WL), and narrow-lane (NL) ambiguities, and a cascading ambiguity resolution (CAR) method of fixing EWL/WL/NL ambiguities sequentially is proposed. Meanwhile, a partial ambiguity fixing (PAF) strategy with ambiguity subset adaptively selected based on the successively increased elevations is also adopted in each step to improve the fixing rate. Further, experiments with globally distributed stations are carried out to verify the algorithm. With the constraints of EWL/WL AR, the precision of NL ambiguity and its variance-covariance matrix can be effectively optimized, so the time to first fix (TTFF) is significantly shortened, and the ratio value is also improved to varying degrees. As for BDS-only solution, the average TTFF is shortened from 23.7 min to 10.9 min, with an improvement over 50%; for GPS/BDS, GPS/Galileo, and GPS/Galileo/BDS combined solutions, the TTFF is shortened from 14.3 min, 9.4 min, and 6.7 min to 8.1 min, 2.6 min, and 1.8 min, which are, respectively, shortened by 43.4%, 72.3%, and 73.1%. In general, the proposed CAR strategy can shorten the TTFF of multi-GNSS multi-frequency PPP to about 2 min. The performance of EWL/WL/NL ambiguity-fixed solutions is also analyzed. The NL solution is generally at centimeter-level accuracy over the entire period; however, limited by the atmosphere errors during the convergence stage, the EWL/WL solutions can only obtain decimeter-level accuracy, and the difference between them and NL solution gradually decreases with the continuous improvement of atmosphere accuracy.
Analysis on Deformation Failure and Structural Mechanical Characteristics of Multistage Loess Slope Supported by Frame Structure with Anchors
Authors: Yang Kui-bin , Zhu Yan-peng , Wu Lin-ping , Duan Xin-guo , Shi Duo-bang , Du Xiao-tao
Published: January 2022

Frame anchor supporting structure is widely accepted in the loess area, especially in the multistage slopes along the road. However, the development between theory and practice is not synchronous, and there exist experience and uncertainty in the design process to a great extent. In response to this problem, the multistage loess slope supported by frame structure with anchors is taken as the research object, and the model test is carried out with the help of the large‐scale geotechnical centrifuge under the condition of using prototype materials as much as possible. Then, according to the test data and phenomena, the structural stress and slope deformation concerned in the project are analyzed. The main differences in stress and deformation between the multistage loess slope supported by frame structure with anchors and other types of slopes are pointed out, and some targeted suggestions are given. The research results show that the frame anchor supporting structure and soil can always maintain coordinated deformation during centrifugal loading, and the failure process has certain toughness characteristics. The stress characteristics of the anchor rod and the sliding deformation range of the slope in the multistage loess slope supported by frame structure with anchors are different from the slope with structural surface and single‐stage slope. The length of the anchoring section cannot be completely determined based on the potential sliding surface in the design. It is reasonable to strictly control the end position of the anchoring section from the perspective of changing the position of the potential sliding surface. The results obtained can enrich and improve the stability theory of multistage loess slope and provide guidance for engineering practice.
VSHR: A Mathematical Model for the Prediction of Second-Wave COVID-19 Epidemics in Malaysia
Authors: Yu Xiang , Lu Lihua , Guo Jiangfan , Qin Haihuan , Ji Chunlei
Published: January 2022

Since December 2019, a novel coronavirus (COVID-19) has spread all over the world, causing unpredictable economic losses and public fear. Although vaccines against this virus have been developed and administered for months, many countries still suffer from secondary COVID-19 infections, including the United Kingdom, France, and Malaysia. Observations of COVID-19 infections in the United Kingdom and France and their governance measures showed a certain number of similarities. A further investigation of these countries’ COVID-19 transmission patterns suggested that when a turning point appeared, the values of their stringency indices per population density (PSI) were nearly proportional to their absolute infection rate (AIR). To justify our assumptions, we developed a mathematical model named VSHR to predict the COVID-19 turning point for Malaysia. VSHR was first trained on 30-day infection records prior to the United Kingdom, Germany, France, and Belgium’s known turning points. It was then transferred to Malaysian COVID-19 data to predict this nation’s turning point. Given the estimated AIR parameter values in 5 days, we were now able to locate the turning point’s appearance on June 2nd, 2021. VSHR offered two improvements: (1) gathered countries into groups based on their SI patterns and (2) generated a model to identify the turning point for a target country within 5 days with 90% CI. Our research on COVID-19’s turning point for a country is beneficial for governments and clinical systems against future COVID-19 infections.