bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspofungin-induced β(1,3)-glucan exposure in
Candida albicans
is driven by increased chitin levels
Authors: Wagner Andrew S. , Lumsdaine Stephen W. , Mangrum Mikayla M. , Reynolds Todd B. 
Published: June 2023

ABSTRACT

To successfully induce disease,
Candida albicans
must effectively evade the host immune system. One mechanism used by
C. albicans
to achieve this is to mask immunogenic β(1,3)-glucan epitopes within its cell wall under an outer layer of mannosylated glycoproteins. Consequently, induction of β(1,3)-glucan exposure (unmasking)
via
genetic or chemical manipulation increases fungal recognition by host immune cells
in vitro
and attenuates disease during systemic infection in mice. Treatment with the echinocandin caspofungin is one of the most potent drivers of β(1,3)-glucan exposure. Several reports using murine infection models suggest a role for the immune system, and specifically host β(1,3)-glucan receptors, in mediating the efficacy of echinocandin treatment
in vivo
. However, the mechanism by which caspofungin-induced unmasking occurs is not well understood. In this report, we show that foci of unmasking co-localize with areas of increased chitin within the yeast cell wall in response to caspofungin, and that inhibition of chitin synthesis
via
nikkomycin Z attenuates caspofungin-induced β(1,3)-glucan exposure. Furthermore, we find that both the calcineurin and Mkc1 mitogen-activated protein kinase pathways work synergistically to regulate β(1,3)-glucan exposure and chitin synthesis in response to drug treatment. When either of these pathways are interrupted, it results in a bimodal population of cells containing either high or low chitin content. Importantly, increased unmasking correlates with increased chitin content within these cells. Microscopy further indicates that caspofungin-induced unmasking correlates with actively growing cells. Collectively, our work presents a model in which chitin synthesis induces unmasking within the cell wall in response to caspofungin in growing cells.

IMPORTANCE

Systemic candidiasis has reported mortality rates ranging from 20% to 40%. The echinocandins, including caspofungin, are first-line antifungals used to treat systemic candidiasis. However, studies in mice have shown that echinocandin efficacy relies on both its cidal impacts on
Candida albicans
, as well as a functional immune system to successfully clear invading fungi. In addition to direct
C. albicans
killing, caspofungin increases exposure (unmasking) of immunogenic β(1,3)-glucan moieties. To evade immune detection, β(1,3)-glucan is normally masked within the
C. albicans
cell wall. Consequently, unmasked β(1,3)-glucan renders these cells more visible to the host immune system and attenuates disease progression. Therefore, discovery of how caspofungin-induced unmasking occurs is needed to elucidate how the drug facilitates host immune system-mediated clearance
in vivo
. We report a strong and consistent correlation between chitin deposition and unmasking in response to caspofungin and propose a model in which altered chitin synthesis drives increased unmasking during drug exposure.
Numerical Investigation of the Effect of Porous Wing Elements on the Properties of Supersonic Tip Vortices
Authors: Lutskii A. E. , Severin A. V. 
Published: June 2023

Abstract
The effect of a porous wingtip on tip vortex formation and properties in a supersonic flow is studied. It is established that a porous wingtip has a considerable effect on the vortex structure and parameters reducing its intensity.
The Holocene Explosive Eruption on Vetrovoi Isthmus (Iturup Island) as a Source of the Marker Tephra Layer of 2000 cal. yr BP in the Central Kuril Island Arc
Authors: Bergal-Kuvikas O. V. , Smirnov S. Z. , Agatova A. R. , Degterev A. V. , Razjigaeva N. G. , Pinegina T. K. , Portnyagin M. V. , Karmanov N. S. , Timina T. Yu. 
Published: June 2023

Abstract
Geochemical study of volcaniclastic material and radiocarbon dating of charred plant debris from Holocene deposits of the Guram site, which is located in vicinity of Vetrovoi Isthmus on Iturup Island, demonstrate that an explosive eruption (VEI 4-5) occurred there about 2000 years ago. The geochemical and age similarity with the tephra of marker layer CKr that was distinguished on Iturup, Urup, Simushir, Rasshua, and Matua islands of the Kuril Island Arc led to the conclusion that this eruption is possibly a source of this tephra. The data presented are proposed as a motivation for revision of the volcanic hazard on Iturup Island.
Instruments in general practice to identify and to measure (over)burden due to informal care for caring relatives: a scoping review protocol
Authors: Marx Yvonne , Bauer Alexander , Unverzagt Susanne , Stark Undine , Frese Thomas 
Published: June 2023

IntroductionFamily caregivers provide by far the largest share of long-term, unpaid care for their primarily elderly and chronically ill relatives or friends. This is associated with a higher risk of psychological and physical overload for the caregivers due to the persistently high time, financial and emotional burden.Recognising the effects of persistent burden on caring relatives at an early stage significantly contributes to the appropriate coordination of available resources and mediation of individual support to maintain a functional caring relationship without excessive demands. General practitioners are usually responsible for the early detection of burden arising from informal care and the coordination of adequate measures. The objective of this review is to give an overview of instruments to identify and measure (over)burden of caring relatives in German general practice and to describe their characteristics.Methods and analysisWe used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist in addition to the Joanna Briggs Institute Reviewer’s Manual to describe the aims and methods of the planned scoping reviews. This protocol has been registered with Open Science Framework (OSF),https://osf.io/9ce2k. Two reviewers will run the search to identify studies in four databases (PubMed, LIVIVO, the Cochrane Library and CINAHL) in June and July 2023. Abstracts, titles and full-text publications will be screened to extract data from each included study using a data extraction form. Additionally, an overview of all studies including main study characteristics and detailed information on identification instruments will be given to map the different instruments and tools and to clarify statements concerning their use and practicability in general practice.Ethics and disseminationEthical approval or consent to participate is not required, as data in this study consists of published studies and not individual data from human or animal participants. Dissemination will consist of publications, presentations and other knowledge translation activities.
Palliative care in the treatment of women with breast cancer: a scoping review protocol
Authors: Velasco Yanez Romel Jonathan , Carvalho Fernandes Ana Fátima , Miranda Mattos Samuel , Moreira Thereza Maria Magalhães , Moura Barbosa Castro Régia Christina , Corpes Erilaine de Freitas , Lopes-Júnior Luís Carlos 
Published: June 2023

IntroductionCurrently, breast cancer ranks first among female malignancies; hence, there are strong recommendations for the early inclusion of these patients in palliative care. Palliative care aims to alleviate symptoms improving the quality of life of dying patients, an essential component of breast cancer care. This study aimed to map and synthesise the available evidence on palliative care for women with breast cancer and to discuss the review results with stakeholders.MethodsA scoping review protocol is presented in this article, consisting of two phases. In the first phase, a scoping review study will be conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines and guided by the Joanna Briggs Institute Manual for Evidence Synthesis. Nine databases, an electronic repository, a trial register website, grey literature and additional sources will be searched. A focus group discussion with six stakeholders will occur in the second phase. The analysis will be performed through inductive and manifest content analysis using the IRaMuTeQ V.0.7 alpha software.Ethics and disseminationThe scoping review protocol did not require ethical approval. However, the study’s second phase has been approved by the institutional review board of Maternidade Escola Assis Chateaubriand/MEAC/UFC. The findings will be disseminated through professional networks, conference presentations and publications.
Outcomes and prognosis of non-small cell lung cancer patients who underwent curable surgery: a protocol for a real-world, retrospective, population-based and nationwide Chinese National Lung Cancer Cohort (CNLCC) study
Authors: Wang Xin , Liang Yicheng , Wang Yuanzhuo , Meng Xiangzhi , Zhou Boxuan , Xu Zhenyi , Wang Hui , Yang Wenjing , Li Ning , Gao Yushun , He Jie 
Published: June 2023

IntroductionSurgery is one of the main approaches for the comprehensive treatment of early and locally advanced non-small cell lung cancer (NSCLC). This study conducts a nationwide multicentre study to explore factors that could influence the outcomes of patients with I–IIIA NSCLC who underwent curable surgery in real-world scenarios.Methods and analysisAll patients diagnosed with NSCLC between January 2013 and December 2020 will be identified from 30 large public medical services centres in mainland China. The algorithm of natural language processing and artificial intelligence techniques were used to extract data from electronic health records of enrolled patients who fulfil the inclusion criteria. Six categories of parameters are collected and stored from the electronic records, then the parameters will be structured as a high-quality structured case report form. The code book will be compiled and each parameter will be classified and designated a code. In addition, the study retrieves the survival status and causes of death of patients from the Chinese Centre for Disease Control and Prevention. The primary endpoints are overall survival and the secondary endpoint is disease-free survival. Finally, an online platform is formed for data queries and the original records will be stored as secure electronic documents.Ethics and disseminationThe study has been approved by the Ethical Committee of the Chinese Academy of Medical Sciences. Study findings will be disseminated via presentations at conferences and publications in open-access journals. This study has been registered in the Chinese Trial Register (ChiCTR2100052773) on 11 May 2021,http://www.chictr.org.cn/showproj.aspx?proj=136659.Trial registration numberChiCTR2100052773.
Approach to hyperuniformity in a metallic glass-forming material exhibiting a fragile to strong glass transition
Authors: Zhang Hao , Wang Xinyi , Zhang Jiarui , Yu Hai-Bin , Douglas Jack F. 
Published: June 2023

AbstractWe investigate a metallic glass-forming (GF) material (Al90Sm10) exhibiting a fragile-strong (FS) glass-formation by molecular dynamics simulation to better understand this highly distinctive pattern of glass-formation in which many of the usual phenomenological relations describing relaxation times and diffusion of ordinary GF liquids no longer apply, and where instead genuine thermodynamic features are observed in response functions and little thermodynamic signature is exhibited at the glass transition temperature, Tg. Given the many unexpected similarities between the thermodynamics and dynamics of this metallic GF material with water, we first focus on the anomalous static scattering in this liquid, following recent studies on water, silicon and other FS GF liquids. We quantify the “hyperuniformity index” H of our liquid, which provides a quantitative measure of molecular “jamming”. To gain insight into the T-dependence and magnitude of H, we also estimate another more familiar measure of particle localization, the Debye–Waller parameter 〈u2〉 describing the mean-square particle displacement on a timescale on the order of the fast relaxation time, and we also calculate H and 〈u2〉 for heated crystalline Cu. This comparative analysis between H and 〈u2〉 for crystalline and metallic glass materials allows us to understand the critical value of H on the order of 10–3 as being analogous to the Lindemann criterion for both the melting of crystals and the “softening” of glasses. We further interpret the emergence of FS GF and liquid–liquid phase separation in this class of liquids to arise from a cooperative self-assembly process in the GF liquid.
Graphical abstract
Small and Medium-Scale Industries in Indonesia
Authors: Suhartono R.B. 
Published: June 2023

Until the late 1960s, when the issue of perceived massive and rising unemployment came to the fore, the promotion of small and medium-scale industries had not become a major concern of development policy. Since then, because of the employment generation potential of small and medium-scale industries, more and more governments in the developing countries have adopted policies and measures for the promotion of these industries. In any developing country, most manufacturing activities take place in small and medium industries and these account for an overwhelming proportion of the manufacturing establishments in the country. Available data do not suggest that the importance of small and medium industries declines as the levels of development rise. In fact, since the mid-1970s, small and medium industries may have made a comeback in the developed countries, due to, among other things, the shortening of the product life cycle and the need for flexible responses to changes in currency exchange rates, product markets and technological development. This article attempts to describe the experience of Indonesia in the promotion of small and medium industries for development. In doing so, however, it first briefly examines the general features of small and medium-scale industries and the problems they face.
The Role of Multilateral Lending Institutions in the Development Process
Authors: Krueger Anne O. 
Published: June 2023

The 1980s are a turning point for the multilateral lending institutions. The progress and differentiation of developing countries, international debt difficulties, and the unwillingness or inability of the United States to provide its historic leadership for these institutions have raised a series of important questions about their future role in the international economy. Their future contribution to the growth of developing countries will depend, in large part, on achieving a consensus as to their role in an altered international economic environment and then gaining adequate political support for them to carry out that role. Achieving an intellectual understanding of the issues raised in an altered environment will be an important step in resolving those questions and reaching a consensus. As a contribution toward that understanding, this article addresses that topic. It starts with an evaluation of the analytical underpinnings of the formation and early activities of the multilateral lending institutions and then briefly considers their evolution and contributions to the international economy in the years prior to the 1980s. Thereafter, it notes the changes in the international economy and in our understanding of the development process. Next, it addresses the issues that must be resolved for a clear mandate for multilateral lending institutions. Finally, the article considers issues pertaining to the division of functions between the global institutions, on the one hand, and between the World Bank and the regional development banks, on the other.
A refractive index sensor based on the MIM waveguide with a semi-elliptical and a rectangular ring resonant cavity
Authors: Chen Jia-Hua , Wang Liu , Chen Jun-Xue , Zeng Ya-Ping , Liang Qiu-Qun , Xia Xiong-Ping 
Published: June 2023

In this paper, a novel nanosensor comprising the metal–insulator–metal (MIM) plasmonics waveguide with a semi-elliptical and rectangular ring resonant cavity is designed. In near-infrared waveband, the propagation properties of electromagnetic waves in the structure are studied using the finite-difference time-domain (FDTD) method. The results show that, based on the coupling between the semi-elliptical and the rectangular ring resonant cavity, the transmission spectrum of the structure exhibits a sharp Fano resonance shape. Next, the influence of the refractive index and sensor structure parameters on performance is systematically investigated. The simulation results show that the sensor structure has the best sensitivity of 1384[Formula: see text]nm/RIU (refractive index unit), and the figure of merit (FOM) is 28.4. The simple MIM structure could be applied to sensitive plasmonic sensors.
Mapping intragranular microstructures in quartz: the significance of Dauphiné twinning
Authors: Lloyd Geoffrey E. 
Published: June 2023

Abstract
Mapping on the microstructural scale can contribute significantly to conventional field and larger scale mapping and understanding of spatial, temporal and process-oriented relationships. Here, electron backscattered diffraction (EBSD)-based microstructural maps are presented of subgrain and Dauphiné twin boundaries in undeformed sedimentary quartzite. ‘Plane matching’ analysis permits determination of the complete orientation of boundaries. A workflow is presented to facilitate the necessary crystallographic calculations. The resulting maps indicate: (1) boundary plane rotation angle/axis pairs, including tilt–twist components; (2) boundary migration vectors; and (3) conventional EBSD misorientation angle/axis pairs. Subgrain boundaries are general with small misorientations and boundary plane normal directions sub-parallel to grain boundary stress concentrations; rotation axes are oriented sub-parallel to the bedding dip (017°/10°E). Most exhibit bi-direction boundary migration vectors parallel to bedding normal. The EBSD misorientation analysis results are different as they only recognize the parallelism of adjacent crystal lattices. The differences are especially apparent for Dauphiné twin boundaries. Maps are presented of twin boundaries using matched plane analysis, including explanation for lateral twin migration. Driving forces to move twin boundaries are also estimated by mapping variations in Young's modulus between parents and twins; differences are significant, indicating that the Young's modulus and driving forces do not need to be large, explaining the propensity for twinning in many quartzites.
Drosophila Screening Identifies Dual Inhibition of MEK and AURKB as an Effective Therapy for Pancreatic Ductal Adenocarcinoma
Authors: Sekiya Sho , Fukuda Junki , Yamamura Ryodai , Ooshio Takako , Satoh Yusuke , Kosuge Shinya , Sato Reo , Hatanaka Kanako C. , Hatanaka Yutaka , Mitsuhashi Tomoko , Nakamura Toru , Matsuno Yoshihiro , Hirano Satoshi , Sonoshita Masahiro 
Published: June 2023

Abstract

Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the genetic signature in PDAC (KRAS, TP53, CDKN2A, and SMAD4 alterations), which is associated with the worst prognosis in patients. The ‘4-hit’ flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK inhibitor trametinib and the AURKB inhibitor BI-831266 suppressed the growth of human PDAC xenografts in mice. In patients with PDAC, the activity of AURKB was associated with poor prognosis. This fly-based platform provides an efficient whole-body approach that complements current methods for identifying therapeutic targets in PDAC.

Significance:
Development of a Drosophila model mimicking genetic alterations in human pancreatic ductal adenocarcinoma provides a tool for genetic screening that identifies MEK and AURKB inhibition as a potential treatment strategy.
PD-1 Monotherapy Reigns Supreme in Adjuvant Melanoma…But for How Long?
Authors: Augustin Ryan C. , Luke Jason J. 
Published: June 2023

SummaryThe results of CheckMate-238 led to the original FDA approval of anti–PD-1 therapy in high-risk, resectable melanoma. In this CCR Translations, we discuss the 5-year update of this pivotal trial and contextualize its results in the face of limited survival data, neoadjuvant therapy, next-generation biomarkers, and novel immunotherapy combinations.See related article by Larkin et al., p. 3352
BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis
Authors: Liu Xia , Ye Qinlian , Huang Zhengzheng , Li Xiuping , Zhang Liping , Liu Xuan , Wu Yun-Cheng , Brockmeier Ulf , Hermann Dirk M. , Wang Ya-Chao , Ren Lijie 
Published: June 2023

BACKGROUND:
The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke.

METHODS:
Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation–induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis.

RESULTS:
The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro.

CONCLUSIONS:
Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.