bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Health Care and Disasters: Applying a “Whole-of-Health System” Approach through Reverse Triage in Mass-Casualty Management
Authors: Alesi Andrea , Bortolin Michelangelo , Ragazzoni Luca , Lamberti-Castronuovo Alessandro 
Published: September 2023

AbstractIntroduction:In 2019, the World Health Organization (WHO) published the Health Emergency and Disaster Risk Management (H-EDRM) framework detailing how effective management of disasters, including mass-casualty incidents (MCIs), can be achieved through a whole-of-health system approach where each level of the health care system is involved in all phases of the disaster cycle. In light of this, a primary health care (PHC) approach can contribute to reducing negative health outcomes of disasters, since it encompasses the critical roles that primary care services can play during crises. Hospitals can divert non-severe MCI victims to primary care services by applying reverse triage (RT), thereby preventing hospital overloading and ensuring continuity of care for those who do not require hospital services during the incident.Study Objective:This study explores the topic by reviewing the literature published on early discharge of MCI victims through RT criteria and existing referral pathways to primary care services.Methods:A scoping literature review was performed and a total of ten studies were analyzed.Results:The results showed that integrating primary care facilities into disaster management (DM) through the use of RT may be an effective strategy to create surge during MCIs, provided that clear referral protocols exist between hospitals and primary care services to ensure continuity of care. Furthermore, adequate training should be provided to primary care professionals to be prepared and be able to provide quality care to MCI victims.Conclusion:The results of this current review can serve as groundwork upon which to design further research studies or to help devise strategies and policies for the integration of PHC in MCI management.
Earth stewardship, water resilience, and ethics in the Anthropocene
Authors: Schmidt Jeremy J. 
Published: September 2023

Non-technical summaryThis article uses water to examine how the relationships of ethics to science are modified through the pursuit of Earth stewardship. Earth stewardship is often defined as the use of science to actively shape social–ecological relations by enhancing resilience. The changing relations of science to values are explored by considering how ideas of resilience operate to translate different ways of knowing water into the framework of Earth stewardship. This is not a neutral process, and Earth stewardship requires careful appraisal to ensure other ways of knowing water are not oppressed.Technical summaryScientific disclosures of anthropogenic impacts on the Earth system – the Anthropocene – increasingly come with ethical diagnoses for value transformation and, often, Earth stewardship. This article examines the changing relationship of science to values in calls for Earth stewardship with special attention to water resilience. The article begins by situating recent efforts to reconceptualize human–water relations in view of anthropogenic impacts on the global water system. It then traces some of the ways that Earth stewardship has been articulated, especially as a framework supporting the use of science to actively shape social–ecological relations by enhancing resilience. The shift in relations of ethics and science entailed by Earth stewardship is placed in historical context before the issues of water resilience are examined. Resilience, and critiques of it, are then discussed for how they operate to translate different ways of knowing water into the framework of Earth stewardship. The ethical stakes of such translations are a core concern of the conclusion. Rather than reducing different ways of knowing water to those amendable to the framework of Earth stewardship, the article advances a pluralized approach as needed to respect multiple practices for knowing and relating to water – and resilience.Social media summaryWater resilience is key to Earth stewardship; Jeremy Schmidt examines how it changes relations of science and ethics.
The Co-Twin Control Design: Implementation and Methodological Considerations
Authors: Gonggrijp Bodine M. A. , van de Weijer Steve G. A. , Bijleveld Catrien C. J. H. , van Dongen Jenny , Boomsma Dorret I. 
Published: September 2023

AbstractEstablishing causal relationships in observational studies is an important step in research and policy decision making. The association between an exposure and an outcome can be confounded by multiple factors, often making it hard to draw causal conclusions. The co-twin control design (CTCD) is a powerful approach that allows for the investigation of causal effects while controlling for genetic and shared environmental confounding factors. This article introduces the CTCD and offers an overview of analysis methods for binary and continuous outcome and exposure variables. Tools for data simulation are provided, along with practical guidance and accompanying scripts for implementing the CTCD in R, SPSS, and Stata. While the CTCD offers valuable insights into causal inference, it depends on several assumptions that are important when interpreting CTCD results. By presenting a broad overview of the CTCD, this article aims to equip researchers with actionable recommendations and a comprehensive understanding of the design’s strengths and limitations.
Formation of Electron Butterfly Distribution by a Contracting Dipolarization Front
Authors: Yu Y. , Fu H. S. , Wang Z. , Fu W. D. , Cao J. B. 
Published: September 2023

AbstractThe electron butterfly distribution, characterized by pitch angles (PA) primarily at 45° and 135°, was rarely observed in Earth's magnetotail. Here using the high‐resolution measurements from Magnetospheric Multiscale mission, we present the observation of electron butterfly distribution in a contracting dipolarization front (DF), and propose a new physical mechanism to explain its formation. Specifically, we discover that the electron butterfly distribution only exhibited in the locally contracted DF and was observed above 1.7 keV. We infer that local contraction of the DF transformed its configuration from a magnetic bottle to an hourglass‐shaped magnetic structure, and the butterfly distribution was formed by the magnetic mirror effect of this magnetic hourglass. Additionally, the theoretically estimated loss cone of the magnetic hourglass fits well with the observations of electrons, validating our inference about the formation mechanism. These findings can improve our understanding of electron dynamics in Earth's magnetosphere.
Three-dimensional growth sensitizes breast cancer cells to treatment with ferroptosis-promoting drugs
Authors: Chipurupalli Sandhya , Jiang Peijia , Liu Xiaoyang , Santos Julia Linhares , Marcato Paola , Rosen Kirill V. 
Published: September 2023

AbstractDrugs causing ferroptosis, iron-mediated cell death, represent promising tools for cancer treatment. While exploring the effect of these drugs on breast cancer (BC), we found that a ferroptosis-inducing drug erastin dramatically inhibits tumorigenicity of human BC cells in mice but when used at a concentration known to effectively kill other cell types only modestly reduces such growth in 2D monolayer culture. BCs grow in vivo as 3D masses, and we found that ferroptosis inducers erastin and sulfasalazine inhibit growth of multiple human BC cell lines in 3D culture significantly stronger than in 2D culture. To understand the mechanism of this differential effect, we found that ferroptosis inducers upregulate mRNAs encoding multiple direct and indirect autophagy stimulators, such as ATG16L2, ATG9A, ATG4D, GABARAP, SQSTM/p62, SEC23A and BAX, in tumor cells growing in 2D but not in 3D culture. Furthermore, these drugs promoted autophagy of tumor cells growing in a 2D but not in a 3D manner. We observed that pharmacological inhibition of autophagy-stimulating protein kinase ULK1 or RNA interference-mediated knockdown of autophagy mediator ATG12 significantly sensitized tumor cells to erastin treatment in 2D culture. We also found that ferroptosis-promoting treatments upregulate heme oxygenase-1 (HO-1) in BC cells. HO-1 increases cellular free iron pool and can potentially promote ferroptosis. Indeed, we observed that HO-1 knockdown by RNA interference reversed the effect of ferroptosis inducers on BC cell 3D growth. Hence, the effect of these drugs on such growth is mediated by HO-1. In summary, autophagy triggered by ferroptosis-promoting drugs reduces their ability to kill BC growing in a 2D manner. This protection mechanism is inhibited in BC cells growing as a 3D mass, and ferroptosis-promoting drugs kill such cells more effectively. Moreover, this death is mediated by HO-1. Thus, ferroptosis induction represents a promising strategy for blocking 3D BC growth.
Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22–CCR4–ATF6–GRP78 axis
Authors: Zhang Lichao , Lu Xiaoqing , Xu Yuanzhi , La Xiaoqin , Tian Jinmiao , Li Aiping , Li Hanqing , Wu Changxin , Xi Yanfeng , Song Guisheng , Zhou Zhaocai , Bai Wenqi , An Liwei , Li Zhuoyu 
Published: September 2023

AbstractChemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.
Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance
Authors: Wang Chenyuan , Xia Yushan , Wang Runming , Li Jingru , Chan Chun-Lung , Kao Richard Yi-Tsun , Toy Patrick H. , Ho Pak-Leung , Li Hongyan , Sun Hongzhe 
Published: September 2023

AbstractThe rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.
Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans
Authors: Yaakub Siti N. , White Tristan A. , Roberts Jamie , Martin Eleanor , Verhagen Lennart , Stagg Charlotte J. , Hall Stephen , Fouragnan Elsa F. 
Published: September 2023

AbstractLow-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation.
Neural tuning instantiates prior expectations in the human visual system
Authors: Harrison William J. , Bays Paul M. , Rideaux Reuben 
Published: September 2023

AbstractPerception is often modelled as a process of active inference, whereby prior expectations are combined with noisy sensory measurements to estimate the structure of the world. This mathematical framework has proven critical to understanding perception, cognition, motor control, and social interaction. While theoretical work has shown how priors can be computed from environmental statistics, their neural instantiation could be realised through multiple competing encoding schemes. Using a data-driven approach, here we extract the brain’s representation of visual orientation and compare this with simulations from different sensory coding schemes. We found that the tuning of the human visual system is highly conditional on stimulus-specific variations in a way that is not predicted by previous proposals. We further show that the adopted encoding scheme effectively embeds an environmental prior for natural image statistics within the sensory measurement, providing the functional architecture necessary for optimal inference in the earliest stages of cortical processing.
The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis
Authors: Schoeler Marc , Ellero-Simatos Sandrine , Birkner Till , Mayneris-Perxachs Jordi , Olsson Lisa , Brolin Harald , Loeber Ulrike , Kraft Jamie D. , Polizzi Arnaud , Martí-Navas Marian , Puig Josep , Moschetta Antonio , Montagner Alexandra , Gourdy Pierre , Heymes Christophe , Guillou Hervé , Tremaroli Valentina , Fernández-Real José Manuel , Forslund Sofia K. , Burcelin Remy , Caesar Robert 
Published: September 2023

AbstractDietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.
Unconventional specular optical rotation in the charge ordered state of Kagome metal CsV3Sb5
Authors: Farhang Camron , Wang Jingyuan , Ortiz Brenden R. , Wilson Stephen D. , Xia Jing 
Published: September 2023

AbstractKagome metals AV3Sb5 (A = K, Cs, Rb) provide a rich platform for intertwined orders, where evidence for time-reversal symmetry breaking, likely due to the long-sought loop currents, has emerged in STM and muon spin relaxation experiments. An isotropic component in the spontaneous optical rotation has also been reported and was interpreted as the magneto-optic Kerr effect. Intriguingly, the observed rotations differ by five orders of magnitude between different wavelengths and samples, suggesting more intricate physics. Here we report optical rotation and polar Kerr measurements in CsV3Sb5 crystals at the same wavelength. We observe large isotropic components of 1 milliradian in the optical rotation that do not respond to applied magnetic fields, while the spontaneous Kerr signal is less than 20 nanoradians. Our results prove unambiguously that the reported isotropic rotation is not from time-reversal symmetry breaking but represents the long-sought specular optical rotation and indicates a new intertwined order.
CENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly
Authors: Eibes Susana , Rajendraprasad Girish , Guasch-Boldu Claudia , Kubat Mirela , Steblyanko Yulia , Barisic Marin 
Published: September 2023

AbstractAccurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores that are built on the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules. In early mitosis, unattached kinetochores expand a crescent-shaped structure called fibrous corona whose function is to facilitate initial kinetochore-microtubule attachments and chromosome transport by microtubules. Subsequently, the fibrous corona must be timely disassembled to prevent segregation errors. Although recent studies provided new insights on the molecular content and mechanism of fibrous corona assembly, it remains unknown what triggers the disassembly of the outermost and dynamic layer of the kinetochore. Here, we show that Aurora A and B kinases phosphorylate CENP-E to release it from an autoinhibited state. At kinetochores, Aurora B phosphorylates CENP-E to prevent its premature removal together with other corona proteins by dynein. At the spindle poles, Aurora A phosphorylates CENP-E to promote chromosome congression and prevent accumulation of corona proteins at the centrosomes, allowing for their intracellular redistribution. Thus, we propose the Aurora A/B-CENP-E axis as a critical element of the long-sought-for mechanism of fibrous corona disassembly that is essential for accurate chromosome segregation.
Suppression of alpha-carbon racemization in peptide synthesis based on a thiol-labile amino protecting group
Authors: Zhou Yifei , Li Hongjun , Huang Yi , Li Jiahui , Deng Guiyu , Chen Gong , Xi Zhen , Zhou Chuanzheng 
Published: September 2023

AbstractIn conventional solid-phase peptide synthesis (SPPS), α-amino groups are protected with alkoxycarbonyl groups (e.g., 9-fluorenylmethoxycarbonyl [Fmoc]). However, during SPPS, inherent side reactions of the protected amino acids (e.g., α-C racemization and aspartimide formation) generate by-products that are hard to remove. Herein, we report a thiol-labile amino protecting group for SPPS, the 2,4-dinitro-6-phenyl-benzene sulfenyl (DNPBS) group, which is attached to the α-amino group via a S–N bond and can be quantitatively removed in minutes under nearly neutral conditions (1 M p-toluenethiol/pyridine). The use of DNPBS greatly suppresses the main side reactions observed during conventional SPPS. Although DNPBS SPPS is not as efficient as Fmoc SPPS, especially for synthesis of long peptides, DNPBS and Fmoc are orthogonal protecting groups; and thus DNPBS SPPS and Fmoc SPPS can be combined to synthesize peptides that are otherwise difficult to obtain.
Integration of microbattery with thin-film electronics for constructing an integrated transparent microsystem based on InGaZnO
Authors: Jia Bin , Zhang Chao , Liu Min , Li Zhen , Wang Jian , Zhong Li , Han Chuanyu , Qin Ming , Huang Xiaodong 
Published: September 2023

AbstractA full integration of miniaturized transparent energy device (lithium-ion battery), electronic device (thin-film transistor) and sensing device (photodetector) to form a monolithic integrated microsystem greatly enhances the functions of transparent electronics. Here, InGaZnO is explored to prepare the above devices and microsystem due to its multifunctional properties. A transparent lithium-ion battery with InGaZnO as anode (capacity~9.8 μAh cm−2) is proposed as the on-chip power source. Then, thin-film transistor with InGaZnO as channel (mobility~23.3 cm2 V−1 s−1) and photodetector with InGaZnO as photosensitive layer (responsivity~0.35 A W−1) are also prepared on the substrate for constructing an fully integrated transparent microsystem. Each device displays acceptable performance. Moreover, alternating-current signals can be successfully charged into the lithium-ion battery by using the thin-film transistor as the on-chip rectifier and also the photodetector works well by using the charged battery as the on-chip power, demonstrating collaborative capabilities of each device to achieve systematic functions.
Theranostic approach to specifically targeting the interloop region of BCL2 i-motif DNA by crystal violet
Authors: Das Sinjan , Takahashi Shuntaro , Ohyama Tatsuya , Bhowmik Sudipta , Sugimoto Naoki 
Published: September 2023

AbstractLigands that recognise specific i-motif DNAs are helpful in cancer diagnostics and therapeutics, as i-motif formation can cause cancer. Although the loop regions of i-motifs are promising targets for ligands, the interaction between a ligand and the loop regions based on sequence information remains unexplored. Herein, we investigated the loop regions of various i-motif DNAs to determine whether these regions specifically interact with fluorescent ligands. Crystal violet (CV), a triphenylmethane dye, exhibited strong fluorescence with the i-motif derived from the promoter region of the human BCL2 gene in a sequence- and structure-specific manner. Our systematic sequence analysis indicated that CV was bound to the site formed by the first and third loops through inter-loop interactions between the guanine bases present in these loops. As the structural stability of the BCL2 i-motif was unaffected by CV, the local stabilisation of the loops by CV could inhibit the interaction of transcription factors with these loops, repressing the BCL2 expression of MCF-7 cells. Our finding suggests that the loops of the i-motif can act as a novel platform for the specific binding of small molecules; thus, they could be utilised for the theranostics of diseases associated with i-motif DNAs.