bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future Temperature‐Related Deaths in the U.S.: The Impact of Climate Change, Demographics, and Adaptation
Authors: Lee Jangho , Dessler Andrew E. 
Published: August 2023

AbstractMortality due to extreme temperatures is one of the most worrying impacts of climate change. In this analysis, we use historic mortality and temperature data from 106 cities in the United States to develop a model that predicts deaths attributable to temperature. With this model and projections of future temperature from climate models, we estimate temperature‐related deaths in the United States due to climate change, changing demographics, and adaptation. We find that temperature‐related deaths increase rapidly as the climate warms, but this is mainly due to an expanding and aging population. For global average warming below 3°C above pre‐industrial levels, we find that climate change slightly reduces temperature‐related mortality in the U.S. because the reduction of cold‐related mortality exceeds the increase in heat‐related deaths. Above 3°C warming, whether the increase in heat‐related deaths exceeds the decrease in cold‐related deaths depends on the level of adaptation. Southern U.S. cities are already well adapted to hot temperatures and the reduction of cold‐related mortality drives overall lower mortality. Cities in the Northern U.S. are not well adapted to high temperatures, so the increase in heat‐related mortality exceeds the reduction in cold‐related mortality. Thus, while the total number of climate‐related mortality may not change much, climate change will shift mortality in the U.S. to higher latitudes.
Storylines of Sahel Precipitation Change: Roles of the North Atlantic and Euro‐Mediterranean Temperature
Authors: Monerie Paul‐Arthur , Biasutti Michela , Mignot Juliette , Mohino Elsa , Pohl Benjamin , Zappa Giuseppe 
Published: August 2023

AbstractFuture changes in Sahel precipitation are uncertain because of large differences among projections from various models. In order to explore this uncertainty, we use a storyline approach which seeks to identify alternative plausible evolutions of Sahel precipitation and their driving factors. By analyzing projections from the CMIP6 climate models, we show that changes in North Atlantic and in Euro‐Mediterranean temperatures explain up to 60% of the central Sahel precipitation change uncertainty. We then construct several storylines of Sahel precipitation change based on future plausible changes in North Atlantic and Euro‐Mediterranean temperatures. In one storyline, an amplified warming of both the North Atlantic and the Euro‐Mediterranean areas promotes a northward shift of the West African monsoon, increasing precipitation over the central Sahel, while, in the opposite storyline, a moderate warming in both regions is associated with a small change in precipitation over the central Sahel and a decrease in precipitation over the western Sahel, at the end of the 21st century. These results indicate that Sahel precipitation uncertainty will not be substantially reduced unless the uncertainty in the future warming of the North Atlantic and the Euro‐Mediterranean areas is constrained.
FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation
Authors: Qiao Xinran , Lin Jingyu , Shen Jiajia , Chen Yang , Zheng Liyun , Ren Hangjiang , Zhao Xiaoli , Yang Hang , Li Pengyu , Wang Zhen 
Published: August 2023

AbstractFBXO28 is a member of F-box proteins that are the substrate receptors of SCF (SKP1, CULLIN1, F-box protein) ubiquitin ligase complexes. Despite the implications of its role in cancer, the function of FBXO28 in epithelial-mesenchymal transition (EMT) process and metastasis for cancer remains largely unknown. Here, we report that FBXO28 is a critical negative regulator of migration, invasion and metastasis in human hepatocellular carcinoma (HCC) in vitro and in vivo.FBXO28expression is upregulated in human epithelial cancer cell lines relative to mesenchymal counterparts. Mechanistically, by directly binding to SNAI2, FBXO28 functions as an E3 ubiquitin ligase that targets the substrate for degradation via ubiquitin proteasome system. Importantly, we establish a cooperative function for PKA in FBXO28-mediated SNAI2 degradation. In clinical HCC specimens, FBXO28 protein levels positively whereas negatively correlate with PKAα and SNAI2 levels, respectively. LowFBXO28orPRKACAexpression is associated with poor prognosis of HCC patients. Together, these findings elucidate the novel function of FBXO28 as a critical inhibitor of EMT and metastasis in cancer and provide a mechanistic rationale for its candidacy as a new prognostic marker and/or therapeutic target in human aggressive HCC.
Hornerin mediates phosphorylation of the polo-box domain in Plk1 by Chk1 to induce death in mitosis
Authors: Song Haiyu , Kim Eun Ho , Hong Jihee , Gwon Dasom , Kim Jee Won , Bae Gyu-Un , Jang Chang-Young 
Published: August 2023

AbstractThe centrosome assembles a bipolar spindle for faithful chromosome segregation during mitosis. To prevent the inheritance of DNA damage, the DNA damage response (DDR) triggers programmed spindle multipolarity and concomitant death in mitosis through a poorly understood mechanism. We identified hornerin, which forms a complex with checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1) to mediate phosphorylation at the polo-box domain (PBD) of Plk1, as the link between the DDR and death in mitosis. We demonstrate that hornerin mediates DDR-induced precocious centriole disengagement through a dichotomous mechanism that includes sequestration of Sgo1 and Plk1 in the cytoplasm through phosphorylation of the PBD in Plk1 by Chk1. Phosphorylation of the PBD in Plk1 abolishes the interaction with Sgo1 and phosphorylation-dependent Sgo1 translocation to the centrosome, leading to precocious centriole disengagement and spindle multipolarity. Mechanistically, hornerin traps phosphorylated Plk1 in the cytoplasm. Furthermore, PBD phosphorylation inactivates Plk1 and disrupts Cep192::Aurora A::Plk1 complex translocation to the centrosome and concurrent centrosome maturation. Remarkably, hornerin depletion leads to chemoresistance against DNA damaging agents by attenuating DDR-induced death in mitosis. These results reveal how the DDR eradicates mitotic cells harboring DNA damage to ensure genome integrity during cell division.
CRISPR screen identifies the role of RBBP8 in mediating unfolded protein response induced liver damage through regulating protein synthesis
Authors: Wang Heting , Pan Xuya , Xiang Xiaoxin , Zhang Yang , Chen Jianning , Wen Shiyi , Wang Jin , Gao Rong , Yang Jifeng , Zhi Yaping , Wen Siying , Zheng Yubao , Li Ting , Ai Heying , He Xuemin , Lu Yan , Zhu Yanhua , Li Chunliang , Chen Yanming , Shi Guojun 
Published: August 2023

AbstractUnfolded protein response (UPR) maintains the endoplasmic reticulum (ER) homeostasis, survival, and physiological function of mammalian cells. However, how cells adapt to ER stress under physiological or disease settings remains largely unclear. Here by a genome-wide CRISPR screen, we identified that RBBP8, an endonuclease involved in DNA damage repair, is required for ATF4 activation under ER stress in vitro. RNA-seq analysis suggested that RBBP8 deletion led to impaired cell cycle progression, retarded proliferation, attenuated ATF4 activation, and reduced global protein synthesis under ER stress. Mouse tissue analysis revealed that RBBP8 was highly expressed in the liver, and its expression is responsive to ER stress by tunicamycin intraperitoneal injection. Hepatocytes with RBBP8 inhibition by adenovirus-mediated shRNA were resistant to tunicamycin (Tm)-induced liver damage, cell death, and ER stress response. To study the pathological role of RBBP8 in regulating ATF4 activity, we illustrated that both RBBP8 and ATF4 were highly expressed in liver cancer tissues compared with healthy controls and highly expressed in Ki67-positive proliferating cells within the tumors. Interestingly, overexpression of RBBP8 in vitro promoted ATF4 activation under ER stress, and RBBP8 expression showed a positive correlation with ATF4 expression in liver cancer tissues by co-immunostaining. Our findings provide new insights into the mechanism of how cells adapt to ER stress through the crosstalk between the nucleus and ER and how tumor cells survive under chemotherapy or other anticancer treatments, which suggests potential therapeutic strategies against liver disease by targeting DNA damage repair, UPR or protein synthesis.
m6A methylation: a potential key player in understanding and treating COVID-2019 infection
Authors: Qian Weiwei , Zhou Jian , Duan Ligeng , Wang Haoyu , Xu Shuyun , Cao Yu 
Published: August 2023

AbstractSince its discovery in 2019, coronavirus disease 2019 (COVID-2019) spans a wide clinical spectrum from the asymptomatic stage, mild infection, to severe pneumonia. In patients with COVID-2019, factors such as advanced age, diabetes, or hypertension are associated with a significantly increased risk of severe diseases and death. Of note, the mechanisms underlying differences in the risk and symptoms of COVID-2019 among different populations are still poorly characterized. Accordingly, it is imperative to elucidate potential pathophysiological mechanisms and develop targeted therapeutic approaches for COVID-2019 infection. N6-methyladenosine (m6A) is one of the most common modifications in mammalian RNA transcripts and is widely found in messenger RNAs and some non-coding RNAs. It has been reported that m6A methylation modifications are present in viral RNA transcripts, which are of great significance for the regulation of the viral life cycle. Furthermore, m6A methylation has recently been found to be strongly associated with COVID-2019 infection. Therefore, this article reviews recent advances in studies related to the role of m6A methylation in COVID-2019 infection.
Effect of the blend ratio of cyclic and linear polyethylene blends on isothermal crystallization in the quiescent state
Authors: Kobayashi Keiko , Atarashi Hironori , Yamazaki Shinichi , Kimura Kunio 
Published: August 2023

AbstractThe role of entanglements that form between cyclic and linear polymers in crystallization is of particular interest, but it is not fully understood. We investigated the crystallization behaviors of blends of cyclic polyethylene (C-PE) and linear polyethylene (L-PE) in a quiescent state to elucidate the role of this novel entanglement in crystallization. The samples were prepared by mixing the prepared C-PE and L-PE specimens at L-PE weight fraction (ΦL-PE) values of 0–100 wt%, with the weight average molecular weights of C-PE and L-PE being 175 × 103 and 154 × 103, respectively. The isothermal crystallization behaviors were analyzed through polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). The morphology observed through POM was similar to that of ΦL-PE. From the time evolution of the heat flow measured via DSC, we obtained the half-crystallization time (t1/2) values as functions of ΦL-PE at different degrees of supercooling (ΔT). The 1/t1/2 values of the C-PE and L-PE homopolymers were approximately the same at ΔT = 25.5 and 26.5 K. At a larger ΔT value, the 1/t1/2 value of C-PE was significantly larger than that of L-PE. In contrast, 1/t1/2 reached a minimum value at ΦL-PE = 30–40 wt%, irrespective of ΔT. As the entanglement density increased with increasing ΦL-PE, the crystallization rate was expected to decrease monotonically. By considering the experimental relationship between 1/t1/2 and ΦL-PE, we speculated that the suppression of crystallization in the blended system was caused by a novel entanglement formed by the penetration of the L-PE chain into the C-PE chain.
Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response
Authors: Arora Rohit , Cao Christian , Kumar Mehul , Sinha Sarthak , Chanda Ayan , McNeil Reid , Samuel Divya , Arora Rahul K. , Matthews T. Wayne , Chandarana Shamir , Hart Robert , Dort Joseph C. , Biernaskie Jeff , Neri Paola , Hyrcza Martin D. , Bose Pinaki 
Published: August 2023

AbstractThe spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases (http://www.pboselab.ca/spatial_OSCC/; http://www.pboselab.ca/dynamo_OSCC/) that can be foundational for developing novel targeted therapies.
An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
Authors: Fernández Moro Carlos , Geyer Natalie , Harrizi Sara , Hamidi Yousra , Söderqvist Sara , Kuznyecov Danyil , Tidholm Qvist Evelina , Salmonson Schaad Media , Hermann Laura , Lindberg Amanda , Heuchel Rainer L. , Martín-Bernabé Alfonso , Dhanjal Soniya , Navis Anna C. , Villard Christina , del Valle Andrea C. , Bozóky Lorand , Sparrelid Ernesto , Dirix Luc , Strell Carina , Östman Arne , Schmierer Bernhard , Vermeulen Peter B. , Engstrand Jennie , Bozóky Béla , Gerling Marco 
Published: August 2023

AbstractA perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule’s extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
Heavy quasiparticles and cascades without symmetry breaking in twisted bilayer graphene
Authors: Datta Anushree , Calderón M. J. , Camjayi A. , Bascones E. 
Published: August 2023

AbstractAmong the variety of correlated states exhibited by twisted bilayer graphene, cascades in the spectroscopic properties and in the electronic compressibility occur over larger ranges of energy, twist angle and temperature compared to other effects. This suggests a hierarchy of phenomena. Using a combined dynamical mean-field theory and Hartree calculation, we show that the spectral weight reorganisation associated with the formation of local moments and heavy quasiparticles can explain the cascade of electronic resets without invoking symmetry breaking orders. The phenomena reproduced here include the cascade flow of spectral weight, the oscillations of remote band energies, and the asymmetric jumps of the inverse compressibility. We also predict a strong momentum differentiation in the incoherent spectral weight associated with the fragile topology of twisted bilayer graphene.
Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic
Authors: Staubli Sebastian M. , Raptis Dimitri A. , Ghani Shahi , Davidson Brian R. , Fusai Giuseppe K. , Imber Charles , Iype Sateesh , Nasralla David , Pissanou Theodora , Rahman Sakhawat , Sharma Dinesh , Tinguely Pascale , Haddad Fares , Dodd Miranda , Dann Chris , Walker David , Pollok Joerg-Matthias ,   On behalf of the Royal Free Hospital London HPB team, Banerjee Abhirup , Mohamed Ahmed , Obalogun Aleem , Ramirez Alejandro , Rothnie Alex , Grajn Andrej , Chikkala Bhargava , Ojo-Williams Bose , Hidalgo-Salinas Camilla , Ceresa Carlo , Frola Carlo , Tsakiris Charalampos , Shaw Conrad , Chasiotis Dimitrios , Kontis Elissaios , Froghi Farid , Venkatakrishnan Guhan , Tzerbinis Helen , Kostakis Ioannis D. , Whitehead James , Costa Joao , Patel Krishnakumure , Kathirvel Manikandan , Sharma Mitesh , Elnagar Mohamed , Somasundaram Murali , Dimitrokallis Nikolaos , Morare Nolitha , Kupfuwa Nyasharenee , Bulathsinhala Sandun , Makhdoom Shahroo , Pericleous Stephanos , Kunnuru Supreeth , Ramos-Vazquez Susana , Ibraheem Tameem , Keating Gemma , Lightfoot Linda , Brown Sophie , Gyamfi Lucy , Modi Kajal , Tufuo Vanessa , Walker Harriet Louise 
Published: August 2023

AbstractTo mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien–Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting.
Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression
Authors: Lazniewska Joanna , Li Ka Lok , Johnson Ian R. D. , Sorvina Alexandra , Logan Jessica M. , Martini Carmela , Moore Courtney , Ung Ben S.-Y. , Karageorgos Litsa , Hickey Shane M. , Prabhakaran Sarita , Heatlie Jessica K. , Brooks Robert D. , Huzzell Chelsea , Warnock Nicholas I. , Ward Mark P. , Mohammed Bashir , Tewari Prerna , Martin Cara , O’Toole Sharon , Edgerton Laura Bogue , Bates Mark , Moretti Paul , Pitson Stuart M. , Selemidis Stavros , Butler Lisa M. , O’Leary John J. , Brooks Douglas A. 
Published: August 2023

AbstractProstate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with β3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly β3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.
The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation
Authors: Chawengrum Pornsuda , Luepongpatthana Natthaorn , Thongnest Sanit , Sirirak Jitnapa , Boonsombat Jutatip , Lirdprapamongkol Kriengsak , Keeratichamroen Siriporn , Kongwaen Patcharin , Montatip Phreeranat , Kittakoop Prasat , Svasti Jisnuson , Ruchirawat Somsak 
Published: August 2023

AbstractAnticopalic acid (ACP), a labdane type diterpenoid obtained from Kaempferia elegans rhizomes, together with 21 semi-synthetic derivatives, were evaluated for their cancer cytotoxic activity. Most derivatives displayed higher cytotoxic activity than the parent compound ACP in a panel of nine cancer cell lines. Among the tested compounds, the amide 4p showed the highest cytotoxic activity toward leukemia cell lines, HL-60 and MOLT-3, with IC50 values of 6.81 ± 1.99 and 3.72 ± 0.26 µM, respectively. More interestingly, the amide derivative 4l exhibited cytotoxic activity with an IC50 of 13.73 ± 0.04 µM against the MDA-MB-231 triple-negative breast cancer cell line, which is the most aggressive type of breast cancer. Mechanistic studies revealed that 4l induced cell death in MDA-MB-231 cells through non-apoptotic regulated cell death. In addition, western blot analysis showed that compound 4l decreased the phosphorylation of FAK protein in a concentration-dependent manner. Molecular docking simulations elucidated that compound 4l could potentially inhibit FAK activation by binding to a pocket of FAK kinase domain. The data suggested that compound 4l could be a potential FAK inhibitor for treating triple-negative breast cancer and worth being further investigated.
Novel power distribution short‐circuit testing technique based on supercapacitor and modular multi‐ports AC/DC conversion
Authors: Zhang Guoju , Pei Wei , Li Ningning , Liu Xu , Deng Wei 
Published: August 2023

AbstractWith the growing capacity of the distribution network, the probability of short circuit accidents gradually increases. Accidents such as deformation of distribution transformer windings, shift of laminations, fracture and even explosion of mechanical and insulation components caused by insufficient short‐circuit withstand ability seriously affect the safe and stable operation of the distribution network. The short‐circuit test proved to be an effective way to detect the performance of equipment under fault impact. A power source with supercapacitor is proposed here for short‐circuit test of 10 kV distribution transformers, which can realize the short‐circuit test application economically and flexibly with expandable capacity. First, the advantages and disadvantages of test power source by short‐circuit test generators, special power line, and the proposed method are compared. Second, the structure, working principle, design scheme, and control strategy of the novel short‐circuit testing device are introduced. Furthermore, a 14 MVA/5 MJ energy storage short‐circuit test power source is designed for the testing requirements of 10 kV/630 kVA distribution transformers. Finally, the simulations and experiments are used to verify its feasibility.