bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Assessment of Urban Overheating Impacts on Human Life
Authors: Nazarian N. , Krayenhoff E. S. , Bechtel B. , Hondula D. M. , Paolini R. , Vanos J. , Cheung T. , Chow W. T. L. , de Dear R. , Jay O. , Lee J. K. W. , Martilli A. , Middel A. , Norford L. K. , Sadeghi M. , Schiavon S. , Santamouris M. 
Published: August 2022

AbstractUrban overheating, driven by global climate change and urban development, is a major contemporary challenge that substantially impacts urban livability and sustainability. Overheating represents a multifaceted threat to the well‐being, performance, and health of individuals as well as the energy efficiency and economy of cities, and it is influenced by complex interactions between building, city, and global scale climates. In recent decades, extensive discipline‐specific research has characterized urban heat and assessed its implications on human life, including ongoing efforts to bridge neighboring disciplines. The research horizon now encompasses complex problems involving a wide range of disciplines, and therefore comprehensive and integrated assessments are needed that address such interdisciplinarity. Here, our objective is to go beyond a review of existing literature and instead provide a broad overview and integrated assessments of urban overheating, defining holistic pathways for addressing the impacts on human life. We (a) detail the characterization of heat hazards and exposure across different scales and in various disciplines, (b) identify individual sensitivities to urban overheating that increase vulnerability and cause adverse impacts in different populations, (c) elaborate on adaptive capacities that individuals and cities can adopt, (d) document the impacts of urban overheating on health and energy, and (e) discuss frontiers of theoretical and applied urban climatology, built environment design, and governance toward reduction of heat exposure and vulnerability at various scales. The most critical challenges in future research and application are identified, targeting both the gaps and the need for greater integration in overheating assessments.
Centennial Memory of the Arctic Ocean for Future Arctic Climate Recovery in Response to a Carbon Dioxide Removal
Authors: Oh Ji‐Hoon , An Soon‐Il , Shin Jongsoo , Kug Jong‐Seong 
Published: August 2022

AbstractUnder the ongoing and potential risks from anthropogenic warming, net negative carbon dioxide (CO2) emissions are inevitable to stabilize or recover the Earth's climate. It is important not only to understand climate irreversibility in response to CO2 removal but also to understand how fast each component of the climate system will recover to its original state. Based on idealized CO2 ramp‐up and ‐down ensemble simulations, here we show that the initial buoyancy states of the Arctic Ocean, such as upper ocean salinity and density, are vital to determining how fast Arctic and global mean temperatures will recover on a centennial time scale. The denser initial Arctic oceanic condition is linked to faster recovery of the Atlantic meridional overturning circulation (AMOC) in the ramp‐down period, which is further accelerated by strong positive AMOC‐salt‐advection feedback. Faster AMOC recovery can delay Arctic temperature recovery by transporting warmer water into the northern subpolar Atlantic during the ramp‐down period. In addition, denser Arctic water enhances vertical mixing, which also results in delayed Arctic cooling under a strong vertical temperature gradient in the subpolar‐to‐polar Atlantic. Our findings suggest that the Arctic's initial states have a centennial memory for the future Arctic and global climate changes.
New Insights From the 2003 Halloween Storm Into the Colaba 1600 nT Magnetic Depression During the 1859 Carrington Storm
Authors: Ohtani Shinichi 
Published: August 2022

AbstractThe present study investigates the cause of a sharp horizontal (H) magnetic depression observed on the dayside during the 2003 Halloween storm, and discusses if the same process could cause the 1,600 nT H depression observed at Colaba during the 1859 Carrington storm. For the Halloween H depression, it is found that (a) it developed in correlation with southward interplanetary magnetic field (IMF) BZ in the sheath region of a coronal mass ejection; (b) its magnitude decreased significantly with decreasing magnetic latitude; (c) it was highly correlated with westward and eastward sub‐auroral zone magnetic deflections at earlier and later local times, respectively; and (d) the westward auroral electrojet (AEJ) enhanced simultaneously in the entire nightside auroral zone, whereas the enhancement of the dayside eastward AEJ was unclear. These features suggest that the dayside R1‐sense wedge current system, which was driven by dayside magnetic reconnection, was the cause of the H depression, and the associated field‐aligned currents closed primarily with the westward AEJ through the nightside. The Colaba H depression also took place on the dayside and lasted for ∼2 hr. Furthermore, it took place within a few hours after the storm commencement, and the westward AEJ enhanced simultaneously in the dawn sector. These similarities suggest that the dayside wedge current system was also the cause of this historical event. The sharp recovery of the Colaba H depression, which has been a challenge to explain, may be attributed to the decay of this current system due to a northward IMF turning.
AMPK suppresses Th2 cell responses by repressing mTORC2
Authors: Pandit Mahesh , Timilshina Maheshwor , Gu Ye , Acharya Suman , Chung Yeonseok , Seo Sang-Uk , Chang Jae-Hoon 
Published: August 2022

AbstractAllergic inflammation is a T helper 2 (Th2) cell-driven pathophysiological phenomenon, but the mechanism by which the metabolic cascade affects Th2 cell differentiation remains unclear. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) and intracellular energy sensors in Th2 cell differentiation and the pathogenesis of allergic inflammation. Accordingly, T-cell-specific AMPK or Sirtuin 1 (Sirt1)-knockout mice were subjected to allergic inflammation, and their Th2 cell responses were investigated. The results demonstrated that inducing allergic inflammation in AMPK- and Sirt1-knockout mice increased Th2 cell responses and exacerbated allergic phenotypes. Furthermore, treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, ameliorated allergic inflammation in mice. Mechanistically, our findings revealed that AMPK repressed mechanistic target of rapamycin complex 2 (mTORC2), which downregulated the expression of suppressor of cytokine signaling 5 (SOCS5) in CD4+ T cells. In addition, the loss of AMPK signaling reduced SOCS5 expression and increased interleukin-4-STAT6–GATA3 axis-mediated Th2 cell differentiation. Finally, the T-cell-specific deletion of Rictor, a member of mTORC2, in Sirt1T-KO mice led to the reversal of allergic exacerbation to the level in control mice. Overall, our findings suggest that AMPK in CD4+ T cells inhibits the differentiation of Th2 cells by repressing mTORC2 and thus serves as a potential target for Th2 cell-associated diseases.
Advances in human oxytocin measurement: challenges and proposed solutions
Authors: Tabak Benjamin A. , Leng Gareth , Szeto Angela , Parker Karen J. , Verbalis Joseph G. , Ziegler Toni E. , Lee Mary R. , Neumann Inga D. , Mendez Armando J. 
Published: August 2022

AbstractOxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies—including the design and study of hormone secretion and biochemical assays—present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.
Classical epithelial-mesenchymal transition (EMT) and alternative cell death process-driven blebbishield metastatic-witch (BMW) pathways to cancer metastasis
Authors: Jinesh Goodwin G. , Brohl Andrew S. 
Published: August 2022

AbstractMetastasis is a pivotal event that accelerates the prognosis of cancer patients towards mortality. Therapies that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for better mitigation. Towards this goal, we discuss the details of two distinct but overlapping pathways of metastasis: a classical reversible epithelial-to-mesenchymal transition (hybrid-EMT)-driven transport pathway and an alternative cell death process-driven blebbishield metastatic-witch (BMW) transport pathway involving reversible cell death process. The knowledge about the EMT and BMW pathways is important for the therapy of metastatic cancers as these pathways confer drug resistance coupled to immune evasion/suppression. We initially discuss the EMT pathway and compare it with the BMW pathway in the contexts of coordinated oncogenic, metabolic, immunologic, and cell biological events that drive metastasis. In particular, we discuss how the cell death environment involving apoptosis, ferroptosis, necroptosis, and NETosis in BMW or EMT pathways recruits immune cells, fuses with it, migrates, permeabilizes vasculature, and settles at distant sites to establish metastasis. Finally, we discuss the therapeutic targets that are common to both EMT and BMW pathways.
Validity and reliability of the 2-minute walk test in individuals with spinal cord injury
Authors: Willi Romina , Widmer Mario , Merz Nora , Bastiaenen Caroline H. G. , Zörner Björn , Bolliger Marc 
Published: August 2022

Abstract
Study design
Multicentre-observational study.

Objectives
The 6-minute walk test (6mWT) is an established assessment of walking function in individuals with spinal cord injury (SCI). However, walking 6 min can be demanding for severely impaired individuals. The 2-minute walk test (2mWT) could be an appropriate alternative that has already been validated in other neurological disorders. The aim of this study was to assess construct validity and test-rest reliability of the 2mWT in individuals with SCI. In addition, the influence of walking performance on sensitivity to change of the 2mWT was assessed.

Setting
Swiss Paraplegic Center Nottwil, Switzerland; Balgrist University Hospital, Zürich, Switzerland.

Methods
Fifty individuals (aged 18–79) with SCI (neurological level of injury: C1-L3, AIS: A-D) were assessed on two test days separated by 1 to 7 days. The first assessment consisted of a 2mWT familiarization, followed by a 2mWT and 10-meter walk test (10MWT) (including the Walking Index for Spinal Cord Injury (WISCI II)) in randomized order. The second assessment consisted of 2mWT and 6mWT in randomized order. Tests were separated by at least 30 min of rest.

Results
The interclass correlation coefficient between the 2mWT assessed on the first and second test day was excellent (r = 0.980, p < 0.001). The 2mWT correlated very strongly with the 6mWT (r = 0.992, p < 0.001) and the 10MWT (r = 0.964, p < 0.001), and moderately with the WISCI II (r = 0.571, p < 0.001). Sensitivity to change was slightly affected by walking performance.

Conclusion
The 2mWT is a valid and reliable alternative to the 6mWT to measure walking function in individuals with SCI.

Trial registration
NCT04555759.
CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer
Authors: Hsieh Chi-Che , Hsu Sen-Huei , Lin Chih-Yu , Liaw Hung-Jiun , Li Ting-Wei , Jiang Kuan-Ying , Chiang Nai-Jung , Chen Shang-Hung , Lin Bo-Wen , Chen Po-Chuan , Chan Ren-Hao , Lin Peng-Chan , Yeh Yu-Min , Shen Che-Hung 
Published: August 2022

Abstract
Background
Colorectal cancer (CRC), the most common cancer type, causes high morbidity and mortality. Patients who develop drug resistance to oxaliplatin-based regimens have short overall survival. Thus, identifying molecules involved in the development of oxaliplatin resistance is critical for designing therapeutic strategies.

Methods
A proteomic screen was performed to reveal altered protein kinase phosphorylation in oxaliplatin-resistant (OR) CRC tumour spheroids. The function of CHK2 was characterised using several biochemical techniques and evident using in vitro cell and in vivo tumour models.

Results
We revealed that the level of phospho-CHK2(Thr68) was elevated in OR CRC cells and in ~30% of tumour samples from patients with OR CRC. We demonstrated that oxaliplatin activated several phosphatidylinositol 3-kinase-related kinases (PIKKs) and CHK2 downstream effectors and enhanced CHK2/PARP1 interaction to facilitate DNA repair. A phosphorylation mimicking CHK2 mutant, CHK2T68D, but not a kinase-dead CHK2 mutant, CHK2D347A, promoted DNA repair, the CHK2/PARP1 interaction, and cell growth in the presence of oxaliplatin. Finally, we showed that a CHK2 inhibitor, BML-277, reduced protein poly(ADP-ribosyl)ation (PARylation), FANCD2 monoubiquitination, homologous recombination and OR CRC cell growth in vitro and in vivo.

Conclusion
Our findings suggest that CHK2 activity is critical for modulating oxaliplatin response and that CHK2 is a potential therapeutic target for OR CRC.
A novel age-related gene expression signature associates with proliferation and disease progression in breast cancer
Authors: Ingebriktsen L. M. , Finne K. , Akslen L. A. , Wik E. 
Published: August 2022

Abstract
Background and objective
Breast cancer (BC) diagnosed at ages <40 years presents with more aggressive tumour phenotypes and poorer clinical outcome compared to older BC patients. Here, we explored transcriptional BC alterations to gain a better understanding of age-related tumour biology, also subtype-stratified.

Methods
We studied publicly available global BC mRNA expression (n = 3999) and proteomics data (n = 113), exploring differentially expressed genes, enriched gene sets, and gene networks in the young compared to older patients.

Results
We identified transcriptional patterns reflecting increased proliferation and oncogenic signalling in BC of the young, also in subtype-stratified analyses. Six up-regulated hub genes built a novel age-related score, significantly associated with aggressive clinicopathologic features. A high 6 Gene Proliferation Score (6GPS) demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the molecular subtypes. The 6GPS significantly associated also with disease-specific survival within the luminal, lymph node-negative and Oncotype Dx intermediate subset.

Conclusions
We here demonstrate evidence of higher tumour cell proliferation in young BC patients, also when adjusting for molecular subtypes, and identified a novel age-based six-gene signature pointing to aggressive tumour features, tumour proliferation, and reduced survival—also in patient subsets with expected good prognosis.
HPV self-sampling among long-term non-attenders to cervical cancer screening in Norway: a pragmatic randomised controlled trial
Authors: Aasbø Gunvor , Tropè Ameli , Nygård Mari , Christiansen Irene Kraus , Baasland Ingrid , Iversen Grete Alrek , Munk Ane Cecilie , Christiansen Marit Halonen , Presthus Gro Kummeneje , Undem Karina , Bjørge Tone , Castle Philip E. , Hansen Bo T. 
Published: August 2022

Abstract
Background
Cervical cancer screening participation is suboptimal in most settings. We assessed whether human papillomavirus (HPV) self-sampling may increase screening participation among long-term non-attenders in Norway.

Methods
A pragmatic randomised controlled trial with participation as the primary outcome was initiated in the national cervical screening programme in March 2019. A random sample of 6000 women aged 35–69 years who had not attended screening for at least 10 years were randomised 1:1:1 to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in) for HPV testing or (iii) a self-sampling kit unsolicited (send-to-all) for HPV testing.

Results
Total participation was 4.8%, 17.0% and 27.7% among control, opt-in and send-to-all (P < 0.0001; participation difference (%) send-to-all vs. control: 22.9 (95%CI: 20.7, 25.2); opt-in vs. control: 12.3 (95%CI: 10.3, 14.2); send-to-all vs. opt-in: 10.7 (95% CI: 8.0, 13.3)). High-risk HPV was detected in 11.5% of self-samples and 9.2% of clinician-collected samples (P = 0.40). Most women (92.5%) who returned a positive self-sample attended the clinic for triage testing. Of the 933 women screened, 33 (3.5%) had CIN2 + (1.1%, 3.7%, 3.8% among control, opt-in, and send-to-all, respectively), and 11 (1.2%) had cervical cancer (0%, 1.2%, 1.3% among control, opt-in, send-to-all, respectively).

Conclusion
Opt-in and send-to-all self-sampling increased screening participation among long-term, higher-risk non-attenders.

Clinical trial registration
ClinicalTrials.gov NCT03873376.
Creation of Philadelphia chromosome by CRISPR/Cas9-mediated double cleavages on BCR and ABL1 genes as a model for initial event in leukemogenesis
Authors: Tamai Minori , Fujisawa Shinichi , Nguyen Thao T. T. , Komatsu Chiaki , Kagami Keiko , Kamimoto Kenji , Omachi Kohei , Kasai Shin , Harama Daisuke , Watanabe Atsushi , Akahane Koshi , Goi Kumiko , Naka Kazuhito , Kaname Tadashi , Teshima Takanori , Inukai Takeshi 
Published: August 2022

AbstractThe Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was obtained. In the subline, p210 BCR::ABL1 and its reciprocal ABL1::BCR fusions were generated as a result of balanced translocation corresponding to the Ph chromosome. Another set of sgRNAs targeting intron 1 of the BCR gene and intron 1 of the ABL1 gene induced a factor-independent subline expressing p190 BCR::ABL1. Both p210 and p190 BCR::ABL1 induced factor-independent growth by constitutively activating intracellular signaling pathways for transcriptional regulation of cell cycle progression and cell survival that are usually regulated by GM-CSF. These observations suggested that simultaneous DSBs at the BCR and ABL1 gene breakpoints are initiation events for oncogenesis in Ph+ leukemia. (200/200 words).
CD36 aggravates podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy in lupus nephritis
Authors: Lv Fu , He Yingxin , Xu Hongde , Li Yongchun , Han Lipei , Yan Lijie , Lang Hui , Zhao Yafei , Zhao Zhanzheng , Qi Yuanyuan 
Published: August 2022

AbstractA major cause of proteinuria in lupus nephritis (LN) is podocyte injury, and determining potential therapeutic targets to prevent podocyte injury is important from a clinical perspective in the treatment of LN. CD36 is involved in podocyte injury in several glomerulopathies and was reported to be a vital candidate gene in LN. Here, we determined the role of CD36 in the podocyte injury of LN and the underlying mechanisms. We observed that CD36 and NLRP3 (NLR family pyrin domain containing 3) were upregulated in the podocytes of lupus nephritis patients and MRL/lpr mice with renal impairment. In vitro, CD36, NLRP3 inflammasome, and autophagy were elevated accompanied with increased podocyte injury stimulated by IgG extracted from lupus nephritis patients compared that from healthy donors. Knocking out CD36 with the CRISPR/cas9 system decreased the NLRP3 inflammasome levels, increased the autophagy levels and alleviated podocyte injury. By enhancing autophagy, NLRP3 inflammasome was decreased and podocyte injury was alleviated. These results demonstrated that, in lupus nephritis, CD36 promoted podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy by enhancing which could decrease NLRP3 inflammasome and alleviate podocyte injury.
Multiplex viral tropism assay in complex cell populations with single-cell resolution
Authors: Keng Choong Tat , Guo Ke , Liu Yu-Chi , Shen Kimberle Yanyin , Lim Daryl Shern , Lovatt Matthew , Ang Heng Pei , Mehta Jodhbir S. , Chew Wei Leong 
Published: August 2022

AbstractGene therapy constitutes one of the most promising mode of disease treatments. Two key properties for therapeutic delivery vectors are its transduction efficiency (how well the vector delivers therapeutic cargo to desired target cells) and specificity (how well it avoids off-target delivery into unintended cells within the body). Here we developed an integrated bioinformatics and experimental pipeline that enables multiplex measurement of transduction efficiency and specificity, particularly by measuring how libraries of delivery vectors transduce libraries of diverse cell types. We demonstrated that pairing high-throughput measurement of AAV identity with high-resolution single-cell RNA transcriptomic sequencing maps how natural and engineered AAV variants transduce individual cells within human cerebral and ocular organoids. We further demonstrate that efficient AAV transduction observed in organoids is recapitulated in vivo in non-human primates. This library-on-library technology will be important for determining the safety and efficacy of therapeutic delivery vectors.
Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing
Authors: Diricks Margo , Merker Matthias , Wetzstein Nils , Kohl Thomas A. , Niemann Stefan , Maurer Florian P. 
Published: August 2022

AbstractMycobacterium abscessus is an emerging multidrug-resistant non-tuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Whole genome sequencing data of 1991 isolates were employed to validate the scheme, re-analyze global population structure and set genetic distance thresholds for cluster detection and taxonomic identification. We confirmed and amended the nomenclature of the main dominant circulating clones and found that these also correlate well with traditional 7-loci MLST. Dominant circulating clones could be linked to a corresponding reference genome with less than 250 alleles while 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.