bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distress, demoralization, and fulfillment among palliative care providers during the COVID-19 pandemic
Authors: Tang Michael , Ann-Yi Sujin , Zhukovsky Donna S. , Fellman Bryan , Bruera Eduardo 
Published: December 2023

AbstractObjectivesProlonged distress is a risk factor for burnout among health-care providers (HCP) and may contribute to demoralization. We examined sources of distress during the COVID-19 pandemic and associations with demoralization.MethodsThis prospective cross-sectional survey of HCP was conducted among palliative care providers of an academic medical center. Participants completed a survey evaluating sources of distress and the Demoralization Scale-II (DS-II) to measure the intensity of demoralization.ResultsOf 106 eligible participants, 74 (70%) completed the survey. DS-II median (range) score was 2 (0–19). There were no statistically significant associations with demographic characteristics. Participants reported high rates of distress for multiple reasons and high rates of sense of fulfillment (90%) and satisfaction (89%) with their profession.Significance of resultsOur study identified high levels of distress but low demoralization rates. Further study to evaluate fulfillment and satisfaction as protective factors against demoralization and burnout is indicated.
Do mountains kill states? Exploring the diversity of Southeast Asian highland communities
Authors: Leadbetter Michael Paul , Sastrawan Wayan Jarrah 
Published: December 2023

AbstractMountains and highlands are not what scholars have conventionally imagined them to be: environments that limit and constrain their inhabitants in deterministic ways. Rather, mountains and highlands provide unique opportunities for people to engage in creative transformation of their societies. Highland communities are connected to a wider world, and they radically remake and experiment with their landscapes, settlements, and societies. Mountains serve as birthplaces and testing grounds for statecraft, urbanism, irrigation, and monumental landscape engineering. Here we explore the diversity of highland communities by analysing the latest archaeological and historical discoveries from three regions across Southeast Asia: the Kulen mountains (Cambodia), the volcanoes of central Java (Indonesia), and the Ifugao highlands (the Philippines). We find that, far from being a negative image of the ‘civilized’ lowlands, mountains were creative, diverse, dynamic, and well-connected places. This compels us to change the way we conceive of today’s highland communities and their relationships to modern nation-states.
Gender- and sexuality-minoritised adolescents in DBT: a reflexive thematic analysis of minority-specific treatment targets and experience
Authors: Camp J. , Morris A. , Wilde H. , Smith P. , Rimes K. A. 
Published: December 2023

Abstract

Gender- and sexuality-minoritised (GSM) adolescents are at increased risk of self-harm and suicidal behaviours compared with their cisgender and heterosexual peers. This increased risk is thought to be explained in part by exposure to stigma and societal oppression. Dialectical behaviour therapy (DBT) is an evidence-based intervention for self-harm and suicidal behaviour that may have advantages for supporting GSM young people in distress. No study has yet sought to understand what GSM-associated difficulties may be important to consider in DBT for adolescents, or the experiences of GSM young people in a standard DBT programme. Therefore, this study aimed to understand the experiences of GSM young people in DBT and what difficulties and dilemmas associated with their gender and sexuality diversity were thought by them to be important to target in DBT. Qualitative interviews were conducted with 14 GSM young people in a comprehensive DBT programme and were analysed using reflexive thematic analysis. The analysis was supported by two further GSM young people who had finished DBT. The findings were split into three over-arching themes (Identity, Impact of Others, and Space for Sexual and Gender Identity in DBT), each with themes within. The identity-based theme included ‘identity confusion and acceptance’; the relationship-based themes included ‘cis-Heterosexism’ and ‘community connectedness’; and the space within DBT themes included ‘negotiating focus and targeting in DBT’ and ‘creating safety in DBT’. Findings are discussed in relation to implications and recommendations for therapists working with GSM young people within and outside of DBT.

Key learning aims

(1)
To learn about what gender- and sexuality-minoritised (GSM) young people consider to be important GSM-associated contributors to distress and thus potential treatment targets in DBT.

(2)
To learn about what GSM young people felt were barriers to negotiating GSM-associated difficulties as a focus in DBT and how safety was created in the therapeutic relationship.

(3)
To consider potential implications and recommendations for improvements to practice when supporting GSM young people in therapy.
Mapping Mantle Flows and Slab Anisotropy in the Cascadia Subduction Zone
Authors: Liang Xuran , Zhao Dapeng , Hua Yuanyuan , Xu Yi‐Gang 
Published: December 2023

AbstractThe Cascadia margin is an unusual subduction zone characterized by the downdip movement of young and thin oceanic plates, where mantle flow and intraslab deformation are still unclear. Here we present new anisotropic tomography of the Cascadia subduction zone, in which the hexagonal symmetry axis of anisotropy is tilting rather than horizontal or vertical as assumed in previous studies of seismic anisotropy. Subduction‐induced entrained and toroidal flows under the Cascadia margin are discriminated well by the spatial relationship between tilting‐axis anisotropy and slab geometry. The obliquely entrained flow is trapped in a narrow zone (<100 km wide) above and below the subducting slab and reaches ∼200 km depth, which is surrounded by large‐scale sub‐horizontal toroidal flow. The intraslab anisotropy is trench‐normal above 80 km depth but changes to trench‐parallel at 100–400 km depths, which may reflect fossil anisotropy overprinted by deep deformation beneath the arc, or joint effect of serpentinization and hydrous faulting.
Surface Temperature Pattern Scenarios Suggest Higher Warming Rates Than Current Projections
Authors: Alessi Marc J. , Rugenstein Maria A. A. 
Published: December 2023

AbstractAtmosphere‐ocean general circulation models (AOGCMs) struggle to reproduce recently observed sea surface temperature (SST) trend patterns. Here, we quantify the relevance of this SST pattern uncertainty to global‐mean temperature projections through convolving Green's functions with SST pattern scenarios that differ from the ones AOGCMs produce by themselves. We find that future SST pattern uncertainty has a significant impact on projections, such as increasing total model uncertainty by 40% in a high‐emissions scenario by 2085. A reversal of the current cooling trend in the East Pacific over the next few decades could lead to a period of global‐mean warming with a 60% higher rate than currently projected. SST pattern uncertainty works through a destabilization of the shortwave cloud feedback to affect temperature projections. It is critical for climate change impact, adaptation, and mitigation assessments to incorporate this previously unaccounted for uncertainty until we trust the evolution of SST patterns in AOGCMs.
Anisotropy and Deformation Processes in Southern California From Rotational Observations
Authors: Tang Le , Igel Heiner , Montagner Jean‐Paul 
Published: December 2023

AbstractSeismic anisotropy in the upper mantle reveals geodynamic processes and the tectonic evolution of the Earth. The two most powerful methods, surface wave tomography, and shear‐wave splitting observations, cannot investigate the deep local anisotropy with good vertical and lateral resolution, resulting in poor constraints on plate deformation processes of the complex plate boundary beneath the Southern California region. Here, we show that the amplitude ratio of translational displacement and rotation makes it possible to retrieve the local anisotropy in the upper mantle. Azimuthal anisotropy in the asthenosphere is well determined and resolved in lateral and vertical directions. The fast axis retrieved from amplitude observations indicates the local rapid changes in plate deformation and complex pattern of mantle flow, which is compatible with the distributions of horizontal mantle flow illuminated by geodetic measurements, providing new insights on geodynamic processes of the Southern California region.
Legacy Phosphorus and Ecosystem Memory Control Future Water Quality in a Eutrophic Lake
Authors: Hanson P. C. , Ladwig R. , Buelo C. , Albright E. A. , Delany A. D. , Carey C. C. 
Published: December 2023

AbstractLake water clarity, phytoplankton biomass, and hypolimnetic oxygen concentration are metrics of water quality that are highly degraded in eutrophic systems. Eutrophication is linked to legacy nutrients stored in catchment soils and in lake sediments. Long lags in water quality improvement under scenarios of nutrient load reduction to lakes indicate an apparent ecosystem memory tied to the interactions between water biogeochemistry and lake sediment nutrients. To investigate how nutrient legacies and ecosystem memory control lake water quality dynamics, we coupled nutrient cycling and lake metabolism in a model to recreate long‐term water quality of a eutrophic lake (Lake Mendota, Wisconsin, USA). We modeled long‐term recovery of water quality under scenarios of nutrient load reduction and found that the rates and patterns of water quality improvement depended on changes in phosphorus (P) and organic carbon storage in the water column and sediments. Through scenarios of water quality improvement, we showed that water quality variables have distinct phases of change determined by the turnover rates of storage pools—an initial and rapid water quality improvement due to water column flushing, followed by a much longer and slower improvement as sediment P pools were slowly reduced. Water clarity, phytoplankton biomass, and hypolimnetic dissolved oxygen differed in their time responses. Water clarity and algal biomass improved within years of nutrient reductions, but hypolimnetic oxygen took decades to improve. Even with reduced catchment loading, recovery of Lake Mendota to a mesotrophic state may require decades due to nutrient legacies and long ecosystem memory.
A Process‐Based Model to Track Water Pollutant Generation at High Resolution and Its Pathway to Discharge
Authors: Zhuang Yujie , Liu Xin , Yuan Zengwei , Sheng Hu , Gao Jianqi 
Published: December 2023

AbstractThe estimation of water pollutant loads is of crucial importance as it decides data inputs for both subsequent water quality models and watershed pollutant mitigation strategy. However, the generation of water pollutant loads at high resolution and the life‐cycle pathway of them from sources, through pipelines and wastewater treatment plants, finally to recipient water bodies remain unclear. This study aims to establish a process‐based Water Pollutant Loads Tracking model and applies it to a rapidly urbanizing watershed in Taihu Lake Basin, China at the resolution of 5 m × 5 m in 2017, whose terrain is flat, slowly lowing from west to east. Results show that, of 261.55 tons of the total phosphorus (TP) generation, 71.28% is collected, and 64.32% is treated, with only 26.46% discharged to the water bodies and 1.25% to the target ones. The spatial hotspots of TP generation are mainly concentrated in residential and industrial areas. Direct discharges from point sources and nonpoint runoffs, especially in rainy seasons, are recognized as the main challenges for local water pollution control. The main innovation of this study is to quantify the generation of water pollutant loads at high resolution and to trace the subsequent pathway to collection and discharge, and then to identify the potential substantial gap between generation and discharge, demonstrating the efficacy and broader applicability of this model.
Tumor-suppressive functions of protein lysine methyltransferases
Authors: Aziz Nur , Hong Yo Han , Kim Han Gyung , Kim Ji Hye , Cho Jae Youl 
Published: December 2023

AbstractProtein lysine methyltransferases (PKMTs) play crucial roles in histone and nonhistone modifications, and their dysregulation has been linked to the development and progression of cancer. While the majority of studies have focused on the oncogenic functions of PKMTs, extensive evidence has indicated that these enzymes also play roles in tumor suppression by regulating the stability of p53 and β-catenin, promoting α-tubulin-mediated genomic stability, and regulating the transcription of oncogenes and tumor suppressors. Despite their contradictory roles in tumorigenesis, many PKMTs have been identified as potential therapeutic targets for cancer treatment. However, PKMT inhibitors may have unintended negative effects depending on the specific cancer type and target enzyme. Therefore, this review aims to comprehensively summarize the tumor-suppressive effects of PKMTs and to provide new insights into the development of anticancer drugs targeting PKMTs.
MiR-1246b, a novel miRNA molecule of extracellular vesicles in bronchoalveolar lavage fluid, promotes nodule growth through FGF14 in patients with lung cancer
Authors: Huang Jing , Ding Ming , Lu Yuan , Xu Lu , Zhang Yu , Han Shuhua , Zhu Xiaoli , Li Yiping , Chen Pingsheng 
Published: December 2023

AbstractWith the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a common problem in the clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients. BALF was obtained, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. We found that FGF14 was the binding target of miR-1246b by luciferase assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further leading to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.
Mitochondrial E3 ligase MARCH5 is a safeguard against DNA-PKcs-mediated immune signaling in mitochondria-damaged cells
Authors: Heo June , Park Yeon-Ji , Kim Yonghyeon , Lee Ho-Soo , Kim Jeongah , Kwon Soon-Hwan , Kang Myeong-Gyun , Rhee Hyun-Woo , Sun Woong , Lee Jae-Ho , Cho Hyeseong 
Published: December 2023

AbstractMitochondrial dysfunction is important in various chronic degenerative disorders, and aberrant immune responses elicited by cytoplasmic mitochondrial DNA (mtDNA) may be related. Here, we developed mtDNA-targeted MTERF1-FokI and TFAM-FokI endonuclease systems to induce mitochondrial DNA double-strand breaks (mtDSBs). In these cells, the mtDNA copy number was significantly reduced upon mtDSB induction. Interestingly, in cGAS knockout cells, synthesis of interferon β1 and interferon-stimulated gene was increased upon mtDSB induction. We found that mtDSBs activated DNA-PKcs and HSPA8 in a VDAC1-dependent manner. Importantly, the mitochondrial E3 ligase MARCH5 bound active DNA-PKcs in cells with mtDSBs and reduced the type І interferon response through the degradation of DNA-PKcs. Likewise, mitochondrial damage caused by LPS treatment in RAW264.7 macrophage cells increased phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA in a DNA-PKcs-dependent manner. Accordingly, in March5 knockout macrophages, phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA were prolonged after LPS stimulation. Together, cytoplasmic mtDNA elicits a cellular immune response through DNA-PKcs, and mitochondrial MARCH5 may be a safeguard to prevent persistent inflammatory reactions.
Class IIa HDACs inhibit cell death pathways and protect muscle integrity in response to lipotoxicity
Authors: Martin Sheree D. , Connor Timothy , Sanigorski Andrew , McEwen Kevin A. , Henstridge Darren C. , Nijagal Brunda , De Souza David , Tull Dedreia L. , Meikle Peter J. , Kowalski Greg M. , Bruce Clinton R. , Gregorevic Paul , Febbraio Mark A. , Collier Fiona M. , Walder Ken R. , McGee Sean L. 
Published: December 2023

AbstractLipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism. This metabolic reprogramming was also associated with impaired apoptosis and ferroptosis responses, and preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis. Redox drivers of ferroptosis derived from oxidative metabolism were also reduced. The relevance of this pathway was demonstrated by overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice, which enhanced oxidative metabolic capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of skeletal muscle oxidative metabolism, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.
Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome
Authors: Nguyen Thu Giang , Ritter Christina , Kummer Eva 
Published: December 2023

AbstractMitochondria contain their own genetic information and a dedicated translation system to express it. The mitochondrial ribosome is assembled from mitochondrial-encoded RNA and nuclear-encoded ribosomal proteins. Assembly is coordinated in the mitochondrial matrix by biogenesis factors that transiently associate with the maturing particle. Here, we present a structural snapshot of a large mitoribosomal subunit assembly intermediate containing 7 biogenesis factors including the GTPases GTPBP7 and GTPBP10. Our structure illustrates how GTPBP10 aids the folding of the ribosomal RNA during the biogenesis process, how this process is related to bacterial ribosome biogenesis, and why mitochondria require two biogenesis factors in contrast to only one in bacteria.
Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche
Authors: Manieri Elisa , Tie Guodong , Malagola Ermanno , Seruggia Davide , Madha Shariq , Maglieri Adrianna , Huang Kun , Fujiwara Yuko , Zhang Kevin , Orkin Stuart H. , Wang Timothy C. , He Ruiyang , McCarthy Neil , Shivdasani Ramesh A. 
Published: December 2023

AbstractPDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA+ cells. Sub-epithelial PDGFRAHi myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRALo CD55+ cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1+ cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55+ cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.
Direct probing of single-molecule chemiluminescent reaction dynamics under catalytic conditions in solution
Authors: Zhang Ziqing , Dong Jinrun , Yang Yibo , Zhou Yuan , Chen Yuang , Xu Yang , Feng Jiandong 
Published: December 2023

AbstractChemical reaction kinetics can be evaluated by probing dynamic changes of chemical substrates or physical phenomena accompanied during the reaction process. Chemiluminescence, a light emitting exoenergetic process, involves random reaction positions and kinetics in solution that are typically characterized by ensemble measurements with nonnegligible average effects. Chemiluminescent reaction dynamics at the single-molecule level remains elusive. Here we report direct imaging of single-molecule chemiluminescent reactions in solution and probing of their reaction dynamics under catalytic conditions. Double-substrate Michaelis–Menten type of catalytic kinetics is found to govern the single-molecule reaction dynamics in solution, and a heterogeneity is found among different catalyst particles and different catalytic sites on a single particle. We further show that single-molecule chemiluminescence imaging can be used to evaluate the thermodynamics of the catalytic system, resolving activation energy at the single-particle level. Our work provides fundamental insights into chemiluminescent reactions and offers an efficient approach for evaluating catalysts.
Origamic metal-organic framework toward mechanical metamaterial
Authors: Jin Eunji , Lee In Seong , Yang D. ChangMo , Moon Dohyun , Nam Joohan , Cho Hyeonsoo , Kang Eunyoung , Lee Junghye , Noh Hyuk-Jun , Min Seung Kyu , Choe Wonyoung 
Published: December 2023

AbstractOrigami, known as paper folding has become a fascinating research topic recently. Origami-inspired materials often establish mechanical properties that are difficult to achieve in conventional materials. However, the materials based on origami tessellation at the molecular level have been significantly underexplored. Herein, we report a two-dimensional (2D) porphyrinic metal-organic framework (MOF), self-assembled from Zn nodes and flexible porphyrin linkers, displaying folding motions based on origami tessellation. A combined experimental and theoretical investigation demonstrated the origami mechanism of the 2D porphyrinic MOF, whereby the flexible linker acts as a pivoting point. The discovery of the 2D tessellation hidden in the 2D MOF unveils origami mechanics at the molecular level.