bluuebunny/crossref_metadata_2025_split huggingface dataset:
Freshwater Displacement Effect on the Weddell Gyre Carbon Budget
Authors: Taylor Benjamin A. , MacGilchrist Graeme A. , Mazloff Matthew R. , Talley Lynne D. 
Published: September 2023

AbstractThe Weddell Gyre mediates carbon exchange between the abyssal ocean and atmosphere, which is critical to global climate. This region also features large and highly variable freshwater fluxes due to seasonal sea ice, net precipitation, and glacial melt; however, the impact of these freshwater fluxes on the regional carbon cycle has not been fully appreciated. Using a novel budget analysis of dissolved inorganic carbon (DIC) mass in the Biogeochemical Southern Ocean State Estimate, we highlight two freshwater‐driven transports. Where freshwater with minimal DIC enters the ocean, it displaces DIC‐rich seawater outwards, driving a lateral transport of 75 ± 5 Tg DIC/year. Additionally, sea ice export requires a compensating import of seawater, which carries 48 ± 11 Tg DIC/year into the gyre. Though often overlooked, these freshwater displacement effects are of leading order in the Weddell Gyre carbon budget in the state estimate and in regrouped box‐inversion estimates, with implications for evaluating basin‐scale carbon transport.
Sources of Air Pollution Health Impacts and Co‐Benefits of Carbon Neutrality in Santiago, Chile
Authors: Nawaz M. Omar , Henze Daven K. , Huneeus Nicolás J. , Osses Mauricio , Álamos Nicolás , Opazo Mariel A. , Gallardo Laura 
Published: September 2023

AbstractThe population of Santiago, Chile, experiences air pollution above global health guidelines that is attributable in part to large anthropogenic emissions. This is compounded by geographic features and meteorological conditions that are prone to pollution accumulation as well as secondary pollution production. In recent years, there have been improvements in air quality; however, the future of air pollution in Santiago remains unclear due to its growing population and increased vehicle use. Mitigation efforts can be supported by characterizing sources of air pollution and estimating how changes in emissions could affect air quality in future years. In this study, we conduct simulations using a chemical transport model (GEOS‐Chem) and perform adjoint calculations to characterize the relationship between health impacts associated with exposure to PM2.5, O3, and NO2 and anthropogenic emissions. We incorporate model updates in a new nested domain simulation over Central South America including local and regional anthropogenic emissions inventories for Chile. We estimate that 2,490 (1,360, 4,060) PM2.5‐ and O3‐related premature deaths and 5,350 (1,320, 11,330) NO2‐related new pediatric asthma cases were associated with pollution exposure in Santiago in 2015 and that a majority of these health impacts were attributable to anthropogenic emissions. We identify emissions from transportation, energy generation, and residential combustion as the leading contributors to these health impacts. Additionally, we estimate that Chile's commitment to attain carbon neutrality by 2050 could result in benefits in Santiago of 3,230 (1,240, 7,160) avoided deaths and 2,590 (640, 5,500) avoided pediatric asthma cases in 2050 compared to business‐as‐usual emissions.
Predictive Deep Learning for High‐Dimensional Inverse Modeling of Hydraulic Tomography in Gaussian and Non‐Gaussian Fields
Authors: Guo Quan , Liu Ming , Luo Jian 
Published: September 2023

AbstractInverse modeling of hydraulic tomography (HT) is computationally expensive for estimating high‐dimensional hydrogeologic parameter fields. In this work, we develop a novel method called HT‐INV‐NN, which combines dimensionality reduction techniques with a predictive deep learning (DL) model to estimate high‐dimensional Gaussian and non‐Gaussian channel fields. The HT‐INV‐NN model consists of a predictor that directly learns the inverse process from hydraulic head measurements to latent variables of random fields, and a decoder that generates high‐dimensional parameter fields from predicted latent variables. For Gaussian spatially correlated fields, the decoder utilizes principal components derived from spatial covariance, and for non‐Gaussian channel fields, a generative adversarial network (GAN) is trained using generated realizations based on a training image (TI). The predictor is a deep neural network calibrated using the reference data obtained from HT forward simulations, which can be implemented in parallel. HT‐INV‐NN is successfully tested in multiple numerical experiments including steady‐state and transient HT for estimating Gaussian fields in 2D and 3D, as well as binary discontinuous or continuous non‐Gaussian channel fields. The training process is efficient, and the model structure demonstrates robustness for input data with perturbations. The model performance on multiple validation data sets are satisfactory when compared with other numerical and deep learning methods.
Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis
Authors: Chen Jianfan , Xu Xueqing , Chen Song , Lu Ting , Zheng Yingchun , Gan Zhongzhi , Shen Zongrui , Ma Shunfei , Wang Duocai , Su Leyi , He Fei , Shang Xuan , Xu Huiyong , Chen Dong , Zhang Leitao , Xiong Fu 
Published: September 2023

AbstractHereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer
Authors: Advani Rahul , Luzzi Sara , Scott Emma , Dalgliesh Caroline , Weischenfeldt Joachim , Munkley Jennifer , Elliott David J. 
Published: September 2023

AbstractProstate cancer progression is connected to the activity of conventional oncogenes and tumour suppressors and driven by circulating steroid hormones. A key issue has been how to identify and care for aggressively developing prostate tumours. Here we discuss how expression of the splicing regulators ESRP1 and ESRP2, and how their role as “masterminds” of epithelial splicing patterns, have been identified as markers of aggressively proliferating prostate primary tumours. We suggest that the origin of prostate cancer within epithelial cells, and the subsequent association of ESRP1 and ESRP2 expression with more aggressive disease progression, identify ESRP1 and ESRP2 as lineage survival oncogenes. To move this field on in the future it will be important to identify the gene expression targets controlled by ESRP1/2 that regulate prostate cancer proliferation. Potential future therapies could be designed to target ESRP1 and ESRP2 protein activity or their regulated splice isoforms in aggressive prostate tumours. Design of these therapies is potentially complicated by the risk of producing a more mesenchymal splicing environment that might promote tumour metastasis.
PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons
Authors: Li Tao , Zhao Lili , Li Ye , Dang Meijuan , Lu Jialiang , Lu Ziwei , Huang Qiao , Yang Yang , Feng Yuxuan , Wang Xiaoya , Jian Yating , Wang Heying , Guo Yingying , Zhang Lei , Jiang Yu , Fan Songhua , Wu Shengxi , Fan Hong , Kuang Fang , Zhang Guilian 
Published: September 2023

AbstractIschemic stroke is a neurological disorder caused by vascular stenosis or occlusion, accounting for approximately 87% of strokes. Clinically, the most effective therapy for ischemic stroke is vascular recanalization, which aims to rescue neurons undergoing ischemic insults. Although reperfusion therapy is the most effective treatment for ischemic stroke, it still has limited benefits for many patients, and ischemia-reperfusion (I/R) injury is a widely recognized cause of poor prognosis. Here, we aim to investigate the mechanism of protein phosphatase Mg2+/Mn2+ dependent 1 K (PPM1K) mediates metabolic disorder of branched-chain amino acids (BCAA) by promoting fatty acid oxidation led to ferroptosis after cerebral I/R injury. We established the I/R model in mice and used BT2, a highly specific BCAA dehydrogenase (BCKD) kinase inhibitor to promote BCAA metabolism. It was further verified by lentivirus knocking down PPM1K in neurons. We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKD E1α subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. We next demonstrated that BCAA could induce oxidative stress, lipid peroxidation, and ferroptosis in primary cultured cortical neurons in vitro. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown. Furthermore, BT2 was found to alleviate neurological behavior disorders after I/R injury in mice, and the effect was similar to ferroptosis inhibitor ferrostatin-1. Our findings reveal a novel role of BCAA in neuronal ferroptosis after cerebral ischemia and provide a new potential target for the treatment of ischemic stroke.
The oleic/palmitic acid imbalance in exosomes isolated from NAFLD patients induces necroptosis of liver cells via the elongase-6/RIP-1 pathway
Authors: Scavo Maria Principia , Negro Roberto , Arrè Valentina , Depalo Nicoletta , Carrieri Livianna , Rizzi Federica , Mastrogiacomo Rita , Serino Grazia , Notarnicola Maria , De Nunzio Valentina , Lippolis Tamara , Pesole Pasqua Letizia , Coletta Sergio , Armentano Raffaele , Curri Maria Lucia , Giannelli Gianluigi 
Published: September 2023

AbstractExcessive toxic lipid accumulation in hepatocytes underlies the development of non-alcoholic fatty liver disease (NAFLD), phenotypically characterized by necrosis and steato-fibrosis, whose molecular mechanism is not yet fully understood. Patients with NAFLD display an imbalanced palmitic (PA) to oleic acid (OA) ratio. Moreover, increasing experimental evidence points out a relevant involvement of the exosomal content in disease progression. Aim of the study was to highlight the PA/OA imbalance within circulating exosomes, the subsequent intracellular alterations, and the impact on NALFD. Liver cells were challenged with exosomes isolated from both healthy subjects and NAFLD patients. The exosomal PA/OA ratio was artificially modified, and biological effects were evaluated. A NAFLD-derived exosomal PA/OA imbalance impacts liver cell cycle and cell viability. OA-modified NAFLD-derived exosomes restored cellular viability and proliferation, whereas the inclusion of PA into healthy subjects-derived exosomes negatively affected cell viability. Moreover, while OA reduced the phosphorylation and activation of the necroptosis marker, Receptor-interacting protein 1 (phospho-RIP-1), PA induced the opposite outcome, alongside increased levels of stress fibers, such as vimentin and fibronectin. Administration of NAFLD-derived exosomes led to increased expression of Elongase 6 (ELOVL6), Stearoyl-CoA desaturase 1 (SCD1), Tumor necrosis factor α (TNF-α), Mixed-lineage-kinase-domain-like-protein (MLKL) and RIP-1 in the hepatocytes, comparable to mRNA levels in the hepatocytes of NAFLD patients reported in the Gene Expression Omnibus (GEO) database. Genetic and pharmacological abrogation of ELOVL6 elicited a reduced expression of downstream molecules TNF-α, phospho-RIP-1, and phospho-MLKL upon administration of NAFLD-derived exosomes. Lastly, mice fed with high-fat diet exhibited higher phospho-RIP-1 than mice fed with control diet. Targeting the Elongase 6–RIP-1 signaling pathway offers a novel therapeutic approach for the treatment of the NALFD-induced exosomal PA/OA imbalance.
A linear weighted combination of polygenic scores for a broad range of traits improves prediction of coronary heart disease
Authors: Norland Kristjan , Schaid Daniel J. , Kullo Iftikhar J. 
Published: September 2023

AbstractPolygenic scores (PGS) for coronary heart disease (CHD) are constructed using GWAS summary statistics for CHD. However, pleiotropy is pervasive in biology and disease-associated variants often share etiologic pathways with multiple traits. Therefore, incorporating GWAS summary statistics of additional traits could improve the performance of PGS for CHD. Using lasso regression models, we developed two multi-PGS for CHD: 1) multiPGSCHD, utilizing GWAS summary statistics for CHD, its risk factors, and other ASCVD as training data and the UK Biobank for tuning, and 2) extendedPGSCHD, using existing PGS for a broader range of traits in the PGS Catalog as training data and the Atherosclerosis Risk in Communities Study (ARIC) cohort for tuning. We evaluated the performance of multiPGSCHD and extendedPGSCHD in the Mayo Clinic Biobank, an independent cohort of 43,578 adults of European ancestry which included 4,479 CHD cases and 39,099 controls. In the Mayo Clinic Biobank, a 1 SD increase in multiPGSCHD and extendedPGSCHD was associated with a 1.66-fold (95% CI: 1.60–1.71) and 1.70-fold (95% CI: 1.64–1.76) increased odds of CHD, respectively, in models that included age, sex, and 10 PCs, whereas an already published PGS for CHD (CHD_PRSCS) increased the odds by 1.50 (95% CI: 1.45–1.56). In the highest deciles of extendedPGSCHD, multiPGSCHD, and CHD_PRSCS, 18.4%, 17.5%, and 16.3% of patients had CHD, respectively.
Prevalence, temporal course and risk factors for phantom eye symptoms in uveal melanoma
Authors: Brown Stephen L. , Hope-Stone Laura , Hussain Rumana N. , Heimann Heinrich , van der Voort Nicola , Cherry M. Gemma 
Published: September 2023

Abstract
Background
Phantom eye symptoms (PES), particularly phantom visual sensations (PVS) and phantom eye pain (PEP), are common in enucleated patients and can lead to psychological distress. Current cross-sectional studies cannot examine the temporal course of symptoms, nor can they identify dynamic risk factors or consequences of PES.

Methods
Cohort study of 105 enucleated uveal melanoma patients returning self-report questionnaires, within 4 weeks of diagnosis and 6-, 12- and 24-months post-treatment. Questionnaires measuring PVS and PEP symptoms in the week prior to completion, pain severity, Hospital Anxiety and Depression Scale scores and the Functional Assessment of Cancer Therapy scale (FACT-G) measuring quality of life.

Results
PVS and PEP emerged after 6 months, were relatively stable over the study and did not remit. PVS showed 6-, 12- and 24-month prevalence rates of 44.6%, 48.2% and 30.2%, and PEP 16.1%, 18.4% and 17.5% respectively. PVS were generally elementary, with only 10–15% of the total cohort experiencing complex sensations. PEP was generally neither prolonged nor intense, except in a small proportion. PVS and PEP were showed moderate associations but did not predict each other prospectively. Anxiety within 4 weeks of diagnosis was a risk factor for the initiation of PEP. Neither PVS nor PEP prospectively predicted anxiety, depression or quality of life.

Conclusions
PES were prevalent and non-remitting, beginning within 6 months of enucleation. PVS and PEP may not represent symptoms of a coherent syndrome. We discuss findings with reference to theories of phantom sensations, and directions for clinical practise and research.
Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2
Authors: Francis Magen E. , Jansen Ethan B. , Yourkowski Anthony , Selim Alaa , Swan Cynthia L. , MacPhee Brian K. , Thivierge Brittany , Buchanan Rachelle , Lavender Kerry J. , Darbellay Joseph , Rogers Matthew B. , Lew Jocelyne , Gerdts Volker , Falzarano Darryl , Skowronski Danuta M. , Sjaarda Calvin , Kelvin Alyson A. 
Published: September 2023

AbstractSARS-CoV-2 variants and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Importantly, understanding of how previous infection may influence future exposures, especially in the context of seasonal coronaviruses and SARS-CoV-2 variants, is still limited. Here we adopted a step-wise experimental approach to examine the primary immune response and subsequent immune recall toward antigenically distinct coronaviruses using male Syrian hamsters. Hamsters were initially inoculated with seasonal coronaviruses (HCoV-NL63, HCoV-229E, or HCoV-OC43), or SARS-CoV-2 pango B lineage virus, then challenged with SARS-CoV-2 pango B lineage virus, or SARS-CoV-2 variants Beta or Omicron. Although infection with seasonal coronaviruses offered little protection against SARS-CoV-2 challenge, HCoV-NL63-infected animals had an increase of the previously elicited HCoV-NL63-specific neutralizing antibodies during challenge with SARS-CoV-2. On the other hand, primary infection with HCoV-OC43 induced distinct T cell gene signatures. Gene expression profiling indicated interferon responses and germinal center reactions to be induced during more similar primary infection-challenge combinations while signatures of increased inflammation as well as suppression of the antiviral response were observed following antigenically distant viral challenges. This work characterizes and analyzes seasonal coronaviruses effect on SARS-CoV-2 secondary infection and the findings are important for pan-coronavirus vaccine design.
A systematic review of neuroimaging studies of clozapine-resistant schizophrenia
Authors: Pang Tiffanie Sze Wing , Chun Johnny Siu Wah , Wong Ting Yat , Chu Sin Ting , Ma Chak Fai , Honer William G. , Chan Sherry Kit Wa 
Published: September 2023

AbstractThis systematic review aimed to review neuroimaging studies comparing clozapine-resistant schizophrenia patients with clozapine-responding patients, and with first-line antipsychotic responding (FLR) patients. A total of 19 studies including 6 longitudinal studies were identified. Imaging techniques comprised computerized tomography (CT, n = 3), structural magnetic resonance imaging (MRI, n = 7), magnetic resonance spectroscopy (MRS, n = 5), functional MRI (n = 1), single-photon emission computerized tomography (SPECT, n = 3) and diffusion tensor imaging (DTI, n = 1). The most consistent finding was hypo-frontality in the clozapine-resistant group compared with the clozapine-responding group with possible differences in frontal-striatal-basal ganglia circuitry as well as the GABA level between the two treatment-resistant groups. Additional statistically significant findings were reported when comparing clozapine-resistant patients with the FLR group, including lower cortical thickness and brain volume of multiple brain regions as well as lower Glx/Cr level in the dorsolateral prefrontal cortex. Both treatment-resistant groups were found to have extensive differences in neurobiological features in comparison with the FLR group. Overall results suggested treatment-resistant schizophrenia is likely to be a neurobiological distinct type of the illness. Clozapine-resistant and clozapine-responding schizophrenia are likely to have both shared and distinct neurobiological features. However, conclusions from existing studies are limited, and future multi-center collaborative studies are required with a consensus clinical definition of patient samples, multimodal imaging tools, and longitudinal study designs.
Comparison of conventional mechanical ventilation and high-frequency oscillatory ventilation in congenital diaphragmatic hernias: a systematic review and meta-analysis
Authors: Yang Hee-Beom , Pierro Agostino , Kim Hyun-Young 
Published: September 2023

AbstractOutcomes of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) in patients with congenital diaphragmatic hernia (CDH) were compared through a systematic review and meta-analysis. Outcome measures included mortality and incidence of chronic lung disease (CLD). Odds ratio (OR) and 95% confidence interval (95%CI) were evaluated. Subgroup analyses were performed according to the strategy for applying HFOV in CDH patients. Group A: CMV was initially applied in all CDH patients, and HFOV was applied in unstable patients. Group B: chronologically analyzed. (CMV and HFOV era) Group C: CMV or HFOV was used as the initial MV. Of the 2199 abstracts screened, 15 full-text articles were analyzed. Regarding mortality, 16.7% (365/2180) and 32.8% (456/1389) patients died in CMV and HFOV, respectively (OR, 2.53; 95%CI 2.12–3.01). Subgroup analyses showed significantly worse, better, and equivalent mortality for HFOV than that for CMV in group A, B, and C, respectively. CLD occurred in 32.4% (399/1230) and 49.3% (369/749) patients in CMV and HFOV, respectively (OR, 2.37; 95%CI 1.93–2.90). The evidence from the literature is poor. Mortality and the incidence of CLD appear worse after HFOV in children with CDH. Cautious interpretation is needed due to the heterogeneity of each study.
Dual-sense slot-based CP MIMO antenna with polarization bandwidth reconfigurability
Authors: Hussain Niamat , Aljaloud Khaled , Hussain Rifaqat , Alqahtani Ali H. , Khan Zia Ullah , Tahir Farooq A. , Abbasi Qammer H. 
Published: September 2023

AbstractIn this letter, a compact, planar circularly polarized (CP) sub-GHz slot-based multiple-input-multiple-output (MIMO) antenna with dual sense CP along with polarization bandwidth reconfigurability is presented. The pentagonal reactively loaded slot is fed by two folded tapered feedlines to achieve CP. The antenna offers left-hand-circular polarization (RHCP) with the as well as right hand circular polarization (LHCP). The antenna exhibit linearly polarization (LP) by exciting two ports simultaneously. Moreover, the antenna CP resonance can be reconfigured by varying the capacitance of the varactor diode. The antenna has a wide −10 dB operating frequency band from 578–929 MHz. while the axial ratio (AR) bandwidth ranges from 490–810 MHz. Moreover, the two elements MIMO are optimized and placed on compact dimensions 100 × 100 × 0.76 mm3 to realize pattern diversity. The antenna’s key characteristics are compact size, wide-band sub-GHz operation, dual sense CP, polarization bandwidth reconfigurability and good MIMO performance. Thus, it is a suitable candidate to be utilized in CubeSats applications in sub-GHz bands.