bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias‐Adjustment Methods for Future Subdaily Precipitation Extremes Consistent Across Durations
Authors: Van de Vyver Hans , Van Schaeybroeck Bert , De Cruz Lesley , Hamdi Rafiq , Termonia Piet 
Published: March 2023

AbstractModel output from climate projections often requires bias‐adjustment to compensate for systematic model errors. A bias‐adjustment method for extreme precipitation intensity is proposed that preserves the scaling equation for different accumulation levels from hourly to daily, using intensity‐duration‐frequency (IDF) modeling. A validation is performed within a pseudo‐reality setting, based on hourly precipitation from 28 regional climate model projections of the EURO‐CORDEX ensemble over Belgium. The scaling‐based adjustment methods improve upon previous methods, an optimal method is identified, and, analytical quantile mapping methods must be avoided due to three identified problems. The ensemble mean of the adjusted extreme precipitation intensity obeys the above‐mentioned scale‐invariance property, which is consistent with observed extreme intensities. We thus show that IDF modeling provides added value in the context of bias‐adjustment, and, that the particular IDF model proposed balances well between accuracy and the preservation of desired properties such as scale invariance and consistency among rainfall durations.
Geometry‐Based Prediction of Solute Transport Process in Single 3D Rock Fractures Under Laminar Flow Regime
Authors: Zhou Jia‐Qing , Guo Li‐Guo , Jiao Jiu Jimmy , Luo Xin 
Published: March 2023

AbstractSubsurface substance migration in the fractured rock aquifer is mainly controlled by fractures, and prediction of solute transport in fractures is important to many geophysical processes and engineering activities. This study explores the possibility of predicting transport process in single rock fractures from measurable physical properties. For this purpose, we conducted a large number of pore‐scale simulations of solute transport in single 3D rock fractures with different apertures and various degrees of roughness. The numerically‐obtained breakthrough curves under laminar flow regime were reproduced with high fidelity by the classic analytical solution within the framework of macroscopic advection‐dispersion theory. The fitted transport coefficients (hydrodynamic dispersion coefficient and transport velocity) were normalized by the parallel‐plate model's values, and were further parameterized by aperture b and roughness parameter σ/b in form of ωeb/ψ + λ(mσ/b − 1)/bn and 1 − α(σ/b)/βb, respectively. By incorporating these parameterized transport coefficients and the modified cubic law into the classic analytical solution, we proposed a new transport predictive model. This model was adaptively degenerated into the classic analytical solution of parallel‐plate model, and was proved to be capable of predicting macroscopic solute transport only relying on arithmetic‐mean mechanical aperture and its standard deviation, without solving the velocity and concentration fields. By the established model, we quantitatively revealed the impacts of aperture and roughness on the breakthrough curve under laminar flow regime. This study puts a step toward predicting solute transport process in fractured rock aquifers with measurable geometric properties.
An Interpretable Machine Learning Procedure Which Unravels Hidden Interplanetary Drivers of the Low Latitude Dayside Magnetopause
Authors: Li Sheng , Sun Yang‐Yi , Chen Chieh‐Hung 
Published: March 2023

AbstractIn this study, we propose an interpretable machine learning procedure to unravel the importance of multiple interplanetary parameters to the Earth's magnetopause standoff distance (MSD). We construct the interpretable procedure based on SHapley Additive exPlanations. A magnetopause crossings database from the Time History of Events and Macroscale Interactions during Substorms satellites and the multiple interplanetary parameters from OMNI during the period of 2007–2016 are utilized. The solar wind dynamic pressure and the interplanetary magnetic field (IMF) BZ are widely suggested as the important two interplanetary parameters that drive the MSD. However, the examination of the interpretable procedure suggests that the magnitude of the IMF is the second significant parameter after the dynamic pressure. Although the magnetic pressure, which is the function of the IMF magnitude was considered in previous studies, the importance of the IMF magnitude was underestimated. The interpretable procedure also reveals that the IMF magnitude and the BZ have different effects on the MSD. Their joint effect is the formation of the MSD sag near BZ = 5 nT. This is for the first time the interpretable concept is being applied to construct a machine‐learning magnetopause model.
Under What Conditions Does Transverse Macrodispersion Exist in Groundwater Flow?
Authors: Lester Daniel R. , Dentz Marco , Singh Prajwal , Bandopadhyay Aditya 
Published: March 2023

AbstractIn recent years there has been vigorous debate whether asymptotic transverse macrodispersion exists in steady three‐dimensional (3D) groundwater flows in the purely advective limit. This question is tied to the topology of 3D flow paths (termed the Lagrangian kinematics), specifically whether streamlines can undergo braiding motions or can wander freely in the transverse direction. In this study we determine which Darcy flows do admit asymptotic transverse macrodispersion for purely advective transport on the basis of the conductivity structure. We prove that porous media with smooth, locally isotropic hydraulic conductivity exhibit zero transverse macrodispersion under pure advection due to constraints on the Lagrangian kinematics of these flows, whereas either non‐smooth or locally anisotropic conductivity fields can generate transverse macrodispersion. This has implications for upscaling locally isotropic porous media to the block scale as this can result in a locally anisotropic conductivity, leading to non‐zero macrodispersion at the block scale that is spurious in that it does not arise for the fully resolved Darcy scale flow. We also show that conventional numerical methods for computation of particle trajectories do not explicitly preserve the kinematic constraints associated with locally isotropic Darcy flow, and propose a novel psuedo‐symplectic method that preserves these constraints. These results provide insights into the mechanisms that govern transverse macrodispersion in groundwater flow, and unify seemingly contradictory results in the literature in a consistent framework. These insights call into question the ability of smooth, locally isotropic conductivity fields to represent flow and transport in real heterogeneous porous media.
The molecular pathology of schizophrenia: an overview of existing knowledge and new directions for future research
Authors: Nakamura Takumi , Takata Atsushi 
Published: March 2023

AbstractDespite enormous efforts employing various approaches, the molecular pathology in the schizophrenia brain remains elusive. On the other hand, the knowledge of the association between the disease risk and changes in the DNA sequences, in other words, our understanding of the genetic pathology of schizophrenia, has dramatically improved over the past two decades. As the consequence, now we can explain more than 20% of the liability to schizophrenia by considering all analyzable common genetic variants including those with weak or no statistically significant association. Also, a large-scale exome sequencing study identified single genes whose rare mutations substantially increase the risk for schizophrenia, of which six genes (SETD1A, CUL1, XPO7, GRIA3, GRIN2A, and RB1CC1) showed odds ratios larger than ten. Based on these findings together with the preceding discovery of copy number variants (CNVs) with similarly large effect sizes, multiple disease models with high etiological validity have been generated and analyzed. Studies of the brains of these models, as well as transcriptomic and epigenomic analyses of patient postmortem tissues, have provided new insights into the molecular pathology of schizophrenia. In this review, we overview the current knowledge acquired from these studies, their limitations, and directions for future research that may redefine schizophrenia based on biological alterations in the responsible organ rather than operationalized criteria.
L-2hydroxyglutaric acid rewires amino acid metabolism in colorectal cancer via the mTOR-ATF4 axis
Authors: Tabata Sho , Kojima Yasushi , Sakamoto Takeharu , Igarashi Kaori , Umetsu Ko , Ishikawa Takamasa , Hirayama Akiyoshi , Kajino-Sakamoto Rie , Sakamoto Naoya , Yasumoto Ken-ichi , Okano Keiichi , Suzuki Yasuyuki , Yachida Shinichi , Aoki Masahiro , Soga Tomoyoshi 
Published: March 2023

AbstractOncometabolites, such as D/L-2-hydroxyglutarate (2HG), have directly been implicated in carcinogenesis; however, the underlying molecular mechanisms remain poorly understood. Here, we showed that the levels of the L-enantiomer of 2HG (L2HG) were specifically increased in colorectal cancer (CRC) tissues and cell lines compared with the D-enantiomer of 2HG (D2HG). In addition, L2HG increased the expression of ATF4 and its target genes by activating the mTOR pathway, which subsequently provided amino acids and improved the survival of CRC cells under serum deprivation. Downregulating the expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) and oxoglutarate dehydrogenase (OGDH) increased L2HG levels in CRC, thereby activating mTOR-ATF4 signaling. Furthermore, L2HGDH overexpression reduced L2HG-mediated mTOR-ATF4 signaling under hypoxia, whereas L2HGDH knockdown promoted tumor growth and amino acid metabolism in vivo. Together, these results indicate that L2HG ameliorates nutritional stress by activating the mTOR-ATF4 axis and thus could be a potential therapeutic target for CRC.
Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients
Authors: Fonseca Rodrigo , Arribas Mariano , Wiedmeier-Nutor Julia E. , Kusne Yael N. , González Vélez Miguel , Kosiorek Heidi E. , Butterfield Richard J. , Kirsch Ilan R. , Mikhael Joseph R. , Stewart A. Keith , Reeder Craig , Larsen Jeremy , Bergsagel P. Leif , Fonseca Rafael 
Published: March 2023

AbstractMinimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10−6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.
Liver transplantation in metastatic colorectal cancer: are we ready for it?
Authors: Ros Javier , Salva Francesc , Dopazo Cristina , López Daniel , Saoudi Nadia , Baraibar Iosune , Charco Ramon , Tabernero Josep , Elez Elena 
Published: March 2023

AbstractColorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting.
The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis
Authors: Wu Wanzhou , Wang Xuan , Liao Longsheng , Chen Jing , Wang Yue , Yao Meilian , Zhu Lingping , Li Jiayu , Wang Xuan , Chen Alex F. , Zhang Guogang , Zhang Zheng , Bai Yongping 
Published: March 2023

AbstractCancer or endothelial cells preferably catabolize glucose through aerobic glycolysis rather than oxidative phosphorylation. Intracellular ionic signaling has been shown to regulate glucose metabolism, but the underlying ion channel has yet to be identified. RNA-seq, metabolomics and genetic assay revealed that the TRPM7 channel regulated cellular glycolysis. Deletion of TRPM7 suppressed cancer cell glycolysis and reduced the xenograft tumor burden. Deficiency of endothelial TRPM7 inhibited postnatal retinal angiogenesis in mice. Mechanistically, TRPM7 transcriptionally regulated the solute carrier family 2 member 3 (SLC2A3, also known as GLUT3) via Ca2+ influx-induced calcineurin activation. Furthermore, CREB-regulated transcription coactivator 2 (CRTC2) and CREB act downstream of calcineurin to relay Ca2+ signal to SLC2A3 transcription. Expression of the constitutively active CRTC2 or CREB in TRPM7 knockout cell normalized glycolytic metabolism and cell growth. The TRPM7 channel represents a novel regulator of glycolytic reprogramming. Inhibition of the TRPM7-dependent glycolysis could be harnessed for cancer therapy.
USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC
Authors: Wang Nan , Li Tianzi , Liu Wanyu , Lin Jinhua , Zhang Ke , Li Zhenhao , Huang Yanfei , Shi Yufei , Xu Meilan , Liu Xuekui 
Published: March 2023

AbstractGTPase-activating protein-binding protein 2 (G3BP2) is a key stress granule-associated RNA-binding protein responsible for the formation of stress granules (SGs). Hyperactivation of G3BP2 is associated with various pathological conditions, especially cancers. Emerging evidence indicates that post-translational modifications (PTMs) play critical roles in gene transcription, integrate metabolism and immune surveillance. However, how PTMs directly regulate G3BP2 activity is lacking. Here, our analyses identify a novel mechanism that PRMT5-mediated G3BP2-R468me2 enhances the binding to deubiquitinase USP7, which ensures the deubiquitination and stabilization of G3BP2. Mechanistically, USP7- and PRMT5-dependent G3BP2 stabilization consequently guarantee robust ACLY activation, which thereby stimulating de novo lipogenesis and tumorigenesis. More importantly, USP7-induced G3BP2 deubiquitination is attenuated by PRMT5 depletion or inhibition. PRMT5-activity dependent methylation of G3BP2 is required for its deubiquitination and stabilization by USP7. Consistently, G3BP2, PRMT5 and G3BP2 R468me2 protein levels were found positively correlated in clinical patients and associated with poor prognosis. Altogether, these data suggest that PRMT5-USP7-G3BP2 regulatory axis serves as a lipid metabolism reprogramming mechanism in tumorigenesis, and unveil a promising therapeutic target in the metabolic treatment of head and neck squamous carcinoma.
Downregulation of KLF10 contributes to the regeneration of survived renal tubular cells in cisplatin-induced acute kidney injury via ZBTB7A-KLF10-PTEN axis
Authors: Zhang Yang , Bao Siyu , Wang Daxi , Lu Wei , Xu Sujuan , Zhou Weiran , Wang Xiaoyan , Xu Xialian , Ding Xiaoqiang , Zhao Shuan 
Published: March 2023

AbstractAcute kidney injury (AKI) is a common clinical dysfunction with complicated pathophysiology and limited therapeutic methods. Renal tubular injury and the following regeneration process play a vital role in the course of AKI, but the underlining molecular mechanism remains unclear. In this study, network-based analysis of online transcriptional data of human kidney found that KLF10 was closely related to renal function, tubular injury and regeneration in various renal diseases. Three classical mouse models confirmed the downregulation of KLF10 in AKI and its correlation with tubular regeneration and AKI outcome. The 3D renal tubular model in vitro and fluorescent visualization system of cellular proliferation were constructed to show that KLF10 declined in survived cells but increased during tubular formation or conquering proliferative impediment. Furthermore, overexpression of KLF10 significantly inhibited, whereas knockdown of KLF10 extremely promoted the capacity of proliferation, injury repairing and lumen-formation of renal tubular cells. In mechanism, PTEN/AKT pathway were validated as the downstream of KLF10 and participated in its regulation of tubular regeneration. By adopting proteomic mass spectrum and dual-luciferase reporter assay, ZBTB7A were found to be the upstream transcription factor of KLF10. Our findings suggest that downregulation of KLF10 positively contributed to tubular regeneration in cisplatin induced acute kidney injury via ZBTB7A-KLF10-PTEN axis, which gives insight into the novel therapeutic and diagnostical target of AKI.
Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer
Authors: Maccarinelli Federica , Coltrini Daniela , Mussi Silvia , Bugatti Mattia , Turati Marta , Chiodelli Paola , Giacomini Arianna , De Cillis Floriana , Cattane Nadia , Cattaneo Annamaria , Ligresti Alessia , Asperti Michela , Poli Maura , Vermi William , Presta Marco , Ronca Roberto 
Published: March 2023

AbstractProstate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa.
Implementation and scalability of shared care models for chronic eye disease: a realist assessment informed by health system stakeholders in Finland, the United Kingdom, and Australia
Authors: Ford Belinda , Angell Blake , Liu Hueiming , White Andrew , Keay Lisa 
Published: March 2023

Abstract
Background/Objectives
Several health systems have implemented innovative models of care which share the management of patients with chronic eye diseases between ophthalmologists and optometrists. These models have demonstrated positive outcomes for health systems including increased access for patients, service efficiency and cost-savings. This study aims to understand factors which support successful implementation and scalability of these models of care.

Subjects/Methods
Semi-structured interviews were conducted with 21 key health system stakeholders (clinicians, managers, administrators, policy-makers) in Finland, United Kingdom and Australia between October 2018 and February 2020. Data were analyzed using a realist framework to identify the contexts, mechanisms of action, and outcomes of sustained and emerging shared care schemes.

Results
Five key themes relating to successful implementation of shared care were identified as (1) clinician-led solutions, (2) redistributing teams, (3) building inter-disciplinary trust, (4) using evidence for buy-in, and (5) standardized care protocols. Scalability was found to be supported by (6) financial incentives, (7) integrated information systems, (8) local governance, and (9) a need for evidence of longer-term health and economic benefits.

Conclusions
The themes and program theories presented in this paper should be considered when testing and scaling shared eye care schemes to optimize benefits and promote sustainability.
A comparative study between 10-MHz and 15-MHz ultrasound probes for retinal evaluation in silicone-oil-filled globes
Authors: Albadawi Maha A. , Allam Riham S. H. M. , Khalil Noha M. M. , Eissa Iman M. 
Published: March 2023

Abstract
Purpose
To compare 10-MHz and 15-MHz B-scan probes regarding the detection and localization of retinal detachment (RD) in silicone-oil-filled eyes.

Methods
This cross-sectional observational study included 100 eyes (98 patients) -having media opacity precluding fundus examination- scheduled for silicone-oil removal. Patients were examined in the sitting-position using both frequencies one week preoperatively. Longitudinal and transverse scans were taken in primary-gaze, inferior, inferonasal, and inferotemporal positions to detect the presence/absence and extent of RD. Patients were sub-grouped according to axial lengths (AXLs), state of silicone emulsification, and globe filling. Agreement between sonographic and intraoperative observations was compared.

Results
No statistically significant differences were found between 15-MHz and intra-operative findings regarding RD detection (P = 0.752) and accurate localization of inferior, inferonasal, and inferotemporal RD (P = 0.279, 0.606, and 0.599). There were statistically significant differences between 10-MHz and intra-operative findings regarding RD detection and localization (P < 0.001). The 15-MHz probe was superior to 10-MHz probe regarding the accuracy of RD detection and localization (94% and 47%, respectively). The accuracy of 15-MHz probe was 88%, 83%, and 85% in detecting and localizing inferior, inferonasal, and inferotemporal RD compared to 45%, 60%, and 62% with 10-MHz probe. The 15-MHz probe showed better sensitivity while 10-MHz probe showed better accuracy in eyes with short AXLs. The 10-MHz probe showed better sensitivity in patients with sonographic emulsification while15-MHz probe had better sensitivity in detecting vitreoretinal-interface disorders.

Conclusion
The 15-MHz B-scan probe is more accurate in detecting and localizing recurrent RD in silicone-oil-filled globes with higher sensitivity in detecting vitreoretinal-interface disorders.