bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Evolution of Detachment Fault Systems in Necking Domains: Insights From the Klakk Fault Complex and the Frøya High, Mid‐Norwegian Rifted Margin
Authors: Gresseth J. L. S. , Osmundsen P. T. , Péron‐Pinvidic G. 
Published: March 2023

AbstractDetachment fault systems typically record displacements in the order of 10s of kilometers. The principles that control the growth of smaller magnitude normal faults are not fully applicable to the evolution of detachment fault systems. We use interpretation of 2D and 3D seismic reflection data from the mid‐Norwegian rifted margin to investigate how the structural evolution of a detachment fault interacted with the effects of isostatic footwall rollback to produce complex 3D geometries and control the configuration of associated supradetachment basins. We further investigate the effects of lateral interaction and linkage of extensional detachment faults on the necking domain configuration. In our study area, the domain‐bounding Klakk Fault Complex demonstrates how successive incision may induce a complex structural relief in response to faulting and fault plane folding. We interpret the previously proposed metamorphic core complex within its footwall as an extension‐parallel turtleback‐structure. The now eroded turtleback is flanked by a major supradetachment basin, connecting two main basin segments. We attribute footwall‐ and turtleback exhumation to Middle Jurassic‐Early Cretaceous rifting. The study area further demonstrates how detachment fault geometries can change during rifting and lead to the formation of younger, successively incising fault splays. Lateral linkage between the original detachment fault plane and these fault splays enables displacement along a detachment fault system consisting of fault segments generated at different stages in time. Implicitly, detachment faults are complex 3D systems that change configuration during their evolution, perpetually controlling associated basin formation, footwall configuration, subsidence and uplift patterns.
Length of positive surgical margins after radical prostatectomy: Does size matter? – A systematic review and meta-analysis
Authors: John Athul , Lim Alicia , Catterwell Rick , Selth Luke , O’Callaghan Michael 
Published: March 2023

Abstract
Objectives
The prognostic capacity of positive surgical margins (PSM) for biochemical recurrence (BCR) is unclear, with inconsistent findings across published studies. We aimed to systematically review and perform a meta-analysis exploring the impact of Positive surgical margin length on biochemical recurrence in men after radical prostatectomy.

Methods
A search was conducted using the MEDLINE, Scopus, Embase and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The quality of the studies was assessed using the Newcastle-Ottawa scale, and the protocol was registered in advance (PROSPERO: CRD42020195908). This meta-analysis included 16 studies with BCR as the primary outcome measure.

Results
Studies used various dichotomised thresholds for PSM length. A subgroup meta-analysis was performed using the reported multivariable hazard ratio (Continuous, 3, and 1 mm PSM length). PSM length (continuous) was independently associated with an increased risk of BCR (7 studies, HR 1.04 (CI 1.02–1.05), I2 = 8% p < 0.05). PSM length greater than 3 mm conferred a higher risk of BCR compared to less than 3 mm (4 studies, HR 1.99 (1.54–2.58) I2 = 0%, p < 0.05). There was also an increased risk of BCR associated with PSM length of less than 1 mm compared to negative surgical margins (3 studies, HR 1.46 (1.05–2.04), I2 = 0%, P = 0.02).

Conclusion
PSM length is independently prognostic for BCR after radical prostatectomy. Further long-term studies are needed to estimate the impact on systemic progression.
PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway
Authors: Zhang Rui , Dong Mengxue , Tu Juchuanli , Li Fengkai , Deng Qiaodan , Xu Jiahui , He Xueyan , Ding Jiajun , Xia Jie , Sheng Dandan , Chang Zhaoxia , Ma Wei , Dong Haonan , Zhang Yi , Zhang Lixing , Zhang Lu , Liu Suling 
Published: March 2023

AbstractOur previous studies have showed that C-C motif chemokine ligand 20 (CCL20) advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell (BCSC) self-renewal. However, it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment (TME). Here, we observed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors. Mechanistically, CCL20 activated the differentiation of granulocyte-monocyte progenitors (GMPs) via its receptor C-C motif chemokine receptor 6 (CCR6) leading to the PMN-MDSC expansion. PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors (CCL20-modulated PMN-MDSCs) secreted amounts of C-X-C motif chemokine ligand 2 (CXCL2) and increased ALDH+ BCSCs via activating CXCR2/NOTCH1/HEY1 signaling pathway. Furthermore, C-X-C motif chemokine receptor 2 (CXCR2) antagonist SB225002 enhanced the docetaxel (DTX) effects on tumor growth by decreasing BCSCs in CCL20high-expressing tumors. These findings elucidated how CCL20 modulated the TME to promote cancer development, indicating a new therapeutic strategy by interfering with the interaction between PMN-MDSCs and BCSCs in breast cancer, especially in CCL20high-expressing breast cancer.
The role of cytoreductive nephrectomy and systemic therapy in the management of tumour thrombus in patients with metastatic renal cell carcinoma
Authors: Mittal Abhenil , Al-Ezzi Esmail , Li Xuan , Moloney Brian , Wilson Brooke , Spiliopoulou Pavlina , Sridhar Srikala , Fallah-Rad Nazanin , Chung Peter , Hamilton Robert James , O’malley Martin , Hansen Aaron R. 
Published: March 2023

Abstract
Background
Outcomes for patients with metastatic renal cell carcinoma (mRCC) and tumour thrombus remain poor. Recent data suggest limited role for cytoreductive nephrectomy (CN) and data on thrombus response to systemic therapy (ST) is scarce. Here, we describe response and survival of patients with de novo mRCC and thrombi treated with ST with or without CN.

Methods
Demographics, disease characteristics and survival of patients with de novo mRCC were collected. Progression-free survival (PFS) and overall survival (OS) in months (m) was calculated using the Kaplan–Meier method (log-rank).

Results
Between 2002 and 2019, 226 patients with mRCC were identified, 64 (28.3%) had tumour thrombus out of which 18 (28.1%) received only ST. Among 12 evaluable patients, thrombus response, stability and progression were seen in 3 (25%), 6 (50%) and 3 (25%) patients, respectively. Median OS was similar for patients with and without tumour thrombus treated with systemic therapy alone [OS: 12.1 m (8.8–27.7) vs. 13.9 m (7.9–21.5), p = 0.87]. CN predicted for better OS in patients with tumour thrombus [OS: 29.4 m (17.4–48.9) vs. 12.1 m (8.8–27.7), p = 0.01].

Conclusion
In this retrospective series of patients with mRCC and tumour thrombus, addition of CN to ST improved outcomes. Validation of these findings with contemporary regimens is needed.
Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction
Authors: Calabresi Paolo , Mechelli Alessandro , Natale Giuseppina , Volpicelli-Daley Laura , Di Lazzaro Giulia , Ghiglieri Veronica 
Published: March 2023

AbstractAlthough the discovery of the critical role of α-synuclein (α-syn) in the pathogenesis of Parkinson’s disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of α-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other α-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, α-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of α-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting α-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
Crocodile defensin (CpoBD13) antifungal activity via pH-dependent phospholipid targeting and membrane disruption
Authors: Williams Scott A. , Lay Fung T. , Bindra Guneet K. , Banjara Suresh , Poon Ivan K. H. , Phan Thanh Kha , Kvansakul Marc , Hulett Mark D. 
Published: March 2023

AbstractCrocodilians are an order of ancient reptiles that thrive in pathogen-rich environments. The ability to inhabit these harsh environments is indicative of a resilient innate immune system. Defensins, a family of cysteine-rich cationic host defence peptides, are a major component of the innate immune systems of all plant and animal species, however crocodilian defensins are poorly characterised. We now show that the saltwater crocodile defensin CpoBD13 harbors potent antifungal activity that is mediated by a pH-dependent membrane-targeting action. CpoBD13 binds the phospholipid phosphatidic acid (PA) to form a large helical oligomeric complex, with specific histidine residues mediating PA binding. The utilisation of histidine residues for PA engagement allows CpoBD13 to exhibit differential activity at a range of environmental pH values, where CpoBD13 is optimally active in an acidic environment.
Visualizing electroluminescence process in light-emitting electrochemical cells
Authors: Yasuji Kosuke , Sakanoue Tomo , Yonekawa Fumihiro , Kanemoto Katsuichi 
Published: March 2023

AbstractElectroluminescence occurs via recombination reactions between electrons and holes, but these processes have not been directly evaluated. Here, we explore the operation dynamics of ionic liquid-based light-emitting electrochemical cells (LECs) with stable electroluminescence by multi-timescale spectroscopic measurements synchronized with the device operation. Bias-modulation spectroscopy, measuring spectral responses to modulated biases, reveals the bias-dependent behavior of p-doped layers varying from growth to saturation and to recession. The operation dynamics of the LEC is directly visualized by time-resolved bias-modulation spectra, revealing the following findings. Electron injection occurs more slowly than hole injection, causing delay of electroluminescence with respect to the p-doping. N-doping proceeds as the well-grown p-doped layer recedes, which occur while the electroluminescence intensity remains constant. With the growth of n-doped layer, hole injection is reduced due to charge balance, leading to hole-accumulation on the anode, after which LEC operation reaches equilibrium. These spectroscopic techniques are widely applicable to explore the dynamics of electroluminescence-devices.
Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST
Authors: Long Yahui , Ang Kok Siong , Li Mengwei , Chong Kian Long Kelvin , Sethi Raman , Zhong Chengwei , Xu Hang , Ong Zhiwei , Sachaphibulkij Karishma , Chen Ao , Zeng Li , Fu Huazhu , Wu Min , Lim Lina Hsiu Kim , Liu Longqi , Chen Jinmiao 
Published: March 2023

AbstractSpatial transcriptomics technologies generate gene expression profiles with spatial context, requiring spatially informed analysis tools for three key tasks, spatial clustering, multisample integration, and cell-type deconvolution. We present GraphST, a graph self-supervised contrastive learning method that fully exploits spatial transcriptomics data to outperform existing methods. It combines graph neural networks with self-supervised contrastive learning to learn informative and discriminative spot representations by minimizing the embedding distance between spatially adjacent spots and vice versa. We demonstrated GraphST on multiple tissue types and technology platforms. GraphST achieved 10% higher clustering accuracy and better delineated fine-grained tissue structures in brain and embryo tissues. GraphST is also the only method that can jointly analyze multiple tissue slices in vertical or horizontal integration while correcting batch effects. Lastly, GraphST demonstrated superior cell-type deconvolution to capture spatial niches like lymph node germinal centers and exhausted tumor infiltrating T cells in breast tumor tissue.
Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome
Authors: Romero Luis O. , Caires Rebeca , Kaitlyn Victor A. , Ramirez Juanma , Sierra-Valdez Francisco J. , Walsh Patrick , Truong Vincent , Lee Jungsoo , Mayor Ugo , Reiter Lawrence T. , Vásquez Valeria , Cordero-Morales Julio F. 
Published: March 2023

AbstractAngelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function. A linoleic acid (LA)-enriched diet increases PIEZO2 activity, mechano-excitability, and improves gait in male AS mice. Finally, LA supplementation increases PIEZO2 function in stem cell-derived neurons from individuals with AS. We propose a mechanism whereby loss of UBE3A expression reduces PIEZO2 function and identified a fatty acid that enhances channel activity and ameliorates AS-associated mechano-sensory deficits.
Prediction of transition state structures of gas-phase chemical reactions via machine learning
Authors: Choi Sunghwan 
Published: March 2023

AbstractThe elucidation of transition state (TS) structures is essential for understanding the mechanisms of chemical reactions and exploring reaction networks. Despite significant advances in computational approaches, TS searching remains a challenging problem owing to the difficulty of constructing an initial structure and heavy computational costs. In this paper, a machine learning (ML) model for predicting the TS structures of general organic reactions is proposed. The proposed model derives the interatomic distances of a TS structure from atomic pair features reflecting reactant, product, and linearly interpolated structures. The model exhibits excellent accuracy, particularly for atomic pairs in which bond formation or breakage occurs. The predicted TS structures yield a high success ratio (93.8%) for quantum chemical saddle point optimizations, and 88.8% of the optimization results have energy errors of less than 0.1 kcal mol−1. Additionally, as a proof of concept, the exploration of multiple reaction paths of an organic reaction is demonstrated based on ML inferences. I envision that the proposed approach will aid in the construction of initial geometries for TS optimization and reaction path exploration.
The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers
Authors: Halámková Jana , Bohovicová Lucia , Pehalová Lucie , Kazda Tomáš , Goněc Roman , Staněk Teodor , Mouková Lucie , Adámková Krákorová Dagmar , Kozáková Šárka , Svoboda Marek , Demlová Regina , Gabrielová Lucie , Hernychová Lenka , Kiss Igor 
Published: March 2023

AbstractCalcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.
An illusion of disownership over one’s own limb is associated with pain perception
Authors: Nishiyama Yuta , Yamashita Chihiro , Nomura Shusaku 
Published: March 2023

AbstractViewing one’s body and even a fake/virtual body experienced as one’s own has been suggested to modulate pain perception. However, what happens to pain perception when one’s own body part is felt as not belonging to one? We designed a paradigm to induce an illusory feeling of disownership regarding one’s limb, investigating whether the feeling affects pain threshold. Participants observed right-side images of their bodies from a third-person perspective via a head-mounted display in real-time. Following instructions, they moved their left hand while keeping their left elbow behind the upper body, so that the connection of their arm to the torso was not visible (test condition), or in front of it, so they could see the arm being part of them (control condition). Then, pain threshold was tested with a thermal stimulator. We found a significantly higher strength of disownership in the test condition than in the control condition. While there was no pain modulation within and between conditions, disownership ratings negatively correlated with pain-threshold changes, where the participants reporting explicit disownership showed lower pain-threshold changes than the others. The finding suggests that while multisensory disintegration had no modulatory effect, the individual sense of disownership was associated with pain perception.
Biases associated with database structure for COVID-19 detection in X-ray images
Authors: Arias-Garzón Daniel , Tabares-Soto Reinel , Bernal-Salcedo Joshua , Ruz Gonzalo A. 
Published: March 2023

AbstractSeveral artificial intelligence algorithms have been developed for COVID-19-related topics. One that has been common is the COVID-19 diagnosis using chest X-rays, where the eagerness to obtain early results has triggered the construction of a series of datasets where bias management has not been thorough from the point of view of patient information, capture conditions, class imbalance, and careless mixtures of multiple datasets. This paper analyses 19 datasets of COVID-19 chest X-ray images, identifying potential biases. Moreover, computational experiments were conducted using one of the most popular datasets in this domain, which obtains a 96.19% of classification accuracy on the complete dataset. Nevertheless, when evaluated with the
ethical tool Aequitas, it fails on all the metrics. Ethical tools enhanced with some distribution and image quality considerations
are the keys to developing or choosing a dataset with fewer bias issues. We aim to provide broad research on dataset problems,
tools, and suggestions for future dataset developments and COVID-19 applications using chest X-ray images.
Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies
Authors: Yamagiwa Yoko , Tanaka Keitaro , Matsuo Keitaro , Wada Keiko , Lin Yingsong , Sugawara Yumi , Mizoue Tetsuya , Sawada Norie , Takimoto Hidemi , Ito Hidemi , Kitamura Tetsuhisa , Sakata Ritsu , Kimura Takashi , Tanaka Shiori , Inoue Manami ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan, Abe Sarah Krull , Nomura Shuhei 
Published: March 2023

AbstractIn Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33–0.43) for sustained virologic response (SVR) and 1.70 (1.61–1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19–0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19–0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.
Mass flow and consumption calculations of pharmaceuticals in sewage treatment plant with emphasis on the fate and risk quotient assessment
Authors: Badawy Mohamed I. , El-Gohary Fatma A. , Abdel-Wahed Mahmoud S. , Gad-Allah Tarek A. , Ali Mohamed E. M. 
Published: March 2023

AbstractIn Egypt, pharmaceuticals consumption increased dramatically owing to the population growth and the unrestricted sale manner. Accordingly, the occurrence and fate of nine common pharmaceutical active compounds (PhACs) were scrutinized at a sewage treatment plant (STP) in Giza, Egypt. The levels of these PhACs were assessed in different the wastewater treatment stages and dewatered sludge phase using high-performance liquid chromatography coupled with photodiode arrays detector. The average concentrations of the total PhACs detected in influent, primary sedimentation effluent (PSE) and final effluent (FE) were 227, 155 and 89 µg L−1, respectively. The overall removal efficiency of the individual PhACs ranged from 18 to 72% removal. The occurrence trend revealed that biodegradation and adsorption are the concurrently removal mechanisms of the studied PhACs. The overall consumption per day in West of Greater Cairo was estimated based on influent concentration of STP. Sulfamethoxazole, paracetamol and diclofenac were detected with the highest levels in the influent of STP, PSE and FE as well as in the dewatered sludge. Furthermore, the high concentrations of these compounds in the sludge confirm the adsorption pathway removal of theses PhACs. The risk quotient (RQ) assessment for the detected PhACs in FE is greatly higher than the predicted non-effect concentration (PNEC). Conclusively, the FE of STP is considered a risky source for PhACs in adjacent surface water.