bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of m6A-associated genes as prognostic and immune-associated biomarkers in Wilms tumor
Authors: Zhuo Yingquan , Zhang Wengqi , Du Jun , Jiang Hua , Chen Guangtang , Feng Xiaoyun , Gu Huajian 
Published: November 2023

Abstract
Objectives
Wilms tumor (WT) is a common renal malignant tumor in children. We aimed to investigate the potential prognostic value of m6A-related genes and their relationship to the immune microenvironment in WT.

Methods
RNA-seq data and clinical information from 121 WT and 6 normal samples were obtained from the University of California Santa Cruz Xena database. We used various bioinformatics analysis tools to analyze these data and verify the expression level of m6A-related genes by experiments.

Results
Four m6A-related genes were successfully screened, including ADGRG2, CPD, CTHRC1, and LRTM2. Kaplan–Meier survival curves showed that the four genes were closely related to the prognosis of WT, which was also confirmed by receiver operator characteristic curves. Subsequently, in the immune microenvironment of WT, we discovered that Th1_cells were positively correlated with ADGRG2, CCR was negatively correlated with CPD, CCR was positively correlated with CTHRC1, APC_co_stimulation, CCR, Macrophages, inflammation-promoting cells, Treg, and Type_II_IFN_Reponse were negatively correlated with LRTM2. Finally, qRT-PCR showed that expression levels of the four genes were upregulated in the nephroblastoma cell lines (G-401, SK-NEP-1, and WT-CLS1) compared with the human embryonic kidney cell lines (293T).

Conclusions
Taken together, our study first time screened the m6A-related genes and revealed that ADGRG2, CPD, CTHRC1, and LRTM2 are the prognostic and immune-associated biomarkers in WT.
l-Palmitoylcarnitine potentiates plasmin and tPA to inhibit thrombosis
Authors: Yang Juan , Cha Lina , Wang Yepeng , Zhang Quan , Tang Xiaopeng , Shao Jianlin , Duan Zilei 
Published: November 2023

Abstractl-Palmitoylcarnitine (L-PC) is an important endogenous fatty acid metabolite. Its classical biological functions are involved in the regulations of membrane molecular dynamics and the β-oxidation of fatty acids. Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis, implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC, a long-chain acylcarnitine, takes part in coagulation. Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator (tPA). L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant (KD) of 6.47 × 10–9 and 4.46 × 10–9 M, respectively, showing high affinities. In mouse model, L-PC administration significantly inhibited FeCl3-induced arterial thrombosis. It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion (tMCAO) mouse model. L-PC induced little bleeding complications. The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.
Graphical Abstract
Psychisches Wohlbefinden als Prädiktor der frühen körperlichen Gebrechlichkeit
Authors: Lozza-Fiacco Serena , Grötsch Maria , Stute Petra , Ehlert Ulrike 
Published: November 2023

ZusammenfassungNur wenige Studien untersuchten Schutzfaktoren für körperliche Gebrechlichkeit und ihren Zusammenhang mit ersten pathologischen Veränderungen. Der Fokus wurde auf frühe Gebrechlichkeitsmarker und ihre Verbindung zum psychischen Wohlbefinden gesetzt. Da psychisches Wohlbefinden die Stressbewältigung beeinflusst und Stress das Gebrechlichkeitsrisiko erhöhen kann, wurde zusätzlich untersucht, ob chronischer Stress die Beziehung zwischen Wohlbefinden und Gebrechlichkeit erklärt. Insgesamt wurden 532 gesunde Erwachsene (49,44 % Frauen; Durchschnittsalter: 54,36 Jahre; Bereich: 40–73) untersucht. Die Greifkraft (HGS) und der Lean-Body-Mass-Index (LBMI) wurden als Gebrechlichkeitsmarker untersucht. Selbst eingeschätzter chronischer Stress wurde als Stressindikator gemessen. Das psychische Wohlbefinden stand bei Männern (p < 0,001) und Frauen (p < 0,05) in einem positiven Zusammenhang mit der HGS, nicht aber mit dem LBMI. Bei Männern, aber nicht bei Frauen, wurde der Zusammenhang zwischen psychischem Wohlbefinden und HGS (95 %-KI [−0,2135, −0,0028]) teilweise durch selbstberichteten chronischen Stress vermittelt. Dies ist die erste Studie, die darauf hinweist, dass ein höheres psychisches Wohlbefinden mit einem günstigeren HGS einhergeht, und die auf einen geschlechtsspezifischen Einfluss von chronischem Stress hindeutet.
Gallium and germanium static and kinetic sorption and desorption studies on cerium dioxide nanoparticles
Authors: Ondrák Fialová Kateřina , Adámek Kryštof , Štamberg Karel , Šebesta Ferdinand , Vlk Martin , Kozempel Ján 
Published: November 2023

AbstractPositron-emitting 68Ga has become an integral part of nuclear medicine. It is a radionuclide obtained from 68Ge/68Ga radionuclide generators. Apart from other qualities, it is a feature that have caused its growing popularity in medical practice. Nevertheless, the increasing demand for 68Ga supply results in the need of new and improved separation systems to obtain it. Hydrous oxides such as titanium or zirconium dioxide are usually the preferred separation materials, but other oxidic materials are under study. Thorough testing of the sorption behaviour is often overlooked in these studies, though it is indispensable for the applicability and suitability assessment. This work is focused on the sorption behaviour description of cerium dioxide prepared by calcination of ceric nitrate. Both batch and kinetic sorption experiments were conducted. Such a thorough study has never been carried out for this material. In batch experiments, the optimal conditions for separation of 68Ga and 68Ge were found. Kinetic experimental data were used for mathematical modelling. Six kinetic models derived from various rate-controlling processes were used and their applicability was demonstrated. The diffusion in an inert layer is the rate-controlling process of both gallium and germanium sorption and desorption. This model description of sorption kinetics will further enable us to optimise the sorption and desorption processes numerically. Thus far, it was found out that the prepared cerium dioxide can quantitatively adsorb germanium in very short time of 10 min from 1mM hydrochloric acid and the most convenient medium for 68Ge and 68Ga separation is 0.1 M hydrochloric acid.
Machine-Learning-Based Spam Mail Detector
Authors: Charanarur Panem , Jain Harsh , Rao G. Srinivasa , Samanta Debabrata , Sengar Sandeep Singh , Hewage Chaminda Thushara 
Published: November 2023

AbstractThe proliferation of spam emails, a predominant form of online harassment, has elevated the significance of email in daily life. As a consequence, a substantial portion of individuals remain vulnerable to fraudulent activities. Despite Gmail’s “spam mail filtration system,” its effectiveness is not absolute. It occasionally misclassifies legitimate messages, leading to their confinement in the spam folder, or overlooks potentially harmful spam emails. This results in the occurrence of false positives. This research scrutinizes the historical data, cookies, caches, Session Restores, flash artifacts, and super cookies of Internet Explorer, Firefox, and Chrome on the Windows 10 platform. Data was collected through Google, Firefox, and Internet Explorer, operating within the Windows 10 environment. It has been observed that browsers store user behavior data on the host computer’s hard drive. The implications of this study hold substantial value for computer forensics researchers, law enforcement professionals, and digital forensics experts. The study leverages Python, alongside pertinent libraries such as pandas, Numpy, Matplotlib, scikit-learn, and flask, to facilitate its investigation. The experiment result and analysis show KN and NB algorithms have the best accuracy and precision score compared to other Algorithms.
Finerenone and other future therapeutic options for Alport syndrome
Authors: Pearce Helen , Mabillard Holly 
Published: November 2023

AbstractAlport syndrome is a rare genetic disease that results in disordered basement membrane type IV collagen resulting in haematuria, proteinuria and often development of renal fibrosis leading to progressive kidney disease. The therapeutic blockage of the renin-angiotensin-aldosterone system, which slows the progression to kidney failure, is supported by strong evidence. Recent clinical trials using sodium-glucose co-transporter-2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRA) in patients with chronic kidney disease have changed the therapeutic landscape. Patients with Alport syndrome and progressive kidney disease may benefit from treatment with MRAs because research has shown that these drugs are nephroprotective through a variety of mechanisms, including by preventing fibrosis. Ongoing clinical trials show great promise in order to help establish the long-term safety and efficacy of Finerenone, a MRA. This review discusses the evidence for the use of MRAs as a potential treatment in Alport syndrome that may slow the progression of chronic kidney disease and prevent patients reaching kidney failure.
Decentralized research technology use in multicenter clinical research studies based at U.S. academic research centers
Authors: Cummins Mollie R. , Burr Jeri , Young Lisa , Yeatts Sharon D. , Ecklund Dixie J. , Bunnell Brian E. , Dwyer Jamie P. , VanBuren John M. 
Published: November 2023

Abstract

Introduction:
During the COVID-19 pandemic, research organizations accelerated adoption of technologies that enable remote participation. Now, there’s a pressing need to evaluate current decentralization practices and develop appropriate research, education, and operations infrastructure. The purpose of this study was to examine current adoption of decentralization technologies in a sample of clinical research studies conducted by academic research organizations (AROs).

Methods:
The setting was three data coordinating centers in the U.S. These centers initiated coordination of 44 clinical research studies during or after 2020, with national recruitment and enrollment, and entailing coordination between one and one hundred sites. We determined the decentralization technologies used in these studies.

Results:
We obtained data for 44/44 (100%) trials coordinated by the three centers. Three technologies have been adopted across nearly all studies (98–100%): eIRB, eSource, and Clinical Trial Management Systems. Commonly used technologies included e-Signature (32/44, 73%), Online Payments Portals (26/44, 59%), ePROs (23/44, 53%), Interactive Response Technology (22/44, 50%), Telemedicine (19/44, 43%), and eConsent (18/44, 41%). Wearables (7/44,16%) and Online Recruitment Portals (5/44,11%) were less common. Rarely utilized technologies included Direct-to-Patient Portals (1/44, 2%) and Home Health Nurse Portals (1/44, 2%).

Conclusions:
All studies incorporated some type of decentralization technology, with more extensive adoption than found in previous research. However, adoption may be strongly influenced by institution-specific IT and informatics infrastructure and support. There are inherent needs, responsibilities, and challenges when incorporating decentralization technology into a research study, and AROs must ensure that infrastructure and informatics staff are adequate.
Animal model considerations for medical countermeasure development for radiation and sulfur mustard exposures
Authors: Jackson Isabel Lauren , Doyle-Eisele Melanie 
Published: November 2023

Abstract
Development of medical countermeasures (MCM) to mitigate and/or treat the pulmonary complications associated with exposure to chemical, radiological, and/or nuclear weapons is a United States (U.S.) national public health preparedness posture priority. Pulmonary exposure to either sulfur mustard vapor or radiation causes oxidative damage, vascular injury, hyperinflammation, and pro-fibrotic signaling cascades that lead to life-threatening and potentially debilitating lung disease. There is no MCM currently approved by the U.S. Food and Drug Administration (FDA) to mitigate and/or treat lung injury caused by sulfur mustard or radiation exposure. Thus, there remains a major unmet public health need for development of threat-agnostic, host-directed therapeutics that target common pathophysiological mechanisms underlying the progression of acute and/or late lung injury independent of the etiology of disease. This review describes the clinical manifestations and underlying mechanisms of sulfur mustard and radiation-induced lung injury and regulatory considerations for MCM development under the non-traditional Animal Rule pathway.
Measuring the global 21-cm signal with the MWA-II: improved characterisation of lunar-reflected radio frequency interference
Authors: Tiwari Himanshu , McKinley Benjamin , Trott Cathryn M. , Thyagarajan Nithyanandan 
Published: November 2023

Abstract
Radio interferometers can potentially detect the sky-averaged signal from the Cosmic Dawn (CD) and the Epoch of Reionisation (EoR) by studying the Moon as a thermal block to the foreground sky. The first step is to mitigate the Earth-based radio frequency interference (RFI) reflections (Earthshine) from the Moon, which significantly contaminate the FM band

$\approx 88-110$

MHz, crucial to CD-EoR science. We analysed Murchison Widefield Array (MWA) phase I data from 72 to 180 MHz at 40 kHz resolution to understand the nature of Earthshine over three observing nights. We took two approaches to correct the Earthshine component from the Moon. In the first method, we mitigated the Earthshine using the flux density of the two components from the data, while in the second method, we used simulated flux density based on an FM catalogue to mitigate the Earthshine. Using these methods, we were able to recover the expected Galactic foreground temperature of the patch of sky obscured by the Moon. We performed a joint analysis of the Galactic foregrounds and the Moon’s intrinsic temperature

$(T_{\mathrm{Moon}})$

while assuming that the Moon has a constant thermal temperature throughout three epochs. We found

$T_{\mathrm{Moon}}$

to be at

$184.4\pm{2.6}\,\mathrm{K}$

and

$173.8\pm{2.5}\,\mathrm{K}$

using the first and the second methods, respectively, and the best-fit values of the Galactic spectral index

$(\alpha)$

to be within the 5% uncertainty level when compared with the global sky models. Compared with our previous work, these results improved constraints on the Galactic spectral index and the Moon’s intrinsic temperature. We also simulated the Earthshine at MWA between November and December 2023 to find suitable observing times less affected by the Earthshine. Such observing windows act as Earthshine avoidance and can be used to perform future global CD-EoR experiments using the Moon with the MWA.
Reformulation techniques for automated planning: a systematic review
Authors: Alarnaouti Diaeddin , Baryannis George , Vallati Mauro 
Published: November 2023

Abstract
Automated planning is a prominent area of Artificial Intelligence and an important component for intelligent autonomous agents. A cornerstone of domain-independent planning is the separation between planning logic, that is the automated reasoning side, and the knowledge model, that encodes a formal representation of domain knowledge needed to reason upon a given problem to synthesize a solution plan. Such a separation enables the use of reformulation techniques, which transform how a model is represented in order to improve the efficiency of plan generation. Over the past decades, significant research effort has been devoted to the design of reformulation techniques. In this paper, we present a systematic review of the large body of work on reformulation techniques for classical planning, aiming to provide a holistic view of the field and to foster future research in the area. As a tangible outcome, we provide a qualitative comparison of the existing classes of techniques, that can help researchers gain an overview of their strengths and weaknesses.
What is Direct Evidence-Based Policy-Making? Experience from the Drug Benefits Program for Seniors in British Columbia
Authors: Maclure Malcolm , Potashnik Tanya M. 
Published: November 2023

AbstractDrug benefits policy-making for seniors in British Columbia has been increasingly influenced by research since 1993. The "evidence-based medicine" paradigm, which emphasizes the primacy of direct evidence from randomized control trials, inspired key policy-makers and influenced policy concerning coverage of new and existing drugs. New drugs, if more expensive than existing similar drugs, are not covered unless published randomized control trials show superior effectiveness. Indirect evidence of effectiveness, based on surrogates, is given less weight, and non-randomized studies are rarely considered. Evidence of cost-effectiveness of new drugs is reviewed separately. For existing drugs, a new reimbursement policy, Reference Based Pricing (RBP), was introduced, based on both direct and indirect evidence of comparative effectiveness of drugs. Implementation of RBP was complex and necessarily rapid, which meant that independent systematic review of evidence relevant to implementation issues was infeasible, particularly in regard to rapid prior authorization of exemptions to RBP. Contrasts between the processes for new and existing drugs provide insights into the difficulties of applying the idea of direct evidence-based policy-making in practice.
The Variation of Ionospheric O+ and H+ Outflow on Storm Timescales
Authors: Nowrouzi N. , Kistler L. M. , Zhao K. , Lund E. J. , Mouikis C. , Payne G. , Klecker B. 
Published: November 2023

AbstractGeomagnetic storms are primarily driven by stream interaction regions (SIRs) and coronal mass ejections (CMEs). Since SIR and CME storms have different solar wind and magnetic field characteristics, the magnetospheric response may vary accordingly. Using FAST/TEAMS data, we investigate the variation of ionospheric O+ and H+ outflow as a function of geomagnetic storm phase during SIR and CME magnetic storms. The effects of storm size and solar EUV flux, including solar cycle and seasonal effects, on storm time ionospheric outflow, are also investigated. The results show that for both CME and SIR storms, the O+ and H+ fluences peak during the main phase, and then declines in the recovery phase. However, for CME storms, there is also significant increase during the initial phase. Because the outflow starts during the initial phase in CME storms, there is time for the O+ to reach the plasma sheet before the start of the main phase. Since plasma is convected into the ring current from the plasma sheet during the main phase, this may explain why more O+ is observed in the ring current during CME storms than during SIR storms. We also find that outflow fluence is higher for intense storms than moderate storms and is higher during solar maximum than solar minimum.
Evaluation of Summer Non‐Uniform Multidecadal Temperature Variations Over Eurasia in CMIP6 Models
Authors: Hu Yuhan , Hua Wenjian 
Published: November 2023

AbstractThe summer surface air temperatures (SAT) over Eurasia exhibit a non‐uniform multidecadal pattern since the 1990s, with amplified warming over Europe–West Asia (EWA) and Northeast Asia (NEA) but weak warming over Central Asia. However, current climate models may inadequately capture this regional pattern. In this study, we evaluated the performance of 44 coupled models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) in simulating the decadal variability of Eurasian temperatures. Results show that all the CMIP6 models generally reproduce the largest SAT trends from 1985 to 2020 over EWA and NEA. However, the models fail to capture the non‐uniform warming pattern and the SAT magnitudes are underestimated in most CMIP6 models. We compare “good” and “poor” ensemble, which represent the best and worst simulations of the non‐uniform warming, in order to understand the inter‐model spread. The BMME models capture the teleconnection wave trains from northwest Europe to East Asia, and the associated summer North Atlantic Oscillation like circulation changes. In contrast, the WMME models fail to reproduce such teleconnections. The contrast between the BMME and WMME simulations give a measure of confidence that the non‐uniform warming pattern over Eurasia is tightly coupled with the upper‐tropospheric wave‐like pattern over Eurasia. If such atmospheric circulation changes cannot be reproduced, the non‐uniform warming pattern over Eurasia will not be captured. Our results suggest a fundamental pattern of atmospheric circulation changes that determine the non‐uniform warming variations in model simulations.
Improving the Reliability of ML‐Corrected Climate Models With Novelty Detection
Authors: Sanford Clayton , Kwa Anna , Watt‐Meyer Oliver , Clark Spencer K. , Brenowitz Noah , McGibbon Jeremy , Bretherton Christopher 
Published: November 2023

AbstractUsing machine learning (ML) for the online correction of coarse‐resolution atmospheric models has proven effective in reducing biases in near‐surface temperature and precipitation rate. However, ML corrections often introduce new biases in the upper atmosphere and causes inconsistent model performance across different random seeds. Furthermore, they produce profiles that are outside the distribution of samples used in training, which can interfere with the baseline physics of the atmospheric model and reduce model reliability. This study introduces the use of a novelty detector to mask ML corrections when the atmospheric state is deemed out‐of‐sample. The novelty detector is trained on profiles of temperature and specific humidity in a semi‐supervised fashion using samples from the coarsened reference fine‐resolution simulation. The novelty detector responds to particularly biased simulations relative to the reference simulation by categorizing more columns as out‐of‐sample. Without novelty detection, corrective ML occasionally causes undesirably large climate biases. When coupled to a running year‐long coarse‐grid simulation, novelty detection deems about 21% of columns to be novelties. This identification reduces the spread in the root‐mean‐square error (RMSE) of time‐mean spatial patterns of surface temperature and precipitation rate across a random seed ensemble. In particular, the random seed with the worst RMSE is improved by up to 60% (depending on the variable) while the best seed maintains its low RMSE. By reducing the variance in quality of ML‐corrected climate models, novelty detection offers reliability without compromising prediction quality in atmospheric models.