bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic depletion of l‐Met using an engineered human enzyme as a novel therapeutic strategy for melanoma
Authors: Wilder Carly S. , Chiou Jennifer , Battenhouse Anna , Saha Achinto , Chen Zhao , Kim Eunice , Gadallah Mohamed I. , Tiziani Stefano , Georgiou George , Stone Everett , DiGiovanni John 
Published: June 2023

AbstractMany cancers, including melanoma, have a higher requirement for l‐methionine in comparison with noncancerous cells. In this study, we show that administration of an engineered human methionine‐γ‐lyase (hMGL) significantly reduced the survival of both human and mouse melanoma cells in vitro. A multiomics approach was utilized to identify global changes in gene expression and in metabolite levels with hMGL treatment in melanoma cells. There was considerable overlap in the perturbed pathways identified in the two data sets. Common pathways were flagged for further investigation to understand their mechanistic importance. In this regard, hMGL treatment induced S and G2 phase cell cycle arrest, decreased nucleotide levels, and increased DNA double‐strand breaks suggesting an important role for replication stress in the mechanism of hMGL effects on melanoma cells. Further, hMGL treatment resulted in increased cellular reactive oxygen species levels and increased apoptosis as well as uncharged transfer RNA pathway upregulation. Finally, treatment with hMGL significantly inhibited the growth of both mouse and human melanoma cells in orthotopic tumor models in vivo. Overall, the results of this study provide a strong rationale for further mechanistic evaluation and clinical development of hMGL for the treatment of melanoma skin cancer and other cancers.
Activin A/ACVR2A axis inhibits epithelial‐to‐mesenchymal transition in colon cancer by activating SMAD2
Authors: Zhang Hui , Ruan Qiang , Chen Changjiang , Yu Hui , Guan Shen , Hu Dan , Yang Chunkang , Lin Ruirong , Zhuo Changhua 
Published: June 2023

AbstractColorectal cancer is one of the most common malignancies worldwide. Liver metastasis is the major direct cause of colorectal cancer‐related deaths. Although radical resection is the most effective treatment for colorectal cancer liver metastasis, several patients are not eligible for surgery. Therefore, there is a need to develop novel treatments based on the understanding of the biological mechanisms underlying liver metastasis in colorectal cancer. This study demonstrated that activin A/ACVR2A inhibits colon cancer cell migration and invasion, as well as suppresses the epithelial‐to‐mesenchymal transition of mouse colon cancer cells. This finding has been further validated in animal experiments. Mechanistic studies revealed that activin A binds to Smad2 (instead of Smad3) and activates its transcription. Analysis of the paired clinical samples further confirmed that the expression levels of ACVR2A and SMAD2 were the highest in adjacent healthy tissues, followed by primary colon cancer tissues and liver metastasis tissues, suggesting that ACVR2A downregulation may promote colon cancer metastasis. Bioinformatics analysis and clinical studies demonstrated that ACVR2A downregulation was significantly associated with liver metastasis and poor disease‐free and progression‐free survival of patients with colon cancer. These results suggest that the activin A/ACVR2A axis promotes colon cancer metastasis by selectively activating SMAD2. Thus, targeting ACVR2A is a potential novel therapeutic strategy to prevent colon cancer metastasis.
Handicap as a Measure of Perceived‐Health Status in Parkinson's Disease
Authors: Silva Daniela Pimenta , Coelho Miguel , Soares Tiago , Vale Thiago Cardoso , Correia Guedes Leonor , Maciel Ricardo Oliveira Horta , Antunes Ana Patrícia , Camargos Sarah Teixeira , Valadas Anabela , Godinho Catarina , Maia Débora Palma , Pita Lobo Patrícia , Maia Raphael Doyle , Teodoro Tiago , Rieder Carlos R. , Velon Ana Graça , Tumas Vítor , Barbosa Egberto Reis , Teive Hélio A.G. , Ferraz Henrique Ballalai , Rosas Maria José , Calado Ana , Lampreia Tânia , Simões Rita , Vila‐Chã Nuno , Costa Maria Manuela , Rodrigues Ana Margarida , Caniça Verónica , Cardoso Francisco , Ferreira Joaquim J. ,   the MDS‐UPDRS Portuguese Validation Study Group
Published: June 2023

ABSTRACTBackgroundHandicap is a patient‐centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late‐stage Parkinson's Disease (PD).ObjectiveTo characterize the handicap of a broader sample of patients.MethodsA cross‐sectional study of 405 PD patients during the MDS‐UPDRS Portuguese validation study, using the MDS‐UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ‐8 and EQ‐5D‐3L. Handicap was measured using the London Handicap Scale (LHS).ResultsMean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2–3). Mean LHS was 0.652 (±0.204); “Mobility,” “Occupation” and “Physical Independence” were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ‐8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = −0.35), nonmotor experiences of daily living (EDL) (MDS‐UPDRS‐I) (r = −0.51), motor EDL (MDS‐UPDRS‐II) (r = −0.69), motor disability (MDS‐UPDRS‐III) (r = −0.49), axial signs of MDS‐UPDRS‐III (r = −0.55), HY (r = −0.44), presence of nonmotor symptoms (r = −0.51) and PDQ‐8 index (r = −0.64) (all P < 0.05). Motor EDL, MDS‐UPDRS‐III and PDQ‐8 independently predicted Handicap (adjusted R2 = 0.582; P = 0.007).ConclusionsThe LHS was easily completed by patients and caregivers. Patients were mild‐moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived‐health status in a broad sample of PD.
Late Presentation of Chronic Traumatic Encephalopathy in a Former Association Football Player
Authors: Cullinane Patrick W. , Wrigley Sarah , Bradshaw Teisha Y. , Shaw Karen , Shribman Samuel , de Pablo Fernandez Eduardo , Warner Thomas T. , Jaunmuktane Zane 
Published: June 2023

ABSTRACTBackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by widespread accumulation of hyperphosphorylated tau that typically occurs in people who have suffered repetitive head impacts. To date, very few cases have been reported in association football players.ObjectivesTo describe the clinicopathological features of a case of CTE in an 84‐year‐old former football player who was clinically diagnosed as having dementia with Lewy bodies (DLB).MethodsA retrospective review of the patient's primary care and hospital medical records was performed along with a comprehensive neuropathological examination.ResultsThis patient presented at age 84 with symmetrical parkinsonism and cognitive impairment that was exacerbated by prochlorperazine. His condition was rapidly progressive with recurrent falls within 1 year. Other features included headaches, depression, anxiety, suicidal ideation, disturbed sleep and aggression. He received a clinical diagnosis of DLB and died approximately 2 years after the onset of symptoms. A post‐mortem examination revealed stage 4 CTE.ConclusionsWhile the contemporaneous onset of parkinsonism and cognitive symptoms in the context of possible neuroleptic sensitivity is suggestive of DLB, the additional symptoms of aggressive behavior, depression and suicidality in a former football player are consistent with the neuropathological diagnosis of CTE. This case, which is notable for the late presentation, demonstrates that CTE may masquerade as other dementias and highlights the importance of seeking a history of repetitive head impacts.
The effects of fintech development on financing constraints of small and medium‐sized enterprises—Evidence from China
Authors: Chen Chun , Xiao Bowen , Wang Jie , Ye Huanzhuo 
Published: June 2023

AbstractBased on the data of listed small and medium‐sized enterprises (SMEs) from 2011 to 2020, this paper studies the effects of fintech on the financing constraints of SMEs in China. The results denote that fintech can significantly ease financing constraints of SMEs; with a 1% increase in fintech, the financing constraints of SMEs decrease by 0.0767%. The intermediary mechanism analysis illustrates that fintech can ease the financing constraints of SMEs by alleviating financial industry concentration and information asymmetry. Besides, regions with a higher degree of marketization and industries with relatively free competition are both more conducive to fintech alleviating the financing constraints of SMEs.
PETRA: A pencil beam trimming algorithm for analytical proton therapy dose calculations with the dynamic collimation system
Authors: Bennett Laura C. , Hyer Daniel E. , Erhart Kevin , Nelson Nicholas P. , Culberson Wesley S. , Smith Blake R. , Hill Patrick M. , Flynn Ryan T. 
Published: June 2023

AbstractBackgroundThe Dynamic Collimation System (DCS) has been shown to produce superior treatment plans to uncollimated pencil beam scanning (PBS) proton therapy using an in‐house treatment planning system (TPS) designed for research. Clinical implementation of the DCS requires the development and benchmarking of a rigorous dose calculation algorithm that accounts for pencil beam trimming, performs monitor unit calculations to produce deliverable plans at all beam energies, and is ideally implemented with a commercially available TPS.PurposeTo present an analytical Pencil bEam TRimming Algorithm (PETRA) for the DCS, with and without its range shifter, implemented in the Astroid TPS (.decimal, Sanford, Florida, USA).MaterialsPETRA was derived by generalizing an existing pencil beam dose calculation model to account for the DCS‐specific effects of lateral penumbra blurring due to the nickel trimmers in two different planes, integral depth dose variation due to the trimming process, and the presence and absence of the range shifter. Tuning parameters were introduced to enable agreement between PETRA and a measurement‐validated Dynamic Collimation Monte Carlo (DCMC) model of the Miami Cancer Institute's IBA Proteus Plus system equipped with the DCS. Trimmer position, spot position, beam energy, and the presence or absence of a range shifter were all used as variables for the characterization of the model. The model was calibrated for pencil beam monitor unit calculations using procedures specified by International Atomic Energy Agency Technical Report Series 398 (IAEA TRS‐398).ResultsThe integral depth dose curves (IDDs) for energies between 70 MeV and 160 MeV among all simulated trimmer combinations, with and without the ranger shifter, agreed between PETRA and DCMC at the 1%/1 mm 1‐D gamma criteria for 99.99% of points. For lateral dose profiles, the median 2‐D gamma pass rate for all profiles at 1.5%/1.5 mm was 99.99% at the water phantom surface, plateau, and Bragg peak depths without the range shifter and at the surface and Bragg peak depths with the range shifter. The minimum 1.5%/1.5 mm gamma pass rates for the 2‐D profiles at the water phantom surface without and with the range shifter were 98.02% and 97.91%, respectively, and, at the Bragg peak, the minimum pass rates were 97.80% and 97.5%, respectively.ConclusionThe PETRA model for DCS dose calculations was successfully defined and benchmarked for use in a commercially available TPS.
Secured data offloading using reinforcement learning and Markov decision process in mobile edge computing
Authors: Samriya Jitendra Kumar , Kumar Mohit , Gill Sukhpal Singh 
Published: June 2023

AbstractMobile Internet services are developing rapidly for several applications based on computational ability such as augmented/virtual reality, vehicular networks, etc. The mobile terminals are enabled using mobile edge computing (MEC) for offloading the task at the edge of the cellular networks, but offloading is still a challenging issue due to the dynamism, and uncertainty of upcoming IoT requests and wireless channel state. Moreover, securing the offloading data enhanced the challenges of computational complexities and required a secure and efficient offloading technique. To tackle the mentioned issues, a reinforcement learning‐based Markov decision process offloading model is proposed that optimized energy efficiency, and mobile users' time by considering the constrained computation of IoT devices, moreover guarantees efficient resource sharing among multiple users. An advanced encryption standard is employed in this work to fulfil the requirements of data security. The simulation outputs reveal that the proposed approach surpasses the existing baseline models for offloading overhead and service cost QoS parameters ensuring secure data offloading.
Extraction of natural fibers of Catole coconut (Syagrus Cearensis): Application as reinforcing filler in polypropylene‐based composites
Authors: do Nascimento Emanuel Pereira , Luna Carlos Bruno Barreto , Ferreira Eduardo da Silva Barbosa , dos Santos Filho Edson Antonio , Siqueira Danilo Diniz , Wellen Renate Maria Ramos , Araújo Edcleide Maria 
Published: June 2023

AbstractPolypropylene/Syagrus Cearensis fiber composites compatibilized with polypropylene‐graft‐maleic anhydride (PP‐g‐MA) and styrene(ethylene‐butylene)‐styrene copolymer (SEBS‐g‐MA) were successfully produced using a co‐rotating twin‐screw extruder followed by injection molding. The composites were characterized by X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The mechanical properties were determined by Izod impact and tensile testing. Thermal properties were obtained by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). Heat deflection temperature (HDT) was determined to study the thermomechanical properties of the composites. XRD and DSC indicated the presence of two polypropylene polymorphs: α and β. The unmodified PP/Fiber composites showed an incompatible behavior, presenting low fiber/matrix interaction and poor interfacial adhesion. The poor compatibility led to low elongation at break and impact strength but high tensile strength. PP‐g‐MA coupling agent promoted some adhesion to the PP/fiber interfaces but not enough to improve the impact strength. The composites with PP‐g‐MA exhibited improved tensile modulus and strength. The enhanced PP/fiber interfacial interaction promoted by SEBS‐g‐MA generated a better interplay of mechanical properties, improving impact strength and elongation at break while preserving the elastic modulus and tensile strength. In general, the fibers enhanced the thermomechanical stability of PP, as evidenced by higher HDT values.
Kids gone wild – Alcohol use and patient characteristics in pediatric trauma during the coronavirus disease 2019 pandemic
Authors: Patel Neesha S , Waibel Brett H , Berning Bennett J , Terzian WT Hillman , Evans Charity H , Hanna Angela M , Hamill Mark E 
Published: June 2023

ABSTRACTImportanceReported coronavirus disease 2019 (COVID‐19) pandemic effects on pediatric trauma have been variable.ObjectiveWe investigated the characteristics of pediatric trauma including alcohol use during the pandemic at our urban trauma center.MethodsThe trauma database of our adult level 1 trauma center was queried for all pediatric (age ≤ 18 years) patients presenting between March 1, 2020, and October 30, 2020. Data from 2017 to 2019 served as a control. Variables analyzed included demographics, mechanisms, injury severity, hospitalization characteristics, and positive blood alcohol.ResultsPandemic pediatric trauma volumes increased by 67.5% (330/year vs. 197/year). Pandemic patients were younger (median age 13 vs. 14 years, P = 0.011), but similar in gender, ethnicity, severity, hospital length of stay, mortality, and rates of penetrating injury. Falls doubled (79/year vs. 34/year) and shifted away from high falls >6 meters (0% vs. 7.9%) to moderate falls 1–6 meters (58.2% vs. 51.5%) (P = 0.028). Transportation injury rates were similar however mechanisms shifted from motor vehicle crashes (−13.5%) towards recreational vehicles including motorcycles (+2.1%), all‐terrain vehicles (+8.6%), and bicycles (+3.8%) (P = 0.018). Pediatric‐positive blood alcohol was significantly higher (11.2% vs. 5.1%, P < 0.001), especially for ages 14–18 years (21.7% vs. 9.5%, P < 0.001).InterpretationPediatric trauma volumes during the COVID‐19 pandemic increased. Pandemic patients had more recreational vehicle injuries and higher rates of positive blood alcohol. This suggests an increased need for alcohol assessment and targeted interventions in the pediatric population during pandemics or periods of school closures.
Nongrowth regime in microwave chemical vapor deposition reactor due to formation of plasma nonhomogeneity
Authors: Bogdanov Sergey A. , Vikharev Anatoly L. , Gorbachev Aleksey M. , Radishev Dmitry B. , Lobaev Mikhail A. 
Published: June 2023

AbstractA new form of microwave discharge with a filament inside plasma volume was investigated in a microwave plasma‐assisted chemical vapor deposition (CVD) reactor. The threshold values of methane content in a hydrogen–methane gas mixture, gas pressure, and microwave power for discharge transition to the new form were found. The parameters' range of existence of the new form of discharge was investigated in three types of CVD reactors. Measurements of the electron density, gas temperature, and spatial distributions of the plasma optical emission lines intensity were carried out for both forms of the discharge. The reasons for the transition of the discharge to a new form and the possibility of using the new discharge form in the microwave plasma‐assisted (MPA) CVD reactor are discussed.
Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC‐MS metabolomics
Authors: Wu Ming‐Hsiu , Chang Chiz‐Tzung , Lin Yu‐Ning , Chen Chao‐Jung 
Published: June 2023

AbstractPurposeStroke is the sudden death of brain cells in a localized area due to an inadequate blood flow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS).Experimental DesignTo identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS > 2). The identified markers were further absolutely quantified by a targeted MRM approach.ResultsThere were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88.Conclusions and Clinical RelevanceGlycocholic acid was identified as a potential plasma metabolite marker of non‐progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.
Surface denitration structure on dynamic combustion performance and muzzle flame of mixed nitrate gun propellant
Authors: Li Shiying , Chen Hao , Li Yu , Shi Yudong , Yuan Ye , Li Wenjia , Ding Yajun , Zhou Jie , Liang Hao , Xiao Zhongliang 
Published: June 2023

AbstractThe gun propellant is an inaccessible energy and fuel for projectile to achieve destructive capability in a weapon system. Nitrocellulose/nitroglycerine/triethylene glycol dinitrate(NC/NG/TEGDN) based gun propellant with higher energy level than single‐based gun propellant can meet the demands of modern warfare. Currently, deterring strategy is commonly used to improve the combustion progressivity of NC/NG/TEGDN based gun propellant, together with aggravating the harmful emission phenomena such as muzzle smoke and flame. Therefore, it is essential to design and fabricate NC/NG/TEGDN based gun propellant with both good combustion progressivity and low characteristic signal. In this work, a gradiently denitrated NC/NG/TEGDN based gun propellant was successfully prepared by denitration strategy, whose structure was confirmed by FT‐IR, Raman and SEM. Here, closed bomb vessel test and interior ballistic test were conducted. The results showed that the gradiently denitrated NC/NG/TEGDN based gun propellant exhibited better combustion progressivity and interior ballistic performance than raw gun propellant, and these properties can be controlled by modulating the degree of denitration. Meanwhile, the change laws of the muzzle smoke and flame of the gradiently denitrated NC/NG/TEGDN based gun propellant were investigated by the smoke box method and high‐speed photography. Furthermore, a lower characteristic signal for the gradiently denitrated NC/NG/TEGDN based gun propellant was found compared to the deterred gun propellant by theoretical calculations. This work provides a new idea for preparing and applying a gun propellant with excellent comprehensive performance, including high energy, good combustion progressivity and low characteristic signal.
A Miniaturized Spin‐Exchange Relaxation‐Free Atomic Magnetometer Array Based on a 1 × 8 Planar Lightwave Circuit Waveguide Splitter
Authors: Xu Yuting , Chai Zhen , Sun Jie , Bai Dongbi , Huang Kun , Tian Zhongxing , Cui Zhibo , Pei Yuzhuo 
Published: June 2023

AbstractUsing spin‐exchange relaxation‐free (SERF) atomic magnetometer array (AMA) in magnetocardiography and magnetoencephalography has presented a challenge in reducing its packing volume for integrated instrumentation and convenient maintenance. This study presents a novel, space‐saving SERF AMA based on an 8‐channel planar lightwave circuit (PLC) waveguide splitter with a compact footprint of 26 × 2.5 mm2. The PLC splitting configuration allows the synchronization of the pump for a multisensor array, resulting in highly consistent performance among the sensors, with an impressive ultrahigh sensitivity of 34 fT Hz−1/2within a measurement bandwidth of 105 Hz. The PLC splitting method shows great promise in expanding the channel capacity of small‐scale SERF AMAs, offering a cost‐effective method for high‐resolution medical diagnoses through functional magnetic imaging of humans. In addition, this method is expected to find applications in fields such as electromagnetic induction imaging, biological magnetism, and geomagnetic observation.
The impact of heterogeneity and geometry on the proof complexity of random satisfiability
Authors: Bläsius Thomas , Friedrich Tobias , Göbel Andreas , Levy Jordi , Rothenberger Ralf 
Published: June 2023

AbstractSatisfiability is considered the canonical NP‐complete problem and is used as a starting point for hardness reductions in theory, while in practice heuristic SAT solving algorithms can solve large‐scale industrial SAT instances very efficiently. This disparity between theory and practice is believed to be a result of inherent properties of industrial SAT instances that make them tractable. Two characteristic properties seem to be prevalent in the majority of real‐world SAT instances, heterogeneous degree distribution and locality. To understand the impact of these two properties on SAT, we study the proof complexity of random ‐SAT models that allow to control heterogeneity and locality. Our findings show that heterogeneity alone does not make SAT easy as heterogeneous random ‐SAT instances have superpolynomial resolution size. This implies intractability of these instances for modern SAT‐solvers. In contrast, modeling locality with underlying geometry leads to small unsatisfiable subformulas, which can be found within polynomial time.