bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain‐targeted exosome‐mimetic cell membrane nanovesicles with therapeutic oligonucleotides elicit anti‐tumor effects in glioblastoma animal models
Authors: Lee Youngki , Kim Minkyung , Ha Junkyu , Lee Minhyung 
Published: October 2022

AbstractThe brain‐targeted delivery of therapeutic oligonucleotides has been investigated as a new treatment modality for various brain diseases, such as brain tumors. However, delivery efficiency into the brain has been limited due to the blood–brain barrier. In this research, brain‐targeted exosome‐mimetic cell membrane nanovesicles (CMNVs) were designed to enhance the delivery of therapeutic oligonucleotides into the brain. First, CMNVs were produced by extrusion with isolated C6 cell membrane fragments. Then, CMNVs were decorated with cholesterol‐linked T7 peptides as a targeting ligand by hydrophobic interaction, producing T7‐CMNV. T7‐CMNV was in aqueous solution maintained its nanoparticle size for over 21 days. The targeting and delivery effects of T7‐CMNVs were evaluated in an orthotopic glioblastoma animal model. 2′‐O‐metyl and cholesterol‐TEG modified anti‐microRNA‐21 oligonucleotides (AMO21c) were loaded into T7‐CMNVs, and biodistribution experiments indicated that T7‐CMNVs delivered AMO21c more efficiently into the brain than CMNVs, scrambled T7‐CMNVs, lipofectamine, and naked AMO21c after systemic administration. In addition, AMO21c down‐regulated miRNA‐21 (miR‐21) levels in glioblastoma tissue most efficiently in the T7‐CMNVs group. This enhanced suppression of miR‐21 resulted in the up‐regulation of PDCD4 and PTEN. Eventually, brain tumor size was reduced in the T7‐CMNVs group more efficiently than in the other control groups. With stability, low toxicity, and targeting efficiency, T7‐CMNVs may be useful to the development of oligonucleotide therapy for brain tumors.
Safety, Pharmacokinetics, and Pharmacodynamics of CC‐90001 (BMS‐986360), a c‐Jun N‐terminal Kinase Inhibitor, in Phase 1 Studies in Healthy Participants
Authors: Ye Ying , Gaudy Allison , Thomas Michael , Reyes Josephine , Burkhardt Barbara , Horan Gerald , Liu Liangang , Chen Jian , Ghosh Atalanta , Carayannopoulos Leonidas N. , Tatosian Daniel A. , Palmisano Maria 
Published: October 2022

AbstractCC‐90001 selectively inhibits c‐Jun N‐terminal kinase (JNK), a stress‐activated protein implicated in fibrosis. In 3 phase 1 trials evaluating CC‐90001 pharmacokinetics, pharmacodynamics, and safety, healthy adults (N = 184) received oral CC‐90001 in a single dose (10–720 mg) or multiple doses (30–480 mg once daily for 7–18 days) or placebo. CC‐90001 was rapidly absorbed (median time to maximum concentration, 1–4 hours) and eliminated with a mean terminal elimination half‐life of 12–28 hours. Steady state was reached on day 5, with a mean accumulation ratio of 1.5‐ to 2‐fold following daily dosing. Exposure was similar in fed versus fasted participants and in Japanese versus non‐Japanese participants. CC‐90001 demonstrated dose‐ and exposure‐dependent inhibition of JNK as determined by histopathological analysis of c‐Jun phosphorylation in ultraviolet‐irradiated skin. The most common treatment‐emergent adverse events were nausea and headache; all were mild or moderate in intensity. Based on exposure‐response analysis using high‐quality electrocardiogram data, no clinically relevant QT prolongation liability for CC‐90001 was observed. Overall, single‐ and multiple‐dose CC‐90001 were generally safe and well tolerated at the tested doses and demonstrated JNK pathway engagement. These results support further clinical evaluation of CC‐90001.
A multi‐queue priority‐based task scheduling algorithm in fog computing environment
Authors: Fahad Muhammad , Shojafar Mohammad , Abbas Mubashir , Ahmed Israr , Ijaz Humaira 
Published: October 2022

AbstractFog computing is a novel, decentralized and heterogeneous computing environment that extends the traditional cloud computing systems by facilitating task processing near end‐users on computing resources called fog nodes. These diverse and resource‐constrained fog devices process a large volume of tasks generated by various fog applications. These tasks are generated by various applications, some of which may be latency‐sensitive, while others may tolerate some degree of delay in their normal functions. Task scheduling determines when a task should be allocated to a computing resource and how long that task can occupy the assigned resource. The majority of task scheduling algorithms focus on prioritizing the latency‐sensitive tasks only, which results in the long waiting time for the other type of tasks. Hence, these priority‐based schedulers cause task starvation for less important tasks while achieving delay‐optimal results for latency‐sensitive tasks. As a result, in this paper, we propose MQP, a multi‐queue priority‐based preemptive task scheduling approach that achieves a balanced task allocation for those applications that can tolerate a certain amount of processing delay and the latency‐sensitive fog applications. At run‐time, the MQP algorithm categorizes tasks as short and long based on their burst time. MQP algorithm maintains a separate task queue for each task category and dynamically updates the time slot value for preemption. The proposed technique's major purpose is to reduce response time for those data‐intensive applications in the fog computing environment, which include both latency‐sensitive tasks and tasks which are less latency‐sensitive, thereby addressing the starvation problem for less latency‐sensitive tasks. A smart traffic management case study is created to model a scenario with both latency‐sensitive short and less latency‐sensitive long tasks. We implement the MQP algorithm using iFogSim and confirm that it reduces the service latencies for long tasks. Simulation results show that the MQP algorithm allocates tasks to a fog device more efficiently and reduces the service latencies for long tasks. The average value of percentage reduction in the latency across all experimental configurations achieved is 22.68% and 38.45% in comparison to First Come‐First Serve and shortest job first algorithms.
CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer
Authors: Dai Wei , Wu Junhong , Peng Xiaopeng , Hou Wen , Huang Hao , Cheng Qilai , Liu Zhiping , Luyten Walter , Schoofs Liliane , Zhou Jingfeng , Liu Shenglan 
Published: October 2022

AbstractBackgroundHepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC.MethodsThe transcriptional profiles of super‐enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR‐4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells.ResultsWe identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE‐associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE‐associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC.ConclusionsOur data highlight the potential of CDK12 and SE‐associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.
Effect of atmospheric pressure pulsed discharge spatial inhomogeneity on Ar I and H I lines: Electron number density study
Authors: Jovović Jovica , Majstorović Gordana Lj. 
Published: October 2022

AbstractThe spatial inhomogeneity of pulsed atmospheric pressure discharge in argon is investigated using the electron number density Ne diagnostics procedure applied to asymmetrically broadened Ar I lines. A dedicated fitting procedure is used for describing Ar I 703.0 nm line shape recorded from argon gas discharge and H I (at 486.13 and 656.28 nm) lines recorded from Ar‐H2 gas mixture discharge. The results revealed the change in Ne in both axial and radial directions. The additional Ar I lines at 614.5, 710.7, 731.2, and 731.6 nm, recorded from integral spatial radiation, are analysed as well to confirm the results from the plasma column region. The possibility of using AlO (B2∑+–X2∑+) and CN (B2∑+–X2∑+) molecular bands for gas temperature Tg measurements in this type of gas discharge source is demonstrated and Tg used as an input parameter for the Ne diagnostics procedure. For the proper identification of molecular band spectral lines, the Fortrat parabolas are constructed. The results obtained from Ar I 703.0 nm line indicate three different Ne values, with Ne1 ≈ 0.6 × 1016 cm−3, Ne2 ≈ 3.6 × 1016 cm−3, and Ne3 ≈ 19 × 1016 cm−3 measured from the plasma column. These Ne values increase in the cathode and anode region.
Prediction of the information processing speed performance in multiple sclerosis using a machine learning approach in a large multicenter magnetic resonance imaging data set
Authors: Marzi Chiara , d'Ambrosio Alessandro , Diciotti Stefano , Bisecco Alvino , Altieri Manuela , Filippi Massimo , Rocca Maria Assunta , Storelli Loredana , Pantano Patrizia , Tommasin Silvia , Cortese Rosa , De Stefano Nicola , Tedeschi Gioacchino , Gallo Antonio ,   the INNI Network
Published: October 2022

AbstractMany patients with multiple sclerosis (MS) experience information processing speed (IPS) deficits, and the Symbol Digit Modalities Test (SDMT) has been recommended as a valid screening test. Magnetic resonance imaging (MRI) has markedly improved the understanding of the mechanisms associated with cognitive deficits in MS. However, which structural MRI markers are the most closely related to cognitive performance is still unclear. We used the multicenter 3T‐MRI data set of the Italian Neuroimaging Network Initiative to extract multimodal data (i.e., demographic, clinical, neuropsychological, and structural MRIs) of 540 MS patients. We aimed to assess, through machine learning techniques, the contribution of brain MRI structural volumes in the prediction of IPS deficits when combined with demographic and clinical features. We trained and tested the eXtreme Gradient Boosting (XGBoost) model following a rigorous validation scheme to obtain reliable generalization performance. We carried out a classification and a regression task based on SDMT scores feeding each model with different combinations of features. For the classification task, the model trained with thalamus, cortical gray matter, hippocampus, and lesions volumes achieved an area under the receiver operating characteristic curve of 0.74. For the regression task, the model trained with cortical gray matter and thalamus volumes, EDSS, nucleus accumbens, lesions, and putamen volumes, and age reached a mean absolute error of 0.95. In conclusion, our results confirmed that damage to cortical gray matter and relevant deep and archaic gray matter structures, such as the thalamus and hippocampus, is among the most relevant predictors of cognitive performance in MS.
Comparison of propeller flaps versus skin grafts for coverage of osteocutaneous fibula free flap donor site defects
Authors: Kaleem Arshad , Patel Neel , Schubert Enrique , Stanbouly Dani , Shanti Rabie , Tursun Ramzey 
Published: October 2022

AbstractBackgroundAuthors compare use of propeller flaps versus skin grafts in defect coverage after fibula flap harvest.Materials and MethodsRetrospective review of patients who received either PFPF or STSG. Primary predictor variable was technique, and secondary predictor variables were comorbidities. Primary outcome variable was flap/graft healing, and secondary outcome variables were cosmesis, adverse events, effect on activities of daily living (ADLs), pain, additional procedures, and cost. Statistical analysis performed via independent sample t tests, ANOVA, and χ2 tests. Logistic regression analysis was performed.ResultsStudy sample was 50 patients. PFPFs showed higher rates of success, while STSG showed increased complications and adverse events. Pain and ADLs significantly affected in STSG group. Cosmesis was better in the PFPF group, and overall cost was significantly higher in STSG group.ConclusionPFPFs show greater success rates, fewer complications, improved cosmesis, less pain, reduced cost compared to STSG for wound coverage after fibula flap harvest.
Chemosensory Functions After Glossectomy—A Cross‐Sectional Pilot Study
Authors: Grasl Stefan , Janik Stefan , Wiederstein Stephanie , Haymerle Georg , Renner Bertold , Mueller Christan A. 
Published: October 2022

ObjectiveTo evaluate potential interactions and compensatory mechanisms of subjectively impaired taste function with ortho‐ and retronasal olfaction after glossectomy.Study DesignIn this cross‐sectional pilot study, chemosensory functions were assessed in 25 patients with tongue carcinomas after glossectomy. The orthonasal‐, retronasal‐, and gustatory functions were tested with a mean time of 25 months after surgery with the Sniffin’ Sticks odor identification test kit (ISST), the Candy Smell‐27 test (CST‐27) and the Taste strip test (TST). Visual analog scales (VAS) were additionally used for self‐assessment of taste, flavor perception, and odor ranging from 0 (no perception) to 10 (excellent perception) and further correlated with our psychophysical evaluated outcome measures.ResultsThe TST, ISST, and CST‐27 tests revealed that only eight (32%) and 13 (52%) glossectomy patients had normal taste and orthonasal function, e 21 (84%) patients showed normal retronasal function. Importantly, neither extent of resection and reconstruction nor prior radiotherapy affected chemosensory functions. Contrary, 20 (80%) patients rated their taste and flavor perception as acceptable (VAS >5). Results of the TST, ISST, and CST‐27 tests did not correlate with the equivalent self‐assessments of taste (p = 0.260, r = 0.234), odor (p = 0.588, r = −0.114), and flavor (p = 0.728, r = 0.073) perception.ConclusionThere was a significant discrepancy between self‐perception of taste and flavor and assessed gustatory function after glossectomy. A contribution of the intact retronasal olfactory system could be a possible explanation of our results.Level of Evidence4 Laryngoscope, 133:375–382, 2023
Mussel‐Inspired Adhesive, Antibacterial, and Stretchable Composite Hydrogel for Wound Dressing
Authors: Chen Ying , Fan Xiaokun , Lu Jiawei , Liu Xin , Chen Jin , Chen Yi 
Published: October 2022

AbstractHydrogels have attracted extensive attention in the field of biomedicine because of their similar structure to extracellular matrix (ECM) and good biocompatibility. However, the adhesiveness, mechanical properties, and antibacterial properties of conventional hydrogels are not satisfactory. In this study, multifunctional chitosan/polydopamine/polyacrylamide (CS/PDA/PAM) hydrogels are prepared through a nature‐inspired strategy. The catechol group of polydopamine (PDA) component endows CS/PDA/PAM hydrogels with tissue adhesion and self‐healing properties. The introduction of chitosan (CS) not only greatly improves antibacterial ability, but also enhances the mechanical properties of CS/PDA/PAM hydrogels. Skin wound healing experiments show that CS/PDA/PAM hydrogels could accelerate skin tissue regeneration and promote wound healing. Therefore, CS/PDA/PAM hydrogels have great potential in the application of new wound dressings.
Melt Electrowriting of Poly(dioxanone) Filament Using a Multi‐Axis Robot
Authors: Luposchainsky Simon , Jörissen Sven , Nüchter Andreas , Dalton Paul D. 
Published: October 2022

AbstractExcessive thermal degradation is one limitation of scaffold production by melt electrowriting (MEW). This is particularly pertinent when using higher melting point polymers with faster degradation profiles in vivo for tissue engineering applications. This is addressed here by switching from a pneumatic to a filament‐based feeding system and demonstrating the processing of a medical polymer, poly(dioxanone) (PDO). Additionally, by replacing the established cartesian printer configuration with a six‐axis robotic arm, arbitrary nonplanar surfaces can be used as a fiber collector, as shown here by using a spherical collector. The combination of these techniques allows MEW to be used more broadly in tissue engineering where currently established medical polymers are incompatible with the process, or the geometric shapes of scaffold are to be expanded. It demonstrates the required technology to produce nonplanar scaffolds of PDO in a dome shape with dimensions for a biodegradable corneal implant.
Partial privatization with endogenous choice of strategic variable
Authors: Méndez‐Naya José , Novo‐Peteiro José A. 
Published: October 2022

AbstractThis paper analyzes the optimal privatization policy when firms endogenously choose their strategic variable. The level of privatization is shown to determine: (i) the choice of strategic variable, whereby an asymmetric equilibrium could emerge (either Cournot–Bertrand or Bertrand–Cournot); (ii) the stability of equilibrium when the partially privatized firm and the private firm choose quantity and price respectively as the strategic variable; and (iii) the level of welfare, whereby Cournot–Cournot and Bertrand–Cournot games could lead to a greater welfare than the Bertrand–Bertrand model.
Increased Free Water in the Substantia Nigra in Asymptomatic LRRK2 G2019S Mutation Carriers
Authors: Zhang Dongling , Zhou Liche , Shi Yuting , Liu Jun , Wei Hongjiang , Tong Qiqi , He Hongjian , Wu Tao 
Published: October 2022

AbstractBackgroundThe alteration of substantia nigra (SN) degeneration in populations at risk of Parkinson's disease (PD) is unclear.ObjectiveWe investigated free water (FW) values in the posterior SN (pSN) in asymptomatic LRRK2 G2019S mutation carriers.MethodsWe analyzed diffusion imaging data from 28 asymptomatic LRRK2 G2019S mutation carriers and 30 healthy controls (HCs), whereas 11 asymptomatic LRRK2 G2019S carriers and 11 HCs were followed up. FW values in the pSN were measured and compared between the groups. The relationship between longitudinal changes in FW in the pSN and dopamine transporter striatal binding ratio (SBR) was analyzed.ResultsFW values in the pSN were significantly elevated and kept increasing during follow‐up in asymptomatic LRRK2 G2019S carriers. There was a negative correlation between FW changes in the left pSN and SBR changes in the left putamen.ConclusionFW in the pSN has the potential to be a progression imaging marker of early dopaminergic degeneration in the population at risk of PD. © 2022 International Parkinson and Movement Disorder Society.
Development of individual fitness score for conformity of prescriptions to the “Guidelines For Pharmacological Therapy of Schizophrenia”
Authors: Inada Ken , Fukumoto Kentaro , Hasegawa Naomi , Yasuda Yuka , Yamada Hisashi , Hori Hikaru , Ichihashi Kayo , Iida Hitoshi , Ohi Kazutaka , Muraoka Hiroyuki , Kodaka Fumitoshi , Ide Kenta , Hashimoto Naoki , Iga Jun‐ichi , Ogasawara Kazuyoshi , Atake Kiyokazu , Takaesu Yoshikazu , Nagasawa Tatsuya , Komatsu Hiroshi , Okada Tsuyoshi , Furihata Ryuji , Kido Mikio , Kikuchi Saya , Kubota Chika , Makinodan Manabu , Ochi Shinichiro , Takeshima Masahiro , Yamagata Hirotaka , Matsumoto Junya , Miura Kenichiro , Usami Masahide , Kishimoto Taishiro , Onitsuka Toshiaki , Katsumoto Eiichi , Hishimoto Akitoyo , Numata Shusuke , Yasui‐Furukori Norio , Watanabe Koichiro , Hashimoto Ryota 
Published: October 2022

AbstractAimsThe Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence‐practice‐gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'.MethodsTo establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared.ResultIFS points vary and ranged from 0 to100. The average pre‐admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge.ConclusionsWe developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia.
An approach on reactive processing of plastic waste
Authors: Kučera František , Petruš Josef , Žídek Jan , Poláček Petr , Šimonek Michal 
Published: October 2022

AbstractAn approach on the reactive processing and compatibilization of plastic waste was simulated for the mixture of thermoplastics with the major content in municipal plastic waste: low‐density polyethylene, high‐density polyethylene, polypropylene, polystyrene, poly(vinyl chloride) (PVC), polyethylene terephthalate, polymethyl methacrylate, PA6, and acrylonitrile‐butadiene‐styrene. Peroxide initiators 2,5‐bis(tert‐butylperoxy)‐2,5‐dimethylhexane (L101) and hydrogen peroxide (H2O2) and poly(styrene‐b‐ethylene‐b‐butylene‐b‐styrene) grafted with maleic anhydride (SEBS‐g‐MAH) were used for the reactive processing of polymer blend under optimized conditions (concentration, reaction temperature, and time). The compatibilization was evidenced by “online” monitoring of the melt viscosity during reactive processing of polymer blend and examined by melt volume rate, oscillatory rheology, mechanical testing, and scanning electron microscopy. The effect of selected peroxides on the type of radical reaction was also evidenced for individual thermoplastics. Both L101 and hydrogen peroxide modify the melt viscosity with different effectivity due to different miscibility, decomposition mechanism, and limited reactivity of individual thermoplastics toward primary radicals. Therefore, the efficiency of compatibilization is limited. On the other hand, SEBS‐g‐MAH acts is an “universal” and effective reactive compatibilizer for multicomponent polymeric blend due to combination of covalent and non‐covalent interactions with blended thermoplastics, resulting in the improvement of mechanical properties and morphology of polymer blend.