bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study
Authors: Ramaekers Johannes G. , Reckweg Johannes T. , Mason Natasha L. , Kuypers Kim P. C. , Toennes Stefan W. , Theunissen Eef L. 
Published: December 2024

Abstract3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N = 14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. A battery of neurocognitive tests and questionnaires as well as measures of vital signs were repeatedly administered up to 5 h after dosing. Overall, 3-MMC caused dose-dependent increases in heart rate and blood pressure, though not of clinical significance, and feelings of subjective high. Additionally, 3-MMC induced dose-related enhancement of task performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention and memory. Impulse control was not affected by 3-MMC. Participants also reported mild increases in dissociative and psychedelic effects, decreased appetite, and gave greater ratings of liking and wanting for 3-MMC that were transient over time. Overall, the cardiovascular, psychostimulant and psychotomimetic profile of 3-MMC appears consistent with that of compounds structurally related to amphetamine. It is concluded that low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC.
2-year results from an observational study of proactive treatment regimens with intravitreal aflibercept 2 mg in patients with nAMD in clinical practice: XTEND study UK cohort
Authors: Bailey Clare , Chandran Manju , Gale Richard , Narendran Nirodhini , Talks James , McGoey Hellen , Keshk Zinab , Morgan-Warren Peter , Allmeier Helmut , Machewitz Tobias , Patel Praveen J. , Varma Deepali 
Published: December 2024

Abstract
Objectives
The 36-month XTEND (NCT03939767) multicentre, observational, prospective study examined the effectiveness of proactive treatment regimens of intravitreal aflibercept (IVT-AFL) 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. The 12- and 24-month outcomes from the XTEND UK cohort are reported.

Methods
Patients aged ≥50 years with nAMD planned to receive IVT-AFL 2 mg were eligible. After three initial monthly IVT-AFL injections, treatment intervals could be extended in 2- to 4-weekly increments to a maximum of 16 weeks (8-week minimum treatment interval). Endpoints included mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at month (M) 12 and M24. Treatment intervals and safety were assessed. Statistics were descriptive.

Results
In the UK, 496 patients from 23 centres were treated (mean age 79.7 years, 64.3% female). From a baseline BCVA (mean ± SD) of 55.2 ± 15.8 letters, mean (95% confidence interval [CI]) change in BCVA was +3.4 (2.0, 4.9) letters at M12 and +1.3 (− 0.3, 2.9) letters at M24. From a baseline CST (mean ± SD) of 395 ± 143 μm, mean (95% CI) change in CST was −105 ( 121, −89) μm at M12 and −105 (− 122, −88) μm at M24. By M12 and M24, patients had received a mean ± SD of 7.4 ± 2.4 and 10.7 ± 4.6 injections, respectively. Outcomes in patients enrolled prior to and during the COVID-19 pandemic were comparable. No new safety concerns were identified.

Conclusions
Despite the COVID-19 pandemic, patients in the UK achieved and maintained clinically meaningful improvements in functional and anatomic outcomes through M24.

Trial registration
ClinicalTrials.gov identifier, NCT03939767.
4-Hydroxychalcone attenuates AngII-induced cardiac remodeling and dysfunction via regulating PI3K/AKT pathway
Authors: Han Xiao , Zhu Qian-Qiu , Li Zhi , He Jia-Kang , Sun Yan , Zhong Qing-Hua , Tang Sheng-Xing , Zhang Yun-Long 
Published: December 2024

AbstractCardiac remodeling encompasses structural alterations such as hypertrophy, fibrosis, and dilatation, alongside numerous cellular and molecular functional aberrations, constituting a pivotal process in the advancement of heart failure (HF). 4-Hydroxychalcone (4-HCH) is a class of naturally occurring compounds with variable phenolic structures, and has demonstrated the preventive efficacy in hyperaldosteronism, inflammation and renal injury. However, the role of 4-HCH in the regulation of cardiac remodeling remains uncertain. A cardiac remodeling model was established in male C57BL/6 J mice via subcutaneous Ang II (1000 or 300 ng/kg/min) for 2 weeks. Mice were treated with 4-HCH (20 or 40 mg/kg/day) or vehicle control. Systolic blood pressure (SBP) was measured using a tail-cuff method, and echocardiography assessed cardiac function. Histopathological staining evaluated cardiomyocyte hypertrophy, fibrosis, inflammation, and superoxide production. Network pharmacology analysis identified potential core targets and pathways mediating the effects of 4-HCH. Expression of inflammatory cytokines and proteins related to hypertrophy, fibrosis, inflammation, and oxidative stress was assessed by quantitative real-time PCR (qPCR) and Western blotting. Our results indicated that 4-HCH significantly ameliorated Ang II-induced hypertension, cardiomyocyte hypertrophy, fibroblast activation, fibrosis, inflammation, superoxide production, and cardiac function. Network pharmacology analysis identified the PI3K-AKT pathway as a crucial mechanism underlying the effects of 4-HCH, with experimental verification demonstrating that it inhibits cardiac remodeling by downregulating this pathway and its downstream effectors, including mTOR/ERK, TGF-β/Smad2/3, NF-κB, and NOX1 independent of its blood pressure-lowering effects. These results reveal for the first time that 4-HCH alleviates cardiac remodeling, emphasizing its potential as a therapeutic agent for HF.
Robustness assessment of Muscat coastal highway network (CHN) under multi-hazard scenarios focusing on traffic stability and adaptation measures
Authors: Ansari Abdullah , El-Hussain Issa , Al Shijbi Yousuf , Mandhaniya Pranjal , Alluqmani Ayed E. , Al-Jabri Khalifa 
Published: December 2024

AbstractThis study critically examines the reliability and resilience of the Muscat coastal highway network (CHN) under the compounded effects of earthquakes and floods, representing interacting multi-hazard scenarios. The analysis utilized fragility functions for both earthquake-induced and flood-induced landslides, integrating these with traffic data for selected highway links to estimate bridge damage and assess CHN functionality in post-hazard conditions. Economic sensitivity analysis revealed a significant increase in costs due to flood-induced landslides, emphasizing the impact of dominant intensity measures on network costs and traffic flow. The analysis categorized Muscat areas into low, moderate, and high resilience based on hazard susceptibility and infrastructure quality, revealing that over 50% of highway links require retrofitting, highlighting the need for enhanced flood management and infrastructure improvements. The resilience assessment highlighted the necessity for targeted retrofitting to mitigate damage and reduce economic losses, particularly for highway links with bridges of high failure probabilities that face prolonged recovery times. The results provide valuable insights for designers, consultants, policymakers, and decision-makers in developing effective post-hazard mitigation strategies for Muscat and similar coastal cities.
Building a modular and multi-cellular virtual twin of the synovial joint in Rheumatoid Arthritis
Authors: Zerrouk Naouel , Augé Franck , Niarakis Anna 
Published: December 2024

AbstractRheumatoid arthritis is a complex disease marked by joint pain, stiffness, swelling, and chronic synovitis, arising from the dysregulated interaction between synoviocytes and immune cells. Its unclear etiology makes finding a cure challenging. The concept of digital twins, used in engineering, can be applied to healthcare to improve diagnosis and treatment for complex diseases like rheumatoid arthritis. In this work, we pave the path towards a digital twin of the arthritic joint by building a large, modular biochemical reaction map of intra- and intercellular interactions. This network, featuring over 1000 biomolecules, is then converted to one of the largest executable Boolean models for biological systems to date. Validated through existing knowledge and gene expression data, our model is used to explore current treatments and identify new therapeutic targets for rheumatoid arthritis.
Review of methodology and best practice of power system restoration plan
Authors: Fan Yiliang , Chen Nan , Zhao Yucong , Ding Xiaolin , Zhang Ray , Zhang Xiao‐Ping 
Published: December 2024

AbstractWith the increasing penetration of renewable energy and inverter‐based resource (IBR) generation, modern power systems are facing new challenges and issues in the system restoration process, such as the needs of fast response and adaptive protection and control during the restoration. This paper reviews the current restoration strategies of major countries and regions including European Union (EU) ENTSO‐E, North America (NA) Electric Reliability Corporation (NERC), China, Australia. Firstly, the Restoration Plan (RP) of all above countries and regions are briefly summarised. Then the RPs are compared and analysed from perspectives of (a) Activation conditions, (b) Restoration Stage Classification, and (c) Restoration time requirements. By introducing the detailed RPs of UK National Energy System Operator (NESO) and NA New York Independent System Operator (ISO) and PJM, the participants within the RPs are illustrated and compared for the roles of Generation and Interconnector, Transmission, Distribution, Load, System service provider etc. Through a real case study of the restoration process of the south Australian power system blackout, the system restoration procedure is analysed in detail, and the restoration stage classification proposed in this paper is shown. Finally, the challenges of the current RPs of major countries and regions are summarised, and potential solutions and future work are proposed.
Improved conditional diffusion model for image super‐resolution
Authors: Wang Rui , Zhou Ningning 
Published: December 2024

AbstractDiffusion models have achieved remarkable success in image super‐resolution by addressing issues such as transition smoothing, insufficient high‐frequency information, and training instability encountered in regression‐based and GAN‐based models. However, challenges persist when applying diffusion models to image super‐resolution, including randomness, inadequate conditional information, high computational costs, and network architecture complexities. In this article, the authors introduce a diffusion model based on Mean‐Reverting Stochastic Differential Equations (SDE), and propose the use of ENAFBlocks instead of traditional ResBlocks to enhance model performance in noise prediction. The Mean‐Reverting SDE effectively mitigates the randomness of the diffusion model by leveraging low‐resolution images as means. Additionally, an LR Encoder is introduced to capture hidden information from LR images, providing a more robust condition for stable result generation by the noise predictor. To efficiently handle high‐resolution images within limited GPU memory, the method employs adaptive aggregate sampling, which merges overlapping regions smoothly using weighted averaging. Furthermore, color variations are addressed during diffusion model sampling through color correction. Extensive experiments on CelebA, DIV2K, and Urban100 demonstrate that the method outperforms state‐of‐the‐art diffusion models like IDM, with a PSNR improvement of 0.22 dB, FID reduction of 2.35, and LPIPS reduction of 0.05 on the DIV2K dataset, along with a reduced parameter count and faster inference time.
The mechanism of arsenic trioxide and microwave ablation in the treatment of oral squamous cell carcinoma based on high throughput sequencing
Authors: Zhang Xuesong , Liu Yakun , He Shengteng , Bi Liangjia , Liu Bing 
Published: December 2024

AbstractOral squamous cell carcinoma (OSCC) is a common head and neck malignant tumour with high incidence and poor prognosis. Arsenic trioxide (ATO) has therapeutic effects on solid tumours. Microwave ablation (MWA) has unique advantages in the treatment of solid tumours. However, the therapeutic mechanism of ATO and MWA, as well as their combined effect on OSCC were largely unelucidated. Cal‐27 cell‐bearing nude mice were treated with ATO and/or MWA, respectively. RNA sequencing was used to obtain gene expression profiles in tumour tissues of mice treated by ATO or MWA. RNA sequencing results were verified by real‐time polymerase chain reaction (PCR). The lncRNA‐miRNA‐mRNA co‐expression network was constructed based on the competitive endogenous RNA (ceRNA) theory. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed using differentially expressed genes. The combined effect of ATO and MWA on OSCC was evaluated. Finally, CCK‐8 assay, EdU assay and transwell migration assay were performed to detect the effect of HSPA6 on the proliferation and migration of OSCC cells. The reduced volume of tumour tissues was observed in both ATO‐ and MWA‐treated groups. 37.8% decreased in the ATO group and 35.0% in the MWA group. A total of 207 and 539 differentially expressed mRNAs and lncRNAs were identified in the ATO group. And a total of 200 and 522 differentially expressed mRNAs and lncRNAs in the MWA group were identified. The expression levels of 8 genes were verified by real‐time PCR. The differentially expressed genes were closely related to “chemical carcinogenesis”, “herpes simplex infection”, “porphyrin and chlorophyll metabolism”, and “MAPK signalling pathway”. The lncRNA‐miRNA‐mRNA co‐expression networks were constructed. The combined treatment with ATO and MWA showed a better inhibitive effect on OSCC than either of them. The synergistic effect of ATO and MWA was related to the upregulation of HSPA6. The downregulation of HSPA6 could promote the proliferation and migration of OSCC cells. This study detected the long non‐coding RNA and mRNA expression profiles related to the treatment of OSCC and constructed corresponding ceRNA networks. Arsenic trioxide and MWA have a synergistic effect on OSCC, which was related to the upregulation of HSPA6.
A Transdiploic Cerebrospinal Fluid Diversion Device: Potential Use in Intracranial Hypertension Associated with Traumatic Brain Injury
Authors: Moscote-Salazar Luis Rafael , Agrawal Amit , Florez-Perdomo William A. , Chacon Ariana 
Published: December 2024

AbstractIntracranial hypertension (IH) is a critical condition in neurocritical care and needs effective management to avoid severe outcomes like brain herniation and cerebral ischemia. External ventricular drains, although effective in reducing intracranial pressure, pose risks of infection, hemorrhage, and malfunction. This technical note present the transdiploic cerebrospinal fluid (CSF) diversion device, an alternative technique for CSF diversion utilizing the parietal diploic venous system.
Asynchronous-bit-rate differential phase-shift-keying
Authors: Lin You-Cheng , Hu Kuan-Wei , Huang Hsing-Yi , Yang Yueh-Hsun , Wang You-Xin , Hsu Shih-Chang , Cheng Chih-Hsien , Matsumoto Atsushi , Akahane Kouichi , Wu Yuh-Renn , Kuo Hao-Chung , Lin Gong-Ru 
Published: December 2024

An adaptive differential-phase-shifting (DPS) quantum key distribution (QKD) protocol improved by encoding asynchronous-bit-rate with harmonic clock tunability, decoded by shortened delay-line interferometer (DLI) with enhancing stability, and received by single-photon detection with long hold-off is demonstrated to realize low-erroneous transmission. To achieve long-term stabilized visibility with a maintained quantum bit-error-ratio (QBER) and secure key rate, the shortened and polarized DLI enlarges its free-spectral range (FSR) and reduces its power-to-wavelength slope (δP/δλ) to suppress its sensitivity to thermal gradient, channel leakage, and wavelength disturbance. Extremely low power and wavelength drifts of ΔP/P &lt; ±0.02% and Δλ/λ = ±6.45 × 10−8 can be achieved, even when using a single-mode QKD carrier with a relatively broadened 300-kHz linewidth. Flexibly expanding the 1-bit-delay FSR of the polarized DLI from 0.04 to 1.00 GHz improves its immunity to environmental disturbances, enabling the DPS-QKD decoding with 210–213 patterns, 3.2% QBER, and 17.46-kbit/s under 0.22 photon/pulse in average. The asynchronous-bit-rate DPS-QKD protocol enables harmonic expansion of DLI’s FSR at limited single-photon avalanche detector’s bit rate, which lengthens the duration of stable visibility to support long-pattern DPS-QKD.
Design of soft x-ray high diffraction efficiency and spectral flux Au/Ni bilayer coated laminar-type diffraction grating for objective soft x-ray flat-field spectrograph in a region of 250–550 eV
Authors: Koike M. , Hatano T. , Pirozhkov A. S. , Murano T. , Oue Y. , Koshiya S. , Kakio T. , Kondo K. , Terauchi M. 
Published: December 2024

An objective soft x-ray flat-field spectrograph employing a laminar-type bilayer coated, varied-line-spacing, spherical grating was designed to improve the detection limit and sensitivity of soft x-ray flat-field spectrographs in a region of 250–550 eV. As a design criterion, spectral flux, SF, [Hatano et al., Appl. Opt. 60, 4993–4999 (2021)], which is proportional to the amount of optical flux incident onto a detector and correlated with detection sensitivity, was used to be maximized. To enhance reflectivity with the coating design, Au/Ni bilayer coating was investigated to optimize the incidence angle and thickness of the Ni layer. This is based on the consideration that, in an energy region of over 400 eV, refractive indices of Au (bottom layer), Ni (top layer), and vacuum are increased from the bottom to the top of the layers, and a supplemental enhancement of reflectivity can be expected by optimizing the thickness of the top layer. Thus, the thickness of Ni and the incidence angle were chosen to be 8.0 nm and 86.00°, respectively. To maintain dispersion and spectral resolution of the grating used at an incidence angle of 87.07° as previously designed, groove density was increased to 1500 lines/mm from 1200 lines/mm of our previous design. Finally, a holographic, varied-line-spacing, spherical grating was designed assuming an aspherical-wavefront-recording configuration. The numerical simulation results showed that the spectrograph employing newly designed grating with laminar-type grooves and Au/Ni bilayer coating exhibited 2–18 times higher spectral flux as well as an improved spectral resolution compared with those obtained with the previously designed gratings and spectrographs.
Curvature structure triboelectric nanogenerator for harvesting human motion energy and cheerleading training monitoring
Authors: Wang Jing , Feng Anchao 
Published: December 2024

Recently, self-powered wearable sports monitoring devices have garnered widespread attention. However, earlier sensor devices suffer from limitations such as single-mode operation, unstable output, and high power consumption. In this study, we leveraged the curvature effect to enhance the performance of triboelectric nanogenerators (C-TENGs) for harvesting micro-mechanical energy. The C-TENG demonstrated an open-circuit voltage (Voc) of 507.07 V, a short-circuit current (Isc) of 80.03 μA, and a transfer charge (Qsc) of 100.47 nC. Additionally, the C-TENG achieved a high output power of 3.22 mW with a 4 MΩ external resistor. Furthermore, a C-TENG sensor array embedded in shoes can monitor the cheerleading performer’s gait by analyzing the differences in signals from three C-TENG sensors. This includes detecting slow walking, brisk walking, and jumping. This innovative sensing design differs from previous single-signal outputs and effectively avoids sensing errors caused by sensor fatigue and loss.
Preparation of biocrude based on fish proteins and lipids as feedstock by subcritical hydrothermal liquefaction
Authors: Qin Junjie , Wang Yan , Wei Qinhong , Chen Yong , Yang Shuqing , Zheng Xianmin 
Published: December 2024

The fact that aquatic product waste causes environmental pollution and is difficult to handle has become a major challenge globally. Hydrothermal liquefaction (HTL) has provided new ideas for addressing this challenge. In this study, small yellow croaker was used as the raw material for HTL. It was found that the transition temperature point R from P1 (liquefied but without biocrude production) to P2 (biocrude production) lies between 200 and 250 °C. The impact of the pyrolysis temperature on the physical properties and composition of the produced biocrude was examined. The results showed that as the temperature increased, the acidity and density of the biocrude decreased. Furthermore, gas chromatography–mass spectrometry (GC-MS) analysis identified the components, revealing that changes in the physical properties were closely related to changes in the chemical composition. Although the composition remained similar with increasing temperature, the content varied significantly: the content of fatty acids and their derivatives decreased markedly, whereas that of aromatic compounds increased significantly. At 300 °C, the carbon chain distribution of the compounds was notably lower, with most being light oils, resulting in a reduced viscosity and density of the biocrude. Additionally, GC-MS analysis explored the effect of residence time on biocrude quality and found that reaction conditions of 300 °C for 125 min yielded high-quality biocrude and showed great potential for quality improvement with the addition of catalysts. Moreover, by altering the temperature and residence time, the content of the products can be controlled to produce high-value-added products.