bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advantages and Challenges of Platform Trials for Disease Modifying Therapies in Parkinson's Disease
Authors: Fabbri Margherita , Rascol Olivier , Foltynie Tom , Carroll Camille , Postuma Ronald B. , Porcher Raphael , Corvol Jean Christophe 
Published: June 2024

AbstractTraditional drug development in Parkinson's disease (PD) faces significant challenges because of its protracted timeline and high costs. In response, innovative master protocols are emerging and designed to address multiple research questions within a single overarching protocol. These trials may offer advantages such as increased efficiency, agility in adding new treatment arms, and potential cost savings. However, they also present organizational, methodological, funding, regulatory, and sponsorship challenges. We review the potential of master protocols, focusing on platform trials, for disease modifying therapies in PD. These trials share a common control group and allow for the termination or addition of treatment arms during a trial with non‐predetermined end. Specific issues exist for a platform trial in the PD field considering the heterogeneity of patients in terms of phenotype, genotype and staging, the confounding effects of symptomatic treatments, and the choice of outcome measures with no consensus on a non‐clinical biomarker to serve as a surrogate and the slowness of PD progression. We illustrate these aspects using the examples of the main PD platform trials currently in development with each one targeting distinct goals, populations, and outcomes. Overall, platform trials hold promise in expediting the evaluation of potential therapies for PD. However, it remains to be proven whether these theoretical benefits will translate into increased production of high‐quality trial data. Success also depends on the willingness of pharmaceutical companies to engage in such trials and whether this approach will ultimately hasten the identification and licensing of effective disease‐modifying drugs. © 2024 International Parkinson and Movement Disorder Society.
Unraveling the influence of metabolic signatures on immune dynamics for predicting immunotherapy response and survival in cancer
Authors: Ou Qiyun , Lu Zhiqiang , Cai Gengyi , Lai Zijia , Lin Ruicong , Huang Hong , Zeng Dongqiang , Wang Zehua , Luo Baoming , Ouyang Wenhao , Liao Wangjun 
Published: June 2024

AbstractMetabolic reprogramming in cancer significantly impacts immune responses within the tumor microenvironment, but its influence on cancer immunotherapy effectiveness remains uncertain. This study aims to elucidate the prognostic significance of metabolic genes in cancer immunotherapy through a comprehensive analytical approach. Utilizing data from the IMvigor210 trial (n = 348) and validated by retrospective datasets, we performed patient clustering using non‐negative matrix factorization based on metabolism‐related genes. A metabiotic score was developed using a “DeepSurv” neural network to assess correlations with overall survival (OS), progression‐free survival, and immunotherapy response. Validation of the metabolic score and key genes was achieved via comparative gene expression analysis using qPCR. Our analysis identified four distinct metabolic classes with significant variations in OS. Notably, the metabolism‐inactive and hypoxia‐low class demonstrated the most pronounced benefit in terms of OS. The metabolic score predicted immunotherapeutic benefits with high accuracy (AUC: 0.93 at 12 months). SETD3 emerged as a crucial gene, showing strong correlations with improved OS outcomes. This study underscores the importance of metabolic profiling in predicting cancer immunotherapy success. Specifically, patients classified as metabolism‐inactive and hypoxia‐low appear to derive substantial benefits. SETD3 is established as a promising prognostic marker, linking metabolic activity with patient outcomes, advocating for the integration of metabolic profiling into immunotherapy strategies to enhance treatment precision and efficacy.
Clinical characteristics of a case of multiple mitochondrial dysfunction syndrome 3
Authors: Xu Hai , Ma Kai , Gao Yuye , Song Qijun , Chen Chaojin , Xu Xiao , Peng Jiaxi , Sun Yan 
Published: June 2024

AbstractObjectiveTo further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed.MethodsClinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen‐2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.ResultsThe child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole‐exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.ConclusionMMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole‐exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.
Hybrid integration of BAW resonators with an on‐chip inductor to improve the stopband rejection of the N78 band filter
Authors: Jiang Hong , Xuan Weipeng , Ding Rui , Zhang Biao , He Xingli , Jin Hao , Gao Feng , Dong Shurong , Luo Jikui 
Published: June 2024

AbstractThis paper demonstrates a 3.4 GHz micro‐acoustic filter with excellent in‐band insertion loss, rectangle coefficient, and out‐of‐band rejection. The proposed filter was based on a novel topology by integrating the bulk acoustic wave (BAW) resonators with an on‐chip clamping inductor, the introduction of the lumped components is beneficial for improving the filters' stopband rejection while having minimal influence on the rectangle coefficient and in‐band insertion loss. Al0.8Sc0.2N material was selected as the piezoelectric film of the BAW device and the inductor was fabricated on the same wafer with BAW devices. The manufactured filter has a minimum in‐band insertion loss of ~ 1.5 dB, a 3 dB bandwidth of about 170 MHz, and a stopband rejection of nearly ‐30 dB. The experimental results verify the design and show great applications for 5G communication and beyond.
Fine-solids removal by foam fractionation in a low-salinity marine recirculating aquaculture system (RAS)
Authors: Pfeiffer Timothy , Baptiste Richard , Wills Paul S. 
Published: June 2024

Abstract

Objective
We sought to evaluate several methods of operation of a foam fractionator for fine-solids removal (organic matter &lt; 55 μm) in a commercial-scale, low-salinity (11–13‰) recirculating aquaculture system (RAS) for marine finfish production.

Methods
The total suspended solids (TSS) concentrations of the RAS microscreen drum filter inflow and outflow and the foam fractionator outflow were obtained under various foam fractionator operating conditions. The outflow TSS concentration of the drum filter also served as the inflow TSS concentration for the foam fractionator. Sample collection for TSS determination was divided into two categories: particles greater than 55 μm and particles less than 55 μm. The difference between inflow and outflow TSS concentrations was used to determine the removal percentage for each particle class of each unit. Additionally, the volume of foammate produced under operating conditions by the fractionator and the amount of solids contained within the foammate were quantified. Flow through the foam fractionator was also obtained to determine the amount of solids removed per volume of influent water treated.

Result
The influent TSS concentration for the seven different operating conditions evaluated ranged from 4.8 to 6.3 mg/L, with the percentage of particles less than 55 μm ranging from 69.75% to as high as 86.1%. The drum filter removed over 90% of the particles larger than 55 μm and removed 8–26% of the particles smaller than 55 μm. No difference was observed in the overall removal efficiency of the drum filter, which ranged from 19% to 44%. There was no significant difference in the foam fractionator overall removal efficiency, which ranged from 6.5% to 38.5%. Operating the foam fractionator at a high water head height (HHH) with the submersible aspirating impeller provided the greatest removal percentage of particles less than 55 μm (26.9%). However, at the HHH, only half the amount of solids was removed compared to using a Venturi injector with ozone, but energy use was roughly 26% greater.

Conclusion
The foam fractionator was operated at the HHH, about 0.31 m higher than the low water head height, for production operation. Additionally, Venturi injection of ozone provided the greatest removal of solids for the volume of influent water treated over a 12-h operational period. The submersible aspirating impeller showed potential for low-cost use with reasonable solids removal and warrants further evaluation.
An improved MPSP‐based path‐following control method for USV with input disturbances
Authors: Li Ao , Hu Xiaoxiang , Dong Kejun , Xiao Bing 
Published: June 2024

AbstractThis study proposes an improved model predictive static programming (MPSP) based path‐following control method for unmanned surface vessel (USV) subject to input disturbances. The method addresses the challenges of accurate USV dynamics modeling, unpredictable maritime environments, and limited power and energy systems. A trajectory generator is designed to construct smooth reference trajectories, and the MPSP algorithm is adapted to handle path‐following problems while considering state and input constraints. An event‐triggered mechanism is introduced to reduce computational burden and conserve energy. Comparative simulations demonstrate the superiority of the proposed method over open‐loop tracking and the original MPSP approach in terms of tracking accuracy, disturbance rejection, and overall control performance. The improved MPSP‐based control method offers a robust and efficient solution for USV path‐following tasks, ensuring accurate tracking even in the presence of environmental disturbances and system uncertainties.
Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma
Authors: Yang Jing , Lewis James S , Zi Jinghuan , Andl Thomas , Lee Ethan , Andl Claudia D , Liu Qi , Beauchamp Robert D , Means Anna L 
Published: June 2024

AbstractSMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression‐free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4− mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFβ signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Influence of Z‐pin material on the mechanical properties of fine Z‐pin reinforced composites
Authors: Ji Guobiao , Cheng Liang , Wang Qing , Li Jiangxiong , Ke Yinglin 
Published: June 2024

AbstractThe insertion of finer Z‐pins is an effective method to reduce the microstructure damage and maintain the in‐plane performance of composite laminates. In this paper, an ultrasound guided insertion process is proposed to achieve the insertion of fine Z‐pins and the influence of Z‐pin material on the mechanical properties of Ø0.11 mm Z‐pin reinforced composite laminates is revealed based on experiments and simulations. For in‐plane mechanical properties, stainless steel Z‐pins help to reduce the loss of compression modulus and compression strength. For the interlaminar mechanical properties, stainless steel Z‐pins and carbon fiber Z‐pins exhibit bilinear and trilinear bridging laws respectively, resulting in the mode‐I maximum load and fracture toughness of carbon fiber Z‐pin reinforced composites being greater than that of stainless steel Z‐pin reinforced composites. By adjusting the insertion spacing, it is found that for unidirectional composite laminates reinforced by Ø0.11 mm carbon fiber Z‐pins with an insertion spacing of 2 mm, the compression strength reduction is only 3.39% while the mode‐I fracture toughness can be improved by 14.4 times in comparison with the unpinned specimens, achieving a better balance between in‐plane performance loss and interlaminar reinforcement effect.Highlights
The effect of Z‐pin material on fine Z‐pin reinforced composites is studied.
The compression properties are simulated by the RVE model.
The mode‐I fracture properties are simulated by the DCB unit strip model.
Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation
Authors: Liu Jing , Huang Mengjun , Yang Yan , Zeng Yan , Yang You , Guo Qulian , Liu Wenjun , Guo Ling 
Published: June 2024

AbstractIntroductionThe identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated.ObjectivesThe objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation.MethodsFirst, high performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell‐xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation.ResultsA total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z‐VAD).ConclusionDuckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.
First‐year students' psychological resilience and college adjustment: A person‐oriented approach
Authors: Gao Lili , Zhang Na , Yang Weimin , Deng Xiaopeng 
Published: June 2024

AbstractPrevious research has concentrated on psychological resilience as a holistic structure and has found that resilience positively affects college adjustment. However, it is suggested by existing literature that college students' resilience is a multidimensional construct. Furthermore, there is limited understanding regarding the categorizations of resilience among first‐year college students and its influence on their college adjustment. This study aimed to identify the profiles of first‐year college students' resilience, including individual powers and supportive powers, and explore the effects of varying resilience profiles on first‐year students' college adjustment. A valid sample of 771 first‐year college students from 28 Chinese colleges participated in this survey. The online surveys were conducted through Wenjuanxing platform. Data were analyzed using latent profile analysis to identify first‐year college students' different resilience profile and examine the relationships with college adjustment. Four groups featuring unique resilient characteristics were discovered: well‐resilient students, students with low individual power but high supportive power, students with high individual power but low supportive power, and mal‐resilient students with low individual power and low supportive power. Well‐resilient first‐year students reported the best condition of college adjustment compared to the other groups, which supports the conservation of resources (COR) theory. These results provide insight into first‐year college students' particular and heterogeneous circumstances at the beginning of the college experience. They also refined the COR theory by identifying individual‐specific relationships between psychological resilience and college adjustment.
Advancements and challenges in natural fiber‐reinforced hybrid composites: A comprehensive review
Authors: Islam Tarikul , Chaion Mehedi Hasan , Jalil M. Abdul , Rafi Abu Sayed , Mushtari Faujia , Dhar Avik Kumar , Hossain Shahin 
Published: June 2024

AbstractNatural fiber‐reinforced composites have emerged as a promising alternative in various industries, including automotive, aerospace, construction, and civil engineering, owing to their eco‐friendly nature and favorable mechanical properties. However, challenges such as low thermal stability and high moisture absorption limit their widespread use. To overcome these limitations, surface modifications such as mercerization, benzoylation, silane treatment, and acetylation have been extensively explored. Hybrid composites (HCs), combining natural and synthetic fibers, offer a compelling solution by harnessing the unique properties of both materials. This review comprehensively examines the types of fibers and polymers utilized in HCs, along with various chemical treatments to enhance their properties. Additionally, a detailed analysis of different manufacturing processes for HCs is provided, including hand lay‐up, vacuum‐assisted resin transfer molding, autoclave molding, injection molding, and compression molding. Furthermore, this review highlights recent advancements in HCs and their applications. Significant outcomes include a deeper understanding of the synergistic effects between natural and synthetic fibers, improved mechanical and thermal properties, and enhanced applications in diverse industries. The potential of HCs as a sustainable and high‐performance material solution emphasizes the importance of ongoing research and innovation in this field to overcome existing challenges and unlock new possibilities for composite engineering.Highlights
Surface modifications such as mercerization, benzoylation, and silane treatment enhance the properties of natural fibers in composite materials.
Hybrid composites (HCs) offer unique advantages by combining natural and synthetic fibers, including improved thermal, mechanical, and damping properties.
Various chemical treatments and manufacturing processes contribute to enhancing the properties and applications of HCs.
Recent advancements in HCs have led to an improved understanding and utilization of composite engineering across multiple industries.
The review discusses challenges, opportunities, and future prospects for HCs, emphasizing the need for ongoing research and innovation in this field.
Closed vessel burning rate measurements of composite propellants using microwave interferometry
Authors: Oatman Shane A. , Caito August A. , Klinger Daniel J. , Cooper James N. , Manship Tim D. , Son Steven F. 
Published: June 2024

AbstractBurning rate as a function of pressure is one of the primary evaluation metrics of solid propellants. Most solid propellant burning rate measurements are made at a nearly constant pressure using a variety of measurement approaches. This type of burning rate data is highly discretized and requires many tests to accurately determine the burning rate response to pressure. It would be more efficient to measure burning rate dynamically as pressures are varied. Techniques used to make transient burning rate measurements are reviewed briefly and initial results using a microwave interferometry (MI) technique are presented. The MI method used in tandem with a closed bomb enables nearly continuous measurement of burning rates for self‐pressurizing burns, capturing burning rate data over a wide range of pressures. This approach is especially useful for characterization of propellants with complex burning behaviors (e. g., slope breaks or mesa burning). The burning rates of three research propellants were characterized over a pressure range of 0.101–24.14 MPa (14–3500 psi). One research propellant exhibited a slope break at a pressure of 6.63 MPa (960 psi). Using MI in a closed pressure vessel, 14 propellant strand burns resulted in a nearly continuous burning rate curve over a pressure range of 0.41–24.13 MPa (60–3500 psi) that reasonably matched conventional burning rate measurements. The development of this technique provides an opportunity to quickly characterize the burning rate curve of solid propellants with greater fidelity and efficiency than traditional quasi‐static pressure testing techniques.