bluuebunny/crossref_metadata_2025 huggingface dataset:
Jian Pi Hua Tan Fang Reverses Trastuzumab Resistance of HER2‐Positive Gastric Cancer Through PI3K/AKT/mTOR Pathway: Integrating Network Pharmacology, Molecular Docking and Experimental Validation
Authors: Hu Jia , Bu Wenjing , Ding Yongfang , Li Xin , Zhang Bo , Shen Bo , Wu Cong , Xu Youqi , Zhang Xiaoyang
Published: February 2025

Background

Currently, trastuzumab resistance significantly impacts the treatment outcome for individuals with HER2‐positive gastric cancer. In clinical practice, Jian Pi Hua Tan Fang (JPHTF) has been shown to be effective in preventing recurrences and metastases caused by gastric cancer. Yet, the treatment process remains unknown. We aim to evaluate the potential pharmacological mechanism of JPHTF in interfering with resistance to trastuzumab in HER2‐positive gastric cancer (GC).

Methods

In this study, network pharmacology and molecular docking techniques were used to forecast the potential active ingredients, pathways, and targets of JPHTF in overcoming trastuzumab resistance in HER2‐positive GC. Then, in vitro models of NCI‐N87/TR was developed, and JPHTF‐containing serum was utilized for intervention to confirm these crucial targets.

Results

Network pharmacology showed that 92 potential active compounds and 420 therapeutic targets of JPHTF. SRC, EGFR, TP53, and AKT1 were identified as the main targets associated with the PI3K/Akt, MAPK, and Ras pathways, playing crucial roles in angiogenesis, cell apoptosis, cell proliferation, and resistance to chemotherapy in the GC microenvironment. Molecular docking analysis showed that quercetin, formononetin, and luteolin, which are the main active ingredients, exhibit high binding affinity to the central targets PI3K, AKT, and mTOR. In vitro experiment, the JPHTF‐containing serum has a significant alleviating effect on reversing trastuzumab resistance and cell apoptotic and proliferation of NCI‐N87/TR. Further molecular biological experiments showed that JPHTF could regulate the expression of PI3K/AKT/mTOR pathway.

Conclusion

JPHTF has the ability to overcome trastuzumab resistance in NCI‐N87 cells through the regulation of the PI3K/AKT/mTOR pathway.
Comparative analysis of lipolytic enzymes involved in the surface fermentation of dried katsuobushi by xerophilic molds
Authors: Takenaka Shinji , Toyoshima Ryota , Umeki Tomoya , Kimura Yukihiro , Tanaka Shinichi , Matsumoto Jun‐ichi , Doi Mikiharu
Published: February 2025

Background

Fermented katsuobushi, a traditional Japanese seasoning, is produced from skipjack tuna through smoking, drying and fermentation by xerophilic Aspergillus molds, primarily Aspergillus chevalieri and Aspergillus pseudoglaucus. In this study, we characterized lipolytic enzymes (cLip_1 to cLip_5 and pLip_1 to pLip_3) to clarify their roles in lipid hydrolysis during katsuobushi production under low water activity.

Results

The enzymes showed significant diversity in their activity, stability and substrate specificity, and in the hydrolysis profiles of their reactions with fish oil. Phylogenetic analyses revealed that cLip_5 showed a high identity with pLip_2 (94%) and these enzymes formed a phylogenetic cluster with filamentous fungal lipases. Purified recombinant enzymes (rcLip_1, rcLip_2, rcLip_4 and rcLip_5) and wild‐type enzymes (cLip_3 and pLip_3) showed varying substrate preferences toward p‐nitrophenyl esters. The addition of glycerol to reduce the water activity in the reaction mixture led to increased activities of rcLip_1 and rcLip_4, but it did not affect the activity of the other three enzymes. Among the tested six enzymes, cLip_5 showed the highest hydrolytic activity toward fish oil. The cLip_5 and pLip_2 gene transcript levels were moderately high in strains MK86 and MK88, respectively.

Conclusion

cLip_5 and its homolog pLip_2 were identified as the most promising enzymes for katsuobushi fermentation, because of their high hydrolytic activities toward fish oil and adaptability to low water activity conditions. These findings support the selection of optimal Aspergillus strains as starter cultures to potentially shorten the fermentation time and improve the quality and shelf life of katsuobushi. © 2025 Society of Chemical Industry.
Improving Ecological Barrier Area Sustainability Integrating Ecosystem Service Interaction and Social–Ecological System Coupling
Authors: Li Sinan , Pu Junwei , Deng Xiaodong , Dong Baiyu , Su Yue
Published: February 2025

Ecological barrier areas are the natural area with special ecological functions, and play a vital role in maintaining the global ecological balance, protecting biodiversity, and regulating climate. They also profoundly affect the local social system and the inhabitants' lifestyle. Mitigating trade‐offs between distinct ecosystem services and enhancing social–ecological system coupling are essential for the sustainable development of ecological barrier areas. However, the lack of integrating them on topographical gradient features compromises our ability to design precise interventions for regional sustainability. Taking the Sichuan‐Yunnan Ecological Barrier area as a case area, this study developed a management approach by integrating ecosystem service interactions and social–ecological system coupling under multidimensional topographical gradients to provide a reference for assessing and improving the sustainability of the ecological barrier area. The results demonstrated that during 2010–2020, topography played a key role in shaping ecosystem service interactions, with the hilly area showing the highest synergistic level for multiple service pairs. The high and highest relief mountain areas had the lowest coupling index of the social–ecological system; this coupling index decreased rapidly in the flatter areas, while it increased in the low and middle relief mountain areas. Based on the above multi‐dimensional characteristics, six sustainable development zones were subdivided for formulating differentiated management strategies and improving regional sustainability. This research provides essential insights for improving the sustainability of ecological barrier area regarding differentiated territorial spatial management strategies, and delivers guidance for coordinating relationships between social and ecological systems in other similar areas.
Prevalence of Parkinson's Disease in 22q11.2 Deletion Syndrome: A Multicenter Study
Authors: von Scheibler Emma N.M.M. , Swillen Ann , Repetto Gabriela M. , Reyes Nikolai Gil D. , Lang Anthony E. , Marras Connie , Kuijf Mark L. , Rouhl Rob P.W. , van Eeghen Agnies M. , Juri Carlos , Vogels Annick , van Amelsvoort Thérèse A.M.J. , Bassett Anne S. , Boot Erik
Published: February 2025

Background

22q11.2 deletion syndrome (22q11.2DS) has been associated with increased risk of early‐onset Parkinson's disease (PD).

Objective

To determine the prevalence and predictors of PD in a large international 22q11.2DS sample.

Methods

The sample comprised 856 adults (median age 28 (range 16–76) years; 53.0% female). PD was defined as clinical diagnosis by a neurologist (including bradykinesia, rest tremor and/or rigidity). Age‐specific risk and predictors of PD were analyzed using Kaplan–Meier curve and Cox regression.

Results

PD was present in 1.8% (95% CI: 0.9–2.6%) of the sample, 3.4% (95% CI: 2.2–4.6%) when including uncertain PD (clinical diagnosis or suspicion, but not meeting all criteria), and 14.0% (95% CI: 6.9–21.0%) of those aged ≥50 years. Median age at motor onset was 45 (range 20–66) years. None of the factors considered were associated with PD.

Conclusions

Given high PD prevalence and young onset, we propose periodic motor evaluations from age 40 years in 22q11.2DS.
The Emerging Landscape of Tubercular Targets: A Medicinal Chemistry Approach
Authors: Shaik Baji Baba , Moodley Kimeshni , Ghumran Safiyah , Bala Muhammad D. , Singh Parvesh , Karpoormath Rajshekhar
Published: February 2025

Antitubercular drug discovery progress in the last decade, especially research on the biological function, target inhibition and diagnosis of tuberculosis (TB) diagnosis has considerably advanced. The application of target‐based drug discovery techniques have become a more powerful tool for medicinal chemists in developing new therapeutic strategies, such as its application in the identification/validation of new targets, new leads, and drug candidates with optimized efficacy. This has been further evidenced by the recent approval of delamanid and bedaquiline for the treatment of MDR‐TB and XDR‐TB, respectively. While a TB drug pipeline has shown great development, high attrition rates must constantly replenish the pipeline with high‐quality leads acting through the inhibition of new targets. This review provides a critical analysis of the approaches used to advance hit compounds into viable lead candidates as well as the possible influence of new targets on drug development in the near future. Finally, we concluded with the present challenges that are faced in TB drug development.
Novel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt‐Neu‐Cooper Neurodevelopmental Syndrome
Authors: Dainelli Alice , Nosrati Mohammad Sadegh Shams , Romano Ferruccio , Vercellino Fabiana , Mancardi Maria Margherita , Torella Annalaura , Nigro Vincenzo , Capra Valeria , Zara Federico , Scala Marcello
Published: February 2025

Background

RALA is a small GTPase from the RAS superfamily implicated in signal transduction and cytoskeletal dynamics. Recently, de novo variants in RALA have been associated with a neurodevelopmental syndrome characterized by intellectual disability (ID), developmental delay (DD), and seizures. So far, only < 12 patients have been reported.

Methods

In this study, we report two novel patients with neurodevelopmental impairment and epilepsy carrying previously unreported RALA variants. We performed a thorough clinical investigation of these patients and performed brain MRI to detect potential abnormalities. Trio‐exome sequencing and/or NGS panel testing were conducted to identify the genetic variants. Then, we reviewed previous cases reported in the literature.

Results

Affected individuals showed a complex neurodevelopmental phenotype consistent with Hiatt‐Neu‐Cooper neurodevelopmental syndrome. Brain MRI in both subjects showed abnormalities including megalencephaly and ventricular enlargement, previously unreported in RALA patients. Genetic testing revealed two novel de novo missense variants in RALA: c.217G>A, p.(Glu73Lys) in case #1 and c.73G>C, p.(Val25Leu) in case #2. Both variants affect highly conserved residues within the GTP/GDP‐binding site of the protein. These changes are predicted to be deleterious by in silico tools, interfering with the GTPase activity of RALA.

Conclusion

Our findings expand the genotype and phenotype spectrum of Hiatt‐Neu‐Cooper neurodevelopmental syndrome. Our observations also support the important role of variants affecting the GTP/GDP‐binding site of the RALA protein in the pathogenesis of Hiatt‐Neu‐Cooper neurodevelopmental syndrome.
The Estimate of Lifespan and Local Well‐Posedness for the Nonresistive MHD Equations in Homogeneous Besov Spaces
Authors: Luo Wei , Ye Weikui , Yin Zhaoyang
Published: February 2025

In this paper, we mainly investigate the Cauchy problem of the nonresistive MHD equation. We first establish the local existence in the homogeneous Besov space with , and give a lifespan of the solution that depends on the norm of the Littlewood–Paley decomposition of the initial data. Then, we prove that if the initial data in , then the corresponding existence times , which implies that they have a common lower bound of the lifespan. Finally, we prove that the data‐to‐solutions map depends continuously on the initial data when . Therefore, the nonresistive MHD equation is local well‐posedness in the homogeneous Besov space in the Hadamard sense. Our obtained result improves considerably the recent results by Fefferman et al[Arch. Ration. Mech. Anal. 223, no. 7 (2017):677‐691], Chemin et al [Adv. Math. 286(2016):1‐31 ] and Li et al[Adv. Math. 317(2017): 786‐798].
Solving an Augmented Nonnegative Matrix Factorization Model by Modified Scaled Nonmonotone Memoryless BFGS Methods Devised Based on the Ellipsoid Vector Norm
Authors: Dargahi Fatemeh , Babaie‐Kafaki Saman , Aminifard Zohre , Hajian Berenjestanaki Mohammad
Published: February 2025

We suggest a modified version of the nonnegative matrix factorization problem, adding penalty terms to the model with the aim of taking control of the condition number of the decomposition elements. This measure is taken to reinforce computational stability in the solution path of the relevant optimization model. Then, using the ellipsoid vector norm in the Barzilai–Borwein least‐squares model, we gain scaling parameters for the memoryless BFGS updating formula. Therefore, two augmented versions of the Oren–Spedicato self‐scaling parameter are proposed when the BFGS and DFP formulas for the Hessian are employed as the matrix index of the ellipsoid norm. A similar analysis is conducted to obtain two augmented versions of the Oren–Luenberger self‐scaling parameter using the mentioned quasi‐Newton formulas for the inverse Hessian. We address the global convergence of the method under a modified version of a nonmonotone backtracking line search. Then, we discuss accelerating the method using a local memoryless quadratic model considering the given scaling parameters as scalar approximations of the Hessian. Finally, the computational merits of the given augmented nonnegative matrix factorization model as well as the effectiveness of the proposed scaling parameters are assessed on some standard and randomly generated test problems, and also, a classic database of facial images. The outputs generally support our analytical spectrum.
Night‐to‐Day Ratio of Excreted Urinary Sodium Concentration Using Spot Urine in Older Adults With Nocturnal Polyuria
Authors: Natsume Osamu , Nishimura Nobutaka , Shimizu Takuto , Fujimoto Kiyohide
Published: February 2025

Background

The diurnal rhythm in water and solute diuresis is known to be disturbed in older adults with nocturia due to nocturnal polyuria. We estimated the prevalence of increased natriuresis in nocturia due to nocturnal polyuria by comparing individuals with and without nocturnal polyuria.

Methods

We calculated the night‐to‐day ratio of excreted urinary sodium and potassium concentrations adjusted for urinary creatinine concentration and urinary osmolality using spot urine samples collected at 2 PM (daytime) and 6 AM (nighttime) and compared results among controls with nocturia and paitents with nocturia with and without nocturnal polyuria.

Results

Among 83 patients aged 50 to 86 years, the mean night‐to‐day ratio of excreted urinary sodium and potassium concentrations in the nocturia group with nocturnal polyuria (n = 40) was 2.5, which was significantly higher (p = 0.034) than those in the control group (n = 23; 0.7) and the nocturia group without nocturnal polyuria (n = 20; 0.9). After adjustment for age, no difference in potassium and urinary osmolality existed among groups. Thirteen patients (33%) in the nocturia group with nocturnal polyuria showed increased natriuresis when a 2.0 night‐to‐day ratio of excreted urinary sodium was applied as a cut‐off for increased natriuresis, whereas only 3 (7%) patients in the combined groups without nocturnal polyuria had increased natriuresis (p = 0.005).

Conclusions

One‐third of patients with nocturia due to nocturnal polyuria had increased natriuresis. Assessment of a night‐to‐day ratio of excreted urinary sodium using spot urine samples could facilitate a better understanding of the underlying pathophysiology and optimal management of nocturnal polyuria.
Sustainable hemp fiber reinforced polylactic acid/poly(butylene succinate) biocomposites: Assessing the effectiveness of MAH‐g‐PLA as a compatibilizer
Authors: Ucpinar Bedriye , Sivrikaya Taha , Aytac Ayse
Published: February 2025

The unsustainability of petroleum resources and the growing issue of plastic pollution necessitate the development of sustainable biocomposites as alternatives to synthetic materials. On this basis, a blend of biosourced poly(lactic acid) (PLA)/poly(butylene succinate) was reinforced with hemp fibers (HF) in various amounts (5–10–20‐30 wt%). In order to facilitate the interaction between PLA/PBS and HFs, maleic anhydride grafted PLA (MAH‐g‐PLA) was added to the biocomposite containing 20 wt% HF at various ratios to produce compatibilized biocomposites. All samples were processed by melt blending and injection molding and characterized. The Fourier transform infrared spectroscopy was used to determine whether the MAH group interacts with OH groups through reactive processes. However, the compatibility is deemed insufficient due to the low reactive compatibility and inadequacy of the PBS and HF end groups, which failed to enhance the tensile strength property of composites. Differential scanning calorimetry demonstrated that the crystallinity of the matrix, which decreased with the addition of HF, increased markedly with the incorporation of the compatibilizer. The poor interfacial adhesion observed between PLA/PBS and HF in scanning electron microscope images resulted in a reduction in tensile strength while the modulus increased. The compatibilizer did not lead to a considerable enhancement in tensile strength, but the modulus increased considerably. HF and MAH‐g‐PLA slowed the thermal degradation of the matrix and improved its thermomechanical properties. However, it can be concluded that MAH‐g‐PLA is not a sufficiently effective compatibilizer for this biocomposite.
Current Status of Prostate Biopsy in Africa: Are We Ready for a Targeted Biopsy?
Authors: Dieudonne Ziba Ouima Justin , Gebreselassie Kaleab Habtemichae , Mohammed Taofiq Olayinka , Khalid Abdullahi , Nedjim Saleh Abdelkerim , Kifle Anteneh Tadesse , Biyouma Marcella D. C. , Dogo Hassan , Agbo Christian , Emmanuel Muhawenimana , Mahamat Mahamat Ali , Khassim Ndoye Alain , John Lazarus , Donega Yameogo Clotaire Alexis Marie Kiemdiba , Lezrek Mohamed , Brahima Kirakoya , Adama Ouattara , Aristide Kabore Fasnewende
Published: February 2025

Background

Prostate cancer remains a significant public health issue globally, with considerable disparities in diagnostic and management practices, especially in Africa. Traditional diagnostic methods such as transrectal ultrasound‐guided biopsies have limitations in accuracy and are associated with potential complications. Emerging targeted biopsy techniques promise improved cancer detection rates and reduced morbidity but face adoption challenges across the African continent due to variable access to advanced imaging technologies and professional expertise.

Objective

This study aims to evaluate the current practices of prostate biopsy techniques in Africa, focusing particularly on the readiness for and integration of targeted biopsy methods. It assesses the accessibility, quality, volume of procedures, and availability of advanced diagnostic tools across different regions.

Results

The survey included 58 centers across five African regions, representing a 70% response rate from an initial 83 invitations sent. Finger‐guided biopsy was the most common method, used by 41 centers, while only one center reported using MRI fusion biopsy. Thirty‐five centers routinely administered a rectal enema, and nearly all (n = 50) centers employed antibiotic prophylaxis, predominantly fluoroquinolones. For anesthesia, 12 centers used injectable lidocaine, and 38 centers used intrarectal lidocaine gel. The number of biopsy cores taken varied, with most centers taking 12, while others used fewer.

Conclusion

The findings indicate a critical need for concerted efforts to bridge the gap in prostate cancer diagnostics and treatment in Africa. Enhancing the quality of prostate cancer care on the continent requires investments in training, infrastructure, and standardization of practices. Collaborative efforts towards adopting advanced diagnostic tools and methods are essential for aligning African practices with global standards, ultimately improving outcomes for prostate cancer patients.
Intramuscular CMT‐167 Tumours Produce a Mild Cachexia Phenotype in C57BL/6J Mice
Authors: Remaily Bryan C. , Vu Trang T. , Thomas Justin , Kim Kyeongmin , Stanton Camille , Xie Zhiliang , Granchie Lauren , Manna Millennium , Gregorevic Paul , Mo Xiaokui , Lowe Jeovanna , Rafael‐Fortney Jill A. , Kulp Samuel K. , Ganesan Latha P. , Owen Dwight H. , Mace Thomas A. , Coss Christopher C. , Phelps Mitch A.
Published: February 2025

Background

Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without losses in adipose tissue. Cancer cachexia is an underrecognized syndrome that impacts ~50% of all cancer patients and accounts for up to ~20% of all cancer deaths. Lung cancer remains one of the deadliest cancers in the United States with an estimated 137 000 deaths in the year 2021 alone. Lung cancer is highly comorbid with cancer cachexia. Pre‐clinical models are heavily relied upon to study both lung cancer and cancer cachexia; however, there is a need to develop novel models to study the relationship between the two diseases. We therefore characterized the cachexia phenotype in the CMT‐167 syngeneic lung cancer model.

Methods

Male C57BL6/J mice, aged 8–10 weeks, were administered an intramuscular (IM) injection of either 0.5 × 106 CMT‐167 cells or vehicle. Clinically relevant features of cancer cachexia were assessed 23 days after CMT‐167 cell administration in tumour bearing mice by assessment of terminal skeletal muscle and adipose tissue mass, gastrocnemius myofiber cross sectional area (CSA), circulating biomarkers of cachexia, and skeletal muscle E3 ubiquitin ligase mRNA. A single intravenous dose pharmacokinetic study of pembrolizumab was completed to assess tumour status influence upon antibody pharmacokinetics.

Results

Compared to tumour free (TF) mice, we observed lower terminal tumour‐adjusted bodyweight, adipose tissue mass, gastrocnemius mass, quadriceps mass, and gastrocnemius myofiber CSA. CMT‐167 tumour bearing (TB) mice did not lose bodyweight relative to starting weight, but instead failed to gain as much weight as TF controls. CMT‐167 TB mice exhibited increased concentrations of circulating markers of cachexia and muscle wasting, such as IL‐6 and TNF‐α, although there was no difference in transcription of E3 ubiquitin ligases Trim63 (MuRF‐1) and Fbxo32 (atrogin‐1) in skeletal muscle compared to TF mice. CMT‐167 TB mice exhibited increased catabolic clearance (CL) of the human IgG4 anti‐PD‐1, pembrolizumab, agreeing with published literature showing increased CL of immune checkpoint inhibitors in cachectic populations. Comparing the IM CMT‐167 model to historical data with the well‐established IM Lewis Lung Carcinoma model, CMT‐167 TB mice displayed a less severe cachectic phenotype in terms of bodyweight and skeletal muscle effects.

Conclusions

The IM CMT‐167 model is a syngeneic lung cancer model of mild cachexia. CMT‐167 TB mouse is a novel model in which to study cancer cachexia induction, skeletal muscle atrophy and immune checkpoint inhibitor clearance mechanisms in the context of lung cancer.
H∞$$ {H}_{\infty } $$ PID Control for Singularly Perturbed Systems With Randomly Switching Nonlinearities Under Dynamic Event‐Triggered Mechanism
Authors: Jiao Zhenglong , Wang Zidong , Luo Yuqiang , Wang Fan
Published: February 2025

In this article, the observer‐based proportional‐integral‐derivative (PID) control problem is studied for a class of singular perturbed systems with randomly switching nonlinearities. During the modeling process, a set of binary random sequences is introduced to describe the random behaviors of the nonlinear switching encountered in engineering practice. Considering the singular perturbation parameter (SPP), an observer‐based PID controller is constructed for the concerned singularly perturbed systems (SPSs), where the state information is estimated. To improve communication efficiency and reduce resource waste, a dynamic event‐triggered mechanism is employed during the measurement transmission. Meanwhile, an SPP‐dependent Lyapunov‐Krasovskii function is utilized to derive conditions under which the closed‐loop system is guaranteed to be stochastically stable with the desired performance under a specified upper bound on the SPP. All the desired observer and controller gains are determined by solving a set of matrix inequalities. Finally, the effectiveness and superiority of the suggested PID control method are verified through a simulation example.
Integrated optimization and coordination of cascaded reservoir operations: Balancing flood control, sediment transport and ecosystem service
Authors: Cao Xinmiao , Lin Teng , Li Jiahui , Zhou Ting
Published: February 2025

Exploring optimal operational schemes for synergistic development is crucial for sustainable management in river basins. This study introduces a multi‐objective synergistic optimization framework aimed at analyzing the interplay among flood control, ecological integrity, and desilting objectives under varying water‐sediment conditions. The framework encompasses multi‐objective reservoir optimal operation, scheme decision, and trade‐off analysis among competing objectives. To address the optimization model, an elite mutation‐based multi‐objective particle swarm optimization (MOPSO) algorithm that integrates genetic algorithms (GA) is developed. The coupling coordination degree is employed for optimal scheme decision‐making, allowing for the adjustment of weight ratios to investigate the trade‐offs between objectives. This research focuses on the Sanmenxia and Xiaolangdi cascade reservoirs in the Yellow River, utilizing three representative hydrological years: 1967, 1969, and 2002. The findings reveal that: (1) the proposed model effectively generates Pareto fronts for multi‐objective operations, facilitating the recommendation of optimal schemes based on coupling coordination degrees; (2) as water‐sediment conditions shift from flooding to drought, competition intensifies between the flood control and desilting objectives. While flood control and ecological objectives compete during flood and dry years, they demonstrate synergies in normal years (r = 0.22); conversely, ecological and desilting objectives are consistently competitive across all three typical years, with the strongest competition observed in the normal year (r = −0.95); (3) the advantages conferred to ecological objectives increase as water‐sediment conditions shift from flooding to drought. However, the promotion of the desilting objective requires more complex trade‐offs. This study provides a model and methodological approach for the multi‐objective optimization of flood control, sediment management, and ecological considerations in reservoir clusters. Moreover, the methodologies presented herein can be extended to other water resource systems for multi‐objective optimization and decision‐making.
Achieving Superhardness and Enhanced Toughness in High‐Entropy Boride‐Based Composites by Tailoring Their Multi‐Scale Microstructures
Authors: Qiu Shuaihang , Zou Ji , Liu Jingjing , Wang Weimin , Xie Jingjing , Ji Wei , Wu Jinsong , Zhou Yanchun , Fu Zhengyi
Published: February 2025

Unlike strong yet tough high entropy alloys, high entropy ceramics normally exhibit good hardness but poor strength and fracture toughness. To overcome this obstacle, B4C‐(Zr0.2Hf0.2Nb0.2Ta0.2Ti0.2)B2 composites with a unique hierarchical microstructure are designed and prepared by boronizing reaction sintering of dual‐phase multicomponent carbides. In the as‐obtained composites, massive platelet‐like aggregations assembled by core‐rim structured (Zr0.2Hf0.2Nb0.2Ta0.2Ti0.2)B2 fine grains are distributed randomly in the B4C matrix. Such special microstructure makes B4C‐(Zr0.2Hf0.2Nb0.2Ta0.2Ti0.2)B2 composites exhibit excellent mechanical properties. An extra toughening mechanism of crack bridging is provided in as‐obtained composites (fracture toughness of 4.70 ± 0.08 MPa m1/2) by the interaction between cracks and platelet‐like diboride aggregations whilst fine‐grained microstructures guarantee high flexural strength (633 ± 25 MPa). More importantly, during producing indents, homogenization of core‐rim structured (Zr0.2Hf0.2Nb0.2Ta0.2Ti0.2)B2 alongside more difficult lattice glides caused by short‐range ordering and rough glide planes containing different‐dimension transition metal atoms cooperatively induce increased indentation volume work and consequently unparalleled Vickers hardness (>54 GPa at 1.96 N), which is confirmed by in‐depth transmission electron microscopy characterizations. This work gives a new inspiration to design high‐performance high‐entropy ceramics via multi‐scale microstructure tailoring and composition tuning.
Femtosecond‐Laser Preparation of Hydrogel with Micro/Nano‐Structures and their Biomedical Applications
Authors: Ma Jingyun , Wu Jinchi , Lin Zheli , Wang Jin , Yao Wenhao , Zhang Yi , Zhang Xinquan , Zhu Limin , Hayasaki Yoshio , Zhang Honghao
Published: February 2025

Hydrogels with micro/nano‐structures precisely prepared by femtosecond‐laser processing technology are biomaterials that mimic the natural extracellular matrix and can achieve the precise regulation of biological properties, such as cell behavior and structural–mechanical properties. They also play a crucial role in biomedical fields such as regenerative medicine, bionanostructural construction, drug transport, and particle manipulation. This study summarizes the central role of the nonlinear absorption property of femtosecond lasers in the preparation of hydrogel micro/nano‐structures. Based on the electron‐dynamics model and electron‐density flood theory, the two main processing types of the femtosecond laser‐processed hydrogel, additive and subtractive manufacturing, are discussed in depth. The modification mechanisms such as the photon–electron energy‐field conversion, multiphoton absorption effect, and bubble‐driven bio‐link molding are analyzed. Additionally, the stimulus‐response diversification and functional biomimicry properties of the structural hydrogels under the influences of different laser action modes and hydrogel composition ratios are investigated for their biomedical applications, such as microactuators, drug delivery, microscaffolds, and the in vitro simulation of vascular networks. On this basis, the advantages and limitations of the current technology are summarized and a reasonable prediction for future research on the law of action of the femtosecond‐laser preparation of hydrogel micro/nano‐structures is made.
A Multiobjective Optimization of Laser Powder Bed Fusion Process Parameters to Reduce Defects by Modified Taguchi Method
Authors: Kazemi Zahra , Nayebi Ali , Rokhgireh Hojjatollah , Soleimani Meisam
Published: February 2025

This study investigates the optimization of process parameters in laser powder bed fusion (LPBF) to minimize defects caused by insufficient melting and vaporization of metal powder. The research employs a simulation method that incorporates vaporization effects to tackle a multiobjective optimization problem in selective laser melting (SLM), utilizing the Taguchi method for systematic analysis. Validation of the simulation approach is conducted by comparing it with experimental results from Verhaeghe et al. (Acta Mater. 2009) revealing a strong correlation between simulated and experimental data. This underscores the effectiveness of the method and highlights the significance of vaporization in SLM processes. The optimization process focuses on enhancing melting efficiency while minimizing vaporization by adjusting critical parameters such as laser power, scanning speed, and laser spot radius. Results indicate that laser power has a significant impact on insufficient melting, while scan speed is more critical for reducing vaporization. Furthermore, the study explores various weight scenarios for the combined objective function, concluding that equal weight factors for unmelted and vaporized elements do not guarantee a reduction in total defects. This research provides essential insights into the complex interactions within LPBF, emphasizing the need for careful parameter optimization to improve manufacturing quality.
Experimental and theoretical investigation on seismic performance of Seawater Sea sand cementitious columns reinforced with GFRP bars and PVA fibers
Authors: Li Wei , Chen Feng , Cen Kaiwen , Gu Chengqing , Sun Linzhu
Published: February 2025

With the shortage of global freshwater resources and the improvement of seismic requirements in coastal areas, this study investigated the seismic performance of seven seawater sea sand cement‐based composite columns (GC) with glass fiber‐reinforced polymer bars under different parameters. The effects of polyvinyl alcohol (PVA) fiber content, axial compression ratio, cement‐based composite strength grade and stirrup spacing on the bearing capacity, energy dissipation capacity, and ductility of the specimens were analyzed. The experimental results show that the cumulative energy consumption of the specimens with 2% PVA fiber is about 35% higher than that of the specimens without fiber. When the axial compression ratio decreases from 0.4 to 0.2, the comprehensive performance of the specimen can be improved by up to 43%. When the cement‐based strength grade is increased from C30 to C50, the bearing capacity of the specimen is significantly increased, with a maximum increase of 22%. In addition, the restoring force model theory of composite column is established, and the skeleton curve is consistent with the test curve. The modified damage model is established, and the damage assessment of each specimen is carried out. It is found that the low axial compression ratio and the incorporation of PVA fiber are helpful to slow down the damage and failure of the specimen.
Developing Professionally in a Third Space: The Case of Indonesian English Teacher Educators Engaging in an Online Professional Development Community
Authors: Zakaria Faishal
Published: February 2025

English teachers and teacher educators worldwide have engaged in various continuous professional development (PD) activities to catch up with the development and challenges of their profession. In Indonesia, for example, English teacher educators who are also faculty members are pressured to publish in internationally‐indexed journals. Fortunately, nontraditional PD models that are more personalized and timelier for educator's needs are available. One such model is interactive online PD formats, particularly online PD communities, where knowledge is not merely received but also constructed and shared among participants. However, it is still unclear why members remain in such communities and how they sustain their engagement. Situated in the Third Space framework, this case study focused on an online PD community of 33 Indonesian English teacher educators. The study attempted to determine why these teacher educators participated in the community and remained involved over an extended period. The findings revealed two main reasons why they joined and stayed in the community. Also, the community served as a Third Space where members felt empowered to present contradictory voices against government‐sanctioned PD discourses. Some critical implications of the findings are addressed.
Intersectoral Collaboration Between Traditional Bonesetters and Formal Healthcare: A Systematic Review on Past Initiatives and Stakeholder Perspectives
Authors: Binnerts Joost J. , Hendriks Thom C. C. , Hussein Samia , Bempong‐Ahun Nefti , Ibbotson Geoffrey C. , Harrison William J. , Martin Claude , Ranganathan Kavitha , Ehsan Anam N. , Chirangi Bwire M. , Edwards Michael J. R. , Hermans Erik
Published: February 2025

Background

Bone fractures in low‐ and middle‐income countries are commonly managed by traditional bonesetters (TBSs). Past studies emphasize the potential for improved fracture care through intersectoral cooperation. This review gauged support among stakeholders for intersectoral collaboration and the results of previous initiatives.

Methods

Five medical databases were reviewed. Studies focusing on stakeholder perspectives and articles detailing collaborative initiatives were included. Data extraction and synthesis were carried out using the Cochrane Consumers and Communication Review Group's template. Additionally, all studies underwent quality assessment.

Results

Of the 3821 identified articles, 16 were included after full‐text screening. Twelve articles presented stakeholder perspectives, whereas four discussed collaborative initiatives. The overall article quality was low: articles on stakeholder perspectives scored on average 1.42 out of 4 points, whereas articles on collaborative initiatives scored a mean 1.25 points. In total, 62% of stakeholders (75% of TBSs, 92% of hospital staff, and 52% of patients) expressed support for intersectoral collaboration. The ratio between stakeholders expressing support versus those opposing was 4.4:1. No articles presented data on governmental perspectives. The most mentioned collaborative forms were TBS training (24% of stakeholders) and an integrative model (16% of stakeholders). Interventional studies all consisted of TBS training, reporting improved clinical outcomes and increased practice integration.

Conclusion

Despite the limited and low‐quality evidence on collaboration initiatives and perspectives, most stakeholders seem supportive of intersectoral collaboration, with training and integration being commonly suggested. Future research efforts exploring the feasibility of embedding TBSs into current primary care systems should ensure the involvement of local and national government.
Negotiating Consent: Setting Boundaries in the Sexual Contract
Authors: Abel Gillian , Fraser Cherida , Brents Barbara G. , Sanders Teela , Scoular Jane
Published: February 2025

In this chapter, we examine how sex workers learn to negotiate with clients and how they set and maintain boundaries within commercial sex transactions. Expectations for a commercial sex transaction in terms of what services will and will not be provided are set up in the negotiation process. This negotiation constitutes a verbal contract which, in most instances, is adhered to. However, some clients try to push the boundaries of the contract. In some cases, sex workers consider the boundary crossing to be minor and make the decision to accommodate the breach. In other cases, the terms of the contract are themselves breached, and the service becomes non-consensual.
Efficiency of a virtual fracture clinic review protocol in adult patients with distal radial fractures requiring semi-acute surgical treatment
Authors: Salentijn Dorien A. , Willinge Gijs J. A. , van Veen Ruben N. , Dijkgraaf Marcel G. W.
Published: February 2025

Purpose

The aim of this study was to evaluate the effect of implementation of a Virtual Fracture Clinic (VFC) review protocol on the time between injury and surgery, and on secondary healthcare utilization, in patients with Distal Radius Fractures (DRFs) requiring semi-acute surgery.

Methods

Data for this retrospective before-after study were gathered between April 2017 and March 2019 (Pre-VFC n = 269), and between April 2021 and March 2023 (VFC n = 440) in a large level 2 urban trauma center. The primary outcome was the number of days between injury and operation. Furthermore secondary healthcare utilization was assessed.

Results

The average time between injury and surgery was 11.0 days (95% CI: 10.6–11.5) before and 9.2 days (95% CI: 8.9–9.6) after VFC-implementation ( p < 0.001). Following VFC-implementation, 33% (was 17%) of patients underwent surgery within 7 days, 92% (was 84%) within 2 weeks, and 99% (was 96%) within 3 weeks (p < 0.001). This included patients with delays of up to 15 days between injury and their initial hospital presentation. Hospital contacts decreased from 5 (IQR: 4–6) to 4 (IQR: 3–5) whereof physical consults decreased from 4 (IQR: 3–5) to 1 and telephone contacts increased from negligible to 1 (IQR: 1–2). Radiographs reduced from 6 (IQR: 5–7) to 4 (IQR: 3–5).

Conclusions

Implementation of a VFC-review protocol is associated with a reduced time between injury and semi-acute surgery for DRFs and reflects an improvement in quality of timely planning. Secondary healthcare utilization is reduced and a shift to remote delivery of care is observed.

Level of evidence

Level III.
A single-centre, retrospective study on the impact of omitting preoperative antibiotic prophylaxis on wound infections in minor orthopedic implant removals
Authors: Pfammatter Cyrill , Hambrecht Jan , Kalbas Yannik , Neuhaus Valentin , Hierholzer Christian , Canal Claudio
Published: February 2025

Background

The use of preoperative antibiotic prophylaxis (POAP) in elective implant removal (IR) is controversial due to a lack of evidence-based recommendations. First-generation cephalosporins, which are commonly used in orthopedic IR, are believed to reduce wound infection risks. However, the potential for serious side effects had raised concerns about their necessity. This study was intended to evaluate whether omitting POAP in small IR increases the risk of wound infections.

Methods

This retrospective, single-centre cohort study was conducted at a level I trauma centre in Switzerland, including patients who underwent IR between January 1, 2016, and December 31, 2021. The IR procedures involved the upper extremities (UEs), such as the clavicle, olecranon, radius and ulna, as well as the lower extremities (LEs), such as the patella, tibia, fibula, (bi)malleolar and foot. Postoperative follow-up included clinical and radiological evaluations 6 weeks after surgery. The outcomes assessed were deep wound infections, wound healing complications, refractures, persistent pain, bleeding, neurovascular injuries and muscle hernias.

Results

Of the 273 patients (mean age: 42.1 ± 14.5; 44% female), 117 (42.9%) received POAP. In the LE group (n = 141), 51.1% received POAP; in the UE group (n = 132), 34.1% received POAP. Eleven (4.0%) wound-healing disorders were documented, with five (4.3%) in the POAP group and six (3.8%) in the non-POAP group (p = 1). No deep wound infections were observed.

Conclusion

Withholding POAP in elective IR procedures does not significantly increase wound infection rates, suggesting it may be unnecessary in uncomplicated cases.
Partnership and marriage and risk of type 2 diabetes: a narrative review
Authors: Kowall Bernd , Rathmann Wolfgang
Published: February 2025

In this review, we discuss how partnership and marriage influence cardiometabolic risk factors and risk of type 2 diabetes, and how couple-based approaches to type 2 diabetes prevention might complement individual-focused prevention efforts. There is some evidence that being married per se has a small positive effect on type 2 diabetes risk. Moreover, there is spousal concordance for many type 2 diabetes risk factors due to assortative mating and convergence during partnership, with weak to moderate correlations found for anthropometric measures, blood pressure, lipid concentrations, smoking, alcohol consumption and physical activity level. A meta-analysis shows that people have a higher risk of type 2 diabetes if their spouse has diabetes (OR 1.72, 95% CI 1.47, 2.02). However, despite some evidence, there is still a lack of research on similar associations in relation to progression to type 2 diabetes and diabetes complications. Several studies have suggested that behaviour changes, for example smoking cessation or weight loss, in one partner increase the likelihood that the other partner will make the same changes. Subsequent studies of couple-based interventions that focus on both partners have shown that people are more likely to adhere to a diabetes prevention programme if their partners are also involved in the programme. However, the effect of the quality of marriage on the outcome of an intervention is still unclear. Couple-based interventions are promising, but there is a lack of RCTs comparing couple-based interventions with individual-centred interventions.

Graphical Abstract
Analyzing the impact of demand management in rural shared mobility-on-demand systems
Authors: Anzenhofer Fabian , Fleckenstein David , Klein Robert , Steinhardt Claudius
Published: February 2025

In rural areas, shared mobility-on-demand services can improve the sustainability of public transport. However, bundling customer rides is challenging due to an unfavorable spatial and temporal demand distribution. As one potential solution, service providers could apply demand management. By controlling the availability of offered rides on an operational level, they could try to influence the resulting orders to allow more bundling. In practice, however, the introduction of demand management, which is a strategic decision, is often impeded by the inability of stakeholders to assess the exact impact on system performance in advance. In this paper, we tackle this issue by developing a methodology that serves as a basis for the strategic decision on how to implement operational demand management by realizing different types of demand control policies. More precisely, we propose a methodology that evaluates different policies by applying them to a model of the operational planning problem, which itself has not been considered in the existing literature. For this purpose, we first formulate the operational planning problem as a Markov decision process. Second, we apply practical solution algorithms representing different control policies on a model variant supporting the strategic decision. Finally, drawing on real-world data from FLEXIBUS, a rural provider in Germany, we conduct a computational study and present managerial insights into the impact of different control policies on the system performance in terms of profit, which the provider aims at maximizing, and other sustainability-oriented objectives of municipal contracting authorities.
Exploring the effects of synthetic data generation: a case study on autonomous driving for semantic segmentation
Authors: Silva Manuel , Seoane Antonio , Mures Omar A. , López Antonio M. , Iglesias-Guitian Jose A.
Published: February 2025

Rendering 3D virtual scenarios has become a popular alternative for generating per-pixel-labeled image datasets, especially in fields like autonomous driving. The approach is valuable for training neural perception models, such as semantic segmentation models, particularly when data might be scarce, expensive, or difficult to collect. However, fundamental questions persist within the research community regarding the generation and processing of these synthetic images, particularly a better understanding of the key factors influencing the performance of deep learning models trained with such synthetic images. In response, we conducted a series of experiments to elucidate the impact that common aspects involved in the generation of rendered synthetic images may have on the performance of neural semantic segmentation tasks. Our study used a recent autonomous driving synthetic dataset as our main testbed, allowing us to investigate the effect of different approaches when modeling their geometric, material, and lighting details. We also studied the impact of rendering noise, typically produced by path-tracing algorithms, as well as the impact of using different color transformations and tonemapping algorithms.