bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional time of flight magnetic resonance angiography at 5.0T: Visualization of the superior cerebellar artery
Authors: Tian Ning , Jiang Xiangsen , Yu Lei , Yin Zudong , Yu Dan , Gan Jie
Published: September 2024

Background

To explore the utility of 5.0T ultra‐high field magnetic resonance (MR) for the assessment of the superior cerebellar artery (SCA).

Methods

Imaging data from 55 patients (19 men and 36 women) who underwent three‐dimensional time of flight MR angiography (3D‐TOF‐MRA) with 5.0T MRI in the Shandong University Affiliated Shandong Provincial Third Hospital from May 22, 2023 to June 16, 2023 were retrospectively analyzed. The origin, caliber, and course of the SCA were recorded. An independent sample t‐test was used to compare the differences in quantitative indexes between the two groups.

Results

A total of 123 superior cerebellar arteries were detected in 55 patients. We found that 86.99% of superior cerebellar arteries were longer than the P3 segment of the posterior cerebral artery. The superior cerebellar arteries were divided into nine types according to the origin of the SCA, with Type A accounting for the highest proportion (approximately 49.09%). The mean diameter of the SCA was 1.11 ± 0.22 mm, while the mean diameters of the right and left sides were 1.13 ± 0.24 mm and 1.07 ± 0.27 mm, respectively. There were no differences in SCA diameters between the two sides (p > 0.05).

Conclusions

3D‐TOF‐MRA with ultra‐high field 5.0T MR can effectively evaluate the SCA, and provides a new effective imaging evaluation method for clinical practice.
N6‐methyladenosine demethyltransferase FTO alleviates sepsis by upregulating BNIP3 to induce mitophagy
Authors: Qi Pingping , Zhang Wei , Gao Yang , Chen Shengkui , Jiang Minghe , He Rong , Chen Wenzhong , Wei Xiawei , Hu Bingquan , Xu Hao , Wu Minsheng , Tang Rong
Published: September 2024

N6‐methyladenosine (m6A) is known to be crucial in various biological processes, but its role in sepsis‐induced circulatory and cardiac dysfunction is not well understood. Specifically, mitophagy, a specialized form of autophagy, is excessively activated during lipopolysaccharide (LPS)‐induced myocardial injury. This study aimed to investigate the impact of LPS‐induced endotoxemia on m6A‐RNA methylation and its role in regulating mitophagy in sepsis‐induced myocardial dysfunction. Our research demonstrated that FTO (fat mass and obesity‐associated protein), an m6A demethylase, significantly affects abnormal m6A modification in the myocardium and cardiomyocytes following LPS treatment. In mice, cardiac dysfunction and cardiomyocyte apoptosis worsened after adeno‐associated virus serotype 9 (AAV9)‐mediated FTO knockdown. Further analyses to uncover the cellular mechanisms improving cardiac function showed that FTO reduced mitochondrial reactive oxygen species, restored both basal and maximal respiration, and preserved mitochondrial membrane potential. We revealed that FTO plays a critical role in activating mitophagy by targeting BNIP3. Additionally, the cardioprotective effects of AAV‐FTO were significantly compromised by mdivi‐1, a mitophagy inhibitor. Mechanistically, FTO interacted with BNIP3 transcripts and regulated their expression in an m6A‐dependent manner. Following FTO silencing, BNIP3 transcripts with elevated m6A modification levels in their coding regions were bound by YTHDF2 (YT521‐B homology m6A RNA‐binding protein 2), leading to mRNA destabilization and decreased BNIP3 protein levels. These findings highlight the importance of FTO‐dependent cardiac m6A methylation in regulating mitophagy and enhance our understanding of this critical interplay, which is essential for developing therapeutic strategies to protect cardiac mitochondrial function, alleviate cardiac dysfunction, and improve survival during sepsis.
LRRK2G2019S Gene Mutation Causes Skeletal Muscle Impairment in Animal Model of Parkinson's Disease
Authors: Hu Yiying , Yang Huijia , Song Chunli , Tian Lulu , Wang Panpan , Li Tianbai , Cheng Cheng , AlNusaif Murad , Li Song , Liang Zhanhua , Le Weidong
Published: September 2024

Background

While the gradually aggravated motor and non‐motor disorders of Parkinson's disease (PD) lead to progressive disability and frequent falling, skeletal muscle impairment may contribute to this condition. The leucine‐rich repeat kinase2 (LRRK2) is a common disease‐causing gene in PD. Little is known about its role in skeletal muscle impairment and its underlying mechanisms.

Methods

To investigate whether the mutation in LRRK2 causes skeletal muscle impairment, we used 3‐month‐old (3mo) and 14‐month‐old (14mo) LRRK2G2019S transgenic (TG) mice as a model of PD, compared with the age‐matched littermate wild‐type (WT) controls. We measured the muscle mass and strength, ultrastructure, inflammatory infiltration, mitochondrial morphology and dynamics dysfunction through behavioural analysis, electromyography (EMG), immunostaining, transmission electron microscopy (TEM) and other molecular biology techniques.

Results

The 3mo‐TG mice display mild skeletal muscle impairment with spontaneous potentials in EMG (increased by 130%, p < 0.05), myofibre necrosis (p < 0.05) and myosin heavy chain‐II changes (reduced by 19%, p < 0.01). The inflammatory cells and macrophage infiltration are significantly increased (CD8a+ and CD68+ cells up 1060% and 579%, respectively, both p < 0.0001) compared with the WT mice. All of the above pathogenic processes are aggravated by aging. The 14mo‐TG mice EMG examinations show a reduced duration (by 31%, p < 0.01) and increased polyphasic waves of motor unit action potentials (by 28%, p < 0.05). The 14mo‐TG mice present motor behavioural deficits (p < 0.05), muscle strength and mass reduction by 37% and 8% (p < 0.05 and p < 0.01, respectively). A remarkable increase in inflammatory infiltration is accompanied by pro‐inflammatory cytokines in the skeletal muscles. TEM analysis shows muscle fibre regeneration with the reduced length of sarcomeres (by 6%;p < 0.05). The muscle regeneration is activated as Pax7+ cells increased by 106% (p < 0.0001), andmyoblast determination protein elevated by 71% (p < 0.01). We also document the morphological changes and dynamics dysfunction of mitochondria with the increase of mitofusin1 by 43% (p < 0.05) and voltage‐dependent anion channel 1 by 115% (p < 0.001) in the skeletal muscles of 14mo‐TG mice.

Conclusions

Taken together, these findings may provide new insights into the clinical and pathogenic involvement of LRRK2G2019 mutation in muscles, suggesting that the diseases may affect not only midbrain dopaminergic neurons, but also other tissues, and it may help overall clinical management of this devastating disease.
Quantitative evaluation of myocardial perfusion in coronary heart disease by myocardial contrast and dobutamine stress echocardiography
Authors: Guo Liping , Zhang Yuanxiang , Wen Jia , Chen Jing
Published: September 2024

Objective

We aimed to investigate how combining myocardial contrast echocardiography (MCE) with dobutamine stress echocardiography (DSE) could help evaluate myocardial perfusion in coronary heart disease patients and understand changes in microcirculation across different levels of coronary artery blockage.

Methods

We conducted MCE and DSE tests on 53 coronary heart disease patients, categorizing ischemic myocardium into four groups: A (<50%), B (50%–69%), C (70%–89%), and D (≥90%). Dynamic myocardial perfusion images were captured during rest and peak dobutamine stress from various angles, analyzing parameters like plateau value A, slope β, and the product A × β, reflecting different aspects of myocardial blood flow.

Results

Parametric values of myocardial perfusion (PVMPs) were significantly lower in group D at rest compared with other groups (p < 0.001). PVMPs increased notably at peak dobutamine stress in groups A, B, and C (p < 0.001). Groups A and B had higher PVMPs than groups C and D, with group D significantly lower (p < 0.001). β reserve values decreased gradually from group A to D, with significantly lower values of A and A × β in groups C and D compared with A and B (p < 0.001). Sensitivity and specificity for predicting >70% coronary artery blockage was 80%, 66%, and 74%, 80%, respectively, using specific thresholds.

Conclusion

Combining MCE with DSE is highly sensitive and accurate in diagnosing obstructive coronary artery blockages. It also helps assess myocardial microcirculation perfusion and left ventricular reserve function, which decline with increasing severity of coronary artery blockage.
Training a rural oral health workforce: Effects of rural background on dentist practice choice
Authors: Forsyth Anna R. , Melkonyan Arsen A. , Kerns Kristopher , Flake Natasha M. , Greene Rachel M. , Roberts Frank A.
Published: September 2024

Purpose

The Regional Initiatives in Dental Education (RIDE) program is an educational track of the University of Washington School of Dentistry that aims to produce leaders who practice in rural areas of the Pacific Northwest. This study assesses outcomes of the first 10 years of the RIDE program. The hypothesis tested is that rural background is the most important predictor of long‐term rural dental practice.

Methods

This descriptive study assessed existing data including graduates' location of practice, demographics, rurality of origin, parental occupation, and practice type over time. Subjects are all graduates of the RIDE program from 2012 to 2021 (N = 80), and range in age from 25 to 50 years. Statistical analyses were utilized to explore associations.

Results

Within the study sample 78% of graduates practiced in a rural and/or underserved area, 32.5% of graduates pursued post‐graduate dental training, 40% participated in Medicaid, and 78% practiced in the Pacific Northwest at the time of analysis (March 2023). Statistical analysis demonstrated a strong association and medium to large effect sizes between both rural upbringing and training sites and established dental practice in a rural region.

Conclusions

Graduates of the RIDE program practice in rural areas in greater proportion compared to the general population of practicing dentists. RIDE graduates from the study period tended to be male, and white, and practice in a health professional shortage area or rural site. The rurality of origin analysis was confounded by the substantial number of graduates from Spokane, Washington, an urban area surrounded by extensive rural territory.
Assessment of BDNF and sialic acid levels in children with ADHD: Relation of chronotypes
Authors: Demirci Esra , Gul Melike Kevser , Sener Elif Funda , Onal Muge Gulcihan , Dal Fatma
Published: September 2024

Objective

Evaluation of the biomarkers and their relations with sleep in attention deficit hyperactivity disorder (ADHD) is important for understanding the impairments in cognitive functioning. In this study, we aimed to investigate the brain‐derived neurotrophic factor (BDNF) and sialic acid (Sia) levels, and their possible relations with chronotypes in ADHD.

Methods

The study included 100 drug‐naive children with ADHD and 74 healthy children as controls. Conners' Parent Rating Scale‐Revised (CPRS‐R) scores were used for the severity assessment. Morningness Eveningness Questionnaire (MEQ) was used to determine the chronotypes of participants. ELISA kits were used for the assessment of BDNF and Sia plasma levels.

Results

Levels of BDNF and Sia were found to be statistically significantly higher in the ADHD group compared to healthy children (p < 0.001, p < 0.001, respectively). BDNF and Sia levels were found to be higher in the ADHD group with eveningness chronotype (p = 0.045, p = 0.038). The binary logistic regression model was statistically significant (p = 0.033), higher BDNF and Sia levels were assessed as predictive factors for the diagnosis of ADHD. Also, eveningness chronotype was found as a predictive factor of BDNF and Sia levels in ADHD.

Conclusion

The results indicate that BDNF and Sia levels, which are related to cognitive functions and sleep, increase with the age of ADHD. Eveningness chronotype, connected with the severity of ADHD, is related to BDNF and Sia levels. There is a need for further studies to confirm these results.
Patients aged 55 or older undergoing around the knee osteotomy have a higher rate of deep vein thrombosis but not overall early post‐operative complications
Authors: Olivieri Rodrigo , Laso José , Pineda Tomás , Albornoz Pablo , Starocelsky Nicolás , Franulic Nicolás , Ugarte Jaime
Published: September 2024

Purpose

Osteotomies around the knee have been established as an effective method for treating varus or valgus malalignment associated with other knee pathologies in young and middle‐aged patients. There is limited literature regarding the risks and complications based on patient age. The purpose of this study is to determine whether age influences as a risk factor for developing intraoperative and early post‐operative complications in patients undergoing osteotomies around the knee.

Methods

A consecutive series of patients over 18 years old who underwent distal femoral osteotomy (DFO) or high tibial osteotomy (HTO) with a minimum follow‐up period of 90 days were included. Demographic characteristics, surgical technique, intraoperative and post‐operative complications up to 90 days were identified. A statistical comparison based on age younger than 55 years or 55 years and older was conducted to determine if patient age acted as a risk factor in the development of complications.

Results

A total of 159 osteotomies were included, of which 129 were HTOs. The average age was 46.16 years, and 118 patients were younger than 55 years. Seven hinge fractures were identified as the only intraoperative complication, while the overall early post‐operative complication rate was 11.32%. The most frequent was deep venous thrombosis (DVT) in 5.66% of cases, followed by deep infection with a total rate of 2.52%. When performing the subgroup analysis by age, we observed a significantly higher rate of DVT in the group aged 55 years and older (p 0.036) (odds ratio 3.96 95% confidence interval 1.009–15.533; p 0.048); however, no significant differences were observed in the overall complication rate according to the age group of the patients.

Conclusions

This study reveals that in patients undergoing osteotomies around the knee, the most common post‐operative complication was DVT. The rate of DVT was significantly higher in patients aged 55 years and older, although no differences were observed in the overall complication rate according to the patients' age range.

Level of evidence

Level III (retrospective cohort study).
Microstructural Study of the Coloring Variation of Chinese Sauce Glaze Replications
Authors: Wang Tian , Xia Senwei , Ren Zhao , Hole Clement , Wang Fen , Zhu Jianfeng , Luo Hongjie , Li Qiang , Liao Meihong , Sciau Philippe
Published: September 2024

Sauce glazed wares of Yaozhou kilns are famous for their high gloss and distinctive glaze color palette varying from yellowish‐brown to reddish‐brown. In this work, sauce glazes were successfully replicated using the traditional technology of Yaozhou kilns. Micro‐Raman spectroscopy, combined with optical microscopy, scanning electron microscopy, x‐ray fluorescence, and reflective spectroscopy, was systematically applied to analyze the chemical composition, nature and distribution of crystals, and the coloration of the glazes. The results show that the yellowish‐brown glaze is mainly original from dendritic ε‐Fe2O3 crystals, whereas the reddish‐brown color is mainly derived from dendritic hematite crystals. Such dendritic structure could account for slightly color variations of the glaze surface observed in different angles, which also reported in Japanese Bizen ceramics. The principal component analysis (PCA) was further applied to study the Raman spectra of these iron oxides. The PCA results effectively indicates the structural disorders of these crystals introduced by ion substitutions. These substitutions could not only stabilize the crystals but also darken the crystals color. Besides, high Mg in the raw materials was found to benefit the growth of magnesioferrite crystals. The relative low level of Fe2O3, high level of SiO2, and CaO may relate to the formation of ε‐Fe2O3 crystals.
Personal Brand Equity and Telepresence's Role in Tourism Electronic Commerce Live Streaming
Authors: Liu Jing , Hsu Fu‐Chieh , Ma Yiran , Huang Yuqing
Published: September 2024

Despite the increasing popularity of e‐commerce live streaming (ECLS), research development in the hospitality and tourism field lags. Drawing on social impact theory, this study aims to investigate the effects of streamers' personal brand equity (strength) and the live‐streaming broadcasting environment (immediacy) on viewers' tourism product purchase intention. This research developed three experimental studies to examine the causal link between live‐streaming features (i.e., the interactive effect of streamers' personal brand equity and telepresence) and customer responses. The results showed that the interactions between different levels of personal brand equity and telepresence significantly impact positive outcomes related to tourists' behavior and decision‐making. This study contributed to the literature and practices by enhancing the understanding of ECLS as a newly emerging marketing tool in the tourism industry. The findings would encourage more hospitality and tourism companies to leverage ECLS as a new marketing campaign strategy.
Instrumentation Considerations for Calcified Thyroid Cartilage during Chondrolaryngoplasty
Authors: Stevenson Lily A. , Song Phillip C. , Franco Ramon A. , Naunheim Matthew R.
Published: September 2024

Objective

Chondrolaryngoplasty, also known as thyroid cartilage reduction, alleviates gender dysphoria by reducing the thyroid cartilage to conform to a patient's gender identity. Reduction of the thyroid cartilage prominence (“Adam's apple”) is often performed with a scalpel, but in cases of cartilage calcification, rongeurs or drills are utilized. This study aims to characterize the success rate with scalpel‐only excision and relate this to patient age and operative time.

Methods

Billing records were screened for chondrolaryngoplasties performed between 2020 and 2023 by a single surgeon. Patient demographics, operative notes, and operation duration were recorded. Type of instrumentation was categorized as scalpel only, rongeur, or drill. All cases began with attempted scalpel excision of cartilage and were transitioned to rongeur or drill if there was calcification that prevented sharp excision. Descriptive statistics were used to describe patient and surgical factors.

Results

52 individuals underwent chondrolaryngoplasty: 30 cases (57.7%) had soft cartilage requiring only a blade, 22 (42.3%) required use of either drill or rongeur. The average age of these groups was 25.7 (SE 1.8) and 41.3 years (SE 2.2), respectively; this difference was statistically significant (p < 0.0001). Cases requiring a drill or rongeur lasted on average 78.5 min (SE 2.3), whereas those using only a blade were shorter at 66.8 min (SE 2.7); this difference was significant (p = 0.0017).

Conclusion

Cartilage calcification should be expected in a significant number of chondrolaryngoplasties, and surgeons should be prepared for this scenario. The need for alternative instrumentation is higher in older individuals and may extend procedural time.

Level of Evidence

4 Laryngoscope, 135:748–751, 2025
The Role of Spatial Morphology in Forest Landscape Fragmentation: Insights From Planted and Natural Forests of the Chinese Loess Plateau
Authors: Zhang Mei , Yu Shichuan , Zhao Zhong
Published: September 2024

This study aimed to emphasize the key role of spatial morphology of planted and natural forests on landscape fragmentation and to furnish a scientific foundation for the effective assessment of ecological restoration projects of vegetation on the Loess Plateau. The spatial morphological pattern and landscape fragmentation characteristics were analyzed using morphological spatial pattern analysis (MSPA) and forest area density methods. This is the inaugural study to reveal the linear and nonlinear relationships between forest landscape fragmentation and its driving factors using machine learning methods and introducing morphological indicators with two different strategies. The results showed significant differences in the spatial patterns and landscape fragmentation characteristics between planted and natural forests. The spatial patterns of planted and natural forests were found to be dominated by “Core” in terms of area, while “Branch” was more prevalent in terms of number. Compared to natural forests, planted forests were more fragmented. The introduction of the MSPA indicator significantly enhanced the explanatory power and predictive performance of the model despite the disparate contribution rates of the driving factors in planted and natural forests. This study highlights the importance of spatial morphology in understanding forest landscape fragmentation and provides a new combination of analytical techniques to better understand the complexity of forest ecosystems. These provide new insights into forest landscape restoration and sustainable management on the Loess Plateau.
Analysis of Adoption of Soil Nutrient Management Practices: A Case of Rice Farmers in Liberia
Authors: Apeh Chikamso Christian , Chiemela Stella Nwawulu , Apeh Andrew Chiahalam , Okere Richard Anayo , Ukwuaba Sunday Ifeanyi , Onyekuru Anthony NwaJesus
Published: September 2024

The declining level of crop yield in connection with soil infertility poses a major threat to farmers’ food security and income leading to adoption of different soil nutrient management (SNM) practices by rice farmers. The study identified five soil SNM options adopted by rice farmers and the factors influencing their adoption in the South Eastern region of Liberia. A multistage sampling technique was used to select study areas and participants, starting with purposive sampling of 6 high rice‐producing counties and 12 districts, followed by random sampling of 17 rice farmers from each district, resulting in a total of 408 farmers, with data collected through structured questionnaires. Data were analyzed using descriptive statistics and a probit regression model to understand the factors influencing SNM adoption. The result showed that the majority (78.43%) of the rice farmers were into lowland rice farming, 97.55% into integrated SNM with 26.72% in organic fertilizer options. The probit regression analysis revealed that the likelihood of adopting SNM practices was significantly influenced by gender (−4.9%), age (+8.2%), education (+16.7%), land ownership (−6.8%), farm size (+4.4%), agricultural group membership (+32.08%), credit access (+4.9%), and farm distance (−8.8%). It was observed that rice farmers adopt SNM practices primarily to increase yield ( = 4.34), with secondary motivations including maintaining a healthy environment ( = 3.89), increasing income ( = 3.46), and improving food and nutrition security ( = 3.11). To ensure efficient and effective rice production and boost agricultural output, agricultural policymakers and extension services should actively promote the adoption of SNM and integrated practices by providing targeted education and increasing access to credit facilities for farmers.
Unexpected mismatches in population structure among marine mussel life‐history stages reveal the true scales of planktonic larval dispersal
Authors: Oliver Jody‐Carynn , Porri Francesca , Emami‐Khoyi Arsalan , Teske Peter R.
Published: September 2024

Studies investigating gene flow in sessile or sedentary marine species typically draw conclusions about larval dispersal by investigating genetic structure of adults. Here, we generated microsatellite data from adults, recruits, settlers and planktonic larvae of the brown mussel, Perna perna, from the southeast coast of South Africa, and identified a consistent mismatch in genetic structure between the adults and all earlier life stages. While adults could be assigned to two major geographical groups (western and eastern), most of the early‐stage mussels were strongly affiliated with the eastern group. This suggests that few of the early‐stage individuals present in the western portion of the sampling range will eventually establish themselves in the adult population, highlighting the importance of post‐recruitment processes as drivers of population structure. Our findings caution against the exclusive use of genetic data generated from adults to assess population connectivity facilitated by the dispersal of planktonic propagules.
Achromatic Silicon Photonic Waveguide Lenses for Ultra‐Broadband Multimode Spot‐Size Conversion
Authors: Liu Ruoran , Zhao Weike , Dai Daoxin
Published: September 2024

The rapid development of silicon photonics inspired the emergence of on‐chip geometric optics. As one of the most crucial elements, waveguide‐lenses have attracted much attention. Nevertheless, waveguide‐lenses often suffer from large chromatism due to the strong waveguide dispersion, especially for the cases with multiple guided‐modes. In this paper, achromatic waveguide‐lenses available for multimode photonics are proposed and are further utilized for realizing multimode spot size converters (MSSCs) as an example. The present MSSC shows low excess losses < 0.4 dB and low inter‐mode crosstalks <−14 dB within an ultra‐broad bandwidth of 1450–1650 nm, which is realized for the first time by comprising a positive waveguide‐lens and a negative waveguide‐lens. In addition, the present MSSC is applied successfully for realizing high‐performance multimode waveguide corner‐bends. To the best of the knowledge, the proposed MSSC is the unique one with an ultra‐compact footprint and the largest bandwidth for low crosstalks as well as low losses, indicating that on‐chip geometric optics potentially provides a new perspective for on‐chip light manipulation desired in various applications.
Physician Level Assessment of Hirsute Women and of Their Eligibility for Laser Treatment With Deep Learning
Authors: Thomsen Kenneth , Jalaboi Raluca , Winther Ole , Lomholt Hans Bredsted , Lorentzen Henrik F. , Høgsberg Trine , Egekvist Henrik , Hedelund Lene , Jørgensen Sofie , Frost Sanne , Bertelsen Trine , Iversen Lars
Published: September 2024

Objectives

Hirsutism is a widespread condition affecting 5%–15% of females. Laser treatment of hirsutism has the best long‐term effect. Patients with nonpigmented or nonterminal hairs are not eligible for laser treatment, and the current patient journey needed to establish eligibility for laser hair removal is problematic in many health‐care systems.

Methods

In this study, we compared the ability to assess eligibility for laser hair removal of health‐care professionals and convolutional neural network (CNN)‐based models.

Results

The CNN ensemble model, synthesized from the outputs of five individual CNN models, reached an eligibility assessment accuracy of 0.52 (95% CI: 0.42–0.60) and a κ of 0.20 (95% CI: 0.13–0.27), taking a consensus expert label as reference. For comparison, board‐certified dermatologists achieved a mean accuracy of 0.48 (95% CI: 0.44–0.52) and a mean κ of 0.26 (95% CI: 0.22–0.31). Intra‐rater analysis of board‐certified dermatologists yielded κ in the 0.32 (95% CI: 0.24–0.40) and 0.65 (95% CI: 0.56–0.74) range.

Conclusion

Current assessment of eligibility for laser hair removal is challenging. Developing a laser hair removal eligibility assessment tool based on deep learning that performs on a par with trained dermatologists is feasible. Such a model may potentially reduce workload, increase quality and effectiveness, and facilitate equal health‐care access. However, to achieve true clinical generalizability, prospective randomized clinical intervention studies are needed.
Synthesis and Magnetic Property of 4,4′‐(2,6‐Anthracenediyl)bis(2,6‐di‐tert‐butylphenoxyl) Diradicaloids
Authors: Kaneko Takashi , Ogawa Ayako , Teraguchi Masahiro , Aoki Toshiki
Published: September 2024

Anthracene based phenoxyl diradicaloids are synthesized. The UV–vis spectra of them give absorption maxima around 700 nm attributes to the extended quinone structure. The diradical characters y of them are estimated as ∼0.6 from their static magnetic susceptibility and absorption maxima. The extended π‐conjugated anthracene‐linker enhances the diradical characters compared to the phenylene linker. It is noteworthy that these enhanced diradical characters are accomplished without steric effects.
Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells
Authors: Gao Fei , Mora Mauricio Campos , Constantinides Michael , Coënon Loïs , Multrier Caroline , Vaillant Loïc , Peyroux Julien , Zhang Tianxiang , Villalba Martin
Published: September 2024

Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood‐derived NK (PB‐NK) and umbilical cord blood‐derived NK (UCB‐NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB‐NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB‐NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ– NK (eg‐NK) cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine‐producing or cytotoxic eNK cells.
Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype–Phenotype Correlation
Authors: Finnegan Rebecca , O'Regan Mary , White Máire , Cavalleri Gianpiero L. , Delanty Norman , Benson Katherine A. , Greally Marie T.
Published: September 2024

Background

Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG‐1 syndromes, most of which are inherited as autosomal recessive traits, although X‐linked inheritance has also been reported. Pathogenic variants in the asparagine‐linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date.

Methods

We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant.

Results

All three males have a de novo mutation, infantile spasms, DEE, drug‐resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.

Conclusion

The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype–phenotype correlation.
Covalent and non‐covalent action‐enhanced cellulose‐based thermally conductive composite (TCC) films fabricated via vacuum‐assisted self assembly with high thermally conductivity and superior mechanical performance
Authors: Yang Bin , Lu Huijie , Yang Yuqing , Zhang Ting , Wang Xiaohong , Wang Hao , Wang Ziyi , Zhang Yue , Xia Ru , Qian Jiasheng , Jia Ning
Published: September 2024

As is known, to establish covalent or non‐covalent interaction between filler and matrix, which helps to reduce the interface thermal resistance (ITR) as well as construct good thermal conduction channels, is a good strategy for dealing with the risk of thermal runaway in the extreme service environment of electronic equipment. In this paper, carboxylated nanocellulose fiber (c‐CNF) was used as matrix, and a hybrid filler (M‐CoNPs@GNP) was fabricated by coating cobalt‐nanoparticles (CoNPs) and grafting maleimide on graphene nanosheets (GNPs). M‐CoNPs@GNP/c‐CNF thermally conductive composite (TCC) films were successfully fabricated by combining with c‐CNF. As zero‐dimensional particles, CoNPs can effectively prevent GNPs agglomeration due to surface effects, and “‐NH” in maleimide dehydrates with “‐COOH” in c‐CNF to form “C‐N‐C” covalent bonds, with strong hydrogen bond formed between filler and matrix, which remarkably enhances the interface compatibility between matrix and filler. The ITR has been reduced to form a well‐defined three‐dimensional thermal conduction path, achieving an ultra‐high in‐plane TC (35.9 W·m−1·K−1) for MCGC40, which is 7.9 times that of pure c‐CNF film, in addition to a sufficiently high tensile strength of 123.3 MPa. The combination of high in‐plane TC, excellent mechanical flexibility and good electrical insulation jointly justifies the potential application of M‐CoNPs@GNP/c‐CNF TCC films in effective thermal management of flexible electronic products.

Highlights

CoNPs effectively inhibit GNPs agglomeration.

GNPs exhibit hydrophilicity after modification.

Modified fillers interact fairly well with the matrix.

High tensile strength and exceptional flexibility are achieved.

TCC films exhibit both electrical insulation and hydrophobicity.
Universal mechanical modeling of fiber bundle under torsion: An experimental and numerical study
Authors: Zhang Chi , Hu Hongbo , Liu Yang , Zhu Kunkun , Jiang Liquan , Yu Hao , Xu Weilin
Published: September 2024

In this paper, a universal mechanical model for the torsional behavior of fiber bundle was established, grounded in the principles of spatial geometry and continuum mechanics, incorporating differential geometry formulas. The model was validated through self‐designed experimental equipment and finite element simulations using Ansys Workbench, showing strong agreement between predicted torsional fracture behavior and experimental results. The study further examined the contributions of fiber bending, torsion, and tension to the overall torque, revealing that torsion plays the dominant role. Additionally, the effect of filament count on the torsional performance of fiber bundles was analyzed, demonstrating that while the number of fibers significantly influences stress distribution, its impact on overall torque is minimal.

Highlights

A universal mechanical model for fiber bundle torsional is proposed.

High consistency between simulation and experimental results.

Examined filament count effect on torsional strength.

More filaments reduce stress concentration, improving performance.
Prenatal Sonographic Features of Rubinstein–Taybi Syndrome—A Small Case Series of a Rare Syndrome
Authors: Zloto K. , Weissbach T. , Messing B. , Birnbaum R. , Gindes L. , Levy M. , Lerman‐Sagie T. , Hadi E. , Eliyahu A. , Feinstein‐Goren N. , Kassif E.
Published: September 2024

Rubinstein–Taybi syndrome (RSTS) is a rare syndrome characterized by intellectual disability, distinctive facial features and distal limb abnormalities. RSTS is indicated by clinical features and confirmed via genetic testing. In this prenatal case series, we report four cases of RSTS with various sonographic features. Some features, such as corpus callosum dysgenesis, are nonspecific, but they may be the first sign apparent, as they appear early in pregnancy. Others, like beaked nose, shawl scrotum, premature coccygeal ossification, and overly mature scrotal sac with excessive rugae, are distinctive, but they may only be apparent in advanced gestation.
A Theoretical Perspective on the Stereochemistry of Benzoanellated Aroyl‐X,N‐Ketene Acetal Derivatives
Authors: Martins Francisco A. , Freitas Matheus P.
Published: September 2024

Ketene 1,3‐oxazoles and their derivatives present intriguing structures for the study of rotational barriers due to their pseudo–double‐bond character stemming from resonance in the ketene moiety. A diverse range of compounds featuring this motif underwent quantum‐chemical investigation to elucidate the nature of the stereochemical singularity observed in numerous cases. Because rotational barriers in most instances are too high to permit rapid interconversion, the findings are ascribed to thermodynamic rather than kinetic factors in the gas phase and within an implicit polar medium. The stabilities are attributed to internal hydrogen bonding where feasible. However, in cases where this is not possible, chalcogen bonding rather than steric effects governs the stereochemical preferences, particularly when S and Se comprise the heterocycle of these compounds. These findings hold promise for guiding the design of compounds whose properties hinge on stereochemistry and resonant structures, such as dyes.
Exploring Spectral and Electrochemical Behavior of Hydroxy‐N‐Benzylideneanilines by Integrated Theoretical and Experimental Approaches
Authors: Hota Prabhudatta , Biswal Supriya Priyambada , Dash Manas Ranjan , Das Bijnyan Ranjan , Misra Pramila Kumari
Published: September 2024

The present work explored the effect of –OH group substitution (o/p) on the spectral and electrochemical behavior of N‐benzylideneaniline. The geometry optimization of unsubstituted and (o/p)‐OH‐substituted analogs revealed the coplanarity of the molecules. The vibrational spectra of the compounds were computed using density functional theory (DFT) and compared with the experimental data. The observed bands were assigned based on total energy distribution (TED). Predicted electronic absorption spectra from time‐dependent density functional theory (TD‐DFT) calculation were compared with the UV–visible spectra of the molecules. The analysis of the lowest spin‐allowed (singlet‐singlet) excited states divulged possible electronic transition. The o‐substituted benzylideneaniline possessed the lowest highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy gap among the substituted and unsubstituted analogs. The intramolecular contacts were interpreted using natural bond orbital and localized molecular orbital analysis. The –CH=N– linkage was investigated as a bridge for the electron delocalization from the donor to acceptor moieties. The manifestation of a reduction peak in the cyclic voltammetric studies confirmed the electrochemical behavior in the –OH‐substituted molecule, which was diffusion‐controlled. The discrepancy in the electrochemical property concerning the position of the –OH substituent of the candidate molecules was put forward.
Correlating Chemical Structure and Charge Carrier Dynamics in Phenanthrocarbazole‐Based Hole Transporting Materials for Efficient Perovskite Solar Cells
Authors: Hussain Muzammil , Adnan Muhammad , Irshad Zobia , Hussain Riaz , Darwish Hany W. , Lim Jongchul
Published: September 2024

Polymeric hole transport materials (HTMs) have emerged because of their potential to produce dopant‐free, efficient, and stable perovskite solar cells (PSCs). Therefore, we engineered 10 novel donor materials (SMH1–SMH10) containing phenanthrocarbazole‐based polymeric structures for organic and PSCs. These molecules underwent bridging‐core modifications using different spacers, such as furan (N1), pyrrole (N2), benzene (N3), pyrazine (N4), dioxane (N5), isoxazole (N6), isoindole (N7), indolizine (N8), double bond (N9), and pyrimidine (N10), in comparison to reference molecule R. The study examined the structure–property relationship and the impact of these modifications on the optical, photovoltaic, photophysical, and optoelectronic characteristics of the newly designed SMH1–SMH10 series. Density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) calculations were conducted to analyze frontier molecular orbitals, density of states, reorganization energies, open‐circuit voltage, transition density matrix, and charge transfer processes. Results show that the newly designed molecules (SMH1–SMH10) exhibited superior optoelectronics characteristics compared to the R molecule. Among these, SMH4 is the most promising candidate, with a small band gap (2.79 eV), low electron and hole mobility (λe 0.0028 eV, λh 0.0020 eV), lower binding energy (Eb 0.58 eV), high λmax values (656.42 nm in gas, 573.34 nm in chlorobenzene), and a high Voc of 1.30 V. Therefore, this study demonstrated that bridging‐core modifications offer a simple and effective strategy for designing desirable characteristics molecules for photovoltaic applications.
Evaluating the potential of non‐immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies
Authors: Favretto Filippo , Jiménez‐Faraco Eva , Catucci Gianluca , Di Matteo Adele , Travaglini‐Allocatelli Carlo , Sadeghi Sheila J. , Dominici Paola , Hermoso Juan A. , Astegno Alessandra
Published: September 2024

Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets. However, CsA immunosuppressive nature hinders its use as an antitoxoplasmosis agent. Here, we evaluate the potential of three CsA derivatives devoid of immunosuppressive activity, namely, NIM811, Alisporivir, and dihydrocyclosporin A to target a previously characterized cyclophilin from Toxoplasma gondii (TgCyp23). We determined the X‐ray crystal structures of TgCyp23 in complex with the three analogs and elucidated their binding and inhibitory properties. The high resolution of the structures revealed the precise positioning of ligands within the TgCyp23 binding site and the details of protein–ligand interactions. A comparison with the established ternary structure involving calcineurin indicates that substitutions at position 4 in CsA derivatives prevent calcineurin binding. This finding provides a molecular explanation for why CsA analogs can target Toxoplasma cyclophilins without compromising the human immune response.
Plasma and urinary CP I and CP III concentrations in chimeric mice with human hepatocytes after rifampicin administration
Authors: Shishido Yurina , Yoshida Tomohiro , Oshida Keiyu , Uchida Masashi
Published: September 2024

The interest in transporter‐mediated drug interactions has been increasing in the field of drug development. In this study, we measured the plasma and urinary concentrations of coproporphyrin (CP) I and CP III as endogenous substrates for organic anion‐transporting polypeptide (OATP) using chimeric mice with human hepatocytes (PXB mice) and examined the influence of an OATP inhibitor, rifampicin (RIF). CP I and CP III were actively taken up intracellularly, and RIF inhibited the uptake in a concentration‐dependent manner for both CP I and CP III in human hepatocytes (PXB‐cells). Single doses of RIF at 10 and 30 mg/kg were orally or intravenously administered to PXB mice and wild‐type ICR mice. Plasma concentrations (AUC0‐8h) of CP I increased in both mice. However, a marked increase in CP III was only observed in ICR mice, after intravenous administration of RIF at 30 mg/kg. The IC50 values of RIF for intracellular CP I/III uptake and the unbound plasma concentrations of RIF suggested that the increase in plasma CP I is associated with the exposure of RIF to OATPs. The 24‐h cumulative urinary excretions of CP I and CP III increased in both mice, but more markedly in PXB mice. Thus, RIF increased the plasma and urinary concentrations of CP I and CP III in the mice, as reported in humans, and CP I may be a more sensitive biomarker of OATP‐mediated drug interactions in PXB mice.
In‐host modeling of dengue virus and non‐structural protein 1 and the effects of ivermectin in patients with acute dengue fever
Authors: Ding Junjie , Mairiang Dumrong , Prayongkul Dararat , Puttikhunt Chunya , Noisakran Sansanee , Kaewjiw Nattapong , Songjaeng Adisak , Prommool Tanapan , Tangthawornchaikul Nattaya , Angkasekwinai Nasikarn , Suputtamongkol Yupin , Lapphra Keswadee , Chokephaibulkit Kulkanya , White Nicholas J. , Avirutnan Panisadee , Tarning Joel
Published: September 2024

The increased incidence of dengue poses a substantially global public health challenge. There are no approved antiviral drugs to treat dengue infections. Ivermectin, an old anti‐parasitic drug, had no effect on dengue viremia, but reduced the dengue non‐structural protein 1 (NS1) in a clinical trial. This is potentially important, as NS1 may play a causal role in the pathogenesis of severe dengue. This study established an in‐host model to characterize the plasma kinetics of dengue virus and NS1 with host immunity and evaluated the effects of ivermectin, using a population pharmacokinetic–pharmacodynamic (PK–PD) modeling approach, based on two studies in acute dengue fever: a placebo‐controlled ivermectin study in 250 adult patients and an ivermectin PK–PD study in 24 pediatric patients. The proposed model described adequately the observed ivermectin pharmacokinetics, viral load, and NS1 data. Bodyweight was a significant covariate on ivermectin pharmacokinetics. We found that ivermectin reduced NS1 with an EC50 of 67.5 μg/mL. In silico simulations suggested that ivermectin should be dosed within 48 h after fever onset, and that a daily dosage of 800 μg/kg could achieve substantial NS1 reduction. The in‐host dengue model is useful to assess the drug effect in antiviral drug development for dengue fever.
In‐Plane Energy Absorption Properties of Novel Curved‐Ligaments Auxetic Cellular Structures with Dual‐Platform Performance
Authors: Liu Xu , Liu Hai‐Tao , Wang Shun
Published: September 2024

To improve the energy absorption capacity of honeycomb, four novel curved‐ligaments auxetic cellular structures (CLACS‐i [i = 1, 2, 3, 4]) based on the Diabolo‐shaped honeycomb (DSH) are introduced in this article. In the simulation results, it is demonstrated that the energy absorption performance of CLACS‐i (i = 1, 2, 3, 4) surpasses that of DSH under low‐, medium‐, and high‐velocity impacts. However, the negative Poisson's ratio effect of novel structures is inferior to that of DSH. With the increase in impact velocity, the inertial effect of the structure is enhanced, and the deformation mode of the structure changes from global deformation to local deformation. Furthermore, different impact velocities and geometric parameters also affect the energy absorption capacity of the structures. Platform stress and specific energy absorption (SEA) of CLACS‐i (i = 1, 2, 3, 4) increase with the increase of velocity. Under medium‐velocity impact loading, the platform stress and SEA of CLACS‐i (i = 1, 2, 3, 4) increase as the geometric parameter θ decreases and the wall thickness t increases. In this study, a reference is provided for the optimal design and application of honeycomb energy‐absorbing components.