bluuebunny/crossref_metadata_2025 huggingface dataset:
2D MXene Biomaterials for Catalytic Medical Applications
Authors: Song Ziying , Wang Lin , Chen Liang , Chen Yu
Published: July 2024

In recent years, two‐dimensional transition metal carbides, nitrides, and carbonitrides, termed as MXenes, have been widely applied in energy storage, photocatalysis and biomedicine owing to their unique physicochemical properties of large specific surface area, high electrical conductivity, excellent optical performance, good stability, etc. Moreover, due to their strong light absorption capacity in the first and second near‐infrared bio‐window, and their ability of being simply functionalized with multiple organic/inorganic materials, MXene biomaterials have shown great potential in the field of catalytic therapy. This review will summarize the common catalytic mechanism of MXene biomaterials and their latest applications in catalytic medicine such as tumor therapy, antibacterial and anti‐inflammatory, and present the current challenges and opportunities in clinical translation for future development to promote the advancement of MXene biomaterials in the field of catalytic medicine.
Cardiovascular safety of pimitespib in patients with advanced solid tumors: An open‐label, nonrandomized, phase 1 study
Authors: Naoki Katsuhiko , Igawa Satoshi , Uojima Haruki , Tsumura Hideyasu , Sengoku Norihiko , Karayama Masato , Shimomura Akihiko , Ohtake Tohru , Shio Yutaka , Hosokawa Ayumu , Komatsu Yoshito , Kumagai Yuji
Published: July 2024

Background

Pimitespib (TAS‐116), a first‐in‐class, oral, selective heat‐shock protein 90 inhibitor, is approved as fourth‐line treatment for gastrointestinal stromal tumors in Japan. This phase 1 study evaluated the cardiac safety of pimitespib.

Methods

In this open‐label, nonrandomized, multicenter study, Japanese patients (aged ≥20 years) with refractory, advanced solid tumors received placebo on day −1, then pimitespib 160 mg daily on days 1–5 of the cardiac safety evaluation period. Electrocardiograms were conducted at baseline, and on days −2, −1, 1, and 5; and blood samples were collected on days 1 and 5. Patients then received once‐daily pimitespib for 5 days every 3 weeks. The primary end point was the time‐matched difference in QT interval corrected for heart rate using the Fridericia correction (QTcF) between pimitespib and placebo. Pharmacokinetics, safety, and preliminary efficacy were also assessed.

Results

Of the 22 patients in the cardiac safety‐evaluable population, no clinically relevant QTc prolongation was observed; the upper bound of the one‐sided 95% confidence interval for the time‐matched difference in change from baseline in QTcF was <20 msec at all time points on days 1 and 5. Pimitespib pharmacokinetic parameters were consistent with previous data, and the time‐matched difference in change from baseline in QTcF showed no marked increase as plasma concentrations increased. The safety profile was acceptable; 40% of patients experienced grade 3 or greater adverse drug reactions, mostly diarrhea (20%). The median progression‐free survival was 3.1 months.

Conclusions

In Japanese patients with refractory, advanced solid tumors, pimitespib was not associated with clinically relevant QTc prolongation, and there were no cardiovascular safety concerns.

Plain Language Summary

Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors).

This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment.
Machine Learning‐Based Prediction of Supercapacitor Capacitance for MgCo2O4 Electrodes
Authors: Tang Mengfan , Ding Yue , Hu Tanwei , Zhu Xiaolong , Zheng Guang , Tian Yu
Published: July 2024

Electrode materials are essential in the electrochemical process of storing charge in supercapacitors and have a significant impact on the cost and capacitive performance of the final product. Hence, it is imperative to make precise predictions regarding the capacitance of electrode materials in order to further the development of supercapacitors. MgCo2O4, with a theoretical capacitance of up to 3122 F g−1, holds immense research value as an electrode material. The objective of this study is to predict the capacitance of MgCo2O4 with high accuracy. This will be achieved by extracting numerous data from published papers and using some parameters as input features. The Recursive Feature Elimination (RFE) method was employed, using Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Regression Tree (RT) as selectors to identify the optimal feature subset. Then, combining them with these three regression models to construct nine machine learning (ML) models. After performance evaluation and outlier analysis, the XGB‐RFE‐XGB model achieved R‐squared (R2), root mean squared error (RMSE), and mean absolute error (MAE) of 0.95, 111.83 F g−1 and 68.25 F g−1, respectively, demonstrating its stability and reliability. Therefore, the XGB‐RFE‐XGB model can be used as a reliable predictive tool in subsequent experimental designs.
Growth and Optical Properties of Yellow Luminescent [Epy]2[CuBr3] Single Crystals Based on Self Trapping States
Authors: Chen Xinxin , Zhu Shujun , Han Jiali , Zhao Tao , Pan Jianguo , Pan Shangke
Published: July 2024

The low‐dimensional organic‐inorganic lead halide compound has garnered significant attention in recent times due to its exceptional optoelectronic properties. However, its application in the field of optoelectronics has been hindered by the toxicity of lead. Here, a novel inorganic‐organic compound [Epy]2[CuBr3] single crystal material with a 0D structure based on Cu(I) is introduced. The single crystal exhibits a broad band yellow luminescence, a significant Stokes shift, and a microsecond‐scale photoluminescence (PL) lifetime, which is mainly attributed to the self‐trapped excitons (STEs) excitation. In addition, the relevant PL spectra are measured at 78–348 K. The photoluminescence intensity decreases with increasing temperature due to strong electro‐phonon coupling. The exciton binding energy Eb of the crystal is 76.43 meV, and the Huang‐Rhys factor S is 40.55. It is worth noting that the crystal also shows a good response to X‐rays. Overall, [Epy]2[CuBr3] displays its good potential.
Corporate social responsibility (CSR) and earnings management: A structured literature review with a focus on contextual factors
Authors: Velte Patrick
Published: July 2024

The link between corporate social responsibility (CSR) and earnings management represents an attractive empirical research topic in recent years. In view of the heterogeneous research results, the purpose of this structured literature review is to analyze the contextual factors of this complex relationship. We selected 107 quantitative peer‐reviewed archival studies on that topic and explain a possible positive and negative link between CSR and earnings management by the moral licensing hypothesis (principal agent theory) and the moral track hypothesis (stakeholder theory). We focus on firm‐ and country‐related moderator effects as contextual factors. Country‐specific studies are separated in developed (Anglo‐American and Continental European settings) and developing countries (African and Asian settings), code and case law regimes as well as the degree of shareholder protection and legal enforcement. In line with stakeholder theory, we stress that most of the included studies found a negative impact of CSR on earnings management with a focus on CSR performance and accruals‐based earnings management. Other measures, for example, CSR reporting, sub‐pillars of CSR performance, and real earnings management, are inconclusive due to reduced research activity. We do not find any structural changes between developed and developing countries, case and code law regimes, and regarding the strength of shareholder protection and legal enforcement. However, there are clear indications that corporate and country governance strengthens (weakens) the negative (positive) influence of CSR on earnings management. We stress major limitations of prior research and formulate useful recommendations for future research.
Developing Catalysts for Membrane Electrode Assemblies in High Performance Polymer Electrolyte Membrane Water Electrolyzers
Authors: Jeon Sun Seo , Lee Wonjae , Jeon Hyeseong , Lee Hyunjoo
Published: July 2024

Extensive research is underway to achieve carbon neutrality through the production of green hydrogen via water electrolysis, powered by renewable energy. Polymer membrane water electrolyzers, such as proton exchange membrane water electrolyzer (PEMWE) and anion exchange membrane water electrolyzer (AEMWE), are at the forefront of this research. Developing highly active and durable electrode catalysts is crucial for commercializing these electrolyzers. However, most research is conducted in half‐cell setups, which may not fully represent the catalysts’ effectiveness in membrane‐electrode‐assembly (MEA) devices. This review explores the catalysts developed for high‐performance PEMWE and AEMWE MEA systems. Only the catalysts reporting on the MEA performance were discussed in this review. In PEMWE, strategies aim to minimize Ir use for the oxygen evolution reaction (OER) by maximizing activity, employing metal oxide‐based supports, integrating secondary elements into IrOx lattices, or exploring non‐Ir materials. For AEMWE, the emphasis is on enhancing the performance of NiFe‐based and Co‐based catalysts by improving electrical conductivity and mass transport. Pt‐based and Ni‐based catalysts for the hydrogen evolution reaction (HER) in AEMWE are also examined. Additionally, this review discusses the unique considerations for catalysts operating in pure water within AEMWE systems.
Sustainable Production of Biofuels from Biomass Feedstocks Using Modified Montmorillonite Catalysts
Authors: Ban Lin , Wu Deyu , Sun Dalin , Zhou Heng , Wang Hao , Zhang Heng , Charles Xu Chunbao , Yang Song
Published: July 2024

The rampant exploitation of fossil fuels has led to the significant energy scarcity and environmental disruption, affecting the sound momentum of development and progress of human civilization. To build a closed‐loop anthropogenic carbon cycle, development of biofuels employing sustainable biomass feedstocks stands at the forefront of advancing carbon neutrality, yet its widespread adoption is mainly hampered by the high production costs. Montmorillonite, however, has garnered considerable attention serving as an efficient heterogeneous catalyst of ideal economic feasibility for biofuel production, primarily due to its affordability, accessibility, stability, and excellent plasticity. Up to now, nevertheless, it has merely received finite concerns and interests in production of various biofuels using montmorillonite‐based catalysts. There is no timely and comprehensive review that addresses this latest relevant progress. This review fills the gap by providing a systematically review and summary in controllable synthesis, performance enhancement, and applications related to different kinds of biofuels including biodiesel, biohydrogenated diesel, levulinate, γ‐valerolactone, 5‐ethoxymethylfurfural, gaseous biofuels (CO, H2), and cycloalkane, by using montmorillonite catalysts and its modified forms. Particularly, this review critically depicts the design strategies for montmorillonite, illustrates the relevant reaction mechanisms, and assesses their economic viability, realizing sustainable biofuels production via efficient biomass valorization. Overall, this may offer valuable insights into cost‐effective biofuel production and proposes strategic recommendations for advancement of montmorillonite applications and future biofuel development.
BMP4 regulates asymmetric Pkd2 distribution in mouse nodal immotile cilia and ciliary mechanosensing required for left–right determination
Authors: Katoh Takanobu A. , Lange Tim , Nakajima Yoshiro , Yashiro Kenta , Okada Yasushi , Hamada Hiroshi
Published: July 2024

Background

Mouse nodal immotile cilia mechanically sense the bending direction for left–right (L–R) determination and activate the left‐side‐specific signaling cascade, leading to increased Nodal activity. Asymmetric distribution of Pkd2, a crucial channel for L–R determination, on immotile cilia has been reported recently. However, the causal relationship between the asymmetric Pkd2 distribution and direction‐dependent flow sensing is not well understood. Furthermore, the underlying molecular mechanism directing this asymmetric Pkd2 distribution remains unclear.

Results

The effects of several recombinant proteins and inhibitors on the Pkd2 distribution were analyzed using super‐resolution microscopy. Notably, bone morphogenetic protein 4 (BMP4) affected the Pkd2 distribution. Additionally, three‐dimensional manipulation of nodal immotile cilia using optical tweezers revealed that excess BMP4 caused defects in the mechanosensing ability of the cilia.

Conclusions

Experimental data together with model calculations suggest that BMP4 regulates the asymmetric distribution of Pkd2 in nodal immotile cilia, thereby affecting the ability of these cilia to sense the bending direction for L–R determination. This study, for the first time, provides insight into the relationship between the asymmetric protein distribution in cilia and their function.
Comparison between capillary electrophoresis and fluorescence anisotropy competitive immunoassay for glucagon
Authors: Wang Yao , Skinner Emily L. , Roper Michael G.
Published: July 2024

Glucagon plays a crucial role in regulating glucose homeostasis; unfortunately, the mechanisms controlling its release are still unclear. Capillary electrophoresis (CE)‐ and fluorescence anisotropy (FA)‐immunoassays (IA) have been used for online measurements of hormone secretion on microfluidic platforms, although their use in glucagon assays is less common. We set out to compare a glucagon‐competitive IA using these two techniques. Theoretical calibration curves were generated for both CE‐ and FA–IA and results indicated that CE‐IA provided higher sensitivity than FA–IA. These results were confirmed in an experiment where both assays showed limits of detection (LOD) of 30 nM, but the CE‐IA had ∼300‐fold larger sensitivity from 0 to 200 nM glucagon. However, in online experiments where reagents were mixed within the device, the sensitivity of the CE‐IA was reduced ∼3‐fold resulting in a higher LOD of 70 nM, whereas the FA–IA remained essentially unchanged. This lowered sensitivity in the online CE‐IA was likely due to poor sampling by electroosmotic flow from the high salt solution necessary in online experiments, whereas pressure‐based sampling used in FA–IA was not affected. We conclude that FA–IA, despite lowered sensitivity, is more suitable for online mixing scenarios due to the ability to use pressure‐driven flow and other practical advantages such as the use of larger channels.
Experimental and numerical investigations of secondary granular flow
Authors: Wang Jianxin , Liu Chuanzheng , Fan Yunyun , Zhang Feng
Published: July 2024

Among the geological disasters in the form of granular flow, the secondary slide mass is often neglected, potentially leading to unexpected losses. Results indicate that under conditions of a certain sliding total mass, the secondary granular flow in the deposition area is significantly influenced by pre‐formed deposits when tested in a flow flume. When the initial sliding mass is small and the mass ratio of two slides is less than 12.5%, the secondary sliding mass expands the runout distance, thereby increasing potential harm. To elucidate the interaction between the secondary sliding mass and the previously formed deposition, DEM (the discrete element method) was employed based on experimental tests.. The numerical results show that the previous deposition effectively blocks the secondary granular flow. When the initial sliding mass is small, the front edge of the second slide may overtop the previous deposition, extending the runout distance by impact, extrusion, and pushing. The DEM proves to be a reliable and effective tool for studying the secondary granular flow, revealing complex phenomena and processes that complement experimental research. This study provides valuable references for a more in‐depth understanding of multi‐phase continuous disaster processes.
A moderated mediation model of the relationship between Indian elementary school teachers' autonomy and perceived ease of ICT use
Authors: Kundu Arnab , Bej Tripti
Published: July 2024

In the 21st century, Information and Communication Technology (ICT) is a critical component of innovative teaching and learning. This study looked at the impact of teachers' autonomy on their perceived ease of using ICT and the intricate relationship between the two, involving their self‐efficacy, job satisfaction, and perceived incentives to change. Using a descriptive survey approach, 311 (134 female) Indian elementary school teachers participated in the study and provided self‐reported data. A structural equation model was employed to test the mediating roles of self‐efficacy and job satisfaction, and the moderation of perceived incentives. The results affirmed that teacher autonomy had a direct and moderately positive effect on their perceived ease of ICT use. Self‐efficacy and job satisfaction significantly and partially mediated the indirect relationships between autonomy and ease of ICT use. In the three relationship paths the perceived incentive to change had a significantly positive moderation to catalyze the relationships. Considering Indian elementary school teachers' glaring lack of autonomy, this paper suggests a policy shift involving greater teacher autonomy and the use of incentives for improved efficacy, job satisfaction, and ICT use. The relationship matrix will serve as a reference for researchers and practitioners to gain a deeper understanding of the role of teacher autonomy in addressing the global issue of limited adoption and integration of ICT by school teachers.
Innovative postharvest strategies for maintaining the quality of kiwifruit during storage: An updated review
Authors: Xia Yu , Wu Ding‐Tao , Ali Maratab , Liu Yi , Zhuang Qi‐Guo , Wadood Syed Abdul , Liao Qiu‐Hong , Liu Hong‐Yan , Gan Ren‐You
Published: July 2024

Being a respiratory climacteric fruit, kiwifruit is susceptible to age and decay rapidly in the postharvest stage. Therefore, the development of efficient postharvest methods to maintain the kiwifruit quality has been a long‐standing goal. This review summarizes the preservation and disease control methods of kiwifruit conducted over the past 5 years, and the characteristics, advantages, and action mechanisms of various methods are thoroughly discussed. Physical, chemical, and biotechnological methods, such as low‐temperature, essential oil, and endophytic yeast treatment, can enhance postharvest kiwifruit quality to a certain extent by controlling disease, delaying chilling injury, alleviating oxidative damage, inhibiting oversoftening and off‐flavor development. However, all these techniques have limitations per se, such as the inability to prevent secondary infections and potential side effects on human health. Novel approaches such as pulsed light and cold plasma or a synergistic application of several techniques may be the future direction for kiwifruit postharvest preservation.
Identification of polyphenol composition in grape (Vitis vinifera cv. Bidaneh Sefid) stem using green extraction methods and LC–MS/MS analysis
Authors: Beilankouhi Shiva , Pourfarzad Amir , Ghanbarzadeh Babak , Rasouli Mousa , Hamishekar Hamed
Published: July 2024

The utilization of grape stems, a by‐product of the grape processing industry, as a source of valuable bioactive compounds, particularly polyphenols, has gained attention in recent years. This study aimed to investigate different eco‐friendly extraction methods for obtaining polyphenols from grape (Vitis vinifera cv. Bidaneh Sefid) stems, focusing on green solvents and innovative techniques. Four extraction methods were tested, involving the use of water and polyethylene glycol (PEG) as green solvents, along with maceration, microwave, ultrasound, and reduced‐pressure techniques. High‐performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI‐MS/MS) was used to characterize and quantify the bioactive compounds in the extracts. A total of 29 polyphenols, including phenolic acids, flavonoids, proanthocyanidins, and stilbenes, were detected. Among the four extraction methods tested, methods 1 (water + microwave + ultrasound + atmospheric pressure) and 2 (water + microwave + ultrasound + reduced pressure) were found to be the most effective. Our study demonstrated that using water and PEG as green solvents, combined with techniques like microwave, ultrasound, and reduced pressure, effectively extracted both hydrophobic and hydrophilic compounds from the grape stems. These findings suggest that further exploration of these methods could lead to the development of value‐added products from grape stems, emphasizing the significance of green extraction techniques for the recovery of polyphenols from winemaking by‐products.
Plant growth‐promoting rhizobacteria and Trichoderma shift common vetch (Vicia sativa) physiology and phyllosphere bacteria toward antagonism against anthracnose caused by Colletotrichum spinaciae
Authors: Zhu Rui , Yan Wei , Wang Yajie , Li Yingde , Zheng Rongchun , Dong Wanqing , Yao Tuo , Duan Tingyu
Published: July 2024

Background

Plant phyllosphere microbes are important for the host plant's protection. Plant growth‐promoting rhizobacteria (PGPR) and Trichoderma are common biocontrol agents (BCAs) for disease management. Pathogens and BCAs can change the rhizosphere microbial composition; however, the effect of PGPR or Trichoderma on plant phyllosphere microbes, particularly for mesocosms involving the interaction between pathogens and BCAs, is not well known.

Methods

High‐throughput sequencing was used to identify the phyllosphere bacterial community of common vetch interacting with Colletotrichum spinaciae, two PGPRs (Bacillus subtilis and Bacillus licheniformis), and Trichoderma longibrachiatum. We evaluated anthracnose severity, phyllosphere bacteria diversity and composition, and the relationship between the activities of plant defense enzymes and hormonal molecules in plants treated with individual and combined inoculations of PGPRs, Trichoderma, and C. spinaciae.

Results

PGPR or Trichoderma alone reduced disease severity. Trichoderma reduced the salicylic acid content, PGPR increased the catalase activity in plants, and co‐inoculation of PGPR and Trichoderma decreased the salicylic acid content. Inoculation of PGPR and Trichoderma individually or in combination changed the disease‐associated phyllosphere bacteria, and this effect was related to plant defense enzymes and hormonal molecules.

Conclusions

We suggest that the plant defense response induced by PGPR and Trichoderma results in the enrichment of a fraction of favorable chloroplastic bacteria, which facilitates plant defense against diseases.
Vaginal microbiome dysbiosis as a novel noninvasive biomarker for detection of chronic endometritis in infertile women
Authors: Han Yi‐ling , Li Xue‐yao , Li Jie , Xiao Zhuo‐ni , Chen Jiao , Yang Jing
Published: July 2024

Objective

To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE.

Methods

A cross‐sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non‐CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed.

Results

The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism‐related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%.

Conclusion

The results of the current study revealed that, compared with the non‐CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE.
Pythagorean Fuzzy Set for Enhancement of Low Contrast Mammogram Images
Authors: Chaira Tamalika , Sarkar Arun
Published: July 2024

Breast masses are often one of the primary signs of breast cancer, and precise segmentation of these masses is essential for accurate diagnosis and treatment planning. Diagnosis may be complex depending on the size and visibility of the mass. When the mass is not visible clearly, precise segmentation becomes very difficult and in that case enhancement is essential. Inadequate compression, patient movement, or paddle/breast movement during the exposure process might cause hazy mammogram images. Without enhancement, accurate segmentation and detection cannot be done. As there exists uncertainties in different regions, reducing uncertainty is still a main problem and so fuzzy methods may deal these uncertainties in a better way. Though there are many fuzzy and advanced fuzzy methods, we consider Pythagorean fuzzy set as one of the fuzzy sets that may be powerful to deal with uncertainty. This research proposes a new Pythagorean fuzzy methodology for mammography image enhancement. The image is first transformed into a fuzzy image, and the nonmembership function is then calculated using a newly created Pythagorean fuzzy generator. Membership function of Pythagorean fuzzy image is computed from nonmembership function. The plot between the membership value and the hesitation degree is used to calculate a constant term in the membership function. Next, an enhanced image is obtained by applying fuzzy intensification operator to the Pythagorean fuzzy image. The proposed method is compared qualitatively and quantitatively with those of non‐fuzzy, intuitionistic fuzzy, Type 2 fuzzy, and Pythagorean fuzzy methods, it is found that the suggested method outperforms the other methods. To show the usefulness of the proposed enhanced method, segmentation is carried out on the enhanced images.
The effect of plough agriculture on gender roles: A machine learning approach
Authors: Baiardi Anna , Naghi Andrea A.
Published: July 2024

This paper undertakes a replication in a wide sense of a recent study that examines the relationship between historical plough agriculture and current gender roles. We revisit the main research question with recently developed causal machine learning methods, which allow researchers to model the relationship of covariates with the treatment and the outcomes in a more flexible way, while also including interactions and nonlinearities that were not considered in the original analysis. Our results suggest an even larger negative effect of the historical plough adoption on female labor force participation than what the original analysis found. The paper highlights the benefits of using causal machine learning methods in applied empirical economics.
Berberine prevents against myocardial injury induced by acute β‐adrenergic overactivation in rats
Authors: Yang Yalin , Jiang Shuang , Mu Yu , Liu Chilu , Han Yanxing , Jiang Jiandong , Wang Yuhong
Published: July 2024

The overactivation of β‐adrenergic receptors (β‐ARs) can result in acute myocardial ischemic injury, culminating in myocardial necrosis. Berberine (BBR) has exhibited promising potential for prevention and treatment in various heart diseases. However, its specific role in mitigating myocardial injury induced by acute β‐AR overactivation remains unexplored. This study aimed to investigate the effects and underlying mechanisms of BBR pretreatment in a rat model of acute β‐AR overactivation induced by a single dose of the nonselective β‐adrenergic agonist isoprenaline (ISO). Rats were pretreated with saline or BBR (100 mg/kg/day) via gavage for 14 consecutive days, followed by a subcutaneous injection of ISO or saline on the 14th day. The findings indicated that BBR pretreatment significantly attenuated myocardial injury in ISO‐stimulated rats, as evidenced by reduced pathological inflammatory infiltration, necrosis, and serum markers of myocardial damage. Additionally, BBR decreased oxidative stress and inflammation in the system and heart. Furthermore, BBR pretreatment enhanced myocardial ATP levels, improved mitochondrial dysfunction through increased Drp1 phosphorylation, and augmented myocardial autophagy. In a CoCl2‐induced H9c2 cell hypoxic injury model, BBR pretreatment mitigated cellular injury, apoptosis, and oxidative stress while upregulating Drp1 and autophagy‐associated proteins. Mechanistically, BBR pretreatment activated AKT, AMPK, and LKB1 both in vivo and in vitro, implicating the involvement of the AKT and LKB1/AMPK signaling pathways in its cardioprotective effects. Our study demonstrated the protective effects of BBR against myocardial injury induced by acute β‐AR overactivation in rats, highlighting the potential of BBR as a preventive agent for myocardial injury associated with β‐adrenergic overactivation.
Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron‐Deficiency Anemia Using Machine Learning Algorithms
Authors: Abdillahi Kadra Mohamed , Eraldemir Fatma Ceyla , Kösesoy Irfan
Published: July 2024

Objective

In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group.

Methods

This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non‐diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K‐Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model.

Results

According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients.

Discussion

Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision‐making processes.
Investigation of patients with childhood epilepsy in single center: Comprehensive genetic testing experience
Authors: Gerik‐Celebi Hamide Betul , Dokurel Çetin İpek , Bolat Hilmi , Unsel‐Bolat Gul
Published: July 2024

Introduction

Epilepsy is a common multifactorial neurological disease usually diagnosed during childhood. In this study, we present the contribution of consecutive genetic testing to the genetic diagnostic yield of childhood epilepsy.

Methods

In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n = 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co‐occurring findings (including developmental delay/intellectual disability, brain malformations, macro‐/microcephaly, and dysmorphic features).

Results

The overall diagnostic rate in this study was 33% (n = 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro‐/microcephaly 50% (6/12) and without macro‐/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71).

Conclusion

Genotype–phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results.
Early‐life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions
Authors: Mashahadi Zahra , Saadati Hakimeh , Ghaheri Fard Safa
Published: July 2024

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiological and cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early‐life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para‐chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10–20, followed by sleep deprivation‐induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain‐derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.
Professorial intentions of engineering PhDs from historically excluded groups: The influence of graduate school experiences
Authors: Fleming Gabriella Coloyan , Cobb Sydni Alexa , Borrego Maura
Published: July 2024

Background

In addition to the benefits of a diverse faculty, many institutions are under pressure from students and administrators to increase the number of faculty from historically excluded backgrounds. Despite increases in the numbers of engineering PhD earners from these groups, the percentages of Black/African American and Hispanic/Latino tenure‐track faculty have not increased, and the percentage of women remains low.

Purpose

The purpose of this study is to identify how experiences in graduate school encourage or deter PhD earners from historically excluded groups in pursuing an engineering academic career.

Method

We conducted 20 semi‐structured interviews with engineering PhD students and recent graduates, with half of participants interested and half disinterested in pursuing an academic career after graduation.

Results

Three key factors emerged as strongly influential on participants' desire to pursue an academic career: their relationship with their advisor, their perception of their advisor's work–life balance, and their perception of the culture of academia. Participants extrapolated their experiences in graduate school to their imagined lives as faculty. The results illuminate the reasons why engineering PhD earners from historically underrepresented groups remain in or leave the academic career pathway after graduate school.

Conclusions

The findings of this study have important implications for how graduate students' and postdoc's relationships with their advisors as well as perceptions of their advisors' work–life balances and the culture of academia affect future faculty. We make recommendations on what students, faculty, and administrators can do to create a more inclusive environment to encourage students from historically excluded groups to consider academic careers.
Label‐free three‐dimensional imaging and quantitative analysis of living fibroblasts and myofibroblasts by holotomographic microscopy
Authors: Sbrana Francesca , Chellini Flaminia , Tani Alessia , Parigi Martina , Garella Rachele , Palmieri Francesco , Zecchi‐Orlandini Sandra , Squecco Roberta , Sassoli Chiara
Published: July 2024

Holotomography (HT) is a cutting‐edge fast live‐cell quantitative label‐free imaging technique. Based on the principle of quantitative phase imaging, it combines holography and tomography to record a three‐dimensional map of the refractive index, used as intrinsic optical and quantitative imaging contrast parameter of biological samples, at a sub‐micrometer spatial resolution. In this study HT has been employed for the first time to analyze the changes of fibroblasts differentiating towards myofibroblasts – recognized as the main cell player of fibrosis – when cultured in vitro with the pro‐fibrotic factor, namely transforming growth factor‐β1. In parallel, F‐actin, vinculin, α‐smooth muscle actin, phospho‐myosin light chain 2, type‐1 collagen, peroxisome proliferator‐activated receptor‐gamma coactivator‐1α expression and mitochondria were evaluated by confocal laser scanning microscopy. Plasmamembrane passive properties and transient receptor potential canonical channels' currents were also recorded by whole‐cell patch‐clamp. The fluorescence images and electrophysiological results have been compared to the data obtained by HT and their congruence has been discussed. HT turned out to be a valid approach to morphologically distinguish fibroblasts from well differentiated myofibroblasts while obtaining objective measures concerning volume, surface area, projection area, surface index and dry mass (i.e., the mass of the non‐aqueous content inside the cell including proteins and subcellular organelles) of the entire cell, nuclei and nucleoli with the major advantage to monitor outer and inner features in living cells in a non‐invasive, rapid and label‐free approach. HT might open up new research opportunities in the field of fibrotic diseases.

Research Highlights

Holotomography (HT) is a label‐free laser interferometric imaging technology exploiting the intrinsic optical property of cells namely refractive index (RI) to enable a direct imaging and analysis of whole cells or intracellular organelles.

HT turned out a valid approach to distinguish morphological features of living unlabeled fibroblasts from differentiated myofibroblasts.

HT provided quantitative information concerning volume, surface area, projection area, surface index and dry mass of the entire fibroblasts/myofibroblasts, nuclei and nucleoli.
DABCO‐catalyzed highly regioselective synthesis of novel 4H‐pyrano[2,3‐b]quinoline derivatives: One‐pot three‐component reaction
Authors: Heydari Masumeh , Mohammadi Ali A. , Mosleh Mohammad R.
Published: July 2024

A regioselective synthesis of 4H‐pyrano[2,3‐b]quinoline derivatives via DABCO‐mediated Knoevenagel condensation/heterocyclization sequence has been executed. In this way some new fused heterocyclic compounds were synthesized from 2‐chloroquinoline‐3‐carbaldehyde as a versatile and efficient synthetic building block. The one‐pot three‐component reaction of 2‐chloroquinoline‐3‐carbaldehyde and diverse cyclic active methylenes for construction of highly substituted quinolines scaffold has been accomplished under mild condition. The strategy included herein shows significant advantages, including a facile process with easy purification, excellent yields, wide applicability, available substrates, and cost‐effective/eco‐friendly solvent and catalyst.
Fully Automated Cassette‐Based Synthesis of 2‐Deoxy‐2‐[18F]Fluorocellobiose Using Trasis AllInOne Module
Authors: Basuli Falguni , Shi Jianfeng , Shah Swati , Lai Jianhao , Hammoud Dima A. , Swenson Rolf E.
Published: July 2024

Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal‐specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as Aspergillus species. Recently, our group reported fluorine‐18 labeled cellobiose, 2‐deoxy‐2‐[18F]fluorocellobiose ([18F]FCB), for specific imaging of Aspergillus infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal‐specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2‐deoxy‐2‐[18F]fluoroglucose ([18F]FDG), glucose‐1‐phosphate, and enzyme (cellobiose phosphorylase). A Sep‐Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%–70% (n = 6, decay corrected) in 75‐min synthesis time with a radiochemical purity of > 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)–compliant [18F]FCB for clinical PET imaging.
Carpal variability and asymmetry in limb reduced Western lesser sirens (Siren nettingi)
Authors: Barlow Gibson M. , Ledbetter Nicholus M.
Published: July 2024

Trait functionality can act as a constraint on morphological development. Traits that become vestigialized can exhibit unstable developmental patterns such as fluctuating asymmetry (FA) and variation in populations. We use clearing and staining along with morphometric analyzes to compare FA and allometry of limbs in Western lesser sirens (Siren nettingi) to Ouachita dusky salamanders (Desmognathus brimleyorum). Our results describe new carpal phenotypes and carpal asymmetry in our sample of S. nettingi. However, we found no significant evidence of limb length asymmetry in S. nettingi. The degree of relative limb asymmetry correlates inversely with body size in both of our samples. This work provides strong evidence of increased mesopodal variation within a population of S. nettingi. Our work provides a basis for further study of a broader range of morphological traits across salamanders.
Mitral Annulus Disjunction: A Comprehensive Cardiovascular Magnetic Resonance Phenotype and Clinical Outcomes Study
Authors: Custódio Pedro , de Campos Diana , Moura Ana Rita , Shiwani Hunain , Savvatis Konstantinos , Joy George , Lambiase Pier D. , Moon James C. , Khanji Mohammed Y. , Augusto João B. , Lopes Luís R.
Published: July 2024

Background

Clinical importance of mitral annulus disjunction (MAD) is not well established.

Purpose

Characterize a population of MAD all‐comers diagnosed by cardiac magnetic resonance imaging (MRI).

Study Type

Retrospective.

Population

MAD confirmed in 222 patients, age of 49.2 ± 19.3 years, 126 (56.8%) males.

Field Strength/Sequence

1.5 T and 3 T/steady‐state free precession and inversion recovery.

Assessment

Clinical history, outcomes, imaging, and arrhythmia data. MAD defined as a separation ≥2 mm between left ventricular myocardium and mitral annulus. Presence and pattern of late gadolinium enhancement (LGE) were analyzed. LGE in the papillary muscles and adjacent to MAD were identified as MAD related. Ventricular arrhythmias (VA) were grouped into non‐sustained ventricular arrhythmias (NSVA) or sustained. Cardiovascular death assessed.

Statistical Tests

Differences between baseline characteristics were compared. Univariate regression was used to investigate possible associations between ventricular arrhythmia and cardiovascular death with characteristics associated with the severity of MAD. A multivariable logistic regression included significant variables from the univariate analysis and was performed for MAD‐related and global LGE.

Results

MAD extent 5.0 ± 2.6 mm. MV annulus expanded during systole for MAD ≥6 mm. Systolic expansion associated with prolapse, billowing, and curling. LGE present in 82 patients (36.9%). Twenty‐three patients (10.4%) showed MAD‐related LGE by three different observers. No association of LGE with MAD extent (P = 0.545) noted. Follow‐up 4.1 ± 2.4 years. No sustained VA observed. In univariable analysis, NSVA was more prevalent in patients with MAD ≥6 mm (33.3% vs. 9.9%), but this was attenuated on multivariate analysis (P = 0.054). The presence of NSVA was associated with global LGE but not MAD‐related LGE in isolation (P = 0.750). Three patients died of cardiovascular causes (1.4%) and none had MAD‐related LGE. None died of sudden cardiac arrest.

Conclusion

In patients referred for cardiac MRI, mitral valve dysfunction was associated with MAD severity. Scar was not related to the extent of MAD, but associated with NSVA. The risk of sustained arrhythmias and cardiovascular death was low in this population.

Evidence Level

4

Technical Efficacy

Stage 2
Monitoring questing winter tick abundance on traditional moose hunting lands
Authors: Berube Juliana A. , Sirén Alexej P. K. , Simpson Benjamin D. , Klingler Kelly B. , Wilson Tammy L.
Published: July 2024

An important symbolic and subsistence animal for many Native American Tribes, the moose (Alces alces; mos in Algonquin, Penobscot language) has been under consistent threat in the northeastern United States because of winter tick (Dermacentor albipictus) parasitism over the past several decades, causing declines in moose populations throughout the region. This decline has raised concern for Tribes and agencies that are invested in moose. Given this concern, it is increasingly important to effectively monitor and develop strategies to manage winter ticks to address consistent population declines of moose due to winter ticks. The Penobscot Nation developed a novel strategy to sample questing winter ticks (i.e., ticks that are actively seeking hosts) using a plot‐based sampling protocol that may be suitable for heterogeneous habitats. We deployed this protocol in the northeastern United States in 2022 during the tick questing period (Sep–Dec) on Penobscot Nation sovereign trust lands, the White Mountain National Forest and Umbagog National Wildlife Refuge, and western‐central Massachusetts, USA. We analyzed the data using occupancy and N‐mixture models. Detection probability peaked during mid‐October and tick occupancy and abundance were greatest at sites with intermediate understory vegetation height. The sampling protocol was successful at sampling ticks in Massachusetts, where abundances were expected to be low, indicating that it may be useful for studies planning to monitor winter tick distribution and abundance in areas with sub‐optimal moose habitat and where winter tick abundance is expected to be low. This approach may also benefit managers or researchers intending to monitor many species of hard ticks, and where imperfect detection is expected.