bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Semi‐Artificial Photosynthesis of Ethylene by a Self‐Assembled InP‐Cyanobacterial Biohybrid System
Authors: Liang Jun , Chen Zhen , Yin Panqing , Hu Haitao , Cheng Wenbo , Shang Jinlong , Yang Yiwen , Yuan Zuwen , Pan Jinlong , Yin Yongqi , Li Weizhi , Chen Xiongwen , Gao Xiang , Qiu Baosheng , Wang Bo
Published: June 2023

Biomanufacturing of ethylene is particularly important for modern society. Cyanobacterial cells are able to photosynthesize various valuable chemicals. A promising platform for next‐generation biomanufacturing, the semiconductor‐cyanobacterial hybrid systems are capable of enhancing the solar‐to‐chemical conversion efficiency. Herein, the native ethylene‐producing capability of a filamentous cyanobacterium Nostoc sphaeroides is confirmed experimentally. The self‐assembly characteristic of N. sphaeroides is exploited to facilitate its interaction with InP nanomaterial, and the resulting biohybrid system gave rise to further elevated photosynthetic ethylene production. Based on chlorophyll fluorescence measurement and metabolic analysis, the InP nanomaterial‐augmented photosystem I activity and enhanced ethylene production metabolism of biohybrid cells are confirmed, the mechanism underlying the material‐cell energy transduction as well as nanomaterial‐modulated photosynthetic light and dark reactions are established. This work not only demonstrates the potential application of semiconductor‐N. sphaeroides biohybrid system as a good platform for sustainable ethylene production but also provides an important reference for future studies to construct and optimize nano‐cell biohybrid systems for efficient solar‐driven valuable chemical production.
Exosome DNA: An untold story of cancer
Authors: Bhattacharya Bikramjit , Dhar Rajib , Mukherjee Sayantanee , Gorai Sukhamoy , Devi Arikketh , Krishnan Anand , Alexiou Athanasios , Papadakis Marios
Published: June 2023

Exosome is nanosized tiny membrane‐bound vesicles and is a subpopulation of extracellular vesicles (EVs). In general, it participates in intercellular communication and acts as a messenger of several pathological complications. Exosome and cancer interlink is the most exciting domain of current cancer research. The internal molecular cargos (proteins, lipids, metabolites, miRNA, and DNA) of tumor derived exosomes (TEXs) are capable of transforming normal cells into tumor phenotypes. Exosome DNA is the less explored area of EVs research. It is involved in several events in cancer progression such as uncontrol cell growth, reprogramming of immune cells, metastasis, and therapeutic resistance. Exo‐DNA is also involved in epigenetic alteration, which promotes cancer. It has a great impact on cancer theranostics (biomarker and therapeutics) research. Exo‐DNA‐based cancer examination supports more detailed cancer research.
The gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer
Authors: Han Zihan , Cheng Siyuan , Dai Die , Kou Yan , Zhang Xiaotian , Li Fang , Yin Xiaochen , Ji Jingjing , Zhang Zhikuan , Wang Xi , Zhu Ning , Zhang Qi , Tan Yan , Guo Xiaohuan , Shen Lin , Peng Zhi
Published: June 2023

Background

Common treatments for metastatic/unresectable HER2‐negative gastric cancer include chemotherapy, immune checkpoint inhibitor monotherapy and chemotherapy plus immune checkpoint inhibitor. However, significant drug resistance exists regardless of the treatment regimen.

Methods

Patients with metastatic/unresectable HER2‐negative gastric/gastroesophageal junction adenocarcinoma were enrolled. All patients were divided into three groups according to the treatment regimen and were further divided into responders and non‐responders according to efficacy evaluation. Metagenomics sequencing were performed to analyze gut microbiome signature of patients receiving different treatments at baseline and throughout treatment.

Results

One hundred seventeen patients with HER2‐negative advanced gastric or gastroesophageal junction adenocarcinoma receiving chemotherapy alone, anti PD‐1/PD‐L1 immunotherapy alone or combined regimen were included in this study. Microbiome signatures related to clinical response are distinct among the three treatment groups. Among which, 14, 8 and 13 species were significantly different between responders and non‐responders in immunotherapy, immunotherapy plus chemotherapy and chemotherapy group, respectively. Patients with higher relative abundance of Lactobacillus possessed higher microbiome diversity and significantly better response to anti‐PD‐1/PD‐L1 immunotherapy and had a trend to achieve better progression‐free survival. Another cohort of 101 patients has been used as an external validation set to confirm the stability and reliability of these findings.

Conclusions

Gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer in a treatment‐specific way, immunotherapy plus chemotherapy did not equal to a simple superposition of immunotherapy and chemotherapy. Lactobacillus is expected to become a novel choice as an adjuvant agent in promoting the efficacy of immunotherapy in gastric cancer.
Development of a new gastrointestinal endoscope forceps plug that can minimize gas leakage
Authors: Ishida Tomo , Hayashi Yoshinori , Nose Yohei , Goto Kohei , Ishii Yuji , Saito Takuro , Yamashita Kotarou , Tanaka Koji , Yamamoto Kazuyoshi , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Eguchi Hidetoshi , Doki Yuichiro , Nakajima Kiyokazu
Published: June 2023

Background and aims

In our previous study, we visualized and systematically evaluated gas leakage from the forceps plug of the gastrointestinal endoscope system using the Schlieren system. In order to minimize the potential risk of infection from gas leakage from the gastrointestinal endoscope, the development of a new forceps plug was considered urgent. In this study, we analyzed the structure of commercially available forceps plugs and attempted to develop new forceps plugs with improvements.

Methods

Microfocus computed tomography was used to nondestructively analyze the structural changes that occur when forceps are inserted into a commercially available forceps plug. Based on the findings, the basic structure of the newly developed forceps plug was set. We examined the airtightness of these newly developed plugs using the Schlieren system and also compared their fractional resistance with those of commercially available plugs.

Results

As a result of the nondestructive analysis, all of the commercially available plugs had a single valve, and the cleavage created in the valve during forceps, insertion was large in the case of plugs with slit‐type entrances. In the newly developed forceps plugs, all four types of plugs showed less gas leakage and similar or better usability compared to the commercially available plugs.

Conclusions

The structural weaknesses of the existing gastrointestinal endoscopic forceps plugs were identified. Based on the findings, we froze the design of a prototype of a new forceps plug that was airtight and not inferior in usability compared to commercially available plugs.
Microbiome‐modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta‐analysis, and meta‐regression of clinical trials
Authors: Kaul Ridhima , Paul Pradipta , Harfouche Manale , Saliba Reya , Chaari Ali
Published: June 2023

Aims

Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field.

Methods

We conducted a systematic review, meta‐analysis, and meta‐regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random‐effects meta‐analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525.

Results

Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (−9.97 mg/dL [95% CI: −15.08; −4.87], p < 0.0001), low‐density lipoprotein (−6.29 mg/dL [95% CI: −9.25; −3.33], p < 0.0001), high‐density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very‐low‐density lipoprotein (−4.52 mg/dL [95% CI: −6.36; −2.67], p < 0.0001) and triglyceride (−22.93 mg/dL [95% CI: −33.99; −11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration.

Conclusions

Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter‐study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.
Lower skeletal muscle mass is associated with diabetes and insulin resistance: A cross‐sectional study
Authors: Park Jin Hun , Lee Mi-Yeon , Shin Hun-Kyu , Yoon Kyung Jae , Lee JunYeop , Park Jai Hyung
Published: June 2023

Aims

The association between skeletal muscle mass and diabetes incidence/insulin resistance/glycated hemoglobin (HbA1C) is unknown. The aim of this study was to investigate such association in clinically apparently healthy males and females.

Methods

A cross‐sectional study of 372,399 Korean males and females who completed bioelectrical impedance analysis (BIA) in a health‐screening programme was performed. Skeletal muscle index was used as an indicator of skeletal muscle mass. Skeletal muscle index (%) [appendicular skeletal muscle mass (kg)/body weight (kg)X100] was estimated using BIA. The study outcomes were diabetes incidence, homoeostasis model assessment of insulin resistance (HOMA‐IR), and HbA1C.

Results

The mean age of study participants was 38.92 ± 8.54 years. Multiple logistic regression analysis revealed a significant negative association between Skeletal muscle index and diabetes incidence/HOMA‐IR/HbA1C after adjusting for various confounding factors. Odds ratios (95% confidence interval (CI)) of diabetes incidence in Q2, Q3, and Q4 compared to the lowest quantile (Q1) were 0.95 (0.85–1.05), 0.88 (0.78–0.99), and 0.79 (0.69–0.9), respectively. Beta coefficients (95% CI) of HOMA‐IR in Q2, Q3, and Q3 with Q1 were 0.05 (0.03–0.07), −0.06 (−0.09∼−0.04), and −0.19 (−0.22∼−0.16), respectively. Beta coefficients (95% CI) of HbA1C in Q2, Q3, and Q4 with Q1 were 0.02 (0.01–0.03), −0.001 (−0.01∼0.01), and −0.02 (−0.03∼−0.01), respectively.

Conclusions

This study demonstrated negative associations of skeletal muscle mass with diabetes incidence, insulin resistance, and HbA1C levels in healthy adults.
Distinct epiphyte responses to drought in tropical mountain cloud forests
Authors: Tsai Yi‐Chen , Wang Lixin , Wang Chiao‐Ping , Lin Teng‐Chiu
Published: June 2023

Epiphytes are often considered to be significantly impacted by precipitation changes because their lack of direct access to soil water. However, few in situ studies have examined how reduction in water availability may affect epiphyte growth. Using a unique stemflow collection and diversion device, we examined the effects of stemflow reduction of 25% and 50% on the growth and leaf traits of two common but distinct epiphyte species in a subtropical forest. One species (Asplenium nidus) has a large substrate, and another (Haplopteris zosterifolia) without known water storage structure. The 25% stemflow reduction had limited effects on the growth and leaf traits of the two epiphytes, indicating that 25% stemflow reduction did not reach the water stress threshold for the two epiphytes. It is also possible that the actual reduction in water availability was less than 25% since epiphytes do not use all available stemflow and there could be other sources of water such as fog and throughfall. The 50% stemflow reduction reduced leaf number and leaf area of H. zosterifolia, but not A. nidus, likely because water stored in the large substrate of A. nidus mitigated the impact of stemflow reduction. The thinner leaves, smaller leaf dry matter content, and lower δ13C of A. nidus than H. zosterifolia support the role of water storage of the substrate of A. nidus on mitigating water stress. The 50% stemflow reduction increased leaf thickness, leaf dry matter content of H. zosterifolia, and thickness of abaxial cuticle layer of both epiphytes but had no effect on δ13C. Stemflow reduction had no effects on nutrient concentration and nutrient ratios of both epiphytes suggesting that the epiphytes were able to maintain stoichiometry. Our results indicate that the epiphytes minimized nonstomatal water loss when environmental dryness increased but maintained stomata conductance, which could be important in minimizing the impacts of drought on plant growth and quickly resuming growth once drought ends. Our study highlights that not all epiphytes are similarly vulnerable to drought and precipitation reduction may change the relative abundance of epiphytes with and without water storage structure.
Influence of the filter grain morphology on separation efficiency in dielectrophoretic filtration
Authors: Kepper Mariia , Karim Md Nurul , Baune Michael , Thöming Jorg , Pesch Georg R.
Published: June 2023

Recovery of noble materials from waste is essential for industries around the globe. Dielectrophoretic (DEP) filtration, an electrically switchable particle separation technique, can be applied to tackle this challenge. It is highly selective regarding particle size, material or shape. Expanding the scope of DEP towards high throughput and improving the trapping efficiency are vital to make DEP a viable robust alternative to conventional separation methods. DEP filtration works by selective immobilisation of particles in a porous medium by the action of an inhomogeneous electric field. The field inhomogeneity comes from scattering an electric field at the phase boundary between the particle suspension and the filter surface. In this article, we show how the filter structure affects the DEP separation. We study fixed bed filters of three different grain types and find that the morphology of the grains highly influences the DEP filter efficiency. Specifically, grains with irregular surface structure and high perceived angularity show high separation efficiency. We believe these insights into the design of DEP filtration will pave the way towards its application in, for example, the recovery of valuable materials from electronic waste dust.
Phosphonate‐influenced Diels‐Alder chemistry toward multi‐path recyclable, fire safe thermoset and its carbon fiber composites
Authors: Gu Song , Xu Shao‐Dong , Lu Jia‐Hui , Pu Xiao‐Lu , Ren Qing‐Ruo , Xiao Yan‐Fang , Wang Yu‐Zhong , Chen Li
Published: June 2023

Dynamic covalent chemistry offers a solution to tackle the recycling issue of epoxy resins (EPs) and their carbon fiber‐reinforced composites; however, the vulnerability to creep associated with the inflammable nature of the EPs are the key obstacles for their applications. Herein, we propose a feasible and facile strategy to overcome these obstacles by incorporating phosphorus‐influenced Diels‐Alder (DA) chemistry to construct dynamic epoxy networks. In the strategy, the electron‐withdrawing phosphonate in the dienophile maleimide greatly promotes the thermal stability of the DA reaction, exhibiting excellent creep resistance, repairability, and malleability; while its flame‐retardant activity improves the fire safety of the resultant thermosets. Meanwhile, nondestructive recycling of carbon fiber is achieved. The ease with which EP and its composites can be manufactured, used, recycled and re‐used–without losing service performance–points to new orientation in sustainable composites.

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Forecast accuracy of the linear and nonlinear autoregressive models in macroeconomic modeling
Authors: Taiebnia Ali , Mohammadi Shapour
Published: June 2023

Most nonlinear vector autoregressive methods in the econometric literature are based on specific functional forms, such as the smooth transition autoregressive model. This study proposes a general form of the nonlinear vector autoregressive model based on global approximators, such as neural networks, Volterra, and Weiner series. The simulation results of 20 linear and nonlinear multivariate time series processes indicate that nonlinear vector autoregressive methods, especially multi‐output neural networks, are more accurate based on the root mean square error and model confidence set criteria. Applying the global approximator approach to a small‐scale macroeconometric model reveals that the new approach can improve forecast accuracy compared to linear and other nonlinear vector error correction models. In addition, forecasting the relevant variables in a typical exchange rate and monetary policy models based on nonlinear specifications gives more successful results than in the linear case.
Development and validation of a questionnaire to measure association factors with suicide: An instrument for a populational survey
Authors: Rodrigues Juliano Flávio Rubatino , de Araújo Filho Gerardo Maria , Rodrigues Lívia Peregrino , Rubatino Fernando Victor Martins , Fischer Hannes , Payão Spencer Luiz Marques
Published: June 2023

Background and Aims

Our goal was to develop an online questionnaire to survey the prevalence of suicidal behavior.

Methods

We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test−rest.

Results

The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got Kaiser−Meyer−Olkin = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates root mean square error of approximation = 0.000 and comparative fit index = 1.000. The test−retest had an intraclass correlated coefficient of 0.98.

Conclusion

The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors during the pandemic time.

Patient or Public Contribution

The general population of Marília voluntarily responded to the questionnaire, as well as patients from the principal investigator's office.
Osteocyte‐Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model
Authors: Munir Arooj , Reseland Janne Elin , Tiainen Hanna , Haugen Håvard Jostein , Sikorski Pawel , Christiansen Emil Frang , Reinholt Finn Per , Syversen Unni , Solberg Lene Bergendal
Published: June 2023

In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte‐like cells were identified as entrapped, stellate‐shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte‐like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte‐like cell differentiation, cross‐talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue‐specific biochemical, biophysical, and mechanical properties. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
FRAGMENTISE: A user‐friendly, cross‐platform tool to create and analyze comprehensive small‐molecule fragment databases
Authors: Zarnecka Joanna M. , Kaminska Katarzyna H.
Published: June 2023

The ongoing COVID‐19 pandemic, and constant demand for new therapies in unmet clinical needs, necessitates strategies to identify drug candidates for rapid clinical deployment. Over the years, fragment‐based drug design (FBDD) has emerged as a mainstream lead discovery strategy in academia, biotechnology start‐ups, and large pharma. Chemical building block libraries are the fundamental component of virtually any FBDD campaign. Current trends focus on smaller and smarter libraries that offer synthetically amenable starting points for rational lead generation. Therefore, there remains an ever‐increasing need for new methods to generate fragment libraries to seed early‐stage drug discovery programs. Here, we present FRAGMENTISE—a new user‐friendly, cross‐platform tool for user‐tunable retrosynthetic small‐molecule fragmentation. FRAGMENTISE allows for visualization, similarity search, annotation, and in‐depth analysis of the fragment databases in the medicinal chemistry context. FRAGMENTISE is available as standalone software for Linux, Windows, and macOS users, with a graphical interface or command‐line version.
Attenuation of alcohol‐induced hepatocyte damage by ginsenoside Rg1 evaluated using atomic force microscopy
Authors: Zhang Shengli , Weng Zhankun , Wang Zuobin , Wang Bowei , Zeng Yi , Li Jiani , Hu Cuihua
Published: June 2023

Alcoholic liver disease is an important cause of death worldwide. Hepatocyte apoptosis is commonly observed in alcoholic liver disease. In this study, we investigated the effect of ginsenoside Rg1 (G‐Rg1), an organic component of ginseng, on the alcohol‐induced morphological and biophysical properties of hepatocytes. Human hepatocytes (HL‐7702) were treated in vitro with alcohol and G‐Rg1. The cell morphology was observed using scanning electron microscopy. Cell height, roughness, adhesion, and elastic modulus were detected using atomic force microscopy. We found that alcohol significantly induced hepatocyte apoptosis, whereas G‐Rg1 attenuated the alcohol‐induced hepatocyte damage. Scanning electron microscopy revealed that alcohol‐induced significant morphological changes in hepatocytes, including decreased cell contraction, roundness, and pseudopods, whereas G‐Rg1 inhibited these negative changes. Atomic force microscopy revealed that alcohol increased the cell height and decreased the adhesion and elastic modulus of hepatocytes. Following treatment with G‐Rg1, the cell height, adhesion, and elastic modulus of alcohol‐injured hepatocytes were all similar to those of normal cells. Thus, G‐Rg1 can attenuate the alcohol‐induced damage to hepatocytes by modulating the morphology and biomechanics of the cells.

Research Highlights

In this study, the morphological characteristics of hepatocytes were observed using SEM.

The changes in hepatocyte three‐dimensional images and biomechanical action caused by alcohol and G‐Rg1 were examined at the nanoscale using AFM under near‐physiological conditions.

Alcohol‐induced hepatocytes showed abnormal morphology and biophysical properties. G‐Rg1 attenuated the alcohol‐induced damage to hepatocytes by modulating the morphology and biomechanics of the cells.
Antisense lncRNA‐RP11‐498C9.13 promotes bladder cancer progression by enhancing reactive oxygen species‐induced mitophagy
Authors: Song Wei , Li Zhuo , Yang Ke , Gao Zhiyong , Zhou Qiang , Li Ping
Published: June 2023

Background

Urinary system's most prevalent malignant tumor is bladder cancer. The enzyme pyrroline‐5‐carboxylate reductase 1 (PYCR1) has pro‐tumorigenic characteristics. In the present study, the upstream and downstream regulatory mechanisms of PYCR1 in bladder cancer were investigated.

Methods

The relationship between the expression of PYCR1 in bladder cancer and its prognosis was analyzed using a bioinformatics technique. Plasmid transfection and small interfering RNA were utilized to overexpress and silence genes, respectively. Utilizing MTT, colony formation, EdU, and transwell assays, the proliferation and invasiveness of bladder cancer cells were evaluated. Employing an RNA pull‐down experiment and RNA immunoprecipitation, the relationship between RNAs was analyzed. Fluorescence in situ hybridization, immunohistochemistry, and western blotting were used to detect protein expression and localization. Flow cytometry was used to identify reactive species (ROS) expression in cells. Mitophagy was detected using immunofluorescence.

Results

PYCR1 was highly expressed in bladder cancer tissue and was related with a poor prognosis for the patient. By binding to PYCR1, the antisense RNA lncRNA‐RP11‐498C9.13 prevented the degradation of PYCR1 and promoted its production. Down‐regulation of lncRNA‐RP11‐498C9.13 and PYCR1 inhibited the proliferation and invasiveness of bladder cancer cells and decreased tumorigenesis. In addition, it was found that the lncRNA‐RP11‐498C9.13/PYCR1 axis promoted ROS generation and induced mitophagy in bladder cancer cells.

Conclusions

We demonstrated that lncRNA‐RP11‐498C9.13 promoted bladder cancer tumorigenesis by stabilizing the mRNA of PYCR1 and promoted ROS‐induced mitophagy. The lncRNA‐RP11‐498C9.13/PYCR1/mitophagy axis was anticipated to be a significant therapeutic target for bladder cancer.
Key biomarkers in cerebral arteriovenous malformations: Updated review
Authors: Tanzadehpanah Hamid , Modaghegh Mohammad Hadi Saeed , Mahaki Hanie
Published: June 2023

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well‐known that metalloproteinase‐9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras‐mitogen‐activated protein kinase‐extracellular signal‐regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin‐6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient‐specific risk estimation and improving treatment choices.
An efficient one‐pot synthesis of Spiro[indoline‐3,11′‐pyrazolo[3,4‐f]pyrimido[4,5‐b]quinoline] derivatives
Authors: Liu Jia‐Yan , Peng Lan , Li Meng‐Fei , Wei Ming , Chen Sai , Chen Dong‐Sheng
Published: June 2023

An efficient procedure for the synthesis of novel spiro[indoline‐3,11′‐pyrazolo[3,4‐f]pyrimido[4,5‐b]quinoline] derivatives has been developed by one‐pot condensation of 1H‐indazol‐6‐amine, isatin and barbituric acid or 2‐thiobarbituric acid, in the presence of L‐proline in refluxing EtOH. This method has the advantages of operational simplicity, high yield of products via a simple experimental and work‐up procedure. IR, 1H NMR, 13C NMR, 19F NMR and HRMS were used to identify the structures of all the synthesized compounds.
Natural history of GM1 gangliosidosis—Retrospective cohort study of 61 French patients from 1998 to 2019
Authors: Laur Domitille , Pichard Samia , Bekri Soumeya , Caillaud Catherine , Froissart Roseline , Levade Thierry , Roubertie Agathe , Desguerre Isabelle , Héron Bénédicte , Auvin Stéphane
Published: June 2023

GM1 gangliosidosis is a rare lysosomal storage disorder associated with β‐galactosidase enzyme deficiency. There are three types of GM1 gangliosidosis based on age of symptom onset, which correlate with disease severity. In 2019, we performed a retrospective multicentric study including all patients diagnosed with GM1 gangliosidosis in France since 1998. We had access to data for 61 of the 88 patients diagnosed between 1998 and 2019. There were 41 patients with type 1 (symptom onset ≤6 months), 11 with type 2a (symptom onset from 7 months to 2 years), 5 with type 2b (symptom onset from 2 to 3 years), and 4 with type 3 (symptom onset >3 years). The estimated incidence in France was 1/210000. In patients with type 1, the first symptoms were hypotonia (26/41, 63%), dyspnea (7/41, 17%), and nystagmus (6/41, 15%), whereas in patients with type 2a, these were psychomotor regression (9/11, 82%) and seizures (3/11, 27%). In types 2b and 3, the initial symptoms were mild, such as speech difficulties, school difficulties, and progressive psychomotor regression. Hypotonia was observed in all patients, except type 3. The mean overall survival was 23 months (95% confidence interval [CI]: 7, 39) for type 1 and 9.1 years (95% CI: 4.5, 13.5) for type 2a. To the best of our knowledge, this is one of the largest historical cohorts reported, which provides important information on the evolution of all types of GM1 gangliosidosis. These data could be used as a historical cohort in studies assessing potential therapies for this rare genetic disease.
Localizing Hormone Receptor Expression to Cellular Compartments in Idiopathic Subglottic Stenosis
Authors: Talatala Edward Ryan R. , Clark Evan , Ye Wenda , Davis Ruth J. , Hillel Alexander T. , Collins Samuel L. , Ramirez‐Solano Marisol , Sheng Quanhu , Gelbard Alexander
Published: June 2023

Objectives

Idiopathic subglottic stenosis (iSGS) is an unexplained progressive fibrosis of the upper airway. iSGS almost exclusively affects women; as a result, female hormones (estrogen and progesterone) have been proposed to participate in the pathogenesis of iSGS. Our aim was to localize cell‐specific gene expression of estrogen receptors (ESR1 and ESR2) and progesterone receptor (PGR) using an established iSGS single‐cell RNA sequencing (scRNAseq) cell atlas.

Study Design

Ex vivo molecular study of airway scar and healthy mucosa from iSGS patients.

Methods

An established scRNAseq atlas consisting of 25,974 individually sequenced cells from subglottic scar (n = 7) or matched unaffected mucosa (n = 3) in iSGS patients was interrogated for RNA expression of ESR1, ESR2, and PGR. Results were quantified and compared across cell subsets, then visualized using Uniform Manifold Approximation and Projection (UMAP). Confirmatory protein assessment of endocrine receptors in fibroblasts from iSGS patients (n = 5) was performed via flow cytometry.

Results

The proximal airway mucosa in iSGS patients demonstrates differential expression of endocrine receptors (ESR1, ESR2, PGR). Within airway scar, endocrine receptors are primarily expressed by fibroblasts, immune cells, and endothelial cells. Fibroblasts show strong ESR1 and PGR expression, while immune cells possess RNA for both ESR1 and ESR2. Endothelial cells predominantly express ESR2. Epithelial cells in unaffected mucosa express all three receptors, which are all reduced in airway scar.

Conclusions

scRNAseq data localized endocrine receptor expression to specific cell subsets. These results provide the foundation for future work interrogating how hormone‐dependent mechanisms promote, sustain, or participate in iSGS disease pathogenesis.

Level of Evidence

NA; Basic science Laryngoscope, 133:3506–3511, 2023
Spatiotemporal evolution and the detection of key drivers in the resilience of cultivated land system in major grain‐producing regions of China
Authors: Xu Weiyi , Jin Xiaobin , Liu Jing , Li Hangbin , Zhang Xiaolin , Zhou Yinkang
Published: June 2023

Evaluation and improvement of cultivated land system resilience (CLSR) play a significant role in the sustainable development of cultivated land. From the perspective of multifunction of cultivated land, this study revealed the spatiotemporal evolution of CLSR in China's major grain‐producing regions during 2000–2020 by catastrophe model based on a comprehensive evaluation system including production resilience (PR), ecological resilience (ER), and economic resilience (CR), and further identified the key drivers to find scientific paths to improve CLSR. The results demonstrated that the CLSR had significant spatiotemporal differences and stayed at a low level but showed a steady rise. In terms of spatial scope, the number of provinces with middle‐ and high‐grade resilience had increased from 0 to 10. As for time variation, the CLSR showed an upward trend, from 0.78 to 0.95. PR and CR were similar to CLSR, showing an increased tendency, while ER displayed the characteristics of first decreased and then increased. As for the key drivers, PR played a central role in the CLSR, the effect of CR on CLSR was weakened, while the ER was gradually strengthened. Specifically, the stability of grain production, effective irrigated area rate, agricultural pollution, and the contribution of agriculture to GDP were the key factors to CLSR. Hence, stabilizing cultivated land areas, controlling nongrain growing phenomena, strengthening agricultural infrastructure construction, promoting ecological restoration of cultivated land, and ensuring economic contribution of cultivated land were effective ways to improve CLSR.
Some qualitative properties of weak solution for pseudo‐parabolic equation with viscoelastic term and Robin boundary conditions
Authors: Ngo Tran‐Vu , Dao Bao‐Dung , Freitas Mirelson M.
Published: June 2023

In this paper, we consider the initial boundary value problem of the generalized pseudo‐parabolic equation containing viscoelastic terms and associated with Robin conditions. We establish first the local existence of solutions by the standard Galerkin method. Then, we prove blow‐up results for solutions when the initial energy is negative or nonnegative but small enough or positive arbitrary high initial energy, respectively. We also establish the lifespan and the blow‐up rate for the weak solution by finding the upper bound and the lower bound for the blow‐up times and the upper bound and the lower bound for the blow‐up rate. For negative energy, we introduce a new method to prove blow‐up results with a sharper estimate for the upper bound for the blow‐up times. Finally, we prove both the global existence of the solution and the general decay of the energy functions under some restrictions on the initial data.
Wideband receive‐coil array design using high‐impedance amplifiers for broadband decoupling
Authors: Sun Chenhao , Bauer Courtney C. , Hou Jue , Wright Steven M.
Published: June 2023

Purpose

Multinuclear MRI/S is of increasing interest. Currently, most multinuclear receive array coils are constructed by nesting multiple single‐tuned array coils or using switching elements to control the operating frequency, in which case more than one set of conventional isolation preamplifiers and associated decoupling circuits is required. These conventional configurations rapidly become complicated when greater numbers of channels or nuclei are needed. In this work, a novel coil decoupling mechanism is proposed to enable broadband decoupling for array coils with one set of preamplifiers.

Methods

Instead of using conventional isolation preamplifiers, a high‐input impedance preamplifier is proposed to create broadband decoupling of the array elements. A matching network consisting of a single inductor‐capacitor‐capacitor multi‐tuned network and a wire‐wound transformer was used to interface the surface coil to the high‐impedance preamplifier. To validate the concept, the proposed configuration was compared to the conventional preamplifier decoupling configuration on both bench and scanner.

Results

2The approach can provide more than 15dB decoupling over a range of 25MHz, covering the Larmor frequencies of23Na and2H at 4.7T. This multi–tuned prototype obtained 61% and 76% of the imaging SNR at2H and23Na respectively, 76 and 89% in a higher loading test phantom, when compared to the conventional single–tuned preamplifier decoupling configuration.

Conclusion

With the multinuclear array operation and decoupling achieved using only one layer of array coil and preamplifiers, this work provides a simple approach of building high element‐count arrays to enable accelerated imaging or SNR improvement from multiple nuclei.
Heteroatom Chirality
Authors: Vystavkin Nikita , Teskey Christopher
Published: June 2023

Whilst chirality is well‐explored at carbon atoms, many chemists overlook heteroatom chirality, not least because the synthesis of conformationally stable compounds is challenging. Here, we highlight recent syntheses of molecules which are chiral at nitrogen and oxygen.
Aus zwei mach eins – von der Wirkstoffforschung ins Schülerlabor
Authors: Becker Anja , Berg Thorsten , Heimann Rebekka
Published: June 2023

Forschung ist ein langer und keineswegs linear verlaufender Prozess, der Kreativität und Ideen erfordert. Im Schülerlabor können Lernende diesen Prozess nachvollziehen – zum Beispiel an der Entwicklung neuer Wirkprinzipien in der medizinischen Chemie.
A modified reptile search algorithm for parametric estimation of fractional order model of lithium battery
Authors: Ding Jie , Huang Shimeng , Hao Yuefei , Xiao Min
Published: June 2023

In this paper, a Levy reptile search algorithm (LRSA) is proposed to improve the global search capability and convergence speed of reptile search algorithm which has advantages in solving single‐modal, multi‐modal and composite problems. Firstly, circle chaotic mapping is introduced to make the initial distribution of population more uniform and diversified. Secondly, Levy flight strategy is employed in the global search, which can improve the accuracy and convergence speed. In order to test and verify the optimization performance of the LRSA, 12 benchmark functions are tested and compared with four other intelligent optimization algorithms. It can be seen that LRSA is effective and advantageous in average convergence speed. In addition, the proposed LRSA is applied to a fractional order model identification of lithium battery with a very small error (less than 2%). The experimental results show that the LRSA can effectively estimate the parameters of the fractional order model and aid to state of charge and state of health estimation.
Fertility assessment and treatment in adolescent and young adult cancer survivors
Authors: Moravek Molly B. , Pavone Mary Ellen , Burns Karen , Kashanian James A. , Anderson Richard A. , Klosky James L. , Rotz Seth J. , Stern Catharyn J. , Rodriguez‐Wallberg Kenny A. , Levine Jennifer M. , Meacham Lillian R.
Published: June 2023

In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status, and may under‐ or overestimate their treatment‐related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Posttreatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.
Alignment of multiwalled carbon nanotubes‐reinforced epoxy by a novel shear assisted method in the presence of the electric field
Authors: Moaseri Erfan , Moaseri Negin , Maghrebi Morteza , Baniadam Majid
Published: June 2023

The application of multiwall carbon nanotubes (MWCNTs) alignment associated with external field techniques is fairly limited in the industry due to the cost implications of scaling such external fields. To address this problem, a new shear‐assisted method is introduced to increase the effectiveness of MWCNTs alignment techniques using electric field. In addition, the effect of curing temperature of polymer in CNT‐reinforced nanocomposites, is studied on the alignment of MWCNTs using our novel shear‐assisted technique. The results show that increasing the temperature during the curing process of the polymer can help with the alignment of MWCNTs using our shear‐assisted technique. This may be attributed to lower gel‐time of polymer matrix at high temperatures that can prevent agglomeration of the MWCNTs in the matrix. Moreover, fractography of reinforced composites has been studied by scanning electron microscopy to investigate the effects of curing temperature on the alignment of MWCNTs in the epoxy matrix.
Validation of a 1D dynamic thermal finite difference model for the rotational molding of an amorphous polycarbonate resin
Authors: Vandaele Maxim , Buffel Bart , Callewaert Kristof , Martens Jeroen , Thielemans Wim , Desplentere Frederik
Published: June 2023

This study focuses on the heating stage of the rotational molding process. When the mold wall reaches the tacky temperature, free flowing powder starts to adhere, melt, and sinter. In this work, a new modeling strategy is proposed. Compared with the models found in the literature, the model combines the use of a tacky temperature for the adherence of powder, changing boundary conditions, and thermophysical properties as function of temperature and the degree of sintering. The changing boundary conditions are introduced to take into account both wall to air and wall to powder contact. The calculation of the temperature evolution is done by applying the thermal finite difference principle to elements with a fixed polymer mass. The modeling of a uniaxial rotating cylinder is chosen as a case study. The validation is done for an amorphous polycarbonate resin. The performance of the model is evaluated not only by the comparison of temperature‐time data as is the case in most literature, but also by the decrease in free flowing powder weight as function of time, visual data from an in‐mold looking camera, and through thickness analysis of the molded pieces at various moments in the heating process.
Oral fluoroquinolones and risk of aortic aneurysm or dissection: A nationwide population‐based propensity score‐matched cohort study
Authors: Garg Mahek , Venugopalan Veena , Vouri Scott M. , Diaby Vakaramoko , Iovine Nicole M. , Park Haesuk
Published: June 2023

Study Objective

To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real‐world clinical practice among a large US general population.

Design

Retrospective cohort study design.

Data Source

MarketScan commercial and Medicare supplemental databases.

Patients

Adults patients with at least one prescription fill for fluoroquinolone or macrolide antibiotics.

Intervention

Fluoroquinolone or macrolide antibiotics.

Measurements and Main Results

The primary outcome was estimated incidence of aortic aneurysm or dissection associated with the use of fluoroquinolones compared with macrolides during a 60‐day follow‐up period in a 1:1 propensity score‐matched cohort. We identified 3,174,620 patients (1,587,310 in each group) after 1:1 propensity score matching. Crude incidence of aortic aneurysm or dissection was 1.9 cases per 1000 person‐years among fluoroquinolone users and 1.2 cases per 1000 person‐years among macrolide users. In multivariable Cox regression, compared with macrolides, the use of fluoroquinolones was associated with an increased risk of aortic aneurysm or dissection (aHR: 1.34; 95% CI: 1.17–1.54). The association was primarily driven by a high incidence of aortic aneurysm cases (95.8%). Results of sensitivity (e.g., fluoroquinolone exposure ranging from 7 to 14 days (aHR: 1.47; 95% CI: 1.26–1.71)) and subgroup analyses (e.g., ciprofloxacin (aHR: 1.26; 95% CI: 1.07–1.49) and levofloxacin (aHR: 1.44; 95% CI: 1.19–1.52)) remained consistent with main findings.

Conclusions

Fluoroquinolone use was associated with a 34% increased risk of aortic aneurysm or dissection compared with macrolide use among a general US population.
Racial climate reform in independent schools: How coping self‐efficacy buffers systemic and proximal racial stress for students of color
Authors: Collins Jackson A. , Stevenson Howard C.
Published: June 2023

The journey for students of color (SOC) in predominantly White independent schools (PWIS) is paved with significant educational opportunities and challenging racial conflicts. Little is known about how SOC manage the stress of negotiating these struggles and successes in daily relationships with peers and teachers or within the school climates where the policies and practices often reveal a bracketed commitment to diversity. For decades, programs like Prep for Prep have provided academic and social supports to prepare low‐income SOC for matriculation in PWIS. Using Racial Encounter Coping Appraisal and Socialization Theory, we investigated the racial stress and coping experiences of 593 SOC from the Prep for Prep leadership training program. After measuring development on the racial coping self‐efficacy scale, three factors identified that SOC range in their confidence inreadingor noticing racial microaggressions in their schools,recastingstressful racial conflicts from “impossible” to “manageable,” andresolvingracial tensions by confronting microaggressions. Results found that a moderated mediation model explains that the relationship of SOC school climate perceptions to school belonging and affect toward school are mediated through racial coping stress. SOC with high racial coping self‐efficacy (RCSE) show less negative influence from that stress on their academic and social experiences compared to those low in RCSE. Implications for supporting SOC by buffering racial stress within PWIS are discussed.