bluuebunny/crossref_metadata_2025 huggingface dataset:
Low gamma‐butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach
Authors: Kim Kyu‐Shik , Moon Kyoung Min , Min Kyueng‐Whan , Jung Woon Yong , Shin Su‐Jin , Lee Seung Wook , Kwon Mi Jung , Kim Dong‐Hoon , Oh Sukjoong , Noh Yung‐Kyun
Published: March 2023

Gamma‐butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma‐butyrobetaine to l‐carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death‐ligand 1. In vitro drug screening showed that midostaurin, BAY‐61‐3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.
Improved Strategies for Separators in Zinc‐Ion Batteries
Authors: Li Le , Jia Shaofeng , Cheng Zhiyi , Zhang Changming
Published: March 2023

The demand for energy storage is growing, and the disadvantages of lithium‐ion batteries are being explored to overcome them. Accordingly, aqueous zinc‐ion batteries (ZIBs) are developing very rapidly, owing to their high safety, environmental friendliness, high abundance of resources, and high cost performance. Over the last decade, ZIBs have made remarkable progress through extensive efforts in the field of electrode materials and through fundamental understanding of non‐electrode components, such as solid‐electrolyte interphase, electrolytes, separators, binders, and current collectors. In particular, the breakthrough in using separators on non‐electrode elements should not be overlooked as such separators have proven key to conferring ZIBs with high energy and power density. In this Review, recent progress in the development of separators in ZIBs is comprehensively summarized based on their functions and roles in ZIBs, including the modification of conventional separators and the development of novel separators. Finally, the prospects and future challenges of separators are also discussed to facilitate ZIBs development.
Comprehensive review on functional and nutraceutical properties of honey
Authors: Aga Mohsin B. , Sharma Vaibhav , Dar Aamir H. , Dash Kshirod K. , Singh Anurag , Shams Rafeeya , Khan Shafat A.
Published: March 2023

Most physiopathological conditions are oxidative stress prevalent risk factors for cardiovascular diseases and carcinogenesis. Phytochemicals present in honey can mitigate the primary mechanisms of oxidative stress and are deliberated as nutraceutical food responsible for mitigating risk factors for cancer and cardiovascular diseases. Honey has a low glycemic index, loaded with polyphenols, enzymes, minerals, and vitamins. Honey possesses antimicrobial, anti‐inflammatory, antidiabetic, and other functional characteristics in addition to its nutritional properties, as previously demonstrated in preclinical trials. Honey promotes gastrointestinal digestion and increases absorption of nutrients by the epithelial cells of the intestinal mucosa. Bioactive components in honey exhibit free‐radical scavenging ability in preserving the structural orientation of lipids through electron or proton donation, thus playing a pivotal role in suppressing risk factor elements such as kappa‐B pathways. Several factors such as botanical, geographical, soil, climatic conditions, season of harvesting, extraction, storage conditions, degree of maturation, and processing affect the physical and chemical properties of honey. The purpose of this review is to discuss the functional and nutritional qualities of honey also this article discusses honey's cardiovascular protective, gene regulatory, and antiradical characteristics, which are important variables in cancer and cardiovascular disease.
Reactions in Endohedral Functionalized Cages
Authors: Otte Matthias
Published: March 2023

The introduction of enhanced functionalization is a key aspect in the current design of cage chemistry. At the moment, several approaches are intensively investigated. The synthesis of cage compounds that display endohedral functionalization plays a key role among them. Here, the studies of reactions that occur in endohedral‐functionalized cage compounds is reviewed. After an introduction in current trends in cage‐chemistry the discussion of reactions in endohedral‐cage compounds is divided into three sections. These are: 1) Endohedral groups that are by themselves functional, 2) endohedral groups that can bind to a transition‐metal complex and 3) endohedral groups that can bind by themselves to a metal. The article closes with an outlook on additional current developments in the field of endohedral‐functionalized cage‐compounds, which may contribute in the future towards reactivity in cage compounds.
Electrochemical modification of a carbon paste electrode with poly (1,5‐diaminonaphthalene) and copper‐cobalt nanostructures for the determination of thioctic acid in real samples
Authors: AbdAllah Mahmoud , Hathoot A. A. , Abdel‐Azzem M.
Published: March 2023

This study used square‐wave voltammetry and cyclic voltammetry to investigate the electrochemical oxidation of Thioctic Acid (TA) on a Carbon Paste Electrode (CPE) modified with copper‐cobalt nanostructures and poly (1,5‐Diaminonaphthalene). The voltammetric sensor was sensitive to the oxidation of TA. In addition, we optimized the effects of multiple cycles of deposition of Cu‐Co nanostructures, and electro‐polymerization of monomer 1,5‐DAN, scan rate, and pH. The sensor showed good identification capabilities for TA. The linear responses obtained ranged from 0.6 μM to 150 μM with a detection limit of 0.48 μM for the modified CPE. The adsorption process controlled the oxidation of TA. We used the proposed sensor and method to determine TA in real samples.
Risk evaluation and mitigation strategies for newly detected SARS‐CoV‐2 Omicron BF.7 subvariant: A brief report
Authors: Nazmunnahar  , Ahmed Iftekhar , Islam Md. Rabiul
Published: March 2023

Mutations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are always going on. The pathogenic characteristics of a virus are influenced by mutations in the viral genome. Therefore, the recently identified Omicron BF.7 subvariant might harm humans. Here we aimed to evaluate the potential risks of this newly detected variant and identify possible mitigation strategies. The frequent mutation associated with SARS‐CoV‐2 makes it more concerning compared to other viruses. The Omicron variant of SARS‐CoV‐2 has unique changes in the structural amino acid. Thus, Omicron subvariants are different from other coronavirus variants in terms of viral spread, disease severity, vaccine neutralization capacity, and immunity evade. Moreover, Omicron subvariant BF.7 is an offspring of BA.4 and BA.5. Similar S glycoprotein sequences are present among BF.7, BA.4, and BA.5. There is a change in the R346T gene in the receptor binding site of Omicron BF.7 than other Omicron subvariants. This BF.7 subvariant has created a limitation in current monoclonal antibody therapy. Omicron has mutated since it emerged, and the subvariants are improving in terms of transmission as well as antibody evasion. Therefore, the healthcare authorities should pay attention to the BF.7 subvariant of Omicron. The recent upsurge may create havoc all of a sudden. Scientists and researchers across the world should monitor the nature and mutations of SARS‐CoV‐2 variants. Also, they should find ways to fight the current circulatory variants and any future mutations.
Predictors of autism spectrum disorder diagnosis in a spanish sample of preterm children with very low birthweight: A cross‐sectional study
Authors: Magán‐Maganto María , Canal‐Bedia Ricardo , Bejarano‐Martín Álvaro , Martín‐Cilleros Maria Victoria , Hernández‐Fabián Aránzazu , Calvarro‐Castañeda Andrea Luz , Roeyers Herbert , Jenaro‐Río Cristina , Posada de la Paz Manuel
Published: March 2023

Background and Aims

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a higher likelihood of being diagnosed in preterm populations. Likewise, low birthweight has also been connected with an increased likelihood of ASD. The objectives were to study the frequency and define the relationship between ASD, gestational age, birthweight, and growth percentiles for preterm children.

Methods

A sample of preterm children with very low birthweight was selected from the Spanish population at 7–10 years old. Families were contacted from the hospital, and they were offered an appointment to conduct a neuropsychological assessment. The children who showed signs of ASD were referred to the diagnostic unit for differential diagnosis.

Results

A total of 57 children completed full assessments, with 4 confirmed ASD diagnoses. The estimated prevalence was 7.02%. There were statistically significant weak correlations between ASD and gestational age (τb = −0.23), and birthweight (τb = −0.25), suggesting there is a higher likelihood of developing ASD for those born smaller or earlier in their gestation.

Conclusion

These results could improve ASD detection and outcomes for this vulnerable population while also supporting and enhancing previous findings.
On strictly enforced mass conservation constraints for modelling the Rainfall‐Runoff process
Authors: Frame Jonathan M. , Kratzert Frederik , Gupta Hoshin V. , Ullrich Paul , Nearing Grey S.
Published: March 2023

It has been proposed that conservation laws might not be beneficial for accurate hydrological modelling due to errors in input (precipitation) and target (streamflow) data (particularly at the event time scale), and this might explain why deep learning models (which are not based on enforcing closure) can out‐perform catchment‐scale conceptual and process‐based models at predicting streamflow. We test this hypothesis with two forcing datasets that disagree in total, long‐term precipitation. We analyse the roll of strictly enforced mass conservation for matching a long‐term mass balance between precipitation input and streamflow output using physics‐informed (mass conserving) machine learning and find that: (1) enforcing closure in the rainfall‐runoff mass balance does appear to harm the overall skill of hydrological models; (2) deep learning models learn to account for spatiotemporally variable biases in data (3) however this ‘closure’ effect accounts for only a small fraction of the difference in predictive skill between deep learning and conceptual models.
Activity‐Based Protein Profiling – Finding General Solutions to Specific Problems
Authors: Cravatt Benjamin F.
Published: March 2023

In this retrospective/perspective, I will share thoughts on developing and applying the activity‐based protein profiling (ABPP) technology, an endeavor that has consumed much of our lab's attention over our 25+ year existence. Before doing so, I first wish to thank the colleagues who so kindly contributed to this Special Issue. I am appreciative and humbled that they were willing to share their innovative and impactful science in this format.
Ear disease in pet rabbits
Authors: Keeble Emma
Published: March 2023

Background: Ear disease is a common presenting condition in pet rabbits in veterinary practice and can involve any or all parts of the ear – the external ear canal, the middle ear and the inner ear. Our knowledge of ear disease in this species has advanced significantly over the past 10 years, with recent and relevant publications reported in the literature. A higher incidence occurs in lop‐eared rabbits, thought to be due to their pinna anatomy (Johnson and Burn 2019).

Aim of the article: This article reviews rabbit ear disease, focusing on clinical signs, diagnostics and treatment in pet rabbits. Clinical signs may vary depending on the severity, chronicity and anatomical location and range, from ear scratching and head shaking with otitis externa, to facial muscle contracture and neurological deficits with otitis media. The diagnosis of ear disease is also covered in this article, which is based on clinical signs and clinical examination findings, along with diagnostic imaging, ear cytology and culture. Treatment options for rabbits with ear disease are outlined as well; these vary depending on the clinical signs, disease location and severity. Prompt diagnosis and treatment of ear disease in pet rabbits is essential to avoid progression of disease and clinical signs. This article is a useful overview for all veterinary staff treating pet rabbits in veterinary practice.
Performing surgery in goats. Part 2: surgical techniques
Authors: Dustan Benjamin
Published: March 2023

Background: Goats, like other ruminant species, will from time to time require surgicial interventions. This could be a caesarean section following dystocia in a doe while kidding, or the surgical removal of an neoplastic eye in an aging pet pygmy goat.

Aim of the article: This article, the second in a two‐part series, outlines the common surgical techniques that may be required by the general practitioner when working with caprine patients. It aims to equip veterinary practitioners with the necessary knowledge and top tips to perform some of these techniques in goats.
Pterostilbene loaded poly(vinyl alcohol)‐gelatin cryogels as potential bioactive wound dressing material
Authors: Canatar İpek , Zenger Okan , Özdaş Sibel , Baydemir Peşint Gözde
Published: March 2023

Cryogels are support materials which are good at mimicking extracellular matrix due to their excellent hydrophilicity, biocompatibility, and macroporous structure, thus they are useful in facilitating cell activities during healing process. In this study, polyvinyl alcohol‐gelatin (PVA‐Gel) based cryogel membranes loaded with pterostilbene (trans‐3,5‐dimethoxy‐4‐hydroxystilbene; PTS) (PVA‐Gel/PTS) was synthesized as wound dressing materials. PVA‐Gel and PVA‐Gel/PTS were synthesized with the polymerization yields of 96% ± 0.23% and 98% ± 0.18%, respectively, and characterized by swelling tests, Brunauer–Emmett–Teller (BET) and scanning electron microscopy (SEM) analysis. The swelling ratios were calculated as 98.6% ± 4.93% and 102% ± 5.1%, macroporosities were determined as 85% ± 2.13% and 88% ± 2.2%, for PVA‐Gel and PVA‐Gel/PTS, respectively. It was determined that PVA‐Gel and PVA‐Gel/PTS have 17 m2/g ± 0.76 m2/g and 20 m2/g ± 0.92 m2/g surface areas, respectively. SEM studies were demonstrated that they have ~100 μm pore sizes. According to 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), trypan blue exclusion and live‐dead assay results, it was observed that cell proliferation, cell number and cell viability were higher in PVA‐Gel/PTS cryogel at 24, 48, and 72 h compared to PVA‐Gel. A strong and transparent fluorescent light intensity was observed indicating higher cell population in PVA‐Gel/PTS in comparison with PVA‐Gel, according to 4′,6‐diamidino‐2‐phenylindole (DAPI) staining. SEM, F‐Actin, Giemsa staining and inverted‐phase microscope image of fibroblasts in PVA‐Gel/PTS cryogels revealed that dense fibroblast proliferation and spindle‐shaped morphology of cells were preserved. Moreover, DNA agarose gel data demonstrated that PVA‐Gel/PTS cryogels had no effect on DNA integrity. Consequently, produced PVA‐Gel/PTS cryogel can be used as wound dressing material to promote wound therapies, inducing cell viability and proliferation.
Toxicity evaluation of choline ionic liquid‐based nanocarriers of pharmaceutical agents for lung treatment
Authors: Niesyto Katarzyna , Skonieczna Magdalena , Adamiec‐Organiściok Małgorzata , Neugebauer Dorota
Published: March 2023

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, that is, p‐aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS‐2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non‐small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 h, was measured at concentration range of 3.125–100 μg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS‐2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, that is, Annexin‐V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro‐inflammatory activity of tested compounds toward cancer cells, while it was not observed against normal cell line.
Measuring and preliminary modeling of drift interception by plant species
Authors: Dunne Jonnie B. , Grant Shanique L. , Golus Jeffrey A. , Perine Jeffrey W. , Wolf Stefan , Winchell Michael , Ledson T. Mark , Whenham Ian
Published: March 2023

Currently, the concept of plant capture efficiency is not quantitatively considered in the evaluation of off‐target drift for the purposes of pesticide risk assessment in the United States. For on‐target pesticide applications, canopy capture efficiency is managed by optimizing formulations or tank‐mixing with adjuvants to maximize retention of spray droplets. These efforts take into consideration the fact that plant species have diverse morphology and surface characteristics, and as such will retain varying levels of applied pesticides. This work aims to combine plant surface wettability potential, spray droplet characteristics, and plant morphology into describing the plant capture efficiency of drifted spray droplets. In this study, we used wind tunnel experiments and individual plants grown to 10–20 cm to show that at two downwind distances and with two distinct nozzles capture efficiency for sunflower (Helianthus annuus L.), lettuce (Lactuca sativa L.), and tomato (Solanum lycopersicum L.) is consistently higher than rice (Oryza sativa L.), peas (Pisum sativum L). and onions (Allium cepa L.), with carrots (Daucus carota L.) showing high variability and falling between the two groups. We also present a novel method for three‐dimensional modeling of plants from photogrammetric scanning and use the results in the first known computational fluid dynamics simulations of drift capture efficiency on plants. The mean simulated drift capture efficiency rates were within the same order of magnitude of the mean observed rates of sunflower and lettuce, and differed by one to two orders for rice and onion. We identify simulating the effects of surface roughness on droplet behavior, and the effects of wind flow on plant movement as potential model improvements requiring further species‐specific data collection.
Risk factors for postoperative cholangitis after pancreaticoduodenectomy and evaluation of internal stenting on hepaticojejunostomy: A single‐center propensity score‐based analysis
Authors: Sakai Hiroki , Notake Tsuyoshi , Shimizu Akira , Kubota Koji , Masuo Hitoshi , Yoshizawa Takahiro , Hosoda Kiyotaka , Hayashi Hikaru , Yasukawa Koya , Soejima Yuji
Published: March 2023

Background/Purpose

This retrospective study aimed to investigate the risk factors for postoperative cholangitis (POC) after pancreaticoduodenectomy (PD) and the efficacy of stenting on hepaticojejunostomy (HJ).

Methods

We investigated 162 patients. Postoperative cholangitis occurring before and after discharge was defined as early‐onset POC (E‐POC) and late‐onset POC (L‐POC), respectively. Risk factors for E‐POC and L‐POC were identified using univariate and multivariate logistic regression analyses. Propensity score matching (PSM) between the stenting group (group S) and the non‐stenting group (group NS), and subgroup analysis in patients with risk factors were performed to evaluate the efficacy of stenting on HJ in preventing POC.

Results

Body mass index (BMI) ≥ 25 kg/m2 and preoperative non‐biliary drainage (BD) were risk factors for E‐POC and L‐POC, respectively. PSM analysis revealed that E‐POC occurrence was significantly higher in group S than in group NS (P = .045). In the preoperative non‐BD group (n = 69), E‐POC occurrence was significantly higher in group S than in group NS (P = .025).

Conclusions

BMI ≥ 25 kg/m2 and preoperative non‐BD status were risk factors for E‐POC and L‐POC, respectively. Stenting on HJ implants did not prevent POC after PD.
Unbalance between working memory task‐activation and task‐deactivation networks in epilepsy: Simultaneous EEG‐fMRI study
Authors: Qin Yun , Jiang Sisi , Xiong Siwei , Li Sipei , Fu Qiankun , Yang Lili , Du Peishan , Luo Cheng , Yao Dezhong
Published: March 2023

Working memory (WM) is a cognitive function involving emergent properties of theta oscillations and large‐scale network interactions. The synchronization of WM task‐related networks in the brain enhanced WM performance. However, how these networks regulate WM processing is not well known, and the alteration of the interaction among these networks may play an important role in patients with cognitive dysfunction. In this study, we used simultaneous EEG‐fMRI to examine the features of theta oscillations and the functional interactions among activation/deactivation networks during the n‐back WM task in patients with idiopathic generalized epilepsy (IGE). The results showed that there was more enhancement of frontal theta power along with WM load increase in IGE, and the theta power was positively correlated with the accuracy of the WM tasks. Moreover, fMRI activations/deactivations correlated with n‐back tasks were estimated, and we found that the IGE group had increased and widespread activations in high‐load WM tasks, including the frontoparietal activation network and task‐related deactivation areas, such as the default mode network and primary visual and auditory networks. In addition, the network connectivity results demonstrated decreased counteraction between the activation network and deactivation network, and the counteraction was correlated with the higher theta power in IGE. These results indicated the important role of the interactions between activation and deactivation networks during the WM process, and the unbalance among them may indicate the pathophysiological mechanism of cognitive dysfunction in generalized epilepsy.
Lactobacillus plantarumHF02 alleviates lipid accumulation and intestinal microbiota dysbiosis in high‐fat diet‐induced obese mice
Authors: Chen Haoran , Zhao Haiding , Qi Xiaofen , Sun Yue , Ma Ying , Li Qiming
Published: March 2023

BACKGROUND

Obesity is closely associated with lipid accumulation and intestinal microbiota dysbiosis. It has been proved that probiotics supplement contributes to alleviate obesity. The objective of this study was to investigate the mechanism by which Lactobacillus plantarum HF02 (LP‐HF02) alleviated lipid accumulation and intestinal microbiota dysbiosis in high‐fat diet‐induced obese mice.

RESULTS

Our results showed that LP‐HF02 ameliorated body weight, dyslipidemia, liver lipid accumulation, and liver injury in obese mice. As expected, LP‐HF02 inhibited pancreatic lipase activity in small intestinal contents and increased fecal triglyceride levels, thereby reducing dietary fat hydrolysis and absorption. Moreover, LP‐HF02 ameliorated the intestinal microbiota composition, as evidenced by the enhanced ratio of Bacteroides to Firmicutes, the decreased abundance of pathogenic bacteria (including Bacteroides, Alistipes, Blautia, and Colidextribacter) and the increased abundance of beneficial bacteria (including Muribaculaceae, Akkermansia, Faecalibaculum, and Rikenellaceae_RC9_gut_group). LP‐HF02 also increased fecal short‐chain fatty acids (SCFAs) levels and colonic mucosal thickness, and subsequently decreased serum lipopolysaccharide (LPS), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) levels in obese mice. Additionally, reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot results demonstrated that LP‐HF02 ameliorated hepatic lipid accumulation via activating the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway.

CONCLUSION

Therefore, our results indicated that LP‐HF02 could be considered as a probiotic preparation for preventing obesity. © 2023 Society of Chemical Industry.
Nutritional significance, value‐added applications, and consumer perceptions of food legumes: A review
Authors: Affrifah Nicole S. , Uebersax Mark A. , Amin Samir
Published: March 2023

Legume crops are widely grown worldwide and a primary source of proteins across many least developed countries. These food crops are inherently produced in environmentally sustainable manner and are also an economical source of plant‐based proteins versus animal‐based proteins. The nutrient composition of legumes is very rich, that is, high content of protein, fiber, and bioactive compounds and relatively lower carbohydrates than cereal crops. Although food legumes are a staple in more than 70 countries mostly in Asian, African, and South American regions, the per capita consumption in the Western countries continues to be low in spite of legumes' demonstrated health benefits. However, emerging consumer trends and preferences toward heathy foods, animal protein alternatives, and environmental concerns can enhance the consumption of legume‐based foods. The functional attributes of legume ingredients (e.g., thickening, water‐holding index, gelation, emulsification, and foaming capacity) make legumes suitable for replacing proteins from other sources. The development and marketing of legume‐based ingredients for use in various value‐added food applications have been increasing. The value‐added use of pulse protein isolates and concentrates is expanding fast with substantial use as meat extenders/replacers and meat analogs, milk substitutes, and gluten‐free applications. To increase the utilization of legumes, including legume‐based foods, it is important to focus on research and development efforts that promote “easy‐to‐cook”/prepare foods for consumers, who often avoid legumes due to long cooking times. Addressing this aspect of convenience is particularly critical in developed countries due to the busy lifestyles of consumers and potentially increase legume consumption.
Real‐world burden and treatment of chronic rhinosinusitis in Japan: A retrospective claims database analysis
Authors: Yoshikawa Mamoru , Sunaga Yoshinori , Koshiba Ryuji , Inukai Miho , Takeuchi Makiko
Published: March 2023

Objectives

Chronic rhinosinusitis (CRS) is a heterogeneous disease, which can be subdivided into CRS with (CRSwNP) or without (CRSsNP) nasal polyps. An intractable form of CRSwNP that is associated with an eosinophil‐dominant inflammatory cell infiltration (eosinophilic CRS) has become more prevalent in Japan. There is currently limited information on the burden of CRS in Japan and treatment approaches used in real‐world practice.

Methods

This retrospective, observational, comparative cohort study used information from the Japanese JMDC insurance claims database (study period April 1, 2015, to March 31, 2020). A CRS cohort was identified and matched with a control group without CRS. The primary objective was to clarify disease burden and treatment approaches by comparing comorbidities, healthcare resource utilization (HRU), and drug prescriptions in the CRS and non‐CRS groups.

Results

In total, 23,256 individuals with CRS (1762 with CRSwNP and 21,494 with CRSsNP) were matched with 23,256 controls. The mean age was 45 years and the majority of individuals were male (57%). Individuals with CRS had a higher disease burden than controls, with more frequent comorbidities (particularly, type 2 inflammatory disease [e.g., allergic rhinitis and asthma], and those caused by systemic corticosteroids [SCS]), and higher HRU (including outpatient visits, laboratory examinations and surgical procedures). Further, individuals with CRS were prescribed more medications, both for CRS (including SCS) and non‐CRS conditions, than controls.

Conclusion

In Japan, CRS is associated with a high disease burden, and multiple treatment approaches are used in affected individuals, including long‐term SCS, which is generally not recommended.

Level of Evidence

3
Structure–Property Relationships in Epoxyurethane Polymers Based on Erythritol Dicarbonate
Authors: Guo Xin , Fang Xinxin , Fan Songhong , Gao Junfei , Gu Qun
Published: March 2023

The highly reactive erythritol dicarbonate (EDC) allows facile design and preparation of solvent‐ and catalyst‐free epoxyurethane polymers. Diglycidyl ether of bisphenol‐A (DGEBA) and oligo polyhydroxyurethanes are used to produce epoxyurethane polymers (o‐PHUs). The o‐PHUs are prepared using cyclic carbonates derived from erythritol and various diamines (aliphatic amine and polyether amine) or polyamines (diethylene triamine (DETA) and triethylne tetramine (TETA)). Active secondary amino groups derived from o‐PHUs polyamines form hydrogen bonds between urethane carbonyls in epoxy hybrid networks with the highest cross‐linking density (1293 mol m−3), glass transition temperature Tg (93 °C), and ultimate tensile strength (34 MPa). And the ether bond provides a significant potential for hydrogen bonding between hydroxyl group and ether oxygen, forming strong hydrogen bond cross‐linking between molecular chains, with cross‐linking density and ultimate tensile strength comparable to polyepoxyurethane derived from polyamines, except for a lower Tg (27 °C). In addition, these polyepoxyurethanes have superior adhesion to wood, aluminum alloy, and polymethyl methacrylate (PMMA) substrates. This versatile oligo PHUs would provide a wide range of fabrication options for adhesive epoxyurethane polymers.
Chromosome Microarray Analysis for the Investigation of Deletions in Pediatric Movement Disorders: A Systematic Review of the Literature
Authors: Soliani Luca , Alcalá San Martín Adrián , Balsells Sol , Hernando‐Davalillo Cristina , Ortigoza‐Escobar Juan Darío
Published: March 2023

Background

Chromosome microarray analysis (CMA) can detect copy number variants (CNV) beyond the resolution of standard G‐banded karyotyping. De novo or inherited microdeletions may cause autosomal dominant movement disorders.

Objectives

The purpose of this study was to analyze the clinical characteristics, associated features, and genetic information of children with deletions in known genes that cause movement disorders and to make recommendations regarding the diagnostic application of CMA.

Methods

Clinical cases published in English were identified in scientific databases (PubMed, ClinVar, and DECIPHER) from January 1998 to July 2019 following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Cases with deletions or microdeletions greater than 300 kb were selected. Information collected included age, sex, movement disorders, associated features, and the size and location of the deletion. Duplications or microduplications were not included.

Results

A total of 18.097 records were reviewed, and 171 individuals were identified. Ataxia (30.4%), stereotypies (23.9%), and dystonia (21%) were the most common movement disorders. A total of 16% of the patients demonstrated more than one movement disorder. The most common associated features were intellectual disability or developmental delay (78.9%) and facial dysmorphism (57.8%). The majority (77.7%) of microdeletions were smaller than 5 Mb. We find no correlation between movement disorders, their associated features, and the size of microdeletions.

Conclusions

Our results support the use of CMA as an investigational test in children with movement disorders. As the majority of identified articles were case reports and small case series (low quality), future efforts should focus on larger prospective studies to examine the causation of microdeletions in pediatric movement disorders.
Effects of Fish Meal Replacement with Composite Mixture of Soybean Protein Hydrolysates and Other Plant Proteins on Growth Performance, Antioxidant Capacity, and Target of Rapamycin Pathway in Largemouth Bass
Authors: Wang Zhenjie , Tao Jiajie , Xie Ruitao , Zhang Yu , Zhang Haitao , Chen Naisong , Li Songlin
Published: March 2023

A feeding trial was conducted to evaluate the effect of fish meal replacement with a composite mixture of soybean protein hydrolysates and other plant proteins on growth performance, antioxidant capacity, and target of rapamycin pathway in Largemouth Bass Micropterus salmoides. Triplicate groups of Largemouth Bass were fed the diet formulated with 40% (FM40; control), 35% (FM35), 30% (FM30), or 25% (FM25) fish meal for 10 weeks. The results revealed that the best growth performance was achieved in the FM35 group, while a negative effect on growth was observed in the FM25 group. The feed intake of the FM30 and FM25 groups was significantly lower than the other two groups, while no significant difference was observed in feed efficiency ratio and protein efficiency ratio. No statistical difference was observed in the activity of serum alanine transaminase and aspartate transaminase with the replacement of fish meal. However, the replacement of fish meal with composite plant protein significantly reduced hepatic malondialdehyde content, and a significant improvement in total antioxidant capacity was observed in the FM35 group. Gene expression analysis revealed that the expression of amino acid transporter LAT1 was significantly elevated in the FM35 group, while no significant difference was observed in the LAT2 expression among different treatments. No significant difference was observed in the expression of target of rapamycin among treatments. However, the expression of ribosomal protein S6 in the FM35 and FM30 groups was significantly higher than in the other two groups, while the replacement of fish meal significantly decreased the expression of eukaryotic initiation factor 4EBP1. In summary, the composite mixture of soybean protein hydrolysates and other plant proteins can reduce the use of fish meal from 40% to 35%.
Obstructive sleep apnea and metabolic syndrome
Authors: Giampá Sara Q. C. , Lorenzi‐Filho Geraldo , Drager Luciano F.
Published: March 2023

Metabolic syndrome (MS) is a heterogeneous condition associated with increased cardiovascular risk. There is growing evidence from experimental, translational, and clinical investigations that has suggested that obstructive sleep apnea (OSA) is associated with prevalent and incident components of MS and MS itself. The biological plausibility is supportive, primarily related to one of the main features of OSA, namely intermittent hypoxia: increased sympathetic activation with hemodynamic repercussions, increased hepatic glucose output, insulin resistance through adipose tissue inflammation, pancreatic β‐cell dysfunction, hyperlipidemia through the worsening of fasting lipid profiles, and the reduced clearance of triglyceride‐rich lipoproteins. Although there are multiple related pathways, the clinical evidence relies mainly on cross‐sectional data preventing any causality assumptions. The overlapping presence of visceral obesity or other confounders such as medications challenges the ability to understand the independent contribution of OSA on MS. In this review, we revisit the evidence on how OSA/intermittent hypoxia could mediate adverse effects of MS parameters independent of adiposity. Particular attention is devoted to discussing recent evidence from interventional studies. This review describes the research gaps, the challenges in the field, perspectives, and the need for additional high‐quality data from interventional studies addressing the impact of not only established but promising therapies for OSA/obesity.
Changes in body composition and homeostatic control of resting energy expenditure during dietary weight loss
Authors: Müller Manfred J. , Heymsfield Steven B. , Bosy‐Westphal Anja
Published: March 2023

Adaptive thermogenesis (AT) is the mass‐independent decrease in energy expenditure (EE) in response to caloric restriction and weight loss. AT becomes manifest throughout all periods of weight loss and persists during subsequent weight maintenance. AT occurs in resting and nonresting energy expenditure as ATREE and ATNREE, respectively. ATREE appears in different phases of weight loss, each with likely different mechanisms. By contrast, during weight maintenance after weight loss, ATNREE exceeds ATREE. Some of the mechanisms of AT are known now and others are not. Future studies on AT will need an appropriate conceptual framework within which to design experiments and interpret results.
Safety of elexacaftor/tezacaftor/ivacaftor dose reduction: Mechanistic exploration through physiologically based pharmacokinetic modeling and a clinical case series
Authors: Hong Eunjin , Li Regina , Shi Alan , Almond Lisa M. , Wang Joshua , Khudari Amin Z. , Haddad Soumar , Sislyan Sarkis , Angelich Marissa , Chung Peter S. , Rao Adupa P. , Beringer Paul M.
Published: March 2023

Introduction

Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is associated with significant improvement in lung function in people with cystic fibrosis (pwCF); however, some patients experience adverse effects (AEs) including hepatotoxicity. One potential strategy is dose reduction in ETI with the goal of maintaining therapeutic efficacy while resolving AEs. We report our experience of dose reduction in individuals who experienced AEs following ETI therapy. We provide mechanistic support for ETI dose reduction by exploring predicted lung exposures and underlying pharmacokinetics–pharmacodynamics (PK‐PD) relationships.

Method

Adults prescribed ETI who underwent dose reduction due to the AEs were included in this case series, and their percent predicted forced expiratory volume in 1 s (ppFEV1) and self‐reported respiratory symptoms were collected. The full physiologically based pharmacokinetic (PBPK) models of ETI were developed incorporating physiological information and drug‐dependent parameters. The models were validated against available pharmacokinetic and dose–response relationship data. The models were then used to predict lung concentrations of ETI at steady‐state.

Results

Fifteen patients underwent dose reduction in ETI due to AEs. Clinical stability without significant changes in ppFEV1 after dose reduction was observed in all patients. Resolution or improvement of AEs occurred in 13 of the 15 cases. The model‐predicted lung concentrations of reduced dose ETI exceeded the reported half maximal effective concentration (EC50) from measurement of in vitro chloride transport, providing a hypothesis as to why therapeutic efficacy was maintained.

Conclusion

Albeit in a small number of patients, this study provides evidence that reduced ETI doses in pwCF who have experienced AEs may be effective. The PBPK models enable exploration of a mechanistic basis for this finding by simulating target tissue concentrations of ETI that can be compared with drug efficacy in vitro.
A Physics‐Aware Deep Learning Model for Energy Localization in Multiscale Shock‐To‐Detonation Simulations of Heterogeneous Energetic Materials
Authors: Nguyen Phong C. H , Nguyen Yen‐Thi , Seshadri Pradeep K. , Choi Joseph B. , Udaykumar H. S , Baek Stephen
Published: March 2023

Predictive simulations of the shock‐to‐detonation transition (SDT) in heterogeneous energetic materials (EM) are vital to the design and control of their energy release and sensitivity. Due to the complexity of the thermo‐mechanics of EM during the SDT, both macro‐scale response and sub‐grid mesoscale energy localization must be captured accurately. This work proposes an efficient and accurate multiscale framework for SDT simulations of EM. We introduce a new approach for SDT simulation by using deep learning to model the mesoscale energy localization of shock‐initiated EM microstructures. The proposed multiscale modeling framework is divided into two stages. First, a physics‐aware recurrent convolutional neural network (PARC) is used to model the mesoscale energy localization of shock‐initiated heterogeneous EM microstructures. PARC is trained using direct numerical simulations (DNS) of hotspot ignition and growth within microstructures of pressed HMX material subjected to different input shock strengths. After training, PARC is employed to supply hotspot ignition and growth rates for macroscale SDT simulations. We show that PARC can play the role of a surrogate model in a multiscale simulation framework, while drastically reducing the computation cost and providing improved representations of the sub‐grid physics. The proposed multiscale modeling approach will provide a new tool for material scientists in designing high‐performance and safer energetic materials.
Mechanism on Material Strengthening of Metastable Precipitate and Edge Dislocation in Al–Mg–Si Alloy
Authors: Kong Shining , Liu Qingfeng , Zhang Zhao
Published: March 2023

The metastable precipitate β″ plays a key role in material strengthening in Al–Mg–Si alloys. To investigate the mechanism on material strengthening of metastable precipitates, the interaction between β″ metastable precipitates and edge dislocations is studied using molecular dynamics. It is indicated in the results that the precipitate can be overcome by shearing without the formation of Orowan loops in case of smaller precipitate sizes. By increasing the temperature and reducing the shear strain rate, the critical resolved shear stress (CRSS) can be decreased. Larger precipitate sizes can lead to higher CRSS due to larger interaction area. Shear deformation can be clearly found on the precipitate when dislocations interact with the precipitate. When newly generated dislocations further interact with the sheared precipitate, the strengthening can be reduced due to the smaller cut width. This is the reason that strain hardening decreases with the increase of plastic deformation in macro scale.
Growth of (101¯1) Semipolar GaN‐Based Light‐Emitting Diode Structures on Silicon‐on‐Insulator
Authors: Wannous Beatrice , Coulon Pierre-Marie , Dupré Ludovic , Rol Fabian , Rochat Névine , Zuniga-Perez Jesus , Vennéguès Philippe , Feuillet Guy , Templier François
Published: March 2023

The growth and characterization of semipolar GaN buffer, InGaN multiple quantum wells (MQWs), and light‐emitting diode (LED) structure on patterned silicon‐on‐insulator (SOI) substrates, implementing the aspect ratio technique (ART), are reported. The early growth stages of GaN result in continuous and uniform stripes with small height variations that cause the formation of chevrons. Three coalescence strategies are tested to improve surface morphology and optical quality. Scanning electron microscopy identifies no crack formation but undulations of the surface. A roughness of ≈10 nm is measured by atomic force microscopy on large areas. The impact of MQW growth temperature shows similar surface morphology in terms of undulations and roughness. Room temperature photoluminescence spectra show wavelength emission redshifting when decreasing the MQW growth temperature. Room‐temperature cathodoluminescence (CL) highlights first the presence of threading dislocations (TDs) in between the coalescence boundary despite the use of the ART technique. Second, CL shows a spatially homogeneous emission wavelength of around 485 nm only perturbed by lower‐wavelength emission (455 nm) arising from the chevrons. Blue LED structures exhibit uniform emission wavelength at 450 nm, having a crack‐free surface, and roughness of ≈5 nm. These results pave the way for the fabrication of semipolar micro‐LEDs on SOI substrates.
Utilization of treatment effect on a surrogate endpoint for planning a study to evaluate treatment effect on a final endpoint
Authors: Quan Hui , Xu Zhixing , Luo Junxiang , Paux Gautier , Cho Meehyung , Chen Xun
Published: March 2023

To design a phase III study with a final endpoint and calculate the required sample size for the desired probability of success, we need a good estimate of the treatment effect on the endpoint. It is prudent to fully utilize all available information including the historical and phase II information of the treatment as well as external data of the other treatments. It is not uncommon that a phase II study may use a surrogate endpoint as the primary endpoint and has no or limited data for the final endpoint. On the other hand, external information from the other studies for the other treatments on the surrogate and final endpoints may be available to establish a relationship between the treatment effects on the two endpoints. Through this relationship, making full use of the surrogate information may enhance the estimate of the treatment effect on the final endpoint. In this research, we propose a bivariate Bayesian analysis approach to comprehensively deal with the problem. A dynamic borrowing approach is considered to regulate the amount of historical data and surrogate information borrowing based on the level of consistency. A much simpler frequentist method is also discussed. Simulations are conducted to compare the performances of different approaches. An example is used to illustrate the applications of the methods.
Response to ‘Eruptive Keratoacanthomas Associated with Dupilumab Therapy’
Authors: Patchinsky Alexandra , Kalita Victoria , Muller Philippe , Petitpain Nadine
Published: March 2023

Case of a patient developing multiple rashes of squamous cell carcinoma 6 weeks after the introduction of dupilumab due to atopic eczema.
New Ligandless C−H Activation Procedure for The Decoration of C‐3 Position of 1H‐Indazole Derivatives
Authors: Guariento Sara , Chesi Mattia , Bellina Fabio , Copelli Diego , Venturi Luca , Bua Emanuela , Moretti Elisa , Ronchi Paolo
Published: March 2023

Arylation of heteroaromatic rings is one of the most important strategy for the chemical space exploration (e. g. applied in medicinal chemistry). In the last two decades C−H activation reactions emerged as powerful and more sustainable synthetic methods for this kind of functionalization if compared to the classical Pd‐catalysed cross‐coupling reactions (e. g. Suzuki, Stille, Negishi, Hiyama). A further step in the direction of greater sustainability has been done developing ligandless C−H activation procedures with higher appeal for industrial application. Among the various N‐based heterocycles exploited in medicinal chemistry, there is no reported ligandless C−H activation for 1H‐indazole core, although its potential pharmaceutical applications. In this work we describe a novel synthetic procedure for the direct arylation/heteroarylation of C‐3 position of 1H‐indazole which was optimized using the Design of Experiment (DoE) (yield up to 72 %) and confirmed a fulfilling robustness among various aryl/heteroaryl and indazole scopes.