bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking Biomolecular Activity through Pd‐Catalyzed Azides Reduction†
Authors: Fu Fang , Xiong Wei , Xu Xinyan , Liu Yongjie , Li Ming , Qi Qianqian , Liu Xingyu , Zhang Yuanyuan , Tian Tian , Zhou Xiang
Published: May 2024

Comprehensive Summary

Pd‐mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules, precise regulation of protein function, and cellular engineering. However, the availability of cleavable "caging" groups is quite limited, and their application in nucleic acid modification has seldom been reported. Herein, we introduce a method based on Pd‐catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules. We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function, followed by the release of biological activity through Pd‐catalyzed NaBH4 reduction amination reaction. This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes, prodrugs, and to regulate the biological function of RNA, including reverse transcription extension, binding to ligands, and cleavage activity of the CRISPR‐Cas system. All results confirm that this strategy provides an efficient and controllable "OFF to ON" biological switch, capable of achieving significant regulatory effects substoichiometrically, and is expected to be extended to other biological applications.
Efficient Chemical Synthesis and Folding of Mirror‐Image Tropomyosin Receptor Kinase A Using the Strategy of Removable Glycosylation Modification†
Authors: Wang Tongyue , Shi Weiwei , Chu Guo‐Chao , Li Yi‐Ming
Published: May 2024

Comprehensive Summary

The strategy of removable glycosylation modification was used to overcome the low‐efficiency problem encountered in the chemical synthesis of the mirror‐image D‐version of the immunoglobulin (Ig)‐like domain of tropomyosin receptor kinase A (DlgCTrkA), a protein molecule needed for mirror‐image screening of D‐peptide ligands targeting this cell membrane receptor. It was found that O‐linked‐β‐N‐acetyl‐D‐glucosamine (O‐GlcNAc) modification at DSer312, or DSer320 can significantly improve the efficiency of DlgCTrkA synthesis and folding, while O‐GlcNAc modification at DSer330 showed barely any improvement. This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult‐to‐obtain proteins. It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy.
Extractive Mass Transfer of Zr(IV) into a Hydrophobic Ionic Liquid Medium Containing Diglycolamide Extractant: Solvent Extraction and Spectroscopic Analysis
Authors: Rout Alok , Ramanathan Nagarajan
Published: May 2024

Solvent extraction of Zr(IV) in ionic liquid (IL) medium is less known and Zr(IV) – IL chemistry indeed needs exploration to realize the coordination approach of Zr(IV) in IL phase. In view of this, in the present work, a strongly hydrophobic imidazolium based IL: 1‐methyl‐3‐octylimidazolium bis(trifluoromethylsulfonyl)imide ([C8mim][NTf2]) as the medium containing a diglycolamide (DGA) extractant: N,N,N’,N’‐tetra‐n‐octyldiglycolamide (TODGA) was opted to understand the extraction behavior of Zr(IV) from nitric acid medium. Different experimental parameters such as the concentration of initial nitric acid, initial feed metal concentration, equilibration time and ligand concentration were tuned to unravel the extraction efficiency of the proposed IL phase towards Zr(IV). The extraction scenario was completely dependent on the hydrophobicity of IL diluent and increasing extraction trend with an increase in feed acidity along with the coordination of two TODGA molecules ensured Zr(IV) ‐ complex formation in a neutral solvation mechanistic pathway. The extraction trend of Zr(IV) was compared with molecular diluent (n‐dodecane (n‐DD)) containing TODGA and a phase modifier: N,N‐dihexyloctanamide (DHOA). The coordination aspect of Zr(IV) with ligand in IL phase was ascertained spectroscopically to validate Zr(IV) loading in IL phase. Thermodynamics of Zr(IV) extraction revealed the nature of the extraction process and the complex formation.
Association of Pharmacogenomic Phenotypes in CYP2D6, CYP2C9, CYP2C19, and CYP3A5 on Polypharmacy in Veterans
Authors: Krulikas Linas , Bates Jill , Chanfreau Catherine , Coleman Heather , Dalton Shawn , Voora Deepak
Published: May 2024

The Department of Veterans Affairs (VA) utilizes a pharmacogenomic (PGx) program that analyzes specific “pharmacogenes.” This study evaluates the effect that pharmacogenes may have on prevalence of polypharmacy. This retrospective cohort study included patients with VA prescriptions who underwent PGx testing. We quantified prescriptions active or recently expired at the time of PGx testing. We constructed two co‐primary polypharmacy (≥10 medications) end points: (i) based on all medications and (ii) requiring that at least one medication was affected by a pharmacogene of interest. Pharmacogenes and actionable phenotypes of interest included poor and ultrarapid metabolizers for CYP2D6, CYP2C9, and CYP2C19 and intermediate and normal metabolizers for CYP3A5. Patients were classified as having 0, 1, and 2+ total phenotypes across all genes. Of the 15,144 patients screened, 13,116 met eligibility criteria. Across phenotype cohorts, there was no significant association with polypharmacy using all medications, number of total medications, or number of medications affected by phenotypes. However, there was a significant difference in patients with polypharmacy prescribed ≥1 medication impacted by PGx across phenotype groups: 2,514/4,949 (51%), 1,349/2,595 (52%), 204/350 (58%) (P = 0.03, OR 1.31, 95% CI 1.02–1.67). The median number of medications affected by PGx phenotypes with ≥1 PGx‐impacted medication across phenotype groups was a median of 0 (IQR 0, 0), 0 (IQR 0, 0), and 1 (IQR 0, 1) (P < 0.001). In patients prescribed ≥1 medication impacted by PGx, those with more actionable pharmacogenomic phenotypes were more likely to meet polypharmacy criteria.
Validation of Single‐Nucleotide Mosaic Variants Through Droplet Digital PCR
Authors: Grochowski Christopher M. , Gibbs Richard A. , Doddapaneni Harsha
Published: May 2024

The detection, validation, and subsequent interpretation of potentially mosaic single‐nucleotide variants (SNV) within next‐generation sequencing data remains a challenge in both research and clinical laboratory settings. The ability to identify mosaic variants in high genome coverage sequencing data at levels of ≤1% underscores the necessity for developing guidelines and best practices to verify these variants orthogonally. Droplet digital PCR (ddPCR) has proven to be a powerful and precise method that allows for the determination of low‐level variant fractions within a given sample. Herein we describe two precise ddPCR methods using either a fluorescent TaqMan hydrolysis probe approach or an EvaGreen fluorescent dye protocol. The TaqMan approach relies on two different fluorescent probes (FAM and HEX/VIC), each designed to amplify selectively only in the presence of a single nucleotide change denoting the variant or reference position. The fractional abundance is then calculated to determine the relative quantities of both alleles in the final sample. The EvaGreen protocol relies on two independent reactions with oligonucleotide primers designed with the single nucleotide change denoting the variant at the penultimate position of the primer. The relative amplification efficiency of both primer sets (reference and variant) can be compared to determine the mosaic level of a given variant. As the cost of high‐coverage sequencing continues to decrease, the identification of potentially mosaic variants will also increase. The approaches outlined will allow clinicians and researchers a more precise determination of the true mosaic level of a given variant allowing them to better assess not only its potential pathogenicity but also its possible recurrence risk when offering genetic counseling to families. © 2024 Wiley Periodicals LLC.

Basic Protocol: Droplet digital PCR (ddPCR) with TaqMan hydrolysis probes

Alternate Protocol: EvaGreen oligonucleotide‐specific ddPCR
Cytokine/Antibody Fusion Protein Design and Evaluation
Authors: Fabilane Charina S. , Stephenson A. Carson , Leonard Elissa K. , VanDyke Derek , Spangler Jamie B.
Published: May 2024

Cytokines constitute a class of secreted proteins that activate transmembrane receptors to coordinate a vast array of physiological processes, particularly those related to immune activity. Due to their vital role in immune regulation, cytokines have garnered great interest as potential therapeutic agents. Unfortunately, the clinical success of cytokine drugs has been limited by their multifunctional activities, which hinder therapeutic performance and lead to harmful toxicities. In addition, the strikingly short circulation half‐life of cytokines further hampers their efficacy as drugs. To overcome the translational challenges associated with natural cytokines, significant efforts have focused on engineering cytokines to target their activities and improve their pharmacological properties. One such strategy is the design of fusion proteins that tether a cytokine to an anti‐cytokine antibody that selectively biases its functions and extends its serum half‐life. These cytokine/antibody fusion proteins (termed immunocytokines) assemble intramolecularly to bias cytokine signaling behavior through multi‐layered structural and molecular effects. Here, we present a detailed workflow for the design, production, and functional validation of intramolecularly assembled immunocytokines. In‐depth procedures are presented for gene manipulation, mammalian cell‐based expression and purification, binding analysis via bio‐layer interferometry, and interrogation of cytokine signaling activity on human primary cells. In contrast with immunocytokines in which the tethered cytokine and antibody do not bind one another, intramolecularly assembled immunocytokines require special considerations with respect to their production to avoid oligomerization and/or aggregation. The protocol herein was developed based on experience with immunocytokines that incorporate interleukin‐2 (IL‐2); however, this modular approach can be extended to any cytokine of interest for a broad range of biomedical applications. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Design and generation of immunocytokine genes

Basic Protocol 2: Immunocytokine expression and purification

Basic Protocol 3: Validation of immunocytokine assembly and binding by bio‐layer interferometry

Basic Protocol 4: Analysis of immunocytokine signaling on human primary cells
Alkaline Modified Mesoporous Silica Supported Ruthenium Catalyst for Improved α‐Amino Acid Synthesis
Authors: Gao Mingxia , Ma Jiping , Fan Xiaomeng , Shi Song , Xu Jie
Published: May 2024

Amino acids are a class of compounds with wide‐ranging applications. The synthesis of amino acids from biomass‐derived α‐keto acids and ammonia is a sustainable way but the unstable primary imine intermediates (R−C=NH) easily form oligomers. Herein, targeting this problem, alkaline modified mesoporous silica was employed as a support for ruthenium (Ru/M‐MCM‐41), which could be used as a bifunctional catalyst in the reductive amination of α‐keto acids to synthesize α‐amino acids. The incorporation of Sr improved the dispersion of Ru nanoparticles and enhanced metal‐support interactions via electron transfer from Sr to Ru, and the active Ru sites could efficiently hydrogenate primary imine intermediates to α‐amino acids, thus prohibiting the formation of oligomers. Moreover, the Sr‐dopant introduces base sites that could catalyze the hydrolysis of oligomers back to primary imine intermediates and finally hydrogenated to α‐amino acids. As a result, >99 % yield of glycine was achieved from glyoxylic acid over Ru/Sr‐MCM‐41, which is nearly three times that achieved over Ru/MCM‐41 (32.2 %).
Amplitude modulation and nonlinear dynamics of small amplitude ion‐acoustic waves in five component cometary plasmas
Authors: Kolay Debaditya , Dutta Debjit , Sahu Biswajit
Published: May 2024

The formation and propagation dynamics of the finite‐amplitude ion‐acoustic wave (IAW) structures (e.g., soliton, breather, rogue wave, etc.) is theoretically investigated in a plasma comprising of kappa distributed solar and cometary electrons of different temperatures, a hot drift ion component, and a pair of oppositely charged oxygen ion components. The modified‐KdV (mKdV) equation is derived in order to study the propagation dynamics of the ion‐acoustic solitary wave (IASW). It is then converted into the nonlinear Schrödinger equation (NLS) through appropriate algebraic manipulation in order to observe the amplitude modulation of the IAWs. Also, the appearance of envelope soliton and the possibility of breather structure formation have been studied from the NLS equation. The dependence of plasma parameters on the formation and propagation of IAW structures has been briefly discussed. The modified‐KdV equation is reduced in a dynamical system through the application of coordinate transformation. The existence of finite‐amplitude nonlinear and supernonlinear IAWs is demonstrated by phase plane analysis. Due to the fact that the results are primarily associated with cometary plasma, they possibly provide greater insight of the nonlinear characteristics of cometary plasma.
Population density and ranging behaviour of a generalist carnivore varies with human population
Authors: Alting Brendan F. , Pitcher Benjamin J. , Rees Matthew W. , Ferrer‐Paris José R. , Jordan Neil R.
Published: May 2024

Canid species are highly adaptable, including to urban and peri‐urban areas, where they can come into close contact with people. Understanding the mechanisms of wild canid population persistence in these areas is key to managing any negative impacts. The resource dispersion hypothesis predicts that animal density increases and home range size decreases as resource concentration increases, and may help to explain how canids are distributed in environments with an urban‐natural gradient. In Australia, dingoes have adapted to human presence, sometimes living in close proximity to towns. Using a targeted camera trap survey and spatial capture‐recapture models, we estimated spatial variation in the population density and detection rates of dingoes on Worimi Country in the Great Lakes region of the NSW coast. We tested whether dingo home range and population densities varied across a gradient of human population density, in a mixed‐use landscape including, urban, peri‐urban, and National Park environs. We found human population density to be a strong driver of dingo density (ranging from 0.025 to 0.433 dingoes/km2 across the natural‐urban gradient), and to have a negative effect on dingo home range size. The spatial scale parameter changed depending on survey period, being smaller in the peak tourism period, when human population increases in the area, than in adjacent survey periods, potentially indicating reduced home range size when additional resources are available. Our study highlights the potential value of managing anthropogenic resource availability to manage carnivore densities and potential risk of human‐carnivore interactions.
Chronic wasting disease alters the movement behavior and habitat use of mule deer during clinical stages of infection
Authors: Barrile Gabriel M. , Cross Paul C. , Stewart Cheyenne , Malmberg Jennifer , Jakopak Rhiannon P. , Binfet Justin , Monteith Kevin L. , Werner Brandon , Jennings‐Gaines Jessica , Merkle Jerod A.
Published: May 2024

Integrating host movement and pathogen data is a central issue in wildlife disease ecology that will allow for a better understanding of disease transmission. We examined how adult female mule deer (Odocoileus hemionus) responded behaviorally to infection with chronic wasting disease (CWD). We compared movement and habitat use of CWD‐infected deer (n = 18) to those that succumbed to starvation (and were CWD‐negative by ELISA and IHC; n = 8) and others in which CWD was not detected (n = 111, including animals that survived the duration of the study) using GPS collar data from two distinct populations collared in central Wyoming, USA during 2018–2022. CWD and predation were the leading causes of mortality during our study (32/91 deaths attributed to CWD and 27/91 deaths attributed to predation). Deer infected with CWD moved slower and used lower elevation areas closer to rivers in the months preceding death compared with uninfected deer that did not succumb to starvation. Although CWD‐infected deer and those that died of starvation moved at similar speeds during the final months of life, CWD‐infected deer used areas closer to streams with less herbaceous biomass than starved deer. These behavioral differences may allow for the development of predictive models of disease status from movement data, which will be useful to supplement field and laboratory diagnostics or when mortalities cannot be quickly retrieved to assess cause‐specific mortality. Furthermore, identifying individuals who are sick before predation events could help to assess the extent to which disease mortality is compensatory with predation. Finally, infected animals began to slow down around 4 months prior to death from CWD. Our approach for detecting the timing of infection‐induced shifts in movement behavior may be useful in application to other disease systems to better understand the response of wildlife to infectious disease.
It's not easy being green: Comparing typical skin colouration among amphibians with colour abnormalities associated with chromatophore deficits
Authors: Gould John , McHenry Colin
Published: May 2024

Amphibians can obtain their colour from a combination of several different pigment and light reflecting cell types called chromatophores, with defects in one or several of the cells leading to colour abnormalities. There is a need for better recording of colour abnormalities within wild amphibian populations, as this may provide baseline data that can be used to determine changes in environmental conditions and population dynamics, such as inbreeding. In this study, we provide records of several types of chromatophore deficiencies, including those involving iridophores, xanthophores and melanophores, among two Australian tree frog species; the green and golden bell frog, Litoria aurea, and the eastern dwarf tree frog, L. fallax. We explore these colour abnormalities in terms of the chromatophores that have likely been affected and associated with their expression, in combination with typical colour phenotypes, colour variations and colour changes for these species. We intend for our photographs to be used as a visual guide that addresses the need for more accessible information regarding the physical manifestation of different chromatophore defects among amphibians.
Spatial ecology and microhabitat selection of the nocturnal pitviper Viridovipera stejnegeri (Squamata: Viperidae) in relation to prey
Authors: Tan Song‐Wen , Wu Ya‐Yong , Wang Jia‐Jun , Lyu Bing , Yu Min , Zhang He , Guo Peng , Shi Lei
Published: May 2024

Habitat is fundamental for facilitating various life activities in animals, for instance, snakes procure essential energy for survival and reproduction by selecting ambush microhabitats. While there has been extensive research on the selection of microhabitat for feeding in terrestrial and aquatic snakes, little is known about arboreal snakes. In the present study, we analyzed the ambush microhabitat preferences of Viridovipera stejnegeri, a widely distributed Asian pitviper in China, conducted association analysis between snake microhabitat and prey microhabitat and abundance to determine the ro5le of microhabitat selection in feeding. Employing random forest analysis and habitat selection functions, we further constructed a predictive framework for assessing the probability of ambush site selection by V. stejnegeri. Our results revealed that V. stejnegeri exhibited a distinct microhabitat preference for ambush prey. Among the 13 environmental factors assessed, V. stejnegeri showed pronounced preferences towards 12 of these factors, including climatic factors, geographical factors, and vegetation factors. Furthermore, although the preferences of V. stejnegeri overlapped substantially with those of its prey across multiple habitat factors, food abundance shows no significant association with various habitat factors of V. stejnegeri, and does not have significant predictive effect on habitat selection of V. stejnegeri. Therefore, we infer that V. stejnegeri does not preferentially select microhabitats with the highest food abundance, which does not support the hypothesis that “snakes select habitats based on the spatial distribution of prey abundance.” By analyzing the characteristics of vegetation, geography, and climate, we conclude that V. stejnegeri tends to choose microhabitats with better ambush conditions to increase attack success rate, thereby achieving the optimal feeding success rate at the microhabitat scale, which is in line with the predictions of optimal foraging theory. This study provides new insights into the predation ecology and habitat selection of snakes.
The influence of climate and management on transpiration of residential trees during a bark beetle infestation
Authors: Litvak Elizaveta , Pataki Diane E.
Published: May 2024

Trees in residential environments are affected by a unique combination of environmental and anthropogenic factors, including occasional insect outbreaks that are increasing in frequency and severity due to climate change. We studied loblolly pine trees infested by bark beetles in a residential backyard in a southeastern US city. We investigated the responses of tree and stand‐level transpiration to environmental factors (solar radiation, atmospheric vapor pressure deficit, and soil moisture), severe weather events (strong winds and heavy storms), bark beetle infestation, and human actions (insecticide treatments and tree removals). We used constant heat dissipation probes to make continuous sap flux measurements (J0) in tree boles. Over 22 months of the study, J0 of trees with confirmed infestation decreased from ~90 to ~60 g cm−2 day−1 and J0 of the rest of the trees increased from ~60 to ~80 g cm−2 day−1. One infested tree died, as its J0 steadily declined from 110 g cm−2 day−1 to zero over the course of 2 months, followed by a loss of foliage and visible signs of severe infestation 6 months later. J0 was sensitive to variations in incoming solar radiation and atmospheric vapor pressure deficit. In most trees, J0 linearly responded to soil water content during drought periods. Yet despite complex dynamics of J0 variations, plot‐level transpiration at the end of the study was the same as at the beginning due to compensatory increases in tree transpiration rates. This study highlights the intrinsic interplay of environmental, biotic, and anthropogenic factors in residential environments where human actions may directly mediate ecosystem responses to climate.
Demonstration of application of redox flow battery for securing demand‐supply reserve power and improvement of grid resiliency
Authors: Omine Eitaro , Murakami Shinichi , Kusunose Nobuhiko , Kitano Riichi , Ooka Toshio , Shibata Toshikazu
Published: May 2024

In order to achieve net‐zero carbon emissions by introducing enormous amount of renewable energy, it is essential to secure the reserve power to improve the power quality of the grid. On the other hand, improvement of the grid resiliency is also needed in case of emergency such as outage of the grid. The energy storage system can be the solution for both of securing the reserve power and improving grid resiliency. The authors have conducted demonstration project to validate the applicability of Redox Flow (RF) battery for securing the reserve power and improving grid resiliency. The results of the demonstration validated that the RF battery makes it possible to be used as reserve power and earn revenue through energy and ancillary market transactions during normal operations, in addition to providing power to blackout areas or the areas that outages are assumed, as an independent power source, during an emergency such as natural disasters and planned outages.
Proposal of angle detection method for concentrated winding bearingless motors with less magnetic interference due to current
Authors: Miyoshi Masahito , Nakamura Yuichiro , Furutani Shinichi , Kajino Keita , Sugimoto Hiroya
Published: May 2024

This paper proposes a method for detecting the angle of a bearingless motor with less magnetic interference due to the current. Bearingless motors have suspension windings and motor windings that generate leakage flux. Owing to this electromagnetic phenomenon, the signal of the linear Hall‐effect sensor for angle detection is disturbed, and it has to be avoided to place Hall sensors near the winding conventionally. To solve this interference problem, this paper clarifies the ideal combinations between sensor positions and the number of poles and slots of concentrated winding bearingless motors.
In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure
Authors: Pfeiffer Michael , Boehmer John , Gorcsan John , Eguchi Shunsuke , Orihara Yoshiyuki , Perl Michal Laufer , Eigler Neal , Abraham William T. , Villota Julio Nuñez , Lee Elizabeth , Bayés‐Genís Antoni , Moravsky Gil , Kar Saibal , Zile Michael R. , Holcomb Richard , Anker Stefan D. , Stone Gregg W. , Rodés‐Cabau Josep , Lindenfeld JoAnn , Bax Jeroen J.
Published: May 2024

Aims

Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE).

Methods and results

Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12.

Conclusions

When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.
Effect of a gamified mobile‐based self‐management application on disease activity index, quality of life, and mental health in adults with inflammatory bowel disease: A protocol of a randomized controlled trial study
Authors: Norouzkhani Narges , Faramarzi Mahbobeh , Bahari Ali , Shokri Shirvani Javad , Shirvani Yeganeh Ebrahimnia , Eslami Saeid , Tabesh Hamed
Published: May 2024

Background and Aims

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal tract disease subdivided into Crohn's disease (CD) and ulcerative colitis (UC). There is currently no cure for IBD, and individuals with IBD frequently experience a lower health‐related quality of life (HRQOL) than the general population. Gamification has become an increasingly popular topic in recent years. Adapting game design concepts to nongaming contexts represents a novel and potential approach to changing user engagement. This study will be conducted with the aim of evaluating the effect of a gamified mobile‐based self‐management application on disease activity index, quality of life, and mental health in adults with IBD.

Methods

A multicenter, parallel, two‐arm, exploratory randomized controlled trial with a 6‐month follow‐up per patient will be designed to compare the impact of the gamified mobile‐based tele‐management system on primary and secondary health outcomes and outpatient visits in 210 patients with all types of IBD which are divided equally into a control group with standard care and an intervention group which will use the developed mobile application named MY IBD BUDDY. All patients will attend study visits at baseline, 12 and 24 weeks, and routine IBD clinic visits or telephone consultations based on randomization group assignment. Disease activity or disease activity index, mental health (anxiety and depression) symptoms, quality of life, self‐efficacy, and IBD‐specific knowledge will be measured at baseline with two follow‐ups at 12 and 24 weeks.

Conclusions

In sum, the outcomes of our trial will demonstrate the impact of the gamified mobile‐based self‐management system on disease activity, quality of life, and anxiety and depression by means of interactive care and patient empowerment.

Trial Registration

IRCT: IRCT20200613047757N1. Registered November 16, 2021. Prospectively registered and visible at OSF (https://doi.org/10.17605/OSF.IO/AWFY9).
Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway
Authors: Zhang Meng , Zhi Deyuan , Liu Pei , Wang Yajun , Duan Meili
Published: May 2024

Background

Dioscin has many pharmacological effects; however, its role in sepsis‐induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model.

Methods

The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4‐Hydroxy‐2‐nonenal (4‐HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B‐cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated‐p65 (p‐p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real‐time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and dihydroethidium staining assays.

Results

Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4‐HNE level in SIC rats. Dioscin reversed LPS‐induced reduction on SOD, CAT, GSH, and Bcl‐2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p‐p65/p65 value in LPS‐induced H9c2 cells.

Conclusion

Protective effects of Dioscin against LPS‐induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.
Knowledge framework of intravenous immunoglobulin resistance in the field of Kawasaki disease: A bibliometric analysis (1997−2023)
Authors: Zhang Jiaying , Huang Hongbiao , Xu Lei , Wang Shuhui , Gao Yang , Zhuo Wenyu , Wang Yan , Zheng Yiming , Tang Xuan , Jiang Jiaqi , Lv Haitao
Published: May 2024

Background

Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research.

Methods

Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots.

Results

Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and the Journal of Pediatrics had the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers.

Conclusion

Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor‐alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS‐C). “Treatment,” “risk factor,” and “prediction” were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high‐throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.
Parental sensitivity and family conversation: A naturalistic longitudinal study with both mothers and fathers across three time‐points in early infancy
Authors: Fink Elian , Foley Sarah , Browne Wendy , Hughes Claire
Published: May 2024

Parental verbal sensitivity is known to promote child language skills, but few studies have considered: (a) links between global (i.e., verbal, behavioral, and affective) measures of parental sensitivity and infant‐initiated conversations, an important precursor to language development; (b) whether maternal and paternal sensitivity show similar links with infant‐initiated conversation; or (c) the transactional role of infant conversation for later parental sensitivity. Addressing these gaps, this study of 186 British first‐time parents (93 families) examines the developmental dynamics between parental sensitivity and infant communication across the first year of life. We explore; (i) the role of maternal and paternal sensitivity (assessed during structured home observations at 4 months post‐partum) for parent‐infant conversational interactions at 7 months (indexed by day‐long naturalistic recordings), and (ii) whether these mother‐infant and father‐infant conversations at 7 months shape maternal and paternal sensitivity at 14 months (also assessed via structured home observations). For both male and female infants, maternal (but not paternal) sensitivity at 4 months predicted infant vocalisations and conversational initiation at 7‐months. By contrast, neither index of infant talk predicted maternal or paternal sensitivity at 14 months. Together these findings refine understanding of theoretical models of social development and suggest new possibilities for future research.
Molecular Epidemiology and Antifungal Susceptibility Profile in Nakaseomyces glabrata Species Complex: A 5‐Year Countrywide Study
Authors: Salimi Maryam , Javidnia Javad , Faeli Leila , Moslemi Azam , Hedayati Mohammad Taghi , Haghani Iman , Aghili Seyed Reza , Moazeni Maryam , Badiee Parisa , Roudbari Maryam , Zarrinfar Hossein , Mohammadi Rasoul , Lotfali Ensieh , Nouripour‐Sisakht Sadegh , Seyedmousavi Seyedmojtaba , Shokohi Tahereh , Abastabar Mahdi
Published: May 2024

Background

The current study aimed to identify Iranian Nakaseomyces (Candida) glabrata complex species in the clinical isolates and determine their antifungal susceptibility profile.

Methods

In total, 320 N. glabrata clinical isolates were collected from patients hospitalized in different geographical regions of Iran. The initial screening was performed by morphological characteristics on CHROMagar Candida. Each isolate was identified by targeting the D1/D2 rDNA using a multiplex‐PCR method. To validate the mPCR method and determine genetic diversity, the ITS‐rDNA region was randomly sequenced in 40 isolates. Additionally, antifungal susceptibility was evaluated against nine antifungal agents following the CLSI M27‐A4 guidelines.

Results

All clinical isolates from Iran were identified as N. glabrata. The analysis of ITS‐rDNA sequence data revealed the presence of eight distinct ITS clades and 10 haplotypes among the 40 isolates of N. glabrata. The predominant clades identified were Clades VII, V, and IV, which respectively accounted for 22.5%, 17.5%, and 17.5% isolates. The widest MIC ranges were observed for voriconazole (0.016–8 μg/mL) and isavuconazole (0.016–2 μg/mL), whereas the narrowest ranges were seen with itraconazole and amphotericin B (0.25–2 μg/mL).

Conclusion

Haplotype diversity can be a valuable approach for studying the genetic diversity, transmission patterns, and epidemiology of the N. glabrata complex.
Dietary characteristics associated with the risk of non‐alcoholic fatty liver disease and metabolic dysfunction‐associated steatotic liver disease in non‐obese Japanese participants: A cross‐sectional study
Authors: Taniguchi Hirokazu , Ueda Miho , Sano Fumika , Kobayashi Yukiko , Shima Takatomo
Published: May 2024

Background and Aim

Dietary characteristics associated with non‐alcoholic fatty liver disease (NAFLD) and metabolic dysfunction‐associated steatotic liver disease (MASLD) in non‐obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status.

Methods

We performed a cross‐sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35–74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty‐liver‐related dietary characteristics were assessed using a self‐administered questionnaire.

Results

For non‐obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non‐obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable‐adjusted stepwise logistic regression analysis indicated that, in males, both non‐obese NAFLD and non‐obese MASLD were significantly and negatively associated with “often eat sesame/nuts”, and positively associated with “often eat noodles/rice bowl” and “often eat evening meal” (P < 0.05). For non‐obese women, both NAFLD and MASLD were significantly and positively associated with “often eat sweet buns/bread with fillings” (P < 0.05). Adjusted analyses showed that all dietary characteristics were not significantly associated with the risk of NAFLD/MASLD in obese men and women.

Conclusion

This cross‐sectional study indicates the existence of sex and obesity differences in the association of NAFLD and MASLD with dietary characteristics. Our findings suggest that some dietary characteristics are associated with NAFLD and MASLD prevalence in non‐obese Japanese participants.
Clinical validation and accuracy assessment of the Capsule Endoscopy‐Crohn's Disease index (CE‐CD)
Authors: Arcos‐Machancoses José Vicente , Kapoor Akshay , Schluckebier Dominique , Thomson Mike
Published: May 2024

Objectives

To compare the recently proposed Capsule Endoscopy‐Crohn's Disease index (CE‐CD) to pre‐existing capsule endoscopy (CE) scores, to measure its precision and accuracy to predict adverse clinical outcomes in children with Crohn's disease (CD).

Methods

Children with CD who underwent CE at diagnosis and had, at least, 1‐year follow‐up postprocedure were selected. Capsule study was viewed and the different indices were independently scored by two trained paediatric gastroenterologists. The relationship between pre‐existing scores and CE‐CD was assessed by linear regression analysis. Clinical outcomes prediction assessment was based on receiver operating characteristics curves, survival analysis and Cox regression. Finally, interobserver agreement was measured.

Results

Fifty‐nine patients were finally included. CE‐CD showed a strong positive correlation with the Lewis score (ρ = 0.947) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) (ρ = 0.982). Both CE‐CD and CECDAI were significant predictors of treatment escalation (hazard ratio 1.07 and 1.09, respectively, with both p‐values < 0.01). However, no score predicted risk of hospital admission, surgery or clinical/endoscopic relapse. The presence of moderate‐to‐severe small bowel (SB) inflammation, defined as a score of ≥9 on CE‐CD, provided a hazard ratio of treatment escalation of 2.6 (95% confidence interval: 1.3–5.3). This cut‐off provided the optimal sensitivity/specificity pair: 48.4%/89.3%. No interobserver misclassification among inflammation categories given by CE‐CD were observed (kappa 100%).

Conclusion

CE‐CD is a useful tool to document SB inflammation in children with CD. It correlates strongly with classical scores, can better predict need for treatment escalation and shows good interobserver agreement.
Knowledge, attitude, intentional practice and individualized determinants of COVID‐19 vaccine uptake among adults: A cross‐sectional study in Tanzania
Authors: Nassoro Amimu A. , Millanzi Walter C. , Herman Patricia Z.
Published: May 2024

Aim

The study assessed the knowledge, attitude, intentional practice and individualized factors of COVID‐19 vaccine uptake among adults in Tanzania.

Design

Hospital‐based analytical cross‐sectional study.

Methods

Quantitative approaches were adopted to study 312 randomly selected adults using an interviewer‐administered structured questionnaire. Descriptive analysis established frequencies and percentages of variables at a 95% confidence interval and a 5% significance level.

Results

Mean age was 24.66 ± 6.503 of which 61.5% were males. 86.9% of them were not vaccinated. 57.7% of respondents had inadequate knowledge about the COVID‐19 vaccine, and 61.5% had negative attitudes towards it. 63.8% of adults demonstrated an unwillingness to be vaccinated. Participants' sociodemographic characteristics profiles were significantly associated with COVID‐19 vaccine knowledge, attitude and willingness to uptake it (p < 0.05). Findings highlight the need for large‐scale interventions to address the low uptake vaccine. Adults' willingness to get a coronavirus vaccine was comparatively low. Sociodemographic profiles, knowledge and attitude were associated significantly with low uptake of the COVID‐19 vaccine among adults in Tanzania.
Cluster analysis of patients with alcohol use disorder featuring alexithymia, depression, and diverse drinking behavior
Authors: Kurihara Kazuhiro , Enoki Hiroyuki , Shinzato Hotaka , Takaesu Yoshikazu , Kondo Tsuyoshi
Published: May 2024

Aim

This study aimed to identify subgroups of alcohol use disorder (AUD) based on a multidimensional combination of alexithymia, depression, and diverse drinking behavior.

Method

We recruited 176 patients with AUD, which were initially divided into non‐alexithymic (n = 130) and alexithymic (n = 46) groups using a cutoff score of 61 on the Toronto Alexithymia Scale (TAS‐20). Subsequently, the profiles of the two groups were compared. Thereafter, a two‐stage cluster analysis using hierarchical and K‐means methods was performed with the Z‐scores from the TAS‐20, the Quick Inventory of Depressive Symptomatology Self‐Report Japanese Version, the 12‐item questionnaire for quantitative assessment of depressive mixed state, and the 20‐item questionnaire for drinking behavior pattern.

Results

In the first analysis, Alexithymic patients with AUD showed greater depressive symptoms and more pathological drinking behavior patterns than those without alexithymia. Cluster analysis featuring alexithymia, depression, and drinking behavior identified three subtypes: Cluster 1 (core AUD type) manifesting pathological drinking behavior highlighting automaticity; Cluster 2 (late‐onset type) showing relatively late‐onset alcohol use and fewer depressive symptoms or pathological drinking behavior; and Cluster 3 (alexithymic type) characterized by alexithymia, depression, and pathological drinking behavior featuring greater coping with negative affect.

Conclusion

The multidimensional model with alexithymia, depression, and diverse drinking behavior provided possible practical classification of AUD. The alexithymic subtype may require more caution, and additional support for negative affect may be necessary due to accompanying mood problems and various maladaptive drinking behaviors.
Convergence analysis of a L1‐ADI scheme for two‐dimensional multiterm reaction‐subdiffusion equation
Authors: Jiang Yubing , Chen Hu
Published: May 2024

In this paper, we consider the numerical approximation for a two‐dimensional multiterm reaction‐subdiffusion equation, where we adopt an alternating direction implicit (ADI) method combined with the L1 approximation for the multiterm time Caputo fractional derivatives of orders between 0 and 1. Stability and convergence of the full‐discrete L1‐ADI scheme are established. The final convergence in time direction is point‐wise, that is, at . Numerical results are given to confirm our theoretical results.
Clonal evolution and relapse in early‐stage follicular lymphoma – a tree with many branches†
Authors: Fend Falko , Quintanilla‐Martinez Leticia
Published: May 2024

Follicular lymphoma (FL) is an indolent B‐cell neoplasm characterised by multistep evolution from premalignant precursor cells carrying the hallmark t(14;18) translocation in the majority of cases. In a new article in The Journal of Pathology, samples of relapsed early‐stage FL – primary manifestation and relapse with or without transformation – initially treated with radiotherapy only, were studied for clonal relationships and evolution. Using somatic mutations and the rearranged immunoglobulin sequences as markers, the majority of paired lymphoma samples showed so‐called branched evolution from a common, possibly premalignant progenitor cell, with both shared and private mutations. In addition, clonally unrelated cases were identified. This and previous studies with similar findings clearly document that relapse or transformation of FL in many instances not necessarily represents a linear progression of disease due to acquisition of additional mutations and therapy resistance, but rather new outgrowths derived from a pool of clonally related, long‐lived, and low proliferating precursor cells, or even unrelated second neoplasms. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.