bluuebunny/crossref_metadata_2025 huggingface dataset:
Lauric acid with or without levodopa ameliorates Parkinsonism in genetically modified model of Drosophila melanogaster via the oxidative–inflammatory–apoptotic pathway
Authors: Idowu Olumayowa K. , Dosumu Olufunke O. , Boboye Ayodeji S. , Oremosu Ademola A. , Mohammed Abdullahi A.
Published: September 2024

Background

Parkinson's disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non‐motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α‐synuclein protein plays a significant role in the disease's pathophysiology.

Materials and methods

The UAS‐α‐Syn and Ddc‐Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)‐free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests.

Results

As a result of the overexpression of α‐synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05).

Conclusion

LA, whether combined with LD or not, elicited a significant response in α‐synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.
Antivenom Properties and Chemical Profiling via Molecular Networking of Mimosa gracilis Extracts
Authors: Alexandre Gerso P. , da Silva Marcia M. , Clemente Alan D. , Torres Ana M. , Magalhães Marta R. , Pasqualotto Severino Vanessa G.
Published: September 2024

The species Mimosa gracilis var. capillipes (Benth.) Barneby is used for its antivenom properties in the Coqueiros community, municipality of Catalão, state of Goiás. This study focused on three varieties: M. gracilis Benth. var. gracilis, M. gracilis var. capillipes (Benth.) Barneby, and M. gracilis var. invisiformis Barneby. The chemical profiles of extracts from these varieties were analysed using molecular networking through liquid chromatography with tandem mass spectrometry. Additionally, the study investigated the inhibitory potential of these three varieties against the proteolytic, coagulant, and phospholipase activities of Bothrops and Crotalus venoms. In vitro results confirmed the antivenom potential of nine extracts. Remarkably, the ethanolic extracts of roots from M. gracilis var. capillipes (Benth.) Barneby and the leaves from M. gracilis Benth. var. gracilis exhibited 100 % inhibition of the tested activities. The study also revealed 19 annotated compounds through molecular networking, reported for the first time in the species M. gracilis.
Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor
Authors: Paine Zachary H. , Sharma Mayank , Friedman Simon H.
Published: September 2024

Pseudo‐gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di‐cationic calcium ions with tetra‐anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra‐anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra‐cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo‐gout.
Enhancing Cellular and Enzymatic Properties Through In Vivo Continuous Evolution
Authors: Chu Weiran , Guo Yaxin , Wu Yaokang , Lv Xueqin , Li Jianghua , Liu Long , Du Guocheng , Chen Jian , Liu Yanfeng
Published: September 2024

Directed evolution seeks to evolve target genes at a rate far exceeding the natural mutation rate, thereby endowing cellular and enzymatic properties with desired traits. In vivo continuous directed evolution achieves these purposes by generating libraries within living cells, enabling a continuous cycle of mutant generation and selection, enhancing the exploration of gene variants. Continuous evolution has become powerful tools for unraveling evolution mechanism and improving cellular and enzymatic properties. This review categorizes current continuous evolution into three distinct classes: non‐targeted chromosomal, targeted chromosomal, and extra‐chromosomal hypermutation approaches. It also compares various continuous evolution strategies based on different principles, providing a reference for selecting suitable methods for specific evolutionary goals. Furthermore, this review discusses the two primary limitations for further widespread application of in vivo continuous evolution, which are lack of general applicability and insufficient mutagenic capability. We envision that developing generally applicable mutagenic components and methods to enhance mutation rates for in vivo continuous evolution are promising future directions for wide range applications of continuous evolution.
Clinical outcomes and coronary artery lesion characteristics of young patients with ST elevation myocardial infarction and no standard modifiable risk factors
Authors: Lan Nick S. R. , Chih HuiJun , Brennan Angela L. , Dwivedi Girish , Figtree Gemma A. , Dinh Diem , Stub Dion , Reid Christopher M. , Ihdayhid Abdul Rahman ,   The ASPECT Investigators
Published: September 2024

Background

Among ST‐elevation myocardial infarction (STEMI) patients, those with no standard modifiable risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, and smoking) have higher 30‐day mortality than those with SMuRFs. Differences in coronary lesion characteristics remain unclear.

Methods

Data from STEMI patients aged ≤60 years from the Asia Pacific Evaluation of Cardiovascular Therapies Network (Australia, Hong Kong, Malaysia, Singapore, and Vietnam) was retrospectively analysed. Exclusion criteria included incomplete SMuRF data, prior myocardial infarction, or prior coronary revascularisation. Lesion type was defined using the American College of Cardiology criteria. Major adverse cardiovascular events (MACE) were defined as peri‐procedural myocardial infarction, emergency coronary artery bypass surgery, cerebrovascular event, or mortality. Multiple logistic regressions were used.

Results

Of 4404 patients, 767 (17.4%) were SMuRFless. SMuRFless patients were more frequently younger (median age 51 vs. 53 years; p < 0.001), female (22.6% vs. 15.5%; p < 0.001), thrombolysed (20.1% vs. 12.5%; p < 0.001), and in cardiogenic shock (11.2% vs. 8.6%; p = 0.020). SMuRFless patients had significantly higher in‐hospital MACE (7.2% vs. 4.3%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 1.24–4.08; p = 0.008) but 1‐year mortality was not significantly different (3.6% vs. 5.7%, aOR 0.58; 95% CI 0.06–6.12; p = 0.549). Compared with patients with SMuRFs (4918 lesions), the SMuRFless (940 lesions) had fewer type B2/C lesions (60.8% vs. 65.6%; p = 0.020) and fewer lesions ≥20 mm (51.1% vs. 57.1%; p = 0.002) but more procedural complications (5.1% vs. 2.7%; p < 0.001).

Conclusions

Among young STEMI patients, the SMuRFless have shorter and less complex lesions, but worse procedural and short‐term MACE outcomes.
Recent Advantages on Mass Transfer Structure Construction in Transition Metal‐Based Cost‐Effective Catalyst Toward Alkaline Oxygen Evolution
Authors: Zhang Xuehua , Zhang Li , Lv Songlei , Xu Guodong , Shi Jiawei , Li Jing , Cai Weiwei
Published: September 2024

The electrochemical oxygen evolution reaction (OER) can be combined with various reactions to fabricate electrochemical energy conversion and storage devices while the slow kinetics and poor mass transfer capability at high current densities are the key constraints to its large‐scale application. Therefore, this review primarily focuses on design and optimization of mass transfer structures of TM‐metal‐based OER catalysts. Nanostructuring, porous design, and the creation of hierarchical architectures have been applied during catalyst synthesis to enhance the surface area and accessibility, thereby improving mass transfer and catalytic OER efficiency. Strategies including doping, substrate invitation, soft/hard templating have been utilized to accelerate mass transfer as well as the ion/electron conduction efficiency for the overall improvement of OER performance of the catalysts. These developments underline the critical role of advanced material design in achieving high‐performance OER catalysts and highlight the potential of TM‐based materials in cost‐effective and scalable applications.
Protocol: Factors contributing to the discontinuation of breastfeeding upon women's return to work: A systematic review protocol
Authors: Scotta Ana Veronica , Barral Paula Eugenia , Farre Ailin , Soria Elio Andrés
Published: September 2024

This is the protocol for a Campbell systematic review. The objectives are as follows. In order to understand the variables affecting breastfeeding in working women, this systematic review will aim to determine the factors associated with early breastfeeding cessation upon women's return to work within a Social‐Ecological framework. This will be achieved by answering the following questions: Which individual factors are associated with early discontinuation of breastfeeding upon returning to work?; Which interpersonal factors are associated with early discontinuation of breastfeeding upon returning to work?; Which community factors are associated with early discontinuation of breastfeeding upon returning to work?; Which institutional factors are associated with early discontinuation of breastfeeding upon returning to work?; Which public policies are associated with early discontinuation of breastfeeding upon returning to work?
Low‐Density Lipoprotein Cholesterol, Cardiovascular Risk Factors, and Predicted Risk in Young Adults
Authors: Zheutlin Alexander R. , Luebbe Samuel , Chaitoff Alexander , Stulberg Eric L. , Wilkins John T.
Published: September 2024

Background

Young adults with elevated LDL‐C may experience increased burden of additional cardiovascular disease (CVD) risk factors. It is unclear how much LDL‐C levels, a modifiable factor, correlate with non‐LDL‐C CVD risk factors among young adults or how strongly these CVD risk factors are associated with long‐term predicted CVD risk. We quantified clustering of non‐LDL‐C CVD risk factors by LDL‐C among young adults to assess the association between non‐LDL‐C and LDL‐C risk factors with predicted CVD risk in young adults.

Methods

The current analysis is a cross‐sectional study of adults < 40 years with an LDL‐C< 190 mg/dL participating in the National Health and Nutrition Examination Survey (NHANES) between January 2015 and March 2020. We measured the prevalence of non‐LDL‐C risk factors by LDL‐C and association between LDL‐C and non‐LDL‐C risk factors with predicted risk of CVD by the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations.

Results

Among 2108 young adults, the prevalence of LDL‐C ≥ 130 mg/dL was 15.5%. Compared with young adults with LDL‐C < 100 mg/dL, those with LDL‐C 100–< 130, 130–< 160, and 160–< 190 mg/dL had greater non‐LDL‐C risk factors. Both LDL‐C and non‐LDL‐C risk factors were independently associated with a 30‐year risk of CVD (OR 1.05, 95% CI 1.03–1.07 and OR 1.17, 95% CI 1.12–1.23, respectively). The association of LDL‐C and 30‐year risk did not vary by non‐LDL‐C risk factor burden (pinteraction = 0.43).

Conclusion

Non‐LDL‐C risk factors cluster among increasing levels of LDL‐C in young adults. Greater guidance on how to manage cardiovascular risk factors in young adults is needed.
Development of Integrin Targeting Chimeras (ITACs) for the Lysosomal Degradation of Extracellular Proteins
Authors: Zhou Yaxian , Liao Yaxian , Zhao Yuan , Tang Weiping
Published: September 2024

The emerging of lysosomal targeting chimera (LYTAC) expands the field of targeted protein degradation (TPD) to include the extracellular proteins for precise depletion. However, most of the reported LYTACs either induce ubiquitous degradation of the protein of interest (POI) in a broad range of tissues or specifically target liver cells. More tissue‐selective degraders are highly desirable. Herein, we describe the development of cyclic RGD (cRGD) peptide‐antibody conjugates as a novel class of integrin targeting chimeras (ITACs) with potential cancer selectivity. Our results indicate that the ITACs are able to recruit integrin to induce the degradation of both soluble and membrane targets in the lysosome. We observed higher efficiency of ITACs on degrading membrane protein in cancer cells, providing a promising platform for cancer‐selective TPD strategy.
Phenotypic‐Based Discovery and Exploration of a Resorufin Scaffold with Activity against Mycobacterium tuberculosis
Authors: Tran Eric , Cheung Chen‐Yi , Li Lucy , Carter Glen P. , Gable Robert W. , West Nicholas P. , Kaur Amandeep , Gee Yi Sing , Cook Gregory M. , Baell Jonathan B. , Jörg Manuela
Published: September 2024

Tuberculosis remains a leading cause of death by infectious disease. The long treatment regimen and the spread of drug‐resistant strains of the causative agent Mycobacterium tuberculosis (Mtb) necessitates the development of new treatment options. In a phenotypic screen, nitrofuran‐resorufin conjugate 1 was identified as a potent sub‐micromolar inhibitor of whole cell Mtb. Complete loss of activity was observed for this compound in Mtb mutants affected in enzyme cofactor F420 biosynthesis (fbiC), suggesting that 1 undergoes prodrug activation in a manner similar to anti‐tuberculosis prodrug pretomanid. Exploration of the structure‐activity relationship led to the discovery of novel resorufin analogues that do not rely on the deazaflavin‐dependent nitroreductase (Ddn) bioactivation pathway for their antimycobacterial activity. These analogues are of interest as they work through an alternative, currently unknown mechanism that may expand our chemical arsenal towards the treatment of this devastating disease.
Model order reduction and sensitivity analysis for complex heat transfer simulations inside the human eyeball
Authors: Saigre Thomas , Prud'homme Christophe , Szopos Marcela
Published: September 2024

Heat transfer in the human eyeball, a complex organ, is significantly influenced by various pathophysiological and external parameters. Particularly, heat transfer critically affects fluid behavior within the eye and ocular drug delivery processes. Overcoming the challenges of experimental analysis, this study introduces a comprehensive three‐dimensional mathematical and computational model to simulate the heat transfer in a realistic geometry. Our work includes an extensive sensitivity analysis to address uncertainties and delineate the impact of different variables on heat distribution in ocular tissues. To manage the model's complexity, we employed a very fast model reduction technique with certified sharp error bounds, ensuring computational efficiency without compromising accuracy. Our results demonstrate remarkable consistency with experimental observations and align closely with existing numerical findings in the literature. Crucially, our findings underscore the significant role of blood flow and environmental conditions, particularly in the eye's internal tissues. Clinically, this model offers a promising tool for examining the temperature‐related effects of various therapeutic interventions on the eye. Such insights are invaluable for optimizing treatment strategies in ophthalmology.
Molecular Mechanism of Physical and Mechanical Improvement in Graphene/Graphene Oxide‐Epoxy Composite Materials
Authors: Budak Deniz , Sarikurt Sevil , Gur Tugce , Ozkanakti Harun , Alagoz Huseyin , Eryol Feyza , Yildirim Erol
Published: September 2024

The performance provided by graphene (Gr) and graphene oxide (GO) additives can be improved by achieving strong adhesion and uniform dispersion in the epoxy resin matrix. In this study, molecular modeling and simulation of DGEBA/DETA based epoxy nanocomposites containing Gr and GO additives were performed. Density functional theory and molecular dynamics simulations were used to investigate interfacial interaction energies and Young's Modulus. Improvement in the interaction energies was studied by controlling the epoxy:hardener ratio, type and the number of oxygen‐containing functional groups on the GO, the mass percentage of Gr/GO filler in the epoxy matrix, size and dispersion of GO in the cell. It was demonstrated that functional groups with up to 10 % oxygen content in GO significantly increase interfacial interaction energy for large size Gr/GO. Increasing DETA type amine ratio in the preparation of epoxy polymers increases the interaction energy for high oxygen content while decreasing the interaction energy for low oxygen content in GO for small size GO with edge functional groups. The performance of material dramatically decreased even at high DETA hardener and high GO mass percentages when the aggregation factor of Gr/GO was included in simulations that explain lower Gr/GO percentages in the experimental studies.
Chromogenic Chemosensor for Simultaneous Detection of PO43− and CO32− Anions in Organo‐Aqueous Solutions: Application in Arduino Based Electronic Color Sensor Device and Logic Gate
Authors: Dhawale Annasaheb , Trivedi Darshak R.
Published: September 2024

Three new chromogenic receptors have been synthesized with the primary objective of facilitating the selective recognition of PO43−and CO32− ions in an organo‐aqueous medium. R1 and R2 exhibit an extraordinary detection limit aligning with both EPA and WHO guidelines. R1 shows LOD of 0.135 ppm for PO43− and 0.175 ppm for CO32−, while R2 sets forth a LOD of 0.427 ppm for PO43− and 0.729 ppm for CO32−. The binding mechanism involves intramolecular charge transfer (ICT) band are substantiated by comprehensive studies that include UV‐Vis titration, 1H‐NMR titration, DFT studies and electrochemical studies. Chemosensors were employed in the formulation of logic gate, the fabrication of a paper strip test kit and its application in RGB color sensor device.
Partial Residual Plots as an Integrated Model Diagnostic Tool in Model‐Based Meta‐Analysis
Authors: Maringwa John , Diderichsen Paul Matthias , Valiathan Chandni
Published: September 2024

The use of partial residual plots (PRPs) was explored as a model diagnostic tool in Model‐based Meta‐Analysis (MBMA). Mathematical derivations illustrating the concepts were followed by an MBMA example using publicly available literature data of anti‐depressive treatments with fluoxetine and venlafaxine. An Emax dose–response model was identified for venlafaxine while a constant drug effect combining all dose levels vs. placebo was identified for fluoxetine. The larger the mean baseline Hamilton Depression Rating (HAMD) score, the larger the expected drug effect (P = 0.0122), based on the likelihood ratio test. Mean baseline HAMD score (range) was 25.4 (23.5, 29.4) and 20.8 (15, 26) while mean placebo change from baseline (range) was −9.02 (−12.2, −4.8) and − 6.22 (−10.9, −1.3) for venlafaxine and fluoxetine, respectively. Average baseline HAMD score appeared larger for venlafaxine compared to fluoxetine, albeit a wider range for fluoxetine. Placebo response seemed lower but also more variable in fluoxetine compared to venlafaxine studies. Observed data points tended to deviate from model predictions when the mean baseline HAMD and placebo response values associated with those data points differed substantially from the corresponding values used for the model prediction. Normalizing observed data addressed this, providing a “like‐to‐like” comparison with model predictions in PRP when assessing the effect of one covariate (dose) after normalizing for other covariates/effects (placebo response and mean baseline). PRPs provide a robust integrated diagnostic tool in MBMA that uses all data to show the correlation between response and any covariate while controlling for other covariates included in the model.
The abundance and distributional (in)equalities of forageable street tree resources in Lagos Metropolis, Nigeria
Authors: Adeyemi Opeyemi , Shackleton Charlie M.
Published: September 2024

Foraging for wild resources links urban citizens to nature and biodiversity while providing resources important for local livelihoods and culture. However, the abundance and distributional (in)equity of forageable urban tree resources have rarely been examined. Consequently, this study assessed the abundance of forageable street trees and their distribution in Lagos metropolis, Nigeria. During a survey of 32 randomly selected wards across 16 local government areas (LGAs) in the metropolis, 4017 street trees from 46 species were enumerated. The LGA with the highest number of street trees was Ikeja, with 818 trees, while Lagos Island had the lowest count, with two trees. This disparity in tree numbers could be attributed to variations in human population density within each LGA. Ninety‐four percent of the street trees surveyed had at least one documented use and 76% had two, making them potentially forageable. However, the most common species had relatively low forageability scores. Only 5.6% of the total street tree population was rated as highly forageable, with a usability score of at least 11 out of 15. The most forageable street trees were fruit trees and non‐native species. The forageable street trees in the LGAs showed a significant disparity in their distribution, as evidenced by a Gini coefficient of 0.81. Overall, richer neighborhoods had a higher street tree abundance, richness, and forageability potential. To meet greening and foraging goals and address the current inequitable distribution, we suggest allocating more funds for greening, particularly in low‐income neighborhoods. Further research should evaluate forageable species from other sites to acquire a detailed understanding of the distribution and abundance of forageable resources in Lagos metropolis.
ThymoSpheres culture: A model to study human polyclonal unconventional T cells
Authors: Billiet Lore , Jansen Hanne , Pille Melissa , Boehme Lena , Sanchez Sanchez Guillem , De Cock Laurenz , Goetgeluk Glenn , Pascal Eva , De Munter Stijn , Deseins Lucas , Ingels Joline , Michiels Thomas , De Vos Robrecht , Zolfaghari Amin , Vandamme Niels , Roels Jana , Kerre Tessa , Dmitriev Ruslan I. , Taghon Tom , Vermijlen David , Vandekerckhove Bart
Published: September 2024

In vitro cultures remain crucial for studying the fundamental mechanisms of human T‐cell development. Here, we introduce a novel in vitro cultivation system based on ThymoSpheres (TS): dense spheroids consisting of DLL4‐expressing stromal cells and human hematopoietic precursor cells, in the absence of thymic epithelial cells. These spheroids are subsequently cultured at the air–liquid interphase. TS generate large numbers of mature T cells, are easy to manipulate, scalable, and can be repeatably sampled to monitor T‐cell differentiation. The mature T cells generated from primary human hematopoietic precursor cells were extensively characterized using single‐cell RNA and combined T‐cell receptor (TCR) sequencing. These predominantly CD8α T cells exhibit transcriptional and TCR CDR3 characteristics similar to the recently described human polyclonal αβ unconventional T cell (UTC) lineage. This includes the expression of hallmark genes associated with agonist selection, such as IKZF2 (Helios), and the expression of various natural killer receptors. The TCR repertoire of these UTCs is polyclonal and enriched for CDR3‐associated autoreactive features and early rearrangements of the TCR‐α chain. In conclusion, TS cultures offer an intriguing platform to study the development of this human polyclonal UTC lineage and its inducing selection mechanisms.
Experimental and Computational Investigations of Supramolecular Interactions in Cd(II)–Organic Hydrate: Catalytic Applications in the Knoevenagel Condensation Reaction under Solvent‐Free Conditions
Authors: Sadhukhan Arijit , Nath Patra Birendra , Maity Tanmoy , Kumar Das Asit , Kumar Ghosh Chandan , Brandao Paula , Gil Diego M. , Bera Debabrata , Roy Choudhury Chirantan , Kumar Bhaumik Prasanta , Mal Dasarath , Frontera Antonio
Published: September 2024

A dinuclear cadmium(II) complex, [Cd2(Hhqc)2(H2O)4] (H3hqc=4,8‐dihydroxyquinoline‐2‐carboxylic acid) was synthesized and characterized by single crystal X‐ray diffraction studies, elemental analyses and thermo‐gravimetric studies. The metal centers are found to be six coordinated with distorted pentagonal pyramidal geometry around them. The complex shows few significant intermolecular hydrogen bonding interactions to produce a three dimensional supramolecular network comprising of T8(2) water tapes. Besides these non‐covalent interactions few other supramolecular interactions are also involved within the molecular dimer like π⋅⋅⋅π stacking, Cd⋅⋅⋅π etc. They have been analyzed using DFT calculations, MEP surface analyses and NCI plot index analyses. The detailed study highlights the complex interplay of π‐stacking, H‐bonding, and spodium interactions in stabilizing the dimers of complex, which providing precious insights into their energetic and structural characteristics. Further more, the catalytic efficiency of the synthesized complex has been investigated as an effective heterogeneous catalyst in the Knoevenagel condensation reactionunder solvent‐free conditions.
Adolescent predictors of substance use in young adulthood among individuals with childhood‐onset chronic pain: A follow‐up study
Authors: Rogers Andrew H. , Palermo Tonya M. , Groenewald Cornelius B. , Murray Caitlin B.
Published: September 2024

Background

Adolescent chronic pain is a substantial public health problem, and pain symptoms often persist into adulthood. Young adults with chronic pain are at elevated risk for more frequent tobacco, alcohol and cannabis use, and cross‐sectional research highlights the importance of psychosocial vulnerability factors. Limited research has examined how adolescent predictors, including mental health symptoms, pain, sleep and family functioning, impact later, young adult substance use.

Methods

A prospective cohort of 229 young adults (77.3% female; Mage = 21.0, SD = 1.6) with childhood‐onset chronic pain completed measurements in adolescence and a follow‐up assessment in young adulthood of past 3‐month substance use frequency.

Results

Adolescent sleep quality and male sex were associated with more frequent tobacco use; adolescent depression was associated with more frequent alcohol use, and adolescent pain severity was associated with less frequent, and male sex was associated with more frequent cannabis use.

Conclusions

Adolescent predictors of young adult substance use among youth with childhood‐onset chronic pain represent important factors that may inform assessment, prevention and treatment of substance use in this population. Identifying and testing psychological interventions that target these vulnerability factors may reduce overall substance use risk in young adulthood.

Significance

This prospective observational study of young adults with childhood‐onset chronic pain identified adolescent depression and sleep quality as vulnerability factors associated with substance use. Given the increasing risk for substance use during adolescence and young adulthood, these findings highlight the potential importance of early intervention to reduce substance use among young adults with childhood‐onset chronic pain.
Implementation of a visualization teaching approach for mechanical analysis in civil engineering structures
Authors: Sun Panxu , Liang Kaixuan , Wang Dongwei , Zhang Xiangcheng
Published: September 2024

The visualization method for mechanics knowledge in civil engineering courses is very important, which can help students learn abstract mechanics. Combined with the structural analysis software, this paper develops a visualization teaching approach for mechanical analysis in civil engineering structures based on the proposed deformation decomposition method, such as elastic mechanics, material mechanics and structural dynamics. Compared with traditional strain analysis method, the proposed method is more intuitive and can identify more macroscopic basic deformations. By aid of a survey for undergraduate students and master students, the teaching effectiveness of the visualization course is higher than that of the blackboard writing course. Besides, Mann–Whitney test results show that there is a significant difference. The proportion of undergraduate students that think the combination of visualization has good effects are greater than those of master students. The proposed visualization teaching approach can be promoted in mechanics courses of civil engineering.
Simulation‐based generation and analysis of multidimensional future scenarios with time series clustering
Authors: Steinmann Patrick , van der Zwet Koen , Keijser Bas
Published: September 2024

Scenarios are commonly used for decision support and future exploration of complex systems. Using simulation models to generate these scenarios, called scenario discovery, has received increased attention in the literature as a principled method of capturing the uncertainty, complexity, and dynamics inherent in such problems. However, current methods of incorporating dynamics into scenario discovery are limited to a single outcome of interest. Furthermore, there is little work on the post‐generation evaluation of the generated scenarios. In this work, we extend scenario discovery to multiple dynamic outcomes of interest, and present a number of visual and statistical approaches for evaluating the resulting scenario sets. These innovations make model‐based scenario generation more widely applicable in decision support for complex societal problems, and open the door to multimethod scenario generation combining model‐based and model‐free methods such as Intuitive Logics or futures cones.
Chemoradiotherapy plus immunotherapy for locoregionally advanced nasopharyngeal carcinoma: A cost‐effectiveness analysis
Authors: Liu Kun , Zhu Youwen , Li Shan , Zhu Hong
Published: September 2024

Background

Research focused on the addition of immune checkpoint inhibitors (ICIs) to radiotherapeutic regimens in patients with cancer has become increasingly common, revealing promising improvements in efficacy outcomes. In patients with locoregionally advanced nasopharyngeal carcinoma (NPC), combining immunotherapy with chemoradiotherapy can facilitate the significant prolongation of survival, emphasizing the need for pharmacoeconomic studies focused on the clinical uptake of these innovative treatment regimens.

Methods

A three‐state Markov model was developed based on clinical data from the randomized phase 3 CONTINUUM trial and used to compare the cost‐effectiveness of chemoradiotherapy plus sintilimab (sintilimab group) to chemoradiotherapy alone (standard group), analyzing outcomes including incremental cost‐effectiveness ratio (ICER), incremental net monetary benefit (INMB), and incremental net‐health benefit (INHB) values at a willingness‐to‐pay (WTP) threshold corresponding to three times the Chinese GDP per capita ($37 035 per quality‐adjusted life year [QALY]).

Results

The total costs for patients in the sintilimab and standard groups (QALYs [LYs]) were $92 116 (6.68 [10.03]) and $53 255 (3.75 [5.55]), respectively, for an ICER of $13 230/QALY ($8672/LY), an INMB of $70 021 with INHB of 1.89 QALYs. Using the selected WTP threshold. On the standard WTP threshold, the prevalence of sintilimab group as the primary treatment was 90.55% in China. The establishment of the model is stable.

Conclusions

Adding sintilimab to chemoradiotherapeutic regimens represents an innovative and cost‐effective means for patients with locoregionally advanced NPC management in China.
Knee temperature remains abnormal in patients successfully treated with anterior cruciate ligament reconstruction: An infrared thermography analysis
Authors: De Marziani Luca , Orazi Simone , Boffa Angelo , Andriolo Luca , Di Martino Alessandro , Zaffagnini Stefano , Filardo Giuseppe
Published: September 2024

Purpose

The aim of this study was to evaluate if the operated knee environment remains abnormal in patients successfully treated with anterior cruciate ligament reconstruction (ACL‐R).

Methods

Thirty asymptomatic patients were enrolled (28 men, 2 women, age 28.6 ± 6.54 years, body mass index: 24.9 ± 3.0 kg/m2) and evaluated at 42.2 ± 12.5 months after surgery. Patients were assessed with patient‐reported outcome measurements and with a triaxial accelerometer. The temperature of the knees as well as four regions of interest were evaluated with an infrared thermographic camera FLIR T1020 (FLIR® Systems) according to a standardised protocol including a baseline evaluation and further evaluations immediately after exercise and after 5, 10 and 20 min. The temperature of the ACL‐R knee was compared to that of the contralateral healthy knee for the purpose of the study.

Results

The mean temperature of the knee was higher (p = 0.010) for the ACL‐R knees (31.4 ± 1.4°C) compared to the healthy knees (31.1 ± 1.6°C), as well as for the patellar area (p = 0.005), the lateral area (p = 0.016) and the medial area (p = 0.014). The analysis of the response to the exercises of the ACL‐R knees showed similar trends to the healthy knees but higher temperature values at all time points (p < 0.05). Patients who underwent ACL‐R with concomitant meniscal treatment showed higher knee temperatures compared to ACL‐R knees without concomitant meniscal treatment after 5 (p = 0.047), 10 (p = 0.027) and 20 min (p = 0.048).

Conclusions

The temperature of asymptomatic knees previously treated with ACL‐R is higher than the contralateral healthy knee, both at rest and after exercise, with a further increase in knees that underwent both ACL‐R and meniscal treatment. These results suggest an inflammatory state persisting years after the surgery, which could predispose to the early onset of knee degeneration.

Level of Evidence

III, Case–control study.
Characteristics and outcomes of minimally invasive surgery for congenital biliary dilatation in children aged <6 years: Comparison between children and adults
Authors: Nakagawa Yoichi , Uchida Hiroo , Shirota Chiyoe , Tainaka Takahisa , Makita Satoshi , Satomi Miwa , Yasui Akihiro , Kano Yoko , Kato Daiki , Maeda Takuya
Published: September 2024

Background/Purpose

We evaluated the minimally invasive surgery for congenital biliary dilatation (CBD) in adults and children and analyzed the surgical outcomes, especially in children aged <6 years.

Methods

Characteristics and surgical outcomes of patients with CBD who underwent minimally invasive surgery at our hospital between 2013 and 2023 were retrospectively reviewed.

Results

Overall, 129 patients (89 children aged <6 years, 9 children aged between 6 and 18 years, and 21 adults) were included in this study. Children exhibited more protein plug presence and abnormal biochemical data than adults. Incidence of postoperative pancreatic fistulas was highest in the adult group (3.4%, 11%, and 33%, respectively, p < .01). In children aged <6 years, postoperative bile leakage and pancreatic fistulas occurred in 9.0% and 3.4% of patients, respectively. Multivariate logistic regression analysis revealed that the Todani IVA was associated with a decrease in postoperative bile leakage (odds ratio: −1.7; 95% confidence interval: (−3.3)–(−0.22), p = .03).

Conclusion

Adults with CBD required prolonged operative times and had more short‐term complications than children with CBD. In children aged <6 years, minimally invasive surgery for CBD can be safely performed; however, a small diameter of the bile duct may be associated with bile leakage.
Feasibility of biliary atresia newborn screening in an integrated health network
Authors: Guthery Stephen L. , Kyle Jensen M. , Sean Esplin M. , O'Brien Elizabeth , Krong Jake , Srivastava Rajendu
Published: September 2024

Diagnostic delay remains a barrier to improving biliary atresia (BA) outcomes. We tested the implementation feasibility of a two stage BA newborn screening program in an integrated healthcare system.

Methods

Under a waiver of consent, we measured direct bilirubin (DB) levels in well newborns undergoing standard of care hyperbilirubinemia screening at four hospitals. Initial DB was measured by modifying nursery admission electronic medical record order sets. Second‐stage DB was obtained at ~2 weeks of age under parental permission/informed consent (PP/IC). Implementation measures included the proportions of (1) eligible newborns that were screened before nursery discharge, (2) newborns undergoing second stage screening at ~2 weeks of age, and (3) newborns that underwent clinical evaluation for persistently elevated DB.

Results

A total of 12,276 newborns met eligibility criteria for screening, of which 12,055 (98.2%) underwent first‐stage screening in the newborn nursery. Ninety‐four (0.78%) had elevated positive initial screens. Ninety newborns (95.7%) underwent second‐stage screening (n = 20) or contact was made with the primary care provider to recommend second‐stage screening (n = 70). Among all screened newborns, 15 (0.12%) had abnormal second screens. All had follow‐up clinical evaluation for potential cholestatic liver disease. No BA cases were identified through screening, though two infants who met exclusion criteria (admission to the newborn intensive care unit) were subsequently diagnosed with BA during the screening period.

Conclusions

BA newborn screening is feasible in an integrated health network. Low consent rates have implications for future studies. Program infrastructure is required for implementation success and sustainability.
Investigation of the impact of papain on the volatile and non‐volatile metabolites of soybean meal yogurt
Authors: Yan Yaxin , Hua Dong , Liu Xiaoqing , Fan Xiangrong , Bai Miao , Liu He
Published: September 2024

Background

Soybean meal yogurt was prepared from soybean meal using papain and Bifidobacterium animalis subsp. lactis. A non‐targeted metabolomics approach was employed to analyze the relevance of papain to the differences in volatile and non‐volatile metabolites of soybean meal yogurt.

Results

The results showed that the main up‐regulated metabolites and metabolic pathways after enzymatic digestion were dominated by amino acids and their derivatives. Conversely, the main down‐regulated metabolites and pathways were predominantly associated with flavonoid metabolism. Amino acids and their derivatives, as well as flavonoids, were found to be highly correlated with the formation of sweet, umami, astringent, and bitterness. The addition of papain enriched the content of aromatic compounds in soybean meal yogurt. Aromatic components such as 2‐heptanone, naphthalene, and p‐xylene increased in concentration. Synthetic peptide of aspartate and serine, gramine, geissospermine, N‐desmethyl vinblastine, and 3,7‐dihydroxyflavone were the major non‐volatile differential metabolites distinguishing the soybean meal yogurt.

Conclusion

This study provided a comprehensive analysis of the metabolic traits of products co‐fermented by papain and Bifidobacterium animalis subsp. lactis, offering insights for the application of papain in fermented goods. © 2024 Society of Chemical Industry.
Fetal Cystic Lymphatic Malformations
Authors: Nzelu Diane , Panayotidis Ismini , Smith Gill D. , Pandya Pranav
Published: September 2024

Objective

Evaluate pregnancy and neonatal outcomes with fetal cystic lymphatic malformations (LMs), excluding those arising from the posterior neck, to facilitate patient counseling.

Method

A systematic review was performed in accordance with PRISMA guidance. Case series and case reports published between 2000 and 2022 were included.

Results

Sixty‐five studies (96 fetuses) met the inclusion criteria. The average gestational age at diagnosis was 25.5 weeks with the commonest location being the anterior neck (28%). All patients were diagnosed with LM using two‐dimensional (2D) ultrasound. Prenatal progression in LM size, presence of intralesional bleeding, or fetal hydrops occurred in 70% (41/59), 9% (5/59), and 3% (2/59), respectively. Chromosomal and structural abnormalities were reported in 4% (2/52) and 2% (2/96), respectively. Overall livebirth rate was 94% (79/84); 12/96 resulted in termination and 5/84 in in utero demise.

The average gestational age of delivery was 37.7 weeks. Exactly 19% (15/79) had a vaginal birth, of which shoulder dystocia occurred in one infant. Ex utero intrapartum treatment (EXIT) procedure was performed in 13% (10/79). Postnatal treatment commonly involved surgical excision 38% (30/79), sclerotherapy in 21.5% (17/79), or combination of both in 11.4% (9/79). Of those with reported follow‐up, 4 died within 1 year, 1 developed heart failure at 2 years of life, and the remaining 44 had normal developmental outcomes.

Conclusion

Fetal cystic LMs, excluding those in the posterior neck, are not commonly associated with chromosomal, or additional structural abnormalities. They usually increase in size before delivery with only a minority developing complications. The good developmental outcome was reported in all survivors.
Variability in Liver Size Measurements Using Different View Angles in Ultrasound Imaging
Authors: Gao Jing , Flick Andrew , Allen Austin , Krasnoff Masha , Kinder Dennis , Nguyen Trinh
Published: September 2024

Purpose

The aim of this study was to compare liver size measurements in different conventional B‐mode ultrasound image (US) field views using magnetic resonance imaging (MRI) measurement as a reference.

Methods

After receiving Institutional Review Board approval and informed consent, three operators measured the largest sagittal and transverse dimensions of adult livers on three US image field views (90°, 120°, and 140°) with a single curvilinear transducer. We analyzed the differences in liver size across three image field views using one‐way analysis of variance (ANOVA) and examined the correlations between MRI and ultrasound measurements using Spearman regression. We used 95% Bland–Altman limits of agreement (95% LOA) to analyze the confidence interval for liver size measurements between MRI and US. Intra‐observer and inter‐observer reliability in measuring liver size were assessed using intraclass correlation coefficient (ICC).

Results

Based on sagittal liver length, 28 adult participants (7 men and 21 women, mean age 43 years) were divided into Group 1 (<17 cm, n = 10) or Group 2 (≥17 cm, n = 18). There was a significant difference in the liver size measurements across the three image field views (P < .001) in both groups. The highest correlation in liver size measurements between MRI and US was with ultra‐wide‐view (R2 = .87 in sagittal; R2 = .79 in transverse). Bland–Altman LOA also indicated good agreement between MRI and ultra‐wide‐view measurements. Intra‐observer and inter‐observer reliability in measuring liver size were good (ICC = 0.82–0.98).

Conclusion

The study suggests that ultrasound ultra‐wide‐view provides the most accurate liver size measurement and good intra‐ and inter‐operator reliability.
Parallel inertial forward–backward splitting methods for solving variational inequality problems with variational inclusion constraints
Authors: Thang Tran Van , Tien Ha Manh
Published: September 2024

The inertial forward–backward splitting algorithm can be considered as a modified form of the forward–backward algorithm for variational inequality problems with monotone and Lipschitz continuous cost mappings. By using parallel and inertial techniques and the forward–backward splitting algorithm, in this paper, we propose a new parallel inertial forward–backward splitting algorithm for solving variational inequality problems, where the constraints are the intersection of common solution sets of a finite family of variational inclusion problems. Then, strong convergence of proposed iteration sequences is showed under standard assumptions imposed on cost mappings in a real Hilbert space. Finally, some numerical experiments demonstrate the reliability and benefits of the proposed algorithm.
Precise ablation zone segmentation on CT images after liver cancer ablation using semi‐automatic CNN‐based segmentation
Authors: Le Quoc Anh , Pham Xuan Loc , van Walsum Theo , Dao Viet Hang , Le Tuan Linh , Franklin Daniel , Moelker Adriaan , Le Vu Ha , Trung Nguyen Linh , Luu Manh Ha
Published: September 2024

Background

Ablation zone segmentation in contrast‐enhanced computed tomography (CECT) images enables the quantitative assessment of treatment success in the ablation of liver lesions. However, fully automatic liver ablation zone segmentation in CT images still remains challenging, such as low accuracy and time‐consuming manual refinement of the incorrect regions.

Purpose

Therefore, in this study, we developed a semi‐automatic technique to address the remaining drawbacks and improve the accuracy of the liver ablation zone segmentation in the CT images.

Methods

Our approach uses a combination of a CNN‐based automatic segmentation method and an interactive CNN‐based segmentation method. First, automatic segmentation is applied for coarse ablation zone segmentation in the whole CT image. Human experts then visually validate the segmentation results. If there are errors in the coarse segmentation, local corrections can be performed on each slice via an interactive CNN‐based segmentation method. The models were trained and the proposed method was evaluated using two internal datasets of post‐interventional CECT images ( = 22, = 145; 62 patients in total) and then further tested using an external benchmark dataset ( = 12; 10 patients).

Results

To evaluate the accuracy of the proposed approach, we used Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), Hausdorff distance (HD), and volume difference (VD). The quantitative evaluation results show that the proposed approach obtained mean DSC, ASSD, HD, and VD scores of 94.0%, 0.4 mm, 8.4 mm, 0.02, respectively, on the internal dataset, and 87.8%, 0.9 mm, 9.5 mm, and −0.03, respectively, on the benchmark dataset. We also compared the performance of the proposed approach to that of five well‐known segmentation methods; the proposed semi‐automatic method achieved state‐of‐the‐art performance on ablation segmentation accuracy, and on average, 2 min are required to correct the segmentation. Furthermore, we found that the accuracy of the proposed method on the benchmark dataset is comparable to that of manual segmentation by human experts ( = 0.55, ‐test).

Conclusions

The proposed semi‐automatic CNN‐based segmentation method can be used to effectively segment the ablation zones, increasing the value of CECT for an assessment of treatment success. For reproducibility, the trained models, source code, and demonstration tool are publicly available at https://github.com/lqanh11/Interactive_AblationZone_Segmentation.