bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond body mass index: Body composition profiling for perioperative risk stratification in intrahepatic cholangiocarcinoma patients
Authors: Kolck Johannes , Hosse Clarissa , Beetz Nick Lasse , Auer Timo Alexander , Marth Adrian Alexander , Segger Laura , Krenzien Felix , Lurje Georg , Pelzer Uwe , Geisel Dominik , Schöning Wenzel , Fehrenbach Uli
Published: September 2024

Background and Aims

Intrahepatic cholangiocarcinoma (iCC) is an aggressive tumor, usually detected at an advanced stage. Our aim was to investigate the potential of body composition analysis (BCA) derived from presurgical staging computed tomography (CT) in predicting perisurgical complications.

Methods

In this retrospective cohort study, we enrolled 86 patients who underwent CT imaging prior to liver surgery. Cox and logistic regression were performed to assess risk factors for prolonged hospital and intensive care unit (ICU) stays, as well as the occurrence of various complications. BCA parameters served as covariates besides conventional risk factors.

Results

Postoperative complications after resection of iCC significantly prolonged the overall length of hospitalization (p < .001). Presence of sarcopenia was associated with longer ICU stays. Complications were common, with 62.5% classified as Clavien–Dindo grade IIIa or lower and 37.5% as more severe. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were identified as risk factors for complications, including bile leakage (in 24 cases, p = .025), pleural effusions (in 26 cases, p = .025), and intra‐abdominal abscess formation (in 24 cases, p = .043). SAT was associated with severe complications requiring interventional therapy, whereas VAT was correlated with abscess formation. Despite normal prevalence of obesity (22%), body mass index (BMI) did not have an impact on the development of perioperative complications.

Conclusion

BCA is a useful tool for preoperative risk stratification in patients with iCC and is superior to BMI assessment. Increased SAT and VAT were associated with the risk of perisurgical complications, prolonging hospitalization. Therefore, BCA derived from routine staging CT should be considered in the preoperative assessment of patients with iCC.
Pseudonormal Morphology of Salivary Gland Adenoid Cystic Carcinoma Cells Subverts the Antitumor Reactivity of Immune Cells: A Tumour‐Cell–Based Initiation of Immune Evasion
Authors: Chakraborty Rajdeep , Zaw Thiri , Khodlan Pallavi , Darido Charbel , Palmisano Giuseppe , Chien Arthur , Tay Aidan , Ranganathan Shoba , Liu Fei
Published: September 2024

Introduction

Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti‐tumour reactivity of immune cells towards head and neck cancer.

Method

To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer‐immune cells co‐culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics.

Results

ACC cells morphed into pseudonormal morphology in immune co‐culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co‐culture models.

Conclusion

Overall, we conclude that the presence of Gipie has a confounding role during the ACC–immune cell interaction.
Case Report: Primary Squamous Cell Carcinoma of the Orbit in a Patient With Carney's Syndrome Treated With Multidisciplinary Approaches
Authors: Rahman Md. Arifur , Balakrishnan Rajesh , Mostofa Mohammad Golam , Islam Mohammed Rashedul , Kabir Enamul , Islam Md. Shariful , Naznin Bidoura , Das Arunangshu , Chowdhury Qamruzzaman
Published: September 2024

Background

Squamous cell carcinoma (SCC) is a rare malignancy of invasive epithelium with keratinocyte differentiation, and it is the most common form of eyelid malignant neoplasm, comprising 5%–10% of malignancies. While SCC rarely affects the orbit, it may be involved through local invasion from a cutaneous primary site or extension by perineural invasion. Only 12 cases of primary orbital SCC have been reported until now. Here, we present a case of primary carcinoma of the right orbit with coexisting Carney's syndrome, a rare genetic disorder associated with multiple endocrine neoplasias (MEN) syndromes.

Case

A 62‐year‐old South Asian male presented with a painful swelling in the lateral aspect of the right eyebrow and protrusion of the eyeball in August 2020. He had a history of excision of Right atrial Myxoma in March 2020. Orbital computerized tomography (CT) and positron emission tomography (PET‐CT) scans revealed an enhancing soft tissue lesion in the right orbit with the involvement of frontal and ethmoid sinuses. Biopsy confirmed HPV‐related poorly differentiated SCC, positive for HPV‐related markers. The patient received concurrent chemo irradiation with Cisplatin. Follow‐up PET‐CT done 3 months later showed a new lesion appeared in the right orbital region and right lobe of thyroid. Later had surgical excision and total thyroidectomy, and histopathological examination (HPE) from orbit was reported as invasive SCC and from the thyroid was reported as synchronous papillary thyroid cancer. The patient's proptosis resolved, and subsequent PET‐CT and magnetic resonance imaging (MRI) scans did not show any residual or recurrent disease.

Conclusion

Primary SCC of the orbit is an extremely rare disease, and this case report presents the 13th reported case and the first one associated with Carney's syndrome. As there is no standard treatment regimen for primary SCC of the orbit, this case highlights the use of multimodality treatment, including surgical excision and chemo irradiation. The findings emphasize the importance of early detection and management of this uncommon and life‐threatening condition, providing hope for patients and aiding in the prevention of recurrence.
Exome Sequencing Starting from Single Cells
Authors: Andreou Ioanna , Storbeck Markus , Hahn Peter , Rulli Samuel , Lader Eric
Published: September 2024

Single‐cell genomic analysis enables researchers to gain novel insights across diverse research areas, including developmental biology, tumor heterogeneity, and disease pathogenesis. Conducting single‐cell genomic analysis using next‐generation sequencing (NGS) methods has traditionally been challenging as the amount of genomic DNA present in a single cell is limited. Advancements in multiple displacement amplification (MDA) technologies allow the unbiased amplification of limited quantities of DNA under conditions that maintain its integrity. This method of amplification results in high yield and facilitates the generation of high‐complexity NGS libraries that ensure the highest coverage to effectively allow variant calling.

With the introduction of new sequencing platforms and chemistry, whole genome sequencing became a more cost‐effective application, but enrichment of specific regions of interest further reduces the amount of required sequencing output and associated costs. There are two enrichment methods, polymerase chain reaction (PCR)–based and hybrid‐capture‐based methods. PCR‐based methods are very flexible and highly effective but focus on specific loci, typically known to be associated with disease. Inherited diseases of unknown genetic origin require a more comprehensive approach to capture the genetic variation that is not yet associated with a specific disease. Hybrid capture enrichment methods require considerable amounts of DNA such that exome enrichment from single cells is only possible after preamplification of this limited material.

This article describes the complete workflow from single cells and small quantities of DNA to exome‐NGS libraries for Illumina sequencing instruments and includes the following protocols: © 2024 QIAGEN GmbH. Current Protocols published by Wiley Periodicals LLC.

This article was corrected on 04 October 2024. See the end of the full text for details.

Basic Protocol 1: Whole genome amplification from single cells or small amounts of gDNA

Basic Protocol 2: NGS library generation of MDA‐amplified material

Basic Protocol 3: Exome enrichment
Critical Challenges, Cooperative Solutions
Authors: Joosse Tess
Published: September 2024

Agriculture in the United States faces significant challenges, including food insecurity, climate change, environmental degradation, and rural prosperity issues. The USDA Long‐Term Agroecosystem Research (LTAR) Network, which comprises 18 national sites, aims to address these challenges through sustainable intensification. Each site conducts a “Common Experiment” to compare traditional management practices with new alternative strategies. Upcoming special sections in the Journal of Environmental Quality will highlight the LTAR Network’s work and progress in implementing these experiments nationwide.
Estimating Treatment Goal Weights in Adolescents With Anorexia Nervosa and Atypical Anorexia Nervosa: Comparison of the Median BMI and Historical BMI Percentile
Authors: Jary (Franklin) Jessica M. , Winnie Samantha L. , Prohaska Natalie , Bravender Terrill , Van Huysse Jessica L.
Published: September 2024

Background

Determining an accurate treatment goal weight (TGW) is critical for treating eating disorders requiring weight restoration. This is challenging in adolescents since body mass index (BMI) normally increases over time. Median BMI (mBMI) is often used to determine TGW, though use of historical growth trajectories is increasingly common. Using the appropriate method to set TGW may be particularly important in treating individuals with anorexia nervosa (AN) whose prior growth was substantially above or below the median, and in atypical anorexia (AAN) where prior growth is, by definition, above the median.

Objectives

(1) Compare differences between TGWs based on mBMI and historical BMI percentile (hBMI) in patients with AN and AAN. (2) Determine whether either TGW method better predicted scores on the Eating Disorder Examination (EDE), heart rate, and menstrual status during treatment.

Method

Retrospective chart review of 197 adolescents with AN or AAN completing a partial hospitalization program (PHP).

Results

For AN, the within‐person variation between methods varied up to 11.3 kg, though the average TGW was similar if derived from the mBMI or hBMI. In AAN, the average hBMI TGW was higher than mBMI TGW, and within‐person variation was up to 19.3 kg. Associations between hBMI TGW and mBMI with heart rate, menstrual status, and EDE scores varied.

Discussion

Within‐person differences in TGWs derived from hBMI versus mBMI can be large, with prominent differences in AAN, where hBMI TGW is significantly higher.
Biological and physical controls of methane uptake in grassland soils across the US Great Plains
Authors: Koyama Akihiro , Johnson Nels G. , Brewer Paul , Webb Colleen T. , von Fischer Joseph C.
Published: September 2024

The grassland biome is an important sink for atmospheric methane (CH4), a major greenhouse gas. There is considerable uncertainty in the grassland CH4 sink capacity due to diverse environmental gradients in which grasslands occur, and many environmental conditions can affect abiotic (e.g., CH4 diffusivity into soils) and biotic (e.g., methanotrophy) factors that determine spatial and temporal CH4 dynamics. We investigated the relative importance of a soil's gas diffusivity versus net methanotroph activity in 22 field plots in seven sites distributed across the US Great Plains by making approximately biweekly measures during the growing seasons over 3 years. We quantified net methanotroph activity and diffusivity by using an approach combining a gas tracer, chamber headspace measurements, and a mathematical model. At each plot, we also measured environmental characteristics, including water‐filled pore space (WFPS), soil temperature, and inorganic nitrogen contents, and examined the relative importance of these for controlling diffusivity and net methanotroph activity. At most of the plots across the seven sites, CH4 uptake rates were consistently greatest when WFPS was intermediate at the plot level. Our results show that variation in net methanotroph activity was more important than diffusivity in explaining temporal variations in net CH4 uptake, but the two factors were equally important for driving spatial variation across the seven sites. WFPS was a significant predictor for diffusivity only in plots with sandy soils. WFPS was the most important control on net methanotroph activity, with net methanotroph activity showing a parabolic response to WFPS (concave down), and the shape of this response differed significantly among sites. Moreover, we found that the WFPS level at peak net methanotroph activity was strongly correlated with the mean annual precipitation of the site. These results suggest that the local precipitation regime determines unique sensitivity of CH4 uptake rates to soil moisture. Our findings indicate that grassland CH4 uptake may be predicted using local soil water conditions. More variable soil moisture, potentially induced through predicted future extremes of rainfall and drought, could reduce grassland CH4 sink capacity in the future.
Densimetric sorting of olives to control olive oil quality
Authors: Spadi Agnese , Corti Ferdinando , Angeloni Giulia , Calamai Luca , Masella Piernicola , Parenti Alessandro
Published: September 2024

Extra virgin is the most valuable commercial category among olive oils, and its quality is influenced by various factors, among which the olive fruit plays a fundamental role. The olives that enter the mill exhibit significant variability in physical and chemical characteristics, potentially impacting the quality of the extracted oil. Therefore, selecting the olives in post‐harvest could be a crucial step, especially for differentiating the final product and producing high‐quality oil. This work aimed to conduct post‐harvest densimetric sorting of the olives. For this purpose, a saline solution was used with different concentrations of salt over the 3 days of harvesting, which made it possible to divide the initial olive batch into two sub‐batches with different densities. The respective oil was extracted from each sub‐batch, called low‐ and high‐density oils, respectively, and then appropriate physical–chemical analyses were performed to characterize both the olives and the oils. Although both oils were classified as extra virgin, significant differences were observed, with higher concentrations of phenolic and volatile compounds associated with positive sensory attributes in the low‐density oils. Densimetric sorting of olives could represent a novel approach in the field of extra virgin olive oil production, enabling potential differentiation of the final product.

Practical Applications: The results obtained in the study could be applied at an industrial level to classify olives in the post‐harvest phase. This could allow to produce extra virgin olive oils (EVOOs) with different chemical and sensory characteristics, particularly in terms of volatile and phenolic compounds. This would make it possible to diversify the production of EVOO, satisfy the diverse needs of consumers, allow producers to be more competitive in the market, and, in general, improve the overall quality of the final product.
Fragility functions for low‐damage post‐tensioned timber frames
Authors: Matteoni Michele , Ciurlanti Jonathan , Bianchi Simona , Pampanin Stefano
Published: September 2024

The growing concern over environmental impact and the significant improvement in the quality of engineered wood products have led to the rapid growth of the timber building industry in the last decades. Although traditional, yet recent, mass timber structural systems, such as cross‐laminated timber walls, can provide satisfactory seismic performance during earthquakes in terms of life‐safety, the crucial need for more resilient timber buildings has prompted the development of low‐damage high‐performance self‐centring and dissipative solutions based on unbonded post‐tensioned hybrid connections, referred to as Pres‐Lam technology. The flexibility of design and construction speed, combined with the enhanced seismic performance, create a unique potential towards an earthquake‐proof sustainable building system. Despite the growing popularity of the technology, a comprehensive framework for the fragility analysis, to be used in risk and loss modelling applications, has not yet been developed for both component and building levels.

This article aims to develop a framework for assessing the fragility curves of moment‐resisting Pres‐Lam frame systems, at both structural system and connection levels, by using and comparing different approaches that involve nonlinear static (pushover) and time history dynamic analyses. A Python‐based parametric workflow was developed to evaluate fragility curves for a wide range of case‐study buildings. Particularly, three distinct structures were selected, and their fragility curves were evaluated utilizing alternative methodologies at a building structural‐system level. Finally, fragility models were fitted for individual structural connections using the results of time‐history analyses. These models are intended for use in a component‐based loss assessment.
Do Crops Grown at Urban Dumpsites Contain Metals at Levels that Pose Unacceptable Health Risks to Consumers?
Authors: Awino Florence Barbara , Maher William A. , Fai Patricia Bi Asanga
Published: September 2024

Excessive dietary metal intake from crops grown on contaminated urban dumpsites poses a global health risk to consumers. We evaluated the health risk to adult and child consumers from dietary exposure to metals and metalloids in crops cultivated at the Mbale (Uganda) dumpsite centre. Thirteen crop types grown on the dumpsite soil were sampled and analyzed for concentrations of 11 metals: Fe, Al, Zn, Mn, Cu, Pb, Cr, Hg, Co, Ni, Cd, and two metalloids: Se and As. Different proportions of the crops were combined into 12 meal classes to simulate the diets of residents and estimate noncancer and cancer risks. The findings indicated that most individual crop types and simulated diets lacked sufficient selenium for bodily functions. Furthermore, their metal accumulations exceeded the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) permissible limits (mg/kg) for Al (20), Fe (100), Ni (10), Cu (20), Mn (10), Pb (0.3), Se (0.05), and Zn (99.4). The four most abundant metals in the various crop types and diets were Al, Fe, Mn, and Zn. A positive correlation between the metals in the crops indicated a common origin, which could possibly be the dumpsite soil. The chronic dietary intake (CDI) of metals was higher in children, and thus children faced higher noncancer and cancer risks compared with adults. The overall CDI values for each metal ranged from 0.000718 to 2.171 in adults, and 0.00125 to 3.781662 in children, which is approximately 1.74 times higher in children than in adult consumers. The noncancer and cancer risks ranged from moderate to high with Co, Cr, Fe, Mn, and Zn being mostly responsible for the high noncancer risks, and Al being the predominant contributor to cancer risks. The total noncancer risk levels equally ranged from moderate (1.4–3.3) for adults, and moderate to high (2.4–5.7) for children; the cancer risks were moderate to high in adults, with Al contributing to between 68% and 92% of the total risks across the 12 meal classes. Overall, CDI values and noncancer and cancer risks were all higher in children than in adults. The vegetables Amaranthus hybridus, Vigna unguiculate, Amaranthus dubius, and Cucurbita maxima significantly contributed to the high noncancer risk to both adults and children, particularly when they constituted 40% or more of the meal. Four additional vegetables (Cocorhrous olitorous, Brassica oleracea, Amaranthus cruentus, and Gynandropsis gynandra) also posed a high risk to children when consumed in large quantities. Our results highlight the urgent need to develop regulatory frameworks and/or rigorously enforce existing land and food governance policies to protect consumers' health from unsafe metal concentrations in crops grown on dumpsites. Environ Toxicol Chem 2024;43:2628–2644. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Contribution of crop types to cancer risk exposure.
The strategic role of biotics in dental caries prevention: A scoping review
Authors: Banakar Morteza , Fernandes Gustavo Vicentis Oliveira , Etemad‐Moghadam Shahroo , Frankenberger Roland , Pourhajibagher Maryam , Mehran Majid , Yazdi Mohammad Hossein , Haghgoo Roza , Alaeddini Mojgan
Published: September 2024

Dental caries is a global oral health issue that is prevalent and preventable. Biotics (probiotics, prebiotics, symbiotics, and postbiotics) are recommended as low‐cost methods for preventing dental caries. This scoping review aimed to critically review the scientific evidence concerning the role of biotics in caries prevention and maintaining oral health benefits. A systematic search was conducted in several databases from 2012 onward, using specific keywords. The search resulted in 69 articles. While there is limited research on the mechanism of biotics in preventing caries, numerous studies have investigated the impacts of probiotics on decreasing caries risk factors. Probiotics can reduce cariogenic bacteria, reduce acidogenic bacteria, increase pH, and produce antimicrobial compounds. Probiotics can be used as a therapeutic approach to manage caries by restoring eubiosis at the host–microbial interface, which may not be accomplished with traditional therapies. Its positive effect on reducing dental caries is influenced by the choice of potent probiotic strains, appropriate dosage, treatment period, vehicle, and microbial interaction with the host. Specific oral bacteria have also been shown to utilize prebiotics such as urea and arginine, increasing pH levels. This highlights the potential of combining prebiotic and probiotic bacteria for caries prevention. In addition, this review is focused on bacterial‐derived compounds, namely postbiotics, due to their valuable effects in preventing caries. Biotics have demonstrated potential in preventing dental caries and maintaining oral health. Further research is needed to optimize their use and explore the potential of postbiotics for caries prevention.
Neonatal sex and maternal factors associated with small‐for‐gestational‐age neonates: A nationwide population‐based study
Authors: Fu Pei‐Han , Yu Chia‐Hung , Chung Hao‐Wei , Wu Pei‐Hua , Huang Chiao‐Yun , Liang Fu‐Wen
Published: September 2024

Background and Aims

Small‐for‐gestational‐age (SGA) newborns have a higher risk of morbidity and mortality. Recognizing the risk factors for SGA helps raise early awareness of the issue and provides valuable insights for both healthcare providers and pregnant women. We aimed to identify determinants of SGA using population‐based databases in Taiwan.

Methods

Data were retrieved from the National Health Insurance, Birth Reporting, and Maternal and Child Health databases for this nationwide case‐control study. Live births between 20 and 44 weeks of gestation from 2005 to 2014 were enrolled and linked to their mothers to determine maternal conditions during pregnancy. For every SGA newborn, four controls matched by gestational age and birth year were randomly selected. Multivariable logistic regression was used to identify risk factors for SGA, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) accounting for potential confounders and interaction terms.

Results

A total of 158,405 live SGA births were identified, with 623,584 controls randomly selected. Independent risk factors for SGA included maternal age <20 years (aOR 1.68, 95% CI 1.62, 1.75); female sex in newborns (aOR 1.28, 95% CI 1.27, 1.30); socioeconomic deprivation (aOR 1.29, 95% CI 1.21, 1.38); hypertension (aOR 1.6, 95% CI 1.52, 1.67); kidney disorders (aOR 1.29, 95% CI 1.16, 1.44); thyroid disorders (aOR 1.13, 95% CI 1.09, 1.17); systemic lupus erythematosus (aOR 2.59, 95% CI 2.33, 2.89); antiphospholipid syndrome (aOR 2.08, 95% CI 1.64, 2.64); gestational hypertension (aOR 1.69, 95% CI 1.61, 1.76); pre‐eclampsia (aOR 3.12, 95% CI 3.01, 3.25); and antepartum hemorrhage (aOR 1.05, 95% CI 1.03, 1.07) after adjustment for other covariates.

Conclusions

SGA was associated with younger maternal age, female newborns, underlying comorbidities, and obstetric conditions. Gestational hypertension and pre‐eclampsia were significant risk factors affecting infants of both sexes and all age groups and could mask the effects of maternal age and infant sex.
Teaching trainees to implement functional communication training with multiple schedules: An evaluation of training effects and durability
Authors: Yassa Rana R. , Mitteer Daniel R. , Greer Brian D. , Angley Shannon M. , McCabe Liam H. , Elwasli Omar M.
Published: September 2024

We evaluated the effects of behavioral skills training on improving participant implementation of functional communication training with multiple schedules when working with a confederate. Behavioral skills training produced mastery‐level responding for all six participants who required training, providing the first empirically supported training for this functional communication training approach. Next, we assessed durability during training challenges with (a) procedural changes to the original protocol, (b) a novel confederate with different discriminative stimuli and reinforcers, and (c) relapsed confederate destructive behavior. Training effects degraded at least once for all participants and in 62% of training challenges, although continuing to expose the participant to the challenging situations or providing postsession booster training resolved the degradation in most cases. We discuss these findings in relation to their clinical implications and directions for future research.
The Innovative Role of Nuclear Receptor Interaction Protein in Orchestrating Invadosome Formation for Myoblast Fusion
Authors: Chen Hsin‐Hsiung , Lin Chia‐Yang , Han Ya‐Ju , Huang Yun‐Hsin , Liu Yi‐Hsiang , Hsu Wan‐En , Tsai Li‐Kai , Lai Hsing‐Jung , Tsao Yeou‐Ping , Huang Hsiang‐Po , Chen Show‐Li
Published: September 2024

Background

Nuclear receptor interaction protein (NRIP) is versatile and engages with various proteins to execute its diverse biological function. NRIP deficiency was reported to cause small myofibre size in adult muscle regeneration, indicating a crucial role of NRIP in myoblast fusion.

Methods

The colocalization and interaction of NRIP with actin were investigated by immunofluorescence and immunoprecipitation assay, respectively. The participation of NRIP in myoblast fusion was demonstrated by cell fusion assay and time‐lapse microscopy. The NRIP mutants were generated for mechanism study in NRIP‐null C2C12 (termed KO19) cells and muscle‐specific NRIP knockout (NRIP cKO) mice. A GEO profile database was used to analyse NRIP expression in Duchenne muscular dystrophy (DMD) patients.

Results

In this study, we found that NRIP directly and reciprocally interacted with actin both in vitro and in cells. Immunofluorescence microscopy showed that the endogenous NRIP colocalized with components of invadosome, such as actin, Tks5, and cortactin, at the tips of cells during C2C12 differentiation. The KO19 cells were generated and exhibited a significant deficit in myoblast fusion compared with wild‐type C2C12 cells (3.16% vs. 33.67%, p < 0.005). Overexpressed NRIP in KO19 cells could rescue myotube formation compared with control (3.37% vs. 1.00%, p < 0.01). We further confirmed that NRIP directly participated in cell fusion by using a cell–cell fusion assay. We investigated the mechanism of invadosome formation for myoblast fusion, which depends on NRIP–actin interaction, by analysing NRIP mutants in NRIP‐null cells. Loss of actin‐binding of NRIP reduced invadosome (enrichment ratio, 1.00 vs. 2.54, p < 0.01) and myotube formation (21.82% vs. 35.71%, p < 0.05) in KO19 cells and forced NRIP expression in KO19 cells and muscle‐specific NRIP knockout (NRIP cKO) mice increased myofibre size compared with controls (over 1500 μm2, 61.01% vs. 20.57%, p < 0.001). We also found that the NRIP mRNA level was decreased in DMD patients compared with healthy controls (18 072 vs. 28 289, p < 0.001, N = 10 for both groups).

Conclusions

NRIP is a novel actin‐binding protein for invadosome formation to induce myoblast fusion.
Incidence and dynamics of mobility device use among community‐dwelling older adults in the United States
Authors: Liu Xinran , Baumann Sara E. , Rosso Andrea L. , Venditti Elizabeth M. , Yao Yao , Albert Steven M.
Published: September 2024

Mobility devices are crucial in enhancing activities and participation for individuals with mobility disability, particularly among the rapidly expanding population of older adults worldwide. This paper explores patterns of mobility device use among a nationally representative cohort of community‐dwelling older adults in the United States, using data from the National Health and Aging Trends Study (NHATS) waves 1–9 (2011–2019). Our descriptive analysis focuses on the characteristics of incident mobility device use, its influencing factors, and related user experiences, aligning with the NHATS late‐life disability framework. Mobility devices were categorized into walking aids (WAs), wheeled and seated mobility devices (WSMDs), and mixed use of both. We identified 2,943 incidents of mobility device use among 2,591 participants, spanning 47,722 person‐years in community settings, yielding an incidence rate of 61.7 per 1,000 person‐years. Over half (51.3%) of mobility device use ended in 1 year, with WAs being the predominantly used (63.8%). About one‐third (30.5%) of these incidents involved a change in device combinations, with a notable shift towards WSMDs and mixed use over time. We found that older adults using WSMDs or changing their device combinations were in a more vulnerable state, while those using mixed devices or changing their device combinations experienced poorer user experiences. This study advocates for the implementation of rental and recycling programs, the involvement of NGOs and professional associations, and the adoption of flexible policies responding to the dynamic patterns of mobility device use among community‐dwelling older adults. It also recommends expanding services to better serve vulnerable subgroups.
Exploring vision transformers for classifying early Barrett's dysplasia in endoscopic images: A pilot study on white‐light and narrow‐band imaging
Authors: Tan Jin L , Pitawela Dileepa , Chinnaratha Mohamed A , Beany Andrawus , Aguila Enrik J , Chen Hsiang‐Ting , Carneiro Gustavo , Singh Rajvinder
Published: September 2024

Background and Aim

Various deep learning models, based on convolutional neural network (CNN), have been shown to improve the detection of early esophageal neoplasia in Barrett's esophagus. Vision transformer (ViT), derived from natural language processing, has emerged as the new state‐of‐the‐art for image recognition, outperforming predecessors such as CNN. This pilot study explores the use of ViT to classify the presence or absence of early esophageal neoplasia in endoscopic images of Barrett's esophagus.

Methods

A BO dataset of 1918 images of Barrett's esophagus from 267 unique patients was used. The images were classified as dysplastic (D‐BO) or non‐dysplastic (ND‐BO). A pretrained vision transformer model, ViTBase16, was used to develop our classifier models. Three ViT models were developed for comparison based on imaging modality: white‐light imaging (WLI), narrow‐band imaging (NBI), and combined modalities. Performance of each model was evaluated based on accuracy, sensitivity, specificity, confusion matrices, and receiver operating characteristic curves.

Results

The ViT models demonstrated the following performance: WLI‐ViT (Accuracy: 92%, Sensitivity: 82%, Specificity: 95%), NBI‐ViT (Accuracy: 99%, Sensitivity: 97%, Specificity: 99%), and combined modalities‐ViT (Accuracy: 93%, Sensitivity: 87%, Specificity: 95%). Combined modalities‐ViT showed greater accuracy (94% vs 90%) and sensitivity (80% vs 70%) compared with WLI‐ViT when classifying WLI images on a subgroup testing set.

Conclusion

ViT exhibited high accuracy in classifying the presence or absence of EON in endoscopic images of Barrett's esophagus. ViT has the potential to be widely applicable to other endoscopic diagnoses of gastrointestinal diseases.
Syntheses of 2,4‐Substituted Quinazolines via One‐Pot Three‐Component Reactions Based on Manganese Dioxide/tert‐Butyl Hydrogen Peroxide Co‐Oxidation Using Alcohols
Authors: Wang Yihong , Huang Sheng , Chen Xuehua , Zhu Haibo , Le Zhanggao , Xie Zongbo
Published: September 2024

Quinazolines and their derivatives occur in various natural products and pharmaceuticals, and thus, various methods of synthesizing quinazolines have been explored. They have traditionally been synthesized via two‐component reactions, but these strategies often suffer from the unavailability of the starting materials and limited substrate scopes. To overcome these problems, three‐component reactions using additional N sources were developed. Aldehydes were initially used in these reactions, but alcohols are greener and less toxic than aldehydes. However, the previously reported methods involving the use of alcohols require the utilization of transition metal catalysts, ultrahigh temperatures, and extended durations. Thus, an efficient, practical method of synthesizing quinazolines using alcohol is desirable. A facile one‐pot three‐component method of synthesizing quinazolines utilizing alcohols, 2‐aminobenzoketones, and ammonium acetate is reported for the first time, using active MnO2 and tert‐butyl hydrogen peroxide (TBHP) as synergistic oxidants. MnO2 and TBHP play dual roles: First, they oxidize the alcohol to the aldehyde and then facilitate the transformation of the intermediate into the product. During alcohol oxidation, the synergistic effect of MnO2 and TBHP is particularly evident. The aldehydes generated in situ via alcohol oxidation undergo immediate subsequent reactions, thereby minimizing their volatilization and side reactions, such as oxidation and polymerization.
Discovery of Combustion‐Like in‐Source Oxidation of Linear Saturated Hydrocarbons Using GC‐APCI‐HRMS
Authors: Brown Lindsay P. , Seaton Wesley B. , Powers Joshua B. , Campagna Shawn R.
Published: September 2024

Atmospheric pressure chemical ionization (APCI) is often used in the analysis of linear saturated hydrocarbons (LSHs) as this ionization technique commonly produces [M − H]+ ions in high abundance. However, APCI (along with other atmospheric pressure sources) is often impacted by in‐source oxidation, leading to a variety of ionic products. Identifying these products and understanding their mechanisms of formation is crucial for characterizing complex mixtures with substantial hydrocarbon content, such as those found in the petrochemical industry. In this study, in‐source oxidation of LSHs was observed in gas chromatography (GC) coupled to high‐resolution mass spectrometry (HRMS) via a custom‐built APCI interface. Studies showed that the abundance of these oxidized ions correlated positively with atmospheric water, yet occurred without the inclusion of water‐based oxygen as judged by experiments with stable isotope‐labeled water. The oxidation of LSHs was further influenced by the reactive species in the ionization atmosphere. Fragmentation data using stable isotope‐labeled LSH standards unveiled multiple structurally unique ions with one or more oxidation sites on both primary and secondary carbons. These ionic products bear resemblance to combustion byproducts, suggesting the instrumental configuration fosters plasma‐assisted combustion‐like processes that encourage the radical‐mediated oxidation of LSHs rather than generate [M − H]+. Through these investigative efforts, a mechanism analogous to combustion was proposed for the formation of LSH oxidation products in GC‐APCI‐HRMS. Data demonstrate that these ions are robustly generated in petrochemical products, allowing for proper characterization of these complex mixtures.
Divergent autoantibody and cytokine levels in COVID‐19 sepsis patients influence survival
Authors: Kühn Daniel , Heinen Natalie , Sutter Kathrin , Herrmann Simon T. , Nocke Maximilian K. , Todt Daniel , Burbelo Peter D. , Steinmann Eike , Ziehe Dominik , Koos Björn , Adamzik Michael , Putensen Christian , Zarbock Alexander , Gravemann Ute , Jork Christine , Pfaender Stephanie ,   SepsisDataNet.NRW and CovidDataNet.NRW research group
Published: September 2024

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID‐19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID‐19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung‐associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID‐19‐Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)‐λ1 and IP‐10 were higher in the COVID‐19‐Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30‐day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID‐19.
Uncertain about uncertainty in matching‐adjusted indirect comparisons? A simulation study to compare methods for variance estimation
Authors: Chandler Conor O. , Proskorovsky Irina
Published: September 2024

In health technology assessment, matching‐adjusted indirect comparison (MAIC) is the most common method for pairwise comparisons that control for imbalances in baseline characteristics across trials. One of the primary challenges in MAIC is the need to properly account for the additional uncertainty introduced by the matching process. Limited evidence and guidance are available on variance estimation in MAICs. Therefore, we conducted a comprehensive Monte Carlo simulation study to evaluate the performance of different statistical methods across 108 scenarios. Four general approaches for variance estimation were compared in both anchored and unanchored MAICs of binary and time‐to‐event outcomes: (1) conventional estimators (CE) using raw weights; (2) CE using weights rescaled to the effective sample size (ESS); (3) robust sandwich estimators; and (4) bootstrapping. Several variants of sandwich estimators and bootstrap methods were tested. Performance was quantified on the basis of empirical coverage probabilities for 95% confidence intervals and variability ratios. Variability was underestimated by CE + raw weights when population overlap was poor or moderate. Despite several theoretical limitations, CE + ESS weights accurately estimated uncertainty across most scenarios. Original implementations of sandwich estimators had a downward bias in MAICs with a small ESS, and finite sample adjustments led to marked improvements. Bootstrapping was unstable if population overlap was poor and the sample size was limited. All methods produced valid coverage probabilities and standard errors in cases of strong population overlap. Our findings indicate that the sample size, population overlap, and outcome type are important considerations for variance estimation in MAICs.
Mechanism Underlying the Influence of Family Travel on Adolescent Self‐Differentiation: A Social Learning Theory Perspective
Authors: Tang Jinwen , Xiang Xu , Wang Jingna , Schänzel Heike
Published: September 2024

Most tourism studies have investigated adolescent experiences and their subjective feelings toward family travel. However, the research regarding how family travel influences adolescent mental development is still fragmented. To fill this research gap, this study used social learning theory and a grounded theory approach to explore the identity development and self‐growth of 12 adolescents from families in China with family travel experiences. Taking a child‐centered and participatory approach, the adolescents and their parents (one per family) were interviewed. The data indicated that the away‐from‐home of family travel could lead adolescents to undergo internalization‐based learning as a stress response; such learning could increase adolescents' self‐differentiation by improving their self‐efficacy and enable behavioral growth and achievement. This study developed a new theory for social learning, that is environment–cognition–stress response–behavior, and the mechanisms underlying the influence of family travel on adolescent self‐differentiation emerged. This study provides theoretical contributions useful in the development of family travel experiences and products.
Connectivity between Siberian river runoff and the lower limb of the Atlantic Meridional Overturning Circulation
Authors: Gjelstrup Caroline V. B. , Myers Paul G. , Lee Craig M. , Azetsu‐Scott Kumiko , Stedmon Colin A.
Published: September 2024

Freshwater from the Arctic participates in the globally important Atlantic Meridional Overturning Circulation (AMOC). We use high‐resolution, in situ observations of dissolved organic matter (DOM) fluorescence to trace the origins of freshwater and organic carbon in the densest component of the AMOC, namely Denmark Strait Overflow Water (DSOW). We find a distinct terrestrial DOM signal in DSOW and trace it upstream to the Siberian shelves in the Arctic Ocean. This implies a riverine origin of freshwater in DSOW. We estimate that the Siberian Shelf water contribution constitutes approximately 1% of DSOW. Ocean circulation modeling confirms the inferred pathway and highlights Denmark Strait as an important location for the entrainment of the riverine signal into DSOW. Our proposed method can be deployed on a range of observing systems to elucidate freshwater dispersion across the Arctic and subarctic, thereby contributing to the broader discussion on freshwater impacts and organic carbon sequestration in the AMOC.
Equivariant birational types and derived categories
Authors: Böhning Christian , von Bothmer Hans‐Christian Graf , Tschinkel Yuri
Published: September 2024

We investigate equivariant birational geometry of rational surfaces and threefolds from the perspective of derived categories.
Fatty acid composition MRI of epicardial adipose tissue: Methods and detection of proinflammatory biomarkers in ST‐segment elevation myocardial infarction patients
Authors: Echols John T. , Wang Shuo , Patel Amit R. , Hogwood Austin C. , Abbate Antonio , Epstein Frederick H.
Published: September 2024

Purpose

To develop a method for quantifying the fatty acid composition (FAC) of human epicardial adipose tissue (EAT) using accelerated MRI and identify its potential for detecting proinflammatory biomarkers in patients with ST‐segment elevation myocardial infarction (STEMI).

Methods

A multi‐echo radial gradient‐echo sequence was developed for accelerated imaging during a breath hold using a locally low‐rank denoising technique to reconstruct undersampled images. FAC mapping was achieved by fitting the multi‐echo images to a multi‐resonance complex signal model based on triglyceride characterization. Validation of the method was assessed using a phantom comprised of multiple oils. In vivo imaging was performed in STEMI patients (n = 21; 14 males/seven females). FAC was quantified in EAT, subcutaneous AT, and abdominal visceral AT.

Results

Phantom validation demonstrated strong correlations (r > 0.97) and statistical significance (p < 0.0001) between measured and reference proton density fat fraction and FAC values. In vivo imaging of STEMI patients revealed a distinct EAT FAC profile compared to subcutaneous AT and abdominal visceral AT. EAT FAC parameters had significant correlations with left ventricular (LV) end‐diastolic volume index (p < 0.05), LV end‐systolic volume index (p < 0.05), and LV mass index (p < 0.05).

Conclusions

Accelerated MRI enabled accurate quantification of human EAT FAC. The relationships between the EAT FAC profile and LV structure and function in STEMI patients suggest the potential of EAT FAC MRI as a biomarker for adipose tissue quality and inflammatory status in cardiovascular disease.
Investigating microstructural changes between in vivo and perfused ex vivo marmoset brains using oscillating gradient and b‐tensor encoded diffusion MRI at 9.4 T
Authors: Santini Tales , Shim Alyson , Liou Jr‐Jiun , Rahman Naila , Varela‐Mattatall Gabriel , Budde Matthew D. , Inoue Wataru , Everling Stefan , Baron Corey A.
Published: September 2024

Purpose

To investigate microstructural alterations induced by perfusion fixation in brain tissues using advanced diffusion MRI techniques and estimate their potential impact on the application of ex vivo models to in vivo microstructure.

Methods

We used oscillating gradient spin echo (OGSE) and b‐tensor encoding diffusion MRI to examine in vivo and ex vivo microstructural differences in the marmoset brain. OGSE was used to shorten effective diffusion times, whereas b‐tensor encoding allowed for the differentiation of isotropic and anisotropic kurtosis. Additionally, we performed Monte Carlo simulations to estimate the potential microstructural changes in the tissues.

Results

We report large changes (˜50%–60%) in kurtosis frequency dispersion (OGSE) and in both anisotropic and isotropic kurtosis (b‐tensor encoding) after perfusion fixation. Structural MRI showed an average volume reduction of about 10%. Monte Carlo simulations indicated that these alterations could likely be attributed to extracellular fluid loss possibly combined with axon beading and increased dot compartment signal fraction. Little evidence was observed for reductions in axonal caliber.

Conclusion

Our findings shed light on advanced MRI parameter changes that are induced by perfusion fixation and potential microstructural sources for these changes. This work also suggests that caution should be exercised when applying ex vivo models to infer in vivo tissue microstructure, as significant differences may arise.