bluuebunny/crossref_metadata_2025 huggingface dataset:
Refining the pool of RNA-binding domains advances the classification and prediction of RNA-binding proteins
Authors: Wassmer Elsa , Koppány Gergely , Hermes Malte , Diederichs Sven , Caudron-Herger Maïwen
Published: June 2024

From transcription to decay, RNA-binding proteins (RBPs) influence RNA metabolism. Using the RBP2GO database that combines proteome-wide RBP screens from 13 species, we investigated the RNA-binding features of 176 896 proteins. By compiling published lists of RNA-binding domains (RBDs) and RNA-related protein family (Rfam) IDs with lists from the InterPro database, we analyzed the distribution of the RBDs and Rfam IDs in RBPs and non-RBPs to select RBDs and Rfam IDs that were enriched in RBPs. We also explored proteins for their content in intrinsically disordered regions (IDRs) and low complexity regions (LCRs). We found a strong positive correlation between IDRs and RBDs and a co-occurrence of specific LCRs. Our bioinformatic analysis indicated that RBDs/Rfam IDs were strong indicators of the RNA-binding potential of proteins and helped predicting new RBP candidates, especially in less investigated species. By further analyzing RBPs without RBD, we predicted new RBDs that were validated by RNA-bound peptides. Finally, we created the RBP2GO composite score by combining the RBP2GO score with new quality factors linked to RBDs and Rfam IDs. Based on the RBP2GO composite score, we compiled a list of 2018 high-confidence human RBPs. The knowledge collected here was integrated into the RBP2GO database at https://RBP2GO-2-Beta.dkfz.de.
Comparative analysis of RNA 3D structure prediction methods: towards enhanced modeling of RNA–ligand interactions
Authors: Nithin Chandran , Kmiecik Sebastian , Błaszczyk Roman , Nowicka Julita , Tuszyńska Irina
Published: June 2024

Accurate RNA structure models are crucial for designing small molecule ligands that modulate their functions. This study assesses six standalone RNA 3D structure prediction methods—DeepFoldRNA, RhoFold, BRiQ, FARFAR2, SimRNA and Vfold2, excluding web-based tools due to intellectual property concerns. We focus on reproducing the RNA structure existing in RNA-small molecule complexes, particularly on the ability to model ligand binding sites. Using a comprehensive set of RNA structures from the PDB, which includes diverse structural elements, we found that machine learning (ML)-based methods effectively predict global RNA folds but are less accurate with local interactions. Conversely, non-ML-based methods demonstrate higher precision in modeling intramolecular interactions, particularly with secondary structure restraints. Importantly, ligand-binding site accuracy can remain sufficiently high for practical use, even if the overall model quality is not optimal. With the recent release of AlphaFold 3, we included this advanced method in our tests. Benchmark subsets containing new structures, not used in the training of the tested ML methods, show that AlphaFold 3′s performance was comparable to other ML-based methods, albeit with some challenges in accurately modeling ligand binding sites. This study underscores the importance of enhancing binding site prediction accuracy and the challenges in modeling RNA–ligand interactions accurately.
Methods of Assessment of Zinc Status in Humans: An Updated Review and Meta-analysis
Authors: Ceballos-Rasgado Marena , Brazier Anna K M , Gupta Swarnim , Moran Victoria H , Pierella Elisa , Fekete Katalin , Lowe Nicola M
Published: June 2024

Context

The assessment of zinc status is difficult but essential for the identification of zinc deficiency and evaluation of interventions to improve zinc status.

Objective

The purpose of this systematic review (SR) and meta-analysis was to update the previously published SR of biomarkers of zinc status, conducted by the European Micronutrient Recommendations Aligned (EURRECA) network in 2009, to answer the question: Which putative measures (biomarkers) of zinc status appropriately reflect a change in zinc intake of at least 2 weeks?

Data Sources

A structured search strategy was used to identify articles published between January 2007 and September 2022 from MEDLINE (Ovid), Embase (Ovid), Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles were identified using previously defined eligibility criteria.

Data Extraction

Data were extracted and combined with data from the previous SR.

Data Analysis

A random-effects model was used to calculate pooled mean differences using STATA (StataCorp). The risk of bias and the certainty of evidence for all outcomes were assessed. Additional data on 7 of the 32 previously reported biomarkers were identified, along with data on an additional 40 putative biomarkers from studies published since 2007. Pooled data analysis confirmed that, in healthy participants, both plasma/serum zinc concentration and urinary zinc excretion responded to changes in zinc intake (plasma/serum: mean effect [95% CI], controlled studies: 2.17 µmol/L [1.73, 2.61]; P < .005, I2 = 97.8; before-and-after studies: 2.87 µmol/L [2.45, 3.30]; P < .005, I2 = 98.1%; urine zinc: 0.39 mmol/mol creatinine [0.17, 0.62]; P < .005, I2 = 81.2; 3.09 µmol/day [0.16, 6.02]; P = .039, I2 = 94.3).

Conclusion

The updated analyses support the conclusion that plasma/serum and urinary zinc respond to changes in zinc intake in studies of healthy participants. Several additional putative biomarkers were identified, but more studies are needed to assess the sensitivity and reliability.

Systematic Review Registration

PROSPERO no. CRD42020219843.
Relationship of Curcumin with Aging and Alzheimer and Parkinson Disease, the Most Prevalent Age-Related Neurodegenerative Diseases: A Narrative Review
Authors: Turer Büşra Yurt , Sanlier Nevin
Published: June 2024

The elderly population is increasing worldwide every day. Age is a significant factor in the progression of neurological diseases, which can also cause cognitive decline and memory disorders. Inflammation and oxidative stress are primary drivers of senescence and disorders, particularly those associated with aging and neurodegenerative diseases. Bioactive phytochemicals are considered a promising therapeutic strategy in combating aging and age-related pathological conditions. One of the phytochemicals with diverse biological properties encompassing antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, antifungal, antidepressant, anti-allergic, and anti-aging properties is curcumin. Curcumin, a polyphenolic structure with a distinct orange hue and unique chemical properties, is derived from the roots of Curcuma longa, a member of the Zingiberaceae family, commonly known as turmeric. It has been noted that the incidence of neurodegenerative diseases is low in societies that consume curcumin widely. Therefore, this review investigates the effect of curcumin on aging and Alzheimer and Parkinson disease, which are the most prevalent age-related neurodegenerative diseases.
The Association of Oral Processing Factors and Nutrient Intake in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis
Authors: Nitsuwat Supatchayaporn , Webster James , Sarkar Anwesha , Cade Janet
Published: June 2024

Context

Oral health and food oral-processing issues emerge with functional decline in the older adult population, potentially increasing the risk of malnutrition. Impairment of oral health is associated with poorer nutrition status; however, the relationship between oral factors and the intake of each nutrient remains poorly understood.

Objective

The associations between different oral factors and nutrient intakes among community-dwelling older adults were investigated.

Data Sources

A literature search from 5 databases (Web of Science, Scopus, Cochrane Library, Ovid [MEDLINE and Embase], and CINAHL) was completed on February 1, 2022. The search was limited to peer-reviewed articles published between the years 2012 and 2022.

Data Extraction

Six cross-sectional studies were included in the meta-analysis. Two authors independently completed the data extraction and summarized the study characteristics, factors adjusted for in the statistical analysis, the outcome, and summary statistics of the results.

Data Analysis

Meta-analyses showed evidence of a significant association between compromised oral factors (namely, denture status, chewing ability, and the number of teeth) with lower energy (weighted mean difference [WMD], –107 kcal d–1 (95% CI, –132 to –81), protein (WMD, –5.2 g d–1; 95% CI, –6.6 to –3.8), fat (WMD, –4.6 g d–1; 95% CI, –6.7 to –2.6), carbohydrate (WMD, –8.8 g d–1; 95% CI, –13.9 to –3.7), and vitamin C intakes (WMD, –12.9 mg d–1; 95% CI, –16.6 to –9.2) in older adults.

Conclusion

Oral health can be an indicator of compromised daily energy, protein, fat, carbohydrate, and vitamin C intakes in older adults. However, the small sample size of the studies included in this review and the heterogeneity among macronutrient studies should be considered. Because of the lack of studies covering all aspects of food oral processing (eg, salivary flow rate, tongue pressure), the associations between oral processing and nutrient intake were not thoroughly explored.

Systematic Review Registration

PROSPERO registration no. CRD42022308823.
Cryptococcosis Associated With Biologic Therapy: A Narrative Review
Authors: Li Xin , Paccoud Olivier , Chan Koon-Ho , Yuen Kwok-Yung , Manchon Romain , Lanternier Fanny , Slavin Monica A , van de Veerdonk Frank L , Bicanic Tihana , Lortholary Olivier
Published: June 2024

Cryptococcus is an opportunistic fungal pathogen that can cause disseminated infection with predominant central nervous system involvement in patients with compromised immunity. Biologics are increasingly used in the treatment of neoplasms and autoimmune/inflammatory conditions and the prevention of transplant rejection, which may affect human defense mechanisms against cryptococcosis. In this review, we comprehensively investigate the association between cryptococcosis and various biologics, highlighting their risks of infection, clinical manifestations, and clinical outcomes. Clinicians should remain vigilant for the risk of cryptococcosis in patients receiving biologics that affect the Th1/macrophage activation pathways, such as tumor necrosis factor α antagonists, Bruton tyrosine kinase inhibitors, fingolimod, JAK/STAT inhibitors (Janus kinase/signal transducer and activator of transcription), and monoclonal antibody against CD52. Other risk factors—such as age, underlying condition, and concurrent immunosuppressants, especially corticosteroids—should also be taken into account during risk stratification.
Genetic factors of grain cadmium concentration in Polish wheat (Triticum polonicum L.)
Authors: Cheng Yiran , Liu Rui , Yang Tian , Yang Shan , Chen Jia , Huang Yiwen , Long Dan , Zeng Jian , Wu Dandan , Kang Houyang , Fan Xing , Sha Lina , Zhang Haiqin , Zhou Yonghong , Wang Yi
Published: June 2024

Wheat (Triticum aestivum L.) is one of the most important crops worldwide and a major source of human cadmium (Cd) intake. Limiting grain Cd concentration (Gr_Cd_Conc) in wheat is necessary to ensure food safety. However, the genetic factors associated with Cd uptake, translocation and distribution and Gr_Cd_Conc in wheat are poorly understood. Here, we mapped quantitative trait loci (QTLs) for Gr_Cd_Conc and its related transport pathway using a recombinant inbred line (RIL) population derived from 2 Polish wheat varieties (RIL_DT; dwarf Polish wheat [DPW] and tall Polish wheat [TPW]). We identified 29 novel major QTLs for grain and tissue Cd concentration; 14 novel major QTLs for Cd uptake, translocation, and distribution; and 27 major QTLs for agronomic traits. We also analyzed the pleiotropy of these QTLs. Six novel QTLs (QGr_Cd_Conc-1A, QGr_Cd_Conc-3A, QGr_Cd_Conc-4B, QGr_Cd_Conc-5B, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A) for Gr_Cd_Conc explained 8.16% to 17.02% of the phenotypic variation. QGr_Cd_Conc-3A, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A pleiotropically regulated Cd transport; 3 other QTLs were organ-specific for Gr_Cd_Conc. We fine-mapped the locus of QGr_Cd_Conc-4B and identified the candidate gene as Cation/Ca exchanger 2 (TpCCX2-4B), which was differentially expressed in DPW and TPW. It encodes an endoplasmic reticulum membrane/plasma membrane–localized Cd efflux transporter in yeast. Overexpression of TpCCX2-4B reduced Gr_Cd_Conc in rice. The average Gr_Cd_Conc was significantly lower in TpCCX2-4BDPW genotypes than in TpCCX2-4BTPW genotypes of the RIL_DT population and 2 other natural populations, based on a Kompetitive allele-specific PCR marker derived from the different promoter sequences between TpCCX2-4BDPW and TpCCX2-4BTPW. Our study reveals the genetic mechanism of Cd accumulation in wheat and provides valuable resources for genetic improvement of low–Cd-accumulating wheat cultivars.
How does pornography change desires? A pragmatic account
Authors: Lee Junhyo , Neufeld Eleonore
Published: June 2024

Rae Langton and Caroline West famously argue that pornography operates like a language game, in that it introduces certain views about women into the common ground via presupposition accommodation. While this pragmatic model explains how pornography has the potential to change its viewers’ beliefs, it leaves open how pornography changes people's desires. Our aim in this paper is to show how Langton and West's discourse-theoretic account of pornography can be refined to close this lacuna. Using tools from recent developments in discourse theory, we propose that pornography issues implicit directives, and thereby introduces bouletic components into the discourse.
Falling Interest Rates and Credit Reallocation: Lessons from General Equilibrium
Authors: Asriyan Vladimir , Laeven Luc , Martin Alberto , Van der Ghote Alejandro , Vanasco Victoria
Published: June 2024

We show that in a canonical model with heterogeneous entrepreneurs, financial frictions, and an imperfectly elastic supply of capital, a fall in the interest rate has an ambiguous effect on aggregate economic activity. In partial equilibrium, a lower interest rate raises aggregate investment both by relaxing financial constraints and by prompting relatively less productive entrepreneurs to invest. In general equilibrium, however, this higher demand for capital raises its price and crowds out investment by more productive entrepreneurs. When this reallocation is strong enough, a fall in the interest rate reduces aggregate output. A numerical exploration of the model suggests that this reallocation effect is quantitatively significant and—in response to persistent changes in the interest rate—stronger than the traditional balance-sheet channel. We provide evidence of the reallocation effect using U.S. firm-level data.
Brain regulation training improves emotional competences in patients with alcohol use disorder
Authors: Hack Ramona L , Aigner Martin , Musalek Michael , Crevenna Richard , Konicar Lilian
Published: June 2024

Alcohol use disorder (AUD) is defined as the impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences and still represents one of the biggest challenges for society regarding health conditions, social consequences, and financial costs, including the high relapse rates after traditional alcohol rehabilitation treatment. Especially, the deficient emotional competence in AUD is said to play a key role in the development of AUD and hinders the interruption of substance compulsion, often leading to a viscous circle of relapse. Although the empirical evidence of a neurophysiological basis of AUD is solid and increases even further, clinical interventions based on neurophysiology are still rare for individuals with AUD. This randomized controlled trial investigates changes in emotional competences, alcohol-related cognitions, and drinking behavior before and after an established alcohol rehabilitation treatment (control group: nCG = 29) compared to before and after an optimized, add-on neurofeedback (NF) training (experimental group: nEG = 27). Improvements on the clinical–psychological level, i.e. increases in emotional competences as well as life satisfaction, were found after the experimental electroencephalography (EEG) NF training. Neurophysiological measurements via resting-state EEG indicate decreases in low beta frequency band, while alpha and theta bands remained unaffected.
Toward a Semi-Supervised Learning Approach to Phylogenetic Estimation
Authors: Silvestro Daniele , Latrille Thibault , Salamin Nicolas
Published: June 2024

Models have always been central to inferring molecular evolution and to reconstructing phylogenetic trees. Their use typically involves the development of a mechanistic framework reflecting our understanding of the underlying biological processes, such as nucleotide substitutions, and the estimation of model parameters by maximum likelihood or Bayesian inference. However, deriving and optimizing the likelihood of the data is not always possible under complex evolutionary scenarios or even tractable for large datasets, often leading to unrealistic simplifying assumptions in the fitted models. To overcome this issue, we coupled stochastic simulations of genome evolution with a new supervised deep-learning model to infer key parameters of molecular evolution. Our model is designed to directly analyze multiple sequence alignments and estimate per-site evolutionary rates and divergence without requiring a known phylogenetic tree. The accuracy of our predictions matched that of likelihood-based phylogenetic inference when rate heterogeneity followed a simple gamma distribution, but it strongly exceeded it under more complex patterns of rate variation, such as codon models. Our approach is highly scalable and can be efficiently applied to genomic data, as we showed on a dataset of 26 million nucleotides from the clownfish clade. Our simulations also showed that the integration of per-site rates obtained by deep learning within a Bayesian framework led to significantly more accurate phylogenetic inference, particularly with respect to the estimated branch lengths. We thus propose that future advancements in phylogenetic analysis will benefit from a semi-supervised learning approach that combines deep-learning estimation of substitution rates, which allows for more flexible models of rate variation, and probabilistic inference of the phylogenetic tree, which guarantees interpretability and a rigorous assessment of statistical support.
A Transmission Assay of ‘Candidatus Liberibacter asiaticus’ Using Citrus Phloem Sap and Topical Feeding to Its Insect Vector, Diaphorina citri
Authors: Killiny Nabil , Jones Shelley E.
Published: June 2024

‘ Candidatus Liberibacter asiaticus’, the putative causal agent of citrus greening disease, is transmitted by the Asian citrus psyllid, Diaphorina citri, in a propagative, circulative, and persistent manner. Unfortunately, ‘ Ca. L. asiaticus’ is not yet available in pure culture to carry out Koch's postulates and to confirm its etiology. When a pure culture is available, an assay to test its infectivity in both the insect vector and the plant host will be crucial. Herein, we described a transmission assay based on the use of phloem sap extracted from infected citrus plants and topical feeding to D. citri nymphs. Phloem sap was collected by centrifugation, diluted with 0.1 M phosphate buffer pH 7.4 containing 20% (wt/vol) sucrose and 0.1% ascorbic acid (wt/vol) as an antioxidant, and delivered to third through fifth instar nymphs by placing droplets on the mouthparts. Nymphs unfolded the stylets and acquired the phloem sap containing the bacterial pathogen. Nymphs were then placed onto Citrus macrophylla seedlings (10 nymphs per seedling) for an inoculation period of 2 weeks. A transmission rate of up to 80% was recorded at 6 months postinoculation. The method could be a powerful tool to test the transmissibility of the bacterial pathogen after various treatments to reduce the viability of the bacteria or to block its transmission. In addition, it might be a potent assay to achieve Koch's postulates if a pure culture of ‘ Ca. L. asiaticus’ becomes available.
Yellow Dwarf Virus Resistance in Barley: Phenotyping, Remote Imagery, and Virus–Vector Characterization
Authors: Massman Chris , Rivedal Hannah M. , Dorman Seth J. , Tanner K. Christy , Fredrickson Chance , Temple Todd N. , Fisk Scott , Helgerson Laura , Hayes Patrick M.
Published: June 2024

Yellow dwarf viruses (YDVs) spread by aphids are some of the most economically important barley ( Hordeum vulgare) virus–vector complexes worldwide. Detection and control of these viruses are critical components in the production of barley, wheat, and numerous other grasses of agricultural importance. Genetic control of plant diseases is often preferable to chemical control to reduce the environmental and economic cost of foliar insecticides. Accordingly, the objectives of this work were to (i) screen a barley population for resistance to YDVs under natural infection using phenotypic assessment of disease symptoms, (ii) implement drone imagery to further assess resistance and test its utility as a disease screening tool, (iii) identify the prevailing virus and vector types in the experimental environment, and (iv) perform a genome-wide association study to identify genomic regions associated with measured traits. Significant genetic differences were found in a population of 192 barley inbred lines regarding their YDV symptom severity, and symptoms were moderately to highly correlated with grain yield. The YDV severity measured with aerial imaging was highly correlated with on-the-ground estimates ( r = 0.65). Three aphid species vectoring three YDV species were identified with no apparent genotypic influence on their distribution. A quantitative trait locus impacting YDV resistance was detected on chromosome 2H, albeit undetected using aerial imaging. However, quantitative trait loci for canopy cover and mean normalized difference vegetation index were successfully mapped using the drone. This work provides a framework for utilizing drone imagery in future resistance breeding efforts for YDVs in cereals and grasses, as well as in other virus–vector disease complexes.
Impact of Prophylactic Cerclage Location on Femoral Fracture Propagation: A Biomechanical Study
Authors: Han Shuyang , Reddy Kartik I. , Lanfermeijer Nicholas D. , Frangie Robert , Ismaily Sabir K. , Gold Jonathan E. , Lundberg Hannah J. , Rodriguez-Quintana David
Published: June 2024

OBJECTIVES:

Prophylactic cerclage cables are often placed intraoperatively about a fracture to prevent propagation. However, biomechanical data supporting optimal cable placement location are lacking. The objective of this study was to evaluate the impact of prophylactic cerclage placement location on the propagation of femoral shaft fractures.

METHODS:

The diaphysis of 14 fresh-frozen cadaveric femora were included. Volumetric bone mineral density in the femoral shaft was obtained from quantitative computed tomography scans. For each specimen, a 5-mm longitudinal fracture was created proximally to simulate a pre-existing fracture. After reaming of the femoral canal, a 3 degrees tapered wedge was advanced with an MTS machine at 0.2 mm/s until failure. The tests were conducted with a CoCr cable placed at varying distances (5 mm, 10 mm, 15 mm, 20 mm, and cableless) from the distal tip of the initial fracture. A compression loadcell was used to measure the cable tension during the tests. The axial force, displacement, and cable tension were monitored for comparison between groups.

RESULTS:

In the cableless group, the mean force needed to propagate the fracture was 1017.8 ± 450.3 N. With the addition of a cable at 5 mm below the fracture, the failure force nearly doubled to 1970.4 ± 801.1 N (P < 0.001). This also led to significant increases in stiffness (P = 0.006) and total work (P = 0.001) when compared with the control group. By contrast, in the 15 and 20 mm groups, there were no significant changes in the failure force, stiffness, and total work as compared with the control group (P > 0.05).

CONCLUSIONS:

Propagation of femoral shaft fracture was effectively resisted when a prophylactic cable was placed within 5 mm from the initial fracture, whereas cables placed more than 10 mm below the initial fracture were not effective in preventing fracture propagation.
Revision Rates After Single-Level Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion
Authors: Gordon Adam M. , Elali Faisal R. , Saleh Ahmed
Published: June 2024

Study Design.

A retrospective case-control study.

Objectives.

This study aimed to compare rates and risk factors for all-cause 5-year revisions for patients undergoing primary single-level cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

Prospective studies have compared patient-reported outcomes, adjacent segment degeneration, and long-term revisions between CDA and ACDF. Despite these high-level evidence studies, well-powered, large investigations have not been adequately reported.

Patients and Methods.

A nationwide database was queried for patients undergoing primary single-level CDA or ACDF for degenerative cervical spine pathology. Further inclusion criteria consisted of patients having a minimum 5-year follow-up. Patients undergoing CDA were in a 1:5 ratio matched to patients undergoing ACDF by age, sex, comorbidities, and overall Elixhauser comorbidity index (ECI). Objectives were to compare the rates and risk factors of all-cause 5-year revisions for those undergoing single-level CDA versus ACDF. Multivariate logistic regression models computed the odds ratios (ORs) of revisions within 5 years. P values of less than 0.001 were significant.

Results.

A total of 32,953 patients underwent single-level CDA (N=5,640) or ACDF (N=27,313) with a 5-year minimum follow-up. The incidence of all-cause revisions within 5 years was 1.24% for CDA and 9.23% for ACDF (P<0.001). After adjustment, patients undergoing single-level ACDF had significantly higher odds of all-cause revisions within 5 years (OR: 8.09; P<0.0001). Additional patient-specific factors associated with revisions were a history of reported drug abuse (OR: 1.51; P<0.0001), depression (OR: 1.23; P<0.0001), cardiac arrhythmias (OR: 1.21; P=0.0008), hypertension (OR: 1.20; P=0.0006), and tobacco use (OR: 1.18; P=0.0003).

Conclusions.

In this study of nearly 33,000 single-level cervical spine surgeries with minimum 5-year follow-up, all-cause revision rates were significantly lower for patients undergoing CDA. Surgeons may use this data to counsel patients regarding 5-year revisions following single-level CDA or ACDF.

Level of Evidence.

III.
Revision Thumb Metacarpophalangeal Joint Ulnar Collateral Ligament Reconstruction With Autograft and Button Suspension
Authors: Pflug Emily M. , Rodriguez-Fontan Francisco , Lauder Alexander
Published: June 2024

Recurrent instability following thumb ulnar collateral ligament repair or reconstruction may result in pain and poor function. The use of certain suture anchors during the index procedure may predispose patients to the development of osteolysis and subsequent fixation failure. In this article, we describe an effective surgical technique for revision reconstruction of ulnar collateral ligament injuries using autograft and suture suspensionplasty. This technique restores joint stability and allows functional recovery with minimal postoperative complications.
Brain injury biomarkers and applications in neurological diseases
Authors: Zhang Han , Wang Jing , Qu Yang , Yang Yi , Guo Zhen-Ni
Published: June 2024

Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer’s disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Pediatric Terrien Marginal Degeneration
Authors: Eskenazi-Betech Ruth , Fabregas-Sanchez-Woodworth Daniela , Ramirez-Miranda Arturo , Navas Alejandro , González José M. , Mangwani-Mordani Simran , Graue-Hernández Enrique O.
Published: June 2024

Purpose:

To describe 2 cases of Terrien marginal degeneration (TMD) in young children.

Methods:

A total of 2 pediatric patients aged 5 and 10 years with unremarkable familial history underwent routine ophthalmological examination because of the presence of superior corneal opacities with no other associated symptoms. The younger patient showed lipid deposition adjacent to the superior limbus and peripheral thinning with vessels coursing across the left eye. The visual acuity was 20/20 in both eyes. The older patient had similar clinical features. The visual acuity improved from 20/25 and 20/60 in the right and left eye, respectively, to 20/20 with subjective refraction in both eyes. The left eye revealed a superior crescent-shaped corneal opacity and superotemporal peripheral thinning associated with lipid deposition and superficial vascularization. Serological markers for autoimmune diseases were negative. The patients were diagnosed with TMD.

Results:

Corneal tomography (Pentacam, Oculus, Wetzlar, Germany) revealed steepening of the superior cornea of the affected eye in both patients. Anterior segment optical coherence tomography of the younger patient confirmed marked furrow indentation and peripheral thinning. The older patient showed peripheral stromal thinning on Scheimpflug imaging. These findings supported the diagnosis of TMD.

Conclusions:

Ophthalmologists should acknowledge that TMD can present with or without ocular inflammation, especially at a young age. Given the variable progression rate of TMD, ongoing and thorough monitoring is crucial for effective management and prognosis in affected patients.
Pedunculated Neoplasm of the Vulva
Authors: Zeng Ziyuan , Xiong Xia , Liu Zongjunlin , Lei Qirong , He Yuanmin
Published: June 2024

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy, typically presenting as eczema-like lesions in areas rich in apocrine glands such as the perineum. Here, we report a case of EMPD presenting as a prominent pedunculated neoplasm in a 65-year-old woman. Despite initial misdiagnosis and treatment, biopsy confirmed EMPD infiltration. Following surgical excision, the patient developed brain metastases, indicating a poor prognosis. EMPD's pathogenesis remains unclear, but distinguishing primary from secondary forms is crucial for prognosis and treatment. Our case underscores the importance of recognizing atypical EMPD presentations for timely intervention and improved outcomes.
A Rare Case of Adenocarcinoma With Micropapillary Structure and Apocrine Differentiation Arising in a Sebaceous Tumor
Authors: Shojiguchi Naoko , Arai Eiichi , Kamimura Anna , Yasuda Masanori
Published: June 2024

A 77-year-old Japanese man presented to our hospital with subcutaneous tumors of the right upper arm and axilla. A biopsy revealed a cutaneous adnexal tumor, showing apocrine differentiation, and axillary lymph node metastasis. After chemoradiotherapy to shrink the tumors, both lesions were resected. A resected specimen of the arm tumor showed a variegated histology: (1) a classic sebaceoma with an organoid pattern and sebocytes; (2) a sebaceous tumor with cellular atypia; (3) a papillotubular tumor showing a biphasic pattern of pale eosinophilic cells with apocrine differentiation and basaloid cells; and (4) an invasive adenocarcinoma with a micropapillary structure, reminiscent of an invasive micropapillary carcinoma of the breast. The axillary tumor was regressed. To our knowledge, this is the first reported case of an adnexal tumor of the skin with an invasive micropapillary structure arising in a sebaceous tumor.
Cellular Schwannoma Mimicking a Nodular Melanoma on the Sole of the Foot, an Avoidable Diagnostic Pitfall
Authors: Ruz Portero Begoña , García de Sola Llamas Carmen , Pérez Pérez Manuel , Sánchez Bernal María Luisa , Moreno Ramírez David , Ríos Martín Juan José
Published: June 2024

We report a rare case of cellular schwannoma (CS) manifesting as an ulcerated nodular lesion, mimicking spindle cell melanoma on the sole of the foot. CS, a benign variant of schwannoma, typically occurs in deep soft tissues but can rarely present cutaneously. The diagnosis of CS heavily relies on histopathological examination and immunohistochemical staining for specific markers such as SOX10 and S100. In this case, initial clinical suspicion of nodular melanoma was confirmed on biopsy, which revealed a spindle cell neoplasm positive for SOX10 and negative for melanocytic markers. Misdiagnosis of nodular melanoma was averted through complete excision. CS diagnosis demands careful consideration due to its resemblance to other spindle cell neoplasms, especially melanoma. Meticulous histopathological evaluation and immunostaining are important to differentiate CS from similar lesions, ensuring accurate diagnosis and appropriate management. This report contributes valuable insights into the diagnostic challenges and management of CS, particularly in unusual cutaneous presentations.
Usefulness of a virtual reality educational program for reducing preoperative anxiety in children
Authors: Carbó Adriana , Tresandí Daniel , Tril Cristina , Fernández-Rodríguez Diego , Carrero Enrique
Published: June 2024

BACKGROUND

Preoperative anxiety (PA) is common in children and has detrimental effects on surgical outcome. Strategies based on virtual reality (VR) have recently been introduced to address this problem.

OBJECTIVE

This study evaluated the usefulness of a virtual reality educational program (VREP) for reducing preoperative anxiety in elective low-complexity paediatric surgery.

DESIGN

Randomised clinical trial.

SETTING

Single tertiary centre in Barcelona, Spain. Between January 2019 and June 2022.

PATIENTS

Children aged 3–13 years of age, American Society of Anesthesiologists (ASA) I–II, scheduled for elective low-complexity surgery were enrolled in the study.

INTERVENTION

Children were randomised into a control group (received oral/written information about the anaesthetic-surgical process, and patients and their parents remained in a playroom waiting for the surgery) or VREP (viewed a VR-based educational video on the surgical process, 7–10 days prior to surgery) using the MATLAB application.

MAIN OUTCOME MEASURE

PA using the modified Yale Preoperative Anxiety Scale (mYPAS) during separation from parents.

RESULTS

In total, 241 children aged 3–12 years of age were studied (120 patients with VREP and 121 controls). Randomisation eliminated the differences between the groups, except for a greater male presence in the VREP group (83.3% vs. 71.1%; P = 0.023). The mYPAS yielded was lower in the VREP group (29.2% vs. 83.5%; P < 0.001). Sex did not influence VREP-mediated decrease in PA (P < 0.001). In turn, VREP patients were more cooperative (Induction Compliance Checklist [ICC] score 0 points vs. 2 points; P < 0.001) during anaesthesia induction, presented less delirium (Pediatric Anesthesia Emergence Delirium [PAED] score 1 point vs. 3 points; P = 0.001) on leaving the recovery room, and experienced less pain upon arrival in the hospital ward (Wong-Baker Faces Pain Rating Scale: 0-points vs. 1 point; P < 0.001).

CONCLUSIONS

The VREP-based prevention strategy reduced preoperative anxiety in children undergoing elective low-complexity surgery.

TRIAL REGISTRATION

NCT03578393.
Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots
Authors: Ramadan Ola , Opitz Patrick , Hempel Georg
Published: June 2024

Background:

In neonatal and pediatric intensive care units, Gram-positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram-positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram-positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS).

Methods:

A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods.

Results:

The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%–114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin.

Conclusions:

A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics.
Simultaneous Reconstruction of the Bilateral Maxillae and Nasal Hard Structure Using a Vascularized and Nonvascularized Fibula
Authors: Tsuge Itaru , Yamanaka Hiroki , Katsube Motoki , Sakamoto Michiharu , Morimoto Naoki
Published: June 2024

Midfacial reconstruction for extensive defects of the hard nasal structures and bilateral maxillae is challenging. Postoperative radiotherapy causes skin contracture, making secondary reconstruction extremely difficult. A 57-year-old man underwent resection of the nasal bone, nasal cartilage, and hard palate for cancer of the nasal cavity. Postoperative radiotherapy (70 Gy) resulted in bilateral osteoradionecrosis. Severe depression deformity of the midface causes a disorder in closing the mouth, resulting in difficulty in conversation and oral intake. We performed simultaneous reconstruction of the bilateral maxillary and nasal hard structures using double free flaps (fibular osteocutaneous and anterolateral thigh flaps). A 16-cm right fibular osteocutaneous flap was elevated, and an 8-cm proximal bone was resected to obtain the length of the peroneal vessels. The distal 8 cm was cut into three pieces while maintaining the blood flow. The removed nonvascularized fibula was processed into two pieces of cortex: nasal bridge and columella. All areas of the skin island were de-epithelialized to bilaterally fill the maxillary sinuses. Next, the ipsilateral anterolateral thigh flap was elevated with the central 6-cm part for closure of the palate and the proximal area to fill the nasal cavity. The distal area consisted of a fascial flap to cover the reconstructed nasal structure. The chimeric double flap allowed for oral intake, conversation, and nasomaxillary prominence. Computed tomography performed 8 months postoperatively showed maintained bony structures. We used the extra fibula as a nonvascularized cortex piece to prevent infection and exposure, which enabled simultaneous reconstruction of the bilateral maxillae and hard nasal structure.
Aramchol improves hepatic fibrosis in metabolic dysfunction–associated steatohepatitis: Results of multimodality assessment using both conventional and digital pathology
Authors: Ratziu Vlad , Yilmaz Yusuf , Lazas Don , Friedman Scott L. , Lackner Caroline , Behling Cynthia , Cummings Oscar W. , Chen Li , Petitjean Mathieu , Gilgun-Sherki Yossi , Gorfine Tali , Kadosh Shaul , Eyal Eli , Sanyal Arun J.
Published: June 2024

Background and Aims:

Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction–associated steatohepatitis.

Approach and Results:

Fifty-one patients with metabolic dysfunction–associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; “improved” by ranked pair assessment; reduction in Ph-FCS (“any” for ≥0.3 absolute reduction and “substantial” for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction −0.54 (SD: 1.22) versus −1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness.

Conclusions:

Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.
Research Letter: Concussion-Related General Startle Suppression in Adolescent Athletes
Authors: Oldham Jessie R. , DeFalco Angelica , Willwerth Sarah , Nagle Shannon , Whittaker Freya , Mannix Rebekah , Meehan William P. , Bradford Daniel E.
Published: June 2024

Objectives:

We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls.

Methods:

We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups.

Results:

Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00).

Conclusion:

Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.
Declining Incidence of Kawasaki Disease During the COVID-19 Pandemic: A Time Series Analysis
Authors: Lin Yi-Hsuan , Lin Ching-Heng , Lin Ming-Chih
Published: June 2024

Background:

In 2020, Taiwan experienced a dramatic disruption of daily life due to measures aimed at limiting the spread of coronavirus disease 2019 (COVID-19), although domestic COVID-19 cases were extremely rare. This provided a chance to investigate the change of incidence and possible triggers of Kawasaki disease (KD) without the interference of multisystem inflammatory syndrome in children.

Methods:

This population-based study used Taiwan’s National Health Insurance Research Database. To detect the change in KD incidence in children less than 6 years old during the period of social distancing policy in 2020, the autoregressive integrated moving average model was used based on seasonal variation and the increasing trend of KD incidence over the past 10 years. The trends in population mobility and common infectious diseases were also analyzed to observe their effects on KD incidence.

Results:

The predicted monthly incidence [95% confidence interval (CI)] of KD in April, May and June 2020 were 5.26 (3.58–6.94), 5.45 (3.70–7.20) and 5.41 (3.61–7.21) per 100,000 person-months. The actual observed incidences were 2.41, 2.67 and 2.60 per 100,000 person-months, respectively, representing a 51.2%, 51.0% and 51.9% reduction in incident rates in the 3-month period of stringent COVID-19 mitigation measures. The trend was not proportionate to the profound decline of common infectious cases.

Conclusions:

KD incidence decreased by approximately 50% during the period of stringent COVID-19 mitigation measures in 2020 in Taiwan. Human-to-human contact may be a potential KD trigger, but there are likely other contributing factors aside from infection.
Central Nervous System Infection by Group a Streptococcus in Children in Spain (2019–2023)
Authors: Cobo-Vázquez Elvira , Aguilera-Alonso David , Rello-Saltor Victoria , Gamell Anna , Mellado-Sola Isabel , Oltra-Benavent Manuel , Martín-Pedraz Laura , Manzanares-Casteleiro Ángela , Carrasco-Colom Jaime , Cervantes Eloisa , Sanz-Santaeufemia Francisco , Colino-Gil Elena , Jiménez-Montero Beatriz , Soto Beatriz , Calvo Cristina , Saavedra-Lozano Jesús ,   on behalf of PedGAS-net Working Group
Published: June 2024

Central nervous system infections in children caused by group A Streptococcus are rare. This study, conducted across 52 hospitals in Spain from 2019 to 2023, identified 32 cases of central nervous system infections in children caused by group A Streptococcus, with a significant increase from October 2022 onward (1.1% vs. 5.9%, P = 0.002). Half required pediatric intensive care unit admission, 12.5% exhibited sequelae and the mortality rate was 6.2%. Mastoiditis was the predominant primary infection.