bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene
Authors: Amate-García Guillermo , Ballesta-Martínez María Juliana , Serrano-Lorenzo Pablo , Garrido-Moraga Rocío , González-Quintana Adrián , Blázquez Alberto , Rubio Juan C. , García-Consuegra Inés , Arenas Joaquín , Ugalde Cristina , Morán María , Guillén-Navarro Encarnación , Martín Miguel A.
Published: January 2023

We report a neonatal patient with hypertrophic cardiomyopathy (HCM), lactic acidosis and isolated complex I deficiency. Using a customized next-generation sequencing panel, we identified a novel hemizygous variant c.338G>A in the X-linked NDUFB11 gene that encodes the NADH: ubiquinone oxidoreductase subunit B11 of the mitochondrial respiratory chain (MRC) complex I (CI). Molecular and functional assays performed in the proband’s target tissues—skeletal and heart muscle—showed biochemical disturbances of the MRC, suggesting a pathogenic role for this variant. In silico analyses initially predicted an amino acid missense change p.(Arg113Lys) in the NDUFB11 CI subunit. However, we showed that the molecular effect of the c.338G>A variant, which is located at the last nucleotide of exon 2 of the NDUFB11 gene in the canonical ‘short’ transcript (sized 462 bp), instead causes a splicing defect triggering the up-regulation of the expression of an alternative ‘long’ transcript (sized 492 bp) that can also be detected in the control individuals. Our results support the hypothesis that the canonical ‘short’ transcript is required for the proper NDUFB11 protein synthesis, which is essential for optimal CI assembly and activity, whereas the longer alternative transcript seems to represent a non-functional, unprocessed splicing intermediate. Our results highlight the importance of characterizing the molecular effect of new variants in the affected patient’s tissues to demonstrate their pathogenicity and association with the clinical phenotypes.
Vertebral Bone Marrow Clot towards the Routine Clinical Scenario in Spine Surgeries: What about the Antimicrobial Properties?
Authors: Contartese Deyanira , Sartori Maria , Tedesco Giuseppe , Gasbarrini Alessandro , Giavaresi Gianluca , Salamanna Francesca
Published: January 2023

Exploring innovative techniques and treatments to improve spinal fusion procedures is a global challenge. Here, we provide a scientific opinion on the ability of a vertebral bone marrow (vBM) clot to provide a local combined delivery system not only of stem cells, signaling biomolecules and anti-inflammatory factors but also of molecules and proteins endowed with antimicrobial properties. This opinion is based on the evaluation of the intrinsic basic properties of the vBM, that contains mesenchymal stem cells (MSCs), and on the coagulation process that led to the conversion of fibrinogen into fibrin fibers that enmesh cells, plasma but above all platelets, to form the clot. We emphasize that vBM clot, being a powerful source of MSCs and platelets, would allow the release of antimicrobial proteins and molecules, mainly cathelicidin LL- 37, hepcidin, kinocidins and cationic host defense peptides, that are per se gifted with direct and/or indirect antimicrobial effects. We additionally highlight that further studies are needed to deepen this knowledge and to propose vBM clot as multifunctional bioscaffold able to target all the main key challenges for spinal fusion surgery.
The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study
Authors: Anpalakhan Shobana , Huddar Prerana , Behrouzi Roya , Signori Alessio , Cave Judith , Comins Charles , Cortellini Alessio , Addeo Alfredo , Escriu Carles , McKenzie Hayley , Barone Gloria , Murray Lisa , Bhatnagar Gagan , Pinato David J. , Ottensmeier Christian , Gomes Fabio , Banna Giuseppe Luigi
Published: January 2023

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10–20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1–2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1–2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1–2 adverse effects and Grade 1–2 immunotherapy-related adverse effects.
Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway in Pichia pastoris
Authors: Chen Sheng-Ling , Liu Ting-Shan , Zhang Wei-Guo , Xu Jian-Zhong
Published: January 2023

α-Farnesene, an acyclic volatile sesquiterpene, plays important roles in aircraft fuel, food flavoring, agriculture, pharmaceutical and chemical industries. Here, by re-creating the NADPH and ATP biosynthetic pathways in Pichia pastoris, we increased the production of α-farnesene. First, the native oxiPPP was recreated by overexpressing its essential enzymes or by inactivating glucose-6-phosphate isomerase (PGI). This revealed that the combined over-expression of ZWF1 and SOL3 increases α-farnesene production by improving NADPH supply, whereas inactivating PGI did not do so because it caused a reduction in cell growth. The next step was to introduce heterologous cPOS5 at various expression levels into P. pastoris. It was discovered that a low intensity expression of cPOS5 aided in the production of α-farnesene. Finally, ATP was increased by the overexpression of APRT and inactivation of GPD1. The resultant strain P. pastoris X33-38 produced 3.09 ± 0.37 g/L of α-farnesene in shake flask fermentation, which was 41.7% higher than that of the parent strain. These findings open a new avenue for the development of an industrial-strength α-farnesene producer by rationally modifying the NADPH and ATP regeneration pathways in P. pastoris.
Multiple S-Layer Proteins of Brevibacillus laterosporus as Virulence Factors against Insects
Authors: Ruiu Luca
Published: January 2023

S-layers are involved in the adaptation of bacteria to the outside environment and in pathogenesis, often representing special virulence factors. Vegetative cells of the entomopathogenic bacterium Brevibacillus laterosporus are characterized by an overproduction of extracellular surface layers that are released in the medium during growth. The purpose of this study was to characterize cell wall proteins of this bacterium and to investigate their involvement in pathogenesis. Electron microscopy observations documented the presence of multiple S-layers, including an outermost (OW) and a middle (MW) layer, in addition to the peptidoglycan layer covering the plasma membrane. After identifying these proteins (OWP and MWP) by mass spectrometry analyses, and determining their gene sequences, the cell wall multilayer-released fraction was successfully isolated and used in insect bioassays alone and in combination with bacterial spores. This study confirmed a central role of spores in bacterial pathogenicity to insects but also detected a significant virulence associated with fractions containing released cell wall multilayer proteins. Taken together, S-layer proteins appear to be part of the toxins and virulence factors complex of this microbial control agent of invertebrate pests.
Plasma Cytokine Levels and Cytokine Genetic Polymorphisms in Patients with Metastatic Breast Cancer Receiving High-Dose Chemotherapy
Authors: Lafrenie Robert , Bewick Mary , Buckner Carly , Conlon Michael
Published: January 2023

Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1β, IL-2, IL-6 and TNFα in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFα indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFα SNPs were not associated with differences in outcome. The plasma levels of IL-1β and IL-2 and the genotype of the IL-1β SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.
Deep Learning and Vision-Based Early Drowning Detection
Authors: Shatnawi Maad , Albreiki Frdoos , Alkhoori Ashwaq , Alhebshi Mariam
Published: January 2023

Drowning is one of the top five causes of death for children aged 1–14 worldwide. According to data from the World Health Organization (WHO), drowning is the third most common reason for unintentional fatalities. Designing a drowning detection system is becoming increasingly necessary in order to ensure the safety of swimmers, particularly children. This paper presents a computer vision and deep learning-based early drowning detection approach. We utilized five convolutional neural network models and trained them on our data. These models are SqueezeNet, GoogleNet, AlexNet, ShuffleNet, and ResNet50. ResNet50 showed the best performance, as it achieved 100% prediction accuracy with a reasonable training time. When compared to other approaches, the proposed approach performed exceptionally well in terms of prediction accuracy and computational cost.
Tool Support for Improving Software Quality in Machine Learning Programs
Authors: Cheng Kwok Sun , Huang Pei-Chi , Ahn Tae-Hyuk , Song Myoungkyu
Published: January 2023

Machine learning (ML) techniques discover knowledge from large amounts of data. Modeling in ML is becoming essential to software systems in practice. The accuracy and efficiency of ML models have been focused on ML research communities, while there is less attention on validating the qualities of ML models. Validating ML applications is a challenging and time-consuming process for developers since prediction accuracy heavily relies on generated models. ML applications are written by relatively more data-driven programming based on the black box of ML frameworks. All of the datasets and the ML application need to be individually investigated. Thus, the ML validation tasks take a lot of time and effort. To address this limitation, we present a novel quality validation technique that increases the reliability for ML models and applications, called MLVal. Our approach helps developers inspect the training data and the generated features for the ML model. A data validation technique is important and beneficial to software quality since the quality of the input data affects speed and accuracy for training and inference. Inspired by software debugging/validation for reproducing the potential reported bugs, MLVal takes as input an ML application and its training datasets to build the ML models, helping ML application developers easily reproduce and understand anomalies in the ML application. We have implemented an Eclipse plugin for MLVal that allows developers to validate the prediction behavior of their ML applications, the ML model, and the training data on the Eclipse IDE. In our evaluation, we used 23,500 documents in the bioengineering research domain. We assessed the ability of the MLVal validation technique to effectively help ML application developers: (1) investigate the connection between the produced features and the labels in the training model, and (2) detect errors early to secure the quality of models from better data. Our approach reduces the cost of engineering efforts to validate problems, improving data-centric workflows of the ML application development.
A Comparison of Undersampling, Oversampling, and SMOTE Methods for Dealing with Imbalanced Classification in Educational Data Mining
Authors: Wongvorachan Tarid , He Surina , Bulut Okan
Published: January 2023

Educational data mining is capable of producing useful data-driven applications (e.g., early warning systems in schools or the prediction of students’ academic achievement) based on predictive models. However, the class imbalance problem in educational datasets could hamper the accuracy of predictive models as many of these models are designed on the assumption that the predicted class is balanced. Although previous studies proposed several methods to deal with the imbalanced class problem, most of them focused on the technical details of how to improve each technique, while only a few focused on the application aspect, especially for the application of data with different imbalance ratios. In this study, we compared several sampling techniques to handle the different ratios of the class imbalance problem (i.e., moderately or extremely imbalanced classifications) using the High School Longitudinal Study of 2009 dataset. For our comparison, we used random oversampling (ROS), random undersampling (RUS), and the combination of the synthetic minority oversampling technique for nominal and continuous (SMOTE-NC) and RUS as a hybrid resampling technique. We used the Random Forest as our classification algorithm to evaluate the results of each sampling technique. Our results show that random oversampling for moderately imbalanced data and hybrid resampling for extremely imbalanced data seem to work best. The implications for educational data mining applications and suggestions for future research are discussed.
The Complete Mitogenomes of Three Grasshopper Species with Special Notes on the Phylogenetic Positions of Some Related Genera
Authors: Zhang Chulin , Mao Benyong , Wang Hanqiang , Dai Li , Huang Yuan , Chen Zhilin , Huang Jianhua
Published: January 2023

Clarifying phylogenetic position and reconstructing robust phylogeny of groups using various evidences are an eternal theme for taxonomy and systematics. In this study, the complete mitogenomes of Longzhouacris mirabilis, Ranacris albicornis, and Conophyma zhaosuensis were sequenced using next-generation sequencing (NGS), and the characteristics of the mitogenomes are presented briefly. The mitogenomes of the three species are all circular molecules with total lengths of 16,164 bp, 15,720 bp, and 16,190 bp, respectively. The gene structures and orders, as well as the characteristics of the mitogenomes, are similar to those of other published mitogenomes in Caelifera. The phylogeny of the main subfamilies of Acrididae with prosternal process was reconstructed using a selected dataset of mitogenome sequences under maximum likelihood (ML) and Bayesian inference (BI) frameworks. The results showed that the genus Emeiacris consistently fell into the subfamily Melanoplinae rather than Oxyinae, and the genus Choroedocus had the closest relationship with Shirackiacris of the subfamily Eyprepocnemidinae in both phylogenetic trees deduced from mitogenome protein coding genes (PCGs). This finding is entirely consistent with the morphological characters, which indicate that Emeiacris belongs to Melanoplinae and Choroedocus belongs to Eyprepocnemidinae. In addition, the genera Conophymacris and Xiangelilacris, as well as Ranacris and Menglacris, are two pairs of the closest relatives, but their phylogenetic positions need further study to clarify.
The Tribe Hyrtanellini Allen, 1980 (Ephemeroptera: Ephemerellidae) of Western and Central Asia with Description of a New Species
Authors: Martynov Alexander V. , Palatov Dmitry M. , Godunko Roman J.
Published: January 2023

A new species, Serratella leonidi Martynov & Palatov, sp. nov., is described from Tajikistan based on immature stage. Based on larval material from Iran including the topotypes, Serratella elissa Jacobus, Zhou & McCafferty, 2009 is complementary described, and its generic placement is clarified. The delimitation of three genera that are members of the tribe Hyrtanellini Allen, 1980, namely Serratella Edmunds, 1959, Torleya Lestage, 1917 and Quatica Jacobus & McCafferty, 2008 is briefly discussed. The phylogenetic reconstruction of Hyrtanellini based on the COI gene showed the relations of representatives of these genera on the one hand, and distinct delimitation of Serratella leonidi sp. nov. and S. elissa on the other. A list of species from Western and Central Asia attributed to Hyrtanellini, their currently known distribution and a key for the determination of the larvae are proposed.
Insect Freeze-Tolerance Downunder: The Microbial Connection
Authors: Morgan-Richards Mary , Marshall Craig J. , Biggs Patrick J. , Trewick Steven A.
Published: January 2023

Insects that are freeze-tolerant start freezing at high sub-zero temperatures and produce small ice crystals. They do this using ice-nucleating agents that facilitate intercellular ice growth and prevent formation of large crystals where they can damage tissues. In Aotearoa/New Zealand the majority of cold adapted invertebrates studied survive freezing at any time of year, with ice formation beginning in the rich microbiome of the gut. Some freeze-tolerant insects are known to host symbiotic bacteria and/or fungi that produce ice-nucleating agents and we speculate that gut microbes of many New Zealand insects may provide ice-nucleating active compounds that moderate freezing. We consider too the possibility that evolutionary disparate freeze-tolerant insect species share gut microbes that are a source of ice-nucleating agents and so we describe potential transmission pathways of shared gut fauna. Despite more than 30 years of research into the freeze-tolerant mechanisms of Southern Hemisphere insects, the role of exogenous ice-nucleating agents has been neglected. Key traits of three New Zealand freeze-tolerant lineages are considered in light of the supercooling point (temperature of ice crystal formation) of microbial ice-nucleating particles, the initiation site of freezing, and the implications for invertebrate parasites. We outline approaches that could be used to investigate potential sources of ice-nucleating agents in freeze-tolerant insects and the tools employed to study insect microbiomes.
Improvement in the Identification Technology for Asian Spongy Moth, Lymantria dispar Linnaeus, 1758 (Lepidoptera: Erebidae) Based on SS-COI
Authors: Ji Wenzhuai , Dou Fengrui , Zhang Chunhua , Xiao Yuqian , Yin Wenqi , Yu Jinyong , Kurenshchikov D. K. , Zhu Xiue , Shi Juan
Published: January 2023

Lymantria dispar (Linnaeus, 1758), which is commonly known as spongy moth, with two subspecies, is found in Asia: Lymantria dispar asiatica and Lymantria dispar japonica, collectively referred to as the Asian spongy moth (ASM). The subspecies Lymantria dispar dispar occurs in Europe and is commonly known as the European spongy moth (ESM). The ASM is on the quarantine list of many countries because it induces greater economic losses than the ESM. Accurate identification is essential to prevent the invasion of ASM into new areas. Although several techniques for identifying ASMs have been developed, the recent discovery of complex patterns of genetic variation among ASMs in China as well as new subspecies in some areas has necessitated the development of new, improved identification techniques, as previously developed techniques are unable to accurately identify ASMs from all regions in China. Here, we demonstrate the efficacy of an improved technique for the identification of the ASM using ASM-specific primers, which were designed based on cytochrome oxidase I sequences from samples obtained from all sites where ASMs have been documented to occur in China. We show that these primers are effective for identifying a single ASM at all life stages and from all ASM populations in China, and the minimum detectable concentration of genomic DNA was 30 pg. The inclusion of other Lymantria samples in our analysis confirmed the high specificity of the primers. Our improved technique allows the spread of ASMs to be monitored in real time and will help mitigate the spread of ASMs to other areas.
Precision Monitoring of Honey Bee (Hymenoptera: Apidae) Activity and Pollen Diversity during Pollination to Evaluate Colony Health
Authors: McKinnon Aimee C. , Collins Luke , Wood Jennifer L. , Murphy Nick , Franks Ashley E. , Steinbauer Martin J.
Published: January 2023

Certain crops depend upon pollination services for fruit set, and, of these, almonds are of high value for Australia. Stressors, such as diseases, parasites, pesticides, and nutrition, can contribute to honey bee Apis mellifera L. colony decline, thereby reducing bee activity and pollination efficiency. In Australia, field studies are required to monitor honey bee health and to ascertain whether factors associated with colony decline are impacting hives. We monitored honey bee colonies during and after pollination services of almond. Video surveillance technology was used to quantify bee activity, and bee-collected pollen was periodically tested for pesticide residues. Plant species diversity was also assessed using DNA metabarcoding of the pollen. Results showed that bee activity increased in almond but not in bushland. Residues detected included four fungicides, although the quantities were of low risk of oral toxicity to bees. Floral diversity was lower in the pollen collected by bees from almonds compared to bushland. However, diversity was higher at the onset and conclusion of the almond bloom, suggesting that bees foraged more widely when availability was low. Our findings suggest that commercial almond orchards may sustain healthier bee colonies compared to bushland in early spring, although the magnitude of the benefit is likely landscape-dependent.
Reducing the Immunogenicity of Pulchellin A-Chain, Ribosome-Inactivating Protein Type 2, by Computational Protein Engineering for Potential New Immunotoxins
Authors: Maleki Reza , Fu Libing , Diaz Ricardo Sobhie , Guimarães Francisco Eduardo Gontijo , Cabral-Marques Otávio , Cabral-Miranda Gustavo , Sadraeian Mohammad
Published: January 2023

Pulchellin is a plant biotoxin categorized as a type 2 ribosome-inactivating protein (RIPs) which potentially kills cells at very low concentrations. Biotoxins serve as targeting immunotoxins (IT), consisting of antibodies conjugated to toxins. ITs have two independent protein components, a human antibody and a toxin with a bacterial or plant source; therefore, they pose unique setbacks in immunogenicity. To overcome this issue, the engineering of epitopes is one of the beneficial methods to elicit an immunological response. Here, we predicted the tertiary structure of the pulchellin A-chain (PAC) using five common powerful servers and adopted the best model after refining. Then, predicted structure using four distinct computational approaches identified conformational B-cell epitopes. This approach identified some amino acids as a potential for lowering immunogenicity by point mutation. All mutations were then applied to generate a model of pulchellin containing all mutations (so-called PAM). Mutants’ immunogenicity was assessed and compared to the wild type as well as other mutant characteristics, including stability and compactness, were computationally examined in addition to immunogenicity. The findings revealed a reduction in immunogenicity in all mutants and significantly in N146V and R149A. Furthermore, all mutants demonstrated remarkable stability and validity in Molecular Dynamic (MD) simulations. During docking and simulations, the most homologous toxin to pulchellin, Abrin-A was applied as a control. In addition, the toxin candidate containing all mutations (PAM) disclosed a high level of stability, making it a potential model for experimental deployment. In conclusion, by eliminating B-cell epitopes, our computational approach provides a potential less immunogenic IT based on PAC.
Cross-Sectional and Longitudinal Performance of Non-Invasive Tests of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Armandi Angelo , Rosso Chiara , Younes Ramy , Leeming Diana Julie , Karsdal Morten A. , Caviglia Gian Paolo , Pérez-Diaz-del-Campo Nuria , D’Amato Daphne , Abdulle Amina , Nicolosi Aurora , Castelnuovo Gabriele , Saracco Giorgio Maria , Ribaldone Davide Giuseppe , Bugianesi Elisabetta
Published: January 2023

Background and aims: Non-invasive tests (NITs) are needed in clinical practice to replace histology for the identification of liver fibrosis and prognostication in Non-Alcoholic Fatty Liver Disease (NAFLD). Novel collagen-derived fibrogenesis markers including N-terminal type III collagen pro-peptide (PRO-C3) are among the most promising tools in this field. The aim of this study was to assess the diagnostic accuracy of PRO-C3, the derivative ADAPT score, and other NITs for the identification of advanced fibrosis (stages 3–4) and changes over 12 months of follow-up. Methods: In this longitudinal study, 96 patients with biopsy-proven NAFLD were evaluated at baseline, of which 50 underwent a follow-up visit after 12 months. Clinical-biochemical parameters, liver stiffness (LS) by transient elastography, PRO-C3, and other NITs (ADAPT, FIB-4, NFS, APRI) were collected at baseline and follow-up. Results: LS showed the best accuracy for the identification of advanced fibrosis, with Area under the Receiving Operator Curve (AUROC) 0.82 (0.73–0.89) for a cut-off value of 9.4 kPa. Among the other NITs, the ADAPT score showed the best accuracy, with AUROC 0.80 (0.71–0.88) for a cut-off of 5.02 (Se 62%, Sp 89%, PPV 74%, NPV 83%). The comparison between the AUROC of LS with that of ADAPT was not statistically different (DeLong test p value 0.348). At follow-up, LS was slightly reduced, whilst PRO-C3 displayed a significant increase from baseline median 11.2 ng/mL to 13.9 ng/mL at follow-up (p = 0.017). Accordingly, ADAPT score increased from median 5.3 to 6.1 (p = 0.019). The other NITs did not significantly change over 12 months. Conclusions: The ADAPT score shows the best performance among non-invasive scores for the identification of advanced fibrosis, not different from LS. Collagen-derived biomarker PRO-C3 and the derivative score ADAPT display significant changes over time, and may be useful tools for monitoring the progression of liver disease or assessing responses to treatments.
Craniofacial Morphology of Temporomandibular Disorder Patients with Different Disc Positions: Stratifying Features Based on Sex and Sagittal Skeletal Pattern
Authors: Ye Chengxinyue , Fan Peidi , Zhang Jie , Cheng Qiaoyu , Xiong Xin , Wang Jun
Published: January 2023

Disc displacement (DD) appears in the majority of temporomandibular disorder (TMD) patients. The correlation between craniofacial morphology and different disc positions has been underlined, while the craniofacial morphological differences based on sex and sagittal skeletal pattern stratification have been insufficiently studied. In this study, 304 patients with TMD complaints were included and classified into normal position, disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR) groups according to magnetic resonance imaging. A total of 24 cephalometric measurements, covering the cranial base, vertical relationship, sagittal relationship, mandible position and morphology, and dental relationship, were assessed using lateral cephalograms. A stratified analysis was performed based on the sex and sagittal skeletal pattern. Overall, DD patients had distinctive craniofacial morphological features. The posterior cranial base length and mandibular arc angle were statistically different only in females, while the Y-axis angle, occlusal plane angle and sella nasion point A angle (SNA) might be unique features in males. Skeletal class II had the most statistically different measurements compared to the others. Differences in the Frankfort mandibular incisor angle (FMIA) and saddle angle were especially displayed in skeletal class III patients. The sex and skeletal sagittal pattern could affect the morphological differences in TMD patients with different disc positions.
Plasma Extracellular Vesicles as Liquid Biopsy to Unravel the Molecular Mechanisms of Cardiac Reverse Remodeling Following Resynchronization Therapy?
Authors: van Nieuwenhoven Frans A. , Schroen Blanche , Barile Lucio , van Middendorp Lars , Prinzen Frits W. , Auricchio Angelo
Published: January 2023

Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients.
Age-Related Dichotic Listening Skills in Impaired and Non-Impaired Readers: A Comparative Study
Authors: Reynard Pierre , Joly Charles-Alexandre , Damien Maxime , Le Normand Marie-Thérèse , Veuillet Evelyne , Thai-Van Hung
Published: January 2023

Dichotic listening is the high-level auditory process which enables the perception of different verbal stimuli delivered simultaneously to the right and left ears (binaural integration), as well as the perception of a verbal stimulus presented to one ear while ignoring a different stimulus in the other ear (binaural separation). Deficits in central auditory processing have been reported in children with learning disabilities. The present study aimed to compare dichotic listening performances in right-handed impaired readers (IR) and non-impaired readers (non-IR) according to age. For this, a cross-sectional study was conducted in 120 IR (56 males and 64 females) divided into five age groups and 120 non-IR (63 male and 57 female) matched on chronological age (8 to 9 years; 9 to 10 years; 10 to 12 years; 12 to 18 years; adult). They were tested for binaural integration and binaural separation, allowing for the calculation of dichotic aptitude (DA), ear prevalence (EP), and attentional shift index (ASI). A series of ANOVAs showed an effect of age and of the reading group for all the dichotic-related measures, except for EP. Binaural separation scores were lower in IR who also showed more intrusive responses compared to non-IR. These intrusive responses, which were more frequent on the right ear for IR, decreased with age in both groups. Overall, these results suggest that dichotic listening scores improve with age as the central auditory pathways mature. However, whatever the age, performances are lower in IR than in non-IR. This might be explained by an incomplete maturation of the auditory pathways in IR; an early start for long-term follow-up and auditory training is suggested.
Antiphospholipid Syndrome in Renal Allograft Recipients—A Long-Term Multicenter Analysis
Authors: Furmańczyk-Zawiska Agnieszka , Bułło-Piontecka Barbara , Komorniczak Michał , Dębska-Ślizień Alicja , Augustyniak-Bartosik Hanna , Durlik Magdalena
Published: January 2023

Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown. Aim: The aim of the study was to assess renal allograft function and survival in recipients with APS. Methods: Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. Results: The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Conclusions: Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.
Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results
Authors: La Vignera Sandro , Condorelli Rosita A. , Calogero Aldo E. , Cannarella Rossella , Aversa Antonio
Published: January 2023

Purpose: To prospectively investigate the effects of treatment with liraglutide, a glucagon-like peptide 1 (GLP1) analog, on reproductive and sexual function in men with metabolic hypogonadism who are of childbearing age. Materials and Methods: To accomplish this purpose, 110 men of childbearing age (18–35 years) with metabolic hypogonadism were enrolled and divided into three groups, according to their desire to have children. Group A was made up of men actively seeking fatherhood, Group B, of men who did not seek fatherhood, and Group C, of men who had already fathered a child. Group A patients were treated with gonadotropins (urofollitropin at 150 IU, three times a week, and human chorionic gonadotropin at 2000 IU, twice a week), Group B patients with liraglutide (3 mg daily), and Group C patients with transdermal testosterone (60 mg per day). All patients were treated for 4 months. Results: Patients treated with liraglutide (Group B) showed significant improvement in conventional sperm parameters, compared to baseline and Group A patients, and in the quality of erectile function compared to baseline and patients of Groups A and C. In addition, they had significantly higher levels of total testosterone and sex hormone-binding globulin serum levels after 4 months of treatment with liraglutide than those achieved by patients in the other two groups at the end of the respective treatments. Finally, Group B patients also showed significantly higher serum gonadotropin levels than the other groups. Conclusions: The results of this study showed, for the first time, the efficacy of liraglutide, a GLP1 analog, for the pharmacological treatment of male patients with metabolic hypogonadism. Liraglutide has also shown advantages over traditional treatments on both reproductive and sexual function and appears to offer greater benefits in terms of metabolic protection. These findings suggest that liraglutide is a useful drug for the treatment of obese males with metabolic hypogonadism.
A Novel Technique of Arthroscopic Femoral Tunnel Placement during Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation
Authors: Hu Fengyi , Shi Weili , Wang Haijun , Wang Cheng
Published: January 2023

Recurrent patellar dislocation is a commonly encountered patellofemoral disease. Prompt surgical intervention is indicated for recurrent dislocation to restore patellofemoral stability. As one of the most preferred procedures, medial patellofemoral ligament (MPFL) reconstruction has been implemented on a large scale. Femoral tunnel placement remains a crucial technical issue during MPFL reconstruction and is critical to ensure the isometry and proper tension of the graft. Currently, visual–palpatory anatomic landmarks and fluoroscopy-guided radiographic landmarks comprise the main approaches to intraoperative femoral tunnel positioning. However, the accuracy of both methods has been questioned. This article introduces an arthroscopic femoral tunnel placement technique. Apart from traditional anteromedial and anterolateral portals, two auxiliary arthroscopic portals are specially designed. The adductor tubercle, the medial epicondyle and the posterior edge are selected as main anatomic landmarks and are directly visualized in sequence under arthroscope. The relative position between the femoral attachment of the MPFL and the three landmarks is measured on preoperative three-dimensional computed tomography, providing semi-quantified reference for intraoperative localization. This technique achieves minimally invasive tunnel placement without X-ray exposure, and especially suits obese patients for whom palpatory methods are difficult to perform.
Obstetric Considerations in Pregnant Women with Crohn’s Disease
Authors: Rosiou Konstantina , Selinger Christian P.
Published: January 2023

Crohn’s disease affects many women of childbearing age. Fecundity rates are often lower than in the general population due to reduced fertility during active inflammation, effects of pelvic surgery or voluntary childlessness. Many women have concerns regarding the effects of pregnancy on their Crohn’s, any potential effect of medication on the fetus, and passing on Crohn’s disease to the offspring. International guidelines on reproduction for women with Crohn’s disease provide evidence-based advice to patients and health care professionals. There is an increasing literature on the safety of advanced medication for Crohn’s disease during pregnancy. This review article therefore focuses on obstetric considerations beyond medication safety. We provide information on fertility, factors affecting pregnancy and fetal outcomes, obstetric complications, factors influencing mode of delivery, management of intestinal stomas during pregnancy and general considerations around breast feeding.
The Role of Maxillofacial Structure and Malocclusion on Condylar Displacement in Maximum Intercuspation and Centric Relation in Patients Seeking Orthodontic Treatment—A Scoping Review
Authors: Radej Ilona , Dargiewicz Ewelina , Sawczuk-Siemieniuk Magdalena , Ferrando Cascales Raúl , Ferrando Cascales Álvaro , Agustín-Panadero Rubén , Szarmach Izabela
Published: January 2023

Background: Available knowledge about malocclusion and cephalometric variables and their connection with an increased risk of condylar displacement (CD) is scarce. This article aims to present current information on the relationship between centric relation-maximum intercuspal position discrepancies and maxillofacial morphology and malocclusion in patients seeking orthodontic treatment as well as to identify those who require expanded diagnostic evaluation for this disorder. Methods: This review analyzed the PubMed, Cochrane Library, Web of Science, and Scopus electronic databases up to February 2022. Keywords and additional manual searches were performed. Literature selection was based the PRISMA-ScR checklist. The JBI Critical Appraisal Tool assessed the methodological quality of included studies. Results: The databases search provided 2321 studies. A total of 10 studies were included in this review after eligibility criteria and JBI assessment. This review was separated into five parts that evaluated CD correlations depending on the following: maxillofacial structure in different vertical and sagittal skeletal patterns, vertical, horizontal, and transverse malocclusions. Conclusions: A hyperdivergent facial skeletal structure is a risk factor for increased CD, particularly in the vertical dimension. The condylar processes are usually displaced in a posteroinferior direction. Further studies are warranted to elucidate the relationship among remaining skeletal and dental malocclusions and the occurrence of CD.
Long-Term Tailor-Made Exercise Intervention Reduces the Risk of Developing Cardiovascular Diseases and All-Cause Mortality in Patients with Diabetic Kidney Disease
Authors: Tamiya Hajime , Tamura Yuma , Nagashima Yasuko , Tsurumi Tomoki , Terashima Masato , Ochiai Kaori , Ehara Kyosuke , Furuya Tomoki , Banba Nobuyuki , Nakatani Yuki , Hoshiai Megumi , Ueno Asuka , Tomoe Takashi , Kawabe Atsuhiko , Sugiyama Takushi , Kawamoto Shinya , Yasu Takanori
Published: January 2023

This study aimed to determine the effect of long-term exercise on the risk of developing cardiovascular diseases (CVD) and all-cause mortality in patients with diabetic kidney disease (DKD). A single-center, prospective intervention study using propensity score matching was performed over 24 months. The intervention group (n = 67) received six months of individual exercise instruction from a physical therapist, who performed aerobic and muscle-strengthening exercises under unsupervised conditions. New events were defined as the composite endpoint of stroke or CVD requiring hospitalization, initiation of hemodialysis or peritoneal dialysis, or all-cause mortality. The cumulative survival rate without new events at 24 months was significantly higher in the intervention group (0.881, p = 0.016) than in the control group (n = 67, 0.715). Two-way analysis of variance revealed a significant effect of the group factor on high density lipoprotein-cholesterol (HDL-C) which was higher in the intervention group than in the control group (p = 0.004); eGFRcr showed a significant effect of the time factor, which was lower at 24 months than before intervention (p = 0.043). No interactions were observed for all items. In conclusion, aerobic exercises combined with upper and lower limb muscle strengthening for six months reduce the risk of developing CVD and all-cause mortality in patients with DKD.
Characterization of Non-Obstructive Azoospermia in Men Using Gut Microbial Profiling
Authors: Cao Yalei , Wang Haojie , Jin Zirun , Hang Jing , Jiang Hui , Wu Huajun , Zhang Zhe
Published: January 2023

(1) Background: Non-obstructive azoospermia (NOA) is a complex multifactorial disease and the causes of most NOA cases remain unknown. (2) Methods: Here, we performed comprehensive clinical analyses and gut microbial profiling using shotgun metagenomic sequencing in patients with NOA and control individuals. (3) Results: The gut microbial alpha and beta diversity significantly differed between patients with NOA and controls. Several microbial strains, including Bacteroides vulgatus and Streptococcus thermophilus, were significantly more abundant in the NOA group, whereas Bacteroides thetaiotaomicron and Parabacteroides sp. CT06 were enriched in the control group. Moreover, functional pathway analysis suggested that the altered microbiota in NOA suppressed the carbohydrate metabolism pathway, while amino acid metabolism and methane metabolism pathways were enhanced. We observed that the differential microbial species, such as Acinetobacter johnsonii, had a strong correlation with clinical parameters, including age, body mass index, testosterone, and follicle-stimulating hormone. Communication and interplay among microbial genera were significantly increased in NOA than in the control group. (4) Conclusions: Altered microbial composition and functional pathways in the NOA group were revealed, which highlight the utility of gut microbiota in understanding microbiota-related pathogenesis of NOA and might be helpful to the clinical management of NOA.
Estimating Prevalence and Characteristics of Statin Intolerance among High and Very High Cardiovascular Risk Patients in Germany (2017 to 2020)
Authors: Parhofer Klaus , Anastassopoulou Anastassia , Calver Henry , Becker Christian , Rathore Anirudh , Dave Raj , Zamfir Cosmin
Published: January 2023

Statin intolerance (SI) (partial and absolute) could lead to suboptimal lipid management. The lack of a widely accepted definition of SI results into poor understanding of patient profiles and characteristics. This study aims to estimate SI and better understand patient characteristics, as reflected in clinical practice in Germany using supervised machine learning (ML) techniques. This retrospective cohort study utilized patient records from an outpatient setting in Germany in the IQVIA™ Disease Analyzer. Patients with a high cardiovascular risk, atherosclerotic cardiovascular disease, or hypercholesterolemia, and those on lipid-lowering therapies between 2017 and 2020 were included, and categorized as having “absolute” or “partial” SI. ML techniques were applied to calibrate prevalence estimates, derived from different rules and levels of confidence (high and low). The study included 292,603 patients, 6.4% and 2.8% had with high confidence absolute and partial SI, respectively. After deploying ML, SI prevalence increased approximately by 27% and 57% (p < 0.00001) in absolute and partial SI, respectively, eliciting a maximum estimate of 12.5% SI with high confidence. The use of advanced analytics to provide a complementary perspective to current prevalence estimates may inform the identification, optimal treatment, and pragmatic, patient-centered management of SI in Germany.