bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Large Language Models in Chinese Medical Named Entity Recognition
Authors: Zhu Zhichao , Zhao Qing , Li Jianjiang , Ge Yanhu , Ding Xingjian , Gu Tao , Zou Jingchen , Lv Sirui , Wang Sheng , Yang Ji-Jiang
Published: September 2024

The emergence of large language models (LLMs) has provided robust support for application tasks across various domains, such as name entity recognition (NER) in the general domain. However, due to the particularity of the medical domain, the research on understanding and improving the effectiveness of LLMs on biomedical named entity recognition (BNER) tasks remains relatively limited, especially in the context of Chinese text. In this study, we extensively evaluate several typical LLMs, including ChatGLM2-6B, GLM-130B, GPT-3.5, and GPT-4, on the Chinese BNER task by leveraging a real-world Chinese electronic medical record (EMR) dataset and a public dataset. The experimental results demonstrate the promising yet limited performance of LLMs with zero-shot and few-shot prompt designs for Chinese BNER tasks. More importantly, instruction fine-tuning significantly enhances the performance of LLMs. The fine-tuned offline ChatGLM2-6B surpassed the performance of the task-specific model BiLSTM+CRF (BC) on the real-world dataset. The best fine-tuned model, GPT-3.5, outperforms all other LLMs on the publicly available CCKS2017 dataset, even surpassing half of the baselines; however, it still remains challenging for it to surpass the state-of-the-art task-specific models, i.e., Dictionary-guided Attention Network (DGAN). To our knowledge, this study is the first attempt to evaluate the performance of LLMs on Chinese BNER tasks, which emphasizes the prospective and transformative implications of utilizing LLMs on Chinese BNER tasks. Furthermore, we summarize our findings into a set of actionable guidelines for future researchers on how to effectively leverage LLMs to become experts in specific tasks.
Investigation Methods for Vocal Onset—A Historical Perspective
Authors: Richter Bernhard , Echternach Matthias , Traser Louisa
Published: September 2024

The topic of phonation onset gestures is of great interest to singers, acousticians, and voice physiologists alike. The vocal pedagogue and voice researcher Manuel Garcia, in the mid-19th century, first coined the term “coup de la glotte”. Given that Garcia defined the process as “a precise articulation of the glottis that leads to a precise and clean tone attack”, the term can certainly be linked to the concept of “vocal onset” as we understand it today. However, Garcia did not, by any means, have the technical measures at his disposal to investigate this phenomenon. In order to better understand modern ways of investigating vocal onset—and the limitations that still exist—it seems worthwhile to approach the subject from a historical perspective. High-speed video laryngoscopy (HSV) can be regarded as the gold standard among today’s examination methods. Nonetheless, it still does not allow the three-dimensionality of vocal fold vibrations to be examined as it relates to vocal onset. Clearly, measuring methods in voice physiology have developed fundamentally since Garcia’s time. This offers grounds for hope that the still unanswered questions around the phenomenon of vocal onset will be resolved in the near future. One promising approach could be to develop ultra-fast three-dimensional MRI further.
Adaptive vs. Conventional Deep Brain Stimulation: One-Year Subthalamic Recordings and Clinical Monitoring in a Patient with Parkinson’s Disease
Authors: Caffi Laura , Romito Luigi M. , Palmisano Chiara , Aloia Vanessa , Arlotti Mattia , Rossi Lorenzo , Marceglia Sara , Priori Alberto , Eleopra Roberto , Levi Vincenzo , Mazzoni Alberto , Isaias Ioannis U.
Published: September 2024

Conventional DBS (cDBS) for Parkinson’s disease uses constant, predefined stimulation parameters, while the currently available adaptive DBS (aDBS) provides the possibility of adjusting current amplitude with respect to subthalamic activity in the beta band (13–30 Hz). This preliminary study on one patient aims to describe how these two stimulation modes affect basal ganglia dynamics and, thus, behavior in the long term. We collected clinical data (UPDRS-III and -IV) and subthalamic recordings of one patient with Parkinson’s disease treated for one year with aDBS, alternated with short intervals of cDBS. Moreover, after nine months, the patient discontinued all dopaminergic drugs while keeping aDBS. Clinical benefits of aDBS were superior to those of cDBS, both with and without medications. This improvement was paralleled by larger daily fluctuations of subthalamic beta activity. Moreover, with aDBS, subthalamic beta activity decreased during asleep with respect to awake hours, while it remained stable in cDBS. These preliminary data suggest that aDBS might be more effective than cDBS in preserving the functional role of daily beta fluctuations, thus leading to superior clinical benefit. Our results open new perspectives for a restorative brain network effect of aDBS as a more physiological, bidirectional, brain–computer interface.
Mathematical Models for Ultrasound Elastography: Recent Advances to Improve Accuracy and Clinical Utility
Authors: Farajpour Ali , Ingman Wendy V.
Published: September 2024

Changes in biomechanical properties such as elasticity modulus, viscosity, and poroelastic features are linked to the health status of biological tissues. Ultrasound elastography is a non-invasive imaging tool that quantitatively maps these biomechanical characteristics for diagnostic and treatment monitoring purposes. Mathematical models are essential in ultrasound elastography as they convert the raw data obtained from tissue displacement caused by ultrasound waves into the images observed by clinicians. This article reviews the available mathematical frameworks of continuum mechanics for extracting the biomechanical characteristics of biological tissues in ultrasound elastography. Continuum-mechanics-based approaches such as classical viscoelasticity, elasticity, and poroelasticity models, as well as nonlocal continuum-based models, are described. The accuracy of ultrasound elastography can be increased with the recent advancements in continuum modelling techniques including hyperelasticity, biphasic theory, nonlocal viscoelasticity, inversion-based elasticity, and incorporating scale effects. However, the time taken to convert the data into clinical images increases with more complex models, and this is a major challenge for expanding the clinical utility of ultrasound elastography. As we strive to provide the most accurate imaging for patients, further research is needed to refine mathematical models for incorporation into the clinical workflow.
The Wound-Healing Effect of a Novel Fibroblasts-Impregnated Hydroxyethylcellulose Gel in a Rat Full-Thickness Burn Model: A Preclinical Study
Authors: Novosad Yury A. , Shabunin Anton S. , Enukashvily Natella I. , Supilnikova Olga V. , Konkina Anastasia I. , Semenova Natalia Yu. , Yatsemirsky Gleb S. , Zinoviev Evgenii V. , Rodionova Kristina N. , Kryshen Kirill L. , Borodina Antonina Yu. , Makarov Alexander Yu. , Fedyuk Andrey M. , Nilov Alexander D. , Chikulaeva Elena V. , Konkova Lidiya S. , Chustrak Irina S. , Traxova Veronika V. , Safonov Platon A. , Vissarionov Sergey V. , Prikhodko Egor M. , Yurkevich Yury V.
Published: September 2024

Background/Objectives: The objective of this study was to assess the efficacy of a cell-containing wound dressing based on fibroblasts in hydroxyethylcellulose (HEC) gel for the local treatment of deep partial-thickness and/or full-thickness skin burns in an animal model. Methods: The rats (male Wistar, n = 100) were subjected to a full-thickness thermal burn (16 cm2). Radical necrectomy was performed one day after the burn. Three days later, the rats were randomly assigned to one of four groups: group 1 (no treatment), group 2 (chloramphenicol and methyluracil ointment, a routine clinical treatment), group 3 (a gel without cells, mock treatment), and group 4 (a dermal fibroblast-impregnated HEC gel). The treatment lasted for five days. The wound-healing process was evaluated by planimetric, cytologic, histologic, and immunohistochemical methods. Results: The differences in the rate of wound healing and the characteristics of wound cytology were identified. In the group 4, a regenerative type of cytogram was revealed, characterized by a significantly increased number of fibroblastic cells in comparison to samples from non-treated and mock-treated animals. Biopsy samples of burn wounds from animals in the group 4l demonstrated the presence of mature granulation tissue and a large number of microvessels. The repair process was stimulated, as evidenced by the increased thickness of newly formed granulation tissue and epidermis in the wound zone, elevated cellularity, and enhanced re-epithelialization activity. The number of Ki-67-positive proliferating cells was significantly higher in group 4 than in the control groups). A small number of non-proliferating donor fibroblasts was observed in the wound area 3 days after the end of treatment. Conclusions: The cell product is an effective agent for promoting wound healing during the regenerative phase. The experiments demonstrated that a gel populated by dermal fibroblasts can stimulate reparative regeneration processes in deep partial- and full-thickness burn wounds.
Kalata B1 Enhances Temozolomide Toxicity to Glioblastoma Cells
Authors: Gerlach Samantha L. , Metcalf James S. , Dunlop Rachael A. , Banack Sandra Anne , Her Cheenou , Krishnan Viswanathan V. , Göransson Ulf , Gunasekera Sunithi , Slazak Blazej , Cox Paul Alan
Published: September 2024

Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin. We analyzed naturally occurring and synthetic cyclotides (Cycloviolacin O3, Cycloviolacin O19, natural Kalata B1, synthetic Kalata B1, and Vitri E) alone and in co-exposure treatments with the drug temozolomide (TMZ) in human glioblastoma cells. The cyclotides were identified by UPLC-PDA and HPLC-UV. The synthetic Kalata B1 sequence was verified with orbitrap LC-MS, and structural confirmation was provided by NMR spectroscopy. The cyclotides displayed dose-dependent cytotoxicity (IC50 values 2.4–21.1 µM) both alone and as chemosensitizers of U-87 MG and T 98 cells to TMZ. In fact, a 16-fold lower concentration of TMZ (100 µM) was needed for significant cytotoxicity in U-87 MG cells co-exposed to synthetic Kalata B (0.5 µM). Similarly, a 15-fold lower concentration of TMZ (75 µM) was required for a significant reduction in cell viability in T 98 cells co-exposed to synthetic Kalata B1 (0.25 µM). Kalata B1 remained stable in human serum stability assays. The data support the assertion that cyclotides may chemosensitize glioblastoma cells to TMZ.
Busulfan Chemotherapy Downregulates TAF7/TNF-α Signaling in Male Germ Cell Dysfunction
Authors: Huang Daoyuan , Tu Zhenbo , Karnoub Antoine E. , Wei Wenyi , Rezaeian Abdol-Hossein
Published: September 2024

Background: Busulfan is an FDA-approved alkylating drug used in the chemotherapy of advanced acute myeloid leukemia. The precise mechanisms by which Busulfan kills spermatogonia stem cells (SSCs) are not yet completely understood. Methods: Using a murine model, we evaluated Busulfan-induced apoptosis and DNA damage signaling between testis and ovary tissues. We executed RT-qPCR, analyzed single-nuclei RNA sequencing data and performed in situ hybridization for the localization of the gene expression in the tissues. Results: The results indicate that, in contrast to female germ cells, haploid male germ cells undergo significant apoptosis following Busulfan chemotherapy. Moreover, a gene enrichment analysis revealed that reactive oxygen species may activate the inflammatory response in part through the TNF-α/NF-κB signaling pathway. Interestingly, in the testis, the mRNA levels of TNF-α and TAF7 (TATA box-binding protein-associated factor 7) are downregulated, and testosterone levels suppressed. Mechanistically, the promoter of TNF-α has a conserved motif for binding TAF7, which is necessary for its transcriptional activation and may require further in-depth study. We next analyzed the tumorigenic function of TAF7 and revealed that it is highly overexpressed in several types of human cancers, particularly testicular germ cell tumors, and associated with poor patient survival. Therefore, we executed in situ hybridization and single-nuclei RNA sequencing, finding that less TAF7 mRNA is present in SSCs after chemotherapy. Conclusions: Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings may account for the therapeutic effects of Busulfan and underlie its potential impact on cancer chemotherapy prognosis.
The Silent Threat: A Retrospective Cohort Study on the Impact of Prediabetes on ST-Elevation Myocardial Infarction Survival—A Call to Action!
Authors: Boxhammer Elke , Hammerer Matthias , Schernthaner Christiana , Prinz Erika , Brandt Mathias C. , Lichtenauer Michael , Berezin Alexander E. , Wintersteller Wilfried , Hoppe Uta C. , Kopp Kristen L.
Published: September 2024

Background: Prediabetes is frequently underdiagnosed and undertreated, yet it poses significant cardiovascular risks. This study investigates the impact of prediabetes on short- and long-term survival outcomes in patients who experienced ST-elevation myocardial infarction (STEMI). Methods: In this retrospective, single-center cohort study, we evaluated 725 STEMI patients stratified into non-diabetic, prediabetic, and diabetic groups based on HbA1c levels at presentation. A Kaplan–Meier survival analysis was employed to compare long-term outcomes over a three-year follow-up period. Cardiovascular risk factors, including hypertension and dyslipidemia, were analyzed across the groups. The discriminatory power of HbA1c for predicting all-cause mortality was assessed using an Area Under the Receiver Operating Characteristic (AUROC) analysis. Results: Of the 725 patients, 407 (56.1%) were non-diabetic, 184 (25.4%) were prediabetic, and 134 (18.5%) were diabetic. Prediabetic patients exhibited significant additional cardiovascular risk factors, such as arterial hypertension (67.4%) and dyslipidemia (78.3%), with prevalence rates between those of non-diabetic and diabetic patients. The Kaplan–Meier analysis revealed that at a three-year follow-up, prediabetic patients faced a survival disadvantage, with a significant decrease in survival rates compared to non-diabetic patients (log-rank p = 0.016); their survival outcomes approached those of diabetic patients (p = 0.125). The AUROC analysis demonstrated that HbA1c was a significant predictor of short- and long-term mortality, with a cut-off value of 5.75% and an Area Under the Curve (AUC) of 0.580–0.617 (95% CI: 0.458–0.721), indicating a moderate ability to predict survival in patients with STEMI. Conclusions: Prediabetes significantly worsens survival outcomes following STEMI, nearly approaching the risk level of diabetes. Integrating rigorous cardiovascular risk management strategies for prediabetic individuals, including lifestyle interventions and potentially pharmacological treatments, could prevent the progression to diabetes and mitigate associated cardiovascular risks.
Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease
Authors: Susman Stephen , Santoso Breanna , Makary Mina S.
Published: September 2024

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.
Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells
Authors: Higashide Megumi , Watanabe Megumi , Sato Tatsuya , Ogawa Toshifumi , Umetsu Araya , Suzuki Soma , Furuhashi Masato , Ohguro Hiroshi , Nishikiori Nami
Published: September 2024

Objectives: To study the effects of all-trans retinoic acid (ATRA) on TGF-β2-induced effects of human retinal pigment epithelium cells under normoxia and hypoxia conditions. Methods: Two-dimensionally (2D) and three-dimensionally (3D) cultured ARPE19 cells were subjected to cellular functional analyses by transepithelial electrical resistance (TEER) and an extracellular flux assay (2D), measurement of levels of reactive oxygen species (ROS), gene expression analyses of COL1, αSMA, Zo-1, HIF1α, and PGC1α (2D), and physical property analyses (3D). Results: Under a normoxia condition, treatment with 100 nM ATRA substantially decreased barrier function regardless of the presence of 5 ng/mL TGF-β2 in 2D ARPE19 monolayer cells. Under a hypoxia condition, treatment with ATRA conversely increased barrier function, but the effect was masked by a marked increase in effects induced by TGF-β2. Although ATRA alone did not affect cellular metabolism and ROS levels in 2D ARPE cells, treatment with ATRA under a hypoxia condition did not affect ROS levels but shifted cellular metabolism from mitochondrial respiration to glycolysis. The changes of cellular metabolism and ROS levels were more pronounced with treatment of both ATRA and TGF-β2 independently of oxygen conditions. Changes in mRNA expressions of some of the above genes suggested the involvement of synergistical regulation of cellular functions by TGF-β2 and hypoxia. In 3D ARPE spheroids, the size was decreased and the stiffness was increased by either treatment with TGF-β2 or ATRA, but these changes were unexpectedly modulated by both ATRA and TGF-β2 treatment regardless of oxygen conditions. Conclusions: The findings reported herein indicate that TGF-β2 and hypoxia synergistically and differentially induce effects in 2D and 3D cultured ARPE19 cells and that their cellular properties are significantly altered by the presence of ATRA.
Liver Fibrosis Leading to Cirrhosis: Basic Mechanisms and Clinical Perspectives
Authors: Somnay Kaumudi , Wadgaonkar Priyanka , Sridhar Nidhishri , Roshni Prarath , Rao Nachiketh , Wadgaonkar Raj
Published: September 2024

Liver fibrosis is the pathological deposition of extracellular matrix rich in fibrillar collagen within the hepatocytes in response to chronic liver injury due to various causes. As the condition advances, it can progress to cirrhosis, the late stages of which are irreversible. Multiple pathophysiological mechanisms and cell types are responsible for the progression of liver fibrosis and cirrhosis. Hepatic stellate cells and myofibroblast activation represent a key event in fibrosis. Capillarization of liver sinusoidal endothelial cells further contributes to extracellular matrix deposition and an increase in portal pressure. Macrophages and neutrophils produce inflammatory cytokines and participate in activating hepatic stellate cells. Although initially believed to be irreversible, early stages of fibrosis are now found to be reversible. Furthermore, advances in noninvasive imaging and serum studies have changed and improved how cirrhosis can be evaluated and monitored. Although there are currently no specific approved therapies to reverse liver fibrosis, management of underlying diseases has been found to halt the progression, and to an extent, even reverse liver fibrosis, preventing further liver injury and cirrhosis-related complications.
Inferior Vena Cava Filter in Cancer-Associated Thrombosis: A Vade Mecum for the Treating Physicians: A Narrative Review
Authors: Fioretti Agnese Maria , La Forgia Daniele , Scicchitano Pietro , Brunetti Natale Daniele , Inchingolo Riccardo , Tocchetti Carlo Gabriele , Oliva Stefano
Published: September 2024

Cancer is a remarkable prothrombotic disease, and cancer-associated thrombosis acts as a dreadful omen for poor prognosis. The cornerstone of venous thromboembolism therapy is anticoagulation; however, in patients with venous thromboembolism who are not suitable for anticoagulation (contraindication, failure, or complication), the inferior vena cava filter appears a valuable option in the therapeutic arsenal. The recently heightened trend of steady rise in filter placement mirrors the spread of retrievable devices, together with improvements in physicians’ insertion ability, medico-legal issue, and novel and fewer thrombogenic materials. Nevertheless, the exact role of the inferior vena cava filter in cancer has yet to be endorsed due to a dearth of robust evidence. Indeed, data that support the inferior vena cava filter are weak and even controversial, resulting in discrepancies in the interpretation and application of guidelines in daily practice. In this narrative review, we aim at clarifying the state of the art on inferior vena cava filter use in malignancies. Furthermore, we provide a feasible, conclusive 4-step algorithm for the treating physicians in order to offer a practical strategy to successfully employ the inferior vena cava filter as a priceless device in the current armamentarium against cancer.
TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells
Authors: Wang Qian , Zhang Qiuning , Wang Xiaohu , Luo Hongtao , Du Tianqi , Wu Luyao , Tan Mingyu , Chen Yanliang , Wu Xun , Sun Shilong , Liu Zhiqiang , Xie Yi , Yuan Wenzhen
Published: September 2024

Objectives: Cancer cells with ‘stemness’ are generally resistant to chemoradiotherapy. This study aims to compare the differences in radiation sensitivity of A549 and CD44+A549 stem-like cells to X-rays and carbon ion radiation (C-ions), and to find a target that can kill cancer stem-like cells (CSCs) of non-small cell lung cancer (NSCLC). Methods: The study used two cell lines (A549 and CD44+A549). The tumorigenicity of cells was tested with animal experiments. The cells were irradiated with X-rays and C-ions. Cell viability was detected using the CCK-8 and EdU assay. A liquid chromatograph-mass spectrometer (LC–MS) helped detect metabolic differences. Protein and mRNA expression were detected using a Western blot, reverse transcription-quantitative (RT-qPCR), and PCR array. The autophagic activity was monitored with a CYTO-ID® Autophagy Detection Kit 2.0. Immunofluorescence and co-immunoprecipitation helped to observe the localization and interaction relationships. Results: First, we verified the radio-resistance of CD44+A549 stem-like cells. LC-MS indicated the difference in autophagy between the two cells, followed by establishing a correlation between the radio-resistance and autophagy. Subsequently, the PCR array proved that TGM2 is significantly upregulated in CD44+A549 stem-like cells. Moreover, the TGM2 knockdown by small interfering RNA could decrease the radio-resistance of CD44+A549 cells. Bioinformatic analyses and experiments showed that TGM2 is correlated with the expression of CD44 and LC3B. Additionally, TGM2 could directly interact with LC3B. Conclusions: We established the CD44-TGM2-LC3 axis: CD44 mediates radio-resistance of CD44+A549 stem-like cells through TGM2 regulation of autophagy. Our study may provide new biomarkers and strategies to alleviate the radio-resistance of CSCs in NSCLC.
Biomimetic Studies on the Antimicrobial Activity of Some Biocides Based on Garlic and Lavender in Surface Waters
Authors: Grinzeanu Mădălina , Orbuleț Oanamari Daniela , Dăncilă Annette Madelene , Bobirică Constantin , Modrogan Cristina , Bobirică Liliana , Pandele Mădălina Andreea
Published: September 2024

For a given aquatic ecosystem that will be used as a water source, it is necessary to establish the quality of the water from a microbiological point of view by identifying the pathogens present in the water. The aim of this study was to determine and analyze the antimicrobial activity of some biocides derived from garlic (garlic–methanol extract) and lavender (lavender–water extract). Their efficiency was evaluated at different concentrations and contact times. Initially, through specific laboratory analyses, the microbiological characteristics of the river were determined. Biomimetic studies on the antimicrobial activity of biocides based on garlic and lavender in surface waters involved detailed exploration of how the natural antimicrobial properties of these plants can be effectively utilized to treat water contaminated with harmful microorganisms. Both the contact time and the amount of biocide used have a significant effect on the microorganisms of interest. Thus, to describe the degradation rate of coliform bacteria, a pseudo-first-order and zero-order kinetic model was used, r=−(dN/dt)=kobs·t şi r0=kobs·N0=k0, where r is the rate of degradation of microorganisms (CFU/min), N0 is the initial number of microorganisms in the aqueous solution (colony-forming unit, CFU), N is the final number of microorganisms after a contact time t (CFU), kobs is the pseudo-first-order rate constant (min−1), t is the contact time (min), r0 is the initial rate of degradation of microorganisms (CFU/min), and k0 is the pseudo-rate constant zero order (min−1). Following 60 min of treatment with 1 mL of lavender-water biocide, the inhibition rate of pathogenic microorganisms in the water reached 59.09%, whereas, under the same conditions, the garlic–methanol biocide achieved an inhibition rate of 40.86%. This study confirms the antimicrobial activity of both lavender and garlic biocides, highlighting their potential in mitigating water pollution caused by pathogens.
A Motion Planner Based on Mask-D3QN of Quadruped Robot Motion for Steam Generator
Authors: Xu Biying , Zhang Xuehe , Yu Xuan , Ou Yue , Zhang Kuan , Cai Hegao , Zhao Jie , Fan Jizhuang
Published: September 2024

Crawling robots are the focus of intelligent inspection research, and the main feature of this type of robot is the flexibility of in-plane attitude adjustment. The crawling robot HIT_Spibot is a new type of steam generator heat transfer tube inspection robot with a unique mobility capability different from traditional quadrupedal robots. This paper introduces a hierarchical motion planning approach for HIT_Spibot, aiming to achieve efficient and agile maneuverability. The proposed method integrates three distinct planners to handle complex motion tasks: a nonlinear optimization-based base motion planner, a TOPSIS-based base orientation planner, and a Mask-D3QN (MD3QN) algorithm-based gait motion planner. Initially, the robot’s base and foot workspace were delineated through envelope analysis, followed by trajectory computation using Larangian methods. Subsequently, the TOPSIS algorithm was employed to establish an evaluation framework conducive to foundational turning planning. Finally, the MD3QN algorithm trained foot-points to facilitate robot movement along predefined paths. Experimental results demonstrated the method’s adaptability across diverse tube structures, showcasing robust performance even in environments with random obstacles. Compared to the D3QN algorithm, MD3QN achieved a 100% success rate, enhanced average overall scores by 6.27%, reduced average stride lengths by 39.04%, and attained a stability rate of 58.02%. These results not only validate the effectiveness and practicality of the method but also showcase the significant potential of HIT_Spibot in the field of industrial inspection.
Non-Invasive Ventilation with Neurally Adjusted Ventilatory Assist (NAVA) Improves Extubation Outcomes in Extremely Low-Birth-Weight Infants
Authors: Louie Kevin , Amatya Shaili , Alpan Gad , Parton Lance A.
Published: September 2024

Objective: This study investigates the effectiveness of extubation from conventional mechanical ventilation using an endotracheal tube (MVET) compared to synchronized non-invasive positive-pressure ventilation (sNIPPV) using neurally adjusted ventilatory assist (NAVA) and conventional non-invasive positive-pressure ventilation (NIPPV) in extremely low-birth-weight (ELBW) infants. Methods: An institutional review board (IRB) approved this study (#12175) to conduct a single-center randomized control trial including 60 ELBW infants assigned in a one-to-one computer-generated scheme to either sNIPPV using NAVA or NIPPV. The primary outcome involved the need for reintubation, and the secondary outcome involved the assessment of moderate/severe BPD, defined as an oxygen requirement at 36 weeks, as in #NCT03613987 (clinicaltrials.gov). Results: There were 60 ELBW infants enrolled and randomized. The overall gestational age was 26 (1.5) weeks, and the birth weight was 773 (157) g [mean (SD)]. There were no statistically significant differences between the NAVA and NIPPV patient characteristics. There was a 41% extubation failure rate in the NIPPV group and 35% in the NAVA group (p = NS). The NAVA group had less moderate and severe BPD (p = 0.03), a shorter oxygen therapy duration (p = 0.002), a decreased length of stay (p = 0.03), and less need for home oxygen (0, 43%; p = 0.0004). Conclusions: This study found similar extubation failure rates among ELBW infants as in prior studies. However, the NAVA group had lower rates of moderate/severe BPD and need for oxygen at discharge, as well as shorter oxygen therapy duration and length of stay. The use of NAVA may be a reasonable alternative mode of non-invasive ventilation in the ELBW population.
Stabilometry in Relation to Hip and Knee Muscle Force in Children with Surgically Treated Unilateral Slipped Capital Femoral Epiphysis
Authors: Negru Marius , Dinu Anca Raluca , Amaricai Elena , Catan Liliana , Bolovan Andrei Daniel , Lazarescu Adrian Emil , Stanciulescu Corina Maria , Boia Eugen Sorin , Popoiu Calin Marius
Published: September 2024

Background/Objectives: The main aim of our study was to analyze the stabilometric parameters in relation to hip and knee muscle force in children with unilateral slipped capital femoral epiphysis (SCFE) who had undergone surgical treatment. Another objective was to compare the stabilometry in three testing situations (eyes open, eyes closed, and head retroflexed). Methods: In total, 26 patients with unilateral right SCFE treated via in situ fixation with one percutaneous screw performed stabilometry assessments under three different situations (with their eyes open, with their eyes closed, and with their head retroflexed) and isometric muscle force assessment of the bilateral hip flexors, extensors, abductors and adductors and bilateral knee flexors and extensors. Results: No significant differences between the right side (affected hip) and left side (non-affected hip) were recorded for all of the tested muscle groups. We found significant negative correlations between the 90% confidence ellipse area (eyes open condition) and left knee extensors (p = 0.028), right knee flexors (p = 0.041), and left knee flexors (p = 0.02), respectively. When performing the comparison between the eyes open and eyes closed situations, there were significant differences in CoP path length (p < 0.0001) and maximum CoP speed (p = 0.048); the parameters increased in the eyes closed situation. Conclusions: Better postural stability is acquired when assessed with eyes open or with the head retroflexed in contrast with eyes closed testing.
Vitamin D Supplementation for Children with Epilepsy on Antiseizure Medications: A Randomized Controlled Trial
Authors: Bashiri Fahad A. , Hudairi Abrar , Hamad Muddathir H. , Al-Sulimani Lujain K. , Al Homyani Doua , Al Saqabi Dimah , Kentab Amal Y. , Al Khalifah Reem A.
Published: September 2024

Background: Antiseizure medications (ASMs) are crucial for managing epilepsy in children. However, a well-documented side effect of ASMs is their impact on bone health, often due to interference with vitamin D metabolism. This can lead to vitamin D deficiency in children with epilepsy. This study aimed to determine if a daily dose of 400 IU or 1000 IU would maintain adequate vitamin D levels in children with epilepsy. Methods: A phase IV randomized controlled trial enrolled children aged 2–16 years with epilepsy and receiving antiseizure medications. Children were divided into two groups: the monotherapy group, which was defined as children on one antiseizure medication (ASM), and the polytherapy group, which was defined as children receiving two or more ASMs. Eligible children with levels above 75 nmol/L were randomized to receive a maintenance dose of either 400 IU/day or 1000 IU/day of cholecalciferol. Baseline and 6-month assessments included demographic data, anthropometric measurements, seizure type, medications, seizure control, and 25(OH)D level. Results: Out of 163 children, 90 were on monotherapy and 25 on polytherapy. After 6 months of vitamin D maintenance, the proportion of children with 25(OH)D concentration below 75 nmol/L was 75.0% in the 400 IU group and 54.8% in the 1000 IU group. In the monotherapy group, baseline seizure-free children increased from 69% to 83.6% after treating vitamin D deficiency. Conclusion: Daily vitamin D supplementation with 1000 IU may be beneficial for children with epilepsy, particularly those receiving monotherapy, to maintain sufficiency and potentially improve seizure control.
Interlimb Coordination and Auditory—Motor Synchronization in Children with Developmental Coordination Disorder: Examining Antiphase Knee Movements with Auditory Metronomes While Seated
Authors: Goetschalckx Mieke , Moumdjian Lousin , Rameckers Eugene , Feys Peter
Published: September 2024

Background: Children with developmental coordination disorder (DCD) exhibit reduced interlimb coordination compared to typically developing children (TDC) during complex tasks like running, which requires dynamic postural control. However, the extent of interlimb coordination difficulties in DCD during tasks that demand minimal dynamic balance, such as self-paced and externally auditory-paced tasks, remains unclear. This study aimed to compare interlimb coordination and auditory–motor synchronization between children with DCD and TDC during a seated antiphase coordination task of the lower limbs, which has minimal postural control requirements. Methods: Twenty-one children with DCD and 22 TDC performed an antiphase knee flexion and extension task while seated, in three conditions (baseline silence, metronome discrete, and metronome continuous), for three minutes. The interlimb coordination, synchronization, and spatiotemporal movement parameters were analyzed using a mixed model analysis; Results: Children with DCD displayed less coordinated interlimb movements compared to TDC (p = 0.0140), which was the result of the greater variability in coordinating antiphase knee flexion–extension movements (p < 0.0001). No group differences in spatiotemporal movement parameters were observed. Children with DCD, compared to TDC, had a lower synchronization consistency to metronomes (p = 0.0155). Discrete metronomes enhanced interlimb coordination compared to the baseline silence condition (p = 0.0046); Conclusions: The study highlights an inferior interlimb coordination and auditory–motor synchronization in children with DCD compared to TDC. Implementing metronomes with a discrete temporal structure improved the interlimb coordination of both groups during the used fundamental seated interlimb coordination task, supporting theorical frameworks of event-based timing.
Gender Differences in Adolescents’ Body Complaints in Eight Countries: What Do Culture and Parents Have to Do with It?
Authors: Weitkamp Katharina , Seiffge-Krenke Inge
Published: September 2024

Objective: Although medically unexplained body complaints occur relatively frequently in adolescents, the causes are little-researched. This study examines the influence of cultural and family-related factors on somatic complaints. Methods and Measures: In a cross-cultural and cross-sectional study of 2415 adolescents from eight countries (Argentina, France, Germany, Greece, Pakistan, Peru, Poland, and Turkey), the associations of family variables with body complaints were tested and the cultural impact analyzed. Body complaints were assessed via self-reporting with a translated version of the body complaints scale of the Youth Self Report (YSR). In addition, Perceived Maternal/Paternal Behavior was assessed, as well as cultural dimensions of the eight counties. Results: Overall, females reported higher rates of body complaints than boys did. An additional negative impact of parental psychological control and anxious rearing was found that generalized across cultures, with a particularly strong impact on girls. Girls in stepparent families and boys in single-parent families reported more body complaints. Finally, body complaints were associated with Hofstede’s cultural factors in both genders, like individualism vs. collectivism, power distance, uncertainty avoidance, and masculinity vs. femininity. Conclusion: These findings are particularly important for primary care providers, as they stress the relevance of taking into account family and cultural factors in body complaints which affect boys and girls differently, to provide adequate care.
Obesity as a Risk Factor for the Severity of COVID-19 in Pediatric Patients: Possible Mechanisms—A Narrative Review
Authors: Mîndru Dana Elena , Țarcă Elena , Adumitrăchioaiei Heidrun , Anton-Păduraru Dana Teodora , Ștreangă Violeta , Frăsinariu Otilia Elena , Sidoreac Alexandra , Stoica Cristina , Bernic Valentin , Luca Alina-Costina
Published: September 2024

Obesity, the current pandemic, is associated with alarming rises among children and adolescents, and the forecasts for the near future are worrying. The present paper aims to draw attention to the short-term effects of the excess adipose tissue in the presence of a viral infection, which can be life-threatening for pediatric patients, given that the course of viral infections is often severe, if not critical. The COVID-19 pandemic has been the basis of these statements, which opened the door to the study of the repercussions of obesity in the presence of a viral infection. Since 2003, with the discovery of SARS-CoV-1, interest in the study of coronaviruses has steadily increased, with a peak during the pandemic. Thus, obesity has been identified as an independent risk factor for COVID-19 infection and is correlated with a heightened risk of severe outcomes in pediatric patients. We sought to determine the main mechanisms through which obesity is responsible for the unfavorable evolution in the presence of a viral infection, with emphasis on the disease caused by SARS-CoV-2, in the hope that future studies will further elucidate this aspect, enabling prompt and effective intervention in obese patients with viral infections, whose clinical progression is likely to be favorable.
Effectiveness of Respiratory Muscle Training in Pompe Disease: A Systematic Review and Meta-Analysis
Authors: Lin Mu-Yun , Chen Szu-Han , Lee Jen-Ting , Hsu Po-Cheng
Published: September 2024

Background: Pompe disease is a rare metabolic myopathy caused by the lack or deficiency of the lysosomal acid alpha-glucosidase, resulting in skeletal muscle weakness and cardiomyopathy. The disease varies by onset age and genetic mutations and is categorized into infantile-onset and late-onset Pompe disease. Respiratory muscle weakness may persist regardless enzyme replacement therapy. This systemic review and meta-analysis aim to assess the effect of respiratory muscle training (RMT) on respiratory muscle strength, functional endurance, and pulmonary function in patient with Pompe disease. Methods: PubMed, EMBASE, and Cochrane databases were searched up until Aug 2024. Studies examining the therapeutic effects of RMT in patients with Pompe disease were included. Outcome measures included the change in maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), six-minute walking test (6MWT), pulmonary function before after RMT, quality of life and adverse events. Results: The meta-analysis consisted of 5 single-arm studies, including 31 patients in total. Regarding inspiratory muscle strength, RMT has significantly improving MIP (8.71 cmH2O; 95% CI, 6.23–11.19, p < 0.001) and MEP (12.15 cmH2O; 95% CI, 10.55–13.74, p < 0.001) in both types of Pompe disease. However, no significant change regarding 6MWT. No serious adverse events were reported. Conclusions: Our meta-analysis revealed that RMT may increase inspiratory muscle and expiratory muscle strength, but may not have an effect on 6MWT in patients with Pompe disease. RMT has potential to be integrated into the cardioplulmonary rehabilitation for patients with Pompe disease. Further large randomized controlled trials are needed to verify the efficacy and safety of RMT in patients with Pompe disease.
Genetic Predisposition to Prediabetes in the Kazakh Population
Authors: Svyatova Gulnara , Berezina Galina , Murtazaliyeva Alexandra , Dyussupov Altay , Belyayeva Tatyana , Faizova Raida , Dyussupova Azhar
Published: September 2024

The aim of this study was to conduct a comparative analysis of the population frequencies of the minor allele of polymorphic variants in the genes TCF7L2 (rs7903146) and PPARG (rs1801282), based on the genome-wide association studies analysis data associated with the risk of developing prediabetes, in an ethnically homogeneous Kazakh population compared to previously studied populations worldwide. This study utilized a genomic database consisting of 1800 ethnically Kazakh individuals who were considered in healthy condition. Whole-genome genotyping was performed using Illumina OmniChip 2.5–8 arrays, which interrogated approximately 2.5 million single nucleotide polymorphisms. The distribution of genotypes for the TCF7L2 (rs7903146) and PPARG (rs1801282) polymorphisms in the Kazakh sample was found to be in Hardy–Weinberg equilibrium (p > 0.05). The minor G allele of the “Asian” protective polymorphism rs1801282 in the PPARG gene was observed at a frequency of 13.8% in the Kazakh population. This suggests a potentially more significant protective effect of this polymorphism in reducing the risk of prediabetes among Kazakhs. The frequency of the unfavorable T allele of the insulin secretion-disrupting gene TCF7L2 (rs7903146) in Kazakhs was 15.2%. Studying the associations of genetic markers for prediabetes enables the timely identification of “high-risk groups” and facilitates the implementation of effective preventive measures. Further results from replicative genomic research will help identify significant polymorphic variants of genes underlying the alteration of prediabetes status.
Improving Lipid Content in the Diatom Phaeodactylum tricornutum by the Knockdown of the Enoyl-CoA Hydratase Using CRISPR Interference
Authors: Guo Wenfeng , Weng Yuwei , Ma Wenkai , Chang Chaofeng , Gao Yuqing , Huang Xuguang , Zhang Feng
Published: September 2024

The diatom Phaeodactylum tricornutum shows potential as a source for biofuel production because of its considerable lipid content. Fatty acid β-oxidation plays a critical role in lipid breakdown. However, we still have a limited understanding of the role of fatty acid β-oxidation in lipid content in this microalga. In our study, we utilized a CRISPR interference method to reduce the expression of enoyl-CoA hydratase (PtECH), which is involved in the hydration of trans-2-enoyl-CoA to produce 3-hydroxyacyl-CoA during the β-oxidation pathway. Using this method, we developed two transgenic lines, PtECH21 and PtECH1487, which resulted from interference at two different sites of the PtECH gene, respectively. RT-qPCR analysis confirmed that the mRNA levels of PtECH in both mutants were significantly lower compared to the wild type. Surprisingly, the lipid content of both mutants increased notably. Additionally, both knockdown mutants exhibited higher chlorophyll content and improved photosynthetic efficiency of the photosystem II compared to the wild type. This study introduces a new approach for enhancing lipid content in P. tricornutum and expands our knowledge of the functions of enoyl-CoA hydratase in microalgae.
Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma
Authors: Liu Rui , Ma Mingshen , Li Jing , Luan Fuxiao , Ren Tingting , Wang Nan , Ma Jianmin
Published: September 2024

Abstract: To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, <0.001, <0.001, <0.001, =0.020, <0.001, respectively) and lower expression of CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.
Undamped Higgs Modes in Strongly Interacting Superconductors
Authors: Lorenzana José , Seibold Götz
Published: September 2024

In superconductors, gauge U(1) symmetry is spontaneously broken. According to Goldstone’s theorem, this breaking of a continuous symmetry establishes the existence of the Bogoliubov phase mode while the gauge-invariant response also includes the amplitude fluctuations of the order parameter. The latter, which are also termed ‘Higgs’ modes in analogy with the standard model, appear at the energy of the spectral gap 2Δ, when the superconducting ground state is evaluated within the weak-coupling BCS theory, and, therefore, are damped. Previously, we have shown that, within the time-dependent Gutzwiller approximation (TDGA), Higgs modes appear inside the gap with a finite binding energy relative to the quasiparticle continuum. Here, we show that the binding energy of the Higgs mode becomes exponentially small in the weak-coupling limit converging to the BCS solution. On the other hand, well-defined undamped amplitude modes exist in strongly coupled superconductors when the interaction energy becomes of the order of the bandwidth.