bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease
Authors: Bashi Alaijah , Lekpor Cecilia , Hood Joshua L. , Thompson Winston E. , Stiles Jonathan K. , Driss Adel
Published: November 2023

Hemolytic disorders, like malaria and sickle cell disease (SCD), are responsible for significant mortality and morbidity rates globally, specifically in the Americas and Africa. In both malaria and SCD, red blood cell hemolysis leads to the release of a cytotoxic heme that triggers the expression of unique inflammatory profiles, which mediate the tissue damage and pathogenesis of both diseases. MicroRNAs (miRNAs), such as miR-451a and let-7i-5p, contribute to a reduction in the pro-inflammatory responses induced by circulating free hemes. MiR-451a targets both IL-6R (pro-inflammatory) and 14-3-3ζ (anti-inflammatory), and when this miRNA is present, IL-6R is reduced and 14-3-3ζ is increased. Let-7i-5p targets and reduces TLR4, which results in anti-inflammatory signaling. These gene targets regulate inflammation via NFκB regulation and increase anti-inflammatory signaling. Additionally, they indirectly regulate the expression of key heme scavengers, such as heme-oxygenase 1 (HO-1) (coded by the HMOX1 gene) and hemopexin, to decrease circulating cytotoxic heme concentration. MiRNAs can be transported within extracellular vesicles (EVs), such as exosomes, offering insights into the mechanisms of mitigating heme-induced inflammation. We tested the hypothesis that miR-451a- or let-7i-5p-loaded artificial EVs (liposomes) will reduce heme-induced inflammation in brain vascular endothelial cells (HBEC-5i, ATCC: CRL-3245) and macrophages (THP-1, ATCC: TIB-202) in vitro. We completed arginase and nitric oxide assays to determine anti- and pro-inflammatory macrophage presence, respectively. We also assessed the gene expression of IL-6R, TLR4, 14-3-3ζ, and NFκB by RT-qPCR for both cell lines. Our findings revealed that the exposure of HBEC-5i and THP-1 to liposomes loaded with miR-451a or let-7i-5p led to a reduced mRNA expression of IL-6R, TLR4, 14-3-3ζ, and NFκB when treated with a heme. It also resulted in the increased expression of HMOX1 and hemopexin. Finally, macrophages exhibited a tendency toward adopting an anti-inflammatory differentiation phenotype. These findings suggest that miRNA-loaded liposomes can modulate heme-induced inflammation and can be used to target specific cellular pathways, mediating inflammation common to hematological conditions, like malaria and SCD.
Comparative Analysis of Transposable Elements in Strawberry Genomes of Different Ploidy Levels
Authors: Lyu Keliang , Xiao Jiajing , Lyu Shiheng , Liu Renyi
Published: November 2023

Transposable elements (TEs) make up a large portion of plant genomes and play a vital role in genome structure, function, and evolution. Cultivated strawberry (Fragaria x ananassa) is one of the most important fruit crops, and its octoploid genome was formed through several rounds of genome duplications from diploid ancestors. Here, we built a pan-genome TE library for the Fragaria genus using ten published strawberry genomes at different ploidy levels, including seven diploids, one tetraploid, and two octoploids, and performed comparative analysis of TE content in these genomes. The TEs comprise 51.83% (F. viridis) to 60.07% (F. nilgerrensis) of the genomes. Long terminal repeat retrotransposons (LTR-RTs) are the predominant TE type in the Fragaria genomes (20.16% to 34.94%), particularly in F. iinumae (34.94%). Estimating TE content and LTR-RT insertion times revealed that species-specific TEs have shaped each strawberry genome. Additionally, the copy number of different LTR-RT families inserted in the last one million years reflects the genetic distance between Fragaria species. Comparing cultivated strawberry subgenomes to extant diploid ancestors showed that F. vesca and F. iinumae are likely the diploid ancestors of the cultivated strawberry, but not F. viridis. These findings provide new insights into the TE variations in the strawberry genomes and their roles in strawberry genome evolution.
Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review
Authors: Contartese Deyanira , Di Sarno Laura , Salamanna Francesca , Martini Lucia , Fini Milena , Giavaresi Gianluca , Veronesi Francesca
Published: November 2023

Musculoskeletal frailty—a common and debilitating condition linked to aging and chronic diseases—presents a major public health issue. In vivo models have become a key tool for researchers as they investigate the condition’s underlying mechanisms and develop effective interventions. This systematic review examines the current body of research on in vivo models of musculoskeletal frailty, without any time constraints. To achieve this aim, we utilized three electronic databases and incorporated a total of 11 studies. Our investigation delves into varied animal models that simulate specific features of musculoskeletal frailty, including muscle loss, bone density reduction, and functional decline. Furthermore, we examine the translational prospects of these models in augmenting our comprehension of musculoskeletal frailty and streamlining the production of groundbreaking therapeutic approaches. This review provides significant insights and guidance for healthcare researchers and practitioners who aim to combat musculoskeletal frailty, ultimately enhancing the quality of life for older adults and individuals affected by this condition.
Multifunctional Nanoplatform for NIR-II Imaging-Guided Synergistic Oncotherapy
Authors: Wang Qingluo , Xia Guoyu , Li Jianmin , Yuan Longlong , Yu Shujie , Li Dingyang , Yang Nan , Fan Zhongxiong , Li Jinyao
Published: November 2023

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people’s lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.
Comparison of Conformations and Interactions with Nicotinic Acetylcholine Receptors for E. coli-Produced and Synthetic Three-Finger Protein SLURP-1
Authors: Kost Vladimir , Sukhov Dmitry , Ivanov Igor , Kasheverov Igor , Ojomoko Lucy , Shelukhina Irina , Mozhaeva Vera , Kudryavtsev Denis , Feofanov Alexey , Ignatova Anastasia , Utkin Yuri , Tsetlin Victor
Published: November 2023

SLURP-1 is a three-finger human protein targeting nicotinic acetylcholine receptors (nAChRs). The recombinant forms of SLURP-1 produced in E. coli differ in added fusion fragments and in activity. The closest in sequence to the naturally occurring SLURP-1 is the recombinant rSLURP-1, differing by only one additional N-terminal Met residue. sSLURP-1 can be prepared by peptide synthesis and its amino acid sequence is identical to that of the natural protein. In view of recent NMR analysis of the conformational mobility of rSLURP-1 and cryo-electron microscopy structures of complexes of α-bungarotoxin (a three-finger snake venom protein) with Torpedo californica and α7 nAChRs, we compared conformations of sSLURP-1 and rSLURP-1 by Raman spectroscopy and CD-controlled thermal denaturation, analyzed their competition with α-bungarotoxin for binding to the above-mentioned nAChRs, compared the respective receptor complexes with computer modeling and compared their inhibitory potency on the α9α10 nAChR. The CD revealed a higher thermostability of sSLURP-1; some differences between sSLURP-1 and rSLURP-1 were observed in the regions of disulfides and tyrosine residues by Raman spectroscopy, but in binding, computer modeling and electrophysiology, the proteins were similar. Thus, sSLURP-1 and rSLURP-1 with only one additional Met residue appear close in structure and functional characteristics, being appropriate for research on nAChRs.
Pharmacokinetics of Novel Dopamine Transporter Inhibitor CE-123 and Modafinil with a Focus on Central Nervous System Distribution
Authors: Spreitzer Iva , Keife Josefin , Strasser Tobias , Kalaba Predrag , Lubec Jana , Neuhaus Winfried , Lubec Gert , Langer Thierry , Wackerlig Judith , Loryan Irena
Published: November 2023

S-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of S-CE-123 and R-modafinil. To address this objective, a precise liquid chromatography–high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, S-CE-123 demonstrates a significantly superior extent of transport across the blood–brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (Kp,uu,brain) of 0.5, compared to R-modafinil’s Kp,uu,brain of 0.1. A similar pattern was observed for the transport across the blood–spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that S-CE-123 primarily localizes in the brain interstitial space, whereas R-modafinil distributes more evenly across both sides of the plasma membrane of the brain’s parenchymal cells (Kp,uu,cell). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with S-CE-123 having a 9.3-fold faster metabolism compared to R-modafinil. In summary, the combination of improved BBB transport and higher affinity of S-CE-123 to dopamine transporters in comparison to R-modafinil makes S-CE-123 a promising candidate for further testing for the treatment of cognitive decline.
Stepping into a Preclinical Course as a Clinical Guest Lecturer
Authors: Coppola Kristen M. , Rashid Hanin , Kim Sarang , Lebeau Robert
Published: November 2023

Medical schools often rely on clinicians to provide guest lectures in foundational science courses. These guest lecturers may teach only once or sporadically in the undergraduate curriculum, which brings about several challenges that can impact their effectiveness. This guide, drawn from evidence-based teaching principles, medical student feedback, the authors’ training in educational and cognitive psychology, and experience as a clinical teacher, is designed to support clinical guest lecturers in meeting the educational standards and expectations for teaching in the preclinical setting as well as give insight into the needs of foundational science course directors and students.
Virtual Reality for Patient Education about Hypertension: A Randomized Pilot Study
Authors: Jiravska Godula Bogna , Jiravsky Otakar , Matheislova Gabriela , Kuriskova Veronika , Valkova Alena , Puskasova Kristina , Dokoupil Martin , Dvorakova Veronika , Prifti Arber , Foral Daniel , Jiravsky Filip , Hecko Jan , Hudec Miroslav , Neuwirth Radek , Miklik Roman
Published: November 2023

Background: Hypertension challenges arise in part from poor adherence due to inadequate patient education. VR offers immersive learning to improve hypertension knowledge. Objective: To compare VR education with traditional verbal education to improve hypertension knowledge. Methods: In this randomised trial, 182 patients with hypertension were assigned to receive either traditional physician-led education (n = 88) or VR education (n = 94) with equivalent content. The VR group experienced a 3D video using Oculus Quest 2 headsets. Knowledge was assessed post-intervention using a 29-item questionnaire. The primary outcome was the objective score. Subjective satisfaction and responder characteristics were secondary outcomes. Results: Median objective scores were significantly higher for VR (14, IQR 3) versus traditional education (10, IQR 5), p < 0.001, indicating superior hypertension knowledge acquisition with VR. Subjective satisfaction was high in both groups. Participants were categorized into low (first quartile) and medium-high (second to fourth quartiles) responders based on their scores. Low responders had a significantly higher prevalence of older women than medium-high responders (57% vs. 40% female, p = 0.024; 68 vs. 65 years), p = 0.036). Conclusions: VR outperforms traditional education. Tailoring to groups such as older women can optimise learning.
Artificial Intelligence in Scoliosis: Current Applications and Future Directions
Authors: Zhang Haozhi , Huang Changfa , Wang Daoyun , Li Kuan , Han Xiao , Chen Xin , Li Zheng
Published: November 2023

Scoliosis is a three-dimensional deformity of lateral bending and rotation of the spine. Artificial intelligence (AI) is a set of theories and techniques for studying artificial intelligence, which realizes machine intelligence by simulating and expanding human intelligence. With the continuous development of the multidisciplinary integration trend of modern medicine, artificial intelligence is used more and more in the diagnosis and treatment of scoliosis. Artificial intelligence has been widely used in the study of scoliosis and has penetrated into all fields of clinical practice of scoliosis. At present, artificial intelligence has shown good application prospects in early screening, diagnosis, treatment decision making, intraoperative operation, and prognosis prediction of scoliosis. This paper mainly summarizes the application of artificial intelligence in the clinical practice of scoliosis, and briefly introduces the AI model and its specific applications. In addition, this paper also discusses the limitations and future development of artificial intelligence. In the future, artificial intelligence will bring greater convenience to the diagnosis and treatment of scoliosis and provide better therapeutic effects for patients.
Application of Technology in Cardiopulmonary Resuscitation, a Narrative Review
Authors: Levitt Catherine V. , Boone Kirsten , Tran Quincy K. , Pourmand Ali
Published: November 2023

Novel medical technologies are designed to aid in cardiopulmonary resuscitation both in and out of the hospital. Out-of-hospital innovations utilize the skills of paramedics, bystanders, and other prehospital personnel, while in-hospital innovations traditionally aid in physician intervention. Our review of current literature aims to describe the benefits and limitations of six main technologic advancements with wide adoption for their practicality and functionality. The six key technologies include: extracorporeal membrane oxygenation (ECMO), real-time feedback devices, smart devices, video review, point-of-care ultrasound, and unmanned aerial vehicle (drone) automated external defibrillator (AED) delivery. The benefits and limitations of each technology were independently reviewed and expounded upon. Newer technologies like drone AED delivery, paramedic ultrasound use, and smart devices have been demonstrated to be safe and feasible, however, further studies are needed to compellingly demonstrate improved patient outcomes. In-hospital use of ECMO and ultrasound is well established by current literature to aid in cardiopulmonary resuscitation and improve patient outcomes.
Acute Vascular Response to Hemodialysis as Measured by Serum Syndecan-1 and Endothelin-1 Levels as Well as Vascular Stiffness
Authors: Sági Balázs , Kun Szilárd , Jakabfi-Csepregi Rita Klaudia , Sulyok Endre , Csiky Botond
Published: November 2023

Background: Chronic hemodialysis (HD) patients have a very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. The aim of this article is to study the acute vascular changes during HD. Methods: In 29 consecutive chronic HD patients (age: 65.6 ± 10.4 years), their pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. Results: Their SDC-1 levels increased during HD (p = 0.004). Males had higher ET-1 levels. The patients were divided into two groups based on their pre-HD pulse wave velocity (PWV): PWV ≥ 12 m/s and PWV < 12 m/s. The pre-HD and mid-HD SDC-1 levels were higher in the group with a PWV ≥ 12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/mL, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/mL, p = 0.044, respectively). The post-HD ET-1 levels were higher in the patient group with a PWV ≥ 12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients with a PWV ≥ 12 m/s had higher pre-HD peripheral and aortic systolic blood pressures (p < 0.05). The total cholesterol correlated with the SDC-1 decrease during HD (r = 0.539; p = 0.008). The pre-, mid-, and post-HD SDC-1 correlated with ultrafiltration (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion: SDC-1 and ET-1 contribute to the vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.
Using Renal Elastography to Predict the Therapeutic Response of Nephrological Patients
Authors: Mancianti Nicoletta , Garosi Guido , Iadanza Ernesto , Tripodi Sergio Antonio , Guarnieri Andrea , Belluardo Massimo , La Porta Edoardo , Calatroni Marta , Mazzei Maria Antonietta , Sacco Palmino
Published: November 2023

Background: The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue elasticity and can be used to determine Young’s modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement. Methods: Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP). Results: The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (p = 0.037). Conclusions: Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population.
Deep Learning in Coeliac Disease: A Systematic Review on Novel Diagnostic Approaches to Disease Diagnosis
Authors: Sharif Kassem , David Paula , Omar Mahmud , Sharif Yousra , Patt Yonatan Shneor , Klang Eyal , Lahat Adi
Published: November 2023

Background: Coeliac disease affects approximately 1% of the global population with the diagnosis often relying on invasive and time-demanding methods. Deep learning, a powerful tool in medical science, shows potential for non-invasive, accurate coeliac disease diagnosis, though challenges remain. Objective: This systematic review aimed to evaluate the current state of deep-learning applications in coeliac disease diagnosis and identify potential areas for future research that could enhance diagnostic accuracy, sensitivity, and specificity. Methods: A systematic review was conducted using the following databases: PubMed, Embase, Web of Science, and Scopus. PRISMA guidelines were applied. Two independent reviewers identified research articles using deep learning for coeliac disease diagnosis and severity assessment. Only original research articles with performance metrics data were included. The quality of the diagnostic accuracy studies was assessed using the QUADAS-2 tool, categorizing studies based on risk of bias and concerns about applicability. Due to heterogeneity, a narrative synthesis was conducted to describe the applications and efficacy of the deep-learning techniques (DLT) in coeliac disease diagnosis. Results: The initial search across four databases yielded 417 studies with 195 being removed due to duplicity. Finally, eight studies were found to be suitable for inclusion after rigorous evaluation. They were all published between 2017 and 2023 and focused on using DLT for coeliac disease diagnosis or assessing disease severity. Different deep-learning architectures were applied. Accuracy levels ranged from 84% to 95.94% with the GoogLeNet model achieving 100% sensitivity and specificity for video capsule endoscopy images. Conclusions: DLT hold substantial potential in coeliac disease diagnosis. They offer improved accuracy and the prospect of mitigating clinician bias. However, key challenges persist, notably the requirement for more extensive and diverse datasets, especially to detect milder forms of coeliac disease. These methods are in their nascent stages, underscoring the need of integrating multiple data sources to achieve comprehensive coeliac disease diagnosis.
Complex Relationship of Left Ventricular Rotational Mechanics and Deformation Represented by Strain Parameters in Healthy Adults—Detailed Analysis from the Three-Dimensional Speckle-Tracking Echocardiographic MAGYAR-Healthy Study
Authors: Nemes Attila , Kormányos Árpád , Ambrus Nóra , Lengyel Csaba
Published: November 2023

Introduction: Left ventricular (LV) strains are measures of deformation that reflect LV function quantifying the rate of LV contraction, providing information in three directions in space: radial (RS), longitudinal (LS) and circumferential directions (CS). The LV moves around its longitudinal axis in a special movement called LV rotational mechanics. The present study aimed to assess associations between three-dimensional speckle-tracking echocardiography (3DSTE)-derived LV rotational mechanics and LV strains in healthy adult subjects. Methods: The present study consisted of 174 healthy adults (mean age: 32.8 ± 12.2 years, 79 males). Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all subjects. Results: While LV-gRS and LV-gLS did not show associations with increased basal LV rotation, the lowest LV-gCS was seen in the presence of the highest LV basal rotation. An increase in basal LV rotation and consequential LV twist were not associated with apical LV rotation. While LV-gLS was not associated with the increase in apical LV rotation, LV-gRS and LV-gCS showed a trend towards increasing values. An increase in LV-gRS was associated with an increasing trend towards apical LV rotation, LV twist and LV-gCS and the preservation of basal LV rotation. LV-gLS also increased but only up to a certain value. An increase in LV-gCS was associated with a tendency towards a decrease in basal LV rotation and a tendency towards an increase in LV-gRS and LV-gLS. The highest LV-gCS was associated with the highest apical LV rotation and LV twist. The highest apical LV rotation, LV twist and LV-gCS were seen in the presence of the highest LV-gLS, while basal LV rotation and LV-gRS were not associated with increasing LV-gLS. Conclusions: Basal LV rotation has been shown to have an inverse relationship with LV-gCS, but without being related to LV-gRS and LV-gLS, while apical LV rotation is associated with LV strains in all directions, but to a different extent, suggesting a complex relationship between LV rotational mechanics and LV strains in healthy adults.
Bicuspid Morphology and Rapid Deployment Valve Replacement: Is This Still a Contraindication?
Authors: von der Linden Julia , Herrmann Florian , Belyaev Sergey , Juchem Gerd , Peterss Sven , Hagl Christian , Dashkevich Alexey
Published: November 2023

When using rapid deployment surgical aortic valve replacement (RD SAVR) in treating bicuspid aortic valve morphology (BAV), several challenges are faced due to annular asymmetry. The Sievers classification has been traditionally used for the description of BAV morphology. In this study, we aimed to conduct a retrospective feasibility analysis of RD SAVR in relation to the Sievers classification. From January 2014 to March 2022, 31 patients with BAV morphology (15 patients with Sievers type 0 BAV and 16 with Sievers type 1 BAV) underwent RD SAVR. Specific surgical techniques were applied depending on the BAV morphology. Comparable clinical outcomes were observed. No paravalvular leaks and no valvular re-interventions occurred in either group. CPB and cross-clamping times, as well as the prosthesis sizes used, were also not significantly different. Postoperative mean gradients were comparable in both groups. No significant distinction was found between the groups in terms of postoperative pacemaker indication, postoperative stroke, or death. Annular symmetry can be adequately restored through precise prosthesis sizing and placement according to an individual’s valve morphology regardless of the Sievers classification of BAV by choosing a different landmark for the initial suture. RD SAVR seems to be a safe approach for any bicuspid morphology, with good hemodynamic results and time-saving potential in experienced hands.
Work Ability in the Year after Rehabilitation—Results from the RehabNytte Cohort
Authors: Skinnes Mari Nilsen , Moe Rikke Helene , Johansen Thomas , Lyby Peter Solvoll , Dahl Kjersti , Eid Idun , Fagertun Tor Christian , Habberstad Andreas , Johnsen Tonje Jossie , Kjeken Ingvild , Klokkerud Mari , Linge Anita Dyb , Lyken Anne Dorte , Orpana Anders , Rajalahti Tarja , Wilkie Ross , Uhlig Till ,   on behalf of the RehabNytte Consortium
Published: November 2023

Background: There is limited knowledge regarding the impact of rehabilitation on work ability. The aim of this study was to explore factors associated with work ability 12 months following a multidisciplinary rehabilitation program in a cohort with different diagnoses. Methods: Of 9108 potentially eligible participants for the RehabNytte research project, 3731 were eligible for the present study, and 2649 participants (mean age 48.6 years, 71% female) consented to contribute with work-related data, and were included. Self-perceived work ability was assessed by the Work Ability Score (WAS) (0–10, 10 = best), during the follow-up period using paired t-tests and logistic regression to examine associations between demographic and disease-related factors and work ability at 12-month follow-up. Results: The mean baseline WAS for the total cohort was 3.53 (SD 2.97), and increased significantly to 4.59 (SD 3.31) at 12-month follow-up. High work ability (WAS ≥ 8) at 12 months was associated with high self-perceived health at the baseline (OR 3.83, 95% CI 2.45, 5.96), while low work ability was associated with a higher number of comorbidities (OR 0.26, 95% CI 0.11, 0.61), medium pain intensity (OR 0.56, 95% CI 0.38, 0.83) and being married or cohabiting (OR 0.61, 95% CI 0.43, 0.88). There were no significant differences in work ability between participants receiving occupational and standard rehabilitation. Conclusions: Work ability increased significantly over the follow-up period. High work ability at 12-month follow-up was associated with high self-perceived health at baseline, while being married or cohabiting, having higher number of comorbidities, and experiencing medium baseline pain intensity was associated with lower work ability. Rehabilitation interventions targeting these factors may potentially enhance work ability, leading to a positive impact on work participation among people in need of rehabilitation.
Cardio–Splenic Relationship in Patients Receiving Trans-Catheter Aortic Valve Replacement
Authors: Imamura Teruhiko , Fujioka Hayato , Ushijima Ryuichi , Sobajima Mitsuo , Fukuda Nobuyuki , Ueno Hiroshi , Kinugawa Koichiro
Published: November 2023

Background: The spleen seems to be a significant buffer of the effective circulating blood volume by changing its size dramatically according to hemodynamics. The cardio–splenic relationship has been recently proposed in the literature regarding heart failure cohorts, and the splenic size has been proposed as a prognostic factor in these cohorts. However, the clinical implication of the splenic size in patients receiving trans-catheter aortic valve replacement (TAVR) remains unknown. Methods: Patients who underwent TAVR at our institute between 2015 and 2022 were eligible. Of these, the patients whose abdominal computed tomography imaging was obtained before TAVR were included. The volume of the spleen was measured in all the participants. The prognostic impact of the indexed splenic volume (SVI) on the 2-year cardiac death or heart failure readmissions was evaluated. Results: A total of 343 patients (86 years, 98 males) were included. The median value of the peak velocity at the aortic valve was 4.4 (4.0, 4.8) m/s and the median SVI was 65.5 (48.9, 86.9) mL/m2. A lower SVI tended to be associated with a lower cardiac output, whereas a higher SVI was associated with a higher plasma volume. The SVI was independently associated with the 2-year cardiac death or heart failure readmission after TAVR with a hazard ratio of 1.09 (95% confidence interval 1.01–1.18, p = 0.041), adjusted for potential confounders. A calculated cutoff of SVI was 70.2 mL/m2, which significantly stratified the cumulative incidence of the primary outcome (10% versus 4%, p = 0.033). Conclusion: A high baseline SVI, which was associated with systemic congestion, was associated with a higher incidence of cardiac death or heart failure readmission after TAVR. Further studies are warranted to clarify the detailed cardio–splenic relationship and implication of measuring the SVI in this cohort.
Better Detection of Peripheral Arterial Disease with Toe-Brachial Index Compared to Ankle-Brachial Index among Taiwanese Patients with Diabetic Kidney Disease
Authors: Chang Chia-Wei , Sung Ya-Wen , Huang Yu-Ting , Chung Yong-Chuan , Lee Mei-Yueh
Published: November 2023

Background: Ankle-brachial index (ABI) is a simple method for diagnosing peripheral artery disease (PAD) but has limited reliability in patients with diabetes mellitus (DM) because of medial artery calcification. Our study aims to investigate whether the toe brachial index (TBI) or the cardio-ankle vascular index (CAVI) has a better detection over the ABI for diagnosing PAD in diabetic kidney disease (DKD). Materials and Methods: A cohort of 368 patients (mean age 68.59 ± 13.14 years, 190 males and 178 females) with type 2 DM underwent ABI, TBI, and CAVI measurements at our outpatient clinic. Results: Of all enrolled patients, the TBI is significant in evaluating PAD, especially in patients whose chronic kidney disease (CKD) stage 3a with adjusted odds ratio (AOR) = 6.50, 95% confidence interval (CI) 1.63–25.97, p = 0.0080, stage 3b AOR = 7.47, 95% CI 1.52–36.81, p = 0.0135, and stage 4–5 AOR = 20.13, 95% CI 1.34–94.24, p = 0.0116. CAVI is also significant in CKD stage 1 with AOR = 0.16, 95% CI 0.03–0.77, p = 0.0223, stage 2 with AOR = 0.18, 95% CI 0.04–0.74, p = 0.0180, and stage 3a AOR = 0.31, 95% CI 0.10–0.93, p = 0.0375. Conclusion: TBI has a better yield of detection of PAD compared to ABI among Taiwanese patients with DKD. CAVI may play a role in the early stage of DKD.
The Mixed Tendency in Bipolar Disorder: An Operational Proposal for the Integration of Mixed Episodes in Predominant Polarity
Authors: Fico Giovanna , Anmella Gerard , De Prisco Michele , Oliva Vincenzo , Possidente Chiara , Bracco Lorenzo , Bort Marta , Fernandez-Plaza Tabatha , Giménez-Palomo Anna , Vieta Eduard , Murru Andrea
Published: November 2023

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the “mixed tendency”, and establish a practical threshold to identify patients with a “mixed phenotype”. Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings.
Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review
Authors: Trandafir Alexandra-Ioana , Sima Oana-Claudia , Gheorghe Ana-Maria , Ciuche Adrian , Cucu Anca-Pati , Nistor Claudiu , Carsote Mara
Published: November 2023

Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.
A Pilot Multisensory Approach for Emotional Eating: Pivoting from Virtual Reality to a 2-D Telemedicine Intervention during the COVID-19 Pandemic
Authors: Malighetti Clelia , Schnitzer Ciara Kelly , YorkWilliams Sophie Lou , Bernardelli Luca , Runfola Cristin D. , Riva Giuseppe , Safer Debra L.
Published: November 2023

Background and Objectives: Emotional eating (EE), or eating in response to negative emotions or stress, can be understood as a manifestation of difficulties regulating emotions among individuals with eating disorders. To date, many virtual reality treatments for eating disorders have focused on body image or exposure methods and have not exclusively targeted EE. There has been a call made by experts in the field for a “new generation” of virtual reality interventions, capable of utilizing virtual reality’s potential more fully. We developed a novel emotion regulation (ER) intervention based upon virtual reality to improve EE among adults with an eating disorder diagnosis. The study hypothesized that a novel ER protocol utilizing evidence-based strategies, as well as innovative techniques, would be feasible and acceptable and show preliminary signals of effectiveness for EE. Materials and Methods: Due to COVID-19, the study pivoted from the original completely immersive intervention to a 2-D intervention deliverable over telehealth. Twenty-one patients were recruited from the Adult Eating Disorders Program within Stanford University to receive seven weekly one-hour virtual experiences (VEs) focusing on ER. Participants were not randomized but, as part of a pragmatic study design, chose between the novel VE-Emotion Regulation (VE-ER) intervention or continuing their treatment as usual. Before and after the seven sessions, participants completed an assessment by filling out online questionnaires. Results: Overall, VE-ER treatment was feasible, and the participant and therapist acceptability of VE-ER treatment was fairly high. In terms of preliminary effectiveness, the results showed a significant reduction in the frequencies of disordered eating behaviors in both groups, but a greater improvement in EE in the VE-ER group and a significant reduction in emotion dysregulation after the treatment. Conclusions: This novel pilot study makes a valuable contribution to the scant literature by demonstrating the feasibility, acceptability, and preliminary effectiveness of combining somatic, multisensory, and cognitive manipulations delivered via telemedicine to help patients with EE to manage their emotions. The findings can serve as the basis for larger, controlled studies evaluating the translation of the somatic marker theory from the research literature into real-world U.S. clinic settings.
Enhanced Precision in Genioplasty: A Novel Intraoperative Spatial Repositioning Using Computer-Aided Design and Manufacturing Technology and a Holographic Mixed Reality Application
Authors: Koyachi Masahide , Sugahara Keisuke , Tachizawa Kotaro , Nishiyama Akihiro , Odaka Kento , Matsunaga Satoru , Sugimoto Maki , Tachiki Chie , Nishii Yasushi , Katakura Akira
Published: November 2023

Genioplasty is performed for the orthognathic surgical correction of dentofacial deformities. This article reports a safe and accurate method for genioplasty combining a novel three-dimensional (3D) device with mixed reality (MR)-assisted surgery using a registration marker and a head-mounted display. Four types of devices were designed based on the virtual operation: a surgical splint with a connector; an osteotomy device; a repositioning device; and a registration marker. Microsoft HoloLens 2 and Holoeyes MD were used to project holograms created using computed tomography (CT) data onto the surgical field to improve the accuracy of the computer-aided designed and manufactured (CAD/CAM) surgical guides. After making an incision on the oral vestibule, the splint was fitted on the teeth and the osteotomy device was mounted at the junction site, placed directly on the exposed mandible bone surface. Temporary screws were fixed into the screw hole. An ultrasonic cutting instrument was used for the osteotomy. After separating the bone, a repositioning device was connected to the splint junction and bone segment, and repositioning was performed. At the time of repositioning, the registration marker was connected to the splint junction, and mandible repositioning was confirmed three-dimensionally through HoloLens 2 into the position specified in the virtual surgery. The rate of overlay error between the preoperative virtual operation and one-month postoperative CT data within 2 mm was 100%. CAD/CAM combined with MR enabled accurate genioplasty.
The Correlation between Elevated HDL-Cholesterol, Body Mass Index, and Presence of Thyroid Nodules: A Retrospective Analysis
Authors: Zorkun Cafer , Yalta Kenan , Eren Alara , Yetkin Ertan
Published: November 2023

Background: Elevated high-density lipoprotein-cholesterol (HDL-cholesterol) levels have been linked to unfavorable outcomes in various clinical settings, but the association with thyroid nodules remains unclear. We aimed to analyze the correlation between elevated HDL-cholesterol and the presence of thyroid nodules along with certain demographic and clinical findings. Methods: In this retrospective study, the patients were divided into three groups based on their body mass index (BMI): <25, 25–29, and >30 and evaluated. Data of 677 patients aged between 15 and 95 years (52.6 ± 15.6) were evaluated. The entire study population comprised 516 females (76.2%). Results: Thyroid nodules (67.1%) and left ventricle diastolic dysfunction (LVDD) (58.1%) were the two most frequent findings in the overall cohort. In the multivariate regression model, BMI, heart rate, and HDL-cholesterol values were significant and independent predictors (p = 0.000 for all) of the presence of thyroid nodules. The presence of thyroid nodules is higher in females, particularly within the higher BMI groups [odds ratio (OR) = 1.048 (CI = 1.02–1.08) for BMI < 25, p = 0.003; OR = 1.094 (CI = 1.05–1.14) for BMI 25–29, p = 0.000; OR = 1.115 (CI = 1.05–1.19) for BMI ≥ 30]. This higher incidence is not observed in males. Conclusion: While the precise mechanisms underlying this association are yet to be fully elucidated, elevated HDL-cholesterol may serve as an indicator of thyroid nodules rather than a marker of cardiovascular protection.
Challenging Assumptions of Normality in AES s-Box Configurations under Side-Channel Analysis
Authors: Carper Clay , Olguin Stone , Brown Jarek , Charlton Caylie , Borowczak Mike
Published: November 2023

Power-based Side-Channel Analysis (SCA) began with visual-based examinations and has progressed to utilize data-driven statistical analysis. Two distinct classifications of these methods have emerged over the years; those focused on leakage exploitation and those dedicated to leakage detection. This work primarily focuses on a leakage detection-based schema that utilizes Welch’s t-test, known as Test Vector Leakage Assessment (TVLA). Both classes of methods process collected data using statistical frameworks that result in the successful exfiltration of information via SCA. Often, statistical testing used during analysis requires the assumption that collected power consumption data originates from a normal distribution. To date, this assumption has remained largely uncontested. This work seeks to demonstrate that while past studies have assumed the normality of collected power traces, this assumption should be properly evaluated. In order to evaluate this assumption, an implementation of Tiny-AES-c with nine unique substitution-box (s-box) configurations is conducted using TVLA to guide experimental design. By leveraging the complexity of the AES algorithm, a sufficiently diverse and complex dataset was developed. Under this dataset, statistical tests for normality such as the Shapiro-Wilk test and the Kolmogorov-Smirnov test provide significant evidence to reject the null hypothesis that the power consumption data is normally distributed. To address this observation, existing non-parametric equivalents such as the Wilcoxon Signed-Rank Test and the Kruskal-Wallis Test are discussed in relation to currently used parametric tests such as Welch’s t-test.
Lightweight Robotic Joint with Thermally Activated Paraffin Actuator in the Deep Sea
Authors: Ning Dayong , He Xiaokang , Hou Jiaoyi , Liang Gangda , Zhang Kang
Published: November 2023

The abundance of resources in the deep sea continues to inspire mankind’s desire for exploration. However, the extreme environments pose a huge challenge for designing deep-sea mechanical devices that are primarily driven by hydraulic and electric motor technology. Researchers are beginning to explore more flexible and innovative drive methods suitable for the deep-sea environment. This paper presents a simple joint mechanism based on a paraffin phase change thermal expansion drive. Its unique design combines a flexible cell with an open structure that allows it to adapt to different pressures at different water depths. Paraffin is enclosed in multiple sets of smaller paraffin cells, which act as thermal expansion material for generating hydraulic pressure. The software comsol was used to perform a finite element analysis of the phase change process in paraffin. By fabricating the mechanical structure, the displacement generated by the thermal expansion is amplified and converted, thus enabling a bi-directional rotational displacement output from the joint while reducing the complexity of the structure. The joints in this paper provide a reliable reference for the design of small deep-sea robot drive systems.
Special Issue on Smart Control of Ship Propulsion System
Authors: Xing Bowen , Altosole Marco , Acanfora Maria , Balsamo Flavio
Published: November 2023

Currently, smart technologies are rapidly gaining popularity in various industries, including the maritime sector [...]
A Hybrid Design for the Functional Assay of LvLRRm (Protein Containing LRR Domain) of the White Leg Shrimp, Litopenaeus vannamei
Authors: Cho Jaemin , Lee Wooyong , Kim Taewon , Park Beomseok
Published: November 2023

In the crustacean immune system, leucine-rich repeat (LRR) is one of the major structures for recognizing pathogen-associated molecular patterns (PAMPs). LRR domain-containing proteins belong to the LRR family, which is a large group of proteins with more than 6000 genes in the database. They are involved in very diverse physiological functions, mainly by interacting with other proteins. In a previous study, the LvLRRm, a transmembrane protein containing only LRR domain, was identified in the white leg shrimp, Litopenaeus vannamei. Its versatile role in performing multiple immunomodulation activities has been reported. However, there is still a lack of research on its efficient function at the protein level. To investigate its interactions with other proteins, we applied a convenient method called the ‘Hybrid LRR technique’ to produce a recombinant LvLRRm. The LvLRRm and hagfish’s variable lymphocyte receptors (VLRs) fragments were fused to the conserved LxxLxLxxN motif while retaining the β-strand. In addition, we established interactions between hybrid proteins and the flagellin of Salmonella typhimurium by performing surface plasmon resonance (SPR) analysis. The results of the SPR analysis demonstrated notable affinity for both LvLRRm and hybrid proteins towards Salmonella flagellin. The designed LvLRRm hybrid proteins bring insight for universal applications without losing protein functions.