bluuebunny/crossref_metadata_2025 huggingface dataset:
Salinity Stress in Calendula officinalis: Negative Growth Impacts Offset by Increased Flowering Yield and the Mitigating Role of Zinc
Authors: Soliman Wagdi Saber , El-Soghayer Mohamed H. , Salaheldin Sabri , Abbas Ahmed M. , Gahory Abd-Allah
Published: December 2024

Salinity stress is a significant abiotic factor that limits plant growth and productivity by causing ionic imbalances and oxidative damage. Chelated zinc (Zn) has gained attention as an effective micronutrient to mitigate salinity-induced stress by enhancing antioxidant defense mechanisms, osmotic regulation, and physiological processes. This study aimed to investigate the impact of foliar-sprayed chelated Zn on the alleviation of salinity stress in Calendula officinalis. A pot experiment was conducted with varying salinity levels (0, 1000, 2000, and 3000 ppm NaCl) and Zn concentrations (0, 200, 400, and 600 ppm). The results demonstrated that chelated Zn significantly enhanced the growth parameters, flower yield, and biochemical traits, particularly under high-salinity conditions. Salinity stress was associated with a marked increase in the Na+ and K+ concentrations and a reduction in the Zn levels in the leaves. However, the foliar application of chelated Zn reduced the Na+ and increased the K+ concentrations in the leaves, resulting in an elevated K+/Na+ ratio with higher salinity and Zn application rates. Furthermore, the salinity and chelated Zn treatments stimulated the production of proline, phenols, flavonoids, and antioxidant activity, indicating the plant’s adaptive mechanism to enhance its secondary metabolite production under stress. These findings highlight the potential of chelated Zn to improve the salinity tolerance, supporting sustainable agricultural practices in saline-affected areas. Although salinity reduced the overall growth of C. officinalis, farmers are encouraged to cultivate this plant for its valuable inflorescences under saline irrigation conditions (up to 2000 ppm), combined with chelated Zn foliar applications at 400–600 ppm. We also recommend further research on other micronutrients.
Heat Stress Prevention in Construction: A Systematic Review and Meta-Analysis of Risk Factors and Control Strategies
Authors: Torbat Esfahani Mehdi , Awolusi Ibukun , Hatipkarasulu Yilmaz
Published: December 2024

In hot and humid work environments, construction workers can experience heat stress and heat-related illnesses (HRIs). While several studies have investigated engineering and administrative control methods to prevent certain heat stress risk factors, a comprehensive understanding of all existing risk factors and their corresponding control strategies is still lacking. It is crucial to identify gaps in current control strategies and develop a safety management framework for effective heat stress control by implementing existing measures. In addition, the effectiveness of the most common control strategies must be rigorously evaluated to ensure their efficacy and to guide future research aimed at enhancing these strategies or developing more effective ones. This study employed a mixed literature review methodology to address this knowledge gap. A structured literature review investigated and synthesized heat stress risk factors and control methods to find the gaps in control options to address underestimated risk factors. Furthermore, a comprehensive systematic literature review, including trend analysis, scientometric analysis, and meta-analysis, determined research foci and evaluated the effectiveness of the heat stress control methods. The scientometric analysis identified 11 clusters, encompassing key research themes such as environmental risk factors (e.g., high-temperature environments, climate change), administrative controls (e.g., work–rest schedules, climate change risk assessment), and personal interventions (e.g., cooling vests and sleep-related strategies). These findings highlight that the most commonly studied control methods are cooling vests, work–rest schedules, and cooling interventions. According to these results and the availability of quantitative results, the meta-analysis evaluated nine datasets of reductions in core body temperature by using types of cooling vests and anti-heat-stress uniforms and established the significant effectiveness of this control strategy in mitigating heat stress with a medium effect size. Moreover, five potential research studies have been identified to address gaps in control strategies for certain underestimated risk factors, including leveraging sensor technologies, conducting control training, dynamic work–rest schedules, using cutting-edge PPE, and governmental initiatives. Insights gained from this study enhance decision making for resource allocation, selection of control options, and intervention prioritization within a heat-stress-control framework based on the safety management system. The findings also highlight the effectiveness of cooling vests and areas that need to be developed, and evaluate potential heat-stress-control methods in construction.
Network-Based Hierarchical Feature Augmentation for Predicting Road Classes in OpenStreetMap
Authors: Hacar Müslüm , Altafini Diego , Cutini Valerio
Published: December 2024

The need to enrich the semantic completeness of OpenStreetMap (OSM) data is crucial for its effective use in geographic information systems and urban studies. Addressing this challenge, our research introduces a novel hierarchical feature augmentation approach to developing machine learning classifiers by the features retrieved from various levels of road network connectivity. This method systematically augments the feature space by incorporating measure values of connected road features, thereby integrating extensive contextual information from the network hierarchy. In our evaluation, conducted across diverse urban landscapes in six cities in Italy and Türkiye, we tested two geometry-, six centrality-, and eight semantic-based features to predict road functional classes stored as a highway = * key in OSM. The findings indicate a marginal impact of geometric features and city identifiers on classification performance. Utilizing centrality attributes alongside semantic features in a direct, non-hierarchical manner results in an F1 score of 80%. However, integrating these features in our network-based hierarchical feature augmentation process remarkably increases the F1 score up to 85%. The success of our approach underlines the importance of network-based feature engineering in capturing the complex dependencies of geographic data, considering a more accurate and contextually aware OSM classification framework.
Discovery of Glucose Metabolism-Associated Genes in Neuropathic Pain: Insights from Bioinformatics
Authors: Yu Ying , Cheung Yan-Ting , Cheung Chi-Wai
Published: December 2024

Metabolic dysfunction has been demonstrated to contribute to diabetic pain, pointing towards a potential correlation between glucose metabolism and pain. To investigate the relationship between altered glucose metabolism and neuropathic pain, we compared samples from healthy subjects with those from intervertebral disc degeneration (IVDD) patients, utilizing data from two public datasets. This led to the identification of 412 differentially expressed genes (DEG), of which 234 were upregulated and 178 were downregulated. Among these, three key genes (Ins, Igfbp3, Plod2) were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated the enrichment of hub genes in pathways such as the positive regulation of the ErbB signaling pathway, monocyte activation, and response to reactive oxygen species; thereby suggesting a potential correlation between these biological pathways and pain sensation. Further analysis identified three key genes (Ins, Igfbp3, and Plod2), which showed significant correlations with immune cell infiltration, suggesting their roles in modulating pain through immune response. To validate our findings, quantitative real-time polymerase chain reaction (qPCR) analysis confirmed the expression levels of these genes in a partial sciatic nerve ligation (PSNL) model, and immunofluorescence studies demonstrated increased immune cell infiltration at the injury site. Behavioral assessments further corroborated pain hypersensitivity in neuropathic pain (NP) models. Our study sheds light on the molecular mechanisms underlying NP and aids the identification of potential therapeutic targets for future drug development.
Insights into Within-Host Evolution and Dynamics of Oral and Intestinal Streptococci Unveil Niche Adaptation
Authors: Abdelbary Mohamed M. H. , Hatting Maximilian , Dahlhausen Andrea , Bott Alexandra , Conrads Georg
Published: December 2024

The oral–gut axis is a complex system linking the oral cavity and gastrointestinal tract, impacting host health and microbial composition. This study investigates genetic changes and adaptive mechanisms employed by streptococci—one of the few genera capable of colonizing oral and intestinal niches—within the same individual. We conducted whole-genome sequencing (WGS) on 218 streptococcal isolates from saliva and fecal samples of 14 inflammatory bowel disease (IBD) patients and 12 healthy controls. Our analysis identified 16 streptococcal species, with Streptococcus infantis, S. mitis, S. parasanguinis, S. australis, and S. salivarius being the most prevalent. S. infantis dominated the oral niche in both IBD patients (33%) and healthy controls (26%). It was also the primary species in fecal samples from IBD patients and the second most prevalent in those from healthy controls. S. parasanguinis was more prevalent in the gut than in the oral cavity in both groups. Comparative genomics demonstrated a within-host microevolution of streptococci, showing adaptations via recombination and acquisition of mobile genetic elements (MGEs). Intestinal streptococcal genomes exhibited a higher proportion of intact phages and a significantly greater acquisition of the tetA gene, which confers tetracycline resistance compared to oral genomes. Core-genome single-nucleotide polymorphisms (SNPs) analysis showed significant genetic divergence between oral and intestinal streptococcal genomes within the same individual. Our findings also unveil distinct niche-specific mutation signatures within intestinal genomes, indicating the emergence of distinct clonal lineages within each niche and suggesting that within-host streptococcal evolution is individual-dependent, initiated in the oral cavity.
Investigation of Impact of Oxidative Stress on Human Periodontal Ligament Cells Exposed to Static Compression
Authors: Hosseini Samira , Diegelmann Julia , Folwaczny Matthias , Frasheri Iris , Wichelhaus Andrea , Sabbagh Hisham , Seidel Corrina , Baumert Uwe , Janjic Rankovic Mila
Published: December 2024

Oxidative stress (OS) is a common feature of many inflammatory diseases, oral pathologies, and aging processes. The impact of OS on periodontal ligament cells (PDLCs) in relation to oral pathologies, including periodontal diseases, has been investigated in different studies. However, its impact on orthodontic tooth movement (OTM) remains poorly understood. This study used an in vitro model with human PDLCs previously exposed to H2O2 to investigate the effects of OS under a static compressive force which simulated the conditions of OTM. Human PDLCs were treated with varying concentrations of H2O2 to identify sub-lethal doses that affected viability minimally. To mimic compromised conditions resembling OTM under OS, the cells were pretreated with the selected H2O2 concentrations for 24 h. Using an in vitro loading model, a static compressive force (2 g/cm2) was applied for an additional 24 h. The cell viability, proliferation, and cytotoxicity were evaluated using live/dead and resazurin assays. Apoptosis induction was assessed based on caspase-3/7 activity. The gene expression related to bone remodeling (RUNX2, TNFRSF11B/OPG, BGLAP), inflammation (IL6, CXCL8/IL8, PTGS2/COX2), apoptosis (CASP3, CASP8), and autophagy (MAP1LC3A/LC3, BECN1) was analyzed using RT-qPCR. This study suggests an altering effect of previous OS exposure on static-compression-related mechanosensing. Further research is needed to fully elucidate these mechanisms.
Sheaf Cohomology of Rectangular-Matrix Chains to Develop Deep-Machine-Learning Multiple Sequencing
Authors: Lecian Orchidea Maria
Published: December 2024

The sheaf cohomology techniques are newly used to include Morse simplicial complexes in a rectangular-matrix chain, whose singular values are compatible with those of a square matrix, which can be used for multiple sequencing. The equivalence with the simplices of the corresponding graph is proven, as well as that the filtration of the corresponding probability space. The new protocol eliminates the problem of stochastic stability of deep Markov models. The paradigm can be implemented to develop deep-machine-learning multiple sequencing. The construction of the deep Markov models for sequencing, starting from a profile Markov model, is analytically written. Applications can be found as an amino-acid sequencing model. As a result, the nucleotide-dependence of the positions on the alignments are fully modelized. The metrics of the manifolds are discussed. The instance of the application of the new paradigm to the Jukes–Cantor model is successfully controlled on nucleotide-substitution models.
ADGRB3-High and POSTN-High Fibroblasts Are Markers of Endotypic Traits in Chronic Rhinosinusitis
Authors: Takahashi Hideyuki , Matsuyama Toshiyuki , Kawabata-Iwakawa Reika , Morishita Yohei , Kawamoto Takayuki , Chikamatsu Kazuaki
Published: December 2024

Background: Chronic rhinosinusitis (CRS) is a disease characterized by persistent sinonasal mucosal inflammation. Fibroblasts play a crucial role in extracellular matrix production and inflammation. We investigated the heterogeneity of fibroblasts in patients with CRS. Methods: Fibroblasts were isolated from nasal polyp tissues. RNA sequencing was then performed. We also analyzed the GSE136825 dataset obtained from the Gene Expression Omnibus database. Alternatively, fibroblasts were stimulated in vitro. Results: Hierarchical clustering of samples indicated ADGRB3-high and POSTN-high fibroblasts. A Gene Set Enrichment Analysis (GSEA) revealed that cytotoxic immune responses were enriched in ADGRB3-high fibroblasts, while cell cycle pathways were enriched in POSTN-high fibroblasts. Similar GSEA results were observed in the GSE136825 dataset. Additionally, type 1 and type 3 inflammation-related genes were highly expressed in ADGRB3-high samples, whereas type 2-related genes were highly expressed in POSTN-high samples. In vitro, ADGRB3 expression increased in fibroblasts stimulated with IFN-γ, while POSTN increased in those stimulated with IL-4 and IL-13. Conclusions: Our study demonstrates that type 1 inflammation induces ADGRB3-high fibroblasts, associated with the cytotoxic immune response, while type 2 inflammation induces POSTN-high fibroblasts, linked to CRS progression via an elevated cell cycle. The further characterization of fibroblasts could provide insights into the stromal networks in the CRS microenvironment.
On the Functional Nature of Cognitive Systems
Authors: Manca Vincenzo
Published: December 2024

The functional nature of cognitive systems is outlined as a general conceptual model where typical notions of cognition are analyzed apart from the physical realization (biological or artificial) of such systems. The notion of function, one of the main logical bases of mathematics, logic, linguistics, physics, and computer science, is shown to be a unifying concept in analyzing cognition components: learning, meaning, comprehension, language, knowledge, and consciousness are related to increasing levels in the functional organization of cognition.
Detection of the Leg-Crossing Position Using Pressure Distribution Sensor and Machine Learning
Authors: Yuda Emi , Ando Tomoki , Yoshida Yutaka
Published: December 2024

Humans often cross their legs unconsciously while sitting, which can lead to health problems such as shifts in the center of gravity, lower back pain, reduced blood circulation, and pelvic distortion. Detecting unconscious leg crossing is important for promoting correct posture. In this study, we investigated the detection of leg-crossing postures using machine learning algorithms applied to data from body pressure distribution sensors. Pressure data were collected over 180 s from four male subjects (25.8 ± 6.29 years old) under three conditions: no leg crossing, right-leg crossing, and left-leg crossing. Seven classifiers, including support vector machine (SVM), random forest (RF), and k-nearest neighbors (k-NN), were evaluated based on accuracy, recall, precision, and specificity. Among the tested methods, k-NN demonstrated the highest classification performance, suggesting it may be the most effective approach for identifying leg-crossing postures in this study.
D3S: A Drone Security Scoring System
Authors: Branco Bruno , Silva José Silvestre , Correia Miguel
Published: December 2024

This paper explores the problem of the security of unmanned aerial vehicles (UAV) by introducing the drone security scoring system (D3S). D3S is a security assessment method that analyzes the security of a UAV model by analyzing its components. Penetration tests were carried out to support D3S and identify potential vulnerabilities in UAVs. Specific cyber-attacks, such as deauthentication, flooding, and replay, were executed in an effort to take full control of the UAVs. Eight different UAV models were assessed using D3S, revealing notable variations in performance, both in control communications and video transmission. Security scores ranging from 0.9 to 4.5 out of 5 were obtained, showing significantly divergent security levels.
Integrating Citizen Participation in the Development of New ICT Services for Smart Cities
Authors: Ricardo Alexander Jesus , Vallejo Mónica Ayde , Aedo José Edinson
Published: December 2024

The transition of cities towards a smarter approach significantly benefits from citizen participation in the development and implementation of innovative information and communication technology (ICT) products and services. Despite the emergence of various initiatives in recent years aimed at guiding the development of smart cities, there is still a lack of effective strategies to actively engage citizens, businesses, and educational institutions during the creation of these products and services. This study describes a set of practices that includes four co-creation techniques to facilitate the effort of software system development in collaboration with citizens and other stakeholders. The SEMAT standard is used to create and represent a method in which these practices are distributed across four stages: focus, definition, development, and validation. In each stage, a practice is proposed that incorporates a co-creation technique and complementary activities from various software engineering disciplines to promote active citizen participation; stimulate idea generation; and facilitate the creation of necessary documents and components for the development of the desired software system, including design systems, code files, conceptual representations, and technical diagrams, among others. Finally, the applicability and completeness of the method are validated through expert consultation in the fields of software engineering and smart cities. Recognized procedures are followed to obtain qualitative and quantitative results, such as improvement actions (addition or removal of elements), levels of consensus or acceptance, and opportunities for future work.
The Effect of Access to Waterbodies and Parks on Walking and Cycling in Urban Areas
Authors: Sitohang Irene , Belaroussi Rachid , Adelé Sonia , Imine Hocine
Published: December 2024

This pilot study investigated whether good and bad access to waterbodies and parks have different impacts on walking and cycling in neighborhoods in urban areas. Focusing on Paris, France, the neighborhoods were classified based on their access to the two natural environments through GIS analysis. Active mobility, past behavior, trip purpose, and subjective evaluation were collected through an online survey. The subjective evaluation included infrastructure satisfaction and the perception of transport mode choice, urban area aesthetic level, safety, health, and preference for active mobility over car use. Descriptive analyses, Mann–Whitney tests, and Fisher’s exact tests were conducted to compare between two access groups and between cycling and walking. Active mobility was mainly performed for utilitarian purposes. Weekly cycling frequency was found to be lower than walking. Access to natural environments mainly impacts walking. Contrary to general belief, cycling frequency is higher in neighborhoods with bad access to waterbodies than in ones with good access. Contrary to expectations, this study found little significant effect on active mobility in the accessibility to both natural environments. This study also highlights the influence of dominant active mobility purposes in urban areas with respect to access to natural environments, and provides a subjective evaluation for active mobility.
Ecological Profile of the Flea Beetle Genus Calotheca Heyden in South Africa (Chrysomelidae, Galerucinae, Alticini)
Authors: Biondi Maurizio , Iannella Mattia , D’Alessandro Paola
Published: December 2024

In this work, the 25 species of the flea beetle genus Calotheca Heyden recorded for South Africa are considered. Starting from the updated species distribution and the topographic, temperature, and precipitation variables, as well as the vegetation types in the occurrence sites, through an analysis of ecological niche modelling, a possible ecological profile is provided, both for each species and the entire genus, highlighting some of the factors that drive their occurrence and distribution patterns. Along with the vegetation type, some climatic variables were found to be particularly influential, such as the mean temperature of both the wettest and driest quarters and also the mean precipitation of the wettest period. Finally, comparing the distribution of the areas of highest suitability returned by the model obtained for Calotheca, they largely overlap with the highest-density areas of Searsia, genus of Anacardiaceae, including the main host plants for these flea beetles.
The Effect of Cropping Systems on the Dispersal of Mycotoxigenic Fungi by Insects in Pre-Harvest Maize in Kenya
Authors: Riungu Ginson M. , Muthomi James , Wagacha Maina , Buechs Wolfgang , Philip Esther S. , Meiners Torsten
Published: December 2024

Maize productivity has remained low and has worsened in the wake of a changing climate, resulting in new invasive pests, with pests that were earlier designated as minor becoming major and with pathogens being transported by pests and/or entering their feeding sites. A study was conducted in 2021 in the Kisumu and Makueni counties, Kenya, to determine how different maize cropping systems affect insect diversity, insect damage to maize, and insects’ ability to spread mycotoxigenic fungi in pre-harvest maize. The field experiments used a randomized complete block design, with the four treatments being maize monocrop, maize intercropped with beans, maize–bean intercrop with the addition of Trichoderma harzianum at planting, and push–pull technology. The FAW, Spodoptera frugiperda (J.E Smith) (Lepidoptera: Noctuidae), was the most damaging pest in the two regions. The push–pull and the maize–bean intercropping technologies significantly reduced the maize foliage and ear damage caused by the FAW. Beetles passively spread mycotoxigenic Aspergillus spp. and Fusarium verticillioides on pre-harvest maize. Maize weevils, namely, Sitophilus zeamais Motschulsky, 1855 (Coleoptera: Curculionidae), and Carpophilus dimidiatus Fabricius, 1792 (Coleoptera: Nitidulidae), earwigs, namely, Forficula spp. L. (Dermaptera: Forficulidae), and carpenter ants, namely, Camponotus spp. L. (Hymenoptera: Formicidae) carried the highest number of spores on their exoskeletons. This study stresses the role of insects in the spread of fungi on pre-harvest maize and their possible control by intercropping and other cropping technologies.
The Ability to Digest Cellulose Can Significantly Improve the Growth and Development of Silkworms
Authors: Wu Jinxin , Zhang Yungui , Chen Han , Xia Qingyou , Zhao Ping , Lin Ying , Shen Guanwang
Published: December 2024

Cellulose is essential in the growth and development of herbivores. However, its limited utilization by herbivores is a key factor restricting their feed conversion rates. Cellulase can hydrolyze cellulose into glucose, and the addition of exogenous cellulase preparations to feed is an effective method for improving the cellulose utilization rate of ruminants. Nevertheless, the decomposition efficiency of exogenous cellulase is unstable and susceptible to various external factors. In this study, the endoglucanase III gene from Apriona germari (AgEGase III) was introduced into silkworms to investigate whether transgenic silkworms with cellulose-digesting capabilities outperformed normal silkworms in terms of growth, reproduction, and economic traits. The results show that the transgenic silkworms exhibited increased body size, weight, feeding efficiency, and digestibility compared to the wild-type silkworms. The cocoon weight, shell weight, cocoon–shell ratio, and pupa weight were notably elevated by 11%, 37%, 23%, and 9%, respectively. Additionally, the egg weight and egg-laying quantity of the female moth were also significantly increased compared to those of the wild type. Furthermore, feeding transgenic silkworms with an artificial feed containing additional cellulose demonstrated their ability to digest and utilize cellulose, leading to improved growth and development. This study offers theoretical support for the development of transgenic ruminant species that express cellulolytic enzymes.
Silencing ACE1 Gene with dsRNA of Different Lengths Impairs Larval Development in Leptinotarsa decemlineata
Authors: Julian-Chávez Brenda , Siqueiros-Cendón Tania S. , Torres-Castillo Jorge Ariel , Sinagawa-García Sugey Ramona , Abraham-Juárez María Jazmín , González-Barriga Carmen Daniela , Rascón-Cruz Quintín , Siañez-Estrada Luis Ignacio , Arévalo-Gallegos Sigifredo , Espinoza-Sánchez Edward Alexander
Published: December 2024

In the search for effective strategies to control the Colorado Potato Beetle, RNA interference technology has emerged as a promising method due to its capacity to suppress genes selectively. Factors such as the target gene and double-stranded RNA (dsRNA) length are critical for optimizing gene silencing efficiency. In this study, we designed and synthesized in vitro dsRNAs of varying lengths targeting the ACE1 gene, which encodes the AChE1 isoform of acetylcholinesterase in the beetle. All tested dsRNA lengths (222 bp, 543 bp, 670 bp, and 870 bp) promoted transcript reduction. The 670 bp dsRNA was the most effective, reducing transcript levels by approximately 40% by day seven, followed by the 543 bp dsRNA. No significant differences were observed between the 222 bp and 870 bp dsRNAs. Furthermore, all of the dsRNA lengths resulted in reduced weight gain and increased mortality in larvae, with the 670 bp dsRNA showing the highest mortality rate, leaving only 63% larval survival, a trend that persisted through day nine. These findings emphasize that dsRNA length is a key factor in the silencing response, underscoring the importance of selecting the optimal length while considering the gene’s target, stability, and delivery methods. This study contributes to establishing design criteria for dsRNA, aiding in the development of more effective and sustainable pest management strategies.
Improving Dementia Home Caregiving and Restructuring the Dementia Narrative Through Creating a Graphic Memoir and Engaging in a Psychoanalytic Narrative Research Method
Authors: Nash Carol
Published: December 2024

Informal dementia home caregiving is viewed negatively by society and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative while engaging in it, and a psychoanalytic narratology method may reduce experienced depression and anxiety associated with burnout. This investigation examines writing, illustrating, and publishing a graphic memoir by one informal dementia home caregiver. As the mother of the illustrator and the editor and publisher of this graphic memoir, I provide the perspective of this investigation based on communications with the author and illustrator. My historical analysis, in which the author participated, represents psychoanalytic narrative research, serving as the historical method. The effects of writing, illustrating, and publishing the graphic memoir were able to reduce the informal dementia home caregivers’ symptoms during the entire process and extend the effect of this endeavor until the death of the mother. Engaging in the psychoanalytic narrative research process was additionally effective in this regard. The outcomes demonstrate the viability of writing and illustrating a publishable graphic memoir for other informal dementia home caregivers and the possibility of it and the narrative research method to help decrease their depression and anxiety regarding burnout.
Characterizing Protracted Febrile Myalgia: Fasciitis and Vasculitis of the Fascia and Muscle as Novel Histopathological Features
Authors: Hernández-Rodríguez José , Mestre-Trabal Lola , Gómez-Caverzaschi Verónica , Araújo Olga , Terenas Magda , Robaina Ricardo , Bolaños Julio , Prieto-González Sergio , Antón Jordi , Yagüe Jordi , Tomás Xavier , Aldecoa Iban , Grau Josep M.
Published: December 2024

Background: Protracted febrile myalgia (PFM) is a rare but severe form of myalgia mainly occurring in pediatric patients with familial Mediterranean fever (FMF). PFM imaging and histopathological data remain scarce. Objectives: A comprehensive clinical, imaging, and histopathological characterization of PFM was performed by retrospectively analyzing a reference center cohort of adult patients with FMF and myalgia, and by a PubMed search of well-described cases with PFM. Results: Among 56 adults with FMF from our center, 32 (57.1%) experienced myalgia, which was generalized in 21 (37.5%) and affected lower limbs in 11 (19.6%) subjects. One (1.8%) patient suffered PFM, mainly affecting calves and Achilles tendons. From our patient’s detailed information and the data from 123 PFM cases reported in the literature, PFM was characterized as usually presenting with fever and severe generalized myalgia, with occasional involvement of lower legs and calves. It is mainly associated (in >90% of cases) with the pathogenic mutation M694V in the MEFV gene. Raised acute phase reactants and normal creatine kinase levels are constant. High glucocorticoid doses are useful in most patients, and sustained colchicine treatment protects from PFM recurrences. MRI may identify a variable degree of muscle inflammatory changes, especially subfascial and myofascial lesions with extension to tendinous structures. PFM histopathology is characterized by T-cell rich inflammatory infiltrates and vasculitis mainly involving the fasciae and myofascial areas, with a lower muscle extent. Conclusions: PFM can occur in children and adults and appears to be clinically manifested as fasciitis/tendinitis caused by a vasculitis of the fasciae rather than a major muscle vasculitis.
Effects of Transcranial and Trans-Spinal Direct Current Stimulation Combined with Robot-Assisted Gait Training on Gait and Fatigue in Patients with Multiple Sclerosis: A Double-Blind, Randomized, Sham-Controlled Study
Authors: Cinbaz Gülser , Sarı Zübeyir , Oğuz Semra , Tombul Temel , Hanoğlu Lütfü , Fernández-Pérez Juan J. , Gómez-Soriano Julio
Published: December 2024

Background/Objectives: Multiple Sclerosis (MS) is a chronic neurological condition that impairs motor and sensory functions, particularly gait. Non-invasive neuromodulation techniques aim to enhance functional recovery and motor–cognitive outcomes, though their effectiveness remains debated. This study compared the effects of transcranial direct current stimulation (tDCS) and trans-spinal direct current stimulation (tsDCS), combined with robotic-assisted gait training (RAGT), on motor function and fatigue in people with MS (pwMS). Methods: This double-blind, randomized, sham-controlled clinical trial included 35 pwMS, who participated in 12 sessions of 20 min anodal tDCS (n = 11), cathodal tsDCS (n = 12), or sham treatment (n = 12), in addition to RAGT. Primary outcomes were assessed using the Timed 25-foot Walk (T25-FW), Timed Up and Go (TUG), walking speed, and Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). ClinicalTrials number: NCT06121635. Results: Significant improvements in gait speed, T25-FW, MSWS-12, TUG scores, and fatigue (FSS) favored tDCS and tsDCS over sham stimulation. While no differences were found between tDCS and tsDCS, the tsDCS group showed a significant improvement in the FIS physical subscale compared to sham, unlike the tDCS group. Conclusions: tDCS and tsDCS, combined with RAGT, improve walking and reduce fatigue in pwMS, highlighting their potential in motor rehabilitation.
Gastric Adenocarcinomas with CDX2 Induction Show Higher Frequency of TP53 and KMT2B Mutations and MYC Amplifications but Similar Survival Compared with Cancers with No CDX2 Induction
Authors: Voutsadakis Ioannis A.
Published: December 2024

Background: Gastric cancer is one of the most prevalent gastrointestinal cancers. Mortality is high, and improved treatments are needed. A better understanding of the pathophysiology of the disease and discovery of biomarkers for targeted therapies are paramount for therapeutic progress. CDX2, a transcription factor of hindgut specification, is induced in several gastric cancers, especially with intestinal differentiation, and could be helpful for defining sub-types with particular characteristics. Methods: Gastric cancers with induced CDX2 mRNA expression were identified from the gastric cohort of The Cancer Genome Atlas (TCGA) and were compared with cancers that had no CDX2 mRNA induction. Induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples above 0, and non-induced CDX2 mRNA expression was defined as mRNA expression z-score relative to all samples below −1. Results: Patients with gastric cancers with CDX2 mRNA induction were older, had less frequently diffuse histology, and more often had mutations in TP53 and KMT2B and amplifications in MYC. CDX2 induction was correlated with HNF4α induction and was reversely correlated with SOX2. Gastric cancers with CDX2 mRNA induction showed lower PD-L1 expression than cancers with lower CDX2 expression but did not differ in CLDN18 mRNA expression. Progression-free and overall survival of the two groups was also not significantly different. Conclusion: Gastric cancers with CDX2 mRNA induction displayed specific characteristics that differentiate them from cancers with no CDX2 induction and could be of interest for optimizing current and future therapies.
Pneumopericardium, a Heart in a Trap
Authors: Rak Małgorzata , Fogiel Oskar , Chesi Marcos , Starosolski Michał , Ilczak Tomasz , Śmiałowski Adam , Krakowiak Anna
Published: December 2024

Background: The text discusses the case of a patient who experienced pneumopericardium because of a traumatic incident. It discusses pneumopericardium’s causes, symptoms, and complications, including tamponade symptoms and imaging modalities, to confirm the diagnosis and assess complications. Present various treatment options emphasize the importance of ongoing monitoring and damage control principles. Methods: Retrieved pneumopericardium cases with complete clinical databases (Pubmed, Medline) and summarised the clinical symptoms and prognosis of different treatment schemes. Results: A 33-year-old male patient, after a suicide attempt, fell from a height estimated at 15 m. The patient was intubated at the scene and mechanically ventilated. Initial assessment revealed signs of tension pneumothorax, which was decompressed and stabilized. Subsequent deterioration led to the discovery of pneumopericardium through diagnostic imaging. Conclusions: The case highlights the need for a comprehensive and multidisciplinary approach to address the complex nature of injuries associated with pneumopericardium. It examines the principles of damage control, which focus primarily on the patient’s general condition, leaving some injuries for later treatment.
Risk Factors and Clinical Outcomes of Arterial Re-Occlusion After Successful Mechanical Thrombectomy for Emergent Intracranial Large Vessel Occlusion
Authors: Lee In-Hyoung , Ha Sung-Kon , Lim Dong-Jun , Choi Jong-Il
Published: December 2024

Background: Re-occlusion of initially recanalized arteries after thrombectomy is a significant concern that may lead to poor outcomes. This study aimed to identify the risk factors and evaluate the prognosis of arterial re-occlusion following successful thrombectomy in patients diagnosed with emergent large-vessel occlusion (ELVO). Methods: We retrospectively analyzed data from 155 consecutive patients with ELVO who underwent mechanical thrombectomy (MT). Patients were classified into two groups according to whether the initial recanalized artery was re-occluded within 7 days after successful thrombectomy: re-occlusion and non-occlusion groups. Multivariate analysis was performed for potentially associated variables with p < 0.20 in the univariate analysis to identify the independent risk factors of re-occlusion. Differences in clinical outcomes were also assessed in these two groups. Results: Re-occlusion occurred in 10.3% of patients (16/155). Multivariate analysis demonstrated that large artery atherosclerosis (odds ratio [OR]: 3.942, 95% confidence interval [CI]: 1.247–12.464; p = 0.020), the number of device passes (OR: 2.509, 95% CI: 1.352–4.654; p = 0.004), and residual thrombus/stenosis (OR: 4.123, 95% CI: 1.267–13.415; p = 0.019) were independently associated with re-occlusion. Patients with re-occlusion had significantly worse NIHSS scores at discharge and lower opportunities for achieving functional independence at 3 months after MT than patients without re-occlusion. Conclusions: Large artery atherosclerosis, a high number of thrombectomy device passes, and residual thrombus/stenosis seemed to promote re-occlusion after successful recanalization. Timely identification and proper treatment strategies to prevent re-occlusion are warranted to improve clinical outcomes, especially among high-risk patients.
Nanomedicine in Ophthalmology: From Bench to Bedside
Authors: Mahaling Binapani , Baruah Namrata , Dinabandhu Aumreetam
Published: December 2024

Ocular diseases such as cataract, refractive error, age-related macular degeneration, glaucoma, and diabetic retinopathy significantly impact vision and quality of life worldwide. Despite advances in conventional treatments, challenges like limited bioavailability, poor patient compliance, and invasive administration methods hinder their effectiveness. Nanomedicine offers a promising solution by enhancing drug delivery to targeted ocular tissues, enabling sustained release, and improving therapeutic outcomes. This review explores the journey of nanomedicine from bench to bedside, focusing on key nanotechnology platforms, preclinical models, and case studies of successful clinical translation. It addresses critical challenges, including pharmacokinetics, regulatory hurdles, and manufacturing scalability, which must be overcome for successful market entry. Additionally, this review highlights safety considerations, current marketed and FDA-approved nanomedicine products, and emerging trends such as gene therapy and personalized approaches. By providing a comprehensive overview of the current landscape and future directions, this article aims to guide researchers, clinicians, and industry stakeholders in advancing the clinical application of nanomedicine in ophthalmology.
Asymmetrical Damage of the Wrist Joint Induces Lateralized Cortical Bone Loss in the Metacarpal Diaphysis in Patients with Rheumatoid Arthritis
Authors: Nakashima Akikatsu , Fujii Hiroshi , Kuroda Masahiro , Zoshima Takeshi , Mizushima Ichiro , Nomura Hideki , Kawano Mitsuhiro
Published: December 2024

Background/Objectives: Osteoporosis is common in rheumatoid arthritis (RA), occurring either systemically or locally around inflamed joints. Decreased metacarpal bone density is a known marker of RA progression and hand function impairment. Although RA is generally characterized by symmetrical arthritis, some patients exhibit asymmetrical joint involvement. This study investigates the frequency of unilateral metacarpal bone density reduction in RA patients and aims to identify associated factors. Methods: This study included 143 RA patients (107 females, mean age 62.4 yrs., mean disease duration 11.1 yrs.). Bilateral hand X-rays were used to measure the cortical thickness rate (CTR) of the 2nd to 4th metacarpals. Unilateral bone density reduction was defined as a thin-to-thick-side CTR ratio (CTRR) < 0.8. Associations between CTR reduction and unilateral wrist joint damage (WJD) were analyzed. Results: Unilateral CTR reduction (CTRR < 0.8) was observed in 16.8% of patients, significantly associated with unilateral WJD. Among patients with unilateral WJD, 50.0% showed CTRR lateral (+) compared to 10.1% without unilateral WJD (p < 0.01). ANCOVA revealed significant effects of WJD laterality on CTRR, with an interaction effect showing greater CTRR laterality when thin-side WJD was present without thick-side WJD. Post-biologic treatment, CTR values decreased in both hands, indicating no improvement in bone density reduction. Conclusions: Approximately 17% of RA patients exhibited unilateral relative metacarpal bone density reduction, closely associated with unilateral WJD. This first detailed report on bone density laterality in RA underscores the need for early intervention and rehabilitation strategies in RA patients with hand involvement.
Clinical Evaluation of an Electronic Guidance System for Optimizing the Ultrasound Screening for Developmental Hip Dysplasia in Newborns
Authors: Heisinger Stephan , Chiari Catharina , Willegger Madeleine , Windhager Reinhard , Kolb Alexander
Published: December 2024

Background: Graf ultrasound screening is considered an established method for early detection of developmental dysplasia of the hip (DDH). Although characterized by a high degree of standardization to allow for good reproducibility of results, examination-related factors may still affect sonographic measurements. The relative tilt angle between the hip and the probe is a potential pitfall as it significantly influences sonographic measurements and consequently classification of DDH according to Graf. Objectives: Evaluation of an electronic guidance system developed to reduce relative tilt angles and increase reliability and comparability in ultrasound screening of DDH. Materials and Methods: Twenty-five newborns were examined using a prototype guidance system, which tracks the position of the transducer and the pelvis to calculate the relative tilt angles. Two ultrasound images were obtained, one conventionally and the other one using the guidance system. Subsequently, relative roll and pitch angles and sonographic measurements were determined and analyzed. Results: The relative inclination angles in the conventional group ranged from −12.6° to 14.3° (frontal plane) and −23.8° to 32.5° (axial plane). vs. −3.7° to 3.0° and −3.2° to 4.5° in the guidance system group. The variances were significantly lower in the guidance system-assisted group for both planes (p < 0.001 and p < 0.001, respectively). The optimized transducer position showed significant effects and consequently significantly reduced alpha angles were observed (p = 0.001, and p = 0.003). Conclusions: The guidance system allowed a significant reduction in the relative tilt angles, supporting optimal positioning of the transducer, resulting in significant effects on Graf sonographic measurements. This technique shows great potential for enhancing the reproducibility and reliability of ultrasound screening for DDH.
Sacubitril/Valsartan and Dapagliflozin in Patients with a Failing Systemic Right Ventricle: Effects on the Arrhythmic Burden
Authors: Ciriello Giovanni Domenico , Altobelli Ippolita , Fusco Flavia , Colonna Diego , Correra Anna , Papaccioli Giovanni , Romeo Emanuele , Scognamiglio Giancarlo , Sarubbi Berardo
Published: December 2024

Background/Objectives: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are essential medications in heart failure (HF) therapy, and their potential antiarrhythmic effects have been reported. Recently, ARNI and SGLT2i use for HF in adult congenital heart disease (ACHD) has been studied. However, whether any beneficial effects may be achieved on the arrhythmic burden in the complex population of ACHD with a systemic right ventricle (sRV) is still to be determined. Methods: We retrospectively collected all significant arrhythmic events from a cohort of patients with a failing sRV attending our tertiary care center on optimal guideline-directed medical therapy (GDMT) with ARNI and/or SGLT2i. Results: A total of 46 patients (mean age 38.2 ± 10.7 years, 58% male) on sacubitril/valsartan were included. Twenty-three (50%) patients were also started on dapagliflozin. After a median follow-up of 36 [Q1–Q3: 34–38] months, arrhythmic events occurred globally in 13 (28%) patients. Survival analysis showed significant reduction of clinically relevant atrial and ventricular arrhythmia at follow-up (p = 0.027). Conclusions: Our findings suggest that GDMT including sacubitril/valsartan and dapagliflozin may also offer an antiarrhythmic effect in ACHD patients with a failing sRV, by reducing the incidence of arrhythmic events at follow-up.
Diabetes Mellitus: A Risk Factor in Schlemm’s Canal-Based Minimally Invasive Glaucoma Surgery
Authors: Chihara Etsuo , Nakano Eri , Chihara Tomoyuki
Published: December 2024

Objectives: The objective of this study was to evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal-based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, postoperative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic patients and 84 non-diabetic patients, with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3 ± 24.8 months. There was no significant difference in preoperative IOP between cohorts with or without diabetes. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the cohort with diabetes (p = 0.019 to 0.001). The 3-year survival probability of achieving an IOP ≤ 15 mmHg was 17.8 ± 0.09% in patients with diabetes, significantly lower than the 30.4 ± 0.06% observed in patients without diabetes (p = 0.042 Log-rank test). The 3-year survival probability of achieving an IOP ≤ 18 mmHg was 56.7 ± 0.12% in patients with diabetes compared to 79.5 ± 0.05% in patients without diabetes, indicating a marginally significant difference between cohorts with and without diabetes (p = 0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error, and the extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (p < 0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal-based MIGS, particularly in achieving lower postoperative IOP.