bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a Role of the Long Non-Coding RNA ITGB2-AS1 in Eosinophil Differentiation and Functions
Authors: Fettrelet Timothée , Hosseini Aref , Wyss Jacqueline , Boros-Majewska Joanna , Stojkov Darko , Yousefi Shida , Simon Hans-Uwe
Published: November 2024

Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (ITGB2-AS1) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable ITGB2-AS1 knockdown in the HL-60 cell line. Interestingly, ITGB2-AS1 deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, ITGB2-AS1-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that ITGB2-AS1 plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology.
Exploring the Immunoresponse in Bladder Cancer Immunotherapy
Authors: Ruiz-Lorente Inmaculada , Gimeno Lourdes , López-Abad Alicia , López Cubillana Pedro , Fernández Aparicio Tomás , Asensio Egea Lucas Jesús , Moreno Avilés Juan , Doñate Iñiguez Gloria , Guzmán Martínez-Valls Pablo Luis , Server Gerardo , Escudero-Bregante José Félix , Ferri Belén , Campillo José Antonio , Pons-Fuster Eduardo , Martínez Hernández María Dolores , Martínez-Sánchez María Victoria , Ceballos Diana , Minguela Alfredo
Published: November 2024

Bladder cancer (BC) represents a wide spectrum of diseases, ranging from recurrent non-invasive tumors to advanced stages that require intensive treatments. BC accounts for an estimated 500,000 new cases and 200,000 deaths worldwide every year. Understanding the biology of BC has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to BC, immunotherapy with bacillus Calmette–Guérin (BCG) remains the gold standard in high-risk non-muscle invasive BC. For muscle-invasive BC and metastatic stages, immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have emerged as potent therapies, enhancing immune surveillance and tumor cell elimination. This review aims to unravel the immune responses involving innate and adaptive immune cells in BC that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer.
Investigation of Biological Activity of Fucoidan and Laminarin as Bioactive Polysaccharides from Irish Brown Macroalgae
Authors: Karuppusamy Shanmugapriya , Wanigasekara Janith , Fitzpatrick Stephen , Lyons Henry , Curtin James , Rajauria Gaurav , Tiwari Brijesh K. , O’Donnell Colm
Published: November 2024

This study aimed to investigate the biological activity of crude and purified laminarin and fucoidan samples extracted from Irish brown macroalgae species Laminaria digitata and Fucus vesiculosus. The antioxidant capacity of the samples was evaluated using the 2,2-diphenyl-1-picrylhydrazyl and ferric-reducing antioxidant power assays. The anti-inflammatory potential of the samples was analysed using the cyclooxygenases inhibition activity, and the antidiabetic activity was evaluated using a dipeptidyl peptidase-4 inhibitor screening assay. The cytotoxicity of the samples was measured using the Alamar Blue™ assay with different types of cancer cell lines. The crude laminarin and fucoidan samples exhibited higher antioxidant activity (p < 0.05) than the purified samples and commercial standards. Similarly, the crude extracts showed stronger anti-inflammatory and antidiabetic effects compared to the purified samples. Additionally, the crude laminarin and fucoidan samples showed higher cytotoxic activity. Specifically, as confirmed in the flow cytometry analysis, 3D tumour spheres using different cancer cell lines showed significantly higher resistance to bioactive compounds compared to 2D monolayer cells. The laminarin and fucoidan polysaccharide samples investigated are suitable for potential nutraceutical applications based on the biological activity values observed. Future research is necessary to purify the bioactive compounds investigated and improve their selectivity for targeted therapeutic uses in food and biomedical applications.
A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1
Authors: García-Puga Mikel , Gerenu Gorka , Bargiela Ariadna , Espinosa-Espinosa Jorge , Mosqueira-Martín Laura , Sagartzazu-Aizpurua Maialen , Aizpurua Jesús M. , Vallejo-Illarramendi Ainara , Artero Rubén , López de Munain Adolfo , Matheu Ander
Published: November 2024

Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress. Methods: Human primary fibroblasts from DM1 patients and control donors, treated with MP compounds or not, were used for functional studies of cell viability, proliferation, and metabolism. The gene expression profile in treated cells was determined using RNA sequencing. The impact of MP compounds in vivo was evaluated in a Drosophila model of the disease using locomotor activity and longevity studies. Results: The treatment with different MP compounds reversed oxidative stress and impaired cell viability and proliferation, mitochondrial activity, and metabolic defects in DM1-derived primary fibroblasts. RNA sequencing analysis confirmed the restoration of molecular pathways related to calcium and redox homeostasis and additional pathways, including the cell cycle and metabolism. This analysis also revealed the rescue of alternative splicing events in DM1 fibroblasts treated with MP compounds. Importantly, treatment with MP compounds significantly extended the lifespan and improved the locomotor activity of a Drosophila model of the DM1 disease, and restored molecular defects characteristic of the disease in vivo. Conclusions: Our results revealed that MP compounds rescue multiple premature aging phenotypes described in DM1 models and decipher the benefits of this new family of compounds in the pre-clinical setting of DM1.
Peripheral Blood Leukocyte Subpopulation Changes in Reaction to an Acute Psychosocial Stressor as Compared to an Active Placebo-Stressor in Healthy Young Males: Mediating Effects of Major Stress-Reactive Endocrine Parameters
Authors: Walther Lisa-Marie , Gideon Angelina , Sauter Christine , Leist Marcel , Wirtz Petra H.
Published: November 2024

Psychosocial stress has been proposed to induce a redistribution of immune cells, but a comparison with an active placebo-psychosocial stress control condition is lacking so far. We investigated immune cell redistribution due to psychosocial stress compared to that resulting from an active placebo-psychosocial stress but otherwise identical control condition. Moreover, we tested for mediating effects of endocrine parameters and blood volume changes. The final study sample comprised 64 healthy young men who underwent either a psychosocial stress condition (Trier Social Stress Test; TSST; n = 38) or an active placebo-psychosocial stress control condition (PlacTSST; n = 26). Immune cell counts and hemoglobin, epinephrine, norepinephrine, ACTH, renin, and aldosterone levels, as well as those of saliva cortisol, were determined before and up to 30 min after the TSST/PlacTSST. The TSST induced greater increases in total leukocyte, monocyte, and lymphocyte levels as compared to the PlacTSST (p’s ≤ 0.001), but in not granulocyte counts. Neutrophil granulocyte counts increased in reaction to both the TSST and PlacTSST (p’s ≤ 0.001), while eosinophil and basophil granulocyte counts did not. The psychosocial stress-induced increases in immune cell counts from baseline to peak (i.e., +1 min after TSST cessation) were independently mediated by parallel increases in epinephrine (ab’s ≤ −0.43; 95% CIs [LLs ≤ −0.66; ULs ≤ −0.09]). Subsequent decreases in immune cell counts from +1 min to +10 min after psychosocial stress cessation were mediated by parallel epinephrine, renin, and blood volume decreases (ab’s ≥ 0.17; 95% CIs [LLs ≥ 0.02; ULs ≥ 0.35]). Our findings indicate that psychosocial stress specifically induces immune cell count increases in most leukocyte subpopulations that are not secondary to the physical or cognitive demands of the stress task. Increases in the number of circulating neutrophil granulocytes, however, are not psychosocial stress-specific and even occur in situations with a low probability of threat or harm. Our findings point to a major role of epinephrine in mediating stress-induced immune cell count increases and of epinephrine, renin, and blood volume changes in mediating subsequent immune cell count decreases from +1 min to +10 min after psychosocial stress cessation.
Intranasal Treatment with Cannabinoid 2 Receptor Agonist HU-308 Ameliorates Cold Sensitivity in Mice with Traumatic Trigeminal Neuropathic Pain
Authors: Ma Simeng , Nakamura Yoki , Uemoto Suzuna , Yamamoto Kenta , Hisaoka-Nakashima Kazue , Morioka Norimitsu
Published: November 2024

Post-traumatic trigeminal neuropathy (PTTN) is a sensory abnormality caused by injury to the trigeminal nerve during orofacial surgery. However, existing analgesics are ineffective against PTTN. Abnormal microglial activation in the caudal part of the spinal trigeminal nucleus caudal part (Sp5C), where the central trigeminal nerve terminals reside, plays an important role in PTTN pathogenesis. Therefore, regulating microglial activity in Sp5C appears to be an important approach to controlling pain in PTTN. Cannabinoid receptor 2 (CB2) is expressed in immune cells including microglia, and its activation has anti-inflammatory effects. The current study demonstrates that the repeated intranasal administration of CB2 agonist HU-308 ameliorates the infraorbital nerve cut (IONC)-induced hyperresponsiveness to acetone (cutaneous cooling). The therapeutic efficacy of oral HU-308 was found to be less pronounced in alleviating cold hypersensitivity in IONC mice compared to intranasal administration, indicating the potential advantages of the intranasal route. Furthermore, repeated intranasal administration of HU-308 suppressed the activation of Sp5C microglia in IONC mice. Additionally, pretreatment with the CB2 antagonist, SR 144528, significantly blocked the anti-nociceptive effect of repeated intranasal administration of HU-308 on cold hypersensitization in IONC mice. These data suggest that the continuous stimulation of CB2 ameliorates PTTN-induced pain via the inhibition of microglial activation. Thus, CB2 agonists are potential candidates for novel therapeutic agents against PTTN.
Recent Advances in Metal Oxide Semiconductor Heterojunctions for the Detection of Volatile Organic Compounds
Authors: Zhang Shengming , Zhang Heng , Yao Haiyu , Wang Peijie , Zhu Min , Shi Xuerong , Xu Shusheng
Published: November 2024

The efficient detection of volatile organic compounds (VOCs) is critically important in the domains of environmental protection, healthcare, and industrial safety. The development of metal oxide semiconductor (MOS) heterojunction gas-sensing materials is considered one of the most effective strategies to enhance sensor performance. This review summarizes and discusses the types of heterojunctions and their working principles, enhancement strategies, preparation methodologies, and applications in acetone and ethanol detection. To address the constraints pertaining to low sensitivity, sluggish response/recovery times, and elevated operating temperatures that are inherent in VOC sensors, several improvement methods are proposed, including doping with metals like Ag and Pd, incorporating additives such as MXene and polyoxometalates, optimizing morphologies through a fine design, and self-doping via oxygen vacancies. Furthermore, this work provides insights into the challenges faced by MOSs heterojunction-based gas sensors and outlines future research directions in this field. This review will contribute to foundational theories to overcome existing bottlenecks in MOS heterojunction technology while promoting its large-scale application in disease screening or agricultural food quality assessments.
Nurturing Sustainability in Toddlerhood: Investigating Preschool Teachers’ Views and Daily Practices in a Swedish Preschool
Authors: Kahriman-Pamuk Deniz , Pramling Samuelsson Ingrid
Published: November 2024

Background/Objectives: While studies suggest that young children can learn and think about sustainability, most research has focused on children aged three to five, leaving a significant gap in understanding how to engage toddlers (one to three years of age) in early-childhood education in sustainability (ECEfS). This study aims to address this gap, a crucial and often overlooked area, by investigating preschool teachers’ views of ECEfS and their daily practices for nurturing sustainability in a toddler group in a Swedish preschool. Methods: We employed a case study approach, incorporating observations, interviews, and document analysis for data collection. Qualitative techniques were used for data analysis. The research was conducted with a strong commitment to ethical considerations, including obtaining participants’ consent, ensuring confidentiality and privacy, informing them of their right to withdraw, and maintaining anonymity. Results: The findings demonstrate that the teachers possessed a solid understanding of education for sustainability and were capable of effectively implementing sustainability-related daily practices in toddler groups. By creating suitable learning environments and integrating sustainability issues into daily classroom activities, they enhanced the children’s overall learning experiences. Conclusions: This study’s findings underscore the pivotal role of educators in shaping the mindsets and behaviors of future generations, thereby supporting the long-term goals of sustainable development. By nurturing toddlers’ innate curiosity and harnessing their brains’ plasticity, educators can effectively engage toddlers in ECEfS and promote sustainable development from an early age. This study’s implications highlight the need to prioritize ECEfS during toddlerhood to realize the full potential of this critical investment in the future of our planet.
Comprehensive Transcriptomic and Physiological Insights into the Response of Root Growth Dynamics During the Germination of Diverse Sesame Varieties to Heat Stress
Authors: Su Xiaoyu , Li Chunming , Yu Yongliang , Li Lei , Wang Lina , Lu Dandan , Zhao Yulong , Sun Yao , Tan Zhengwei , Liang Huizhen
Published: November 2024

Heat stress constitutes a serious threat to sesame (Sesamum indicum L.). Root development during seed germination plays an essential role in plant growth and development. Nevertheless, the regulatory mechanisms underlying heat stress remain poorly understood. In this study, two sesame varieties differing in leaf heat tolerance (Zheng Taizhi 3 (heat-tolerant) and SP19 (heat-sensitive)) have been employed to investigate the impact of heat stress on root growth during germination. The results showed that heat stress significantly reduced the radicle length by 35.71% and 67.02% in Zheng Taizhi 3 and SP19, respectively, while germination rates remained unchanged. In addition, heat stress induced oxidative stress, as evidenced by increased reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and reduced indole-3-acetic acid (IAA) content, accompanied by enhanced antioxidant enzyme activities, including those of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the abscisic acid (ABA) content significantly increased in both varieties. However, the oxidation resistance in the roots of Zheng Taizhi 3 was enhanced compared to that of SP19 under heat stress, while IAA production was maintained and ABA content was reduced. A comparative transcriptome analysis identified 6164 and 6933 differentially expressed genes (DEGs) in Zheng Taizhi 3 and SP19, respectively, with 4346 overlapping DEGs. These DEGs included those related to stress tolerance, such as heat-shock proteins (HSPs), the antioxidant defense system, hormone signal transduction, and the biosynthetic pathway of phenylpropanoid. These findings provide insights into the physiological and molecular mechanisms underlying the adaptation of sesame to heat stress, which could inform breeding strategies for developing heat-tolerant sesame varieties.
Genome-Wide Development of InDel-SSRs and Association Analysis of Important Agronomic Traits of Taro (Colocasia esculenta) in China
Authors: Pan Rao , Zhu Qianglong , Jia Xinbi , Li Bicong , Li Zihao , Xiao Yao , Luo Sha , Wang Shenglin , Shan Nan , Sun Jingyu , Zhou Qinghong , Huang Yingjin
Published: November 2024

Taro (Colocasia esculenta (L.) Schott) is a tropical tuber crop whose underground corms are used as an important staple food. However, due to a lack of molecular markers, the genetic diversity, germplasm identification, and molecular breeding of taro are greatly limited. In this study, high-density InDel-SSR molecular markers covering the whole genome were developed based on the resequencing data of taro core germplasm. A total of 1,805,634 InDel-SSR loci were identified, and 219 highly polymorphic markers with an average polymorphism information content PIC value of 0.428 were screened. Furthermore, a genetic diversity analysis of 121 taro germplasm resources was conducted based on 219 markers, dividing the resources into three groups. In addition, an association analysis showed that, of the multiple InDel-SSR markers, g13.52 and g12.82 were significantly associated with leaf area and average cormel weight, respectively; the candidate genes CeARF17 (EVM0014444) and CeGA20ox (EVM0001890) were related to cormel expansion; and we excavated the candidate genes CeXXT2 (EVM0016820) and CeLOG1 (EVM0017064), which regulate leaf development. The InDel-SSRs and candidate genes identified in this study are expected to provide important support for genetically improving and breeding new varieties of taro.
Beaches’ Expulsion from Paradise: From a Natural to an Artificial Littoral in Tuscany (Italy)
Authors: Pranzini Enzo , Cinelli Irene , Anfuso Giorgio
Published: November 2024

This study investigated the shoreline evolution of the Tuscany coast (Italy) from 1878–1883 to 2019. The 205 km sandy coastline, divided into 821 sectors, each one 250 m long, was analyzed to understand how human activities have altered this once-pristine coast. Sub-period analyses highlighted the impacts, both positive and negative, of various shore-protection projects. Initially, regional beaches were undeveloped and accreting, except for a few river deltas where alternating phases of erosion and accretion were observed. Coastal erosion began at deltas’ areas due to the reduction in sediment inputs and, at other areas, enhanced by the development of human settlements and tourism activities. This triggered the construction of protection structures that shifted erosion processes downdrift, a process that induced the downdrift extension of the structures (according to the “domino” effect), determining the transformation of a completely natural and resilient environment into a largely rigid one. Beach nourishment projects, mostly using inland quarries, added about 1 million cubic meters of sediment from the 1980s to 2019. Currently, 57.8% of beaches are larger than in the 1880s, 9.4% did not change and 32.8% are narrower. Overall, the Tuscan coast gained 6.5 km2 of beach surface with an average shoreline advancement of 32 m. Recent trends (2005–2019) show that 37.7% of the coast is eroding, 21.1% is stable, and 41.2% is accreting, with a total surface area increase of about 200,000 m2. The beach surface area is still increasing despite the existing reduced sediment input due to the limited sediment loss resulting from the presence of morphological cells enclosed by very prominent headlands and the absence of submarine canyons that would otherwise direct sediments to the continental shelf.
Nonlinear Oxidation Behavior at Interfaces in Coated Steam Dual-Pipe with Initial Waviness and Cooling Temperature
Authors: Yuan Bo , Wang Ke , Guo Xiaofeng , Gao Junxiang , Chen Pengfei
Published: November 2024

A numerical simulation method is proposed to investigate the nonlinear growth of thermally grown oxide (TGO) on a novel coated steam dual-pipe system operating at 700 °C. Utilizing oxidation kinetics data from high-temperature water vapor experiments, the study examines interface stresses and morphology evolution, considering initial surface waviness and cooling temperature effects. The findings indicate that the parabolic law accurately describes the nonlinear growth of TGO during high-temperature water vapor oxidation, with the TGO growth oxidation rate constant being 4.5×10−4μm2/h. The growth rate of TGO thickness decreases with increasing oxidation duration. Stress concentrations are found to develop at TGO interfaces, particularly in regions with high curvature, and those with elevated wavy amplitudes. The primary factor influencing stress redistribution and morphology evolution is the wavy amplitude of the TGO. Additionally, variations in cooling temperature affect interface stresses along the axial direction of the pipe system during nonlinear oxidation, resulting in relatively minor changes in morphology.
Performance and Thermal Properties of 3D Printed CF-Reinforced PLA Monofilaments
Authors: Jin Pen , Pan Tuo , Li Yaxuan , Zhong Tianran , Jiang Jing , Pu Chengcui , Ma Chunyang
Published: November 2024

This study reports the fabrication of carbon fiber-reinforced poly(lactic acid) (CF-PLA) monofilaments using 3D printing technology. The effects of print head movement speed and retraction rate on the diameter of the CF-PLA monofilaments were investigated. The surface morphology and properties were analyzed using scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The CF-PLA monofilaments were also printed into boards with varying CF content, and the mechanical properties of these boards were assessed. The results showed that the optimal printing parameters were a nozzle diameter of ϕ0.4 mm, fiber feed rate (Vf) of 3 mm/s, print head movement speed (Vm) of 40 mm/s, and retraction speed (Vr) of 5 mm/s. At a CF-PLA monofilament diameter of ϕ135 µm, the tensile strength and Young’s modulus reached maximum values of 48.3 MPa and 2481.8 MPa, respectively. Numerous CF monofilaments (approximately 135 µm in diameter) were observed on the surface and within the CF-PLA boards, significantly enhancing their strength. When the CF content was 4 vol%, the thermal decomposition temperature of the CF-PLA monofilament was 312.53 °C. At 8 vol% CF content, the thermal decomposition temperature increased to 342.62 °C—approximately 30 °C higher than that of the monofilament with 4 vol% CF. The CF-PLA monofilaments fabricated at 8 vol% demonstrated high thermal stability.
High Fracture Risk of Femoral Bone Metastasis Treated with Palliative Radiotherapy in Recent Years
Authors: Makita Kenji , Hojo Hidehiro , Oyoshi Hidekazu , Fujisawa Takeshi , Nakamura Masaki , Uchida Gyo , Koike Yume , Zhou Yuzheng , Tomizawa Kento , Fukushi Keiko , Zenda Sadamoto
Published: November 2024

Bone-modifying agents (BMAs) have been widely used to reduce skeletal-related events, including pathological fractures. Herein, we aimed to clarify the incidence of pathological fractures caused by high-risk femoral bone metastases after palliative radiotherapy (RT) in the BMA era and evaluate the necessity of prophylactic surgical stabilization. We assessed 90 patients with high-risk femoral bone metastases, indicated by Mirels’ scores ≥ 8, without pathological fractures and surgical fixations, who received palliative RT at our institution between January 2009 and December 2018. Pathological fracture incidence was analyzed using the Kaplan–Meier method and was 22.8% and 31.0% at 2 and 6 months, respectively. Pathological fractures were caused by 17 of 65 lesions (26.2%) and 9 of 25 lesions (36.0%) in patients who received BMAs and those who did not, respectively (p = 0.44). Additionally, 17 of 42 lesions (40.5%) and 9 of 48 lesions (18.8%) with axial cortical involvement ≥30 and <30 mm, respectively, caused pathological fractures (p = 0.02). The incidence of pathological fractures was high among patients with high-risk femoral bone metastases treated with palliative RT, particularly those with axial cortical involvement ≥30 mm. Therefore, aggressive indications for prophylactic surgical stabilization are warranted for high-risk femoral metastases despite BMA administration.
New Insights About Distribution Areas of Telestes souffia and Telestes muticellus: Changes and Overlapping Zones for Community Interest Fish Species
Authors: Bertoli Marco , Manfrin Chiara , Giulianini Piero Giulio , Pallavicini Alberto , Pastorino Paolo , Pizzul Elisabetta
Published: November 2024

Fish geographical distribution has pivotal importance in management/conservation policies, especially for community interest species, requiring careful protection measures. However, distribution areas could be difficult to define if the taxonomy has only recently been resolved, and particular attention must be paid where co-generic species share their ranges. Our work reports new insights about the distribution of T. muticellus and T. souffia in Northeastern Italy, where their geographical ranges overlap, and these native species share a cross-border area. Fish samplings and meristic and genetical investigations were performed, and our results showed that T. muticellus seems to expand its range east due to human-induced translocations, while T. souffia occurs only in the cross-border hydrological networks between Italy and Slovenia. Telestes genetic characterization for the Tagliamento River Basin and Northeastern Italy lowland is reported, improving the genus distribution dataset in the Po Plain watershed, where T. muticellus is endemic. The main meristic feature to discriminate the species was the number of lateral line scales, explaining 44.5% of the dissimilarity among the analyzed populations. Findings about the distribution of the investigated populations highlight the critical need for targeted conservation strategies in biodiversity hotspots, where overlapping species distributions, such as T. muticellus and T. souffia, play a vital role in preserving regional biodiversity.
Different Selection Levels of Mitogenomes: New Insights into Species Differentiation of the Triops longicaudatus (LeConte, 1846) Complex (Branchiopoda: Notostraca)
Authors: Sun Xiaoyan , Kozai Takeshi
Published: November 2024

Lineages of the Triops longicaudatus (LeConte, 1846) complex, originally endemic to the Americas, have been able to successfully colonize extreme environments such as temporary aquatic systems through shifts in their reproductive modes. To gain insights into their stress adaptations and species differentiation, we explored the genetic diversity of populations of the T. longicaudatus complex and constructed their haplotype networks. Using maximum likelihood and Bayesian analyses, we analyzed the complete mitogenome sequences of seven Triops species to infer their phylogenetic relationships. To identify the possible role of mtDNA evolution in stress adaptation, the evolutionary rates and molecular signatures of natural selection for all 13 PCGs were investigated using multiple approaches of selection tests. The results showed that signals of relaxed purifying selection and positive selection were found in specific genes of complexes I, IV, and V, indicating that mitogenomes in the T. longicaudatus complex have undergone adaptive evolution. Different patterns of selection in the mitochondrial genes between the hermaphroditic and gonochoric branches imply that functional constraints have played a significant role in the evolution of T. longicaudatus complex mitogenomes, which was essential for survival in extreme environments.
Nobiletin Regulates Lysosome Function in Bovine Endometrial Epithelial Cells
Authors: Koshimizu Karen , Ozawa Ren , Kuribayashi Sohei , Taru Maho , Iwata Hisataka , Miura Ryotaro , Hamano Seizo , Shirasuna Koumei
Published: November 2024

The existence of repeat breeder cows (RBCs) causes low reproductive performance. The causes of RBCs include low-quality oocytes and embryos, hormonal dysregulation, and unsuitable uterine environments. To improve unsuitable uterine conditions for RBCs, we focused on nobiletin (NOB), a natural citrus flavone with various beneficial roles. The role of NOB in bovine endometrial epithelial cells (BEECs) was examined. An analysis of BEECs showed that gene expression and altered pathways differed between the control and NOB treatment, with NOB regulating the pathways of steroid biosynthesis, lysosomal function, and inflammatory responses. NOB treatment significantly increased the number and activation of endosomes and lysosomes in BEECs. Moreover, we performed phagocytosis assays using fluorescence-conjugated lipopolysaccharide (LPS) with lysosomes in NOB-treated BEECs, which resulted in an increase in the co-localization of phagocytosed LPS with lysosomes. NOB treatment stimulated the mRNA expression of various lysosomal hydrolases, including cathepsin B and cathepsin K, and suppressed the gene expression of cytokines in inflammation-associated pathways (rheumatoid arthritis, the IL-17 signaling pathway, etc.). NOB significantly suppressed the LPS-induced mRNA expression of the inflammatory cytokine IL-8 and its secretion in BEECs. In conclusion, NOB activates the endosome–lysosomal system via phagocytosis to eliminate the bacterial component LPS and suppress inflammatory responses to defense mechanisms in BEECs.
Active Surveillance in Early Thyroid Cancer: A Meta-Analysis
Authors: Liao Li-Jen , Ono Yukiko , Hung Shun-Fa , Chen Yong-Chen , Hsu Wan-Lun
Published: November 2024

Background/Objectives: There remain several challenges to the acceptance and standardization of active surveillance (AS) in patients with early thyroid cancer. The purpose of this study was to update the evidence of tumor progression outcomes in AS to support resolution of clinical concerns and to examine the effect of follow-up duration, period context such as diagnostic techniques, and tumor size at baseline on outcomes. Methods: PubMed, Web of Science, and Embase were used to search for original articles in English until January 2024. The main outcomes were the pooled proportion of patients who showed tumor growth ≥ 3 mm, metastasis to cervical lymph nodes, and conversion to delayed thyroid surgery. A single-arm meta-analysis was performed using a random-effects model. Results: Fourteen studies with 7291 patients were included in the analysis. Pooled results showed that 5.6% (95% CI: 4.2–7.4) of patients increased tumor diameter by more than 3 mm, 1.1% (95% CI: 0.9–1.4) developed cervical lymph node metastases by clinical diagnosis and 3.6% (95% CI: 3.1–4.2) by pathology, 12.7% (95% CI: 9.9–16.1) of patients converted to delayed surgery, with 31.6% (95% CI: 25.3–38.7) of those conversions being due to tumor progression. Subgroup analysis showed a small difference in the proportion of outcomes by baseline tumor size but no increase in the proportion of tumor progression or conversion to surgery due to other factors. Conclusions: This meta-analysis suggests long-term stability in the proportion of tumor progression in AS and less susceptibility to external influences.
Biomarkers of Intestinal Permeability Are Influenced by Diet in Patients with Ulcerative Colitis—An Exploratory Study
Authors: Haskey Natasha , Eisele Maximillian , Bruno Andreina , Reimer Raylene A. , Yousuf Munazza , Taylor Lorian M. , Panaccione Remo , Ghosh Subrata , Raman Maitreyi
Published: November 2024

Background and Objectives: The disruption of the intestinal epithelial barrier leads to increased intestinal permeability (IP), allowing endotoxins and pathogens to enter the bloodstream contributing to chronic inflammation. Western diets are associated with increased IP, while diets rich in polyphenols, fiber, and omega-3 fats are linked to decreased IP. The relationship between diet, disease activity, and IP in ulcerative colitis (UC) is poorly understood. We evaluated the effects of serum zonulin and lipopolysaccharide-binding protein (LBP) and their relationship to dietary factors in UC. Methods: A cross-sectional analysis was conducted on 37 UC participants who had baseline measures of dietary intake, disease activity and serum. Serum LBP and zonulin levels were measured by ELISA. Spearman’s rank correlations explored relationships between baseline IP, diet, and disease activity. Results: The median age was 35 years (29–47 years), 54% were male, and 76% were in clinical remission or had mild disease activity (partial Mayo score ≤ 4). LBP was significantly correlated (p < 0.05) with disease activity (partial Mayo score (r = 0.31), and positively correlated with total fat (r = 0.42) and refined grains (r = 0.35), but negatively correlated with fruit consumption (r = −0.50) and diet quality (r = −0.33). Zonulin was negatively correlated with protein (r = −0.39), niacin (r = −0.52) and vitamin B12 (r = −0.45) with a trend for significance (p = 0.06) with body mass index (r = 0.32). Conclusions: Baseline LBP levels were correlated with disease activity markers and dietary factors, suggesting that it could be a useful biomarker for assessing disease activity and diet quality in UC. Further trials are needed to confirm these findings.
Improving Outcomes of CT-Guided Malignant Lung Lesion Microwave Ablation by Tract Sealing Using Venous Blood Clot
Authors: Mačionis Aurimas , Maziliauskienė Gertrūda , Dubeikaitė Rūta , Vajauskas Donatas , Adukauskienė Dalia , Nedzelskienė Irena , Žemaitis Marius
Published: November 2024

Background: Complications, particularly pneumothorax, are common following lung interventions and occasionally necessitate further examinations, extend hospital stays, increase treatment costs, and result in long-term health impairment or even death. A few lung intervention tract sealants have been explored to reduce procedure-related complications. Objectives: The primary objective of this prospective non-randomized study was to assess the complication rates and risk factors for computed tomography-guided lung microwave ablation (MWA) with autologous blood clot as a tract sealant. Methods: Twenty-one patients underwent a total of 26 MWA sessions for lung malignancy followed by injection of the patient’s clotted venous blood into the ablation tract while retracting the coaxial needle. Ablation tract sealing was successful in all MWA sessions. Results: Pneumothorax was the only complication observed in five (19.2%) sessions, with one patient (3.8%) requiring chest tube insertion. The male sex was a statistically significant risk factor for pneumothorax (p = 0.042), and patients with lung emphysema had almost fivefold higher odds of developing pneumothorax (OR 4.8; 95% CI, 0.617–37.351; p = 0.281). Conclusions: This study concludes that pneumothorax is the primary complication following lung MWA, and the male sex is a risk factor. Ablation tract sealing with autologous venous blood is a straightforward and inexpensive technique that can reduce the incidence of procedure-related pneumothorax.
Cytomegalovirus Enterocolitis in a Patient Treated with Methylprednisolone for Amiodarone Hypersensitivity Pneumonitis
Authors: Purg Darinka , Hojnik Marko , Kravos Tramšek Nika Aleksandra
Published: November 2024

Cytomegalovirus (CMV) is a common cause of infection in immunocompromised individuals, such as patients with hematological malignancies or AIDS, but can also occur in patients with other acquired immunodeficiencies. In tissue-invasive diseases, CMV diagnosis requires CMV DNA in the plasma and the histological confirmation of CMV in a tissue or organ. Evidence of CMV colitis requires a characteristic endoscopic picture with ulcers with a well-defined, convex appearance and CMV viral inclusions in the form of an “owl’s eye” on mucosal sections stained with hematoxylin and eosin. CMV-specific immunohistochemistry is the gold standard for identifying CMV in tissue biopsies. It is important to consider a CMV infection in the diagnostic process, as it may delay the diagnosis and the treatment. We present the case of a 78-year-old patient with amiodarone interstitial lung disease who was treated with methylprednisolone. Two weeks after the start of his treatment, he was admitted to the hospital for acute gastroenterocolitis and Addisonian crisis. An examination had confirmed a tissue-invasive CMV disease. He was treated with valganciclovir for a total of six weeks. After the completion of treatment, the patient showed no clinical signs of CMV infection, and both laboratory and histological examinations revealed no residual CMV disease. Tissue-invasive CMV disease can occur in patients with acquired immunodeficiency, which may result from various causes, including glucocorticoid treatment.
The Impact of the SMOTE Method on Machine Learning and Ensemble Learning Performance Results in Addressing Class Imbalance in Data Used for Predicting Total Testosterone Deficiency in Type 2 Diabetes Patients
Authors: Kivrak Mehmet , Avci Ugur , Uzun Hakki , Ardic Cuneyt
Published: November 2024

Background and Objective: Diabetes Mellitus is a long-term, multifaceted metabolic condition that necessitates ongoing medical management. Hypogonadism is a syndrome that is a clinical and/or biochemical indicator of testosterone deficiency. Cross-sectional studies have reported that 20–80.4% of all men with Type 2 diabetes have hypogonadism, and Type 2 diabetes is related to low testosterone. This study presents an analysis of the use of ML and EL classifiers in predicting testosterone deficiency. In our study, we compared optimized traditional ML classifiers and three EL classifiers using grid search and stratified k-fold cross-validation. We used the SMOTE method for the class imbalance problem. Methods: This database contains 3397 patients for the assessment of testosterone deficiency. Among these patients, 1886 patients with Type 2 diabetes were included in the study. In the data preprocessing stage, firstly, outlier/excessive observation analyses were performed with LOF and missing value analyses were performed with random forest. The SMOTE is a method for generating synthetic samples of the minority class. Four basic classifiers, namely MLP, RF, ELM and LR, were used as first-level classifiers. Tree ensemble classifiers, namely ADA, XGBoost and SGB, were used as second-level classifiers. Results: After the SMOTE, while the diagnostic accuracy decreased in all base classifiers except ELM, sensitivity values increased in all classifiers. Similarly, while the specificity values decreased in all classifiers, F1 score increased. The RF classifier gave more successful results on the base-training dataset. The most successful ensemble classifier in the training dataset was the ADA classifier in the original data and in the SMOTE data. In terms of the testing data, XGBoost is the most suitable model for your intended use in evaluating model performance. XGBoost, which exhibits a balanced performance especially when the SMOTE is used, can be preferred to correct class imbalance. Conclusions: The SMOTE is used to correct the class imbalance in the original data. However, as seen in this study, when the SMOTE was applied, the diagnostic accuracy decreased in some models but the sensitivity increased significantly. This shows the positive effects of the SMOTE in terms of better predicting the minority class.
A Review of White Spot Lesions: Development and Treatment with Resin Infiltration
Authors: Prada Alexandra Maria , Potra Cicalău Georgiana Ioana , Ciavoi Gabriela
Published: November 2024

White spot lesions (WSLs) are demineralized lesions of the enamel that form in the presence of bacterial plaque, affecting the aesthetics by modifying the refractive index of the enamel, giving the characteristic “chalky” aspect. They have various causes, including fixed orthodontic treatments, improper hygiene, fluorosis and genetic factors. Background/Objectives: Considering the latest need for dental aesthetics and the popularization of fixed orthodontic treatments, the need to effectively treat WSLs has increased. The objective of this research is to review the development of WSLs and their treatment with resin infiltration. Methods: The PubMed, Web of Science, Scopus and Google Scholar databases were searched for relevant reviews and studies. Out of all, 56 were included in this research. Results: Prophylactic measures, such as fluorized toothpaste and varnishes, have limited results. Standard caries treatment is too invasive as it removes too much healthy enamel for obturation retentivity. The resin infiltration resin process does not require drilling or tooth structure loss, making it a painless and minimally invasive treatment. The resin used has a refractive index comparable to that of healthy enamel, consequently restoring aesthetics and ensuring the prevention of caries evolvement. The treatment involves five important steps: prophylaxis, acid demineralization, alcohol drying, resin infiltration and UV light curing. Depending on the clinical case, the demineralization and drying steps may need to be repeated. Conclusions: Infiltrations with resin are painless and well tolerated by patients. Out of all minimally invasive treatments, they have an immediate satisfactory outcome, with results stable for a minimum of 45 months.
Changes in Occlusal Contacts upon the Cementation of Zirconia Crowns with Different Cement Spacers
Authors: Wang Yujun , Millstein Philip , Lu Korina Yun-Fan , Lee Jason D. , Lee Sang J.
Published: November 2024

Background/Objectives: Occlusion plays a crucial role in the long-term success and functionality of dental restorations. The purpose of this study was to investigate the changes in occlusal contacts upon the cementation of zirconia crowns with different cement spacer settings in computer-aided design and computer-aided manufacturing (CAD-CAM) software (3Shape Dental System version 2.102.1.0). Methods: A master model of a prepared abutment for a crown on the right maxillary first molar was scanned, and 30 sets of sample casts and zirconia crowns were fabricated with varying cement spaces (70 μm and 120 μm). These casts were mounted in maximal intercuspation (MIP) on a semi-adjustable articulator. Pre-cementation adjustments were made to fit the crowns and maintain the existing occlusion. Occlusal records were taken before and after cementation using polyvinyl siloxane impression material. These records were analyzed using a DC light box and image analyzer to measure changes in contact area, intensity, and patterns. Paired sample t-tests were used to compare pre- and post-cementation occlusal contact areas of each sample (α = 0.05). Results: Significant differences in occlusal contact areas were found between pre- and post-cementation in both groups (p < 0.001). The mean post-cementation contact surface area for the 70 μm group was 6281 ± 3310 μm2, compared to 2339 ± 1206 μm2 before cementation. For the 120 μm group, the post-cementation area was 5545 ± 3491 μm2, compared to 2071 ± 909 μm2 before cementation. An increase in contact intensity was also observed after cementation. Conclusions: This study demonstrates that cementation increases occlusal contact surface area and intensity in both cement space groups.
Efficacy of a Herbal Toothpaste During Active Periodontal Treatment: A Clinical Study
Authors: Vajrabhaya La-ongthong , Benjasupattananan Supranee , Sappayatosok Kraisorn , Dechosilpa Vittawin , Korsuwannawong Suwanna , Sirikururat Papatpong
Published: November 2024

Backgound/Objectives: This study investigated the efficacy of a herbal toothpaste containing Aloe vera (test group) compared with a sodium bicarbonate toothpaste (active control group) and a standard toothpaste (benchmark group) on periodontitis treatment outcomes. Methods: Fifty-four periodontitis patients were randomly allocated into three groups. The patients received mechanical instrumentation and instruction on oral hygiene using a toothbrush with the toothpastes and dental floss. The patients were evaluated at baseline (T0), week 4 (T1), and week 12 (T2) after complete scaling and root planing. During the visits, the plaque score (PS), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) were assessed and analyzed. Results: The comparison groups had similar PS and BOP means at baseline. At T1 and T2, both scores were reduced; however, there was no significant difference in PS among the three groups. A significant reduction in BOP among the groups was observed (p < 0.01) at T1. The PDs in all groups were significantly reduced after treatment. The CAL reduction was greater in the test group compared with the benchmark and the active control group. Furthermore, there was no significant difference in the mean CAL among time points in the benchmark and the active control groups. Conclusions: The herbal toothpaste containing Aloe vera significantly decreased gingival inflammation, PD, and CAL over the standard and active control toothpaste in periodontitis patients during active periodontal treatment.