bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro assessment of chemical surface treatments on the shear bond strength of metal orthodontic brackets to CAD/CAM provisional materials
Authors: Alzaid Abdulaziz A. , Alanazi Khalid K. , Alharbi Maha N. , Alyahya Lulu A. , Alqarni Hatem , Alsaloum Mohammed , Alfallaj Hayam , Alotaibi Ghada S.
Published: December 2024

Introduction

The growing demand for orthodontic treatment in patients irrespective of age highlights the need for effective bonding of brackets to provisional crowns (PCs).

Aims and objectives

This study evaluates the shear bond strength (SBS) of orthodontic brackets to 3D-printed and milled PC materials, comparing the effects of hydrofluoric acid (HFA) and phosphoric acid (PA) etching.

Materials and methods

Forty cylinders were fabricated using a 3D printer with hybrid resin, and forty were milled from cross-linked polymethyl methacrylate (PMMA) resin. Stainless steel brackets were bonded with light-cured composite resin. Twenty specimens from each group were treated with 9.5% HFA, while the rest of the specimens received 37% PA. Post-bonding, specimens underwent thermocycling and were examined with SEM. SBS testing followed ISO/TS 11405-2015 guidelines. The failure patterns and bond interface were assessed by the Adhesive Remnant Index (ARI) and scanning electron microscopy (SEM). Data was analyzed using ANOVA, Tukey's test.

Results

In 3D-printed materials, HFA etching yielded a significantly higher bond strength (12.59 ± 2.64 MPa) than PA etching (7.77 ± 0.83 MPa). The bond strength was inferior in milled materials: HFA (5.98 ± 0.59 MPa) and PA (5.66 ± 0.65 MPa) with no significant difference between both surface treatments. When each material was evaluated separately, a significant difference in SBS was found for surface treatments in 3D-printed materials (p < 0.001) but not for milled materials (p = 0.916). ARI scores showed greater adhesive retention in 3D-printed specimens, particularly those treated with HFA. SEM revealed smoother surfaces in 3D-printed specimens compared to rougher surfaces in milled specimens.

Conclusion

HFA etching improves SBS in 3D-printed PC, while in milled materials, the choice of etching agent has minimal effect.
Follicular development and endometrial receptivity of different androgen phenotypes in women with polycystic ovary syndrome
Authors: Wen Xinling , Wang Li , Lv Shulan
Published: December 2024

Objective

Polycystic ovary syndrome (PCOS) is an important factor contributing to infertility in reproductive-aged women. Hyperandrogenism (HA) plays an important role in the pathogenesis of PCOS. This study was conducted to explore the follicular development and endometrial receptivity of different androgen phenotypes in reproductive-aged patients with PCOS.

Methods

A total of 268 PCOS patients with infertility were recruited and divided into two groups according to the different androgen phenotypes in this study: abnormal menstruation and hyperandrogenism (AM-HA group, n = 127) and abnormal menstruation and polycystic ovarian morphology (AM-PCOM group, n = 141). The follicular development, endometrial receptivity, pregnancy rate, and live birth rate during the natural menstrual cycle were compared between the two groups.

Results

The number of dominant follicles, number of ovulations, and normal ovulation rate in the AM-HA group were significantly lower compared with those in the AM-PCOM group (p < 0.05). The endometrial thickness (ET), endometrial volume (EV), vascularization index (VI), flow index (FI), and vascularization flow index (VFI) on days 14 to 24 of the menstrual cycle before ovulation were significantly lower in the AM-HA group than in the AM-PCOM group (p < 0.05). The endometrial VI, FI, and VFI, the integrin αvβ3, and VEGF concentrations in the uterine fluid during the implantation window were significantly lower in the AM-HA group compared with the AM-PCOM group (p < 0.05). However, no statistically significant differences were observed in the uterine artery blood flow parameters, ET and EV, between the two groups (p > 0.05). The biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate in the AM-HA group were significantly lower compared with those in the AM-PCOM group (p < 0.05).

Conclusion

PCOS patients with the AM-HA phenotype were vulnerable to ovulation disorders and impaired endometrial receptivity, which resulted in reduced pregnancy rate. Treatment with HA is likely to become an effective approach for improving endometrial receptivity and fecundity disorders in patients with PCOS.
Genotype-negative multiple endocrine neoplasia type 1 with prolactinoma, hyperparathyroidism, and subclinical Cushing’s syndrome accompanied by hyperglycemia: a case report
Authors: Kubo Haremaru , Wada Ryota , Sekikawa Naohiro , Nomura Yasuhisa , Yamada Mutsuo , Inoue Minoru , Hattori Naoki , Yamazaki Yuto , Sugimoto Kazuhiro
Published: December 2024

Background

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder, accompanied by multiple endocrine neoplasms of the parathyroid, pancreas, pituitary, and other neoplasms in the adrenal glands. However, in some cases, patients clinically diagnosed with MEN1 may be genotype-negative.

Case presentation

A 56-year-old female was diagnosed with MEN1 based on a macroprolactinoma (19 mm in diameter), primary hyperparathyroidism, and a cortisol-producing adrenal adenoma, without a family history. At first appearance, she had a hemoglobin A1c of 12.0% and a fasting plasma glucose level of 16.3 mmol/L (294 mg/dL). She complained of headaches and had a history of prolactinoma at 28 years of age, with concomitant elevated prolactin 1102.0 μg/L (ng/mL). Insulin therapy was initiated for glucose management following the administration of an oral hypoglycemic agent. Additionally, cabergoline was initiated for due to the prolactinoma, resulting in a normalized prolactin level. Thereafter, medication for diabetes could be withdrawn. Subsequently, surgery was performed for primary hyperparathyroidism and the cortisol-producing adrenal adenoma, which was consistent with the preoperative diagnosis. Additionally, a thyroid tumor resected with primary hyperparathyroidism revealed to be invasive papillary thyroid carcinoma (PTC). Target gene testing revealed a negative genotype for MEN1 gene, with only one common polymorphism that was non-pathogenic.

Conclusions

Genotype-negative MEN1 typically has a favorable clinical course without a third primary MEN1 manifestation. However, the present case had a symptomatic macroprolactinoma with an apparent elevated glucose level and three manifestations of tumors (pituitary, parathyroid, and adrenal) with invasive PTC, and a delayed diagnosis could have caused crucial deterioration. Clinicians should pay attention to the clinical features of MEN1 including glucose intolerance. In such cases, the treatment of endocrine disorders can lead to the normalization of the glucose level.
Low-carbon scheduling strategy for electric vehicles considering carbon emission flow and dynamic electricity prices
Authors: Hu HouPeng , Qian Bin , Xiao YanHong , Tang JianLin , Ou Jiaxiang , Lin XiaoMing , He Peilin , Zhang Fan
Published: December 2024

As the global environmental pollution problem intensifies, the carbon reduction transformation of the power system is urgent. In order to solve the problem of unclear carbon flow and distribution in the operation of the power grid, as well as the mismatch between static time-of-use electricity prices and peak and valley periods in the scheduling of electric vehicle charging loads, a multiperiod dynamic electricity price guidance strategy based on carbon emission flow theory is proposed. First, based on the accurate power flow results of the power system, a complex power distribution matrix of the power system is constructed to obtain the distribution of the power generated by the generator units in each node of the network. Then, the Monte Carlo random sampling method is used to simulate the load situation of electric vehicles in a disordered charging state. A mathematical model based on the carbon trading model is established to minimize the load difference at the grid end and maximize the cost of charging on the user side. Finally, the proposed ordered charging method with a multiperiod dynamic electricity pricing strategy is compared with unordered charging, and considering the participation of electric vehicles in carbon trading, this strategy effectively reduces the peak valley difference between the power grid and user charging costs.
Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
Authors: Brant Eleanor J. , May David , Eid Ayman , Altpeter Fredy
Published: December 2024

Sugarcane (Saccharum spp.) is an important biofuel feedstock and a leading source of global table sugar. Saccharum hybrid cultivars are highly polyploid (2n = 100–130), containing large numbers of functionally redundant hom(e)ologs in their genomes. Genome editing with sequence-specific nucleases holds tremendous promise for sugarcane breeding. However, identification of plants with the desired level of co-editing within a pool of primary transformants can be difficult. While DNA sequencing provides direct evidence of targeted mutagenesis, it is cost-prohibitive as a primary screening method in sugarcane and most other methods of identifying mutant lines have not been optimized for use in highly polyploid species. In this study, non-sequencing methods of mutant screening, including capillary electrophoresis (CE), Cas9 RNP assay, and high-resolution melt analysis (HRMA), were compared to assess their potential for CRISPR/Cas9-mediated mutant screening in sugarcane. These assays were used to analyze sugarcane lines containing mutations at one or more of six sgRNA target sites. All three methods distinguished edited lines from wild type, with co-mutation frequencies ranging from 2% to 100%. Cas9 RNP assays were able to identify mutant sugarcane lines with as low as 3.2% co-mutation frequency, and samples could be scored based on undigested band intensity. CE was highlighted as the most comprehensive assay, delivering precise information on both mutagenesis frequency and indel size to a 1 bp resolution across all six targets. This represents an economical and comprehensive alternative to sequencing-based genotyping methods which could be applied in other polyploid species.
CD73: agent development potential and its application in diabetes and atherosclerosis
Authors: Liu Dan , Zhao Jingjing , Li Ling , Wang Jie , Wang Chao , Wu Yudong , Huang Yucun , Xing Dongming , Chen Wujun
Published: December 2024

CD73, an important metabolic and immune escape-promoting gene, catalyzes the hydrolysis of adenosine monophosphate (AMP) to adenosine (ADO). AMP has anti-inflammatory and vascular relaxant properties, while ADO has a strong immunosuppressive effect, suggesting that CD73 has pro-inflammatory and immune escape effects. However, CD73 also decreased proinflammatory reaction, suggesting that CD73 has a positive side to the body. Indeed, CD73 plays a protective role in diabetes, while with age, CD73 changes from anti-atherosclerosis to pro-atherosclerosis. The upregulation of CD73 with agents, including AGT-5, Aire-overexpressing DCs, Aspirin, BAFFR-Fc, CD4+ peptide, ICAs, IL-2 therapies, SAgAs, sCD73, stem cells, RAD51 inhibitor, TLR9 inhibitor, and VD, decreased diabetes and atherosclerosis development. However, the downregulation of CD73 with agents, including benzothiadiazine derivatives and CD73 siRNA, reduced atherosclerosis. Notably, many CD73 agents were investigated in clinical trials. However, no agents were used to treat diabetes and atherosclerosis. Most agents were CD73 inhibitors. Only FP-1201, a CD73 agonist, was investigated in clinical trials but its further development was discontinued. In addition, many lncRNAs, circRNAs, and genes are located at the same chromosomal location as CD73. In particular, circNT5E promoted CD73 expression. circNT5E may be a promising target for agent development. This mini-review focuses on the current state of knowledge of CD73 in diabetes, atherosclerosis, and its potential role in agent development.
Impact of two high resolution altimetry mission concepts on ocean forecasting
Authors: Benkiran Mounir , Le Traon Pierre-Yves , Rémy Elisabeth , Drillet Yann
Published: December 2024

Observing System Simulation Experiments (OSSEs) with the Mercator Ocean/Copernicus Marine global 1/12° data assimilation system have been carried out to compare and quantify the expected performance of two high resolution altimetry mission concepts envisioned for the long-term evolution (post-2032) of the Copernicus Sentinel-3 topography mission. The two mission concepts are a constellation of two wide-swath altimeters and a constellation of 12 nadir altimeters. These two configurations greatly improve ocean forecasting and monitoring capabilities. Compared to a constellation of three nadir altimeters (the present configuration), analysis and forecast errors are reduced by a factor of 2. Our results also show that a constellation of two wide-swath altimeters has better performance than a constellation of 12 nadirs. Compared to a constellation of 12 nadirs, the error of the Sea Surface Height (SSH) forecast of a two wide swath constellation is reduced by 14% overall. Improvements are also observed when analyzing surface currents and Lagrangian diagnostics. A constellation of two wide-swath altimeters thus seems to be a very promising concept for the long-term evolution of the Sentinel-3 topography mission.
Improved genetic algorithm based on Shapley value for a virtual machine scheduling model in cloud computing
Authors: Chen Lili , Niu Yuxia
Published: December 2024

Introduction

In cloud computing, a common idea to reduce operation costs and improve service quality is to study task scheduling algorithms.

Methods

To better allocate virtual machine resources, a virtual machine resource scheduling algorithm, Shapley value method–genetic algorithm (SVM-GA) is proposed. This algorithm uses the SVM to obtain the contribution values of each component of the virtual machine, refine the topological network, and achieve the optimal solution of scheduling by the genetic algorithm.

Results and Discussion

CloudSim simulation results indicate that SVM-GA has the lowest total task completion time when compared with existing intelligent optimization algorithms (such as the max–min algorithm, logistic regression algorithm, and differential evolution algorithm) with the same number of tasks, and the total task time is 25, 55, 81, 112, 145, and 175 s for 200, 400, 600, 800, 1,000, and 1,200 tasks, respectively. As the number of evolutionary generations increases, the ability of SVM-GA to reach the optimal solution of the model increases. In the simulated light load case, the SVM-GA migration time and Q10 migration count optimal solutions are slightly inferior to those of the logistic regression algorithm (3.02 s > 2.38 s; 1,129 times >999 times), but the migration energy consumption and service level agreement violation rate optimal solutions are superior. The SVM-GAA’s performance in the heavy load case is similar to that in the light load case. The experiments show the feasibility of the algorithm proposed in the study.
SUMO2 rescues neuronal and glial cells from the toxicity of P301L Tau mutant
Authors: Orsini Franca , Pascente Rosaria , Martucci Annacarla , Palacino Sara , Fraser Paul , Arancio Ottavio , Fioriti Luana
Published: December 2024

Introduction

Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer’s disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome. Previous studies suggest that SUMOylation, a posttranslational modification consisting of conjugation of SUMO (Small ubiquitin-like modifier) to target proteins, was decreased in the hippocampus of AD patients and in animal model of AD compared with controls. This decrease in SUMOylation was correlated with increased Tau pathology and cognitive decline. Other studies have reported increased levels of SUMO in AD brains. The goal of our study was to evaluate whether SUMO conjugation modifies the neurodegenerative disease pathology associated with the aggregation-prone mutant TauP301L, in neurons and in glial cells.

Methods

We used viral approaches to express mutant TauP301L and SUMO2 in the hippocampus of wild-type mice. We assessed Tau distribution by immunostaining and Tau aggregation by insolubility assays followed by western blotting. We assessed neuronal toxicity and performed cell count and shape descriptor analyses on astrocytes and microglial cells.

Results

We found that mutant TauP301L, when expressed exclusively in neurons, is toxic not only to neurons but also to glial cells, and that SUMO2 counteracts TauP301L toxicity in neurons as well as in glia.

Discussion

Our results uncover an endogenous neuroprotective mechanism, whereby SUMO2 conjugation reduces Tau neuropathology and protects against toxic effects of Tau in glial cells.
Efficient gaze stabilization during video Active Gaze Shift Test (vAGST) in bilateral vestibulopathy
Authors: Van Nechel Christian , Duquesne Ulla , Toupet Michel , Hautefort Charlotte
Published: December 2024

Introduction

While most head movements in daily life are active, most tools used to assess vestibular deficits rely on passive head movements. A single gain value is not sufficient to quantify gaze stabilization efficiency during active movements in vestibular deficit patients. Moreover, during active gaze shifts, anticipatory mechanisms come into play. Our aim was to explore the extent to which previously described compensatory mechanisms are employed in patients with bilateral vestibular loss.

Methods

We used a Video Head Impulse Test (vHIT) to simultaneously record eye and head movements during a video Active Gaze Shift Test (vAGST). Thirty-eight patients with bilateral vestibular deficits and 61 control subjects were tested.

Results

Despite impaired performance on caloric tests and vHIT, most patients exhibited normal gaze stabilization (gain = 0.92 ± 0.1) during active gaze shifts up to a head speed (‘stall speed’) of approximately 140 ± 60°/sec, compared to 280 ± 65°/sec in controls. Our results indicate that BVD patients spontaneously adopt a head speed during active horizontal movements that significantly improves gaze stabilization compared to passive movements. The stall speed correlates with the spontaneous head speed typically adopted by BVD patients and controls in daily activities. As a consequence of the reduction in head speed and corrective saccades, patients also showed an increased delay in gaze stabilization (413 ± 105 ms in BVD patients versus 358 ± 82 ms in controls) at the end of the gaze shift, which might become disabling for certain tasks.

Discussion

Recent model suggests that compensatory eye movements, which stabilize gaze during the counter rotation phase of active gaze shifts, are predictive in nature. vAGST is not designed to provide an etiological diagnosis but rather a functional assessment of the patient’s ability to generate predictive eye movements that compensate for vestibular sensor deficits. Understanding the quality of the patient’s sensory predictions can also shed light on vestibular symptoms, even in cases where no vestibular sensor deficit is detected. This suggest that quality of life and oscillopsia questionnaires should distinguish between predictable and unpredictable movements.
Excitatory neuron-prone prion propagation and excitatory neuronal loss in prion-infected mice
Authors: Erdenebat Temuulen , Komatsu Yusuke , Uwamori Nozomi , Tanaka Misaki , Hoshika Takashi , Yamasaki Takeshi , Shimakura Ayano , Suzuki Akio , Sato Toyotaka , Horiuchi Motohiro
Published: December 2024

The accumulation of a disease-specific isoform of prion protein (PrPSc) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrPSc and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection. However, the underlying mechanism is largely unknown. In this study, we provided evidence that the prion 22L strain propagates more efficiently in excitatory neurons than inhibitory neurons and that excitatory neurons in the thalamus are vulnerable to prion infection. PrPSc accumulation was less intense in the striatum, where GABAergic inhibitory neurons predominate, compared to the cerebral cortex and thalamus, where glutamatergic excitatory neurons are predominant, in mice intracerebrally or intraperitoneally inoculated with the 22L strain. PrPSc stains were observed along the needle track after stereotaxic injection into the striatum, whereas they were also observed away from the needle track in the thalamus. Consistent with inefficient prion propagation in the striatum, the 22L prion propagated more efficiently in glutamatergic neurons than GABAergic neurons in primary neuronal cultures. RNAscope in situ hybridization revealed a decrease in Vglut1- and Vglut2-expressing neurons in the ventral posterolateral nuclei of the thalamus in 22L strain-infected mice, whereas no decrease in Vgat-expressing neurons was observed in the adjacent reticular nucleus, mainly composed of Vgat-expressing interneurons. The excitatory neuron-prone prion propagation and excitatory neuronal loss in 22L strain-infected mice shed light on the neuropathological mechanism of prion diseases.
Global, regional, and national trends in gastric cancer burden: 1990-2021 and projections to 2040
Authors: Zhang Tao , Zhang Yiqun , Leng Xiaofei
Published: December 2024

Background

Gastric cancer (GC) is a common malignancy of the digestive system, with significant geographical variation in its disease burden.

Methods

This study used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to analyze three key indicators: incidence, mortality, and disability-adjusted life years (DALYs). Initially, a detailed analysis of the GC burden was conducted from global, regional, national, gender, and age perspectives. Subsequently, the percentage change and average annual percent change (AAPC) of GC were calculated to understand the trends in disease burden. Decomposition analysis and frontier analysis were then performed. Finally, the Bayesian age-period-cohort model was used to predict the trends in age-standardized rates (ASRs) of GC up to 2040.

Results

In 2021, there were 1.23 million (95% UI: 1.05-1.41 million) new cases of GC globally, with 0.95 million (95% UI: 0.82-1.10million) deaths and 22.79 million (95% UI: 19.58-26.12 million) DALYs. Compared to 1990, the global ASRs of GC has declined, but new cases and deaths have increased. For females, age-standardized incidence rate, age-standardized mortality rate, and age-standardized DALYs rate were 8.6, 7.1, and 165.6 per 100,000, with AAPCs of -2.1, -2.4, and -2.6. For males, they were 20.9, 16.0, and 371.2 per 100,000, with AAPCs of -1.6, -2.1, and -2.3. ASRs fluctuated with increasing Socio-demographic Index (SDI), being higher in middle and high-middle SDI regions. Decomposition analysis indicated negative effects from epidemiological trends on GC burden, while population growth and aging had positive effects. Frontier analysis showed that middle and high-middle SDI regions had more potential for reducing ASRs. Predictions indicate a continued decline in ASRs for both genders by 2040.

Conclusion

Despite progress in controlling GC, the number of new cases and deaths globally is rising due to population growth and aging. This highlights the need for effective prevention and control strategies.
Twenty years of anastomotic stenosis combined with tracheocolonic fistula after colon replacement esophagectomy: a case report
Authors: Li Xiaofang , Zou Liutao , Shi Lifeng , Zheng Xueting , Xu Cuifang , Guo Jichao
Published: December 2024

Esophageal stricture is the most common and disabling complication of esophageal injury caused by ingestion of corrosive substances. In our case, the patient developed esophageal stenosis due to ingestion of strong alkaline substances and underwent colon replacement surgery after repeated failed dilation treatments. After surgery, anastomotic stenosis and tracheocolonic fistula occurred successively, and the entire diagnosis and treatment cycle of this disease lasted for more than 20 years. Based on experience and the actual situation of the patient, we conclude that esophageal stents should be the primary treatment option, while tracheal stents should be carefully selected, and secondary surgery is not recommended.
Efficacy and safety of immune checkpoint inhibitors rechallenge in advanced solid tumors: a systematic review and meta-analysis
Authors: Cao Jiahui , Ding Xinyao , Ji Jianan , Zhang Lin , Luo Chengyan
Published: December 2024

Introduction

The efficacy and safety of re-administration of immune checkpoint inhibitors (ICIs) in advanced solid tumors lacks consensus and is of great concern to clinicians. This study aimed to investigate the efficacy and adverse effects of ICIs rechallenges in advanced solid tumors.

Methods

We systematically searched the databases of PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI), and screened the relevant literature according to the inclusion and exclusion criteria. Meanwhile, we conducted a meta-analysis of objective response rates (ORR), disease control rates (DCR), and immune-related adverse events (irAEs) for reuse of ICIs using Freeman-Tukey double arcsine transformation method.

Results

Sixty eligible studies were included in the meta-analysis, and the results revealed that those who discontinued ICIs therapy and reused ICIs had an ORR of 21.6% [95% confidence interval (CI): 17.6, 25.7] and a DCR of 55.8% (95% CI: 50.0, 61.5). The overall incidence for grade ≥ 3 irAEs was 16.7% (95% CI: 11.8, 22.2). In the subgroup analysis, patients with renal cell carcinoma presented superior efficacy with an ORR of 30.9%, which was higher than that of melanoma (24.3%) and non-small cell lung cancer (NSCLC) (10.1%). Patients who have been treated with single-agent ICIs, re-treatment with a combination of ICIs directing different targets presents better outcomes, with ORR of 22.5% and DCR of 38%, respectively, compared with those patients who continue to use a single agent.

Conclusion

Patients with advanced solid tumors who have relapsed or progressed after prior treatment with ICIs may benefit from ICIs rechallenge, with a comparable incidence of grade ≥ 3 irAEs to those previously treated with ICIs.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023407409.
Prognostic role of bone erosion in orbital RMS: a report from the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG)
Authors: Di Carlo Daniela , Fichera Giulia , Minard-Colin Veronique , Coppadoro Beatrice , Orbach Daniel , Cameron Alison , Albiac Ramos Monica , Ben Arush Myriam , Merks Johannes H. M. , Bisogno Gianni
Published: December 2024

Background

Orbital rhabdomyosarcoma (RMS) is often limited to the orbital cavity and has a favorable prognosis. In some cases, the tumor can erode the orbital bone and behave as a parameningeal RMS (PM-RMS); thus, it is treated more intensively. However, the current protocols do not provide any guidance on how to consider different grades of bone erosion (BE) that can vary widely, hampering a uniform classification and the subsequent treatment assignment. With the aim of clarifying the role of BE as a risk factor, we analyzed patients with orbital RMS included in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol.

Methods

We retrospectively analyzed the radiological reports of 199 patients with orbital RMS (PM or not) and defined three grades of BE: minimal (thinning of the bone), moderate (focal bone lysis), and extensive (complete cortical destruction).

Results

BE was present in 55 of the 199 (27.6%) patients, which was classified as minimal in 27, moderate in 7, and extensive in 21. Tumors with extensive BE were more frequently large (>5 cm, p = 0.0008) and invasive (T2, p = 0.001). With a median follow-up of 70.4 months (range = 7.1–167.7), a total of 183 patients are alive, with 5-year event-free survival (EFS) and overall survival (OS) rates of 76% (95%CI = 69.2–81.3) and 92% (95%CI = 86.7–94.8), respectively. Patients without any BE had better OS (95% vs. 81%, p = 0.001), but not EFS. Patients with no/minimal/moderate BE had better EFS and OS compared with patients with extensive BE [EFS of 78.1 (95%CI = 71.1–83.5) vs. 57.1 (95%CI = 33.8–74.9), p = 0.0114, respectively, and OS of 94.0 (95%CI = 89.2–96.8) vs. 71.1 (95%CI = 46.6–85.9), p < 0.0001, respectively]. Events and metastatic relapses (in all cases CNS/meningeal) were more frequent in patients with extensive BE.

Conclusions

Only those patients with orbital RMS and extensive BE should be considered as PM and should be treated accordingly.
Chronic myelogenous leukemia coexpressing V-e16a2, V-e13a2, e13a2, and e14a2 BCR::ABL1 fusion transcripts: a case report and review of the literature
Authors: Xu Yang , Fan Yuying , Liu Sijin , Chang Jianmei , Guo Caifeng , Chen Lanhui , Guo Wenzheng , Dang Jinwen , Wang Hongwei , Tan Yanhong
Published: December 2024

The coexistence of three or more transcripts in one patient with chronic myeloid leukemia (CML) is rarely reported. Thus, the disease progression and drug response are still unknown. This case report aimed to explore the drug response of CML with variant transcripts and to enrich the clinical treatment of rare types of CML. A 66-year-old Chinese female patient was diagnosed with chronic myeloid leukemia-chronic phase (CML-CP) expressing four BCR::ABL1 transcripts, including variant e16a2(V-e16a2), variant e13a2(V-e13a2), classical e13a2, and e14a2 transcripts. The patient was treated with flumatinib, a tyrosine kinase inhibitor (TKI).The variant transcripts reported exhibited a favorable response to TKI, and attention should be directed toward monitoring variant transcripts.
Revealing the secrets of Blue Zones
Authors: Ulusu N. Nuray
Published: December 2024

Aging is influenced by cellular senescence mechanisms that are associated with oxidative stress. Oxidative stress is the imbalance between antioxidants and free radicals. This imbalance affects enzyme activities and causes mitochondrial dysfunction. It also slows down cellular energy production and disrupts cellular homeostasis. Additionally, oxidative stress stimulates inflammation, increases the number of point mutations, and alters intercellular communication. It can lead to epigenetic alterations, genomic instability, telomere attrition, and loss of proteostasis. Ultimately, these factors contribute to aging and the development of chronic diseases. Glucose-6-phosphate dehydrogenase (G6PD) is an antioxidant enzyme that protects cells from oxidative and nitrosative damage. It helps restore redox balance, preserve macromolecule function, and rescue cells from cellular senescence, autophagy, and stress-induced apoptosis. G6PD is considered an anti-senescence enzyme. The World Health Organization classifies G6PD variants into five groups based on the enzyme’s residual activity. The first four classes are categorized according to the degree of G6PD deficiency, while the fifth class includes variants with enzyme activities greater than normal. Increased G6PD activity does not exhibit clinical manifestations. Consequently, the full spectrum of mutations and the prevalence of increased G6PD activity in the population remain unknown. The world’s oldest and healthiest people live in Blue Zones. These comprise isolated populations, and there may be a geographic prevalence of high-activity G6PD variants that protect against oxidative stress-induced senescence. To uncover the secret of centenarians’ longevity, additional research is needed to determine whether the hidden factor is the increased activity of the G6PD enzyme.
Pharmacology and mechanisms of apigenin in preventing osteoporosis
Authors: Lin Sun , Yincang Wang , Jiazhe Du , Xilin Xu , Zhang Xiaofeng
Published: December 2024

Osteoporosis (OP) stands as the most prevalent systemic skeletal condition associated with aging. The current clinical management of OP predominantly depends on anti-resorptive and anabolic agents. Nevertheless, prolonged use of some of these medications has been observed to reduce efficacy and elevate adverse effects. Given the necessity for sustained or even lifelong treatment of OP, the identification of drugs that are not only effective but also safe and cost-efficient is of utmost significance. As disease treatment paradigms continue to evolve and recent advancements in OP research come to light, certain plant-derived compounds have emerged, presenting notable benefits in the management of OP. This review primarily explores the pharmacological properties of apigenin and elucidates its therapeutic mechanisms in the context of OP. The insights provided herein aspire to offer a foundation for the judicious use of apigenin in forthcoming research, particularly within the scope of OP.
The advent of chimeric antigen receptor T Cell therapy in recalibrating immune balance for rheumatic autoimmune disease treatment
Authors: Guo Qianyu , Li Jie , Wang Juanjuan , Li Linxin , Wei Jia , Zhang Liyun
Published: December 2024

CAR-T cell therapy, a cutting-edge cellular immunotherapy with demonstrated efficacy in treating hematologic malignancies, also exhibits significant promise for addressing autoimmune diseases. This innovative therapeutic approach holds promise for achieving long-term remission in autoimmune diseases, potentially offering significant benefits to affected patients. Current targets under investigation for the treatment of these conditions include CD19, CD20, and BCMA, among others. However, CAR-T therapy faces difficulties such as time-consuming cell manufacturing, complex and expensive process, and the possibility of severe adverse reactions complicating the treatment, etc. This article examines CAR-T therapy across various rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), systemic sclerosis (SSc), antisynthetase syndrome (ASS), and ANCA-associated vasculitis (AAV), highlighting both therapeutic advancements and ongoing challenges.
Association between anthropometric indices and hypertension: identifying optimal cutoff points for U.S. adults across different populations
Authors: Zhang Xueliang , Nie Yan , Li Dan , Zhou Chunhua
Published: December 2024

Objective

This study compares the relationships between five anthropometric indices, a body shape index (ABSI), body roundness index (BRI), waist circumference (WC), body mass index (BMI) and waist-to-height ratio (WHtR), and hypertension, assessing their predictive capacities. The aim is to determine the specific numerical changes in hypertension incidence, systolic blood pressure (SBP) and diastolic blood pressure (DBP) for each increase in standard deviation of these indices, and to identify the optimal predictive indicators for different populations, including the calculation of cutoff values.

Methods

This study used data from the NHANES datasets spanning 2007 to 2018. Logistic regression analysis was used to quantify the associations between these anthropometric indices and hypertension, calculating β coefficients and odds ratios (ORs). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive ability of each index for hypertension.

Results

For each increase in standard deviation in WC, BMI, WHtR, ABSI and BRI, the prevalence of hypertension increased by 33% (95% CI: 27%–40%), 32% (95% CI: 26%–38%), 35% (95% CI: 28%–42%), 9% (95% CI: 4%–16%) and 32% (95% CI: 26%–38%), respectively. The SBP correspondingly increased by 2.36 mmHg (95% CI: 2.16–2.56), 2.41 mmHg (95% CI: 2.21–2.60), 2.48 mmHg (95% CI: 2.28–2.68), 0.42 mmHg (95% CI: 0.19–0.66) and 2.46 mmHg (95% CI: 2.26–2.66), respectively. Similarly, DBP increased by 1.83 mmHg (95% CI: 1.68–1.98), 1.72 mmHg (95% CI: 1.58–1.87), 1.72 mmHg (95% CI: 1.57–1.88), 0.44 mmHg (95% CI: 0.27–0.62) and 1.64 mmHg (95% CI: 1.48–1.79). In the youth and middle-aged groups, WC had the best predictive ability, with AUCs of 0.749 and 0.603, respectively. Among the elderly group, the AUCs for all five indices ranged between 0.5 and 0.52.

Conclusion

Increases in WC, BMI, WHtR and BRI are significantly associated with higher incidences of hypertension and increases in SBP and DBP, while the impact of ABSI on blood pressure is relatively weak. Stratified analysis indicates significant age-related differences in the predictive value of these indices, with the strongest associations observed in the youth group, followed by the middle age group, and the weakest in the elderly. WC demonstrates excellent predictive ability across youth populations.
Tomatidine relieves neuronal damage in spinal cord injury by inhibiting the inflammatory responses and apoptosis through blocking the NF-κB/CXCL10 pathway activation
Authors: Wang Xu , Huang Wei , Sun Hao , Wang Hua , Wang Dongxu , Wang Yongxiang
Published: December 2024

Background

Spinal cord injury (SCI) is a neurological disease characterized by high disability and mortality rates. Tomatidine, a natural steroid alkaloid, has been evidenced to have neuroprotective properties. However, the underlying mechanisms of tomatidine in treating SCI remain ambiguous. This study aimed to illustrate the molecular mechanisms of tomatidine in modulating the inflammatory response and promoting functional rehabilitation after SCI.

Methods

Sprague–Dawley (SD) rats were used to construct an in vivo SCI model and were intraperitoneally injected with tomatidine (5, 10, or 20 mg/kg) for 7 days, followed by treatment with the nuclear factor-κB (NF-κB) pathway agonist (PMA). In addition, lipopolysaccharide (LPS)-induced PC-12 cells were used to establish an SCI cell model and were stimulated with tomatidine, PMA, or a CXCL10 inhibitor. The pathophysiological changes and neurological function were evaluated using blood-brain barrier (BBB) scoring, water content determination, hematoxylin and eosin (H&E) staining, and TUNEL assay. Levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, were measured. Cell proliferation, apoptosis, and the expression of C-X-C motif chemokine ligand 10 (CXCL10) were determined. Moreover, the expression of cleaved-caspase 3, caspase 3, CXCL10, p-p65, and p65 were analyzed.

Results

Our data revealed that tomatidine promoted neuronal damage recovery, reduced histopathological changes, elevated cell proliferation, and inhibited the apoptosis and inflammatory factor levels in spinal cord tissues and LPS-induced PC-12 cells. Moreover, tomatidine decreased the expression of CXCL10 in vitro and in vivo, which was accompanied by the regulation of the NF-κB pathway. However, the NF-κB pathway agonist PMA reversed the protective effect of tomatidine in vitro. PMA also enhanced the CXCL10 expression and stimulated the activation of the NF-κB pathway, as demonstrated by the upregulation of phosphorylated p65. The CXCL10 inhibitor had effects similar to tomatidine on cleaved-caspase 3 expression, CXCL10 expression, and the NF-κB pathway.

Conclusion

Tomatidine can alleviate neuronal damage in SCI by inhibiting apoptosis and inflammation through the NF-κB/CXCL10 pathway. Our findings provide a novel therapeutic target and candidate for the treatment of SCI.
Effects of endophytes on early growth and ascorbate metabolism in Brassica napus
Authors: Jones-Held Susan , White James F.
Published: December 2024

Understanding the early interactions between plants and endophytes will contribute to a more systematic approach to enhancing endophyte-mediated effects on plant growth and environmental stress resistance. This study examined very early growth and ascorbate metabolism after seed treatment of Brassica napus with three different endophytes. The three endophytes used were Bacillus amyloliquefaciens pb1(Bapb1), Micrococcus luteus (Ml) and Pseudomonas fluorescens SLB4 (SLB4). Seeds of Brassica napus cv. trophy were surface sterilized and plated on 1/2 MS Basal salts (pH 5.7 -5.8) + 0.8% agarose. Under sterile conditions, endophyte suspensions or sterile distilled water (controls) were applied to plated seeds. After two days, all plates were scanned to produce digital images for subsequent growth analysis. Then, seedlings were gently removed from the plates and placed in sterile microfuge tubes. For biochemical analyses, extracts were prepared from samples and assayed spectrophotometrically. We detected slight changes in seedling root tip and/or primary root growth with Bapb1 and Ml. Seedlings treated with SLB4 exhibited significantly increased primary root and root tip length after two days of growth. Ascorbate oxidation, however, was the primary significant change common to all endophyte-treated seedlings. In relation to ascorbate oxidation, soluble ascorbate oxidase (AO) was slightly reduced in Bapb1 and Ml-treated seedlings, whereas ionically-bound AO was reduced in Bapb1 and SLB4-treated seedlings. Total AO activity was significantly reduced in Bapb1-treated seedlings. There were no differences in cytosolic APX activity or glutathione levels between endophyte-treated seedlings and controls. Like pathogens, endophytes can trigger an oxidative burst in the plant. A level of ascorbate oxidation seems required to propagate ROS as signaling molecules as part of the plant immune response. The slight to moderate reductions in plant AO activity that we found mimic the inhibitory effects of pathogens on AO activity, but there was still a level of AO activity that may have been sufficient for the apoplastic ascorbate oxidation required for subsequent ROS signaling. Other studies have suggested that endophytes may elicit a more moderate plant immune response relative to pathogens to facilitate colonization. The AO, APX, and glutathione results would be consistent with a moderate plant immune response to endophytes.
Overview of research on virus-resistant breeding of melon
Authors: Tian Shoubo , Diao Qiannan , Cao Yanyan , Yao Dongwei , Zhang Wenxian , Zhang Hui , Du Xuan , Zhang Yongping
Published: December 2024

The development of virus-resistant melon varieties not only poses challenges in balancing melon quality and resistance but also contributes to sustainable agricultural development. This research focuses on the exploration and application of various breeding techniques to enhance the virus resistance of melon varieties. Molecular markers associated with virus resistance genes have been identified and utilized in marker-assisted selection, enabling more efficient and targeted breeding. Genetic engineering approaches have also shown promise, introducing specific resistance genes into melon genomes. In addition, traditional breeding methods, such as hybridization and selection, continue to play an important role in creating virus-resistant melon lines. The combination of these approaches holds great potential for developing melon varieties with improved virus resistance, thereby increasing yield and quality, and reducing the economic losses caused by viral infections in melon production.
Gender differences in elementary school students’ fraction learning: roles of spatial ability and mathematical anxiety
Authors: Zhang Ruhai , Chen Zhongting , Deng Ciping
Published: December 2024

Aim

In this study, we examined gender differences in fraction learning and explored potential underlying mechanisms.

Methods

The mediating effects of spatial ability and mathematical anxiety on gender differences in fraction learning were tested in elementary school students. A total of 165 sixth-grade students (83 girls) from public elementary schools participated in the study. All participants completed a series of tasks, including a mathematical anxiety test, two spatial ability tasks (spatial working memory and mental rotation tests), and a fraction knowledge test (incorporating fraction arithmetic, fraction number line, and fraction concept knowledge).

Results

Significant gender differences exist in student performance in terms of fractional arithmetic, fractional number line estimation, mathematical anxiety, and spatial working memory. We also identified a chain-mediating effect of spatial working memory and mathematical anxiety on the relationship between gender and fractional arithmetic.

Conclusion

The findings suggest a developmental pathway linking gender differences in spatial cognition to fraction learning, contributing to a better understanding of the cognitive and affective factors underlying gender differences in fraction learning during early adolescence. Furthermore, there are several practical implications for reducing gender differences in mathematics education during school years.
Simulation of granular flows and machine learning in food processing
Authors: Cui X. , Adebayo D. , Zhang H. , Howarth M. , Anderson A. , Olopade T. , Salami K. , Farooq S.
Published: December 2024

Granular materials are widely encountered in food processing, but understanding their behavior and movement mechanisms remains in the early stages of research. In this paper, we present our recent modeling and simulation work on chute granular flow using both the discrete element method (DEM) and continuum method. Based on the simulation data, we apply machine learning techniques such as Random Forest, Linear Regression, and Ridge Regression to evaluate the effectiveness of these models in predicting granular flow patterns. The granular materials in our study consist of soft-sphere particles with a 1 mm diameter, driven by gravity as they flow down a chute inclined relative to the horizontal plane. Our DEM and continuum simulation results show good agreement in modeling the chute flow, and the machine learning approach demonstrates promising potential for predicting flow patterns. The results of this chute flow study can provide a benchmark solution for more complex flow problems involving factors such as particle shape, size, interparticle interactions, and external obstacles.