bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Cancer Targeting: A Study on the Effect of Dual-Ligand Density on Targeting of Cells Having Differential Expression of Target Biomarkers
Authors: Sultana Nayer , David Allan E.
Published: August 2023

Silica nanoparticles with hyaluronic acid (HA) and folic acid (FA) were developed to study dual-ligand targeting of CD44 and folate receptors, respectively, in colon cancer. Characterization of particles with dynamic light scattering showed them to have hydrodynamic diameters of 147–271 nm with moderate polydispersity index (PDI) values. Surface modification of the particles was achieved by simultaneous reaction with HA and FA and results showed that ligand density on the surface increased with increasing concentrations in the reaction mixture. The nanoparticles showed minimal to no cytotoxicity with all formulations showing ≥ 90% cell viability at concentrations up to 100 µg/mL. Based on flow cytometry results, SW480 cell lines were positive for both receptors, the WI38 cell line was positive for CD44 receptor, and Caco2 was positive for the folate receptor. Cellular targeting studies demonstrated the potential of the targeted nanoparticles as promising candidates for delivery of therapeutic agents. The highest cellular targeting was achieved with particles synthesized using folate:surface amine (F:A) ratio of 9 for SW480 and Caco2 cells and at F:A = 0 for WI38 cells. The highest selectivity was achieved at F:A = 9 for both SW480:WI38 and SW480:Caco2 cells. Based on HA conjugation, the highest cellular targeting was achieved at H:A = 0.5–0.75 for SW480 cell, at H:A = 0.75 for WI38 cell and at H:A = 0.5 for Caco2 cells. The highest selectivity was achieved at H:A = 0 for both SW480:WI38 and SW480:Caco2 cells. These results demonstrated that the optimum ligand density on the nanoparticle for targeting is dependent on the levels of biomarker expression on the target cells. Ongoing studies will evaluate the therapeutic efficacy of these targeted nanoparticles using in vitro and in vivo cancer models.
Single-Cell Transcriptional and Epigenetic Profiles of Male Breast Cancer Nominate Salient Cancer-Specific Enhancers
Authors: Kim Hyunsoo , Wisniewska Kamila , Regner Matthew J. , Thennavan Aatish , Spanheimer Philip M. , Franco Hector L.
Published: August 2023

Male breast cancer represents about 1% of all breast cancer diagnoses and, although there are some similarities between male and female breast cancer, the paucity of data available on male breast cancer makes it difficult to establish targeted therapies. To date, most male breast cancers (MBCs) are treated according to protocols established for female breast cancer (FBC). Thus, defining the transcriptional and epigenetic landscape of MBC with improved resolution is critical for developing better avenues for therapeutic intervention. In this study, we present matched transcriptional (scRNA-seq) and epigenetic (scATAC-seq) profiles at single-cell resolution of two treatment naïve MBC tumors processed immediately after surgical resection. These data enable the detection of differentially expressed genes between male and female breast tumors across immune, stromal, and malignant cell types, to highlight several genes that may have therapeutic implications. Notably, MYC target genes and mTORC1 signaling genes were significantly upregulated in the malignant cells of MBC compared to the female counterparts. To understand how the regulatory landscape of MBC gives rise to these male-specific gene expression patterns, we leveraged the scATAC-seq data to systematically link changes in chromatin accessibility to changes in gene expression within each cell type. We observed cancer-specific rewiring of several salient enhancers and posit that these enhancers have a higher regulatory load than lineage-specific enhancers. We highlight two examples of previously unannotated cancer-cell-specific enhancers of ANXA2 and PRDX4 gene expression and show evidence for super-enhancer regulation of LAMB3 and CD47 in male breast cancer cells. Overall, this dataset annotates clinically relevant regulatory networks in male breast tumors, providing a useful resource that expands our current understanding of the gene expression programs that underlie the biology of MBC.
Proteomic Analysis of Mesenchymal Stromal Cells Secretome in Comparison to Leukocyte- and Platelet-Rich Fibrin
Authors: Al-Sharabi Niyaz , Gruber Reinhard , Sanz Mariano , Mohamed-Ahmed Samih , Kristoffersen Einar K. , Mustafa Kamal , Shanbhag Siddharth
Published: August 2023

Secretomes of mesenchymal stromal cells (MSCs) are emerging as a novel growth factor (GF)-based strategy for periodontal and bone regeneration. The objective of this study was to compare the secretome of human bone marrow MSC (BMSC) to that of leukocyte- and platelet-rich fibrin (L-PRF), an established GF-based therapy, in the context of wound healing and regeneration. Conditioned media from human BMSCs (BMSC-CM) and L-PRF (LPRF-CM) were subjected to quantitative proteomic analysis using liquid chromatography with tandem mass spectrometry. Global profiles, gene ontology (GO) categories, differentially expressed proteins (DEPs), and gene set enrichment (GSEA) were identified using bioinformatic methods. Concentrations of selected proteins were determined using a multiplex immunoassay. Among the proteins identified in BMSC-CM (2157 proteins) and LPRF-CM (1420 proteins), 1283 proteins were common. GO analysis revealed similarities between the groups in terms of biological processes (cellular organization, protein metabolism) and molecular functions (cellular/protein-binding). Notably, more DEPs were identified in BMSC-CM (n = 550) compared to LPRF-CM (n = 118); these included several key GF, cytokines, and extracellular matrix (ECM) proteins involved in wound healing. GSEA revealed enrichment of ECM (especially bone ECM)-related processes in BMSC-CM and immune-related processes in LPRF-CM. Similar trends for intergroup differences in protein detection were observed in the multiplex analysis. Thus, the secretome of BMSC is enriched for proteins/processes relevant for periodontal and bone regeneration. The in vivo efficacy of this therapy should be evaluated in future studies.
Huntingtin Interacting Proteins and Pathological Implications
Authors: Liu Li , Tong Huichun , Sun Yize , Chen Xingxing , Yang Tianqi , Zhou Gongke , Li Xiao-Jiang , Li Shihua
Published: August 2023

Huntington’s disease (HD) is caused by an expansion of a CAG repeat in the gene that encodes the huntingtin protein (HTT). The exact function of HTT is still not fully understood, and previous studies have mainly focused on identifying proteins that interact with HTT to gain insights into its function. Numerous HTT-interacting proteins have been discovered, shedding light on the functions and structure of HTT. Most of these proteins interact with the N-terminal region of HTT. Among the various HTT-interacting proteins, huntingtin-associated protein 1 (HAP1) and HTT-interacting protein 1 (HIP1) have been extensively studied. Recent research has uncovered differences in the distribution of HAP1 in monkey and human brains compared with mice. This finding suggests that there may be species-specific variations in the regulation and function of HTT-interacting proteins. Understanding these differences could provide crucial insights into the development of HD. In this review, we will focus on the recent advancements in the study of HTT-interacting proteins, with particular attention to the differential distributions of HTT and HAP1 in larger animal models.
The SbbHLH041–SbEXPA11 Module Enhances Cadmium Accumulation and Rescues Biomass by Increasing Photosynthetic Efficiency in Sorghum
Authors: Wang Huinan , Yu Junxing , Zhu Bin , Gu Lei , Wang Hongcheng , Du Xuye , Zeng Tuo , Tang Heng
Published: August 2023

In plants, expansin genes are responsive to heavy metal exposure. To study the bioremediary potential of this important gene family, we discovered a root-expressed expansin gene in sorghum, SbEXPA11, which is notably upregulated following cadmium (Cd) exposure. However, the mechanism underlying the Cd detoxification and accumulation mediated by SbEXPA11 in sorghum remains unclear. We overexpressed SbEXPA11 in sorghum and compared wild-type (WT) and SbEXPA11-overexpressing transgenic sorghum in terms of Cd accumulation and physiological indices following Cd. Compared with the WT, we found that SbEXPA11 mediates Cd tolerance by exerting reactive oxygen species (ROS)-scavenging effects through upregulating the expression of antioxidant enzymes. Moreover, the overexpression of SbEXPA11 rescued biomass production by increasing the photosynthetic efficiency of transgenic plants. In the pot experiment with a dosage of 10 mg/kg Cd, transgenic sorghum plants demonstrated higher efficacy in reducing the Cd content of the soil (8.62 mg/kg) compared to WT sorghum plants (9.51 mg/kg). Subsequent analysis revealed that the SbbHLH041 transcription factor has the ability to induce SbEXPA11 expression through interacting with the E-box located within the SbEXPA11 promoter. These findings suggest that the SbbHLH041–SbEXPA11 cascade module may be beneficial for the development of phytoremediary sorghum varieties.
Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?
Authors: Batista-Liz Joao Carlos , Calvo-Río Vanesa , Sebastián Mora-Gil María , Sevilla-Pérez Belén , Márquez Ana , Leonardo María Teresa , Peñalba Ana , Carmona Francisco David , Narvaez Javier , Martín-Penagos Luis , Belmar-Vega Lara , Gómez-Fernández Cristina , Caminal-Montero Luis , Collado Paz , Quiroga-Colina Patricia , Uriarte-Ecenarro Miren , Rubio Esteban , Luque Manuel León , Blanco-Madrigal Juan María , Galíndez-Agirregoikoa Eva , Martín Javier , Castañeda Santos , González-Gay Miguel Angel , Blanco Ricardo , Pulito-Cueto Verónica , López-Mejías Raquel
Published: August 2023

ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.
Research Progress of Pyroptosis in Fatty Liver Disease
Authors: Li Rongxuan , Xue Weiyue , Wei Huiting , Fan Qingqing , Li Xiang , Qiu Ye , Cui Di
Published: August 2023

Fatty liver disease (FLD) is a clinical and pathological syndrome characterized by excessive fat deposition and even steatosis in hepatocytes. It has been proven that liver inflammation induced by fat and its derivatives are involved in the pathogenesis of FLD, while the precise mechanism still remains poorly understood. Pyroptosis is programmed inflammatory cell death driving cell swelling and membrane rupture. Pyroptosis is initiated by the activation of inflammasomes and caspases, which further cleaves and activates various gasdermins, leading to pores forming on the cell membrane and the release of pro-inflammatory factors such as interleukin (IL)-1β and IL-18. Recent studies demonstrate that pyroptosis occurs in hepatocytes, and inhibiting pyroptosis could effectively reduce fat deposition in the liver and could ameliorate inflammation from FLD, attracting our prime focus on the role of pyroptosis in FLD. In this manuscript, we reviewed the current understanding of pyroptosis in FLD development, aiming to provide new insights and potential research targets for the clinical diagnosis and intervention of FLD.
Glutathione-Mediated Neuroprotective Effect of Purine Derivatives
Authors: Matsumura Nobuko , Aoyama Koji
Published: August 2023

Numerous basic studies have reported on the neuroprotective properties of several purine derivatives such as caffeine and uric acid (UA). Epidemiological studies have also shown the inverse association of appropriate caffeine intake or serum urate levels with neurodegenerative diseases such as Alzheimer disease (AD) and Parkinson’s disease (PD). The well-established neuroprotective mechanisms of caffeine and UA involve adenosine A2A receptor antagonism and antioxidant activity, respectively. Our recent study found that another purine derivative, paraxanthine, has neuroprotective effects similar to those of caffeine and UA. These purine derivatives can promote neuronal cysteine uptake through excitatory amino acid carrier protein 1 (EAAC1) to increase neuronal glutathione (GSH) levels in the brain. This review summarizes the GSH-mediated neuroprotective effects of purine derivatives. Considering the fact that GSH depletion is a manifestation in the brains of AD and PD patients, administration of purine derivatives may be a new therapeutic approach to prevent or delay the onset of these neurodegenerative diseases.
Identification of the HNSC88 Molecular Signature for Predicting Subtypes of Head and Neck Cancer
Authors: Chuang Yi-Hsuan , Lin Chun-Yu , Lee Jih-Chin , Lee Chia-Hwa , Liu Chia-Lin , Huang Sing-Han , Lee Jung-Yu , Lai Wen-Sen , Yang Jinn-Moon
Published: August 2023

Head and neck squamous cell carcinoma (HNSC) exhibits genetic heterogeneity in etiologies, tumor sites, and biological processes, which significantly impact therapeutic strategies and prognosis. While the influence of human papillomavirus on clinical outcomes is established, the molecular subtypes determining additional treatment options for HNSC remain unclear and inconsistent. This study aims to identify distinct HNSC molecular subtypes to enhance diagnosis and prognosis accuracy. In this study, we collected three HNSC microarrays (n = 306) from the Gene Expression Omnibus (GEO), and HNSC RNA-Seq data (n = 566) from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) and validate our results. Two scoring methods, representative score (RS) and perturbative score (PS), were developed for DEGs to summarize their possible activation functions and influence in tumorigenesis. Based on the RS and PS scoring, we selected candidate genes to cluster TCGA samples for the identification of molecular subtypes in HNSC. We have identified 289 up-regulated DEGs and selected 88 genes (called HNSC88) using the RS and PS scoring methods. Based on HNSC88 and TCGA samples, we determined three HNSC subtypes, including one HPV-associated subtype, and two HPV-negative subtypes. One of the HPV-negative subtypes showed a relationship to smoking behavior, while the other exhibited high expression in tumor immune response. The Kaplan–Meier method was used to compare overall survival among the three subtypes. The HPV-associated subtype showed a better prognosis compared to the other two HPV-negative subtypes (log rank, p = 0.0092 and 0.0001; hazard ratio, 1.36 and 1.39). Additionally, within the HPV-negative group, the smoking-related subgroup exhibited worse prognosis compared to the subgroup with high expression in immune response (log rank, p = 0.039; hazard ratio, 1.53). The HNSC88 not only enables the identification of HPV-associated subtypes, but also proposes two potential HPV-negative subtypes with distinct prognoses and molecular signatures. This study provides valuable strategies for summarizing the roles and influences of genes in tumorigenesis for identifying molecular signatures and subtypes of HNSC.
A Leukemic Target with a Thousand Faces: The Mitochondria
Authors: Maffeo Beatrice , Panuzzo Cristina , Moraca Amedeo , Cilloni Daniela
Published: August 2023

In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years remains unfortunately low. Indeed, the high heterogeneity of AML clones with distinct metabolic and molecular profiles allows them to survive the chemotherapy-induced changes, thus leading to resistance, clonal evolution, and relapse. Moreover, leukemic stem cells (LSCs), the quiescent reservoir of residual disease, can persist for a long time and activate the recurrence of disease, supported by significant metabolic differences compared to AML blasts. All these points highlight the relevance to develop combination therapies, including metabolism inhibitors to improve treatment efficacy. In this review, we summarized the metabolic differences in AML blasts and LSCs, the molecular pathways related to mitochondria and metabolism are druggable and targeted in leukemia therapies, with a distinct interest for Venetoclax, which has revolutionized the therapeutic paradigms of several leukemia subtype, unfit for intensive treatment regimens.
Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder
Authors: Marozio Luca , Nuzzo Anna Maria , Gullo Eugenio , Moretti Laura , Canuto Emilie M. , Tancredi Annalisa , Goia Margherita , Cosma Stefano , Revelli Alberto , Rolfo Alessandro , Benedetto Chiara
Published: August 2023

Recurrent pregnancy loss (RPL) refers to two or more miscarriages before 20 weeks gestation. Its prevalence is 1–2%; its pathogenesis remains unexplained in more than 50% of cases, in which the cause is thought to be abnormal immune activity during placentation leading to a lack of pregnancy-induced immune tolerance. It is unknown whether immune activity is deranged in the endometrium of women with RPL. We studied the gene expression and the quantitative tissue protein levels of three immune checkpoints (CD276, which enhances cytotoxic T-cell activity, cytotoxic T-lymphocyte-associated antigen-4 [CTL-4], which reduces Th1 cytokine production, and lymphocyte activation gene-3 [LAG-3], which shows suppressive activity on Tregs and CD4+ T-cells) in endometrial samples from 27 women with unexplained RPL and in 29 women with dysfunctional uterine bleeding and previous uneventful pregnancies as controls. RNA isolation, real-time PCR, protein isolation, and ELISA were performed. CD276 gene expression and protein tissue levels were significantly lower in the endometrium of the RPL group than in the controls, whereas both CTL-4 and LAG-3 were significantly higher. This difference suggests defective endometrial immune regulation and overactivation of immune response in women with a history of RPL, at least in relation to controls with dysfunctional uterine bleeding and previous normal reproductive history.
Defining Mechanisms of C3 to CAM Photosynthesis Transition toward Enhancing Crop Stress Resilience
Authors: Tan Bowen , Chen Sixue
Published: August 2023

Global climate change and population growth are persistently posing threats to natural resources (e.g., freshwater) and agricultural production. Crassulacean acid metabolism (CAM) evolved from C3 photosynthesis as an adaptive form of photosynthesis in hot and arid regions. It features the nocturnal opening of stomata for CO2 assimilation, diurnal closure of stomata for water conservation, and high water-use efficiency. To cope with global climate challenges, the CAM mechanism has attracted renewed attention. Facultative CAM is a specialized form of CAM that normally employs C3 or C4 photosynthesis but can shift to CAM under stress conditions. It not only serves as a model for studying the molecular mechanisms underlying the CAM evolution, but also provides a plausible solution for creating stress-resilient crops with facultative CAM traits. This review mainly discusses the recent research effort in defining the C3 to CAM transition of facultative CAM plants, and highlights challenges and future directions in this important research area with great application potential.
Digital-Reported Outcome from Medical Notes of Schizophrenia and Bipolar Patients Using Hierarchical BERT
Authors: Khandker Rezaul K. , Prince Md Rakibul Islam , Chekani Farid , Dexter Paul Richard , Boustani Malaz A. , Ben Miled Zina
Published: August 2023

Patient-reported (PRO) and clinician-reported (CRO) outcomes are assessment instruments that are completed by patients and trained healthcare professionals, respectively. A PRO is a report of the direct experience of the patient with a given disease condition. A CRO is an assessment of the condition of the patient by the healthcare provider. PROs may not be accessible to all patients, especially those suffering from severe disease conditions. CROs are time-consuming and therefore administered infrequently. In the present study, we introduce a new form of assessment, the digital-reported outcome (DRO), which is automatically derived from the medical notes of the patient. DROs have a low overhead and can be generated at each patient’s visit to complement other outcome-assessment instruments and enhance clinical decision support by identifying at-risk patients. In this study, a DRO is developed to evaluate the functional impairment in the daily activities of two cohorts of patients suffering from bipolar disorder and schizophrenia. The input of the DRO is a single medical note from the electronic medical record of the patient. This note is submitted to a hierarchical bidirectional encoder representations from transformers (BERT) model. First, a sentence-level embedding is produced for each sentence in the note using a token-level attention mechanism. Second, an embedding for the entire note is constructed using a sentence-level attention mechanism. Third, the final embedding is classified using a feed-forward neural network. The model is trained to classify patients into moderate or severe functioning impairment levels according to the general assessment of functioning (GAF) scale, a CRO instrument for the assessment of the impact of mental illness on the daily activities of the patient. The DRO is validated using medical notes that were labeled by multiple healthcare providers from different healthcare institutions. The results indicate that a general DRO is able to classify patients from the two cohorts according to the two functioning impairment levels (severe versus moderate) prior to the onset of disease with an AUC of 76%. Disease-specific DROs are only applicable after the onset of the disease and produced AUCs of nearly 85%. The methodology introduced in the present paper is practical and can support the automated monitoring of the severity of the functioning impairment of bipolar and schizophrenia patients. Extending the proposed DRO to other psychiatric conditions and types of impairments is the subject of ongoing research work.
Development of a Concurrent Treatment Technique of Ethyl Formate and Mixtures (Nitrogen, Phosphine) to Control Citrus Mealybug (Planococcus citri)
Authors: Kim Bongsu , Park Min-Goo , Kim Gil-Hah , Yang Jeong-Oh
Published: August 2023

Currently, the fumigant ethyl formate (EF) is stored as a liquified gas in metal cylinders mixed with carbon dioxide (CO2), but this product type is expensive to manufacture, transport, and maintain in cylinders. To address these problems, we developed a new EF fumigation technique with a nitrogen (N2) carrier. In this report, the susceptibility of citrus mealybugs, one of the most resistant mealybugs to fumigants, to EF was assessed; the phytotoxicity of an EF + N2 concurrent treatment applied to banana fruit was examined to evaluate the efficacy compared to the current EF + CO2 product; and the increased efficacy with a phosphine (PH3) addition to EF + N2 was also assessed. Concurrent treatment of EF and N2 was performed at an LC50 concentration of EF. N2 was applied in seven doses from concentrations of 79% to 95%. The phytotoxicity of EF to bananas was assessed by applying EF at 35 mg/L with N2 at 79%, and the color, sugar content, and weight loss of bananas were measured for 14 days after treatment. The EF with N2 treatment resulted in more than 50% mortality at all growth stages of the mealybug, and there was no significant difference between the untreated and treated banana fruits. EF mixed with PH3 showed a higher efficacy than treatment with EF alone, but only a slight increase in efficacy was observed when the PH3 concentration increased. These results indicate that concurrent treatment with EF and N2 can be used to control mealybugs on banana fruits, and combined treatment with EF and PH3 can also enhance the efficacy against mealybugs.
Investigating Fumarate Hydratase-Deficient Uterine Fibroids: A Case Series
Authors: Alkhrait Samar , Ali Munira , Kertowidjojo Elizabeth , Romero Iris L , Hathaway Feighanne , Madueke-Laveaux Obianuju Sandra
Published: August 2023

Uterine leiomyomas or uterine fibroids are the most common benign soft tissue tumor in reproductive-aged women. Fumarate hydratase deficient (FH-d) uterine fibroids are a rare subtype that is diagnosed only on pathologic evaluation. FH-d uterine fibroids may be the first indicator of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Therefore, identifying and understanding the clinical implication and diagnosis of FH-d uterine fibroids is critical for early diagnosis of HLRCC. This case series investigates the uncommon yet significant condition of FH-d uterine fibroids. We examined the clinical manifestation, diagnostic imaging, and histopathological characteristics of FH-d uterine fibroids in five cases identified at our institution over the last ten years. All diagnoses were confirmed by pathologic evaluation after surgical treatment. Gynecologists and pathologists play a critical role in the early diagnosis of FH-d uterine fibroids and must recognize the relevant clinical and pathologic findings that raise suspicion about this diagnosis. The detection of these cases is largely dependent on the pathologist’s ability to recognize unique histopathologic features. Once these characteristics are identified, it should prompt a referral to a gynecologist to consider conducting germline genetic testing. The management of FH-d uterine fibroids necessitates a multidisciplinary approach, including proper genetic screening and regular surveillance, especially for renal tumors.
Endovenous Thermal Ablation for Treatment of Symptomatic Saphenous Veins—Does the Body Weight Matter?
Authors: Bossart Simon , Boesch Patricia Fiona , Keo Hak Hong , Staub Daniel , Uthoff Heiko
Published: August 2023

Objective: This study aimed to examine whether body weight may affect the effectiveness and safety of endovenous thermal ablation (ETA) for the treatment of symptomatic varicose veins. Methods: This retrospective single-center cohort study analyzed the outcomes and patient demographic data with a focus on the body weight of all patients who had ETA of symptomatic varicose veins between September 2017 and October 2020. Results: A total of 1178 treated truncal veins from 636 patients were analyzed. The mean ± standard deviation body mass index (BMI) was 25.5 ± 4.9. In 2.3% of cases, the patients were underweight (BMI < 18.5), 31.0% were overweight (BMI > 25), and 16.6% were obese (BMI > 30). Complete truncal occlusion was observed 1 year post intervention in 97.6–100% and patients were satisfied or very satisfied in 96.2–100% across BMI groups. Pain was low but significantly higher in the patients with obesity 6 weeks post intervention (visual analog scale 0.84 ± 1.49) and a higher infection rate was observed in the patients with obesity (n = 4/132; 3.0%). No significant association was observed between BMI and bleeding or thromboembolic events. Conclusions: Patients with obesity experienced prolonged pain and more infections after ETA, but ETA for varicose vein treatment remains effective and safe, independent of the patient’s BMI.
Prospective Study of Vonoprazan-Based First-Line Triple Therapy with Amoxicillin and Metronidazole for Clarithromycin-Resistant Helicobacter pylori
Authors: Sue Soichiro , Suzuki Yuichi , Sasaki Tomohiko , Kaneko Hiroaki , Irie Kuniyasu , Komatsu Kazuto , Maeda Shin
Published: August 2023

Aim: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). Methods: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0–100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9–84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7–85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. Conclusions: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.
Sequential Intraoperative Evaluation of Rotational Stability of Cementless Stem in Total Hip Arthroplasty: A Broach-Based Study
Authors: Kinoshita Sakae , Kinoshita Koichi , Sakamoto Tetsuya , Seo Hajime , Suzuki Masahiro , Yamamoto Takuaki
Published: August 2023

In cementless total hip arthroplasty, the rotational stability of the stem is generally confirmed in a one-time manual evaluation by the surgeon. This study was performed to evaluate the sequential intraoperative changes in rotational stability using a torque wrench. Primary total hip arthroplasty was performed on 52 consecutive hips using a single wedge stem design. Intraoperative evaluation of rotational stability was uniformly performed using a torque wrench. Evaluations were performed immediately after broach insertion and immediately before the final insertion of the stem (after placement of the acetabular cup). Immediately after the insertion of the broach, rotational stability was checked and confirmed to be fully stabilized using a torque wrench in all cases, and the stability was maintained in 17 of 52 (33%) hips immediately before the final insertion of the stem. Among the hips showing instability, 11 of 35 (31%) broaches were upsized, while the remaining 24 hips achieved stabilization through deeper insertion of the broach. In conclusion, the rotational stability achieved immediately after the insertion of the broach was not necessarily maintained during surgery, indicating that rotational stability may need to be checked at multiple time points intraoperatively.
Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes
Authors: Guida Giuseppe , Bertolini Francesca , Carriero Vitina , Levra Stefano , Sprio Andrea Elio , Sciolla Martina , Orpheu Giulia , Arrigo Elisa , Pizzimenti Stefano , Ciprandi Giorgio , Ricciardolo Fabio Luigi Massimo
Published: August 2023

Background: High total IgE levels are weak predictors of T2High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgEHigh and IgELow within the T2High and T2Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and FENO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2Low-IgELow (15.5%); (2) T2Low-IgEHigh (5.1%); (3) T2High-IgELow (33.6%); and T2High-IgEHigh (45.7%). T2Low-IgELow patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2Low-IgEHigh phenotype vs. the T2Low-IgELow phenotype. Within the T2High, low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2Low patients is associated with a peculiar clinical phenotype, similar to T2High in terms of disease severity and nasal comorbidities, while retaining the T2Low features. IgE may represent an additional biomarker for clustering asthma in both T2High and T2Low phenotypes rather than a predictor of T2High asthma “per se”.
Effect of the Correction of Bilateral Differences in Masseter Muscle Functional Pressure on the Mandible of Growing Rats
Authors: Mizuno Shuhei , Matsunaga Satoru , Kasahara Norio , Kasahara Masaaki , Shimoo Yoshiaki , Abe Shinichi , Nakano Takayoshi , Ishimoto Takuya , Hikita Atsuhiko , Nojima Kunihiko , Nishii Yasushi
Published: August 2023

The objective of this study is to clarify the effect of restoring the lowered masticatory muscle functional pressure and correcting bilateral differences in masticatory muscle functional pressure on jawbone growth during growth and development with a quantitative evaluation of the changes in the micro/nanostructural characteristics of entheses. Male Wistar rats aged 4 weeks were divided into an experimental group injected with a botulinum toxin serotype A (BoNT/A) formulation to reduce muscle function (BTX group) and a control group (CTRL group). They were euthanised after 6, 8, 10, 12, and 16 weeks after measuring the difference between the midline of the upper and lower incisors. The mandibles were harvested for histological examination, second harmonic generation imaging, and the quantitative evaluation of biological apatite (BAp) crystal alignment. The midline difference decreased with age in weeks. In rats from 6 weeks after BoNT/A administration to 12 weeks after administration, the collagen fibre bundle diameter was significantly smaller in the BTX group; the difference between the two groups decreased with increasing age. BAp crystal alignment was significantly different on the x-axis and the y-axis on the BTX group from 6 weeks after BoNT/A administration to 10 weeks after administration. Asymmetry of mandibular bone formation caused by load imbalance during growth could be corrected by the adjustment of the function of the masseter muscle on either side.
Spatiotemporal Trends and Age–Period–Cohort Analysis for the Burden of Endometriosis-Related Infertility: An Analysis of the Global Burden of Disease Study 2019
Authors: Liu Jingchun , Han Wuyue , Wang Haoyu , Wang Zhi , Li Bingshu , Hong Li
Published: August 2023

Background: Endometriosis is a common nonfatal gynecological disease, and infertility is one of its main dangers. Endometriosis-related infertility causes serious damage to women’s health and places a burden on women of reproductive age. The aim of this study was to describe the current burden of endometriosis-associated infertility and to analyze its spatiotemporal trends. Methods: Age-standardized prevalence rate (ASPR) data from 1990 to 2019 for Endometriosis-related primary infertility (ERPI) and secondary infertility (ERSI) were obtained from the Global Burden of Disease Study (GBD) 2019. These data spanning three decades cover the global, sociodemographic index (SDI) regions, GBD regions, and 204 countries and territories. Spatiotemporal trends were analyzed by calculating the estimated annual percentage change (EAPC) and using a time–period–cohort model. Results: Globally, the ASPR of ERPI and ERSI showed a weak downward trend from 1990 to 2019, with EAPCs of −1.25 (95% CI: −1.39 to −1.11) and −0.6 (95% CI: −0.67 to −0.53), respectively. The spatiotemporal trends in ERPI and ERSI varied substantially between regions and age groups. When endometriosis-related infertility burden was linked to SDI values, a strong negative correlation was observed between the ASPR of ERSI and its EAPC and SDI values. When modeling with age–period–cohort, ERPI burden was found to be highest at ages 20–25 years, while ERSI burden was persistently higher at ages 20–45 years. Using 2000–2004 as the reference period, both ERPI and ERSI burden decreased with each year among women. Significant variability in burden between regions was found for the birth cohort factor. Conclusions: The global burden of endometriosis-related infertility declined minimally from 1990 to 2019. However, this burden varied considerably across regions, age groups, periods, and birth cohorts. The results of this study reflect spatiotemporal trends in the burden of endometriosis-related infertility over the study period and may be used to help improve health management, develop timely and effective prevention and control strategies, and provide epidemiologic theoretical evidence for reducing the burden for endometriosis-related infertility.
Deep Filter Context Network for Click-Through Rate Prediction
Authors: Yu Mingting , Liu Tingting , Yin Jian
Published: August 2023

The growth of e-commerce has led to the widespread use of DeepCTR technology. Among the various types, the deep interest network (DIN), deep interest evolution network (DIEN), and deep session interest network (DSIN) developed by Alibaba have achieved good results in practice. However, the above models’ use of filtering for the user’s own historical behavior sequences and the insufficient use of context features lead to reduced recommendation effectiveness. To address these issues, this paper proposes a novel article model: the deep filter context network (DFCN). This improves the efficiency of the attention mechanism by adding a filter to filter out data in the user’s historical behavior sequence that differs greatly from the target advertisement. The DFCN pays attention to the context features through two local activation units. This model greatly improves the expressiveness of the model, offering strong environment-related attributes and the adaptive capability of the model, with a significant improvement of up to 0.0652 in the AUC metric when compared with our previously proposed DICN under different datasets.
Biochar Aged for Five Years Altered Carbon Fractions and Enzyme Activities of Sandy Soil
Authors: Zhang Yuxin , Ma Wenqi , Sun Xia , Jiang Jingbailun , Li Dianpeng , Tang Guangmu , Xu Wanli , Jia Hongtao
Published: August 2023

Biochar applied to soil has been considered as an effective tool for mitigation of atmospheric carbon dioxide emission and enhancement of carbon storage in soil, which may also enhance soil quality. However, the effect of biochar aged for 5 years on the different carbon fractions and enzyme activities as well as its changes, is not well understood in the cropland sandy soil of northern China. Therefore, a field trial was carried out in 2014 with biochar applied once at 0, 5.25, 10.50, 21.00 and 42.00 g·kg−1 (BC0, BC1, BC2, BC3, and BC4, respectively). We evaluated the influence of biochar addition to the changes in soil organic carbon (SOC), labile carbon pools (readily oxidized carbon, dissolved organic carbon, and microbial biomass carbon) and enzyme activities (invertase, urease, and catalase). Biochar significantly increased SOC (122.00%) and altered the content of labile carbon (increased ROC, DOC and MBC by 71.29%, 10.35%, and 900.00%, respectively). Soil urease and invertase activities increased by 55.81% and 46.76%, respectively, with an increase in biochar application rate, but catalase activity significantly decreased by 31.79%. The values of the geometric means of labile carbon (0.88) and enzyme activities (2.39) for the BC3 treatment were higher than others, which indicated that the biochar application rate of 21.00 g·kg−1 is suggested for the sandy soil. Our results suggest that the application of biochar in sandy soil for five years increased soil carbon sequestration, changed enzyme activities and ameliorated soil quality.
Nucleoporin Nup358 Downregulation Tunes the Neuronal Excitability in Mouse Cortical Neurons
Authors: Martínez-Rojas Vladimir A. , Pischedda Francesca , Romero-Maldonado Isabel , Khalaf Bouchra , Piccoli Giovanni , Macchi Paolo , Musio Carlo
Published: August 2023

Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophysiology of neurodegenerative diseases (NDDs). Although the downregulation of Nup358 leads to a reduction in the scaffold protein ankyrin-G at the axon initial segment (AIS) of mature neurons, the function of Nup358 in the cytoplasm of neurons remains elusive. To investigate whether Nup358 plays any role in neuronal activity, we downregulated Nup358 in non-pathological mouse cortical neurons and measured their active and passive bioelectrical properties. We identified that Nup358 downregulation is able to produce significant modifications of cell-membrane excitability via voltage-gated sodium channel kinetics. Our findings suggest that Nup358 contributes to neuronal excitability through a functional stabilization of the electrical properties of the neuronal membrane. Hypotheses will be discussed regarding the alteration of this active regulation as putatively occurring in the pathophysiology of NDDs.
Comparison of Wood-Based Biocomposites with Polylactic Acid (PLA) Density Profiles by Desaturation and X-ray Spectrum Methods
Authors: Pycka Seweryn , Roman Kamil
Published: August 2023

Wood–plastic composites (WPCs) represent composite materials that employ shredded wood combined with a thermoplastic substance, such as polylactic acid (PLA), to establish structural cohesion within the product profile. This amalgamation of materials results in a robust structure designed to fulfill specialized roles under the influence of pressure and temperature. Given the nature of the constituent materials, the resultant product can be classified as a biocomposite. The creation of such biocomposites entails a rigorous process necessitating the fine-tuning of specific parameters and suitable technologies. The foundational materials employed in this process must be both natural and biodegradable. However, it is noteworthy that natural components like fibers exhibit anisotropic behavior, wherein their mechanical attributes are contingent on the direction of the applied force. Consequently, predicting their performance during biocomposite production proves challenging. The principal objective of this study was to conduct a comparative analysis of wood-based composites incorporating PLA thermoplastic binding agents. The intention was to discern variations in density profiles arising from distinct measurement methodologies. Two measurement methods were used for the measurement: X-ray and spectrum desaturation. Additionally, the study sought to investigate the impact of introducing PLA additives at 25% and 50% concentrations on the fabrication of WPC from wood chips. The properties of these composites were assessed by considering the inherent traits of the composite materials.
Investigation the Effect of MR Fluid Composition on Properties at Low Strain Ranges
Authors: Fenyk Anna , Horak Wojciech , Zieliński Marek
Published: August 2023

The paper presents the results of eight magnetorheological (MR) fluids of different compositions. Magnetite and carbonyl iron were used as magnetic particles. MR fluids based on glycerin and OKS 352 oil were produced using stabilizers in the form of oleic acid and Aerosil 200 (Evonik Resource Efficiency GmbH, Hanau, Germany) silica; additives such as graphite and yellow dextrin were also used. The aim of the study was to determine the properties of various combinations of components on the dynamic properties of MR fluids, i.e., properties characterizing the fluid within the range of low deformations, as well as to investigate the effect of different compositions on structural yield stress and flow stress prepared MR fluids at different magnetic field induction values.
α-Zirconium(IV) Phosphate: Static Study of 225Ac Sorption in an Acidic Environment and Its Kinetic Sorption Study Using natEu as a Model System for 225Ac
Authors: Ondrák Lukáš , Ondrák Fialová Kateřina , Vlk Martin , Štamberg Karel , Bruchertseifer Frank , Morgenstern Alfred , Kozempel Ján
Published: August 2023

Zirconium phosphate (ZrP), especially its alpha allotropic modification, appears to be a very promising sorbent material for the sorption and separation of various radionuclides due to its properties such as an extremely high ion exchange capacity and good radiation stability. Actinium-225 and its daughter nuclide 213Bi are alpha emitting radioisotopes of high interest for application in targeted alpha therapy of cancer. Thus, the main aim of this paper is to study the sorption of 225Ac on the α-ZrP surface and its kinetics, while the kinetics of the sorption is studied using natEu as a non-radioactive homologue of 225Ac. The sorption properties of α-ZrP were tested in an acidic environment (hydrochloric and nitric acid) using batch sorption experiments and characterized using equilibrium weight distribution coefficients Dw (mL/g). The modeling of the experimental data shows that the kinetics of 225Ac sorption on the surface of α-ZrP can be described using a film diffusion model (FD). The equilibrium weight distribution coefficient Dw for 225Ac in both hydrochloric and nitric acid reached the highest values in the concentration range 5.0–7.5 mM (14,303 ± 153 and 65,272 ± 612 mL/g, respectively). Considering the results obtained in radioactive static sorption experiments with 225Ac and in non-radioactive kinetic experiments with natEu, α-ZrP seems to be a very promising material for further construction of a 225Ac/213Bi generator.