bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decitabine regulates the resistance of Hep3B to sorafenib through demethylation
Authors: zhang Miao , han Qiaoqiao , miao Yu , zhao Tianyu , wang Libo , xu Yongdeng , Wang Ze , Cui Tao , Yi Xiulin 
Published: April 2024

Abstract
Purpose：To investigate the mechanism of drug resistance in hepatocellular carcinoma treated with sorafenib from an epigenetic perspective , and to examine the effect of Sorafenib sensitivity on hepatocellular carcinoma after in vitro and vivo combination with the epigenetic drug decitabine . This research aims to provide new ideas and methods for the clinical treatment of hepatocellular carcinoma.
Methods: Using the GEPIA 2 database, the expression of organic anion transporting polypeptide 1B3 (OATP1B3) gene in different tumors and adjacent normal tissues of 508 patients with primary hepatocellular carcinoma (HCC) was retrieved. The Kaplan-Meier method was used to perform survival analysis by grouping based on the expression levels of this gene.. Using the TCGA-LIHC dataset to analyze the correlation between SLCO1B3 and DNMTs. Additionally, OATP1B3 promoter methylation levels were detected in Hep3B, HepG2, SNU182, LM3, HUH7, and SNU387 cells using bisulfite methylation data. The expression of OATP1B3 was assessed by RT-qPCR and Western Blot. The effect of Sorafenib in combination with DAC on the proliferation of Hep3B cells was dynamically monitored using RTCA-eSight. The mechanism was further verified in vivo using an in situ implantation tumor model in nude mice. The expression of OATP1B3 in tumor tissues was detected by immunohistochemical staining and Western Blot.
Results: Individuals with high expression of the OATP1B3 gene have a significantly higher overall survival rate than individuals with low expression. The negative correlation between SLCO1B3 expression and the DNA methyltransferase DNMT1.In Hep3B,the DNA methylation of OATP1B3 results in decreased protein expression. After DAC incubation, OATP1B3 expression was up-regulated. Following DAC administration, Hep3B proliferated at a considerably lesser rate than the Sorafenib group. The absorption of Sorafenib by Hep3B was raised by 1.87-fold following co-administration of DAC. According to the Hep3B xenograft nude mice model data, the tumor sizes in the combination group were all noticeably lower after 21 days of dosing than those in the Sorafenib alone, DAC, and Control groups. Both the combination group and the DAC group had significantly greater levels of OATP1B3 expression than control and Sorafenib group.
Conclusion: By inhibiting the DNA methylation of SLCO1B3 and increasing the expression of OATP1B3, which mediates Sorafenib transmembrane transporter protein, the epigenetic drug decitabine can enhance the accumulation of Sorafenib in hepatocellular carcinoma cells. This enhances sensitivity in hepatocellular carcinoma cells and reverses resistance to Sorafenib.
TSNet:A Two-stage Network for Image Dehazing with Multi-scale Fusion and Adaptive Learning
Authors: Gong Xiaolin , Zheng Zehan , Du Heyuan 
Published: April 2024

Abstract
Image dehazing has been a popular topic of research for a long time. Previous deep learning-based image dehazing methods have failed to achieve satisfactory dehazing effects on both synthetic datasets and real-world datasets, exhibiting poor generalization. Moreover, single-stage networks often result in many regions with artifacts and color distortion in output images. To address these issues, this paper proposes a two-stage image dehazing network called TSNet, mainly consisting of the multi-scale fusion module (MSFM) and the adaptive learning module (ALM). Specifically, MSFM and ALM enhance the generalization of TSNet. The MSFM can obtain large receptive fields at multiple scales and integrate features at different frequencies to reduce the differences between inputs and learning objectives. The ALM can actively learn of regions of interest in images and restore texture details more effectively. Additionally, TSNet is designed as a two-stage network, where the first-stage network performs image dehazing, and the second-stage network is employed to improve issues such as artifacts and color distortion present in the results of the first-stage network. We also change the learning objective from ground truth images to opposite fog maps, which improves the learning efficiency of TSNet. Extensive experiments demonstrate that TSNet exhibits superior dehazing performance on both synthetic and real-world datasets compared to previous state-of-the-art methods. The related code is released at https://github.com/zzhlovexuexi/TSNet
Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors
Authors: Otuokere Ifeanyi E 
Published: April 2024

Abstract
The transfer of cytochrome c (cyt c) from the mitochondria to the cytosol is commonly regarded as the final stage in the mitochondria-mediated apoptotic response, where there is no possibility of intervention. A potential approach for the development of antiapoptotic medicines involves the inhibition of cyt c interactions. Therefore, it is necessary to develop more effective pharmaceuticals that can inhibit the functioning of cytochrome c peroxidase. The PyRx virtual screening programme was used to conduct a molecular docking investigation on five indolin-2-one (IDL) analogues as inhibitors of cytochrome c peroxidase. The study on ADME was conducted via the SWISSADME server. The Schrondinger suite was utilized to do molecular dynamics (MD) analysis. The binding affinity of the five IDL analogues were − 14.0 to − 15.1 Kcal/mol. The interactions with the receptor (2X08) were facilitated through various mechanisms, including hydrophobic interactions, salt bridges, hydrogen bonds, π-stacking, and electrostatic bonds. These interactions were facilitated by the presence of specific amino acid residues, namely TRP 51A, PHE 158A, LEU 171A, ALA 174A, PHE 266A, PHE 266A, and LEU 239. The present study made predictions for the ADME features of the substances under investigation, revealing favourable pharmacokinetic characteristics. The study additionally predicted the drug-like characteristics of the compounds and determines their oral bioavailability, indicating favourable bioavailability ratings. The molecular dynamics simulations demonstrated the high stability of the optimal IDL analogue with the 2X08 binding pocket. It was concluded that these compounds could be used as potential drugs for the inhibition of cytochrome c peroxidase.
Immediate Fortification of Human Milk with a Bovine Milk Derived Human Milk Fortifier in Very Low Birth Weight Infants: A Randomized Clinical Trial
Authors: STANSFIELD Brian , Wynter Zanna , Gorham Jane Anne , Thompson Amy , Mundy Cynthia , Waller Jennifer 
Published: April 2024

Abstract

Objective
Double-blind randomized control trial of early addition of a bovine milk derived human milk fortifier (HMF) in very low birth weight (VLBW) infants (NCT05228535).
Methods
VLBW infants were randomized to receive bovine milk derived HMF with first feedings or delayed fortification at 80 ml/kg/day. Anthropometrics were assessed weekly through 36 weeks postmenstrual age (PMA). Unadjusted and adjusted (race, gender, gestational age, and birth weight) differences between study arms were examined using two-sample t-test and ANCOVA, respectively.
Results
Fifty-two VLBW infants (57% female, 60% Black) were enrolled. Baseline demographics did not differ between groups. Weight velocity at DOL 28 did not differ between study arms. Secondary outcomes including NPO occurrence, incidence of metabolic acidosis, NEC, retinopathy, or late onset sepsis did not differ between groups.
Conclusion
Immediate fortification of enteral feedings with a bovine milk derived HMF is safe and well-tolerated although no clear growth benefit could be established.
Levels of Evidence: III
Association of comprehensive geriatric assessment with multidisciplinary treatment decision and adherence in elderly breast cancer patients
Authors: Jin Yihua , Yu Jing , Zhang Xu , Zhu Siji , Shen Kunwei , Chen Xiaosong 
Published: April 2024

Abstract

Purpose
To assess the association of comprehensive geriatric assessments (CGA) and multidisciplinary team (MDT) treatment decision and adherence in elderly breast cancer patients.
Methods
Aged ≥ 60 patients were prospectively enrolled between June 2019 and January 2020. CGA was surveyed by 9 questionnaires before breast cancer surgery. Adjuvant treatment decisions were made by MDT discussion. Factors associated with adjuvant treatment decision were analyzed. Patients’ adherence to MDT decision according to CGA were also analyzed.
Results
A total of 211 patients were included: 87 (41.2%), 102 (48.3%), and 22 (10.4%) patients with age between 60–69, 70–79, and over 80, respectively. Patients with lower scores of VES-13 (95.7% vs 77.8%, P = 0.021) and higher scores of BI (96.7% vs 75%, P = 0.003) were more likely to be recommended with adjuvant radiotherapy. Rates of adjuvant chemotherapy recommendation was also higher for patients with lower VES score (46.8% vs 21.1%, P = 0.004) and higher BI score (45.6% vs 27.5%, P = 0.037). Adherence to adjuvant chemotherapy recommendation was found better in patients with fitter scores of CCI-adjustment (80.3% vs 53.8%, P = 0.038)
Conclusion
CGA was associated with adjuvant radiotherapy MDT decision, which also influenced the adherence to MDT adjuvant chemotherapy recommendation in elderly breast cancer patients.
Optimizing the Treatment of Acute Promyelocytic Leukemia: A Maintenance-Free Strategy for Complete Remission
Authors: Kamruzzaman Muhammad , Proma Sanghita Banik , Pramanik Mohit Kumar , Afrin Marzia , Islam Md. Sirajul 
Published: April 2024

Abstract
Background:
Acute promyelocytic leukemia (APL) is a distinct variant of acute myeloid leukemia (AML), comprising 5–10% of all AML cases. Characterized by the t(15;17) chromosomal translocation, APL presents a unique challenge due to its associated bleeding manifestations and coagulopathy, emphasizing the need for urgent and specialized management.
Methods:
This prospective open-label pilot study enrolled ten newly diagnosed APL patients, stratified based on the Sanz risk score. Low and intermediate-risk patients underwent ATRA-ATO induction therapy, followed by consolidation therapy. High-risk patients received additional Daunorubicin or Mitoxantrone alongside ATRA-ATO induction. The study evaluated patient characteristics, clinical findings, laboratory results, and treatment outcomes, focusing on complete remission (CR) after induction therapy and disease-free survival (DFS) at 3 years.
Results:
The study observed a 100% CR rate after induction therapy, with favorable 3-year DFS and event-free survival (EFS). No treatment failures, mortality, or relapses were reported. Laboratory findings and clinical outcomes were consistent with established characteristics of APL. The absence of maintenance therapy minimized associated toxicities, supporting the safety and efficacy of the chemotherapy-free ATRA-ATO approach.
Conclusion:
This pilot study underscores the potential paradigm shift in APL management by demonstrating the safety and efficacy of a chemotherapy-free ATRA-ATO strategy. The results align with the 2023 National Comprehensive Cancer Network (NCCN) update, endorsing the ATRA-ATO regimen for APL. The ongoing nature of the research emphasizes its contribution to evolving APL management practices, encouraging further comprehensive evaluations on a broader scale.
Guidelines for Sport Compressive Garments Design: Finite Element Simulations Approach
Authors: Cudicio Alessandro , Cogliati Marta , Bonardi Alberto , Benedini Marco , Rizzi Gianluca 
Published: April 2024

Abstract

Purpose
Despite compression garments (CG) having acquired significant attention in the sports field, there remains ongoing debate regarding their actual effectiveness in enhancing athletic performance and expediting post-exercise recovery. This article delves into various aspects, with a focus on CG design and the materials they are made of, aiming to analyze the importance of personalized compression strategies based on individual anthropometric measurements and non-linear compression designs.
Methods
Through anthropometric analysis of 40 healthy participants, this study examined the morphological characteristics of the lower limb and their implications for CG design.
Results
Measurements of limb length and circumferences revealed complex interactions among anatomical variables, emphasizing the need for customized and adaptable device design. Finite element simulations further clarified the challenges in achieving uniform pressure gradients along the lower limb, highlighting the limitations of one-piece devices and suggesting tailored segmented designs for individual limb segments.
Conclusion
The results demonstrated that while one-piece devices may offer simplicity, they often fail to provide optimal compression due to non-linear variations in limb dimensions. Conversely, segmented devices, particularly those with bilinear progression, exhibited superior performance in applying targeted compression across different limb segments. This more detailed approach to customization could significantly contribute to optimizing outcomes and user comfort.
Aphid species (Hemiptera: Aphididae) recorded for the first time from the Tunisian network
Authors: Boukhris-Bouhachem Sonia , Souissi Rebha , Boukteb’s Amal 
Published: April 2024

Abstract
In a previous paper, one hundred thirty aphid taxa were recorded in Tunisia including 103 species. In this present work, we give additional records from the Cap Bon region in the North East of Tunisia. Eighty-one new species and 8 taxa were added for the first time. These records are based on daily suction trap and weekly yellow trap catches for 14 years from 2005 to 2018. This addition brings the number of aphids from Tunisia to 219 taxa. The aphid species (86) and subspecies (3) from the Aphididae family were ranged in 7 subfamilies: Aphidinae (64 species and 28 genera), Eriosomatinae (9 species and 6 genera), Chaitophorinae (2 species and 2 genera), Greenideinae (2 species and 1 genus), Lachninae (4 species and 3 genera), Calaphinae (6 species and 5 genera), Saltuaphidinae (2 species and 1 genera). All specimens are conserved in microscopic slides in the Plant Protection Laboratory of INRAT. Furthermore, among this list, other potential aphids as virus vectors were identified in this region.
The efficacy and safety of fluid gelatin for LSS undergoing PE-ULBD : a prospective, randomized controlled trial
Authors: Yan Hao , Yao Ruzhan , Yu Mingdong , Dou Rongsheng , Zhang Yu , Wang Huaibin , Shi Yulin , Liu Weiqiang 
Published: April 2024

Abstract
Background. Absorbable fluid gelatin is a novel collagen hemostatic agent that has been validated in multiple surgical procedures. However, the efficacy of using this hemostatic agent during percutaneous endoscopic unilateral laminectomy for bilateral decompression (PE-ULBD) remains controversial. Our research aims to conduct a prospective randomized controlled trial to investigate the efficacy and safety of this hemostatic material in patients undergoing PE-ULBD for lumbar spinal stenosis (LSS).
Methods. From October2023 to February 2024, a total of 90 patients with LSS who underwent PE-ULBD, were enrolled in this study. The 90 patients were randomly divided into two groups: the TGTMS group (45 cases, using fluid gelatin) and the non-TGTMS group (45 cases, not using fluid gelatin). Primary outcomes included perioperative blood loss and intraoperative clotting time. Secondary outcomes encompassed surgical time, length of stay, hospital expenses, and complications.
Results. There were statistically significant differences in primary outcomes which included perioperative blood loss and intraoperative clotting time between patients who received the TGTMS group and the control. The secondary outcomes of the two groups include surgical time, length of stay, hospital expenses and complications, among which only surgical time has significant statistical differences.
Conclusions. When patients with LSS undergo PE-ULBD, the prophylactic use of fluid gelatin can reduce intraoperative and postoperative bleeding without any observed additional complications. Therefore, the prophylactic use of fluid gelatin in PE-ULBD is an effective and safe strategy.
Trial registration: The study was registered on the Chinese Clinical Trial Registry website(www.chictr.org.cn) with registration number ChiCTR2300077538.
A Reproducible and Robust Representation of Tibiofemoral Kinematics of the Healthy Knee Joint during Stair Descent using REFRAME – Part I: REFRAME Foundations and Validation
Authors: Ortigas-Vásquez Ariana , Taylor William R. , Postolka Barbara , Schütz Pascal , Maas Allan , Woiczinski Matthias , Grupp Thomas M. , Sauer Adrian 
Published: April 2024

Abstract

In clinical movement biomechanics, kinematic measurements are collected to characterise the motion of articulating joints and investigate how different factors influence movement patterns. Representative time-series signals are calculated to encapsulate (complex and multidimensional) kinematic datasets succinctly. Exacerbated by a lack of consensus around joint coordinate frame definitions, the influence of local frame orientation and position on the characteristics of the resultant kinematic signals has been previously proven to be a major limitation. Consequently, for consistent interpretation of joint motion (especially direct comparison) to be possible, differences in local frame position and orientation must first be addressed. Here, building on previous work that introduced a frame orientation optimisation method and demonstrated its potential to induce convergence towards a consistent kinematic signal, we present the REference FRame Alignment MEthod (REFRAME) that addresses both rotational and translational kinematics, is validated here for a healthy tibiofemoral joint, and allows flexible selection of optimisation criteria to fittingly address specific research questions. While not claiming to improve the accuracy of joint kinematics or reference frame axes, REFRAME does enable a representation of knee kinematic signals that accounts for differences in local frames (regardless of how these differences were introduced, e.g. anatomical heterogeneity, use of different data capture modalities or joint axis approaches, intra- and inter-rater reliability, etc.), as evidenced by peak root-mean-square errors of 0.24° ± 0.17° and 0.03 mm ± 0.01 mm after its implementation. By using a self-contained optimisation approach to systematically re-align the position and orientation of reference frames, REFRAME allows researchers to better assess whether two kinematic signals represent fundamentally similar or different underlying knee motion. The openly available implementation of REFRAME could therefore allow the consistent interpretation and comparison of knee kinematic signals across trials, subjects, examiners, or even research institutes.
The Effects of an 8-Week Dynamic Neuromuscular Stabilization Exercise on Pain, Functional Disability, and Quality of Life in Individuals with Non-specific Chronic Low Back Pain: A Two-Month Follow-up Study
Authors: Rabieezadeh Alireza , Mahdavinejad Reza , Sedehi Morteza , Adimi Meisam 
Published: April 2024

Abstract

Background
Low back pain is a common disorder and is considered one of the leading causes of disability worldwide, resulting in adverse health, social, and economic outcomes. This study aimed to investigate the effects and durability of 8-week Dynamic Neuromuscular Stabilization (DNS) exercises on pain, functional disability, and quality of life in individuals aged 30 to 50 years with non-specific chronic low back pain.
Methods
This research employed a pretest, posttest design with a follow-up period, in which 29 participants (16 in the control group and 13 in the exercise group) remained until the end of the study. Pain intensity, functional disability, and quality of life were assessed using the Visual Analog Scale (VAS), the Oswestry Disability Index, and the SF-36 questionnaire, respectively, before intervention, immediately after, and two months post-intervention. The control group continued their routine daily activities, while the exercise group performed DNS exercises three times a week for 8 weeks. Data was analyzed using mixed-design ANOVA (P ≤ 0.05).
Results
The results showed improvements in pain (p < 0.001), functional disability (p = 0.02), and quality of life (p = 0.01) in the exercise group at the posttest compared to the pretest. However, the durability of the exercise effects at the follow-up assessment was not sustainable compared to the posttest and pretest (P > 0.05).
Conclusion
An 8-week period of DNS exercises can improve pain, functional disability, and quality of life in individuals with non-specific chronic low back pain. However, a 2-month period of detraining can reduce the positive outcomes of these exercises.
Molecular, hierarchical and acoustical cues promote mesenchymal stromal cell differentiation toward tympanic membrane regeneration
Authors: Anand Shivesh , Runzer Claudia Del Toro , Balmayor Elizabeth Rosado , Griensven Martijn van , Moroni Lorenzo , Mota Carlos 
Published: April 2024

Abstract
Stem cell therapies using mesenchymal stromal cells (MSCs) have recently emerged as a promising approach for the treatment of tympanic membrane (TM) injuries. However, the role of essential biochemical, biophysical, and biomechanical signals in guiding the MSC differentiation for TM applications remains unexplored. Therefore, this study aims to address the existing knowledge gap by applying three distinct stimulation mechanisms – molecular, hierarchical, and acoustical – on biofabricated TM scaffolds. In this regard, relevant bioactive molecules were identified to trigger the desired expression of TM-specific genes on electrospun meshes. Subsequently, additive-manufactured filaments were deposited on the nanofibrous meshes to investigate the influence of 3D hierarchy. Finally, acoustical stimulation was applied using a custom-built bioreactor setup, partially mimicking the native tissue niche. The acousto-vibrational characterization of the stimulated samples revealed an amplified oscillatory behavior at specific frequencies, which was shown to positively impact the TM wound healing mechanism. In summary, this work demonstrates that a synergistic integration of suitable bioactive agents, 3D hierarchical structures, and acoustical vibrations promotes the formation of an aligned extracellular matrix relevant for TM regeneration.