bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrovascular co-pathology and cholinergic white matter pathways along the Lewy body continuum
Authors: Jerele Cene , Tzortzakakis Antonios , Nemy Milan , Rennie Anna , Arranz Javier , Montal Victor , Bejanin Alexandre , Aarsland Dag , Westman Eric , Fortea Juan , Lleo Alberto , Alcolea Daniel , Kramberger Milica Gregorič , Ferreira Daniel 
Published: April 2024

Abstract

Background:Dementia with Lewy Bodies (DLB) often presents with cholinergic degeneration and varying degrees of cerebrovascular disease (CVD). Radiological methods for assessing cholinergic degeneration in DLB are limited. We investigated the potential of the radiological Cholinergic Pathway Hyperintensities Scale (CHIPS) in identifying CVD-related disruptions in cholinergic white matter pathways. We compared the utility of CHIPS to other radiological and automated methods of evaluation.
Methods: We included 82 individuals (41 patients along the clinical continuum of Lewy body (LB) disease and 41 healthy controls) from the Sant Pau Initiative on Neurodegeneration cohort. We evaluated white matter signal abnormalities (WMSA) and cholinergic pathways integrity on MRI using two clinical radiological methods (CHIPS, Fazekas) and two automated methods (tractography mean diffusivity, FreeSurfer WMSA volume). Between and within study groups, we investigated associations among those measures, as well as regional atrophy, cerebrospinal fluid (CSF) biomarkers of AD co-pathology, core clinical features, and cognitive measures.
Results: Cholinergic white matter methods (CHIPS and tractography) showed a strong correlation, as did global WMSA methods (FreeSurfer WMSA volume and Fazekas). LB patients showed a significantly higher degree of WMSA in the external capsule cholinergic pathway compared to controls, without global WMSA differences. Receiver operating characteristic (ROC) analysis revealed that the CHIPS score in the posterior external capsule and the mean diffusivity in both external capsule and cingulum exceeded the threshold for an optimal biomarker in discriminating LB patients from controls. Higher CHIPS scores, Fazekas scores, and mean diffusivity from tractography were associated with more pronounced frontal atrophy in LB patients. No significant associations were found between the four WMSA and integrity methods and any of the core clinical features, cognitive measures, or CSF biomarkers in the LB group.
Conclusions: Cholinergic WMSA were more pronounced in LB patients than in healthy controls, above and beyond global WMSA. Mechanistically, CVD in cholinergic white matter may be implicated in frontal atrophy along the LB continuum. Clinically, we demonstrate the potential of CHIPS to assess cholinergic WMSA. Our findings show that CVD co-pathology may contribute to the well-known cholinergic degeneration in DLB, allowing for vascular health-focused therapies from prodromal DLB onwards.
Long-term high-intensity aerobic interval training in stage II – III breast cancer patients receiving neoadjuvant chemotherapy
Authors: Cešeiko Rūdolfs , Kļaviņa Aija , Eglītis Kristaps , Llionte Alicia , Čampa Mārtiņš , Linē Aija 
Published: April 2024

Abstract

Background. Although higher-intensity aerobic interval training (HIIT) is recognized as a modality to attenuate breast cancer (BC) treatment-induced decline in cardiorespiratory endurance and mitigate side effects, it is still really offered as an addition to treatment. Thus, this study investigated the 6-month effects and feasibility of HIIT for BC patients undergoing neoadjuvant chemotherapy (NACT).
Methods. Thirty-five women (mean age 47 ± 8 years) diagnosed with stage II-III BC before initial treatment were randomized to either the training group (TG) or non–exercise control group (CG). TG was instructed to perform 4x4 min intervals remotely at an intensity of 85-95% of peak heart rate, 2-3 times a week for 6 months. Treadmill VO2peak and functional performance were assessed before and after the exercise period.
Results. After the intervention, TG maintained VO2peak (P=0.94) but decreased in the CG by (13% ± 7%; P<0.001.), a significant difference between the groups with a large effect was absorbed post-intervention (P=0.005). Significant increases were observed (5% ± 4%; P=0.043) in the time to exhaustion for TG while it reduced in CG (9% ± 6%; P=0.003), a significant difference was apparent between the groups post-intervention (P<0.038). Moreover, the TG increased distance in a 6-min walking test (6MWT) by (7% ± 6%; P=0.006), times in a 30-s chair stand test by (19% ± 10%; P=0.003), and 5x sit-to-stand test by (20% ± 14%; P<0.001). Conversely, no changes were observed in the CG in these variables. Significant changes were present between the groups post-intervention 6MWT (P<0.001), 30 – s char stand test (P=0.05), and 5x sit-to-stand test (P=0.015).
Conclusion. 6 months of HIIT during NACT is feasible, safe, manageable, and effectively improves cardiorespiratory endurance and functional performance. These results advocate that HIIT should be considered in BC treatment.
The Mediating Effect of Bullying on "Parental Support, Peer Support Matching" and NSSI Behavior among Adolescents
Authors: Liu Huaqiang , Lan Zhensong , Huang Xuefang , Wang Qing , Deng Fafang , Li Juchao 
Published: April 2024

Abstract

Background:Being subjected to bullying is a significant risk factor for non-suicidal self-injury (NSSI) among adolescents. On the other hand, parental support, peer support, and social connectedness play protective roles in mitigating NSSI in this population. However, the precise impact of the matching effects of parental support and peer support on bullying and NSSI requires further exploration.
Methods: The study employed the "Child and Adolescent Social Support Scale," the "Delaware Bullying Victimization Scale," the "Social Connectedness Scale," and the "Ottawa Self-injury Inventory" to survey 1277 adolescents. Polynomial regression analysis and response surface analysis were applied to examine the mediating role of bullying and social connectedness in the relationship between "parental support, peer support matching" and NSSI.
Results: The results indicate that parental support (r=0.287, P<0.001), peer support (r=0.288, P<0.001), and social connectedness (r=0.401, P<0.001) serve as protective factors against NSSI in adolescents. Conversely, bullying (r=0.425, P<0.001) acts as a risk factor for NSSI in this population. Adolescents with low parental and peer support experienced more bullying than those with high parental and peer support, and those with low parental and high peer support experienced less bullying than those with high parental support and low peer support (R^2=0.1371,P＜0.001). Social connectedness moderated the effect between bullyingand NSSI in this model (β=0.006,P＜0.001).
Limitations:Due to the underrepresentation of participants and the lack of longitudinal data support, the explanatory power of causality between variables was limited. More studies will expand to the national sample and supplement a longitudinal studies to enhance the generalizability and robustness of the findings in the future.
Conclusion: This study reveals the influence mechanism of parental and peer support matching experienced by adolescents on bullying and NSSI, and the moderating role of socialconnectedness, which enriches the developmental theory of adolescent NSSI and provides a reference for the prevention and intervention of adolescent NSSI behavior.
Predictive and prognostic value of ACSL4 and GPX4 in patients with esophageal squamous cell carcinoma receiving post-operative radiotherapy
Authors: Wang Xiaohang , Xu Xin , Huang Yuhui , Rong Ling , Xu Lei , Ye Qing , Zhang Lei , Ma Xiumei , Bai Yongrui 
Published: April 2024

Abstract

Objective: Although multimodality treatment, including chemoradiotherapy and surgery has significantly improved the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a valid predictor is crucial for individualized treatment. As acyl-CoA synthetase long-chain family member 4 (ACLS4) and glutathione peroxidase 4 (GPX4) are key genes with radiation responses and constituents of the ferroptosis signaling pathway, the present study adopted ACSL4 and GPX4 protein expression to explore their predictive and prognostic value in patients with ESCC receiving adjuvant radiotherapy.
Methods: A total of 108 patients with thoracic ESCC who had undergone radical surgery and adjuvant radiotherapy were enrolled in the present retrospectively study. ACSL4 and GPX4 immunohistochemistry experiments were performed on paraffin-embedded tumor samples. The prognostic value of ACSL4 and GPX4 was examined using survival analysis, and the predictive value of ACSL4 and GPX4 for long-term survival was examined using univariate and multivariate Cox regression analyses, and verified by receiver operating characteristic (ROC) analysis.
Results: The survival analysis revealed that overall survival (OS) and disease-free survival (DFS) were significantly longer in the high ACSL4 expression group, and the DFS was significantly shorter in the high GPX4 expression group. The results of univariate and multivariate Cox regression analyses revealed that the ACSL4 expression level was an independent predictor for OS and DFS, and that the GPX4 expression level was an independent predictor for DFS. ROC analysis verified the predictive role of ACSL4 expression for DFS and OS, with an area under the curve of 0.713 and 0.663.
Conclusion: The present study demonstrates that ACSL4 and GPX4 may serve as valuable prognostic biomarkers for long-term survival, and play a key translational role in individualized therapy for patients with ESCC.
High-dose furmonertinib combined with intraventricular chemotherapy as salvage therapy for leptomeningeal metastasis from EGFR exon 20 insertion-mutated lung cancer
Authors: Yu Chuanyong , Xu Ting , Fang Hehui , Wang Xiaoyue , Liu Na , Yang Liangfeng , Fang Shencun 
Published: April 2024

Abstract

Purpose: The treatment of leptomeningeal metastasis (LM), a serious complication of advanced non-small cell lung cancer (NSCLC), presents challenges, particularly in patients with EGFR exon 20 insertion (ex20ins) mutations.
Methods: This study retrospectively analyzed data from 10 EGFR ex20ins-mutated NSCLC patients with LM admitted at our institution from May 2011 to June 2023. Circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) and matched plasma samples was analyzed using next-generation sequencing. All patients received high-dose furmonertinib combined with intraventricular chemotherapy (IVC) as salvage therapy. Data on patient demographics, treatment efficacy, and safety outcomes were collected.
Results: The most common insertion mutation identified in this study was p.A767_V769dup (n = 4, 40%), followed by D770-N771insY (n = 2, 20%). Nine patients had EGFR ex20ins occurring in the EGFR loop region following the C-helix, whereas only one patient had an EGFR ex20ins (A763_Y764insFQEA) occurring in the C-helix of the tyrosine kinase domain. LM response assessment using the RANO-LM criteria revealed that 6 patients (60%, 95% CI 26.2–87.8%) achieved a response, 3 had stable disease, and 1 had progressive disease. The median progression-free survival and overall survival were estimated to be 6.5 months and 8.8 months, respectively. The most commonly reported treatment-related adverse events were rash (n = 7) and diarrhea (n = 7), with no treatment-related deaths occurring.
Conclusions: The current study demonstrated that high-dose furmonertinib plus IVC as salvage treatment for patients with LM harboring EGFR ex20ins mutations had promising clinical benefits and a manageable safety profile.
The anti-apoptotic protein lifeguard is expressed in osteosarcoma, chondrosarcoma and soft tissue sarcoma
Authors: Senger Sebastian , Schlottmann Frederik , Strauß Sarah , Vogt Peter M. , Bucan Vesna 
Published: April 2024

Abstract

The success of modern chemotherapy in overall survival of patients with advanced stages of osteosarcoma and soft tissue sarcoma has reached a plateau. Therefore a deeper understanding of molecular mechanisms behind deregulated apoptosis in sarcoma is essential for the cure of patients with advanced stages of osteosarcoma and soft tissue sarcoma. Lifeguard (LFG) is a member of the Bax Inhibitor-1 (BI-1) protein family and has anti-apoptotic effects by inhibiting Fas-mediated cell death signaling. Although LFG has been proven to be expressed in several breast cancer tissues, the expression and function of LFG regarding apoptosis in different subtypes of sarcoma remains unclear. In the present study, the expression of LFG in osteosarcoma (50 samples), chondrosarcoma (28 samples) and soft tissue sarcoma (total 55 samples) with different tumor stages for each sarcoma subtype were analyzed. For each subtype, clinical TNM-classification and pathological grading were determined and compared to healthy corresponding tissues. Soft tissue sarcoma subtypes included liposarcoma, dermatofibrosarcoma, angiosarcoma, leiomyosarcoma, malignant schwannoma and synovial cell sarcoma. In this study, significantly higher expressions of anti-apoptotic LFG protein in osteosarcoma, chondrosarcoma and many different subtypes of soft tissue sarcoma were found, compared to corresponding healthy tissues. More importantly a positive correlation between LFG expression and tumor stage for osteosarcoma and chondrosarcoma was found. In conclusion, LFG protein might play an important role in inhibition of Fas-mediated apoptosis in osteosarcoma cells, with possible potential for targeted tumor therapy in osteosarcoma.
AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo
Authors: Tan Biqin , Yang Xinxin , Ma Junjie , Wu Shanshan , Huang Yuyu , Zhu Lulin , Li Ying , Li Qingyu , Yan Youyou , Zhang Bo , Lou Jiang , Wang Gang , Lin Nengming , Dong Rong 
Published: April 2024

Abstract

Background: Pancreatic cancer is a malignant cancer with apoor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, thedevelopment ofsensitive drugsfor pancreatic cancer is essential. AZD5153 is a novel bivalent BET bromodomain inhibitor with multiple antitumor effects on malignancy. Here, we aimed to investigate the effect of AZD5153 on the GEM sensitivity in human pancreatic cancer cells.
Methods: Sulforhodamine B (SRB), clone formation assays were designed to characterize the cell viability and clone formation after treatment with AZD5153 and/or GEM. Flow cytometry and western blotting were used to identify the cell apoptosis. RNA-seq analysis, western blotting and qPCR were also conducted to confirm the signaling pathway involved in it.
Results: As a result, AZD5153 presented a strong anti-proliferation activity, exerted the synergistic effects in combined with GEM both in vitro and in vivo. AZD5153 combined with GEM induced cell apoptosis. Further investigations revealed that the combination of AZD5153 and GEM decreased the phosphorylation of ERK/mTOR signaling proteins. Besides, the expression of BRD4 is unchanged, while the MUC2 expression is remarkable decreased after combination treatment.
Conclusion: In conclusion, these results suggested that AZD5153 might be an excellent GEM sensitizer in pancreatic cancer.
Indian Sign Language Recognition System using GAN and Ensemble based approach
Authors: Shirude Rhuchita , Khurana Soumya , Sreema R , Turuk Mousami , Jagdale Jayashree , Chidrewar Saurabh 
Published: April 2024

Abstract

Sign language is the most prominent mode of communication for people who have hearing problems. Continuous sign language recognition is a poorly supervised job that involves identifying sign gestures with no prior knowledge of the temporal boundaries between consecutive signs. Most modern techniques focus on the extraction of visual features, with no use of text or contextual information to boost recognition accuracy. Furthermore, in the field of sign language recognition, the potential of deep generative models to generate realistic sign language images has not been examined in depth. To achieve that aim, the Recognition System for Indian Sign Language is a novel approach for continuous sign language recognition using a generative adversarial network architecture. The system is trained on the self-created dataset, which includes numbers from 0 to 9, alphabets from A to Z, and 50 distinct words with static gestures. The proposed approach is based on the idea of using a generative adversarial network (GAN) to generate realistic sign language gestures, which are then used to train a recognition model. By training these networks together, the generator learns to produce increasingly realistic gestures, while the discriminator learns to distinguish between real and synthetic generators with increasing accuracy. The network architecture involves the use of DCGAN and SRGAN, while the transfer learning algorithms used are ResNet-50, VGG-19, and AlexNet. The transfer learning algorithms enable the network to learn from pre-trained models and achieve better accuracy in sign language recognition. Overall, the Recognition System for Indian Sign Language is a promising approach for continuous sign language recognition. By using a combination of deep generative models and transfer learning algorithms, the network can accurately detect and translate sign language gestures into textual language. The proposed approach shows recognition accuracy of 92.5% and robustness, and it has the potential to improve the recognition of sign language gestures in real-world scenarios. This has the potential to greatly improve communication for individuals who are speech and hearing impaired.
Rapid real-time quantitative colorimetric LAMP methodology for field detection of Verticillium dahliae in crude olive-plant samples
Authors: Megariti Maria , Panagou Alexandra , Patsis Georgios , Papadakis George , Pantazis Alexandros K. , Paplomatas E. J. , Tzima Aliki K. , Markakis Emmanouil A. , Gizeli Electra 
Published: April 2024

Abstract

Background: Verticilium dahliae is the most important wilt pathogen of olive trees with a broad host range causing devastating diseases currently without any effective chemical control. Traditional detection methodologies are based on symptoms-observation or lab-detection using time consuming culturing or molecular techniques. Therefore, there is an increasing need for portable tools that can detect rapidly V. dahliae in the field.
Results: In this work, we report the development of a novel method for the rapid, reliable and on-site detection of V. dahliae using a newly designed isothermal LAMP assay and crude extracts of olive wood. For the detection of the fungus, LAMP primers were designed targeting the internal transcribed spacer (ITS) region of the rRNA gene. The above assay was combined with a purpose-built prototype portable device which allowed real time quantitative colorimetric detection of V. dahliae in 35 min. The limit of detection of our assay was found to be 0.8 fg/μl reaction and the specificity 100% as indicated by zero cross-reactivity to common pathogens found in olive trees. Moreover, detection of V. dahliae in purified DNA gave a sensitivity of 100% (Ct< 30) and 80% (Ct>30) while the detection of the fungus in unpurified crude wood extracts showed a sensitivity of 80% when multisampling was implemented. The superiority of the LAMP methodology regarding robustness and sensitivity was demonstrated when only LAMP was able to detect V. dahliae in crude samples from naturally infected trees with very low infection levels, while nested PCR, SYBR and TaqMan qPCR failed to detect the pathogen in an unpurified form.
Conclusions: This study describes the development of a new real time LAMP assay, targeting the ITS region of the rRNA gene of V. dahliae in olive trees combined with a 3D-printed portable device for field testing using a tablet. The assay is characterized by high sensitivity and specificity as well as ability to operate using directly crude samples such as woody tissue or petioles. The reported methodology is setting the basis for the development of an on-site detection methodology for V. dahliae in olive trees, but also for other plant pathogens.
Development of a Novel Method to Characterize Shock Waves Interaction With Solid Objects
Authors: Rahman Mohammad , Mohamed Ahmed , Sweis Alexander , Chavez Joshua , Vorobieff Peter 
Published: April 2024

Abstract

Nuclear explosion in a densely populated area is the worst that can happen to any country in the world due to enormous loss of life, property and severe economic damage. Nuclear explosions immediately cause radiological damage and destruction of infrastructure. This hydro-magnetic shock propagation due to blast gives rise to simultaneous signals around the world. The effect of shockwave from nuclear explosion is an area that can be used to handle post and pre-disaster from nuclear explosion. This study focuses on the effects of shockwave on solid objects oriented in different formation. Experiments conducted in a horizontally placed shock tube and a solid object holder on the floor of the test section. These solid objects placed inside the test section of a shock tube collided with a planner shock wave which was generated but rupturing a diaphragm of different thickness. Four high speed pressure transducers strategically placed at different locations of this shock tube were used to characterize the blasts as well as interaction with the samples. A high speed Kronos and Phantom camera were used to record the exact moment of interaction to characterize the solid objects under the impact of different shock waves. Representative results of these experiments are reported here along with review of previous works done on this area.