bluuebunny/crossref_metadata_2025_split huggingface dataset:
L3MBTL1, a polycomb protein, promotes Osimertinib Acquired resistance through Epigenetic Regulation of DNA damage response in lung adenocarcinoma
Authors: Zhang Zihe , Li Yongwen , Shi Ruifeng , Xu Songlin , Zhu Guangsheng , Cao Peijun , Huang Hua , Li Xuanguang , Zhang Hongbing , Liu Minghui , Chen Chen , Liu Hongyu , Kang Chunsheng , Chen Jun 
Published: May 2023

Abstract

Osimertinib is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) that was approved for patients with EGFR T790M resistance mutations as first- or second-line treatment for EGFR-positive patients. Resistance to Osimertinib inevitably develops and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is linked to an abnormal DNA damage response (DDR) and chromatin remodeling in lung adenocarcinoma cells. We found that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) is involved in the DDR and Osimertinib resistance by regulating chromatin structure. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination and stabilized its expression in Osimertinib-resistant cells. L3MBTL1 reduction combined with Osimertinib treatment significantly inhibited DNA damage, proliferation, and invasion of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds to histones throughout the genome and plays a critical role in EGFR-TKI resistance, which also competes with 53BP1 binding to H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings indicate that L3MBTL1 inhibition represents a novel approach to circumvent EGFR-TKI acquired resistance.
A realistic upper-limb musculoskeletal model for overall muscle activation estimation
Authors: Barjavel Tristan , Proietti Tommaso , Pierella Camilla , Micera Silvestro 
Published: May 2023

Abstract
The human upper-limb can perform complex tasks thanks to the ability of the central nervous system (CNS) to control and modulate the activation of more than 40 muscles. A deeper understanding of the strategies implemented by the CNS to perform these movements could help develop more effective rehabilitation protocols. Unfortunately, given the large number of muscles acting on the shoulder and the arm, and their positions with respect to each other, a simultaneous electromyographic (EMG) recording of all the upper-limb's muscles is not feasible in practice. Numerical musculoskeletal models could represent a useful alternative approach to gather this kind of information. Here, we develop a new realistic upper-limb biomechanical model which uses a combination of few recorded EMG data (up to max N=16) and an inverse dynamics model to predict the overall upper-limb muscle activations (N=42). With data from five healthy subjects performing 3D upper-limb movements, the predictions from this EMG-assisted model were compared to: 1) a full set of 16 arm muscles EMG data, 2) a model using none of the these recorded EMG data (standard static-optimization). While predicted signals from the EMG-assisted and static-optimization led to a 3.4% and 2.3% error respectively in the resulting moment of joint when fed into the movement dynamics, the EMG-assisted method presented a more physiological sharing of the muscle activations and variations of errors with respect of the activations from EMG signals for non used muscles in a comparison leave-one-out method. These results demonstrate the ability of the proposed musculoskeletal model to be used as a tool to evaluate healthy motion data, and open up to the application of such a strategy to analyze impaired individuals motion data and to compare inter-subject activation behaviours in the future.
Serum Neurofilament Predicts Mortality and Indicates Accelerated Neurodegeneration in Late-Stage Parkinson’s Disease
Authors: Bendig Jonas , Schnalke Nils , Klingelhoefer Lisa , Reichmann Heinz , Akgün Katja , Ziemssen Tjalf , Falkenburger Björn , Frank Anika 
Published: May 2023

Abstract
Background
A high percentage of dopaminergic axons are already lost at the time of diagnosis, current studies on neuroprotective agents focus mainly on the early stages of Parkinson’s disease (PD). Nevertheless, PD progresses slowly during the first years, making clinical trials challenging. The final phase of the disease, however, is characterized by a rapid deterioration with clinical milestones marking the transition.
Objective
To investigate whether PD is associated with increased neurodegeneration in the late stage rather than a functional or age-dependent deterioration.
Methods
Neurodegeneration was quantified in n = 118 patients with PD using serum neurofilament light chain (sNfL) as a biomarker. Late-stage PD was defined by a minimum disease duration of five years. The presence of clinical milestones (hallucinations, dementia, recurrent falls, and admission to a nursing home) and mortality was determined based on chart review.
Results
sNfL was higher in patients with late-stage PD who presented at least one clinical milestone and increased with a higher number of milestones (Spearman’s ρ = 0.66, p < 0.001). Above a cut-off value of 26.9 pg/ml, death was 13.6 times more likely (95% CI: 3.53–52.3, p < 0.001), corresponding to a sensitivity of 85.0% and a specificity of 86.8% (AUC 0.91, 95% CI: 0.85–0.97). Similar values were obtained when using an age-adjusted cut-off percentile of 90% for sNfL.
Conclusion
Our findings suggest that the rate of ongoing neurodegeneration is higher in advanced PD than in earlier disease stages, turning patients with advanced PD into an interesting target group for neuroprotective strategies. In this context, measuring sNfL could help identify patients at risk for clinical deterioration and in addition serve as an objective outcome measure for clinical trials.
Rehabilitation Assistance System for Limb Motor Function Based on Deep Learning
Authors: Liu Yun-an , Li Zengxi , Yu Yi 
Published: May 2023

Abstract
With the development and dissemination of the concept of smart medical care, people's attention to their own health and smart medical system is gradually increasing. In medical activities, the rehabilitation assistance system is very important for patients, and the family and entertainment of the rehabilitation assistance system is the general trend. At the same time, the role of the rehabilitation assistance system is largely affected by its algorithm and function settings. Therefore, it is necessary to introduce deep learning (DL) algorithms to optimize the rehabilitation assistance system. In view of the above problems, this paper used the pre-training label pre-judgment algorithm and the sample classification training method to conduct scientific research and analysis on the limb motor function rehabilitation assistance system. At the same time, a new rehabilitation assistance system including signal acquisition system, local monitoring system and medical center monitoring system was designed. The results of the experimental test showed that this new limb motor function rehabilitation assistance system could better collect the user's biological signals because of the addition of DL. The recognition of the signal has been improved to an accuracy of about 45%, which showed that the research on the rehabilitation assistance system of limb motor function based on DL could better provide unique services for the rehabilitation of patients.
Magma mass increase under Sakurajima Volcano, Japan, inferred from campaign relative gravity and leveling data from 1975 to 1992: An interpretation from volcanic gas studies
Authors: Oyanagi Ryo , Kazama Takahito , Kazahaya Ryunosuke , Miyagi Isoji , Yamamoto Keigo , Iguchi Masato 
Published: May 2023

Abstract
Temporal variations of volume and mass in the magma chambers of Sakurajima Volcano were modeled using leveling and relative gravity data collected around the volcano during the eruptive period from 1975 to 1992, to reveal a physical mechanism for the excessive gravity increase observed at the volcano. The following two deflation sources were estimated from the leveling data: a deeper source of -4.2 ×106 m3/yr located 8000 m deep beneath Aira Caldera, and a shallower source of -7.25 × 105 m3/yr located 3600 m deep beneath the center of Sakurajima Volcano. These deflation sources cannot fully explain the gravity increase of up to 15.75 microGal/yr observed at the volcano, because a gravity increase of only <3.27 microGal/yr is expected from the two deflation sources. After the effect of the deflation sources was subtracted from the observed gravity change, the residual gravity of up to 12.48 microGal/yr was then modeled by a point mass increase under the volcano. The estimated rate of the mass increase was 4.50 × 1010 kg/yr, and the position of the point mass agreed with that of the shallower magma chamber within its error range. This result suggests that the shallower magma chamber gained mass despite the chamber deflation during the 1975-1992 eruptive period, and can be quantitatively explained by the accumulation of degassed magma in the shallower chamber. Our modeling results also suggest the importance of gravimetry in addition to crustal deformation observations in quantifying the rate of magma mass supply, because the magma supply to the deeper chamber was calculated to be +5.39 × 1010 kg/yr from the gravity and leveling data, which is six times greater than that calculated from the leveling data only.
Congenital Hemangiomas with Hypovolemic Shock, Anemia and Prolonged Jaundice in a Neonate: A Case Report.
Authors: Aslamzai Mansoor , Hakimi Turyalai , Mokhlis Abdul Hakim 
Published: May 2023

Abstract

Background: Congenital hemangioma is an extremely rare congenital anomaly in newborn babies and may complicate life-threatening events, including bleeding.
Case Presentation: We present a very rare case of noninvoluting congenital hemangiomas along with hypovolemic shock, anemia, and prolonged jaundice in a six-day-old girl. Clinically, they were observed at birth and complicated by bleeding, hypovolemic shock, anemia, and jaundice during the first two weeks of life. These diseases were diagnosed by medical history, physical examination, blood analysis, and doppler ultrasonography of the skin lesion. Her critical condition improved after supportive treatment, and she was discharged from the hospital. Since the index case of congenital hemangioma was associated with parental consanguinity, a genetic basis may have played a role in the pathogenesis of this anomaly. Furthermore, there will be an association between congenital hemangioma and prolonged neonatal jaundice.
Discussion and Conclusions: Congenital hemangiomas can result in life-threatening complications and may have a role in the pathogenesis of prolonged neonatal hyperbilirubinemia.
Electric field enhancement breakdown caused by the pulse formation and transmission of parallel-plate Blumlein line
Authors: Shen Yi , Mao Ye , Liu Yi , Zhang Huang , Xia Liansheng 
Published: May 2023

Abstract

The parallel-plate Blumlein line generates pulsed square waveform and is widely used in the field of pulse power technology. This paper finds that the electromagnetic field leakage of planar transmission line will cause the electric field enhancement phenomenon in the planar transmission line far from the switch during the pulse formation and transmission of parallel-plate Blumlein line. As the electromagnetic wave propagates to the load end, the electric field enhancement phenomenon becomes most serious, and which even causes the bulk breakdown of planar transmission line far from the switch. And the breakdown phenomenon caused by the electromagnetic field leakage has been confirmed by statistics of experimental data. In view of this electric field enhancement effect, this paper proposes an electrode structure design that can reduce the electric field enhancement effect, and the simulation result shows that the optimized electrode structure can significantly reduce the electric field enhancement induced by the electromagnetic field leakage of planar transmission line. Understanding the breakdown phenomenon caused by the electromagnetic field leakage is great significance for the design of anti-electromagnetic radiation and the design of pulsed electric field insulation.
Description of Novel Molecular Factors In Lumbar DRGs And Spinal Cord Factors Underlying Development Of Neuropathic Pain Component In The Animal Model Of Osteoarthritis
Authors: Malek-Chudzik Natalia , Mlost Jakub , Kostrzewa Magdalena , Rajca Jolanta , Starowicz Katarzyna 
Published: May 2023

Abstract
Osteoarthritis (OA) is one of the most common joint disorder, with pain accompanied by functional impairment, as the most pronounced clinical symptom. Currently used pharmacotherapy involves symptomatic treatment, that do not always provide adequate pain relief. This may be due to concomitance of central sensitization and development of neuropathic features in OA patients. Here we performed studies in the animal model of OA to investigate of the neuropathic component.
Intraarticular injection of monoiodoacetate (MIA, 1mg) was used to induce OA in Wistar male rats. Development of pain phenotype was assessed by behavioral testing (PAM test and von Frey’s test), while corresponding changes in dorsal root ganglia (DRGs L3-L5) and spinal cord (SC) gene expression were assessed by means of qRT-PCR technique. We also performed microtomography of OA affected knee joints to correlate level of bone degradation with observed behavioral and molecular changes.
We observed gradually developing remote allodynia after MIA treatment, indicating presence of neuropathic component. Our results showed that, amongst DRGs innervating knee joint, development of central sensitization is most likely due to peripheral input of stimuli through DRG L5. In SC, development of secondary hypersensitivity correlated with increased expression of TAC1 and NPY.
Our studies provided molecular records on abnormal activation of pain transmission markers in DRG and SC during development of OA, that are responsible for the manifestation of neuropathic features. Obtained results increase insight into molecular changes occurring in the neuronal tissue during OA development and may contribute to readdressing treatment paradigms.
Peak Detection in Intracranial Pressure Signal Waveforms: A Comparative Study
Authors: Wei Miaomiao , Krakauskaite Solventa , Subramanian Sreya , Scalzo Fabien 
Published: May 2023

Abstract
Background:
The monitoring and analysis of quasi-periodic biological signals such as electrocardiography (ECG), intracranial pressure (ICP), and cerebral blood flow velocity (CBFV) waveforms plays an important role in the early detection of adverse patient events and contributes to improved care management in the intensive care unit (ICU). This work provides a quantitative evaluation of existing computational frameworks for the automatic extraction of peaks within ICP waveforms.
Methods:
Peak detection techniques based on state-of-the-art machine learning models were evaluated in terms of robustness to varying levels of noise. Evaluation was performed on a dataset of ICP signals assembled from 700 hours of monitoring from 64 neurosurgical patients. The groundtruth of the peak locations was established manually on a subset of 13,611 pulses. Additional evaluation was performed using a simulated dataset of ICP with controlled temporal dynamics and noise.
Results:
The quantitative analysis of peak detection algorithms applied to individual waveforms indicates that all techniques provide acceptable accuracy (RMSE <= 0.15) without noise. In presence of higher level of noise, however, only Kernel ridge regression and Random forest remains below that error threshold while the performance of other techniques significantly deteriorates. Our experiments also demonstrated that tracking methods such as Bayesian inference and LSTM can be applied in a continuous fashion and provide additional robustness in situations where single pulse analysis methods tend to fail such as in presence of missing data.
Conclusion:
While machine learning-based peak detection methods require manually labeled data for training, these models outperform conventional signal processing ones based on handcrafted rules and should be considered for peak detection in modern frameworks. In particular, peak tracking methods that incorporate temporal information between successive periods of the signals have demonstrated in our experiments to provide more robustness to temporary artifacts that commonly arise as part of the monitoring setup in the NICU.
Controllable synthesis of iron-introduced cobalt-iron bimetallic MOFs for rapid removal of tetracycline hydrochloride in water
Authors: Hu Junhao , He Yuting , Shu Tingting , Wang Yingxi , Li Ling 
Published: May 2023

Abstract
For sake of further enhancing the catalytic performance of Co-MOFs and reducing th leaching of Co2+, Fe-doped Co-MOFs was prepared by one-step solvothermal method. The Fex/Co1 − x-MOFs with the best catalytic activity (Fe0.25Co0.75-MOFs) was obtained by changing the doping ratio of Fe3+. Under the action of 0.1g/L Fe0.25Co0.75-MOFs, pH = 7 and 0.2g/L PMS, 98.4% TC can be efficiently degraded only within 30 min, Moreover, the degradation efficiency increased with the increase of the catalyst and PMS. The effects of initial pH on tetracycline hydrochloride degradation was discussed, showing that Fe0.25Co0.75-MOFs can degrade tetracycline hydrochloride with excellent stability. Furthermore, the Fe0.25Co0.75-MOFs exhibits good reusability and stability in cycling experiments. Ultimately, free radical quenching experiments show that both SO4−• and •OH participated in the degradation of tetracycline hydrochloride, and SO4−• plays a major role. Based on some intermediates identified by lc-mg, possible degradation pathways are proposed.
EMI shielding and conductive textiles functionalized with (Ti,Cu) nanomaterials for biomedical applications
Authors: Lopes Cláudia , Ferreira Armando , Correa Marcio A. , Rodrigues André Machado , Mendes Paulo M. , Vaz Filipe 
Published: May 2023

Abstract
This study explores the potential of integrating thin film technology in the design of new and effective Electromagnetic Interference (EMI) shielding materials for textiles and wearables. This application is of particular interest to the textile industry as it can bring new functionalities to wearables and protect humans from prolonged exposure to EM radiation. Three different thin films of pure Ti, pure Cu and Ti-doped with Cu prepared by magnetron sputtering were used to functionalize textile knits based on cotton (code 39 F) and lyocell fibres (62 I). The films displayed different crystalline structures, morphologies, and topographies, which depended on their chemical compositions. The shielding effectiveness (SE) of the functionalized knits against EMI was evaluated in the frequency range of 2 GHz to 8 GHz. Also, the electrical response under stress was assessed since the electrical conductivity is closely related to the EMI shielding effectiveness. The results demonstrate the feasibility of using a thin conductive layer based on Cu to obtain shield textiles with great adhesion and low thickness, providing superior shielding efficiency for EMI by blocking the electrical waves.
Transcriptomic and metabolomic insights into the antimicrobial effect of Leuconostoc mesenteroides or lactic acid on pathogenic Gallibacterium anatis
Authors: Zhang Hua , HuangFu HePing , Qin GuangYong , Wu GuoFang , Wang Lei , Tan ZhongFang 
Published: May 2023

Abstract
Gallibacterium anatis (G. anatis) is an opportunistic poultry pathogen that poses a threat to human health via food chain and can also lead to great economic loss in poultry industries. Our previous studies have demonstrated that the lactic acid producing bacteria Leuconostoc mesenteroides QZ1178 can effectively inhibit the growth of G. anatis by acid production whereas the mechanism is unclear. The current research intended to further probe the molecular mechanism underlying this acid induced antimicrobial effect. The TEM results showed that the cell membrane of G. anatis (GAC026) was damaged and cells were even lysed in the presence of cell free supernatants from Leuconostoc mesenteroides (CFS) or lactic acid. Lactic acid showed more antimicrobial effect than CFS. In this study, the changes in the transcriptome and the metabolic profile of G. anatis under acid stress at different stages have been studied. Using culture medium added with CFS (pH 3.6) or lactic acid (pH 3.6) at 1:1 ratio, 677 differentially transcribed genes and 374 metabolites were detected in G. anatis. The interaction network of all identified differentially expressed genes and metabolites was constructed to outline the potential regulatory genes and dominant pathways in response to acid stress. The results of real-time reverse transcription quantitative PCR (RT-qPCR) further confirmed the results of the transcriptomic analyses. Typically, citrate, lactic acid, L-malic acid, and oxaloacetate were reduced by acid stress in G. anatis, which suggested that lactic acid greatly disturbed energy metabolism. Overall, this work provides comprehensive understanding of stress response and cell death of G. anatis by lactic acid.
Fitting the Discrete Swept Skeletal Representation to Slabular Objects
Authors: Taheri Mohsen , Pizer Stephen M. , Schulz Jörn 
Published: May 2023

Abstract

Statistical analysis of the skeletal structure of slabular objects like groups of hippocampi is valuable for medical researchers as it can be useful for diagnoses and understanding diseases. This work proposes a novel object representation based on model fitting and analysis of the locally parameterized discrete swept skeletal representation of such entities where the model fitting procedure is based on boundary division and surface flattening. The goodness of the model fitting is demonstrated according to the skeletal symmetry, the volume of the implied boundary, and skeletal perturbation. The power of the method is demonstrated by visual inspection and statistical analysis of a synthetic and an actual data set in comparison with an available skeletal representation.