bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlocking cardiac motion: assessing software and machine learning for single-cell and cardioid kinematic insights
Authors: Burattini Margherita , Lo Muzio Francesco Paolo , Hu Mirko , Bonalumi Flavia , Rossi Stefano , Pagiatakis Christina , Salvarani Nicolò , Fassina Lorenzo , Luciani Giovanni Battista , Miragoli Michele 
Published: January 2024

AbstractThe heart coordinates its functional parameters for optimal beat-to-beat mechanical activity. Reliable detection and quantification of these parameters still represent a hot topic in cardiovascular research. Nowadays, computer vision allows the development of open-source algorithms to measure cellular kinematics. However, the analysis software can vary based on analyzed specimens. In this study, we compared different software performances in in-silico model, in-vitro mouse adult ventricular cardiomyocytes and cardioids. We acquired in-vitro high-resolution videos during suprathreshold stimulation at 0.5-1-2 Hz, adapting the protocol for the cardioids. Moreover, we exposed the samples to inotropic and depolarizing substances. We analyzed in-silico and in-vitro videos by (i) MUSCLEMOTION, the gold standard among open-source software; (ii) CONTRACTIONWAVE, a recently developed tracking software; and (iii) ViKiE, an in-house customized video kinematic evaluation software. We enriched the study with three machine-learning algorithms to test the robustness of the motion-tracking approaches. Our results revealed that all software produced comparable estimations of cardiac mechanical parameters. For instance, in cardioids, beat duration measurements at 0.5 Hz were 1053.58 ms (MUSCLEMOTION), 1043.59 ms (CONTRACTIONWAVE), and 937.11 ms (ViKiE). ViKiE exhibited higher sensitivity in exposed samples due to its localized kinematic analysis, while MUSCLEMOTION and CONTRACTIONWAVE offered temporal correlation, combining global assessment with time-efficient analysis. Finally, machine learning reveals greater accuracy when trained with MUSCLEMOTION dataset in comparison with the other software (accuracy > 83%). In conclusion, our findings provide valuable insights for the accurate selection and integration of software tools into the kinematic analysis pipeline, tailored to the experimental protocol.
Multi-objective exponential distribution optimizer (MOEDO): a novel math-inspired multi-objective algorithm for global optimization and real-world engineering design problems
Authors: Kalita Kanak , Ramesh Janjhyam Venkata Naga , Cepova Lenka , Pandya Sundaram B. , Jangir Pradeep , Abualigah Laith 
Published: January 2024

AbstractThe exponential distribution optimizer (EDO) represents a heuristic approach, capitalizing on exponential distribution theory to identify global solutions for complex optimization challenges. This study extends the EDO's applicability by introducing its multi-objective version, the multi-objective EDO (MOEDO), enhanced with elite non-dominated sorting and crowding distance mechanisms. An information feedback mechanism (IFM) is integrated into MOEDO, aiming to balance exploration and exploitation, thus improving convergence and mitigating the stagnation in local optima, a notable limitation in traditional approaches. Our research demonstrates MOEDO's superiority over renowned algorithms such as MOMPA, NSGA-II, MOAOA, MOEA/D and MOGNDO. This is evident in 72.58% of test scenarios, utilizing performance metrics like GD, IGD, HV, SP, SD and RT across benchmark test collections (DTLZ, ZDT and various constraint problems) and five real-world engineering design challenges. The Wilcoxon Rank Sum Test (WRST) further confirms MOEDO as a competitive multi-objective optimization algorithm, particularly in scenarios where existing methods struggle with balancing diversity and convergence efficiency. MOEDO's robust performance, even in complex real-world applications, underscores its potential as an innovative solution in the optimization domain. The MOEDO source code is available at:https://github.com/kanak02/MOEDO.
The role of the SIRT1-BMAL1 pathway in regulating oxidative stress in the early development of ischaemic stroke
Authors: Shi Jing , Li Weirong , Ding Xiaobo , Zhou Feng , Hao Chenxi , He Miao , Wang Fan , Li Xinyi 
Published: January 2024

AbstractOxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00–05:59); subgroup 2 (06:00–11:59); subgroup 3 (12:00–17: 59); and subgroup 4 (18:00–23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P < 0.05). Among the four subgroups, the content of MDA, IL-6, and TNF-α was highest in patients with ischaemic stroke onset from subgroup 2 (06:00–11:59), while the expression levels of SOD, BMAL1, and SIRT1 were lowest in patients with ischaemic stroke in subgroup 2. Additionally, myeloperoxidase (MPO) reached the highest value showing the same trends consistent with MDA, IL-6, and TNF-ɑ and opposite trends consistent with SOD, BMAL1, and SIRT1. However, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), immediate blood glucose, immediate diastolic blood pressure, immediate systolic blood pressure, and homocysteine (HCY) did not show any statistically significant circadian rhythm changes (P > 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.
Droplet-based logic gates simulation of viscoelastic fluids under electric field
Authors: Santos F. P , Tryggvason G. , Ferreira G. G. S. 
Published: January 2024

AbstractNano and microfluidic technologies have shown great promise in the development of controlled drug delivery systems and the creation of microfluidic devices with logic-like functionalities. Here, we focused on investigating a droplet-based logic gate that can be used for automating medical diagnostic assays. This logic gate uses viscoelastic fluids, which are particularly relevant since bio-fluids exhibit viscoelastic properties. The operation of the logic gate is determined by evaluating various parameters, including the Weissenberg number, the Capillary number, and geometric factors. To effectively classify the logic gates operational conditions, we employed a deep learning classification to develop a reduced-order model. This approach accelerates the prediction of operating conditions, eliminating the need for complex simulations. Moreover, the deep learning model allows for the combination of different AND/OR branches, further enhancing the versatility of the logic gate. We also found that non-operating regions, where the logic gate does not function properly, can be transformed into operational regions by applying an external force. By utilizing an electrical induction technique, we demonstrated that the application of an electric field can repel or attract droplets, thereby improving the performance of the logic gate. Overall, our research shows the potential of the droplet-based logic gates in the field of medical diagnostics. The integration of deep learning classification algorithms enables rapid evaluation of operational conditions and facilitates the design of complex logic circuits. Additionally, the introduction of external forces and electrical induction techniques opens up new possibilities for enhancing the functionality and reliability of these logic gates.
PRKCSH serves as a potential immunological and prognostic biomarker in pan-cancer
Authors: Wang Qiankun , Wang Xiong , Li Jiaoyuan , Yin Tongxin , Wang Yi , Cheng Liming 
Published: January 2024

AbstractProtein kinase C substrate 80K-H (PRKCSH) plays a crucial role in the protein N-terminal glycosylation process, with emerging evidence implicating its involvement in tumorigenesis. To comprehensively assess PRKCSH’s significance across cancers, we conducted a pan-cancer analysis using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We assessed aberrant PRKCSH mRNA and protein expression, examined its prognostic implications, and identified correlations with clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immunity across cancer types. We explored PRKCSH gene alterations, DNA methylation, and their impact on patient prognosis. Gene Set Enrichment Analysis (GSEA) and single-cell analysis revealed potential biological roles. Additionally, we investigated drug susceptibility and conducted Connectivity Map (Cmap) analysis. Key findings revealed that PRKCSH exhibited overexpression in most tumors, with a significant association with poor overall survival (OS) in six cancer types. Notably, PRKCSH expression demonstrated variations across disease stages, primarily increasing in advanced stages among eleven tumor types. Moreover, PRKCSH exhibited significant correlations with TMB in five cancer categories, MSI in eight, and displayed associations with immune cell populations in pan-cancer analysis. Genetic variations in PRKCSH were identified across 26 tumor types, suggesting favorable disease-free survival. Furthermore, PRKCSH methylation displayed a significant negative correlation with its expression in 27 tumor types, with a marked decrease compared to normal tissues in ten tumors. Cmap predicted 24 potential therapeutic small molecules in over four cancer types. This study highlights that PRKCSH, as a potential oncogene, may be a promising prognostic marker and therapeutic target of immunotherapy for a range of malignancies.
Switching from robotic-assisted extended transabdominal preperitoneal (eTAPP) to totally extraperitoneal (eTEP) hernia repair for umbilical and epigastric hernias
Authors: Pini Ramon , Mongelli Francesco , Iaquinandi Fabiano , Gaffuri Paolo , Previsdomini Marco , Cianfarani Agnese , La Regina Davide 
Published: January 2024

AbstractOur study aimed to assess the safety and effectiveness of the robotic-assisted extended totally extraperitoneal (eTEP) repair compared to transabdominal preperitoneal (eTAPP) repair with a suprapubic trocar insertion to treat umbilical and epigastric hernias. On a prospectively maintained database, we identified patients who underwent either eTEP or eTAPP for treating umbilical and epigastric hernias. During the study period, 53 patients were included, 32 in the eTEP group and 21 in the eTAPP group. The mean age was 59.0 ± 13.9 years, 45 patients (84.9%) were male, and the mean BMI was 28.0 ± 5.9 kg/m2. Most hernias were umbilical (81.1%) and primary (83.0%). The operative time for eTEP was slightly shorter than for eTAPP (106 ± 43 min vs. 126 ± 74 min, p = 0.232). Postoperatively, only one case of bleeding and one seroma were recorded. No complication occurred during a mean follow-up of 11.3 ± 6.4 months in the eTEP group and 20.5 ± 9.7 months in the eTAPP group. In conclusion, our study showed that the eTEP with suprapubic approach was safe and feasible in the treatment of epigastric and umbilical hernias. According to our experience, shorter operative time, integrity of the posterior layers and increased overlap size are the main surgical reasons of switching from eTAPP to eTEP.
hBcl2 overexpression in BMSCs enhances resistance to myelin debris-induced apoptosis and facilitates neuroprotection after spinal cord injury in rats
Authors: Tian Dasheng , You Xingyu , Ye Jianan , Chen Gan , Yu Hang , Lv Jianwei , Shan Fangli , Liang Chao , Bi Yihui , Jing Juehua , Zheng Meige 
Published: January 2024

AbstractAfter spinal cord injury (SCI), the accumulation of myelin debris at the lesion exacerbates cell death and hinders axonal regeneration. Transplanted bone marrow mesenchymal stem cells (BMSCs) have been proven to be beneficial for SCI repair, but they are susceptible to apoptosis. It remains unclear whether this apoptotic process is influenced by myelin debris. Here, we constructed rat BMSCs overexpressing human B-cell lymphoma 2 (hBcl2) alone (hBcl2 group), BMSCs overexpressing hBcl2 with an endoplasmic reticulum-anchored segment (hBcl2-cb) (cb group), and a negative control group (NC group) for transplantation in this study. Immunocytochemistry staining validated the successful expression of hBcl2 in BMSCs within the hBcl2 group and cb group. All BMSCs from each group exhibited the ability to phagocytize myelin debris. Nevertheless, only BMSCs derived from the hBcl2 group exhibited heightened resistance to apoptosis and maintained prolonged viability for up to 5 days when exposed to myelin debris. Notably, overexpression of hBcl2 protein, rather than its endoplasmic reticulum-anchored counterpart, significantly enhanced the resistance of BMSCs against myelin debris-induced apoptosis. This process appeared to be associated with the efficient degradation of myelin debris through the Lamp1+ lysosomal pathway in the hBcl2 group. In vivo, the hBcl2 group exhibited significantly higher numbers of surviving cells and fewer apoptotic BMSCs compared to the cb and NC groups following transplantation. Furthermore, the hBcl2 group displayed reduced GFAP+ glial scarring and greater preservation of NF200+ axons in the lesions of SCI rats. Our results suggest that myelin debris triggers apoptosis in transplanted BMSCs, potentially elucidating the low survival rate of these cells after SCI. Consequently, the survival rate of transplanted BMSCs is improved by hBcl2 overexpression, leading to enhanced preservation of axons within the injured spinal cord.
Lessons from the historical dynamics of environmental law enforcement in the Brazilian Amazon
Authors: Nunes Felipe S. M. , Soares-Filho Britaldo S. , Oliveira Amanda R. , Veloso Laura V. S. , Schmitt Jair , Van der Hoff Richard , Assis Debora C. , Costa Rayane P. , Börner Jan , Ribeiro Sonia M. C. , Rajão Raoni G. L. , de Oliveira Ubirajara , Costa Marcelo Azevedo 
Published: January 2024

AbstractHere, we analyze critical changes in environmental law enforcement in the Brazilian Amazon between 2000 and 2020. Based on a dataset of law enforcement indicators, we discuss how these changes explain recent Amazon deforestation dynamics. Our analysis also covers changes in the legal prosecution process and documents a militarization of enforcement between 2018 and 2022. From 2004 to 2018, 43.6 thousand land-use embargoes and 84.3 thousand fines were issued, targeting 3.3 million ha of land, and totaling USD 9.3 billion in penalties. Nevertheless, enforcement relaxed and became spatially more limited, signaling an increasing lack of commitment by the State to enforcing the law. The number of embargoes and asset confiscations dropped by 59% and 55% in 2019 and 2020, respectively. These changes were accompanied by a marked increase in enforcement expenditure, suggesting a massive efficiency loss. More importantly, the creation of so-called conciliation hearings and the centralization of legal processes in 2019 reduced the number of actual judgments and fines collected by 85% and decreased the ratio between lawsuits resulting in paid fines over filed ones from 17 to 5%. As Brazil gears up to crack-down on illegal deforestation once again, our assessment suggests urgent entry points for policy action.
Topological analysis of tetracyanobenzene metal–organic framework
Authors: Al-Dayel Ibrahim , Nadeem Muhammad Faisal , Khan Meraj Ali 
Published: January 2024

AbstractMetal–organic frameworks (MOFs) are vital in modern material science, offering unique properties for gas storage, catalysis, and drug delivery due to their highly porous and customizable structures. Chemical graph theory emerges as a critical tool, providing a mathematical model to represent the molecular structure of these frameworks. Topological indices/molecular descriptors are mathematical formulations applied to molecular models, enabling the analysis of physicochemical properties and circumventing costly lab experiments. These descriptors are crucial for quantitative structure-property and structure-activity relationship studies in mathematical chemistry. In this paper, we study the different molecular descriptors of tetracyanobenzene metal–organic framework. We also give numerical comparison of computed molecular descriptors.
Peroxisome proliferator-activated receptor γ coactivator 1α regulates downstream of tyrosine kinase-7 (Dok-7) expression important for neuromuscular junction formation
Authors: Sugimoto Takumi , Sakamaki Chihiro , Kimura Tokushi , Eguchi Takahiro , Miura Shinji , Kamei Yasutomi 
Published: January 2024

AbstractThe neuromuscular junction (NMJ)—formed between a motor nerve terminal and skeletal muscle fiber—plays an important role in muscle contraction and other muscle functions. Aging and neurodegeneration worsen NMJ formation and impair muscle function. Downstream of tyrosine kinase-7 (Dok-7), expressed in skeletal muscle fibers, is essential for the formation of NMJ. Exercise increases the expression of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) in skeletal muscles and restores NMJ formation. In this study, we used skeletal muscle-specific PGC1α knockout or overexpression mice to examine the role of PGC1α in regulating Dok-7 expression and NMJ formation. Our findings revealed that Dok-7 expression is regulated by PGC1α, and luciferase activity of the Dok-7 promoter is greatly increased by coexpressing PGC1α and estrogen receptor-related receptor α. Thus, we suggest PGC1α is involved in exercise-mediated restoration of NMJ formation.
Combination strategy exploration for prior treated recurrent or metastatic nasopharyngeal carcinoma in the era of immunotherapy
Authors: Jiang Yaofei , Chen Chun , Liu Guoying , Fang Ting , Lu Nian , Bei Weixin , Dong Shuhui , Li Wangzhong , Xia Weixiong , Liang Hu , Xiang Yanqun 
Published: January 2024

AbstractTo assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123–0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515–1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345–0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events.
Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα
Authors: Hata Kentaro , Tsubouchi Kazuya , Suzuki Kunihiro , Eto Daisuke , Ando Hiroyuki , Yanagihara Toyoshi , Kan-o Keiko , Okamoto Isamu 
Published: January 2024

AbstractMucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, but whether it also exerts direct effects on airway epithelial cells has remained unclear. Therefore, we sought to investigate the inhibitory role of SP-D on mucin production in airway epithelial cells. We prepared air–liquid interface (ALI) cultures of human primary bronchial epithelial cells (HBECs), which recapitulated a well-differentiated human airway epithelium. Benzo(a)pyrene (BaP), a key toxicant in cigarette smoke, induced mucin 5AC (MUC5AC) production in ALI-cultured HBECs, airway secretory cell lines, and airway epithelia of mice. Then, the protective effects of SP-D against the BaP-induced mucin overproduction were examined. BaP increased MUC5AC production in ALI cultures of HBECs, and this effect was attenuated by SP-D. SP-D also suppressed the BaP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and MUC5AC expression in NCI-H292 goblet-like cells, but not in NCI-H441 club-like cells. Signal regulatory protein α (SIRPα) was found to be expressed in HBECs and NCI-H292 cells but absent in NCI-H441 cells. In NCI-H292 cells, SP-D activated SH2 domain-containing tyrosine phosphatase-1 (SHP-1), downstream of SIRPα, and knockdown of SIRPα abolished the suppressive effects of SP-D on BaP-induced ERK phosphorylation and MUC5AC production. Consistent with these in vitro findings, intratracheal instillation of SP-D prevented the BaP-induced phosphorylation of ERK and Muc5ac expression in airway epithelial cells in a mouse model. SP-D acts directly on airway epithelial cells to inhibit mucin secretion through ligation of SIRPα and SHP-1-mediated dephosphorylation of ERK. Targeting of SIRPα is therefore a potential new therapeutic approach to suppression of mucin hypersecretion in chronic airway diseases such as COPD and asthma.