bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized Transfer Learning Framework for Remaining Useful Life Prediction Using Adaptive Deconstruction and Dynamic Weight Informer
Authors: Liu Xue , Ma Jian , Song Dengwei
Published: October 2023

The precise remaining useful life (RUL) prediction of turbofan engines benefits maintenance decisions. The training data quantity and quality are crucial for effective prediction modeling and accuracy improvement. However, the performance degradation process of the same type of turbofan engine usually exhibits different trajectories because of engines’ differences in degradation degrees, degradation rates, and initial health states. In addition, the initial part of the trajectory is a stationary health stage, which contains very little information on degradation and is not helpful for modeling. Considering the differential degradation characteristics and the requirement for accurate prediction modeling of the same type of turbofan engines with individual differences, we specifically propose a personalized transfer learning framework for RUL prediction by answering three key questions: when, what, and how to transfer in prediction modeling. The framework tries to maximumly utilize multi-source-domain data (samples of the same type of engines that run to failure) to improve the training data quantity and quality. Firstly, a transfer time identification method based on a dual-baseline performance assessment and the Wasserstein distance is designed to eliminate the worthless part of a trajectory for transfer and prediction modeling. Then, the transferability of each sample in the multi-source domain is measured by an approach, named the time-lag ensemble distance measurement, and then the source domain is ranked and adaptively deconstructed into two parts according to transferability. Ultimately, a new training loss function considering the transferability of the weighted multi-source-domain data and a two-stage transfer learning scheme is introduced into an informer-based RUL prediction model, which has a great advantage for long-time-series prediction. The simulation data of 100 of the same type of turbofan engine with individual differences and five comparison experiments validate the effectiveness and accuracy of the proposed method.
Klotho Null Mutation Indirectly Leads to Age-Related Lacrimal Gland Degeneration in Mutant Mice
Authors: Wu Chun-Yen , Song Da-Fong , Lu Tsung-Han , Chen Zhi-Jia , Tsai Su-Min , Liu Ya-Jing , Chang Han-Hsin , Lin David Pei-Cheng
Published: October 2023

The Klotho null mutation is known to lead to accelerated aging in many organs, but its effects on tear secretion and lacrimal gland (LG) senescence have not been addressed. This study investigated whether the Klotho null mutation would lead to a dry eye status and the outcome of LG without Klotho function. The Klotho (−/−) mutant mice showed reduced LG size and tear volume on the 8th week, as compared to their littermates (+/+, +/−). Hematoxylin–Eosin and Masson’s trichrome staining were performed to determine morphological changes and collagen deposition. Traits of LG aging, including acinar atrophy, thickened capsules, and more collagen depositions, were observed. Immunohistochemical detections for Klotho, α-SMA, MDA, 8-OHdG, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), MMP-2, MMP-9, and FGF-23 were performed and compared among the three genotypes (+/+, +/−, −/−) at 6 and 8 weeks of age for mechanism analyses. Unexpectedly, the Klotho protein was not detected in the LG of all the three genotypes, indicating indirect effects from the Klotho null mutation. Further analyses showed abundant MDA and 8-OHdG detected in the Klotho (−/−) LG on the 8th week, indicating elevated oxidative stress. In addition, both sympathetic and parasympathetic neural transducing activities, as represented by TH and VIP expression, respectively, and α-SMA were increased in LGs with Klotho mutations. Furthermore, MMP-2 and MMP-9 expression were elevated, with FGF-23 expression being decreased on the 8th week in the Klotho (−/−) LG. In conclusion, characteristics of age-related LG degeneration were found in the Klotho null mutant mice. These traits support the use of Klotho mutant mice as a model of age-related dry eye disease.
Role of Cytokine-Inducible SH2 Domain-Containing (CISH) Protein in the Regulation of Erythropoiesis
Authors: Maymand Saeed , Lakkavaram Asha L. , Naser Wasan , Rasighaemi Parisa , Dlugolenski Daniel , Liongue Clifford , Stambas John , de Koning-Ward Tania F. , Ward Alister C.
Published: October 2023

The cytokine-inducible SH2 domain-containing (CISH) protein was the first member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators discovered, being identified in vitro as an inducible inhibitor of erythropoietin (EPO) signaling. However, understanding of the physiological role played by CISH in erythropoiesis has remained limited. To directly assess the function of CISH in this context, mice deficient in CISH were characterized with respect to developmental, steady-state, and EPO-induced erythropoiesis. CISH was strongly expressed in the fetal liver, but CISH knockout (KO) mice showed only minor disruption of primitive erythropoiesis. However, adults exhibited mild macrocytic anemia coincident with subtle perturbation particularly of bone marrow erythropoiesis, with EPO-induced erythropoiesis blunted in the bone marrow of KO mice but enhanced in the spleen. Cish was expressed basally in the bone marrow with induction following EPO stimulation in bone marrow and spleen. Overall, this study indicates that CISH participates in the control of both basal and EPO-induced erythropoiesis in vivo.
The Antiviral Activity of Varenicline against Dengue Virus Replication during the Post-Entry Stage
Authors: Lin Ching-Lin , Kiu Yan-Tung , Kan Ju-Ying , Chang Yu-Jen , Hung Ping-Yi , Lu Chih-Hao , Lin Wen-Ling , Hsieh Yow-Wen , Kao Jung-Yie , Hu Nien-Jen , Lin Cheng-Wen
Published: October 2023

Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major hurdle. Varenicline is a medication used to aid smoking cessation, with anti-inflammatory and antioxidant effects. In this study, varenicline was investigated for its antiviral potential against DENV. This study provides evidence of the antiviral activity of varenicline against DENV, regardless of the virus serotype or cell type used. Varenicline demonstrated dose-dependent effects in reducing viral protein expression, infectivity, and virus yield in Vero and A549 cells infected with DENV-1 and DENV-2, with EC50 values ranging from 0.44 to 1.66 μM. Time-of-addition and removal experiments demonstrated that varenicline had a stronger inhibitory effect on the post-entry stage of DENV-2 replication than on the entry stage, as well as the preinfection and virus attachment stages. Furthermore, cell-based trans-cleavage assays indicated that varenicline dose-dependently inhibited the proteolytic activity of DENV-2 NS2B-NS3 protease. Docking models revealed the formation of hydrogen bonds and van der Waals forces between varenicline and specific residues in the DENV-1 and DENV-2 NS2B-NS3 proteases. These results highlight the antiviral activity and potential mechanism of varenicline against DENV, offering valuable insights for further research and development in the treatment of DENV infection.
MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate
Authors: Casanova Ignacio , Domínguez-Mozo María I. , De Torres Laura , Aladro-Benito Yolanda , García-Martínez Ángel , Gómez Patricia , Abellán Sara , De Antonio Esther , Álvarez-Lafuente Roberto
Published: October 2023

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing–remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (β = 0.23; 95% CI: 0.04–0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.
Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis
Authors: Chang Yu-Hsiang , Huang Yuan-Li , Tsai Hsiao-Chi , Chang An-Chen , Ko Chih-Yuan , Fong Yi-Chin , Tang Chih-Hsin
Published: October 2023

Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma.
Screen Media Use Affects Subcortical Structures, Resting-State Functional Connectivity, and Mental Health Problems in Early Adolescence
Authors: He Xu , Hu Jiaxin , Yin Mengyun , Zhang Wei , Qiu Boyu
Published: October 2023

The association between excessive screen media use and mental health problems has attracted widespread attention. The literature to date has neglected the biological mechanisms underlying such a relationship and failed to distinguish between different types of screen media activities. A sample from the Adolescent Brain and Cognitive Development study was used in the present study to elucidate the longitudinal associations between specific types of screen media use, brain development, and diverse mental health problems. The results showed that different types of screen media use have differentiated associations with mental health problems, subcortical volume, and cortical–subcortical connectivity. Specifically, more passive media use was associated with increased rule-breaking behavior, while more video game playing was associated with increased withdrawn/depressed symptoms. In addition, more social media use was associated with a reduced volume of the hippocampus, caudate, and thalamus proper. More research is needed to examine the differential effects of screen media use on neurodevelopmental processes and mental health problems across adolescence.
Microglial Activation: Key Players in Sepsis-Associated Encephalopathy
Authors: Hu Jiyun , Xie Shucai , Zhang Haisong , Wang Xinrun , Meng Binbin , Zhang Lina
Published: October 2023

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.
Professional Athletes’ Well-Being: New Challenges in Post-COVID-19 Times
Authors: Assa Ran , Reizer Abira
Published: October 2023

The COVID-19 period was characterized as a traumatic period throughout the world. During the pandemic, sports organizations had to adapt to government rules and social distancing measures frequently and faced a challenging and complex period in keeping their athletes on a normal routine. Many athletes faced uncertainty regarding their present and future competitive context and personal worries, similar to society during the pandemic. Consequently, adverse effects on the mental health and well-being of athletes were reported in individual and team sports. This review seeks to explore the perceived impact of COVID-19 on athletes’ well-being and future considerations. This review suggests professional athletes’ well-being should receive more attention and will be addressed in the future for the benefit of the athletes and not just in favor of performance. Moreover, the emphasis on evidence-based psychological support such as stress management and athletes’ well-being in a high-performance sport context should increase. The post-COVID-19 period highlights the importance of broadening athletic identity into a more holistic scope that includes life–performance balance and personal values outside the sporting context. Lastly, developing and fostering resilience is complex yet fundamental for systems, when considering athletes’ personal context and providing them with professional skills outside of their professional domain.
Post-Secondary Education Outcomes for Individuals with Intellectual and Developmental Disabilities: Self-Determination, Independent Living, Employment, and the Impact of COVID-19
Authors: Zhang Dalun , Roberts Eric , Maddalozzo Robert , Li Yi-Fan , Orsag Meagan , Glass Tracy
Published: October 2023

Post-secondary education (PSE) plays an important role in preparing individuals with an intellectual and developmental disability (IDD) to gain employment and independent living. Despite the recent increase in PSE programs, however, there is a lack of research examining outcomes of individuals with IDD who have attended a PSE program. This study examined three years of data from students who participated in one PSE program that focuses on the acquisition of skills regarding self-determination, employment, and independent living. We analyzed the outcome data of program graduates regarding their acquisition of skills in employment and self-determination, as well as follow-up data on employment. It was found that participation in the program increased self-determination and post-secondary readiness. Our findings also indicated that the COVID-19 pandemic impacted the self-determination scores of participants and their employment outcomes.
Relations between Video Game Engagement and Social Development in Children: The Mediating Role of Executive Function and Age-Related Moderation
Authors: Xu Ke , Geng Shuliang , Dou Donghui , Liu Xiaocen
Published: October 2023

The global proliferation of video games, particularly among children, has led to growing concerns about the potential impact on children’s social development. Executive function is a cognitive ability that plays a crucial role in children’s social development, but a child’s age constrains its development. To examine the association between video game engagement and children’s social development while considering the mediating role of executive function and the moderating role of age, a questionnaire was distributed to a sample of 431 parents. The results revealed a negative relation between video game engagement and social development in children, with executive function found to mediate this relation fully. Additionally, the negative association between video game engagement and executive function became more pronounced as children grew older. In light of these findings, it is advisable to adopt proactive strategies to limit excessive video game use, consider the developmental characteristics of children at different ages, and prioritize the promotion of executive function to facilitate social development among children.
The Impacts of Leaders’ Influence Tactics on Teleworkers’ Job Stress and Performance: The Moderating Role of Organizational Support in COVID-19
Authors: Byun Gukdo , Rhie Jihyeon , Lee Soojin , Dai Ye
Published: October 2023

With the outbreak of COVID-19, organizations have increased non-face-to-face work. This study aims to examine how leaders’ influence tactics affect employees’ psychological state and job performance in a non-face-to-face work (telework) setting. Moreover, based on substitutes for leadership theory, the study proposes that teleworkers’ perceived organizational support moderates the relationship between leaders’ influence tactics and their job stress in telework settings. We collected data via time-lagged surveys among 208 full-time employees in South Korean organizations that began teleworking after the outbreak of the COVID-19 pandemic. The results showed that leaders’ soft tactics (i.e., behaviors used to elicit the followers’ voluntary acceptance of a request) and rational tactics (i.e., behaviors that exert influence by providing empirical evidence based on reason or logic) significantly reduced teleworkers’ job stress, which in turn lowered their turnover intention and increased their task performance. Moreover, these tactics and teleworkers’ perceived organizational support interact to influence the workers’ job stress. By examining how leaders’ influence tactics affect teleworkers’ psychological stress, task performance, and turnover intention in the wake of the COVID-19 pandemic, this study theoretically broadens the influence tactics literature, which previously focused primarily on face-to-face workers. The study concludes with a discussion about the implications of findings and limitations, along with areas for future research.
Co-Living at Its Best—An Empirical Study of Economies of Scale, Building Age, and Amenities of Housing Estates in Hong Kong
Authors: Chen Zhankun , Cheung Ka Shing , Tsang Desmond , Yiu Chung Yim
Published: October 2023

Co-living is commonly considered as an arrangement for rental housing. However, co-living in housing estates by sharing common amenities among co-owners has been practiced for many years in high-density cities. Yet, there have been very few empirical studies on the estate premium and the economies/diseconomies of scale effect on house prices, probably due to the lack of data. This study is a novel attempt to examine the economies/diseconomies of scale effect using the hedonic price model to estimate the impact of the number of housing units in a housing estate on house prices, ceteris paribus, using Hong Kong housing transaction data. The results confirm the hypothesis of estate premium and the economies of scale effect of co-living in housing estates. Economies of scale are observed, with larger estates commanding a premium of up to 5031 units, beyond which the effect declines, hinting at potential diseconomies. Building age moderates this effect, as we observe a larger scale effect in especially younger estates with lower maintenance costs. Additional tests confirm the positive correlation between amenities and prices, with an optimal amenity number enhancing prices, while excess amenities lead to diminishing returns. A case study reinforces these findings, demonstrating a general trend of decreasing management fees with increasing estate size, supporting the notion of economies of scale. Overall, this study contributes valuable insights for developers and homebuyers, emphasizing the importance of balancing estate size and amenities for cost-sharing advantages and effective management in co-living housing estates.
Chemical and Creep Models Applied to Concrete Damaged by Alkali–Silica Reactions
Authors: Roma Rodrigo F. , Silva Fernando A. N. , Bourbatache Mohamed K. , Tahlaiti Mahfoud , Delgado João M. P. Q. , Azevedo António C.
Published: October 2023

Concrete structures that experience internal swelling reactions are often affected by other deleterious mechanisms, such as creep and shrinkage. In Brazil and many other countries around the world, numerous cases of building foundations and concrete dams were investigated due to the damage associated with internal expansions. Macroscopic models for the numerical representation of these expansions must take into account the influence of key environmental parameters such as temperature, degree of saturation, and the rate of development of the chemical reaction. To be relevant in structural applications, concrete creep models must consider several important phenomena, such as non-linearity, multi-axiality, and thermal and drying effects. In order to prevent these pathologies, to plan rehabilitation work, and to develop new design procedures, numerical simulation using the finite element method (FEM) is a very useful tool. This work aimed to implement a chemical model to simulate the advancement of the internal expansion reactions and a mechanical model to simulate creep and shrinkage phenomena in COMSOL Multiphysics® to reassess concrete structures suffering from these mechanisms. Both models were implemented separately to evaluate their responses and compare them with the theoretical results and experimental benchmarks proposed by the developers of these models. The numerical results obtained presented an excellent agreement with the experimental results, with a deviation of less than 10%, which showed that the implementation of the developed numerical models was very efficient. Moreover, this research holds significant importance as the mathematical models used to simulate internal expansions in concrete are currently only available in limited-use FEM software’s. Therefore, demonstrating the successful implementation of these models in widely used finite element programs and their ability to produce reliable results would be a valuable contribution.
Repeated Stereotactic Radiotherapy for Local Brain Metastases Failure or Distant Brain Recurrent: A Retrospective Study of 184 Patients
Authors: Kuntz Laure , Le Fèvre Clara , Jarnet Delphine , Keller Audrey , Meyer Philippe , Mazzara Christophe , Cebula Hélène , Noel Georges , Antoni Delphine
Published: October 2023

Background: The main advantages of stereotactic radiotherapy (SRT) are to delay whole-brain radiotherapy (WBRT) and to deliver ablative doses. Despite this efficacy, the risk of distant brain metastases (BM) one year after SRT ranges from 26% to 77% and 20 to 40% of patients required salvage treatment. The role and consequences of reirradiation remain unclear, particularly in terms of survival. The objective was to study overall survival (OS) and neurological death-free survival (NDFS) and to specify the prognostic factors of long-term survival. Methods: we retrospectively reviewed the data of patients treated between 2010 and 2020 with at least two courses of SRT without previous WBRT. Results: In total, 184 patients were treated for 915 BMs with two-to-six SRT sessions. Additional SRT sessions were provided for local (5.6%) or distant (94.4%) BM recurrence. The median number of BMs treated per SRT was one with a median of four BMs in total. The mean time between the two SRT sessions was 8.9 months (95%CI 7.7–10.1) and there was no significant difference in the delay between the two sessions. The 6-, 12- and 24-month NDFS rates were 97%, 82% and 52%, respectively. The 6-, 12- and 24-month OS rates were 91%, 70% and 38%, respectively. OS was statistically related to the number of SRT sessions (HR = 0.48; p < 0.01), recursive partitioning analysis (HR = 1.84; p = 0.01), salvage WBRT (HR = 0.48; p = 0.01) and brain metastasis velocity (high: HR = 13.83; p < 0.01; intermediate: HR = 4.93; p < 0.01). Conclusions: Lung cancer and melanoma were associated with a lower NDFS compared to breast cancer. A low KPS, a low number of SRT sessions, synchronous extracerebral metastases, synchronous BMs, extracerebral progression at SRT1, a high BMV grade, no WBRT and local recurrence were also associated with a lower NDFS. A high KPS at SRT1 and low BMV grade are prognostic factors for better OS, regardless of the number of BM recurrence events.
Indocyanine Green (ICG) in Robotic Gastrectomy: A Retrospective Review of Lymphadenectomy Outcomes for Gastric Cancer
Authors: Jeon Chul-Hyo , Kim So-Jung , Lee Han-Hong , Song Kyo-Young , Seo Ho-Seok
Published: October 2023

Radical gastrectomy is essential for gastric cancer treatment. While guidelines advise dissecting at least 16 lymph nodes, some research suggests over 30 nodes might be beneficial. This study assessed ICG-guided robotic gastrectomy’s effectiveness in thorough lymph node dissection. We analyzed data from 393 stage II or III gastric cancer patients treated at Seoul St. Mary’s Hospital from 2016–2022. Patients were categorized into conventional laparoscopy (G1, n = 288), ICG-guided laparoscopy (G2, n = 61), and ICG-guided robotic surgery (G3, n = 44). Among 391 patients, 308 (78.4%) achieved proper lymphadenectomy. The ICG-robotic group (G3) showed the highest success rate at 90.9%. ICG-guided robotic surgery was a significant predictor for achieving proper lymphadenectomy, with an odds ratio of 3.151. In conclusion, ICG-robotic gastrectomy improves lymphadenectomy outcomes in selected gastric cancer cases, indicating a promising surgical approach for the future.
Selection of Chemotherapy in Advanced Poorly Differentiated Extra-Pulmonary Neuroendocrine Carcinoma
Authors: Weaver Jamie M. J. , Hubner Richard A. , Valle Juan W. , McNamara Mairead G.
Published: October 2023

Extra-pulmonary poorly differentiated neuroendocrine carcinoma is rare, and evidence for treatment has been limited. In this article, the evidence behind the cytotoxic chemotherapy choices used for metastatic or unresectable EP-PD-NEC is reviewed. In the first-line setting, etoposide and platinum chemotherapy or irinotecan and platinum have been demonstrated to be equivalent in a large phase III trial. Questions remain regarding the optimal number of cycles, mode of delivery, and the precise definition of platinum resistance in this setting. In the second-line setting, FOLFIRI has emerged as an option, with randomized phase 2 trials demonstrating modest, but significant, response rates. Beyond this, data are extremely limited, and several regimens have been used. Heterogeneity in biological behaviour is a major barrier to optimal EP-PD-NEC management. Available data support the potential role of the Ki-67 index as a predictive biomarker for chemotherapy response. A more personalised approach to management in future studies will be essential, and comprehensive multi-omic approaches are required to understand tumour somatic genetic changes in relation to their effects on the surrounding microenvironment.
Prognostic Relevance of Tumor-Infiltrating Immune Cells in Cervix Squamous Cell Carcinoma
Authors: Wild Carl Mathis , Garrido Fabian , Dannecker Christian , Köpke Melitta B. , Chateau Marie-Christine , Boissière-Michot Florence , Heidegger Helene H. , Vattai Aurelia , Kessler Mirjana , Jeschke Udo , Cavaillès Vincent
Published: October 2023

There exists a variety of studies about tumor-infiltrating immune cells (TIICs) in cervical cancer, but their prognostic value in correlation with the histopathological subtype has never been investigated. Therefore, the aim of this study was to quantify TIICs in a panel of 238 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIICs levels were significantly increased in the subgroup of CSCC (191 samples) in comparison to CAC (47 samples). In CSCC, TIICs’ infiltration showed a negative correlation with age, FIGO stage and with the histone protein modification H3K4me3. Moreover, in CAC, it was positively correlated with p16 and with the glucocorticoid receptor and inversely correlated with the MDM2 protein and with H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease-free survival (DFS) in patients with CSCC, those bearing tumors with the strongest TIICs infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIIC levels and prognosis in patients with CSCC vs. patients with CAC.
PTEN, PTENP1, microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics
Authors: Travis Glena , McGowan Eileen M. , Simpson Ann M. , Marsh Deborah J. , Nassif Najah T.
Published: October 2023

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels. PTENP1, the processed pseudogene of PTEN, is an important transcriptional and post-transcriptional regulator of PTEN. PTENP1 expression produces sense and antisense transcripts modulating PTEN expression, in conjunction with miRNAs. Due to the high sequence similarity between PTEN and the PTENP1 sense transcript, the transcripts possess common miRNA binding sites with the potential for PTENP1 to compete for the binding, or ‘sponging’, of miRNAs that would otherwise target the PTEN transcript. PTENP1 therefore acts as a competitive endogenous RNA (ceRNA), competing with PTEN for the binding of specific miRNAs to alter the abundance of PTEN. Transcription from the antisense strand produces two functionally independent isoforms (PTENP1-AS-α and PTENP1-AS-β), which can regulate PTEN transcription. In this review, we provide an overview of the post-transcriptional regulation of PTEN through interaction with its pseudogene, the cellular miRNA milieu and operation of the ceRNA network. Furthermore, its importance in maintaining cellular integrity and how disruption of this PTEN–miRNA–PTENP1 axis may lead to cancer but also provide novel therapeutic opportunities, is discussed. Precision targeting of PTENP1-miRNA mediated regulation of PTEN may present as a viable alternative therapy.
Nuclear Import and Export of YAP and TAZ
Authors: Kofler Michael , Kapus András
Published: October 2023

Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway and the cytoskeleton. Integrating an array of chemical and mechanical signals, they impact growth, differentiation, and regeneration. Accordingly, they also play key roles in tumorigenesis and metastasis formation. Their activity is primarily regulated by their localization, that is, Hippo pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details of such prevailing retention models have been elucidated, much less is known about their actual nuclear traffic: import and export. Although their size is not far from the cutoff for passive diffusion through the nuclear pore complex (NPC), and they do not contain any classic nuclear localization (NLS) or nuclear export signal (NES), evidence has been accumulating that their shuttling involves mediated and thus regulatable/targetable processes. The aim of this review is to summarize emerging information/concepts about their nucleocytoplasmic shuttling, encompassing the relevant structural requirements (NLS, NES), nuclear transport receptors (NTRs, karyophererins), and NPC components, along with the potential transport mechanisms and their regulation. While dissecting retention vs. transport is often challenging, the emerging picture suggests that YAP/TAZ shuttles across the NPC via multiple, non-exclusive, mediated mechanisms, constituting a novel and intriguing facet of YAP/TAZ biology.
Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers
Authors: Xu Jiaxuan , Dong Xiaoqing , Huang David C. S. , Xu Peipei , Zhao Quan , Chen Bing
Published: October 2023

Targeting the intrinsic apoptotic pathway regulated by B-cell lymphoma-2 (BCL-2) antiapoptotic proteins can overcome the evasion of apoptosis in cancer cells. BCL-2 inhibitors have evolved into an important means of treating cancers by inducing tumor cell apoptosis. As the most extensively investigated BCL-2 inhibitor, venetoclax is highly selective for BCL-2 and can effectively inhibit tumor survival. Its emergence and development have significantly influenced the therapeutic landscape of hematological malignancies, especially in chronic lymphocytic leukemia and acute myeloid leukemia, in which it has been clearly incorporated into the recommended treatment regimens. In addition, the considerable efficacy of venetoclax in combination with other agents has been demonstrated in relapsed and refractory multiple myeloma and certain lymphomas. Although venetoclax plays a prominent antitumor role in preclinical experiments and clinical trials, large individual differences in treatment outcomes have been characterized in real-world patient populations, and reduced drug sensitivity will lead to disease recurrence or progression. The therapeutic efficacy may vary widely in patients with different molecular characteristics, and key genetic mutations potentially result in differential sensitivities to venetoclax. The identification and validation of more novel biomarkers are required to accurately predict the effectiveness of BCL-2 inhibition therapy. Furthermore, we summarize the recent research progress relating to the use of BCL-2 inhibitors in solid tumor treatment and demonstrate that a wealth of preclinical models have shown promising results through combination therapies. The applications of venetoclax in solid tumors warrant further clinical investigation to define its prospects.
Vascular and Urinary Tract Anatomic Variants Relevant to Para-Aortic Lymphadenectomy in Women with Gynecological Cancers
Authors: Kovačević Nina , Hočevar Marko , Vivod Gregor , Merlo Sebastjan
Published: October 2023

Background: Para-aortic lymphadenectomy is an essential part of gynecologic oncologic surgical treatment. The surgeon should be aware of the complex usual anatomy and its common variants. Methods: Between January 2021 and May 2023, 58 women underwent para-aortic lymphadenectomy for gynecologic malignancies. Results: Vascular and urinary tract anatomic variants were retrospectively reviewed from the prospective institutional database and results were compared with preoperative contrast-enhanced abdominal CT. Of these 58 women, 47 women had no vascular or urinary tract variants. One woman had a double inferior vena cava, two patients were found to have a retro-aortic left renal vein, four had accessory renal arteries, two had a double left ureter, one had a ptotic kidney in the iliac fossa, and one patient had bilateral kidney malrotation. Anatomic variants in the preoperative CT were described by a radiologist in only two patients, and additional vascular and urinary tract variants were found incidentally at the time of surgery. Conclusions: Acknowledgment of vascular and urinary tract variants is helpful for the surgeon to establish an appropriate surgical plan and to avoid iatrogenic surgical trauma.
An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype
Authors: Vydra Natalia , Toma-Jonik Agnieszka , Janus Patryk , Mrowiec Katarzyna , Stokowy Tomasz , Głowala-Kosińska Magdalena , Sojka Damian Robert , Olbryt Magdalena , Widłak Wiesława
Published: October 2023

HSF1 is a well-known heat shock protein expression regulator in response to stress. It also regulates processes important for growth, development or tumorigenesis. We studied the HSF1 influence on the phenotype of non-tumorigenic human mammary epithelial (MCF10A and MCF12A) and several triple-negative breast cancer cell lines. MCF10A and MCF12A differ in terms of HSF1 levels, morphology, growth in Matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells; MCF12A resemble mesenchymal cells). HSF1 down-regulation led to a reduced proliferation rate and spheroid formation in Matrigel by MCF10A cells. However, it did not affect MCF12A proliferation but led to CDH1 up-regulation and the formation of better organized spheroids. HSF1 overexpression in MCF10A resulted in reduced CDH1 and increased VIM expression and the acquisition of elongated fibroblast-like morphology. The above-mentioned results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype, while a lowering of HSF1 could reverse the mesenchymal phenotype to an epithelial one. Therefore, HSF1 may be involved in the remodeling of mammary gland architecture over the female lifetime. Moreover, HSF1 levels positively correlated with the invasive phenotype of triple-negative breast cancer cells, and their growth was inhibited by the HSF1 inhibitor DTHIB.
Hydroisomerization Catalysts for High-Quality Diesel Fuel Production
Authors: Aljajan Yamen , Stytsenko Valentin , Rubtsova Maria , Glotov Aleksandr
Published: October 2023

Upgrading the properties of diesel fractions is considered one of the crucial processes in the petrochemical industry; and for this purpose in laboratory-scale researching it is studied on the base of the hydroisomerization of n-hexadecane as a main model reaction. Recently, zeolite-based bifunctional catalysts have proven their efficiency due to their remarkable acidity, shape-selectivity and relative resistance to deactivation. In this review, different topological-type zeolite-based catalysts, the mechanism of their catalytic effect in n-C16 isomerization, and the principles of shape-selectivity are reviewed. A comparison of their structural-operational characteristics is made. The impact of some feedstock impurities on the catalyst’s performance and deactivation due to carbonaceous deposits as well as various modern eco-friendly cost-effective synthesis techniques are also discussed.
Intratumoral Administration of High-Concentration Nitric Oxide and Anti-mPD-1 Treatment Improves Tumor Regression Rates and Survival in CT26 Tumor-Bearing Mice
Authors: Confino Hila , Sela Yogev , Epshtein Yana , Malka Lidor , Goldshtein Matan , Chaisson Selena , Lisi Steve , Avniel Amir , Monson Jedidiah Mercer , Dirbas Frederick M.
Published: October 2023

Background: Immune checkpoint inhibitors have transformed clinical oncology. However, their use is limited as response is observed in only ~20–50% of patients. Previously, we demonstrated that treating CT26 tumor-bearing mice with ultra-high-concentration gaseous nitric oxide (UNO) followed by tumor resection stimulated antitumor immune responses. Accordingly, UNO may improve tumor response to immune checkpoint inhibitors. Here, we investigated the ability of UNO to improve the efficacy of a programmed cell death protein-1 (PD-1) antibody in vitro and in treating CT26 tumor-bearing mice. Methods: CT26 cells were injected into the flank of Balb/c mice (n = 15–16 per group). On day 6, CT26 cells were injected into the contralateral flank, and anti-mPD-1 injections commenced. Primary tumors were treated with intratumoral UNO on day 8. Tumor volume, response rates, toxicity, and survival were monitored. Results: (1) Short exposure to 25,000–100,000 parts per million (ppm) UNO in vitro resulted in significant upregulation of PD-L1 expression on CT26 cells. (2) UNO treatment in vivo consistently reduced cell viability in CT26 tumors. (3) Treatment reduced regulatory T-cell (Treg) levels in the tumor and increased levels of systemic M1 macrophages. UNO responders had increased CD8+ T-cell tumor infiltration. (4) Nine days after treatment, primary tumor growth was significantly lower in the combination arm vs. anti-mPD-1 alone (p = 0.0005). (5) Complete tumor regression occurred in 8/15 (53%) of mice treated with a combination of 10 min UNO and anti-mPD-1, 100 days post-treatment, compared to 4/16 (25%) of controls treated with anti-mPD-1 alone (p = 0.1489). (6) There was no toxicity associated with UNO treatment. (7) Combination treatment showed a trend toward increased survival 100 days post-treatment compared to anti-mPD-1 alone (p = 0.0653). Conclusion: Combining high-concentration NO and immune checkpoint inhibitors warrants further assessment especially in tumors resistant to checkpoint inhibitor therapy.
Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis
Authors: Kale Ajinath , Shelke Vishwadeep , Lei Yutian , Gaikwad Anil Bhanudas , Anders Hans-Joachim
Published: October 2023

Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney’s filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations. Voclosporin (VOC), a novel CNI, no longer requires drug level monitoring and seems to lack these adverse effects, although hypertension and drug–drug interactions still occur. VOC demonstrated efficacy superior to standard-of-care in controlling active lupus nephritis in the phase 2 AURA-LV and the phase 3 AURORA-1 trials and was approved for the treatment of active lupus nephritis. However, how to implement VOC into the current and changing treatment landscape of lupus nephritis is still debated. Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL). These include: 1. patient stratification to either VOC or BEL, 2. VOC/BEL combination therapy, 3. VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.
Electro-Optical Nose for Indoor Air Quality Monitoring
Authors: González Víctor , Meléndez Félix , Arroyo Patricia , Godoy Javier , Díaz Fernando , Suárez José Ignacio , Lozano Jesús
Published: October 2023

Nowadays, indoor air pollution is a major problem that affects human health. For that reason, measuring indoor air quality has an increasing interest. Electronic noses are low-cost instruments (compared with reference methods) capable of measuring air components and pollutants at different concentrations. In this paper, an electro-optical nose (electronic nose that includes optical sensors) with non-dispersive infrared sensors and metal oxide semiconductor sensors is used to measure gases that affect indoor air quality. To validate the developed prototype, different gas mixtures (CH4 and CO2) with variable concentrations and humidity values are generated to confirm the discrimination capabilities of the device. Principal Component Analysis (PCA) was used for dimensionality reduction purposes to show the measurements in a plot. Partial Least Squares Regression (PLS) was also performed to calculate the predictive capabilities of the device. PCA results using all the measurements from all the sensors obtained PC1 = 47% and PC2 = 10%; results are improved using only the relevant information of the sensors obtaining PC1 = 79% and PC2 = 9%. PLS results with CH4 using only MOX sensors received an RMSE = 118.8. When using NDIR and MOX sensors, RMSE is reduced to 19.868; this tendency is also observed in CO2 (RMSE = 116.35 with MOX and RMSE = 20.548 with MOX and NDIR). The results confirm that the designed electro-optical nose can detect different gas concentrations and discriminate between different mixtures of gases; also, a better correlation and dispersion is achieved. The addition of NDIR sensors gives better results in measuring specific gases, discrimination, and concentration prediction capabilities in comparison to electronic noses with metal oxide gas sensors.
Design of Nanostructures for Flexible Transparent Conductors
Authors: Li Haixia , Li Zemin , Ding Su
Published: October 2023

With the rapid development of technological evolution, flexible electronics have attracted enormous interest in recent decades due to their flexibility in various working conditions, especially in wearable and implanted devices [...]
Barrier and Antimicrobial Properties of Coatings Based on Xylan Derivatives and Chitosan for Food Packaging Papers
Authors: Roman (Iana-Roman) Mirela , Nechita Petronela , Vasile Mihaela-Aida , Cantaragiu Ceoromila Alina-Mihaela
Published: October 2023

This paper analyzes the potential of coatings based on xylan derivatives and chitosan to provide barrier properties and antimicrobial protection for paper food packaging and also to substitute the synthetic materials currently used in the food packaging industry. Colloidal dispersions of xylan derivatives (hydrophobized xylan with alkyl ketene dimers—XyAKD—and acetylated xylan—XyAc) and a chitosan biopolymer (Ch) were applied as coatings in single and two successive layers on a paper substrate using a laboratory automatic film applicator. The assessment of the water and fatty compound barrier properties of coated paper samples showed differences in effectiveness among xylan derivatives and their combination with chitosan. Generally, xylan derivative coatings improved the barrier and antimicrobial features of coated papers compared with native xylan. However, important improvements were obtained by adding to the coating formula a chitosan biopolymer. Thus, the best barrier properties for water, water vapors, oils and greases were obtained for paper coated with the acetylated xylan and chitosan formula in a single layer, where values of 30 g/m2.day for the water vapor transmission rate (WVTR), a 92.8° contact angle (CA) and a KIT rating of 8 were achieved. All coated paper samples exhibited the total inhibition of Bacillus sp. both after 24 and 48 h. Based on the obtained results in this study, one can conclude that the area of application of xylan hemicelluloses could be extended. Their utilization in appropriate chemical structures and combinations as coatings for paper can be a sustainable alternative for the food packaging industry.