bluuebunny/crossref_metadata_2025 huggingface dataset:
Global and Local Processing of Letters and Faces: The Role of Visual Focal Attention
Authors: Primativo Silvia , Arduino Lisa S.
Published: March 2023

Studies in the literature have shown how the preference towards local or global processing can vary according to different characteristics of the stimuli involved, such as stimulus type and stimulus time duration. In the present study, we investigated whether letters and faces undergo similar or different global/local processing and the attentional mechanisms that might be linked to eventual differences. We used hierarchical, congruent, and incongruent letters and faces in different time conditions (180 and 500 ms) and we conducted three different experiments. The results of Experiment 1 showed that with stimuli shown for 180 ms, letters are processed more efficiently at the local level, with an inversion of the global interference effect. Conversely, faces are still processed more efficiently at the global level, with evidence of global advantage and global interference. The results of Experiment 2 showed that when the same stimuli are presented for longer (500 ms), they are still processed differently. Indeed, we observed faster local processing for letters but still a tendency, even if not significant, toward a global processing advantage for faces. Moreover, the cue-size effect, i.e., the ability to modulate visual focal attention based on the characteristics of the cue, was measured. In Experiment 3, the cue-size effect showed a statistically significant correlation with the local processing advantage for letters but not for faces. We conclude that during the almost automatic processing of letters it is possible to modulate focal attention on the basis of the task, narrowing the field of visual attention during the local task and neglecting the global stimulus. Conversely, during face processing, the holistic mechanism tends to prevail over focal attention modulation skills, even when it is explicitly required to focus on the local stimulus.
Deep Brain Stimulation for Chronic Facial Pain: An Individual Participant Data (IPD) Meta-Analysis
Authors: Qassim Hebatallah , Zhao Yining , Ströbel Armin , Regensburger Martin , Buchfelder Michael , de Oliveira Daniela Souza , Del Vecchio Alessandro , Kinfe Thomas
Published: March 2023

Despite available, advanced pharmacological and behavioral therapies, refractory chronic facial pain of different origins still poses a therapeutic challenge. In circumstances where there is insufficient responsiveness to pharmacological/behavioral therapies, deep brain stimulation should be considered as a potential effective treatment option. We performed an individual participant data (IPD) meta-analysis including searches on PubMed, Embase, and the Cochrane Library (2000–2022). The primary endpoint was the change in pain intensity (visual analogue scale; VAS) at a defined time-point of ≤3 months post-DBS. In addition, correlation and regression analyses were performed to identify predictive markers (age, duration of pain, frequency, amplitude, intensity, contact configuration, and the DBS target). A total of seven trials consisting of 54 screened patients met the inclusion criteria. DBS significantly reduced the pain levels after 3 months without being related to a specific DBS target, age, contact configuration, stimulation intensity, frequency, amplitude, or chronic pain duration. Adverse events were an infection or lead fracture (19%), stimulation-induced side effects (7%), and three deaths (unrelated to DBS—from cancer progression or a second stroke). Although comparable long-term data are lacking, the current published data indicate that DBS (thalamic and PVG/PAG) effectively suppresses facial pain in the short-term. However, the low-quality evidence, reporting bias, and placebo effects must be considered in future randomized-controlled DBS trials for facial pain.
Inhibition of Microglial Activation by Amitriptyline and Doxepin in Interferon-β Pre-Treated Astrocyte–Microglia Co-Culture Model of Inflammation
Authors: Faustmann Timo Jendrik , Wawrzyniak Marisa , Faustmann Pedro M. , Corvace Franco , Ismail Fatme Seval
Published: March 2023

Depression may occur in patients with multiple sclerosis, especially during interferon-β (IFN-β) treatment, and therapy with antidepressants may be necessary. Interactions of IFN-β with antidepressants concerning glia-mediated inflammation have not yet been studied. Primary rat co-cultures of astrocytes containing 5% (M5, consistent with “physiological” conditions) or 30% (M30, consistent with “pathological, inflammatory” conditions) of microglia were incubated with 10 ng/mL amitriptyline or doxepin for 2 h, or with 2000 U/mL IFN-β for 22 h. To investigate the effects of antidepressants on IFN-β treatment, amitriptyline or doxepin was added to IFN-β pre-treated co-cultures. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to measure the glial cell viability, immunocytochemistry was performed to evaluate the microglial activation state, and ELISA was performed to measure pro-inflammatory TNF-α and IL-6 cytokine concentrations. Incubation of inflammatory astrocyte–microglia co-cultures with amitriptyline, doxepin or IFN-β alone, or co-incubation of IFN-β pre-treated co-cultures with both antidepressants, significantly reduced the extent of inflammation, with the inhibition of microglial activation. TNF-α and IL-6 levels were not affected. Accordingly, the two antidepressants did not interfere with the anti-inflammatory effect of IFN-β on astrocytes and microglia. Furthermore, no cytotoxic effects on glial cells were observed. This is the first in vitro study offering novel perspectives in IFN-β treatment and accompanying depression regarding glia.
Broken Ring enVision Search (BReViS): A New Clinical Test of Attention to Assess the Effect of Layout and Crowding on Visual Search
Authors: Facchin Alessio , Simioni Maura , Maffioletti Silvio , Daini Roberta
Published: March 2023

The assessment of attention in neuropsychological patients could be performed with visual search tests. The Broken Rings enVision Search test (BReViS) here proposed represents a novel open access paper-and-pencil tool in which layout and crowding are varied among four cards. These manipulations allow the assessment of different components of attention: a selective component, the visuo-spatial orientation of attention, and the focal attention, involved in a crowding phenomenon. Our purpose was to determine the characteristics of the BReViS test, provide specific normative data, and assess these components across the lifespan. The test was administered to a sample of 550 participants aged between 20 and 79 years old and to a series of patients. Three indexes targeting different components of visuo-spatial attention (selective attention, strategic orientation of visual attention, focal attention) were obtained by combining execution times and accuracy together with the total errors. The results showed that age, education and gender influenced, in different combinations, the four indexes, for which specific norms were developed. Regression-based norms were provided in percentiles and equivalent scores. All patients showed pathological scores and specific patterns of attentional deficits. The BreViS test proved to be a free and easy valuable tool which can be used in the clinical environment to assess attentional deficits in neuropsychological patients.
Locomotion Outcome Improvement in Mice with Glioblastoma Multiforme after Treatment with Anastrozole
Authors: Aguilar-García Irene Guadalupe , Jiménez-Estrada Ismael , Castañeda-Arellano Rolando , Alpirez Jonatan , Mendizabal-Ruiz Gerardo , Dueñas-Jiménez Judith Marcela , Gutiérrez-Almeida Coral Estefania , Osuna-Carrasco Laura Paulina , Ramírez-Abundis Viviana , Dueñas-Jiménez Sergio Horacio
Published: March 2023

Glioblastoma Multiforme (GBM) is a tumor that infiltrates several brain structures. GBM is associated with abnormal motor activities resulting in impaired mobility, producing a loss of functional motor independence. We used a GBM xenograft implanted in the striatum to analyze the changes in Y (vertical) and X (horizontal) axis displacement of the metatarsus, ankle, and knee. We analyzed the steps dissimilarity factor between control and GBM mice with and without anastrozole. The body weight of the untreated animals decreased compared to treated mice. Anastrozole reduced the malignant cells and decreased GPR30 and ERα receptor expression. In addition, we observed a partial recovery in metatarsus and knee joint displacement (dissimilarity factor). The vertical axis displacement of the GBM+anastrozole group showed a difference in the right metatarsus, right knee, and left ankle compared to the GBM group. In the horizontal axis displacement of the right metatarsus, ankle, and knee, the GBM+anastrozole group exhibited a difference at the last third of the step cycle compared to the GBM group. Thus, anastrozole partially modified joint displacement. The dissimilarity factor and the vertical and horizontal displacements study will be of interest in GBM patients with locomotion alterations. Hindlimb displacement and gait locomotion analysis could be a valuable methodological tool in experimental and clinical studies to help diagnose locomotive deficits related to GBM.
Intergenerational Support and Second-Child Fertility Intention in the Chinese Sandwich Generation: The Parallel Mediation Model of Double Burnout
Authors: Fu Wenxiao , Zhao Wenlong , Deng Fei
Published: March 2023

In 2013, the Chinese government implemented a two-child policy to increase the country’s fertility rate. However, the persistently low rates necessitated other measures to boost fertility. This study empirically investigated the association between intergenerational support and second-child fertility intention in the Chinese sandwich generation and demonstrated the mediating role of parental burnout and burnout in caring for grandparents. Survey data collected at Time 1, Time 2, and Time 3 included 2939 participants from different regions of China. Before analyzing the data, coarsened exact matching and propensity score matching was conducted to reduce sampling bias. Regression analysis results indicated that intergenerational support has a significant total positive effect on second-child fertility intention. Furthermore, mediation path analysis revealed that parental burnout and burnout in caring for grandparents play significant but opposite directional mediating roles in the association between intergenerational support and second-child fertility intention. Sensitivity analysis using different calipers yielded similar results. These results indicated that second-child fertility intention can be increased among the Chinese sandwich generation with intergenerational support, by mitigating parental burnout. However, intergenerational support did not alleviate burnout in caring for grandparents in the sandwich generation; therefore, formal older adult care policies are required to help the sandwich generation experience lower burnout, while receiving intergenerational support.
The Phenomenon of Cracking in Cement Concretes and Reinforced Concrete Structures: The Mechanism of Cracks Formation, Causes of Their Initiation, Types and Places of Occurrence, and Methods of Detection—A Review
Authors: Golewski Grzegorz Ludwik
Published: March 2023

Cracks and cavities belong to two basic forms of damage to the concrete structure, which may reduce the load-bearing capacity and tightness of the structure and lead to failures and catastrophes in construction structures. Excessive and uncontrolled cracking of the structural element may cause both corrosion and weakening of the adhesion of the reinforcement present in it. Moreover, cracking in the structure negatively affects its aesthetics and in extreme cases may cause discomfort to people staying in such a building. Therefore, the following article provides an in-depth review of issues related to the formation and development of damage and cracking in the structure of concrete composites. It focuses on the causes of crack initiation and characterizes their basic types. An overview of the most commonly used methods for detecting and analyzing the shape of microcracks and diagnosing the trajectory of their propagation is also presented. The types of cracks occurring in concrete composites can be divided according to eight specific criteria. In reinforced concrete elements, macrocracks depend on the type of prevailing loads, whereas microcracks are correlated with their specific case. The analyses conducted show that microcracks are usually rectilinear in shape in tensioned elements; in shear elements there are wing microcracks with straight wings; and torsional stresses cause changes in wing microcrack morphology in that the tips of the wings are twisted. It should be noted that the subject matter of microcracks and cracks in concrete and structures made of this material is important in many respects as it concerns, in a holistic approach, the durability of buildings, the safety of people staying in the buildings, and costs related to possible repairs to damaged structural elements. Therefore, this problem should be further investigated in the field of evaluation of the cracking and fracture processes, both in concrete composites and reinforced concrete structures.
Investigation of Moisture Condensation on the Surface of the Bottom Chord of a Steel Truss of a Historical Building
Authors: Semko Oleksandr , Yurin Oleg , Filonenko Olena , Semko Volodymyr , Rabenseifer Roman , Mahas Nataliia
Published: March 2023

This paper investigates the conditions under which moisture condensation occurs on the surface of the bottom chord of a steel truss at the ceiling level of the attic hall of a historical building in Poltava, Ukraine. Moisture condensation on steel structural elements leads to steel corrosion and a decrease in the thickness of structural elements. As a result, the load-bearing capacity of both individual elements and the entire structure can be reduced. This paper describes how different parameters affect the process of condensate formation on the surface of steel bottom chord angles of the truss. Three parameters are investigated: the filling of the gap between the angles and precast reinforced concrete elements resting on the lower flange of the angles with thermal insulation; the filling of the gap between the two angles of the bottom chord of the truss with thermal insulation; and the possibility of detachment of the different sizes of finishing layer from the bottom flange surface of the angles. Verification calculations of the possibility of condensation forming on the metal surfaces of the bottom chord of trusses were also performed for the developed design solutions for restoration.
Effect of Block Morphology on Building Energy Consumption of Office Blocks: A Case of Wuhan, China
Authors: Xu Shen , Li Gaomei , Zhang Hailong , Xie Mengju , Mendis Thushini , Du Hu
Published: March 2023

Block morphology refers to critical parameters influencing building energy performance on the block scale. However, analysis of the combined effect of block morphological parameters on building energy consumption with real blocks is lacking. In this paper, the aim is to evaluate the combined effect of office block morphology on building energy consumption in the context of the Hot-summer and Cold-winter zone in China. First, a workflow for the energy assessment of office buildings with the coupled block morphology on the block scale was proposed with evaluation tools. Seventy office blocks in Wuhan were taken as examples and then classified based on building layout typology and building height. Afterwards, the morphological parameters and building energy use intensity (EUI) for different blocks were calculated. Then, the combined effect of block morphology on the buildings’ energy consumption was evaluated and the model on predicting the building energy consumption of office blocks was proposed. Finally, based on the results, low-energy design strategies were projected for office blocks. The results illustrated that the effect of block morphology on building cooling, heating, and lighting is EUI 28.83%, 28.56%, and 23.23%, respectively. Building shape factor (BSF), floor area ratio (FAR), average building height of block (BH), and average building depth of block (BD) are effective block morphological parameters. The key morphological parameters which combined affect the building energy consumption of office blocks are BSF and FAR; BSF has 1.24 times the effect on building energy consumption than FAR. The workflow built in this paper can be applied to other cities around the world for promoting sustainable cities.
Ensuring Efficient Implementation of Lean Construction Projects Using Building Information Modeling
Authors: Uvarova Svetlana S. , Orlov Alexandr K. , Kankhva Vadim S.
Published: March 2023

Modern economic dynamics makes it more expedient to introduce lean construction tools into the activities of all value chain participants in construction. The need to take into account digitalization processes in construction entail an increase in the urgency of the problem related to the integration of digital technologies into the concept of lean construction. Many studies have been devoted to the problems of integrating lean construction with building information modeling (BIM) tools, which have proved their effectiveness and substantiated obstacles to their active implementation. However, issues related to assessing the cost-effectiveness of integrating lean construction with BIM and other digital technologies (if companies refuse to introduce BIM), which allow for improving the interaction of investment and construction project participants, have not been actively studied. This article examines the effectiveness of using digital tools and technologies that will contribute to the development of lean construction and reduce the corresponding losses of investment and construction projects in the example of Russia. A literature review, interviews with experts aimed at summarizing the results, as well as practical calculations taken from the existing project, were used for the purposes of this study. The main losses at each stage of an investment and construction project arising from problems in the interaction of participants in Russian construction were identified, the effects of integrating lean construction with BIM and other digital technologies were determined, an algorithm for selecting digital technologies to be integrated with lean construction was developed. The methodology for calculating the effect of the implementation of tools and principles of lean–digital interaction technologies, as well as recommendations for the implementation of tools in construction practice, were discussed.
Cost-Optimal Renovation Solutions for Detached Rural Houses in Severe Cold Regions of China
Authors: Hu Xinyi , Jokisalo Juha , Kosonen Risto , Lehtonen Matti , Shao Teng
Published: March 2023

High heating expenses are observed in numerous Chinese rural houses located in severe cold regions due to the high heating demand, inferior envelope performance and low-efficiency heating equipment. The local traditional heating methods include Chinese Kangs and coal boilers with water-based radiators. The intermittent operation and manual regulation of these systems result in significant temperature differences and inadequate thermal comfort. This study presents the cost-optimal envelope renovation solutions with the minimized lifecycle cost (LCC) during a 20-year discount period and CO2 emissions of annual delivered energy consumptions. A single-family detached rural house in Harbin was used as a case building, illustrating the typical state of comparable houses in this climate context. Simulation-based multi-optimization analysis was conducted in this study using the building simulation tool IDA ICE and its integrated optimization tool AutoMOO. The results indicate that the cost-optimal renovation solutions with intermittent and continuous heating can cut CO2 emissions by 30% and 40%, respectively. The LCC with intermittent heating is still 7% greater than its pre-renovation case, which may require external financial support to encourage the renovation conduction, while the LCC with continuous heating decreased by 8% after renovation. According to the comparison results, cost-optimal solutions have significant advantages in both reductions of LCC and CO2 emissions over standard-based solutions. Moreover, utilizing intermittent heating is more effective than continuous heating in demonstrating the positive impacts of envelope renovation on increasing average temperature, decreasing temperature differences and lowering occupied time at low thermal comfort levels.
Stress Mechanism and Energy Dissipation Performance Optimization of Prefabricated ECC/RC Combined Shear Walls under Low Cyclic Loading
Authors: Yang Jian , Jiang Liqiang , Guo Haizhu , Yao Guohuang
Published: March 2023

The application of ECC materials in major stress and energy dissipation regions of prefabricated reinforced concrete (RC) shear walls to form prefabricated ECC/RC combined shear walls can improve the seismic capacity of structures. The stress and damage mechanism of a 1/2-scale two-story spatial structure specimen of the prefabricated ECC/RC combined shear wall under low cyclic loading is numerically simulated. By comparing the numerical simulation results with the experimental results, the correctness of the numerical simulation method is verified. On this basis, a detailed whole process analysis is carried out by the numerical simulation method, including the stress distribution of the concrete and ECC, compression damage of the concrete and ECC, crack distribution of the concrete and ECC, stress distribution of the reinforcement, and structural and fabricated joint displacement. The whole process analysis effectively reflects the cracking, damage, and failure law of the specimen and extensively reveals the failure mechanism and internal force distribution law of the fabricated ECC/RC combined shear wall structure. Based on the stress and damage mechanism, the seismic energy dissipation performance with different ranges of ECC use in the bottom of the wall is studied. The results show that when the ECC height of the bottom walls is 400 mm, the energy dissipation performance of the prefabricated ECC/RC combined shear wall structure reaches an optimal value.
Sun-Protective Clothing Worn Regularly during Early Childhood Reduces the Number of New Melanocytic Nevi: The North Queensland Sun-Safe Clothing Cluster Randomized Controlled Trial
Authors: Harrison Simone L. , Buettner Petra G. , Nowak Madeleine J.
Published: March 2023

Numerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers in Townsville (19.25° S), Australia, were matched on shade provision and socioeconomic status. One center from each pair was randomized to the intervention arm and the other to the control arm. Children at 13 intervention centers wore study garments and legionnaire hats at childcare and received sun-protective swimwear and hats for home use, while children at the 12 control centers did not. The 1–35-month-old children (334 intervention; 210 control) were examined for moles at baseline (1999–2002) and were re-examined annually for up to 4 years. Both groups were similar at baseline. Children at intervention centers acquired fewer new moles overall (median 12.5 versus 16, p = 0.02; 0.46 versus 0.68 moles/month, p = 0.001) and fewer new moles on clothing-protected skin (6 vs. 8; p = 0.021 adjusted for confounding and cluster sampling) than controls. Intervention children had 24.3% fewer new moles overall (26.5 versus 35) and 31.6% (13 versus 19) fewer moles on clothing-protected skin than controls after 3.5 years. Sunlight’s influence on nevogenesis is mitigated when children regularly wear UPF 30-50+ clothing covering half their body, implying that increased clothing cover reduces melanoma risk. Sun-protective clothing standards should mandate reporting of the percentage of garment coverage for childrenswear.
Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer
Authors: Viganò Mauro , La Milia Marta , Grassini Maria Vittoria , Pugliese Nicola , De Giorgio Massimo , Fagiuoli Stefano
Published: March 2023

Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs.
Combining CNN Features with Voting Classifiers for Optimizing Performance of Brain Tumor Classification
Authors: Alturki Nazik , Umer Muhammad , Ishaq Abid , Abuzinadah Nihal , Alnowaiser Khaled , Mohamed Abdullah , Saidani Oumaima , Ashraf Imran
Published: March 2023

Brain tumors and other nervous system cancers are among the top ten leading fatal diseases. The effective treatment of brain tumors depends on their early detection. This research work makes use of 13 features with a voting classifier that combines logistic regression with stochastic gradient descent using features extracted by deep convolutional layers for the efficient classification of tumorous victims from the normal. From the first and second-order brain tumor features, deep convolutional features are extracted for model training. Using deep convolutional features helps to increase the precision of tumor and non-tumor patient classification. The proposed voting classifier along with convoluted features produces results that show the highest accuracy of 99.9%. Compared to cutting-edge methods, the proposed approach has demonstrated improved accuracy.
A Systematic Review and Meta-Analysis of Supramarginal Resection versus Gross Total Resection in Glioblastoma: Can We Enhance Progression-Free Survival Time and Preserve Postoperative Safety?
Authors: Wach Johannes , Vychopen Martin , Kühnapfel Andreas , Seidel Clemens , Güresir Erdem
Published: March 2023

To date, gross total resection (GTR) of the contrast-enhancing area of glioblastoma (GB) is the benchmark treatment regarding surgical therapy. However, GB infiltrates beyond those margins, and most tumors recur in close proximity to the initial resection margin. It is unclear whether a supramarginal resection (SMR) enhances progression-free survival (PFS) time without increasing the incidence of postoperative surgical complications. The aim of the present meta-analysis was to investigate SMR with regard to PFS and postoperative surgical complications. We searched for eligible studies comparing SMR techniques with conventional GTR in PubMed, Cochrane Library, Web of Science, and Medline databases. From 3158 initially identified records, 11 articles met the criteria and were included in our meta-analysis. Our results illustrate significantly prolonged PFS time in SMR compared with GTR (HR: 11.16; 95% CI: 3.07–40.52, p = 0.0002). The median PFS of the SMR arm was 8.44 months (95% CI: 5.18–11.70, p < 0.00001) longer than the GTR arm. The rate of postoperative surgical complications (meningitis, intracranial hemorrhage, and CSF leaks) did not differ between the SMR group and the GTR group. SMR resulted in longer median progression-free survival without a negative postoperative surgical risk profile. Multicentric prospective randomized trials with a standardized definition of SMR and analysis of neurologic functioning and health-related quality of life are justified and needed to improve the level of evidence.
A Scoping Review and a Taxonomy to Assess the Impact of Mobile Apps on Cancer Care Management
Authors: Dhar Eshita , Bah Adama Ns , Chicchi Giglioli Irene Alice , Quer Silvia , Fernandez-Luque Luis , Núñez-Benjumea Francisco J. , Malwade Shwetambara , Uddin Mohy , Upadhyay Umashankar , Syed-Abdul Shabbir
Published: March 2023

Mobile Health (mHealth) has a great potential to enhance the self-management of cancer patients and survivors. Our study aimed to perform a scoping review to evaluate the impact and trends of mobile application-based interventions on adherence and their effects on health outcomes among the cancer population. In addition, we aimed to develop a taxonomy of mobile-app-based interventions to assist app developers and healthcare researchers in creating future mHealth cancer care solutions. Relevant articles were screened from the online databases PubMed, EMBASE, and Scopus, spanning the time period from 1 January 2016 to 31 December 2022. Of the 4135 articles initially identified, 55 were finally selected for the review. In the selected studies, breast cancer was the focus of 20 studies (36%), while mixed cancers were the subject of 23 studies (42%). The studies revealed that the usage rate of mHealth was over 80% in 41 of the 55 studies, with factors such as guided supervision, personalized suggestions, theoretical intervention foundations, and wearable technology enhancing adherence and efficacy. However, cancer progression, technical challenges, and unfamiliarity with devices were common factors that led to dropouts. We also proposed a taxonomy based on diverse theoretical foundations of mHealth interventions, delivery methods, psycho-educational programs, and social platforms. We suggest that future research should investigate, improve, and verify this taxonomy classification to enhance the design and efficacy of mHealth interventions.
The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers
Authors: Hsu Sheng-Kai , Jadhao Mahendra , Liao Wei-Ting , Chang Wen-Tsan , Lin I-Ling , Chiu Chien-Chih
Published: March 2023

Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.
Body Composition of Patients Undergoing Radical Cystectomy for Bladder Cancer: Sarcopenia, Low Psoas Muscle Index, and Myosteatosis Are Independent Risk Factors for Mortality
Authors: Engelmann Simon U. , Pickl Christoph , Haas Maximilian , Kaelble Sebastian , Hartmann Valerie , Firsching Maximilian , Lehmann Laura , Gužvić Miodrag , van Rhijn Bas W. G. , Breyer Johannes , Burger Maximilian , Mayr Roman
Published: March 2023

Background: We assessed a wide array of body composition parameters to identify those most relevant as prognostic tools for patients undergoing radical cystectomy (RC) due to bladder cancer (BC). Methods: In this retrospective, single-center study, preoperative computed tomography (CT) scans of 657 patients were measured at the level of the 3rd lumbar vertebra (L3) to determine common body composition indices including sarcopenia, myosteatosis, psoas muscle index (PMI), subcutaneous and visceral fat index (SFI and VFI), visceral-to-subcutaneous fat ratio (VSR), and visceral obesity. Predictors of overall survival (OS) and cancer-specific survival (CSS) were identified in univariate and multivariate survival analysis. Results: Sarcopenia and a low PMI were independently associated with shorter OS (Sarcopenia: HR 1.30; 95% CI 1.02–1.66; p = 0.04 and a low PMI: HR 1.32; 95% CI 1.02–1.70; p = 0.03) and CSS (Sarcopenia: HR 1.64; 95% CI 1.19–2.25; p < 0.01 and a low PMI: HR 1.41; 95% CI 1.02–1.96; p = 0.04). Myosteatosis, measured as decreasing average Hounsfield units of skeletal muscle, was an independent risk factor for OS (HR 0.98; 95% CI 0.97–1.00; p = 0.01) and CSS (HR 0.98; 95% CI 0.96–1.00; p < 0.05). The assessed adipose tissue indices were not significant predictors for OS and CSS. Conclusions: Sarcopenia, a low PMI, and myosteatosis are independent predictors for OS and CSS in patients undergoing radical cystectomy for bladder cancer.
The Melanoma-Associated Antigen Family A (MAGE-A): A Promising Target for Cancer Immunotherapy?
Authors: Alsalloum Alaa , Shevchenko Julia , Sennikov Sergey
Published: March 2023

Early efforts to identify tumor-associated antigens over the last decade have provided unique cancer epitopes for targeted cancer therapy. MAGE-A proteins are a subclass of cancer/testis (CT) antigens that are presented on the cell surface by MHC class I molecules as an immune-privileged site. This is due to their restricted expression to germline cells and a wide range of cancers, where they are associated with resistance to chemotherapy, metastasis, and cancer cells with an increasing potential for survival. This makes them an appealing candidate target for designing an effective and specific immunotherapy, thereby suggesting that targeting oncogenic MAGE-As with cancer vaccination, adoptive T-cell transfer, or a combination of therapies would be promising. In this review, we summarize and discuss previous and ongoing (pre-)clinical studies that target these antigens, while bearing in mind the benefits and drawbacks of various therapeutic strategies, in order to speculate on future directions for MAGE-A-specific immunotherapies.
The Association between Patient’s Age and Head and Neck Cancer Treatment Decision—A Population-Based Diagnoses-Related Group-Based Nationwide Study in Germany
Authors: Kouka Mussab , Hermanns Isabel , Schlattmann Peter , Guntinas-Lichius Orlando
Published: March 2023

Investigations on the association between patient’s age and head and neck cancer (HNC) treatment decision are sparse. Nationwide diagnoses-related group-based data of 1,226,357 cases hospitalized with primary HNC in Germany from 2005 to 2018 were included. Negative binomial regression was performed to study the development of the treatment rates over time. For all treatment options, i.e., biopsies, surgery, radiotherapy, and chemotherapy/biologicals, increases in the treatment rates were seen in patients >80 years (surgery: oral cavity: relative risk [RR]: 1.2, CI: 1.13–1.20; oropharynx: RR: 1.2, CI: 1.15–1.34; hypopharynx: RR: 1.1, CI: 1.02–1.17; larynx: RR: 1.1, CI: 1.04–1.12; radiotherapy: oral cavity: RR: 1.1, CI: 1.07–1.23; oropharynx: RR: 1.3, CI: 1.16–1.49; hypopharynx: RR: 1.3, CI: 1.21–1.46; larynx: RR 1.2, CI: 1.03–1.29; chemotherapy: oral cavity: RR: 1.2, CI: 1.06–1.31; salivary glands: RR: 1.3, CI: 1.09–1.50; oropharynx: RR: 1.4, CI: 1.12–1.83; hypopharynx: RR: 1.3, CI: 1.06–1.48; larynx: RR: 1.3, CI: 1.08–1.52, all p < 0.05). Older age cohorts (≥80 years) need more awareness as they are mainly responsible for the increase in the rates of surgery, radiotherapy, and chemotherapy/biologics in HNC patients.
Biomarkers in the Era of Precision Oncology
Authors: Baxevanis Constantin N.
Published: March 2023

Cancer heterogeneity provides a formidable obstacle to optimizing clinical protocols to achieve durable clinical responses [...]
Construction of NiFe-Layered Double Hydroxides Arrays as Robust Electrocatalyst for Oxygen Evolution Reaction
Authors: Liu Qiyu , Wang Yi , Lu Xihong
Published: March 2023

Electrochemical water splitting is considered to be an important method for efficient hydrogen production to alleviate energy shortage and environmental pollution, but its development is currently limited by the slow oxygen evolution reaction (OER). To solve the sluggish reaction kinetics of OER, the focus is on the exploration of low-cost and efficient electrocatalysts, which is quite significant for the development of electrochemical water splitting. Herein, a NiFe layered double hydroxides (LDH) electrocatalyst (denoted as FNH) is achieved by a simple one-step hydrothermal method. The experimental results show that due to the synergistic interaction of introduced Fe species, the FNH possesses a special three-dimensional (3D) vertical nanosheet array structure, which results in efficient ion access. More importantly, the strong electronic interaction between Fe and Ni sites results in the optimized electronic structure of the Ni sites, which not only generates abundant Ni3+ sites as optimized active sites for OER, but also decrease the charge transfer resistance. Thus, the FNH catalyst exhibits an extraordinary overpotential of 386.8 mV to deliver 100 mA cm−2, showing better activity than that of RuO2, and satisfactory cycling stability after continuous operation for 28 h. Our work provides an easy-to-implement method to obtain high-efficiency OER electrocatalysts.
Transition Metal (Fe2O3, Co3O4 and NiO)-Promoted CuO-Based α-MnO2 Nanowire Catalysts for Low-Temperature CO Oxidation
Authors: Zhang Haiou , Zhang Yixin , Song Huikang , Cui Yan , Xue Yingying , Wu Cai-e , Pan Chao , Xu Jingxin , Qiu Jian , Xu Leilei , Chen Mindong
Published: March 2023

As a toxic pollutant, carbon monoxide (CO) usually causes harmful effects on human health. Therefore, the thermally catalytic oxidation of CO has received extensive attention in recent years. The CuO-based catalysts have been widely investigated due to their availability. In this study, a series of transition metal oxides (Fe2O3, Co3O4 and NiO) promoted CuO-based catalysts supported on the α-MnO2 nanowire catalysts were prepared by the deposition precipitation method for catalytic CO oxidation reactions. The effects of the loaded transition metal type, the loading amount, and the calcination temperature on the catalytic performances were systematically investigated. Further catalyst characterization showed that the CuO/α-MnO2 catalyst modified with 3 wt% Co3O4 and calcined at 400 °C performed the highest CO catalytic activity (T90 = 75 °C) among the investigated catalysts. It was supposed that the loading of the Co3O4 dopant not only increased the content of oxygen vacancies in the catalyst but also increased the specific surface area and pore volume of the CuO/α-MnO2 nanowire catalyst, which would further enhance the catalytic activity. The CuO/α-MnO2 catalyst modified with 3 wt% NiO and calcined at 400 °C exhibited the highest surface adsorbed oxygen content and the best normalized reaction rate, but the specific surface area limited its activity. Therefore, the appropriate loading of the Co3O4 modifier could greatly enhance the activity of CuO/α-MnO2. This research could provide a reference method for constructing efficient low-temperature CO oxidation catalysts.
Autophagy Function and Benefits of Autophagy Induction in Models of Spinocerebellar Ataxia Type 3
Authors: Watchon Maxinne , Luu Luan , Plenderleith Stuart K. , Yuan Kristy C. , Laird Angela S.
Published: March 2023

Background: Spinocerebellar ataxia 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by the expansion of the trinucleotide repeat region within the ATXN3/MJD gene. The presence of this genetic expansion results in an ataxin-3 protein containing a polyglutamine repeat region, which renders the ataxin-3 protein aggregation prone. Formation of ataxin-3 protein aggregates is linked with neuronal loss and, therefore, the development of motor deficits. Methods: Here, we investigated whether the autophagy protein quality control pathway, which is important in the process of protein aggregate removal, is impaired in a cell culture and zebrafish model of SCA3. Results: We found that SH-SY5Y cells expressing human ataxin-3 containing polyglutamine expansion exhibited aberrant levels of autophagy substrates, including increased p62 and decreased LC3II (following bafilomycin treatment), compared to the controls. Similarly, transgenic SCA3 zebrafish showed signs of autophagy impairment at early disease stages (larval), as well as p62 accumulation at advanced age stages (18 months old). We then examined whether treating with compounds known to induce autophagy activity, would aid removal of human ataxin-3 84Q and improve the swimming of the SCA3 zebrafish larvae. We found that treatment with loperamide, trehalose, rapamycin, and MG132 each improved the swimming of the SCA3 zebrafish compared to the vehicle-treated controls. Conclusion: We propose that signs of autophagy impairment occur in the SH-SY5Y model of SCA3 and SCA3 zebrafish at larval and advanced age stages. Treatment of the larval SCA3 zebrafish with various compounds with autophagy induction capacity was able to produce the improved swimming of the zebrafish, suggesting the potential benefit of autophagy-inducing compounds for the treatment of SCA3.
Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions
Authors: Saito Kenji , Cui Huxing
Published: March 2023

The importance of estrogenic signaling for a broad spectrum of biological processes, including reproduction, cancer development, energy metabolism, memory and learning, and so on, has been well documented. Among reported estrogen receptors, estrogen receptor alpha (ERα) has been known to be a major mediator of cellular estrogenic signaling. Accumulating evidence has shown that the regulations of ERα gene transcription, splicing, and expression across the tissues are highly complex. The ERα promoter region is composed of multiple leader exons and 5′-untranslated region (5′-UTR) exons. Differential splicing results in multiple ERα proteins with different molecular weights and functional domains. Furthermore, various post-translational modifications (PTMs) further impact ERα cellular localization, ligand affinity, and therefore functionality. These splicing isoforms and PTMs are differentially expressed in a tissue-specific manner, mediate certain aspects of ERα signaling, and may work even antagonistically against the full-length ERα. The fundamental understanding of the ERα splicing isoforms in normal physiology is limited and association studies of the splicing isoforms and the PTMs are scarce. This review aims to summarize the functional diversity of these ERα variants and the PTMs in normal physiological processes, particularly as studied in transgenic mouse models.
Targeting Lung–Gut Axis for Regulating Pollution Particle–Mediated Inflammation and Metabolic Disorders
Authors: Cheng Tzu-Yu , Chang Chih-Cheng , Luo Ching-Shan , Chen Kuan-Yuan , Yeh Yun-Kai , Zheng Jing-Quan , Wu Sheng-Ming
Published: March 2023

Cigarette smoking (CS) or ambient particulate matter (PM) exposure is a risk factor for metabolic disorders, such as insulin resistance (IR), increased plasma triglycerides, hyperglycemia, and diabetes mellitus (DM); it can also cause gut microbiota dysbiosis. In smokers with metabolic disorders, CS cessation decreases the risks of serious pulmonary events, inflammation, and metabolic disorder. This review included recent studies examining the mechanisms underlying the effects of CS and PM on gut microbiota dysbiosis and metabolic disorder development; one of the potential mechanisms is the disruption of the lung–gut axis, leading to gut microbiota dysbiosis, intestinal dysfunction, systemic inflammation, and metabolic disease. Short-chain fatty acids (SCFAs) are the primary metabolites of gut bacteria, which are derived from the fermentation of dietary fibers. They activate G-protein-coupled receptor (GPCR) signaling, suppress histone deacetylase (HDAC) activity, and inhibit inflammation, facilitating the maintenance of gut health and biofunction. The aforementioned gut microbiota dysbiosis reduces SCFA levels. Treatment targeting SCFA/GPCR signaling may alleviate air pollution–associated inflammation and metabolic disorders, which involve lung–gut axis disruption.
Effects of Socioeconomic Environment on Physical Activity Levels and Sleep Quality in Basque Schoolchildren
Authors: Larrinaga-Undabarrena Arkaitz , Río Xabier , Sáez Iker , Martinez Aguirre-Betolaza Aitor , Albisua Neritzel , Martínez de Lahidalga Aguirre Gorka , Sánchez Isla José Ramón , Urbano Mikel , Guerra-Balic Myriam , Fernández Juan Ramón , Coca Aitor
Published: March 2023

The socioeconomic and built environment of an area are interrelated with health data and have a direct influence on children’s development. There are facilitators and barriers for schools to promote physical activity depending on the socioeconomic status of the school. The aim of this study was to analyse the relationship between physical activity and sleep and the socioeconomic level of children in the Basque Country. The sample consisted of 1139 schoolchildren between the ages of six and seventeen (566 boys and 573 girls) from 75 schools (43 public and 32 private). Differences between groups were compared using the Mann–Whitney U test (two samples), Kruskal–Wallis one-factor ANOVA (k samples), and Spearman’s Rho correlation. There are sex differences in light (200.8 ± 62.5 vs. 215.9 ± 54.7) and moderate (69.0 ± 34.3 vs. 79.9 ± 32.1) physical activity in favour of the female group of higher socioeconomic status compared to male group of higher socioeconomic status. In the case of vigorous physical activity, the female group performed less than the male group across all socioeconomic statuses, which was statistically significant in the groups of high socioeconomic status (11.6 ± 9.3 vs. 6.9 ± 5.7) in group 2 and medium socioeconomic status (11.1 ± 9.3 vs. 7.7 ± 6.1) in group 3. There is an inverse relationship between sedentary behaviour and BMI, total bed time, total sleep time, and night-time awakenings. There is also an inverse relationship between all levels of physical activity performed with respect to BMI and total sleep efficiency. These data point towards notable inequalities in physical activity and daily sleep in Basque schoolchildren, which in turn may be marginalised in our current school system due to the effects of the socioeconomic environment.