bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death
Authors: Lamberti María Julia , Montico Barbara , Ravo Maria , Nigro Annunziata , Giurato Giorgio , Iorio Roberta , Tarallo Roberta , Weisz Alessandro , Stellato Cristiana , Steffan Agostino , Dolcetti Riccardo , Casolaro Vincenzo , Faè Damiana Antonia , Dal Col Jessica
Published: August 2022

Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission of DAMPs during ICD has been well described, whereas the epigenetic mechanisms that regulate ICD hallmarks have not yet been deeply elucidated. Here, we aimed to examine the involvement of miRNAs and their putative targets using well-established in vitro models of ICD. To this end, B cell lymphoma (Mino) and breast cancer (MDA-MB-231) cell lines were exposed to two different ICD inducers, the combination of retinoic acid (RA) and interferon-alpha (IFN-α) and doxorubicin, and to non ICD inducers such as gamma irradiation. Then, miRNA and mRNA profiles were studied by next generation sequencing. Co-expression analysis identified 16 miRNAs differentially modulated in cells undergoing ICD. Integrated miRNA-mRNA functional analysis revealed candidate miRNAs, mRNAs, and modulated pathways associated with Immune System Process (GO Term). Specifically, ICD induced a distinctive transcriptional signature hallmarked by regulation of antigen presentation, a crucial step for proper activation of immune system antitumor response. Interestingly, the major histocompatibility complex class I (MHC-I) pathway was upregulated whereas class II (MHC-II) was downregulated. Analysis of MHC-II associated transcripts and HLA-DR surface expression confirmed inhibition of this pathway by ICD on lymphoma cells. miR-4284 and miR-212-3p were the strongest miRNAs upregulated by ICD associated with this event and miR-212-3p overexpression was able to downregulate surface expression of HLA-DR. It is well known that MHC-II expression on tumor cells facilitates the recruitment of CD4+ T cells. However, the interaction between tumor MHC-II and inhibitory coreceptors on tumor-associated lymphocytes could provide an immunosuppressive signal that directly represses effector cytotoxic activity. In this context, MHC-II downregulation by ICD could enhance antitumor immunity. Overall, we found that the miRNA profile was significantly altered during ICD. Several miRNAs are predicted to be involved in the regulation of MHC-I and II pathways, whose implication in ICD is demonstrated herein for the first time, which could eventually modulate tumor recognition and attack by the immune system.
Accuracy of EEG Biomarkers in the Detection of Clinical Outcome in Disorders of Consciousness after Severe Acquired Brain Injury: Preliminary Results of a Pilot Study Using a Machine Learning Approach
Authors: Di Gregorio Francesco , La Porta Fabio , Petrone Valeria , Battaglia Simone , Orlandi Silvia , Ippolito Giuseppe , Romei Vincenzo , Piperno Roberto , Lullini Giada
Published: August 2022

Accurate outcome detection in neuro-rehabilitative settings is crucial for appropriate long-term rehabilitative decisions in patients with disorders of consciousness (DoC). EEG measures derived from high-density EEG can provide helpful information regarding diagnosis and recovery in DoC patients. However, the accuracy rate of EEG biomarkers to predict the clinical outcome in DoC patients is largely unknown. This study investigated the accuracy of psychophysiological biomarkers based on clinical EEG in predicting clinical outcomes in DoC patients. To this aim, we extracted a set of EEG biomarkers in 33 DoC patients with traumatic and nontraumatic etiologies and estimated their accuracy to discriminate patients’ etiologies and predict clinical outcomes 6 months after the injury. Machine learning reached an accuracy of 83.3% (sensitivity = 92.3%, specificity = 60%) with EEG-based functional connectivity predicting clinical outcome in nontraumatic patients. Furthermore, the combination of functional connectivity and dominant frequency in EEG activity best predicted clinical outcomes in traumatic patients with an accuracy of 80% (sensitivity = 85.7%, specificity = 71.4%). These results highlight the importance of functional connectivity in predicting recovery in DoC patients. Moreover, this study shows the high translational value of EEG biomarkers both in terms of feasibility and accuracy for the assessment of DoC.
Regulation of Insulin Clearance by Non-Esterified Fatty Acids
Authors: Najjar Sonia M. , Abdolahipour Raziyeh , Ghadieh Hilda E. , Jahromi Marziyeh Salehi , Najjar John A. , Abuamreh Basil A. M. , Zaidi Sobia , Kumarasamy Sivarajan , Muturi Harrison T.
Published: August 2022

Insulin stores lipid in adipocytes and prevents lipolysis and the release of non-esterified fatty acids (NEFA). Excessive release of NEFA during sustained energy supply and increase in abdominal adiposity trigger systemic insulin resistance, including in the liver, a major site of insulin clearance. This causes a reduction in insulin clearance as a compensatory mechanism to insulin resistance in obesity. On the other hand, reduced insulin clearance in the liver can cause chronic hyperinsulinemia, followed by downregulation of insulin receptor and insulin resistance. Delineating the cause–effect relationship between reduced insulin clearance and insulin resistance has been complicated by the fact that insulin action and clearance are mechanistically linked to insulin binding to its receptors. This review discusses how NEFA mobilization contributes to the reciprocal relationship between insulin resistance and reduced hepatic insulin clearance, and how this may be implicated in the pathogenesis of non-alcoholic fatty liver disease.
Elevated Vascular Sympathetic Neurotransmission and Remodelling Is a Common Feature in a Rat Model of Foetal Programming of Hypertension and SHR
Authors: Vieira-Rocha Maria Sofia , Sousa Joana Beatriz , Rodríguez-Rodríguez Pilar , Arribas Silvia Madaglena , Diniz Carmen
Published: August 2022

Hypertension is of unknown aetiology, with sympathetic nervous system hyperactivation being one of the possible contributors. Hypertension may have a developmental origin, owing to the exposure to adverse factors during the intrauterine period. Our hypothesis is that sympathetic hyperinnervation may be implicated in hypertension of developmental origins, being this is a common feature with essential hypertension. Two-animal models were used: spontaneously hypertensive rats (SHR-model of essential hypertension) and offspring from dams exposed to undernutrition (MUN-model of developmental hypertension), with their respective controls. In adult males, we assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), sympathetic nerve function (3H-tritium release), sympathetic innervation (immunohistochemistry) and vascular remodelling (histology). MUN showed higher SBP/DBP, but not HR, while SHR exhibited higher SBP/DBP/HR. Regarding the mesenteric arteries, MUN and SHR showed reduced lumen, increased media and adventitial thickness and increased wall/lumen and connective tissue compared to respective controls. Regarding sympathetic nerve activation, MUN and SHR showed higher tritium release compared to controls. Total tritium tissue/tyrosine hydroxylase detection was higher in SHR and MUN adventitia arteries compared to respective controls. In conclusion, sympathetic hyperinnervation may be one of the contributors to vascular remodelling and hypertension in rats exposed to undernutrition during intrauterine life, which is a common feature with spontaneous hypertension.
Characterization of Maladaptive Processes in Acute, Chronic and Remission Phases of Experimental Colitis in C57BL/6 Mice
Authors: Gelmez Elif , Lehr Konrad , Kershaw Olivia , Frentzel Sarah , Vilchez-Vargas Ramiro , Bank Ute , Link Alexander , Schüler Thomas , Jeron Andreas , Bruder Dunja
Published: August 2022

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease with unknown etiology. Dextran sulfate sodium (DSS) induced colitis is a widely used mouse model in IBD research. DSS colitis involves activation of the submucosal immune system and can be used to study IBD-like disease characteristics in acute, chronic, remission and transition phases. Insight into colon inflammatory parameters is needed to understand potentially irreversible adaptations to the chronification of colitis, determining the baseline and impact of further inflammatory episodes. We performed analyses of non-invasive and invasive colitis parameters in acute, chronic and remission phases of the DSS colitis in C57BL/6 mice. Non-invasive colitis parameters poorly reflected inflammatory aspects of colitis in chronic remission phase. We found invasive inflammatory parameters, positively linked to repeated DSS-episodes, such as specific colon weight, inflamed colon area, spleen weight, absolute cell numbers of CD4+ and CD8+ T cells as well as B cells, blood IFN-γ level, colonic chemokines BLC and MDC as well as the prevalence of Turicibacter species in feces. Moreover, microbial Lactobacillus species decreased with chronification of disease. Our data point out indicative parameters of recurrent gut inflammation in context of DSS colitis.
Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases
Authors: Di Pompo Gemma , Kusuzaki Katsuyuki , Ponzetti Marco , Leone Vito Ferdinando , Baldini Nicola , Avnet Sofia
Published: August 2022

Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis.
The Journey of Human Transthyretin: Synthesis, Structure Stability, and Catabolism
Authors: Sanguinetti Chiara , Minniti Marianna , Susini Vanessa , Caponi Laura , Panichella Giorgia , Castiglione Vincenzo , Aimo Alberto , Emdin Michele , Vergaro Giuseppe , Franzini Maria
Published: August 2022

Transthyretin (TTR) is a homotetrameric protein mainly synthesised by the liver and the choroid plexus whose function is to carry the thyroid hormone thyroxine and the retinol-binding protein bound to retinol in plasma and cerebrospinal fluid. When the stability of the tetrameric structure is lost, it breaks down, paving the way for the aggregation of TTR monomers into insoluble fibrils leading to transthyretin (ATTR) amyloidosis, a progressive disorder mainly affecting the heart and nervous system. Several TTR gene mutations have been characterised as destabilisers of TTR structure and are associated with hereditary forms of ATTR amyloidosis. The reason why also the wild-type TTR is intrinsically amyloidogenic in some subjects is largely unknown. The aim of the review is to give an overview of the TTR biological life cycle which is largely unknown. For this purpose, the current knowledge on TTR physiological metabolism, from its synthesis to its catabolism, is described. Furthermore, a large section of the review is dedicated to examining in depth the role of mutations and physiological ligands on the stability of TTR tetramers.
Evaluation of the Anti-Leishmania mexicana and -Trypanosoma brucei Activity and Mode of Action of 4,4′-(Arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)
Authors: Barreiro-Costa Olalla , Quiroga Lozano Cristina , Muñoz Erika , Rojas-Silva Patricio , Medeiros Andrea , Comini Marcelo A. , Heredia-Moya Jorge
Published: August 2022

Trypanosomiasis and leishmaniasis are neglected infections caused by trypanosomatid parasites. The first-line treatments have many adverse effects, high costs, and are prone to resistance development, hence the necessity for new chemotherapeutic options. In line with this, twenty five 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives were synthesized and evaluated in vitro for their anti-trypanosomatid activity. Ten and five compounds from this series showed IC50 ≤ 10 µM against the promastigote and the bloodstream stage of Leishmania mexicana and Trypanosoma brucei brucei, respectively. Overall, derivatives with pyrazole rings substituted with electron-withdrawing groups proved more active than those with electron-donating groups. The hits proved moderately selective towards L. mexicana and T. brucei (selectivity index, SI, compared to murine macrophages = 5–26). The exception was one derivative displaying an SI (>111–189) against T. brucei that surpassed, by >6-fold, the selectivity of the clinical drug nifurtimox (SI = 13–28.5). Despite sharing a common scaffold, the hits differed in their mechanism of action, with halogenated derivatives inducing a rapid and marked intracellular oxidative milieu in infective T. brucei. Notably, most of the hits presented better absorption, distribution, metabolism, and excretion (ADME) properties than the reference drugs. Several of the bioactive molecules herein identified represent a promising starting point for further improvement of their trypanosomatid potency and selectivity.
Highly Sensitive TiO2/Au/Graphene Layer-Based Surface Plasmon Resonance Biosensor for Cancer Detection
Authors: Mostufa Shahriar , Akib Tarik Bin Abdul , Rana Md. Masud , Islam Md. Rabiul
Published: August 2022

In this article, a hybrid TiO2/Au/graphene layer-based surface plasmon resonance (SPR) sensor with improved sensitivity and capability for cancer detection is presented. The finite element method (FEM) was used for numerical analysis. The proposed SPR biosensor was structured based on the angular analysis of the attenuated total reflection (ATR) method for the detection of various types of cancer using the refractive index component. The resonance angle shifted owing to the increment of normal and cancerous cells’ refractive index, which varied between 1.36 and 1.401 for six different types of normal and cancerous cells. According to numerical results, the obtained sensitivities for skin (basal), cervical (HeLa), adrenal gland (PC12), blood (Jurkat), and breast (MCF-7 and MDA-MB-231) cancer cells were 210 deg/RIU, 245.83 deg/RIU, 264.285 deg/RIU, 285.71 deg/RIU, 292.86 deg/RIU, and 278.57 deg/RIU, respectively. Furthermore, the detection accuracy (DA), figure of merits (FOM), and signal-to-noise ratio (SNR) were also obtained, with values of 0.263 deg−1, 48.02 RIU−1, and 3.84, respectively. Additionally, the distribution of the electric field and the propagation of the magnetic field for resonant and non-resonant conditions of the proposed structure were illustrated. It was found that an enhanced field was exhibited on the surface of the plasmonic material for resonant conditions. We also measured the penetration depth of 180 nm using decayed electric field intensity. Furthermore, the impact of using a TiO2/Au/graphene layer was demonstrated. We further conducted analyses of the effects of the thickness of the gold layer and the effects of additional graphene layers on overall sensitivities for six different types of cancer. The proposed TiO2/Au/graphene layered structure exhibited the highest overall sensitivity in terms of detecting cancerous cells from healthy cells. Moreover, the proposed sensor was numerically analyzed for a wide range of biological solutions (refractive index 1.33–1.41), and the sensor linearity was calculated with a linear regression coefficient (R2) of 0.9858. Finally, numerical results obtained in this manuscript exhibited high sensitivity in comparison with previously reported studies.
Machine Learning-Based 30-Day Hospital Readmission Predictions for COPD Patients Using Physical Activity Data of Daily Living with Accelerometer-Based Device
Authors: Verma Vijay Kumar , Lin Wen-Yen
Published: August 2022

Chronic obstructive pulmonary disease (COPD) is a significantly concerning disease, and is ranked highest in terms of 30-day hospital readmission. Generally, physical activity (PA) of daily living reflects the health status and is proposed as a strong indicator of 30-day hospital readmission for patients with COPD. This study attempted to predict 30-day hospital readmission by analyzing continuous PA data using machine learning (ML) methods. Data were collected from 16 patients with COPD over 3877 days, and clinical information extracted from the patients’ hospital records. Activity-based parameters were conceptualized and evaluated, and ML models were trained and validated to retrospectively analyze the PA data, identify the nonlinear classification characteristics of different risk factors, and predict hospital readmissions. Overall, this study predicted 30-day hospital readmission and prediction performance is summarized as two distinct approaches: prediction-based performance and event-based performance. In a prediction-based performance analysis, readmissions predicted with 70.35% accuracy; and in an event-based performance analysis, the total 30-day readmissions were predicted with a precision of 72.73%. PA data reflect the health status; thus, PA data can be used to predict hospital readmissions. Predicting readmissions will improve patient care, reduce the burden of medical costs burden, and can assist in staging suitable interventions, such as promoting PA, alternate treatment plans, or changes in lifestyle to prevent readmissions.
Development of an Electrochemical CCL5 Chemokine Immunoplatform for Rapid Diagnosis of Multiple Sclerosis
Authors: Guerrero Sara , Sánchez-Tirado Esther , Agüí Lourdes , González-Cortés Araceli , Yáñez-Sedeño Paloma , Pingarrón José M.
Published: August 2022

Serum level of CCL5 chemokine is considered an emerging biomarker for multiple sclerosis (MS). Due to the lack of specific assays for this disease, the development of a point-of-care test for rapid detection of MS could lead to avoiding diagnostics delays. In this paper, we report the first electrochemical immunoplatform for quantification of the CCL5 biomarker at the clinically required levels, able to discriminate between patients diagnosed with MS and healthy individuals. The immunosensing device involves protein capture from biological samples by complexation with biotinylated specific antibodies immobilized onto neutravidin-functionalized microparticles and sandwich assay with anti-CCL5 antibody and IgG labelled with horseradish peroxidase (HRP) for the enzyme-catalyzed amperometric detection of H2O2 using hydroquinone (HQ) as the redox mediator. The method shows excellent analytical performance for clinical application with a wide linear range of concentrations (0.1–300 ng·mL−1 CCL5, R2 = 0.998) and a low detection limit (40 pg·mL−1 CCL5). The biosensing platform was applied to the determination of the CCL5 endogenous content in 100-fold diluted sera both from healthy individuals and patients diagnosed with MS, with no further sample treatment in just two hours. The results were successfully compared with those obtained by the ELISA methodology.
Maternal Allergic Asthma Induces Prenatal Neuroinflammation
Authors: Tamayo Juan M. , Rose Destanie , Church Jamie S. , Schwartzer Jared J. , Ashwood Paul
Published: August 2022

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by impaired social interactions and communication skills and repetitive or stereotyped behaviors. Rates of ASD diagnosis continue to rise, with current estimates at 1 in 44 children in the US (Maenner 2021). Epidemiological studies have suggested a link between maternal allergic asthma and an increased likelihood of having a child diagnosed with ASD. However, a lack of robust laboratory models prevents mechanistic research from being carried out. We developed a novel mouse model of maternal asthma-allergy (MAA) and previously reported that offspring from these mothers exhibit behavioral deficits compared to controls. In addition, it was shown that epigenetic regulation of gene expression in microglia was altered in these offspring, including several autism candidate genes. To further elucidate if there is neuroinflammation in the fetus following MAA, we investigated how allergic asthma impacts the maternal environment and inflammatory markers in the placenta and fetal brain during gestation. Female C57Bl/6 mice were primed with ovalbumin (OVA) prior to allergic asthma induction during pregnancy by administering aerosolized ovalbumin or PBS control to pregnant dams at gestational days (GD)9.5, 12.5, and 17.5. Four hours after the final induction, placenta and fetal brains were collected and measured for changes in cytokines using a Luminex bead-based multiplex assay. Placental MAA tissue showed a decrease in interleukin (IL)-17 in male and female offspring. There was a sex-dependent decrease in female monocyte chemoattractant protein 1 (MCP-1). In male placentas, IL-4, C–X–C motif chemokine 10 (CXCL10)—also known as interferon γ-induced protein 10 kDa (IP-10)—and chemokine (C-C motif) ligand 5 (RANTES) were decreased. In fetal brains, elevated inflammatory cytokines were found in MAA offspring when compared to controls. Specifically, interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1α (IL-1α), IL-6, and tumor necrosis factor α (TNFα) were elevated in both males and females. In contrast, a decrease in the cytokine IL-9 was also observed. There were slight sex differences after OVA exposures. Male fetal brains showed elevated levels of macrophage inflammatory protein-2 (MIP-2), whereas female brains showed increased keratinocytes-derived chemokine (KC). In addition, IL-1𝛽 and IP-10 in male fetal brains were decreased. Together, these data indicate that repeated exposure to allergic asthma during pregnancy alters cytokine expression in the fetal environment in a sex-dependent way, resulting in homeostatic and neuroinflammatory alterations in the fetal brain.
Age Differences in the Tradeoff between Proactive and Reactive Cognitive Control in Emotional Information Processing
Authors: Zhang Ni , Wang Jingxin
Published: August 2022

Greater well-being in older adults stems from more effective emotion regulation strategies, highlighting the role of cognitive control. However, cognitive control involves different subsystems, and it is still unclear whether different subsystems have different effects on different emotional information processing. The Dual Mechanisms of Control (DMC) theory postulates that cognitive control can operate in two distinct modes, namely proactive control (a “proactive” preparatory mode) and reactive control (a “reactive” wait-and-see mode). This study created an emotional AX-CPT task to explore differences in cognitive control tradeoff between youth and older adults when processing emotional information. The results found that youth had significantly higher error rates on the emotional-neutral sequence than older adults regardless of the valence of emotional information; only in the negative condition did older adults have higher error rates on both the sad-sad and neutral-sad sequences than youth; this phenomenon was not found in the positive condition. The study showed that, in emotional information processing, youth preferred proactive control over older adults; in negative information processing, older adults preferred reactive control strategies over youth; in positive information processing, older adults showed a similar cognitive control pattern to youth, and proactive control was enhanced.
Comprehensive Assessment of Acute Isolated or Prominent Dysarthria in the Emergency Department: A Neuro-Emergency Expert’s Experience beyond Stroke
Authors: Lee Soon-Ho , Ha Sang-Ook , Kim Jin-Hyouk , Yang Won-Seok , Park Young-Sun , Park Tae-Jin
Published: August 2022

We investigated the clinical characteristics, neuroimaging findings, and final diagnosis of patients with acute isolated or prominent dysarthria who visited the emergency department (ED) between 1 January 2020 and 31 December 2021. Of 2028 patients aged ≥ 18 years with neurologic symptoms treated by a neuro-emergency expert, 75 with acute isolated or predominant dysarthria within 1 week were enrolled. Patients were categorized as having isolated dysarthria (n = 28, 37.3%) and prominent dysarthria (n = 47, 62.7%). The causes of stroke were acute ischemic stroke (AIS) (n = 37, 49.3%), transient ischemic attack (TIA) (n = 14, 18.7%), intracerebral hemorrhage (n = 1, 1.3%), and non-stroke causes (n = 23, 30.7%). The most common additional symptoms were gait disturbance or imbalance (n = 8, 15.4%) and dizziness (n = 3, 13.0%) in the stroke and non-stroke groups, respectively. The isolated dysarthria group had a higher rate of TIA (n = 7, 38.9%), single and small lesions (n = 10, 83.3%), and small-vessel occlusion in Trial of Org 101072 in acute stroke treatment (n = 8, 66.7%). Acute isolated or prominent dysarthria in the ED mostly presented as clinical symptoms of AIS, but other non-stroke and medical causes were not uncommon. In acute dysarthria with ischemic stroke, multiple territorial and small and single lesions are considered a cause.
Building Information Modeling Learning Behavior of AEC Undergraduate Students in China
Authors: Peng Panyu , Ao Yibin , Li Mingyang , Wang Yan , Wang Tong , Bahmani Homa
Published: August 2022

With the popularization and application of Building Information Modeling (BIM), the demand for BIM technical talents in the construction industry is increasing. Exploring college students’ BIM technical learning behavior is of great practical significance to improve education activities. Based on the Unified Theory of Acceptance and Use of Technology (UTAUT), this research adds learning attitude variables to construct a theoretical model of influencing factors of college students’ BIM technology learning behavior. Chinese undergraduate students were asked to complete online questionnaires through peer-to-peer contact with sample colleges and universities. Finally, 1090 valid questionnaires were obtained. The students were sampled from research-oriented, applied research-oriented, application-oriented, and private research-oriented universities in seven regions of China: northeast, north, east, south, central, northwest, and southwest. The structural equation model was used to analyze the sampling data. The results indicate that college students’ BIM learning attitude, performance expectations, and social influence positively and directly impact their learning intention, which indirectly impacts their learning behavior. At the same time, promoting factors and learning intention demonstrate a significant positive and direct impact on learning behavior. Therefore, the following suggestions have been put forward to enhance college students’ learning motivation for BIM technology: increase the popularization of BIM technology in colleges and universities and improve the operation level of full-time BIM teachers. The latter enables colleges and universities to continuously and stably export qualified BIM technical talents to society and the market, resulting in a continuous industry development cycle.
Breast Cancer Survivors’ Motivation to Participate in a Tailored Physical and Psychological Intervention: A Qualitative Thematic Analysis
Authors: Sebri Valeria , Durosini Ilaria , Mazzoni Davide , Pravettoni Gabriella
Published: August 2022

Purpose: Participants’ engagement in a project requires intrinsic motivations, which may evolve during the intervention thanks to lifestyle changes and positive challenges. Over the years, tailored programs based on physical activity and psychological sessions have been promoted to support the quality of life and well-being of breast cancer survivors. Personal expectations and needs are essential to predict participant adherence to the intervention as well as their possibility to reach positive outcomes. This study presents a preliminary understanding of the differences between motives and outcomes obtained after an integrated physical and psychological intervention conducted by professional trainers and psychologists. Methods: Forty-five women with a history of breast cancer answered some questions before and after the program, and the results were analyzed in accordance with the procedure of the thematic analysis. Results: Physical and psychological well-being are the two main themes that emerged from the participants. Interestingly, some differences emerged between the two data collections. Themes such as aesthetic evaluation interest and the need to learn psychological strategies disappeared at the end of the intervention; on the other hand, the need to make a distance from the illness experiences emerged as an obtained outcome. Conclusions: The discussion explains these differences and highlights the importance of considering breast cancer patients’ needs and motives to take part in interventions to promote quality of life.
Experiment Study on the Hysteretic Performance of a Novel Replaceable Beam-to-Column Joint with Energy-Dissipating Steel Hinge
Authors: Ma Yongchao , Qi Ai , Yan Guiyun , Zheng Lianqiong , Xue Panrong
Published: August 2022

A novel precast replaceable beam-to-column joint with energy-dissipating steel hinges was proposed for the connection of precast structures to improve the seismic performance and post-earthquake resilience. The proposed joint was installed in the predetermined plastic hinge region at beams and the flange segments of the proposed joint were weakened to achieve damage concentration. Cyclic loading tests were conducted on the proposed joint and the steel sleeve confined concrete joint to study the hysteretic performance, including failure mode, load–displacement curves, ductility, and energy-dissipation capacity. Moreover, the hystertic performance of the damage-repaired proposed joint was investigated to verify the post-earthquake resilience. Results demonstrated that the proposed joints could develop favorable failure mode with the necking rupture of the weakened steel plate in steel hinge. The damage of the proposed joint was concentrated in the energy-dissipating hinges while no serious damage was observed in the precast framing components, achieving the objective of damage concentration. Compared with steel sleeve confined concrete joint, the hysteresis curve of proposed joint was more plump while an obvious pinching effect was observed in the steel-confined concrete joint. The bearing capacity and energy-dissipation capacity of the proposed joint were about 1.25 times and 1.55 times of that for the steel sleeve confined concrete joint, respectively. In addition, the hysteretic performance of the repaired specimen was identical to the original one, with the desired failure mode caused by the fracture of the steel hinge. It was noted that the hysteretic performance of the repaired joint was better than the steel sleeve confined concrete joint. The bearing capacity was recovered at up to 96.6% of the original joint while the energy-dissipation capacity was recovered at 96.1%, indicating that the proposed joint achieved the post-earthquake resilience to a great extent.
Computational Analysis of Structure–Activity Relationships in Highly Active Homogeneous Ruthenium−Based Water Oxidation Catalysts
Authors: Bury Gabriel , Pushkar Yulia
Published: August 2022

Linear free−energy scaling relationships (LFESRs) and regression analysis may predict the catalytic performance of heterogeneous and recently, homogenous water oxidation catalysts (WOCs). This study analyses thirteen homogeneous Ru−based catalysts—some, the most active catalysts studied: the Ru(tpy−R)(QC) and Ru(tpy−R)(4−pic)2 complexes, where tpy is 2,2’;6’,2”terpyridine, QC is 8−quinolinecarboxylate and 4−pic is 4−picoline. Typical relationships studied among heterogenous catalysts cannot be applied to homogeneous catalysts. The selected group of structurally similar catalysts with impressive catalytic activity deserves closer computational and statistical analysis of multiple reaction step energetics correlating with measured catalytic activity. We report general methods of LFESR analysis yield insufficiently robust relationships between descriptor variables. However, volcano−plot−based analysis grounded in Sabatier’s principle reveals ideal relative energies of the RuIV = O and RuIV−OH intermediates and optimal changes in free energies of water nucleophilic attack on RuV = O. A narrow range of RuIV−OH to RuV = O redox potentials corresponding with the highest catalytic activities suggests facile access to the catalytically competent high−valent RuV = O state, often inaccessible from RuIV = O. Our work incorporates experimental oxygen evolution rates into approaches of LFESR and Sabatier−principle−based analysis, identifying a narrow yet fertile energetic landscape to bountiful oxygen evolution activity, leading to future rational design.
Synergistic Effect in Ag/Fe–MnO2 Catalysts for Ethanol Oxidation
Authors: Kulchakovskaya Ekaterina V. , Dotsenko Svyatoslav S. , Liotta Leonarda F. , La Parola Valeria , Galanov Sergey I. , Sidorova Olga I. , Vodyankina Olga V.
Published: August 2022

Here we report the synergistic effect of OMS-2 catalysts tested in ethanol oxidation, and the effects produced by both the addition of an Fe modifier in the catalyst preparation stage, and the introduction of Ag on its surface by the impregnation method. To analyze the action of each component, the Fe-modified, Ag-containing OMS-2 catalysts with different Mn/Fe ratios were prepared. Combined XPS and XRF elemental analysis confirms the states and distribution of the Ag- and Fe-containing species between the surface and bulk of the OMS-2 catalysts, which form highly dispersed Ag species on the surface of 0.05Fe–OMS-2, and are also incorporated into the OMS-2 crystalline lattice. The cooperative action of Ag and Fe modifiers improves both reoxidation ability (TPO results) and the amount of adsorbed oxygen species on the catalyst surface. The introduction of Ag to the OMS-2 and 0.05 Fe–OMS-2 surface allows a high level of activity (T80 = 150–155 °C) and selectivity (SAc80 = 93%) towards the acetaldehyde formation.
Functional ERAP1 Variants Distinctively Associate with Ankylosing Spondylitis Susceptibility under the Influence of HLA-B27 in Taiwanese
Authors: Wang Chin-Man , Liu Ming-Kun , Jan Wu Yeong-Jian , Lin Jing-Chi , Zheng Jian-Wen , Wu Jianming , Chen Ji-Yih
Published: August 2022

Epistasis of ERAP1 single nucleotide variations (SNVs) and HLA-B27 has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent ERAP1 allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all ERAP1 coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of ERAP1 SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk ERAP1 allelic variants was performed. Two common-risk ERAP1 allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent ERAP1 SNVs and six major ERAP1 allelic variants were discovered. We discovered that in Taiwanese, the most prevalent ERAP1-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with HLA-B27 significantly contributed to the development of AS. In HLA-B27 negative group, however, the second most prevalent ERAP1-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that ERAP1 allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common ERAP1 allelic variants are related with AS susceptibility.
Innovative Treatment Strategies to Accelerate Wound Healing: Trajectory and Recent Advancements
Authors: Kolimi Praveen , Narala Sagar , Nyavanandi Dinesh , Youssef Ahmed Adel Ali , Dudhipala Narendar
Published: August 2022

Wound healing is highly specialized dynamic multiple phase process for the repair of damaged/injured tissues through an intricate mechanism. Any failure in the normal wound healing process results in abnormal scar formation, and chronic state which is more susceptible to infections. Chronic wounds affect patients’ quality of life along with increased morbidity and mortality and are huge financial burden to healthcare systems worldwide, and thus requires specialized biomedical intensive treatment for its management. The clinical assessment and management of chronic wounds remains challenging despite the development of various therapeutic regimens owing to its painstakingly long-term treatment requirement and complex wound healing mechanism. Various conventional approaches such as cell therapy, gene therapy, growth factor delivery, wound dressings, and skin grafts etc., are being utilized for promoting wound healing in different types of wounds. However, all these abovementioned therapies are not satisfactory for all wound types, therefore, there is an urgent demand for the development of competitive therapies. Therefore, there is a pertinent requirement to develop newer and innovative treatment modalities for multipart therapeutic regimens for chronic wounds. Recent developments in advanced wound care technology includes nanotherapeutics, stem cells therapy, bioengineered skin grafts, and 3D bioprinting-based strategies for improving therapeutic outcomes with a focus on skin regeneration with minimal side effects. The main objective of this review is to provide an updated overview of progress in therapeutic options in chronic wounds healing and management over the years using next generation innovative approaches. Herein, we have discussed the skin function and anatomy, wounds and wound healing processes, followed by conventional treatment modalities for wound healing and skin regeneration. Furthermore, various emerging and innovative strategies for promoting quality wound healing such as nanotherapeutics, stem cells therapy, 3D bioprinted skin, extracellular matrix-based approaches, platelet-rich plasma-based approaches, and cold plasma treatment therapy have been discussed with their benefits and shortcomings. Finally, challenges of these innovative strategies are reviewed with a note on future prospects.
Three Binding Conformations of BIO124 in the Pocket of the PICK1 PDZ Domain
Authors: Stevens Amy O. , Luo Samuel , He Yi
Published: August 2022

The PDZ family has drawn attention as possible drug targets because of the domains’ wide ranges of function and highly conserved binding pockets. The PICK1 PDZ domain has been proposed as a possible drug target because the interactions between the PICK1 PDZ domain and the GluA2 subunit of the AMPA receptor have been shown to progress neurodegenerative diseases. BIO124 has been identified as a sub µM inhibitor of the PICK1–GluA2 interaction. Here, we use all-atom molecular dynamics simulations to reveal the atomic-level interaction pattern between the PICK1 PDZ domain and BIO124. Our simulations reveal three unique binding conformations of BIO124 in the PICK1 PDZ binding pocket, referred to here as state 0, state 1, and state 2. Each conformation is defined by a unique hydrogen bonding network and a unique pattern of hydrophobic interactions between BIO124 and the PICK1 PDZ domain. Interestingly, each conformation of BIO124 results in different dynamic changes to the PICK1 PDZ domain. Unlike states 1 and 2, state 0 induces dynamic coupling between BIO124 and the αA helix. Notably, this dynamic coupling with the αA helix is similar to what has been observed in other PDZ–ligand complexes. Our analysis indicates that the interactions formed between BIO124 and I35 may be the key to inducing dynamic coupling with the αA helix. Lastly, we suspect that the conformational shifts observed in our simulations may affect the stability and thus the overall effectiveness of BIO124. We propose that a physically larger inhibitor may be necessary to ensure sufficient interactions that permit stable binding between a drug and the PICK1 PDZ domain.
Endothelial Glycocalyx Morphology in Different Flow Regions of the Aqueous Outflow Pathway of Normal and Laser-Induced Glaucoma Monkey Eyes
Authors: Sosnowik Shayna , Swain David , Liu Neil , Fan Shan , Toris Carol , Gong Haiyan
Published: August 2022

Glycocalyx morphology was examined in the trabecular outflow pathway of monkey eyes with and without experimental glaucoma. Laser burns were administered along ~270 degrees of the trabecular meshwork (TM) of one eye (n = 6) or both eyes (n = 2) of each monkey until intraocular pressure remained elevated. Portions of the TM were not laser-treated. Unlasered eyes (n = 6) served as controls. Enucleated eyes were perfused at 15 mmHg to measure the outflow facility, perfused with fluorescein to evaluate the outflow pattern, perfusion-fixed for glycocalyx labeling, and processed for electron microscopy. Coverage and thickness of the glycocalyx were measured in the TM, Schlemm’s canal (SC), collector channels (CCs), intrascleral veins (ISVs), and episcleral veins (ESVs) in non-lasered regions and high- and low-flow regions of controls. Compared to controls, laser-treated eyes had decreased outflow facility (p = 0.02). Glycocalyx thickness increased from the TM to ESVs in non-lasered regions and controls (p < 0.05). Glycocalyx coverage was generally greater distally in non-lasered regions (p < 0.05). In lasered regions, TM, SC, and CCs were partly to completely obliterated, and ISVs and ESVs displayed minimal glycocalyx. Whether the glycocalyx is decreased in the trabecular outflow pathway of human glaucomatous eyes warrants investigation.
Study on LIBS Standard Method via Key Parameter Monitoring and Backpropagation Neural Network
Authors: Wang Rui , Ma Xiaohong
Published: August 2022

This paper proposes a method based on key parameter monitoring and a backpropagation neural network to standardize LIBS spectra, named KPBP. By monitoring the laser output energy and the plasma flame morphology and using the backpropagation neural network algorithm to fit the spectral intensity, KPBP standardizes spectral segments containing characteristic lines. This study first conducted KPBP experiments on the spectra of pure aluminium, monocrystalline silicon, and pure zinc to optimize the KPBP model and then performed KPBP standardization on the characteristic spectral lines of a GSS-8 standard soil sample. The spectral intensity relative standard deviations (RSDs) of Al 257.51 nm, Si 298.76 nm, and Fe 406.33 nm dropped from 12.57%, 16.60%, and 14.10% to 3.40%, 3.20%, and 4.07%, respectively. Compared with the internal standard method and the standard normal variate method, KPBP obtained the smallest RSD. The study also used a GSS-23 standard soil sample and a Beijing farmland soil sample to conduct KPBP optimization experiments. The RSD of spectral intensity was still significantly reduced, proving that the KPBP method has stable effects and wide applicability to improve the repeatability of LIBS soil analysis.
Characterization of Flexible Copper Selenide Films on Polyamide Substrate Obtained by SILAR Method—Towards Application in Electronic Devices
Authors: Jakubauskas Gediminas , Gilic Martina , Paluckiene Edita , Mitric Jelena , Cirkovic Jovana , Ralevic Uros , Usoviene Egle , Griskonis Egidijus , Petrasauskiene Neringa
Published: August 2022

Thin copper selenide films were synthesized on polyamide sheets using the successive ionic layer adsorption and reaction (SILAR) method at three different temperatures. It was found that elevating the temperature of the solution led to the creation of copper selenide films with different features. X-ray diffraction characterization revealed that all films crystallized into a cubic Cu2−xSe, but with different crystallinity parameters. With elevating the temperature, grain size increased (6.61–14.33 and 15.81 for 40, 60 and 80 °C, respectively), while dislocation density and the strain decreased. Surface topology was investigated with Scanning Electron Microscopy and Atomic Force Microscopy, which revealed that the grains combined into agglomerates of up to 100 nm (80 °C) to 1 μm (40 °C). The value of the direct band gap of the copper selenide thin films, obtained with UV/VIS spectroscopy, varied in the range of 2.28–1.98 eV. The formation of Cu2−xSe was confirmed by Raman analysis; the most prominent Raman peak is located at 260 cm−1, which is attributed to binary copper selenides. The thin Cu2−xSe films deposited on polyamide showed p-type conductivity, and the electrical resistivity varied in the range of 20–50 Ω. Our results suggest that elevated temperatures prevent large agglomeration, leading to higher resistance behavior.
Clinical Question Influence on Radiation Dose of Cardiac CT Scan in Children
Authors: Adla Theodor , Kočí Martin , Suchánek Vojtěch , Šalagovičová Zuzana , Polovinčák Michal , Mikšík Lukáš , Janoušek Jan , Roček Miloslav
Published: August 2022

Background: To assess the impact of different clinical questions on radiation doses acquired during cardiac computed tomography in children. Methods: A total of 116 children who underwent cardiac CT on a third-generation dual-source CT scanner were included. The clinical questions were divided into three main categories: the extent of scanning in the z-axis, coronary artery assessment and cardiac function assessment. Radiation dose values represented as a dose-length product (DLP) in mGy*cm were recorded from the CT scanner protocols. Results: There were significantly higher doses in cases with cardiac function assessment (median DLP 348 versus 59 mGy*cm, p < 0.01) and in cases with coronary artery assessment (median DLP 133 versus 71 mGy*cm, p < 0.01). Conclusion: The most important factor was the assessment of cardiac function, where the median radiation dose was 4.3× higher in patients with a request for cardiac function assessment. We strongly recommend that clinical requests for cardiac CT should be carefully considered in the paediatric population.