bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasensitive and Rapid Visual Detection of Escherichia coli O157:H7 Based on RAA-CRISPR/Cas12a System
Authors: Zhu Lishan , Liang Zhenda , Xu Yongtao , Chen Zhiquan , Wang Jiasi , Zhou Li
Published: June 2023

Escherichia coli (E. coli) O157:H7 is a major foodborne and waterborne pathogen that can threaten human health. Due to its high toxicity at low concentrations, it is crucial to establish a time-saving and highly sensitive in situ detection method. Herein, we developed a rapid, ultrasensitive, and visualized method for detecting E. coli O157:H7 based on a combination of Recombinase-Aided Amplification (RAA) and CRISPR/Cas12a technology. The CRISPR/Cas12a-based system was pre-amplified using the RAA method, which showed high sensitivity and enabled detecting as low as ~1 CFU/mL (fluorescence method) and 1 × 102 CFU/mL (lateral flow assay) of E. coli O157:H7, which was much lower than the detection limit of the traditional real-time PCR technology (103 CFU/mL) and ELISA (104~107 CFU/mL). In addition, we demonstrated that this method still has good applicability in practical samples by simulating the detection in real milk and drinking water samples. Importantly, our RAA-CRISPR/Cas12a detection system could complete the overall process (including extraction, amplification, and detection) within 55 min under optimized conditions, which is faster than most other reported sensors, which take several hours to several days. The signal readout could also be visualized by fluorescence generated with a handheld UV lamp or a naked-eye-detected lateral flow assay depending on the DNA reporters used. Because of the advantages of being fast, having high sensitivity, and not requiring sophisticated equipment, this method has a promising application prospect for in situ detection of trace amounts of pathogens.
Rational Truncation of Aptamer for Ultrasensitive Aptasensing of Chloramphenicol: Studies Using Bio-Layer Interferometry
Authors: Sharma Richa , Mukherjee Monali , Bhatt Praveena , Raghavarao K. S. M. S.
Published: June 2023

Aptamers are an excellent choice for the selective detection of small molecules. However, the previously reported aptamer for chloramphenicol suffers from low affinity, probably as a result of steric hindrance due to its bulky nature (80 nucleotides) leading to lower sensitivity in analytical assays. The present work was aimed at improving this binding affinity by truncating the aptamer without compromising its stability and three-dimensional folding. Shorter aptamer sequences were designed by systematically removing bases from each or both ends of the original aptamer. Thermodynamic factors were evaluated computationally to provide insight into the stability and folding patterns of the modified aptamers. Binding affinities were evaluated using bio-layer interferometry. Among the eleven sequences generated, one aptamer was selected based on its low dissociation constant, length, and regression of model fitting with association and dissociation curves. The dissociation constant could be lowered by 86.93% by truncating 30 bases from the 3′ end of the previously reported aptamer. The selected aptamer was used for the detection of chloramphenicol in honey samples, based on a visible color change upon the aggregation of gold nanospheres caused by aptamer desorption. The detection limit could be reduced 32.87 times (1.673 pg mL−1) using the modified length aptamer, indicating its improved affinity as well as its suitability in real-sample analysis for the ultrasensitive detection of chloramphenicol.
The Potential Use of Sex Robots in Adults with Autistic Spectrum Disorders: A Theoretical Framework
Authors: Pasciuto Fabrizia , Cava Antonia , Falzone Alessandra
Published: June 2023

Although the importance of the sexual sphere for the health of all human beings has been recognized at an international level, often this is underestimated when it comes to disabilities and even more to intellectual disabilities. In fact, the idea that subjects with intellectual disabilities are not aware of their bodies and of their wishes in the sexual and emotional field is still widespread in our society, in such a way that they are considered as children in need of constant supervision. Moreover, further hints of criticism that can be raised are about the poor level of sexual education that is dedicated to these subjects, both by family members and by therapists. The last decades have been characterized by a considerable growth in the technological sector and many new instruments have been successfully used in the field of healthcare of weak or disabled subjects. A particularly fruitful branch has been robotics which, in subjects with autistic spectrum disorders (ASD), has revealed itself as an excellent support to stimulate communication and develop social skills. As in recent years the field of robotics has also been characterized by a strong interest in the sphere of sexuality, building and implementing what we now define as sex robots or sexbots, it could be interesting to start a debate on the potential that these new generation artificial agents could have in the field of care of subjects with ASD. These robots, possessing a technology based on stimulating verbal and nonverbal interaction, could be useful for an education that is not only sexual but also psycho-emotional in subjects with ASD.
A Review on Smartphone Keystroke Dynamics as a Digital Biomarker for Understanding Neurocognitive Functioning
Authors: Nguyen Theresa M. , Leow Alex D. , Ajilore Olusola
Published: June 2023

Can digital technologies provide a passive unobtrusive means to observe and study cognition outside of the laboratory? Previously, cognitive assessments and monitoring were conducted in a laboratory or clinical setting, allowing for a cross-sectional glimpse of cognitive states. In the last decade, researchers have been utilizing technological advances and devices to explore ways of assessing cognition in the real world. We propose that the virtual keyboard of smartphones, an increasingly ubiquitous digital device, can provide the ideal conduit for passive data collection to study cognition. Passive data collection occurs without the active engagement of a participant and allows for near-continuous, objective data collection. Most importantly, this data collection can occur in the real world, capturing authentic datapoints. This method of data collection and its analyses provide a more comprehensive and potentially more suitable insight into cognitive states, as intra-individual cognitive fluctuations over time have shown to be an early manifestation of cognitive decline. We review different ways passive data, centered around keystroke dynamics, collected from smartphones, have been used to assess and evaluate cognition. We also discuss gaps in the literature where future directions of utilizing passive data can continue to provide inferences into cognition and elaborate on the importance of digital data privacy and consent.
Altered Spontaneous Brain Activity in Cirrhotic Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Resting-State Functional Imaging
Authors: Qin Bin , Liang Shuolin , Tang Shiting , Liang Huo , Zhang Yunli , Liang Zhijian
Published: June 2023

(1) Background: Minimal hepatic encephalopathy (MHE) is an important complication of decompensated cirrhosis. Previous studies have demonstrated spontaneous brain activity alterations in cirrhotic patients with MHE. However, the reported results are inconsistent, which has limited our understanding of the potential neural mechanisms. Thus, we conducted a quantitative meta-analysis of resting-state functional imaging studies to identify the regional activity alterations consistently involved in MHE. (2) Methods: We searched six databases to include resting-state functional imaging studies and compared spontaneous brain activity patterns between MHE patients and healthy controls (HCs), and between cirrhotic patients without minimal hepatic encephalopathy (NMHE) and HCs. Then, a separate whole-brain voxel-wise meta-analysis between MHE or NMHE patients and HCs was conducted using seed-based d mapping with permutation of subject images. We further conducted the conjunction analysis to assess the distinct regional activity alterations between MHE and NMHE patients as compared to HCs. (3) Results: Thirteen studies with twenty datasets were included in this meta-analysis. Compared with HCs, MHE patients showed decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. Compared with NMHE patients, MHE patients indicated decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. (4) Conclusions: MHE is associated with spontaneous brain activity alterations involving the left superior frontal gyrus and median cingulate/paracingulate gyri, which may implicate primarily in spatial working memory and emotional disorders. These findings may contribute to a better understanding of the potential neural mechanisms, and guide further research.
Detecting Subtle Cognitive Impairment in Patients with Parkinson’s Disease and Normal Cognition: A Novel Cognitive Control Challenge Task (C3T)
Authors: Resnik Robida Karmen , Politakis Vida Ana , Oblak Aleš , Ozimič Anka Slana , Burger Helena , Pirtošek Zvezdan , Bon Jurij
Published: June 2023

Patients with Parkinson’s disease (PD) often show early deficits in cognitive control, with primary difficulties in flexibility and relatively intact stable representations. The aim of our study was to assess executive function using an ecologically valid approach that combines measures of stability and flexibility. Fourteen patients without cognitive deficits and sixteen comparable control subjects completed a standardized neuropsychological test battery and a newly developed cognitive control challenge task (C3T). We found that the accuracy of C3T performance decreased with age in healthy participants and remained impaired in PD patients regardless of age. In addition, PD patients showed significantly lower overall performance for cognitive control tasks than healthy controls, even when they scored in the normal range on standardized neuropsychological tests. PD Patients responded significantly faster than healthy control subjects regarding flexible cognitive control tasks due to their impulsivity. Correlations showed that the C3T task targets multiple cognitive systems, including working memory, inhibition, and task switching, providing a reliable measure of complex cognitive control. C3T could be a valuable tool for characterizing cognitive deficits associated with PD and appears to be a more sensitive measure than standardized neuropsychological tests. A different assessment approach could potentially detect early signs of the disease and identify opportunities for early intervention with neuroprotective therapies.
Healthy Even through Cancer: What Are the Assumptions and Outcomes for Psychological Intervention?
Authors: Pinto Eleonora
Published: June 2023

Cancer remains a highly fatal disease, a major cause of mortality and a huge health burden around the world, requiring increased primary prevention efforts, screenings and treatments [...]
Psychometric Properties of Interpersonal Regulation Questionnaire for Chinese College Students: Gender Differences and Implications for Well-Being
Authors: Zhao Yanhua , Wang Niu , Niu Jiahui , Li Xingchen , Zhang Lei
Published: June 2023

Intrapersonal emotion dysregulation has been found to be a transdiagnostic predictor in the development of almost all affective disorders. Interpersonal resources are also involved in achieving people’s emotion regulation goals. The Interpersonal Regulation Questionnaire (IRQ) has been developed to assess the tendency and efficacy of people using external resources to help manage their emotions. Under the restrictions of the COVID-19 pandemic, the role of interpersonal emotion regulation in individuals’ adjustment and well-being remains unclear. This study aimed to investigate the optimal factor structure of the IRQ in Chinese culture using an exploratory structural equation modeling approach and to examine the associations between interpersonal emotion regulation, tested by the IRQ, and young people’s intrapersonal emotion dysregulation and social and emotional well-being. The sample consisted of 556 college students aged from 17 to 31 from Mainland China. Factor analyses suggested that the four-factor structure was the optimal model for the current data. Females reported a higher tendency to use external resources to regulate their negative emotions and higher efficacy in regulating negative emotions. The Chinese version of the IRQ (C-IRQ) presented adequate psychometric properties and would be a useful tool for measuring interpersonal emotion regulation behaviors.
About Some Trends in CAAD Research
Authors: Grabska Ewa Janina
Published: June 2023

Computer-aided architectural design (CAAD) is the driving force that connects architecture, technology, and design [...]
Green Solutions for Urban Sustainability: Photobioreactors for Algae Cultivation on Façades and Artificial Trees
Authors: Villalba María Rosa , Cervera Rosa , Sánchez Javier
Published: June 2023

The accumulation of CO2 in the atmosphere carries with it severe consequences, and cities are responsible for 70% of CO2 emissions. With this initiative, we address how innovative green architecture can contribute to removing CO2 from the urban area by implementing elements that incorporate microalgae cultivation into architecture. The presented project incorporates two photobioreactor installations filled with water, where microalgae circulate through methacrylate tubes. Used as two architectural elements: a façade that can fix 720 kg of CO2 per year from the atmosphere and produce 400 kg of biomass that can be used as fertilizer in irrigation water; and three artificial trees that can fix 50 kg of CO2 and produce 28 kg of biomass. To test its efficiency, a Life Cycle Inventory was conducted and compared to the amount of CO2 fixed during its lifetime. It was concluded that the system would need 11.11 years to fix the CO2 produced and would have a negative CO2 impact of 27 tons of CO2 during the useful life of its materials. This project is a starting point towards developing a disruptive and experimental alternative with great potential, being the first in Spain and one of the first in the world.
Unsupervised Machine Learning of MRI Radiomics Features Identifies Two Distinct Subgroups with Different Liver Function Reserve and Risks of Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma
Authors: Wang Qiang , Li Changfeng , Chen Geng , Feng Kai , Chen Zhiyu , Xia Feng , Cai Ping , Zhang Leida , Sparrelid Ernesto , Brismar Torkel B. , Ma Kuansheng
Published: June 2023

Objective: To identify subgroups of patients with hepatocellular carcinoma (HCC) with different liver function reserves using an unsupervised machine-learning approach on the radiomics features from preoperative gadoxetic-acid-enhanced MRIs and to evaluate their association with the risk of post-hepatectomy liver failure (PHLF). Methods: Clinical data from 276 consecutive HCC patients who underwent liver resections between January 2017 and March 2019 were retrospectively collected. Radiomics features were extracted from the non-tumorous liver tissue at the gadoxetic-acid-enhanced hepatobiliary phase MRI. The reproducible and non-redundant features were selected for consensus clustering analysis to detect distinct subgroups. After that, clinical variables were compared between the identified subgroups to evaluate the clustering efficacy. The liver function reserve of the subgroups was compared and the correlations between the subgroups and PHLF, postoperative complications, and length of hospital stay were evaluated. Results: A total of 107 radiomics features were extracted and 37 were selected for unsupervised clustering analysis, which identified two distinct subgroups (138 patients in each subgroup). Compared with subgroup 1, subgroup 2 had significantly more patients with older age, albumin–bilirubin grades 2 and 3, a higher indocyanine green retention rate, and a lower indocyanine green plasma disappearance rate (all p < 0.05). Subgroup 2 was also associated with a higher risk of PHLF, postoperative complications, and longer hospital stays (>18 days) than that of subgroup 1, with an odds ratio of 2.83 (95% CI: 1.58–5.23), 2.41(95% CI: 1.15–5.35), and 2.14 (95% CI: 1.32–3.47), respectively. The odds ratio of our method was similar to the albumin–bilirubin grade for postoperative complications and length of hospital stay (2.41 vs. 2.29 and 2.14 vs. 2.16, respectively), but was inferior for PHLF (2.83 vs. 4.55). Conclusions: Based on the radiomics features of gadoxetic-acid-enhanced MRI, unsupervised clustering analysis identified two distinct subgroups with different liver function reserves and risks of PHLF in HCC patients. Future studies are required to validate our findings.
Early-Onset Colorectal Cancer: Current Insights
Authors: Ullah Fauzia , Pillai Ashwathy Balachandran , Omar Najiullah , Dima Danai , Harichand Seema
Published: June 2023

Over the past decade, the incidence of colorectal cancer has increased in individuals under the age of 50 years. Meanwhile, the incidence has gradually decreased in the older population. As described herein, we reviewed the available literature to summarize the current landscape of early-onset colorectal cancer, including risk factors, clinicopathological presentation, genetic makeup of patients, and management. Currently, early-onset colorectal cancer is treated similarly as late-onset colorectal cancer, yet the available literature shows that early-onset colorectal cancer is more aggressive and different, and this remains a significant unmet need. A detailed understanding of early-onset colorectal cancer is needed to identify risk factors for the increased incidence and tailor treatments accordingly.
Enhancement of Tumor Cell Immunogenicity and Antitumor Properties Derived from Platinum-Conjugated Iron Nanoparticles
Authors: Hernández Ángela-Patricia , Iglesias-Anciones Laura , Vaquero-González José Javier , Piñol Rafael , Criado Julio J. , Rodriguez Emilio , Juanes-Velasco Pablo , García-Vaquero Marina L. , Arias-Hidalgo Carlota , Orfao Alberto , Millán Ángel , Fuentes Manuel
Published: June 2023

From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.
Liquid Biopsy: Current Status and Future Perspectives
Authors: Baev Vesselin , Koppers-Lalic Danijela , Costa-Silva Bruno
Published: June 2023

Since the discovery of the Bence Jones protein in the middle to late 1800s and the subsequent identification of the carcinoembryonic antigen and alpha-fetoprotein in the 1970s, it has been demonstrated that the analysis of biofluids is essential to the diagnostic and follow-up processes of cancer [...]
The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study
Authors: Muscaritoli Maurizio , Modena Alessandra , Valerio Matteo , Marchetti Paolo , Magarotto Roberto , Quadrini Silvia , Narducci Filomena , Tonini Giuseppe , Grassani Teresa , Cavanna Luigi , Di Nunzio Camilla , Citterio Chiara , Occelli Marcella , Strippoli Antonia , Chiurazzi Bruno , Frassoldati Antonio , Altavilla Giuseppe , Lucenti Antonio , Nicolis Fabrizio , Gori Stefania
Published: June 2023

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients’ outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.
Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies
Authors: Schiavoni Valentina , Campagna Roberto , Pozzi Valentina , Cecati Monia , Milanese Giulio , Sartini Davide , Salvolini Eleonora , Galosi Andrea Benedetto , Emanuelli Monica
Published: June 2023

Renal cell carcinoma (RCC) belongs to a heterogenous cancer group arising from renal tubular epithelial cells. Among RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most common variant, characterized by high aggressiveness, invasiveness and metastatic potential, features that lead to poor prognosis and high mortality rate. In addition, diagnosis of kidney cancer is incidental in the majority of cases, and this results in a late diagnosis, when the stage of the disease is advanced and the tumor has already metastasized. Furthermore, ccRCC treatment is complicated by its strong resistance to chemo- and radiotherapy. Therefore, there is active ongoing research focused on identifying novel biomarkers which could be useful for assessing a better prognosis, as well as new molecules which could be used for targeted therapy. In this light, several novel targeted therapies have been shown to be effective in prolonging the overall survival of ccRCC patients. Thus, the aim of this review is to analyze the actual state-of-the-art on ccRCC diagnosis, prognosis and therapeutic options, while also reporting the recent advances in novel biomarker discoveries, which could be exploited for a better prognosis or for targeted therapy.
High-Frequency Electroporation and Chemotherapy for the Treatment of Cutaneous Malignancies: Evaluation of Early Clinical Response
Authors: Lyons Phoebe , Polini Dana , Russell-Ryan Kate , Clover A. James P.
Published: June 2023

High-frequency electroporation (HF-EP) with chemotherapy is a novel therapy proposed for both curative and palliative treatment of cutaneous malignancies. The use of high-frequency biphasic pulses is thought to reduce the painful muscle contractions associated with traditional electrochemotherapy (ECT), allowing treatment administration under local anaesthesia. This proof-of-concept study investigated the efficacy and tolerability of HF-EP protocols on a variety of cutaneous malignancies. A total of 97 lesions of five different histological subtypes were treated across 25 patients. At 12 weeks post-treatment, a 91.3% overall lesion response rate was observed (complete response: 79%; partial response: 12.3%), with excellent intraprocedural patient tolerability under local anaesthetic. HF-EP with chemotherapy shows promising results regarding tumour response rates for cutaneous malignancies of varying histological subtypes when compared to traditional ECT protocols. Improved patient tolerability is important, increasing the possibility of treatment delivery under local anaesthesia and potentially broadening the treatment envelope for patients with cutaneous malignancies.
NiO/AC Active Electrode for the Electrosorption of Rhodamine B: Structural Characterizations and Kinetic Study
Authors: Chennah Ahmed , Khan Moonis Ali , Zbair Mohamed , Ait Ahsaine Hassan
Published: June 2023

In this work, the aim was to enhance the performance of activated carbon (AC) as an electroadsorbent by incorporating NiO particles, thereby increasing its electrochemical capacity and its ability to adsorb Rhodamine B (RhB) dye. The prepared NiO/AC material was characterized using X-ray diffraction, scanning electron microscopy, BET surface area analysis, and infrared spectroscopy. The study involved the preparation of AC from almond shell biomass and the subsequent formation of a composite structure with NiO. The objective was to investigate the electrochemical adsorption capacity of the NiO/AC composite for RhB dye removal from simulated wastewaters. The experimental results demonstrated that the removal efficiency of RhB dye increased with an increase in the applied cell voltage. At a voltage of 1.4 V, a remarkable 100% removal efficiency was achieved. The electroadsorption process was well described by fitting the experimental data to the Freundlich isotherm model. The maximum adsorption capacities for RhB dye at concentrations of 7, 8, and 9 ppm were determined to be 149, 150, and 168 mg/g, respectively. Based on the obtained results, an electroadsorption mechanism was proposed to explain the observed behavior of the NiO/AC composite in adsorbing RhB dye. Overall, this study highlights the potential of the NiO/AC composite as an effective electroadsorbent for the removal of Rhodamine B dye from wastewater. The improved electrochemical capacity, coupled with the high adsorption capacity of the composite, makes it a promising material for wastewater treatment applications.
Synthesis of CaCO3/Cu2O/GO Nanocomposite Catalysts for Hydrogen Production from NaBH4 Methanolysis
Authors: Alshammari Majed , Alhassan Sultan , Alshammari Khulaif , Alotaibi Turki , Taha Taha Abdel Mohaymen , Alshammari Alhulw H. , Ismael Ali
Published: June 2023

The synthesis of CaCO3/Cu2O/GO nanocomposites was developed by sol-gel auto-combustion method. The analysis of structure was completed on X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and environmental scanning electron microscopy (ESEM). The XRD spectra of the nanocomposites matched the crystal structure of CaCO3/Cu2O. The average crystal size was 20 nm for Cu2O and 25 nm for CaCO3 nanoparticles. FTIR data showed the absorption bands of Cu2O and GO. Raman spectroscopy data confirmed the formation of GO sheets. ESEM micrographs displayed spherical nanoparticles dispersed in GO sheets. X-ray photoelectron spectroscopy showed the peaks of Cu 2p, O 1s, C 1s, Cu 3s, and Ca 2p. The spectra of optical absorption revealed an absorption band of around 450 nm. The calcium content increase led to a decrease in the optical energy gap from 2.14 to 1.5 eV. The production of hydrogen from NaBH4 across the methanolysis reaction was accelerated by the CaCO3/Cu2O/GO nanocomposites. Therefore, these nanocomposites are superior in catalytic hydrogen production systems.
Isolation and Characterization of the Primary Marmoset (Callithrix jacchus) Retinal Pigment Epithelial Cells
Authors: Jang Ha Young , Cho Chang Sik , Shin Young Mi , Kwak Jina , Sung Young Hoon , Kang Byeong-Cheol , Kim Jeong Hun
Published: June 2023

Marmosets have emerged as a valuable primate model in ophthalmic research due to their similarity to the human visual system and their potential for generating transgenic models to advance the development of therapies. In this study, we isolated and cultured primary retinal pigment epithelium (RPE) cells from marmosets to investigate the mechanisms underlying RPE dysfunction in aging and age-related macular degeneration (AMD). We confirmed that our culture conditions and materials supported the formation of RPE monolayers with functional tight junctions that closely resembled the in vivo RPE. Since serum has been shown to induce epithelial–mesenchymal transition (EMT) in RPE cells, we compared the effects of fetal bovine serum (FBS) with serum-free supplements B27 on transepithelial electrical resistance (TER), cell proliferation, and morphological characteristics. Additionally, we assessed the age-related morphological changes of in vivo and primary RPE cells. Our results indicate that primary marmoset RPE cells exhibit in vivo-like characteristics, while cells obtained from an older donor show evidence of aging, including a failure to form a polarized monolayer, low TER, and delayed cell cycle. In conclusion, our primary marmoset RPE cells provide a reliable in vitro model for developing novel therapeutics for visual-threatening disorders such as AMD, which can be used before animal experiments using marmosets.
Transcriptomic Analysis Reveals Candidate Ligand-Receptor Pairs and Signaling Networks Mediating Intercellular Communication between Hair Matrix Cells and Dermal Papilla Cells from Cashmere Goats
Authors: Ma Sen , Ji Dejun , Wang Xiaolong , Yang Yuxin , Shi Yinghua , Chen Yulin
Published: June 2023

Hair fiber growth is determined by the spatiotemporally controlled proliferation, differentiation, and apoptosis of hair matrix cells (HMCs) inside the hair follicle (HF); however, dermal papilla cells (DPCs), the cell population surrounded by HMCs, manipulate the above processes via intercellular crosstalk with HMCs. Therefore, exploring how the mutual commutations between the cells are molecularly achieved is vital to understanding the mechanisms underlying hair growth. Here, based on our previous successes in cultivating HMCs and DPCs from cashmere goats, we combined a series of techniques, including in vitro cell coculture, transcriptome sequencing, and bioinformatic analysis, to uncover ligand-receptor pairs and signaling networks mediating intercellular crosstalk. Firstly, we found that direct cellular interaction significantly alters cell cycle distribution patterns and changes the gene expression profiles of both cells at the global level. Next, we constructed the networks of ligand-receptor pairs mediating intercellular autocrine or paracrine crosstalk between the cells. A few pairs, such as LEP-LEPR, IL6-EGFR, RSPO1-LRP6, and ADM-CALCRL, are found to have known or potential roles in hair growth by acting as bridges linking cells. Further, we inferred the signaling axis connecting the cells from transcriptomic data with the advantage of CCCExplorer. Certain pathways, including INHBA-ACVR2A/ACVR2B-ACVR1/ACVR1B-SMAD3, were predicted as the axis mediating the promotive effect of INHBA on hair growth via paracrine crosstalk between DPCs and HMCs. Finally, we verified that LEP-LEPR and IL1A-IL1R1 are pivotal ligand-receptor pairs involved in autocrine and paracrine communication of DPCs and HMCs to DPCs, respectively. Our study provides a comprehensive landscape of intercellular crosstalk between key cell types inside HF at the molecular level, which is helpful for an in-depth understanding of the mechanisms related to hair growth.
A Review of Progress on Targeting LDL Receptor-Dependent and -Independent Pathways for the Treatment of Hypercholesterolemia, a Major Risk Factor of ASCVD
Authors: Srivastava Rai Ajit K.
Published: June 2023

Since the discovery of the LDL receptor in 1973 by Brown and Goldstein as a causative protein in hypercholesterolemia, tremendous amounts of effort have gone into finding ways to manage high LDL cholesterol in familial hypercholesterolemic (HoFH and HeFH) individuals with loss-of-function mutations in the LDL receptor (LDLR) gene. Statins proved to be the first blockbuster drug, helping both HoFH and HeFH individuals by inhibiting the cholesterol synthesis pathway rate-limiting enzyme HMG-CoA reductase and inducing the LDL receptor. However, statins could not achieve the therapeutic goal of LDL. Other therapies targeting LDLR include PCSK9, which lowers LDLR by promoting LDLR degradation. Inducible degrader of LDLR (IDOL) also controls the LDLR protein, but an IDOL-based therapy is yet to be developed. Among the LDLR-independent pathways, such as angiopoietin-like 3 (ANGPTL3), apolipoprotein (apo) B, apoC-III and CETP, only ANGPTL3 offers the advantage of treating both HoFH and HeFH patients and showing relatively better preclinical and clinical efficacy in animal models and hypercholesterolemic individuals, respectively. While loss-of-LDLR-function mutations have been known for decades, gain-of-LDLR-function mutations have recently been identified in some individuals. The new information on gain of LDLR function, together with CRISPR-Cas9 genome/base editing technology to target LDLR and ANGPTL3, offers promise to HoFH and HeFH individuals who are at a higher risk of developing atherosclerotic cardiovascular disease (ASCVD).
LIM Kinases: From Molecular to Pathological Features
Authors: Bénédetti Hélène , Vallée Béatrice
Published: June 2023

LIM kinases (LIMKs), LIMK1 and LIMK2, are atypical kinases, as they are the only two members of the LIM kinase family harbouring two LIM domains at their N-terminus and a kinase domain at their C-terminus [...]
From Active Participant to Active Researcher: What Do Young People Understand about Research?
Authors: Alias Amelia , Mohamad Nasri Nurfaradilla , Awang Mohd Mahzan
Published: June 2023

This paper discusses the outcomes of an initiative to empower young people as active researchers. It highlights participants’ understandings of their role as researchers in terms of the meaning of research, the research processes, and the participants’ competences, knowledge, and skills. It describes a process that a group of 15 child councillors aged between 15 and 17 years went through that was aimed at equipping them with the knowledge and skills to conduct their research. Based on the data presented, it was clear that from the participants’ point of view, the research process was challenging and time-consuming since it entailed several steps that needed to be carried out with careful attention to detail. Despite this, the participants were confident in their ability to undertake independent research, albeit with guidance from adults. Their research abilities and knowledge of child rights improved because of their having conducted research. The participants also noted that their learning was more meaningful when they were engaged in the subject topic, supporting the notion that learning by doing is vital. Due to its emphasis on acquiring children’s meaningful participation and illustrating the complex reality of being a part of research, this study has made important contributions to the small body of literature on child participation in Malaysia.
The Notorious Triumvirate in Pediatric Health: Air Pollution, Respiratory Allergy, and Infection
Authors: Endaryanto Anang , Darma Andy , Sundjaya Tonny , Masita Bertri Maulidya , Basrowi Ray Wagiu
Published: June 2023

A plausible association is suspected among air pollution, respiratory allergic disorder, and infection. These three factors could cause uncontrollable chronic inflammation in the airway tract, creating a negative impact on the physiology of the respiratory system. This review aims to understand the underlying pathophysiology in explaining the association among air pollution, respiratory allergy, and infection in the pediatric population and to capture the public’s attention regarding the interaction among these three factors, as they synergistically reduce the health status of children living in polluted countries globally, including Indonesia.
Longitudinal Characterization of Immune Response in a Cohort of Children Hospitalized with Multisystem Inflammatory Syndrome
Authors: Dotta Laura , Moratto Daniele , Cattalini Marco , Brambilla Sara , Giustini Viviana , Meini Antonella , Girelli Maria Federica , Cortesi Manuela , Timpano Silviana , Galvagni Anna , Viola Anna , Crotti Beatrice , Manerba Alessandra , Pierelli Giorgia , Verzura Giulia , Serana Federico , Brugnoni Duilio , Garrafa Emirena , Ricci Francesca , Tomasi Cesare , Chiarini Marco , Badolato Raffaele
Published: June 2023

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection caused by hyperactivation of the immune system. Methods: this is a retrospective analysis of clinical data, biochemical parameters, and immune cell subsets in 40 MIS-C patients from hospital admission to outpatient long-term follow-up. Results: MIS-C patients had elevated inflammatory markers, associated with T- and NK-cell lymphopenia, a profound depletion of dendritic cells, and altered monocyte phenotype at disease onset, while the subacute phase of the disease was characterized by a significant increase in T- and B-cell counts and a rapid decline in activated T cells and terminally differentiated B cells. Most of the immunological parameters returned to values close to the normal range during the remission phase (20–60 days after hospital admission). Nevertheless, we observed a significantly reduced ratio between recently generated and more differentiated CD8+ T- and B-cell subsets, which partially settled at longer-term follow-up determinations. Conclusions: The characterization of lymphocyte distribution in different phases of MIS-C may help to understand the course of diseases that are associated with dysregulated immune responses and to calibrate prompt and targeted treatments.
Supporting Preschoolers’ Mental Health and Academic Learning through the PROMEHS Program: A Training Study
Authors: Conte Elisabetta , Cavioni Valeria , Ornaghi Veronica , Agliati Alessia , Gandellini Sabina , Santos Margarida Frade , Santos Anabela Caetano , Simões Celeste , Grazzani Ilaria
Published: June 2023

There is compelling evidence that early school intervention programs enhance children’s development of life skills, with a positive knock-on effect on their behaviors and academic outcomes. To date, most universal interventions have displayed gains in children’s social-emotional competencies with a limited reduction in problem behaviors. This may depend on programs’ curricula focused to a greater extent on preschoolers’ social-emotional competencies rather than problem behaviors. Promoting Mental Health at Schools (PROMEHS) is a European, school-based, universal mental health program explicitly focused on both promoting students’ mental health and preventing negative conduct by adopting a whole-school approach. In this study, we set out to evaluate the effectiveness of the program for Italian and Portuguese preschoolers. We recruited 784 children (age range = 4–5 years), assigning them to either an experimental group (six months’ participation in the PROMEHS program under the guidance of their teachers, who had received ad hoc training) or a waiting list group (no intervention). We found that PROMEHS improved preschoolers’ social-emotional learning (SEL) competencies, prosocial behavior, and academic outcomes. The more practical activities were carried out at school, the more children’s SEL competencies increased, and the more their internalizing and externalizing behaviors decreased. Furthermore, marginalized and disadvantaged children were those who benefited most from the program, displaying both greater improvements in SEL and more marked decreases in internalizing problems compared to the rest of the sample.
Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies
Authors: Tsiftsoglou Stefanos A.
Published: June 2023

Heme (Fe2+-protoporphyrin IX) is a pigment of life, and as a prosthetic group in several hemoproteins, it contributes to diverse critical cellular processes. While its intracellular levels are tightly regulated by networks of heme-binding proteins (HeBPs), labile heme can be hazardous through oxidative processes. In blood plasma, heme is scavenged by hemopexin (HPX), albumin and several other proteins, while it also interacts directly with complement components C1q, C3 and factor I. These direct interactions block the classical pathway (CP) and distort the alternative pathway (AP). Errors or flaws in heme metabolism, causing uncontrolled intracellular oxidative stress, can lead to several severe hematological disorders. Direct interactions of extracellular heme with alternative pathway complement components (APCCs) may be implicated molecularly in diverse conditions at sites of abnormal cell damage and vascular injury. In such disorders, a deregulated AP could be associated with the heme-mediated disruption of the physiological heparan sulphate–CFH coat of stressed cells and the induction of local hemostatic responses. Within this conceptual frame, a computational evaluation of HBMs (heme-binding motifs) aimed to determine how heme interacts with APCCs and whether these interactions are affected by genetic variation within putative HBMs. Combined computational analysis and database mining identified putative HBMs in all of the 16 APCCs examined, with 10 exhibiting disease-associated genetic (SNPs) and/or epigenetic variation (PTMs). Overall, this article indicates that among the pleiotropic roles of heme reviewed, the interactions of heme with APCCs could induce differential AP-mediated hemostasis-driven pathologies in certain individuals.
Priority Criteria (PC) Based Particle Swarm Optimization of Reinforced Concrete Frames (PCPSO)
Authors: Alemu Yohannes L. , Habte Bedilu , Lahmer Tom , Urgessa Girum
Published: June 2023

Simplicity and optimality are commonly associated with the particle swarm optimization (PSO) algorithm. As a result, numerous variants and hybrids of PSO have been developed and implemented to address structural optimization problems. The undeniable importance of the initialization technique in determining the overall performance of a given optimization algorithm cannot be overstated. Optimization algorithms, such as PSO, typically rely on a random, uniformly distributed initialization. Through multiple iterations and updates, these algorithms aim to achieve optimal results. The underlying assumption behind such an initialization approach is that a fair or reasonable arrangement of particles is best accomplished through randomization, and thus the entire optimization process is iterated based on this assumption. However, this initialization technique raises concerns regarding the attainment of optimality and convergence, leaving room for further examination. In this paper, we challenge this assumption by introducing a priority concept. The key idea is that particles should not be initialized randomly since randomness alone does not guarantee a reasonable allocation of design variable values in iterative optimization. This can lead to misguided velocity updates and ultimately, a time-consuming pursuit of optimality. To address this issue, we formulate priority criteria (PC) and propose an enhanced PSO variant called Priority Criteria PSO (PCPSO). The PC can be incorporated into any PSO variant or hybrid without impacting the parameter settings, constraints, and penalty approaches of the respective algorithms. A case study involving 2D reinforced concrete frames was conducted to compare the performance of the ordinary PSO algorithm with the PCPSO. The results clearly demonstrate that the introduction of the PC leads to a significant cost reduction when compared to PSO with an inertia damping factor. Additionally, the PCPSO algorithm exhibits accelerated convergence. Furthermore, to alleviate the computational burden associated with structural analysis at each iteration, a reanalysis approach called Combined Approximations (CA) is mathematically formulated and implemented.
Bimetallic 3D Nickel-Manganese/Titanium Bifunctional Electrocatalysts for Efficient Hydrogen and Oxygen Evolution Reaction in Alkaline and Acidic Media
Authors: Barua Sukomol , Balčiūnaitė Aldona , Vaičiūnienė Jūrate , Tamašauskaitė-Tamašiūnaitė Loreta , Norkus Eugenijus
Published: June 2023

In this work, 3D nickel-manganese (NiMn) bimetallic coatings have been studied as electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline (1.0 M KOH) media and the HER in acidic (0.5 M H2SO4) media. The catalysts have been deposited on a titanium substrate (1 × 1 cm2) using low-cost and facile electrochemical deposition method through a dynamic hydrogen bubble template technique. The electrocatalytic performance of these fabricated catalysts was investigated by using Linear Sweep Voltammetry (LSV) for HER and OER at different temperatures ranging from 25 up to 75 °C and also was characterized by scanning electron microscopy (SEM) and inductively coupled plasma optical emission spectroscopy (ICP-OES). It was found that fabricated NiMn/Ti-5 electrocatalyst with Ni2+/Mn2+ molar ratio of 1:5 exhibits excellent HER activity in alkaline media with overpotential of 127.1 mV to reach current density of 10 mA cm−2. On the contrary, NiMn/Ti-1 electrocatalyst that fabricated with Ni2+/Mn2+ molar proportion of 1:1 and lowest Mn-loading of 13.43 µgcm−2 demonstrates exceptional OER activity with minimum overpotential of 356.3 mV to reach current density of 10 mA cm−2. The current densities increase ca. 1.8–2.2 times with an increase in temperature from 25 °C to 75 °C for both HER and OER investigation. Both catalysts also have exhibited excellent long-term stability for 10 h at constant potentials as well as constant current density of 10 mA cm−2 that assure their robustness and higher durability regarding alkaline water splitting.