bluuebunny/crossref_metadata_2025 huggingface dataset:
From Hamamelitannin Synthesis to the Study of Enzymatic Acylations of D-Hamamelose
Authors: Mastihubová Mária , Mastihuba Vladimír
Published: March 2023

The bioactive natural substance, hamamelitannin, was effectively synthesized in two ways. The chemical acylation of 2,3-O-isopropylidene-α,β-D-hamamelofuranose promoted by Bu2SnO using 3,4,5-tri-O-acetylgalloyl chloride, followed by the deprotection provided hamamelitannin in 79%. Pilot enzymatic benzoylation of D-hamamelose using vinyl benzoate (4 equiv.) and Lipozyme TL IM as a biocatalyst in t-butyl methyl ether (t-BuMeO) gave mainly benzoylated furanoses (89%), of which tribenzoates reached (52%). Enzymatic galloylation of 2,3-O-isopropylidene-α,β-D-hamamelofuranose with vinyl gallate under the catalysis of Lipozyme TL IM in t-butyl alcohol (t-BuOH) or t-BuMeO provided only the 5-O-galloylated product. The reaction in t-BuMeO proceeded in a shorter reaction time (61 h) and higher yield (82%). The more hydrophobic vinyl 3,4,5-tri-O-acetylgallate in the same reactions gave large amounts of acetylated products. Vinyl gallate and triacetylgallate in the enzymatic acylation of D-hamamelose with Lipozyme TL IM in t-BuMeO yielded 2′,5-diacylated hamamelofuranoses in a yield below 20%. The use of other vinyl gallates hydrophobized by methylation or benzylation provided 2′,5-diacylated hamamelofuranoses in good yields (65–84%). The reaction with silylated vinyl gallate did not proceed. The best results were obtained with vinyl 2,3,5-tri-O-benzyl gallate, and the only product, 2′,5-diacylated hamamelofuranoside precipitated from the reaction mixture (84% in 96 h). After debenzylation, hamamelitannin was obtained an 82% yield from hamamelose in two steps. This synthesis is preparatively undemanding and opens the way to multigram preparations of bioactive hamamelitannin and its analogues.
A Molecular Mechanism to Explain the Nickel-Induced Changes in Protamine-like Proteins and Their DNA Binding Affecting Sperm Chromatin in Mytilus galloprovincialis: An In Vitro Study
Authors: Carbone Gelsomina , Lettieri Gennaro , Marinaro Carmela , Costabile Martina , Notariale Rosaria , Bianchi Anna Rita , De Maio Anna , Piscopo Marina
Published: March 2023

Nickel is associated with reproductive toxicity, but little is known about the molecular mechanisms of nickel-induced effects on sperm chromatin and protamine-like proteins (PLs). In the present work, we analyzed PLs from Mytilus galloprovincialis by urea-acetic acid polyacrylamide gel electrophoresis (AU-PAGE) and SDS-PAGE and assessed their binding to DNA by Electrophoretic Mobility Shift Assay (EMSA) after exposing mussels to 5, 15, and 35 µM NiCl2 for 24 h. In addition, a time course of digestion with MNase and release of PLs from sperm nuclei by the NaCl gradient was performed. For all exposure doses, in AU-PAGE, there was an additional migrating band between PL-III and PL-IV, corresponding to a fraction of PLs in the form of peptides detected by SDS-PAGE. Alterations in DNA binding of PLs were observed by EMSA after exposure to 5 and 15 µM NiCl2, while, at all NiCl2 doses, increased accessibility of MNase to sperm chromatin was found. The latter was particularly relevant at 15 µM NiCl2, a dose at which increased release of PLII and PLIII from sperm nuclei and the highest value of nickel accumulated in the gonads were also found. Finally, at all exposure doses, there was also an increase in PARP expression, but especially at 5 µM NiCl2. A possible molecular mechanism for the toxic reproductive effects of nickel in Mytilus galloprovincialis is discussed.
Kawain Inhibits Urinary Bladder Carcinogenesis through Epigenetic Inhibition of LSD1 and Upregulation of H3K4 Methylation
Authors: Xu Xia , Tian Xuejiao , Song Liankun , Xie Jun , Liao Joseph C. , Meeks Joshua J. , Wu Xue-Ru , Gin Greg E. , Wang Beverly , Uchio Edward , Zi Xiaolin
Published: March 2023

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.
Spine Bracing: When to Utilize—A Narrative Review
Authors: Cerillo John L. , Becsey Alexander N. , Sanghadia Chai P. , Root Kevin T. , Lucke-Wold Brandon
Published: March 2023

Spinal bracing is a common non-surgical technique that allows clinicians to prevent and correct malformations or injuries of a patient’s spinal column. This review will explore the current standards of practice on spinal brace utilization. Specifically, it will highlight bracing usage in traumatic injuries, pregnancy, pediatrics, osteoporosis, and hyperkyphosis; address radiological findings concurrent with brace usage; and provide an overview of the braces currently available and advancements in the field. In doing so, we aim to improve clinicians’ understanding and knowledge of bracing in common spinal pathologies to promote their appropriate use and improve patient outcomes.
Oral Candidiasis in Adult and Pediatric Patients with COVID-19
Authors: Pisano Massimo , Romano Antonio , Di Palo Maria Pia , Baroni Adone , Serpico Rosario , Contaldo Maria
Published: March 2023

Oral Candidiasis (OC) is an opportunistic fungal infection of the oral cavity, frequently reported under local and systemic predisposing circumstances. While the recurrence of OC HIV-infected subjects has been well described and reported, the association between oral candidiasis and the SARS-CoV-2 infection is a recent finding that still is worthy of further study. The present paper focuses on this novel association, reporting the incidence and prevalence of OC occurring during and after COVID-19 and the possible etiopathogenic mechanisms underlying the onset of OC in COVID-19 subjects. The work found that the immune inflammatory hypo reactions and immunosuppression found in children and adults with COVID-19 could favor the proliferation colonization of Candida species and the following infection. At the same time, poor oral hygiene and iatrogenic causes seem to be the main risk factors.
Evaluation of the Antioxidant Activity of Levetiracetam in a Temporal Lobe Epilepsy Model
Authors: Ignacio-Mejía Iván , Contreras-García Itzel Jatziri , Mendoza-Torreblanca Julieta Griselda , Medina-Campos Omar Noel , Pedraza-Chaverri José , García-Cruz Mercedes Edna , Romo-Mancillas Antonio , Gómez-Manzo Saúl , Bandala Cindy , Sánchez-Mendoza María Elena , Pichardo-Macías Luz Adriana , Cárdenas-Rodríguez Noemí
Published: March 2023

Epilepsy is a neurological disorder in which it has been shown that the presence of oxidative stress (OS) is implicated in epileptogenesis. The literature has shown that some antiseizure drugs (ASD) have neuroprotective properties. Levetiracetam (LEV) is a drug commonly used as an ASD, and in some studies, it has been found to possess antioxidant properties. Because the antioxidant effects of LEV have not been demonstrated in the chronic phase of epilepsy, the objective of this study was to evaluate, for the first time, the effects of LEV on the oxidant–antioxidant status in the hippocampus of rats with temporal lobe epilepsy (TLE). The in vitro scavenging capacity of LEV was evaluated. LEV administration in rats with TLE significantly increased superoxide dismutase (SOD) activity, increased catalase (CAT) activity, but did not change glutathione peroxidase (GPx) activity, and significantly decreased glutathione reductase (GR) activity in comparison with epileptic rats. LEV administration in rats with TLE significantly reduced hydrogen peroxide (H2O2) levels but did not change lipoperoxidation and carbonylated protein levels in comparison with epileptic rats. In addition, LEV showed in vitro scavenging activity against hydroxyl radical (HO•). LEV showed significant antioxidant effects in relation to restoring the redox balance in the hippocampus of rats with TLE. In vitro, LEV demonstrated direct antioxidant activity against HO•.
Using Mean Arterial Pressure in Hypertension Diagnosis versus Using Either Systolic or Diastolic Blood Pressure Measurements
Authors: Kandil Heba , Soliman Ahmed , Alghamdi Norah Saleh , Jennings J. Richard , El-Baz Ayman
Published: March 2023

Hypertension is a severe and highly prevalent disease. It is considered a leading contributor to mortality worldwide. Diagnosis guidelines for hypertension use systolic and diastolic blood pressure (BP) together. Mean arterial pressure (MAP), which refers to the average of the arterial blood pressure through a single cardiac cycle, can be an alternative index that may capture the overall exposure of the person to a heightened pressure. A clinical hypothesis, however, suggests that in patients over 50 years old in age, systolic BP may be more predictive of adverse events, while in patients under 50 years old, diastolic BP may be slightly more predictive. In this study, we investigated the correlation between cerebrovascular changes, (impacted by hypertension), and MAP, systolic BP, and diastolic BP separately. Several experiments were conducted using real and synthetic magnetic resonance angiography (MRA) data, along with corresponding BP measurements. Each experiment employs the following methodology: First, MRA data were processed to remove noise, bias, or inhomogeneity. Second, the cerebrovasculature was delineated for MRA subjects using a 3D adaptive region growing connected components algorithm. Third, vascular features (changes in blood vessel’s diameters and tortuosity) that describe cerebrovascular alterations that occur prior to and during the development of hypertension were extracted. Finally, feature vectors were constructed, and data were classified using different classifiers, such as SVM, KNN, linear discriminant, and logistic regression, into either normotensives or hypertensives according to the cerebral vascular alterations and the BP measurements. The initial results showed that MAP would be more beneficial and accurate in identifying the cerebrovascular impact of hypertension (accuracy up to 95.2%) than just using either systolic BP (accuracy up to 89.3%) or diastolic BP (accuracy up to 88.9%). This result emphasizes the pathophysiological significance of MAP and supports prior views that this simple measure may be a superior index for the definition of hypertension and research on hypertension.
Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing
Authors: Park Ha Young , Lee Joong Seob , Wee Jee Hye , Kang Jeong Wook , Kim Eun Soo , Koo Taeryool , Hwang Hee Sung , Kim Hyo Jung , Kang Ho Suk , Lim Hyun , Kim Nan Young , Nam Eun Sook , Cho Seong Jin , Kwon Mi Jung
Published: March 2023

Data regarding driver mutation profiles in tonsillar squamous cell carcinomas (TSCCs) remain scarce, limiting the understanding of its pathogenesis and unexpected behavior in the updated staging system. We investigated the incidence of clinically relevant mutations and their contribution in the prognosis of the condition, and their association with human papillomavirus (HPV) infection and adjuvant therapy. We subjected 43 surgically resected TSCC samples to targeted next-generation sequencing, determined their HPV status using polymerase chain reaction, and performed The Cancer Genomic Atlas and Gene Set Enrichment analyses. Thirty-five TSCC samples (81.4%) showed at least one oncogenic/likely oncogenic mutation among twenty-nine cancer-related genes. The top five mutated genes were TP53 (46.5%), PIK3CA (25.6%), PTEN (18.6%), EGFR (16.3%), and SMAD4 (14.0%). The EGFR pathway was the most frequently affected (51.2%), followed by the p53 (48.8%), PI3K (39.5%), and RTK (34.9%) pathways. The gene set enrichment analysis confirmed that the genes involved in signal transduction, such as growth factor receptors and second messengers, EGFR tyrosine kinase inhibitors, and PI3K signaling pathways, were mostly related with TSCCs. TP53 mutation was an independent prognostic factor predicting worse overall survival in the adjuvant therapy group. RTK mutations were related to survival in all patients and in the HPV-positive group, but multivariate analyses showed no significance. In conclusion, oncogenic/likely oncogenic mutations were relatively high in TSCCs, and TP53 and RTK mutations may be candidate predictors for poor prognosis in the adjuvant therapy and HPV-positive groups, respectively, under the updated staging system.
Experimentally Induced Burns in Rats Treated with Innovative Polymeric Films Type Therapies
Authors: Grosu Oxana-Madalina , Dragostin Oana-Maria , Gardikiotis Ioannis , Chitescu Carmen Lidia , Lisa Elena Lacramioara , Zamfir Alexandra-Simona , Confederat Luminita , Dragostin Ionut , Dragan Maria , Stan Catalina Daniela , Zamfir Carmen-Lacramioara
Published: March 2023

Considering that microbial resistance to antibiotics is becoming an increasingly widespread problem, burn management, which usually includes the use of topical antimicrobial dressings, is still facing difficulties regarding their efficiency to ensure rapid healing. In this context, the main objective of this research is to include new oxytetracycline derivatives in polymeric-film-type dressings for the treatment of wounds caused by experimentally induced burns in rats. The structural and physico-chemical properties of synthesized oxytetracycline derivatives and the corresponding membranes were analyzed by FT-IR and MS spectroscopy, swelling ability and biodegradation capacity. In vitro antimicrobial activity using Gram-positive and Gram-negative bacterial strains and pathogenic yeasts, along with an in vivo study of a burn wound model induced in Wistar rats, was also analyzed. The newly obtained polymeric films, namely chitosan-oxytetracycline derivative membranes, showed good antimicrobial activity noticed in the tested strains, a membrane swelling ratio (MSR) of up to 1578% in acidic conditions and a biodegradation rate of up to 15.7% on day 7 of testing, which are important required characteristics for the tissue regeneration process, after the production of a burn. The in vivo study proved that chitosan-derived oxytetracycline membranes showed also improved healing effects which contributes to supporting the idea of using them for the treatment of wounds caused by burns.
Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study
Authors: Rutkowski Tomasz Wojciech , Jaroszewicz Jerzy , Piotrowski Damian , Ślosarek Krzysztof , Sobala-Szczygieł Barbara , Słonina Dorota , Włostowska Bożena , Bodusz Dawid , Piasecki Maciej , Nachlik Michał , Oczko-Grzesik Barbara , Gądek Adam , Kowal Dorota , Rutkowski Roman , Wojarska-Tręda Elżbieta , Składowski Krzysztof
Published: March 2023

Purpose: Results of the low-dose radiation therapy (LDRT) in patients with pneumonia due to COVID-19 has been presented. Methods: Fifteen patients received a single-fraction radiation dose of 1 Gy to the bilateral lungs due to pre-ARDS pneumonia in the course of COVID-19. Follow-up was performed on days 1, 3, 5, 7, 14 after LDRT. Results: Eleven patients (73%) were released up until day 28. Median hospitalization was 20 days; 28-day mortality was 13%. Median O2 saturation improved within 24 h after LDRT in 14/15, with median SpO2 values of 84.5% vs. 87.5% p = 0.016, respectively. At day 14 of hospitalization, 46% did not require oxygen supplementation. Significant decline in CRP and IL-6 was observed within 24 h post LDRT. No organ toxicities were noted. Conclusion: LDRT is feasible, well tolerated and may translate to early clinical recovery in patients with severe pneumonia. Further studies are needed to determine optimal candidate, time and dose of LDRT for COVID-19 patients with pneumonia.
Growth Conditions Influence Lactobacillus Cell-Free Supernatant Impact on Viability, Biofilm Formation, and Co-Aggregation of the Oral Periodontopathogens Fusobacterium nucleatum and Porphyromonas gingivalis
Authors: Zanetta Paola , Squarzanti Diletta Francesca , di Coste Alessia , Amoruso Angela , Pane Marco , Azzimonti Barbara
Published: March 2023

Fusobacterium nucleatum and Porphyromonas gingivalis human periodontopathogens play a leading part in oral squamous cell carcinoma through cell proliferation, invasion, and persistent inflammation promotion and maintenance. To explore how the activity of Lactobacillus-derived cell-free supernatants (CFSs) can be influenced by growth medium components, CFSs were produced both in the standard MRS and the novel animal-derivative-free “Terreno Industriale Lattobacilli” (TIL) media, and in vitro screened for the containment of F. nucleatum and P. gingivalis both single and co-cultured and also for the interference on their co-aggregation. The viability assay demonstrated that the Limosilactobacillus reuteri LRE11 and Ligilactobacillus salivarius LS03 MRS-produced CFSs were significantly more effective against single and co-cultured pathogens. All the other CFSs significantly improved their efficacy when produced in TIL. Both MRS- and TIL-produced CFSs significantly inhibited the single and co-cultured pathogen biofilm formation. Only Levilactobacillus brevis LBR01 CFS in MRS specifically reduced F. nucleatum and P. gingivalis co-aggregation, while viable LBR01, LS03, and LRE11 in MRS significantly co-aggregated with the pathogens, but only LS03 cultivated in TIL improved this effect. This work paves the way to better consider environmental growth conditions when screening for probiotic and postbiotic efficacy as crucial to pathogen aggregation, adhesion to the host’s niches, and exclusion.
Rosiglitazone Mitigates Dexamethasone-Induced Depression in Mice via Modulating Brain Glucose Metabolism and AMPK/mTOR Signaling Pathway
Authors: Alhaddad Aisha , Radwan Asmaa , Mohamed Noha A. , Mehanna Eman T. , Mostafa Yasser M. , El-Sayed Norhan M. , Fattah Shaimaa A.
Published: March 2023

Major depressive disorder (MDD) is a common, complex disease with poorly understood pathogenesis. Disruption of glucose metabolism is implicated in the pathogenesis of depression. AMP-activated protein kinase (AMPK) has been shown to regulate the activity of several kinases, including pAKT, p38MAPK, and mTOR, which are important signaling pathways in the treatment of depression. This study tested the hypothesis that rosiglitazone (RGZ) has an antidepressant impact on dexamethasone (DEXA)-induced depression by analyzing the function of the pAKT/p38MAPK/mTOR pathway and NGF through regulation of AMPK. MDD-like pathology was induced by subcutaneous administration of DEXA (20 mg/kg) for 21 days in all groups except in the normal control group, which received saline. To investigate the possible mechanism of RGZ, the protein expression of pAMPK, pAKT, p38MAPK, and 4EBP1 as well as the levels of hexokinase, pyruvate kinase, and NGF were assessed in prefrontal cortex and hippocampal samples. The activities of pAMPK and NGF increased after treatment with RGZ. The administration of RGZ also decreased the activity of mTOR as well as downregulating the downstream signaling pathways pAKT, p38MAPK, and 4EBP1. Here, we show that RGZ exerts a potent inhibitory effect on the pAKT/p38MAPK/mTOR/4EBP1 pathway and causes activation of NGF in brain cells. This study has provided sufficient evidence of the potential for RGZ to ameliorate DEXA-induced depression. A new insight has been introduced into the critical role of NGF activation in brain cells in depression. These results suggest that RGZ is a promising antidepressant for the treatment of MDD.
Polymorphisms within the Tumor Necrosis Factor-Alpha Gene Is Associated with Preeclampsia in Taiwanese Han Populations
Authors: Lin Chih-Wei , Chen Chung-Hwan , Wu Meng-Hsing , Chang Fong-Ming , Kang Lin
Published: March 2023

Preeclampsia (PE) occurs in women pregnant for more than 20 weeks with de novo hypertension and proteinuria, and is a devastating disease in maternal–fetal medicine. Cytokine tumor necrosis factor (TNF)-α may play a key role in the pathogenesis of PE. We conducted this study to investigate the regulatory regions of the TNF genes, by investigating two promoter polymorphisms, TNFA-308G/A (rs1800629) and -238G/A (rs361525), known to influence TNF expression, and their relationship to PE. An observational, monocentric, case–control study was conducted. We retrospectively collected 74 cases of severe PE and 119 pregnant women without PE as control. Polymerase chain reaction (PCR) was carried out for allele analysis. Higher A allele in women with PE was found in rs1800629 but not rs361525. In this study, we first found that polymorphism at the position -308, but not -238, in the promoter region of the TNF-α gene can contribute to severe PE in Taiwanese Han populations. The results of our study are totally different to previous Iranian studies, but have some similarity to a previous UK study. Further studies are required to confirm the roles of rs1800629 and rs361525 in PE with circulating TNF-α in PE.
ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher
Authors: Chen Lihua , Huang Lixiang , Dong Binhua , Gu Yu , Cang Wei , Li Chen , Sun Pengming , Xiang Yang
Published: March 2023

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan–Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281–22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156–10.518), (0.370–8.137), and (0.171–4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.
Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype
Authors: Caltavituro Aldo , Buonaiuto Roberto , Pietroluongo Erica , Morra Rocco , Salomone Fabio , De Placido Pietro , Pagliuca Martina , Vaia Angelo , Ottaviano Margaret , Tortora Marianna , De Placido Sabino , Palmieri Giovannella , Giuliano Mario
Published: March 2023

Sarcomas of the thoracic cavity are rare entities that predominantly affect children and young adults. They can be very heterogeneous encompassing several different histological entities. Ewing Sarcoma (ES) can potentially arise from every bone, soft tissue, or visceral site in the body. However, it represents an extremely rare finding when it affects the thoracic cavity. It represents the second most frequent type of thoracic sarcoma, after chondrosarcoma. ES arises more frequently in sites that differ from the thoracic cavity, but it displays the same biological features and behavior of extra-thoracic ones. Current management of ES often requires a multidisciplinary treatment approach including surgery, radiotherapy, and systemic therapy, as it can guarantee local and distant disease control, at least transiently, although the long-term outcome remains poor. Unfortunately, due to the paucity of clinical trials purposely designed for this rare malignancy, there are no optimal strategies that can be used for disease recurrence. As a result of its complex biological features, ES might be suitable for emerging biology-based therapeutic strategies. However, a deeper understanding of the molecular mechanisms driving tumor growth and treatment resistance, including those related to oncogenic pathways, epigenetic landscape, and immune microenvironment, is necessary in order to develop new valid therapeutic opportunities. Here, we provide an overview of the most recent therapeutic advances for ES in both the preclinical and clinical settings. We performed a review of the current available literature and of the ongoing clinical trials focusing on new treatment strategies, after failure of conventional multimodal treatments.
A Two-Step Approach to Overcoming Data Imbalance in the Development of an Electrocardiography Data Quality Assessment Algorithm: A Real-World Data Challenge
Authors: Kim Hyun Joo , Venkat S. Jayakumar , Chang Hyoung Woo , Cho Yang Hyun , Lee Jee Yang , Koo Kyunghee
Published: March 2023

Continuously acquired biosignals from patient monitors contain significant amounts of unusable data. During the development of a decision support system based on continuously acquired biosignals, we developed machine and deep learning algorithms to automatically classify the quality of ECG data. A total of 31,127 twenty-s ECG segments of 250 Hz were used as the training/validation dataset. Data quality was categorized into three classes: acceptable, unacceptable, and uncertain. In the training/validation dataset, 29,606 segments (95%) were in the acceptable class. Two one-step, three-class approaches and two two-step binary sequential approaches were developed using random forest (RF) and two-dimensional convolutional neural network (2D CNN) classifiers. Four approaches were tested on 9779 test samples from another hospital. On the test dataset, the two-step 2D CNN approach showed the best overall accuracy (0.85), and the one-step, three-class 2D CNN approach showed the worst overall accuracy (0.54). The most important parameter, precision in the acceptable class, was greater than 0.9 for all approaches, but recall in the acceptable class was better for the two-step approaches: one-step (0.77) vs. two-step RF (0.89) and one-step (0.51) vs. two-step 2D CNN (0.94) (p < 0.001 for both comparisons). For the ECG quality classification, where substantial data imbalance exists, the 2-step approaches showed more robust performance than the one-step approach. This algorithm can be used as a preprocessing step in artificial intelligence research using continuously acquired biosignals.
Laser-Cutted Epidermal Microfluidic Patch with Capillary Bursting Valves for Chronological Capture, Storage, and Colorimetric Sensing of Sweat
Authors: He Yuxin , Wei Lei , Xu Wenjie , Wu Huaping , Liu Aiping
Published: March 2023

Flexible wearable microfluidic devices show great feasibility and potential development in the collection and analysis of sweat due to their convenience and non-invasive characteristics in health-level feedback and disease prediction. However, the traditional production process of microfluidic patches relies on resource-intensive laboratory and high-cost facilities. In this paper, a low-cost laser-cutting technology is proposed to fabricate epidermal microfluidic patches for the collection, storage and colorimetric analysis of sweat. Two different types of capillary bursting valves are designed and integrated into microchannel layers to produce two-stage bursting pressure for the reliable routing of sweat into microreservoirs in sequential fashion, avoiding the mixing of old and new sweat. Additionally, an enzyme-based reagent is embedded into the microreservoirs to quantify the glucose level in sweat by using colorimetric methods, demonstrating a high detection sensitivity at the glucose concentration from 0.1 mM to 1 mM in sweat and an excellent anti-interference performance that prevents interference from substances probably existent in sweat. In vitro and on-body experiments demonstrate the validity of the low-cost, laser-cut epidermal microfluidic patch for the chronological analysis of sweat glucose concentration and its potential application in the monitoring of human physiological information.
Lab on a Chip Device for Diagnostic Evaluation and Management in Chronic Renal Disease: A Change Promoting Approach in the Patients’ Follow Up
Authors: Borriello Margherita , Tarabella Giuseppe , D’Angelo Pasquale , Liboà Aris , Barra Mario , Vurro Davide , Lombari Patrizia , Coppola Annapaola , Mazzella Elvira , Perna Alessandra F. , Ingrosso Diego
Published: March 2023

Lab-on-a-chip (LOC) systems are miniaturized devices aimed to perform one or several analyses, normally carried out in a laboratory setting, on a single chip. LOC systems have a wide application range, including diagnosis and clinical biochemistry. In a clinical setting, LOC systems can be associated with the Point-of-Care Testing (POCT) definition. POCT circumvents several steps in central laboratory testing, including specimen transportation and processing, resulting in a faster turnaround time. Provider access to rapid test results allows for prompt medical decision making, which can lead to improved patient outcomes, operational efficiencies, patient satisfaction, and even cost savings. These features are particularly attractive for healthcare settings dealing with complicated patients, such as those affected by chronic kidney disease (CKD). CKD is a pathological condition characterized by progressive and irreversible structural or functional kidney impairment lasting for more than three months. The disease displays an unavoidable tendency to progress to End Stage Renal Disease (ESRD), thus requiring renal replacement therapy, usually dialysis, and transplant. Cardiovascular disease (CVD) is the major cause of death in CKD, with a cardiovascular risk ten times higher in these patients than the rate observed in healthy subjects. The gradual decline of the kidney leads to the accumulation of uremic solutes, with negative effect on organs, especially on the cardiovascular system. The possibility to monitor CKD patients by using non-invasive and low-cost approaches could give advantages both to the patient outcome and sanitary costs. Despite their numerous advantages, POCT application in CKD management is not very common, even if a number of devices aimed at monitoring the CKD have been demonstrated worldwide at the lab scale by basic studies (low Technology Readiness Level, TRL). The reasons are related to both technological and clinical aspects. In this review, the main technologies for the design of LOCs are reported, as well as the available POCT devices for CKD monitoring, with a special focus on the most recent reliable applications in this field. Moreover, the current challenges in design and applications of LOCs in the clinical setting are briefly discussed.
Wavelength-Dependent Metal-Enhanced Fluorescence Biosensors via Resonance Energy Transfer Modulation
Authors: Lee Seungah , Kang Seong Ho
Published: March 2023

Fluorescence can be enhanced or quenched depending on the distance between the surface of a metal nanoparticle and the fluorophore molecule. Fluorescence enhancement by nearby metal particles is called metal-enhanced fluorescence (MEF). MEF shows promising potential in the field of fluorescence-based biological sensing. MEF-based biosensor systems generally fall into two platform categories: (1) a two/three-dimensional scaffold, or (2) a colloidal suspension. This review briefly summarizes the application studies using wavelength-dependent carbon dots (UV-VIS), noble metals (VIS), and upconversion nanoparticles (NIR to VIS), representative nanomaterials that contribute to the enhancement of fluorescence through the resonance energy transfer modulation and then presents a perspective on this topic.
Robust Detection of Cancer Markers in Human Serums Using All-Dielectric Metasurface Biosensors
Authors: Iwanaga Masanobu
Published: March 2023

One of the most significant characteristics, which biosensors are supposed to satisfy, is robustness against abundant molecules coexisting with target biomolecules. In clinical diagnoses and biosensing, blood, plasma, and serum are used daily as samples. In this study, we conducted a series of experiments to examine the robustness of all-dielectric metasurface biosensors, which comprise pairs of a highly fluorescence-enhancing silicon nanopellet array and a transparent microfluidic chip. The metasurface biosensors were shown to have high performance in detecting various targets from nucleic acids to proteins, such as antigens and antibodies. The present results show almost four-order wide dynamic ranges from 0.16 ng/mL to 1 μg/mL for prostate-specific antigen (PSA) and from 2 pg/mL to 25 ng/mL for carcinoembryonic antigen (CEA). The ranges include clinical criteria for PSA, 4 ng/mL and CEA, 5 ng/mL. To date, a systematic demonstration of robustness has not been reported regarding the metasurface biosensors. In detecting cancer markers of PSA and CEA in human serums, we demonstrate that the metasurface biosensors are robust enough in a wide target concentrations, including the clinical diagnosis criteria.
Effects of Paired Associative Stimulation on Cortical Plasticity in Agonist–Antagonist Muscle Representations
Authors: Suzuki Makoto , Saito Kazuo , Maeda Yusuke , Cho Kilchoon , Iso Naoki , Okabe Takuhiro , Suzuki Takako , Yamamoto Junichi
Published: March 2023

Paired associative stimulation (PAS) increases and decreases cortical excitability in primary motor cortex (M1) neurons, depending on the spike timing-dependent plasticity, i.e., long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity, respectively. However, how PAS affects the cortical circuits for the agonist and antagonist muscles of M1 is unclear. Here, we investigated the changes in the LTP- and LTD-like plasticity for agonist and antagonist muscles during PAS: 200 pairs of 0.25-Hz peripheral electric stimulation of the right median nerve at the wrist, followed by a transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 ms (PAS-25 ms) and 10 ms (PAS-10 ms). The unconditioned motor evoked potential amplitudes of the agonist muscles were larger after PAS-25 ms than after PAS-10 ms, while those of the antagonist muscles were smaller after PAS-25 ms than after PAS-10 ms. The γ-aminobutyric acid A (GABAA)- and GABAB-mediated cortical inhibition for the agonist and antagonist muscles were higher after PAS-25 ms than after PAS-10 ms. The cortical excitability for the agonist and antagonist muscles reciprocally and topographically increased and decreased after PAS, respectively; however, GABAA and GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were less topographically decreased after PAS-10 ms. Thus, PAS-25 ms and PAS-10 ms differentially affect the LTP- and LTD-like plasticity in agonist and antagonist muscles.
What’s inside the Mind of a CEO? The Effects of Discretionary Slack Resources on R&D Investment
Authors: Lee Seunghye , Oh Won-Yong , Chang Young Kyun
Published: March 2023

This study investigates the effects of discretionary slack resources on a firm’s R&D investment. Specifically, we examine whether and how a CEO’s psychological traits play a role in the relationship between discretionary slack and R&D investment. Using a panel sample from U.S. manufacturing firms in 2006–2010, we found that slack resources lead to an increase in R&D intensity. Furthermore, this positive effect is stronger when CEOs have a strong promotion focus and perceive an addressable negative attainment discrepancy. Thus, our findings show how (a) the level of discretionary slack and (b) CEOs’ promotion focus and aspiration level jointly shape R&D investment decisions. Considering CEOs’ psychological traits contributes to a more comprehensive view of the conditions under which discretionary slack resources matter for a firm’s strategic decisions.
The Effect of Creators’ Personality Traits and Depression on Teamwork-Based Design Performance
Authors: Wang Szu-Jung , Chen Rain , Lu Hsiu-Ching
Published: March 2023

Many organizations encourage carrying out a project by teamwork for consensus building and managing risks in decision making. When working as a team, the members’ personality traits and depression may affect project performance. This study explored the personality traits and depression of creators on their design performance in teamwork. This study used the Big-Five Personality Traits Scale (Big-5) and the Center for Epidemiologic Studies Depression Scale (CES-D). Forty-four volunteers were chosen to participate in this study as the study subjects. A total of 11 design teams were formed based on the participants’ personality trait score and the depression score. The design performance of the participants was rated by creativity, aesthetics, and completeness. The study results showed that (1) for creativity, PT4 Neuroticism and D1 No Depression performed the best; (2) for aesthetics, PT4 Neuroticism, PT5 Openness, and D2 Mild Depression performed the best; (3) for completeness, PT5 Openness and D4 Severe Depression performed the best; and (4) for member satisfaction and work satisfaction, PT4 Neuroticism and D2 Mild Depression had the lowest scores. Therefore, the overall teamwork performance can be affected by personality traits and depression. Each individual’s personality trait and emotional expression may improve team performance via different dimensions, such as creativity, aesthetics, and completeness. Project managers should have members of different personality traits and with different emotional expression on a team as their personality traits and emotion can facilitate team collaboration.
Mobile Phone Addiction and Sleep Quality: The Mediating Role of Anxiety and the Moderating Role of Emotion Regulation
Authors: Gong Li , Liu Qiang
Published: March 2023

Smartphones have become a fundamental tool in the daily life of mankind, but its excessive use seriously impairs people’s quality of sleep. A specific state of emotion has been shown to play a crucial role in the relationship between mobile phone addiction (MPA) and the sleep quality of college students. However, studies have rarely considered top-down emotion regulation. This study is the first to examine the effects of MPA on the sleep quality of Chinese college students from a top-down emotion regulation perspective. The survey sample comprised 1559 university students (40.73% male; M (SD) age = 19.11 (1.22) years) who completed questionnaires on MPA, sleep quality, anxiety and emotion regulation. The results revealed that (1) Anxiety mediated the relationship between MPA and sleep quality; (2) Cognitive reappraisal (CR) negatively moderated the relationship between MPA and anxiety; and (3) Expressive suppression (ES) positively moderated the relationship between MPA and anxiety. These findings reveal the mechanism of sleep problems in Chinese college students. We provide research ideas and method guidance for the follow-up intervention and treatment of college students’ sleep problems.
Relationship Dysfunction in Couples When One Partner Is Diagnosed with Borderline Personality Disorder: Findings from a Pilot Study
Authors: Kroener Julia , Schaitz Caroline , Karabatsiakis Alexander , Maier Anna , Connemann Bernhard , Schmied Elisa , Sosic-Vasic Zrinka
Published: March 2023

Relationship dysfunction—marked by frequent conflicts—is one of the hallmark features of borderline personality disorder (BPD). However, the BPD couple as a dyad and partner-related features have rarely been taken into account. The aim of the present study was to investigate hormonal, personality, and relationship relevant factors, such as relationship satisfaction, attachment, and trauma in both partners within a dyad where one partner is diagnosed with BPD. The total sample consisted of 26 heterosexual couples. All studies were conducted at 2 p.m. Primary outcomes: Neo-Five-Factor-Inventory, Childhood Trauma Questionnaire, Experiences in Close Relationships Scale. Secondary outcomes: Problem List, Partnership Questionnaire, Questionnaire for Assessing Dyadic Coping. Upon questionnaire completion, one saliva sample was taken via passive drool to assess baseline cortisol and testosterone levels. Results showed that females with BPD have higher scores on childhood maltreatment, dysfunctional attachment styles, and neuroticism than mentally healthy females. Furthermore, they have more relationship-related problems and are less satisfied in their romantic relationship. Male partners of women with BPD showed lower testosterone levels, higher levels of childhood maltreatment, dysfunctional attachment styles, neuroticism, and openness compared with the healthy control partners. Furthermore, childhood trauma, neuroticism as well as dysfunctional attachment styles displayed a significant positive correlation with relationship-related problems. Traumatic childhood experiences, insecure attachment styles as well as neurotic personality characteristics contribute to increased relationship disruptions in couples. Relevant hormonal and psychosocial parameters in BPD partners should be taken into account when treating females with BPD.
Life Cycle Assessment of Concrete Using Copper Slag as a Partial Cement Substitute in Reinforced Concrete Buildings
Authors: de Pedro John Paul Q. , Lagao Jil Andrew T. , Ongpeng Jason Maximino C.
Published: March 2023

Cement, one of the main components of concrete, poses environmental risks, accounting for 7% of total global carbon emissions. To alleviate the environmental hazards related to cement manufacturing, supplementary cementitious materials (SCM) are employed to reduce the usage of cement in concrete. One SCM used is copper slag (CS). In this study, a life cycle assessment (LCA) is conducted by investigating the environmental impacts of concrete replacing different percentage of cement with CS. As a case study, the LCA was performed for low-rise and mid-rise structures designed with varying concrete strengths, and a cost analysis was performed for these structures when replacing different percentages of cement with CS. Based on the results, the usage of CS was established as being beneficial to the impact categories ADP (Abiotic Depletion Potential (Fossil)) and GWP (Global Warming Potential), but exerted damaging effects on ADP (Abiotic Depletion Potential) and HTP (Human Toxicity Potential). On the basis of the cost analysis, the use of CS as a partial cement replacement was found to reduce building costs by a maximum of 1.4%, which is statistically significant. When evaluating the risk in comparison to the benefit of using CS in buildings, it was found that the negative environmental influence outweighed the favorable influence and cost savings resulting from the use of CS as a cement alternative. However, when only considering GWP, which is the standard procedure for environmental assessment in buildings, the use of CS as a partial cement substitute in buildings was regarded as being beneficial, yielding a 12.80% reduction in carbon emissions.
Modelling of CFRP-Strengthened RC Shear Walls with a Focus on End-Anchor Effects
Authors: Sadeghian Vahid , Said Said Ali , Lau David
Published: March 2023

This study first provides an overview of the development of a novel tube anchor system for the seismic strengthening or repair of reinforced concrete (RC) shear walls with carbon fibre-reinforced polymer (CFRP) sheets. The new anchor system can significantly improve the load transfer mechanism between the CFRP and supporting RC structural elements, resulting in ductile behaviour of the strengthened shear walls with increases of lateral load capacity and ductility by up to 2.6 and 8.3 times, respectively. The study then presents a new finite element modelling technique capable of capturing the complete cyclic response, i.e., from the elastic behaviour to the ultimate collapse of CFRP-strengthened RC shear walls with the newly developed tube anchor system. Two different modelling approaches are proposed to consider the effects of the tube anchor system. Additionally, other important CFRP- and RC-related mechanisms, including CFRP debonding effects, confinement enhancement, tension stiffening, compression softening, and strength and stiffness degradation under cyclic loads, are also considered in the model. By comparing the analytical and experimental results, it is demonstrated that the proposed modelling approach can accurately replicate the complex behaviour of CFRP-strengthened shear walls with a wide range of aspect ratios, from the ductile flexural behaviour of slender walls to the brittle shear failure of squat walls, without requiring detailed modelling of the anchor system.
An Experimental Study of Non-Gaussian Properties of Tornado-like Loads on a Low-Rise Building Model
Authors: Yang Hanzhang , Cao Shuyang
Published: March 2023

This paper focuses on the non-Gaussian properties of tornado pressure loading on a Texas Tech University (TTU) building model. External pressures of the model were measured at multiple radial positions in a two-celled tornado-like vortex generated by a tornado-like vortex simulator. High-order statistical moments of pressure coefficients were studied. The spatial distributions of non-Gaussian zones were presented and compared with the figure for boundary layer wind. Four exponential models were used to fit the probability density of tornado pressures. The peak factors obtained by five methods were also investigated. Results indicate that non-Gaussian regions of a low-rise building in a tornado-like vortex significantly differ from that in boundary layer wind. The peak pressure coefficients exhibit a maximum value near the end of windward eaves when the model is located at a tornadic core radius. The probability density of tornado pressure time series cannot be fitted by a single exponential distribution. The gamma distribution and generalized extreme value (GEV) distribution can describe the probabilistic behavior of pressure coefficients at the most unfavorable load position. Compared with other methods, the skewness-dependent peak factor method exhibits the advantages of reliable results, easy calculation, and wide applicability.