bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Spatiotemporal Changes in Selected Ecosystem Services Caused by Free Trade Initiatives in Incheon, Korea
Authors: Choi Jiyoung , Lee Sangdon
Published: February 2023

Expansion of a development area can negatively impact ecosystems by decreasing or fragmenting habitats. With increased awareness of the importance of biodiversity and ecosystem services (BES), ecosystem service evaluations have attracted increased attention. The geography surrounding the city of Incheon is ecologically valuable because of its ecological diversity, attributed to its mudflats and coastal terrain. This study analyzed changes caused by the Incheon Free Economic Zone (IFEZ) agreement in the ecosystem services of this area using uses the Integrated Valuation of Ecosystem Services and Tradeoffs model and assesses the impacts of BES before and after the implementation of the agreement. Results revealed that carbon fixation and habitat quality decreased by approximately 40% and 37%, respectively, owing to the development caused by the agreement (p < 0.01). Additionally, endangered species and migratory birds were not protected by the terms of the IFEZ, and a decline in habitats, prey, and breeding sites was observed. This study suggests that the value of ecosystem services and the expansion of conservation areas should be considered part of ecological research under economic free trade agreements.
The Personal Suicide Stigma Questionnaire (PSSQ): Relation to Self-Esteem, Well-Being, and Help-Seeking
Authors: Maclean Brant R. , Forrester Tahni , Hawgood Jacinta , O’Gorman John , Rimkeviciene Jurgita
Published: February 2023

Two studies are reported that extend the evidence base for use of the Personal Stigma of Suicide Questionnaire (PSSQ). In the first study (N = 117), the Rosenberg Self-Esteem Scale, the WHO-5 measure of well-being, as well as measures of suicidality were examined in relation to the PSSQ. A self-selected sub-sample (N = 30) completed the PSSQ after an interval of two months. In line with the stigma internalization model, when demographic variables and suicidality were accounted for, the PSSQ self-blame subscale was the most significant predictor of self-esteem. As for well-being, the rejection subscale was involved as well as self-blame. The retest stability of the PSSQ for the sub-sample was 0.85 and coefficient alpha for the total sample was 0.95, indicating both good stability and internal consistency for the scale. In the second study (N = 140), PSSQ was studied in relation to intention to seek help from four sources in the case of suicidal ideation. The strongest relationship with PSSQ was with intention not to seek help from anyone (r = 0.35). When other variables were included in the prediction of help-seeking from a general medical practitioner, family or friends, or from nobody, the only significant PSSQ correlate was minimization. For help-seeking from a psychologist or psychiatrist, the most significant predictor was judged helpfulness of prior contact with them. The results from these studies strengthen previous findings of the construct validity of the PSSQ and point to its utility in understanding barriers to help-seeking among those experiencing suicidality.
Making “Joy Pie” to Stay Joyful: Self-Care Interventions Alleviate College Students’ Mental Health Challenges
Authors: Zhong Bu , Xie Lola
Published: February 2023

As more college students are facing mental health challenges, it is imperative to explore innovative ways of improving their mental health, including developing self-care interventions that help mitigate their stressors. Based on the Response Styles Theory and self-care conceptions, this study creates the “Joy Pie” project that consists of five self-care strategies, aiming to regulate negative emotions and increase self-care efficacy. Using an experimental design and two-wave data collected from a representative sample of Beijing college students (n1 = 316, n2 = 127), this study assesses the effects of the five proposed interventions on the students’ self-care efficacy and mental health management. The results show that self-care efficacy helped improve mental health through emotion regulation, which is mediated by age, gender, and family income. The promising results support the effectiveness of the “Joy Pie” interventions in strengthening self-care efficacy and improving mental health. This study offers insights into building back better mental health security among college students at this critical time when the world is recovering from the COVID-19 pandemic.
An Analysis of the Incidence and Cost of Intracranial Aneurysm and Subarachnoid Haemorrhage Treatment between 2013 and 2021
Authors: Śliwczyński Andrzej , Jewczak Maciej , Dorobek Małgorzata , Furlepa Kamila , Gołębiak Izabela , Skibińska Edyta , Sarzyńska-Długosz Iwona
Published: February 2023

The incidence of unruptured intracranial aneurysms (UIAs) amounts to 3.2% among adults. The annual risk of aneurysm rupture is 2–10% and it results in subarachnoid haemorrhage (SAH). The aim of this study is to assess changes in the incidence of unruptured intracranial aneurysms and subarachnoid haemorrhages in Poland between 2013 and 2021 and the cost associated with their in-hospital treatment in the acute phase. The analysis was based on the National Health Fund database. Patients diagnosed with UIA and SAH and hospitalised between 2013 and 2021 were chosen. The statistical analysis was performed with an assumed significance level of α = 0.05. The ratio between the prevalence of SAH and UIA diagnoses was 4:6. The proportion of women in relation to men was higher in both diagnoses. The highest proportions of patients with diagnoses SAH and UIA were found in highly urbanised provinces. The value of medical services in 2021 compared to 2013 increased by 81.8%. The highest values in this period were recorded in Mazowieckie province, and the lowest were recorded in Opolskie province. The overall number of patients hospitalised with diagnosis of UIA or SAH did not decrease, but the risk of aneurysm rupture probably decreased, which resulted in lower incidence of SAH in subsequent years of observation. The recorded changes in the dynamics of the value of medical services per patient or per hospitalisation largely coincided. However, it is difficult to speculate on expected value levels as not all provinces showed linear changes in the value of services provided.
Ultrasound Imaging and Guidance for Cervical Myofascial Pain: A Narrative Review
Authors: Ricci Vincenzo , Mezian Kamal , Chang Ke-Vin , Tarantino Domiziano , Güvener Orhan , Gervasoni Fabrizio , Naňka Ondřej , Özçakar Levent
Published: February 2023

Cervical myofascial pain is a very common clinical condition in the daily practice of musculoskeletal physicians. Physical examination is currently the cornerstone for evaluating the cervical muscles and identifying the eventual presence of myofascial trigger points. Herein, the role of ultrasound assessment in precisely localizing them is progressively mounting in the pertinent literature. Moreover, using ultrasound, not only the muscle tissue but also the fascial and neural elements can be accurately located/evaluated. Indeed, several potential pain generators, in addition to paraspinal muscles, can be involved in the clinical scenario of cervical myofascial pain syndrome. In this article, the authors extensively reviewed the sonographic approach for cervical myofascial pain in order to better diagnose or guide different procedures that can be performed in the clinical practice of musculoskeletal physicians.
Geochemical Characteristics of the Vertical Distribution of Heavy Metals in the Hummocky Peatlands of the Cryolithozone
Authors: Vasilevich Roman , Vasilevich Mariya , Lodygin Evgeny , Abakumov Evgeny
Published: February 2023

One of the main reservoirs depositing various classes of pollutants in high latitude regions are wetland ecosystems. Climate warming trends result in the degradation of permafrost in cryolitic peatlands, which exposes the hydrological network to risks of heavy metal (HM) ingress and its subsequent migration to the Arctic Ocean basin. The objectives included: (1) carrying out a quantitative analysis of the content of HMs and As across the profile of Histosols in background and technogenic landscapes of the Subarctic region, (2) evaluating the contribution of the anthropogenic impact to the accumulation of trace elements in the seasonally thawed layer (STL) of peat deposits, (3) discovering the effect of biogeochemical barriers on the vertical distribution of HMs and As. The analyses of elements were conducted by atom emission spectroscopy with inductively coupled plasma, atomic absorption spectroscopy and scanning electron microscopy with an energy-dispersive X-ray detecting. The study focused on the characteristics of the layer-by-layer accumulation of HMs and As in hummocky peatlands of the extreme northern taiga. It revealed the upper level of microelement accumulation to be associated with the STL as a result of aerogenic pollution. Specifically composed spheroidal microparticles found in the upper layer of peat may serve as indicators of the area polluted by power plants. The accumulation of water-soluble forms of most of the pollutants studied on the upper boundary of the permafrost layer (PL) is explained by the high mobility of elements in an acidic environment. In the STL, humic acids act as a significant sorption geochemical barrier for elements with a high stability constant value. In the PL, the accumulation of pollutants is associated with their sorption on aluminum-iron complexes and interaction with the sulfide barrier. A significant contribution of biogenic element accumulation was shown by statistical analysis.
How Can a Bundled Payment Model Incentivize the Transition from Single-Disease Management to Person-Centred and Integrated Care for Chronic Diseases in the Netherlands?
Authors: Bour Sterre S. , Raaijmakers Lena H. A. , Bischoff Erik W. M. A. , Goossens Lucas M. A. , Rutten-van Mölken Maureen P. M. H.
Published: February 2023

To stimulate the integration of chronic care across disciplines, the Netherlands has implemented single-disease management programmes (SDMPs) in primary care since 2010; for example, for COPD, type 2 diabetes mellitus, and cardiovascular diseases. These disease-specific chronic care programmes are funded by bundled payments. For chronically ill patients with multimorbidity or with problems in other domains of health, this approach was shown to be less fit for purpose. As a result, we are currently witnessing several initiatives to broaden the scope of these programmes, aiming to provide truly person-centred integrated care (PC-IC). This raises the question if it is possible to design a payment model that would support this transition. We present an alternative payment model that combines a person-centred bundled payment with a shared savings model and pay-for-performance elements. Based on theoretical reasoning and results of previous evaluation studies, we expect the proposed payment model to stimulate integration of person-centred care between primary healthcare providers, secondary healthcare providers, and the social care domain. We also expect it to incentivise cost-conscious provider-behaviour, while safeguarding the quality of care, provided that adequate risk-mitigating actions, such as case-mix adjustment and cost-capping, are taken.
Empirical Mode Decomposition and Hilbert Spectrum for Abnormality Detection in Normal and Abnormal Walking Transitions
Authors: Erfianto Bayu , Rizal Achmad , Hadiyoso Sugondo
Published: February 2023

Sensor-based human activity recognition (HAR) is a method for observing a person’s activity in an environment. With this method, it is possible to monitor remotely. HAR can analyze a person’s gait, whether normal or abnormal. Some of its applications may use several sensors mounted on the body, but this method tends to be complex and inconvenient. One alternative to wearable sensors is using video. One of the most commonly used HAR platforms is PoseNET. PoseNET is a sophisticated platform that can detect the skeleton and joints of the body, which are then known as joints. However, a method is still needed to process the raw data from PoseNET to detect subject activity. Therefore, this research proposes a way to detect abnormalities in gait using empirical mode decomposition and the Hilbert spectrum and transforming keys-joints, and skeletons from vision-based pose detection into the angular displacement of walking gait patterns (signals). Joint change information is extracted using the Hilbert Huang Transform to study how the subject behaves in the turning position. Furthermore, it is determined whether the transition goes from normal to abnormal subjects by calculating the energy in the time-frequency domain signal. The test results show that during the transition period, the energy of the gait signal tends to be higher than during the walking period.
Pesticide Exposure of Residents Living in Wine Regions: Protocol and First Results of the Pestiprev Study
Authors: Teysseire Raphaëlle , Barron Emmanuelle , Baldi Isabelle , Bedos Carole , Chazeaubeny Alexis , Le Menach Karyn , Roudil Audrey , Budzinski Hélène , Delva Fleur
Published: February 2023

The PESTIPREV study has been designed to investigate residential exposure to pesticides applied to vines and ultimately propose mitigation measures. A feasibility study was carried out to validate a protocol for measuring six pesticides in three houses located near vineyards in July 2020. Samples included indoor and outdoor surfaces sampled with wipes (n = 214), patches on the resident’s skin (n = 7), hand or foot washing (n = 5), and pets sampled using wipes (n = 2). Limits of quantification for wipes ranged between 0.02 ng for trifloxystrobin and 1.50 ng for pyraclostrobin. Tebuconazole and trifloxystrobin were quantified in nearly 100% of the surface samples, whereas the other fungicides were less frequently found (from 39.7% for pyraclostrobin to 55.1% for boscalid). The median surface loadings ranged from 3.13 ng/m2 for benalaxyl to 82.48 ng/m2 for cymoxanil. The pesticides most frequently quantified in hand washing, patch samples, and pet wipes were the same as those quantified on surfaces. Finally, the analyses proved to be successful. The tools developed to collect information on determinants were well completed. The protocol was well received by the participants and appeared to be feasible and relevant to the objective of the PESTIPREV study, although some improvements have been identified. It was applied on a larger scale in 2021 to study the determinants of pesticide exposure.
Use of Artificial Intelligence in the Classification of Elementary Oral Lesions from Clinical Images
Authors: Gomes Rita , Schmith Jean , Figueiredo Rodrigo , Freitas Samuel , Machado Giovanna , Romanini Juliana , Carrard Vinicius
Published: February 2023

Objectives: Artificial intelligence has generated a significant impact in the health field. The aim of this study was to perform the training and validation of a convolutional neural network (CNN)-based model to automatically classify six clinical representation categories of oral lesion images. Method: The CNN model was developed with the objective of automatically classifying the images into six categories of elementary lesions: (1) papule/nodule; (2) macule/spot; (3) vesicle/bullous; (4) erosion; (5) ulcer and (6) plaque. We selected four architectures and using our dataset we decided to test the following architectures: ResNet-50, VGG16, InceptionV3 and Xception. We used the confusion matrix as the main metric for the CNN evaluation and discussion. Results: A total of 5069 images of oral mucosa lesions were used. The oral elementary lesions classification reached the best result using an architecture based on InceptionV3. After hyperparameter optimization, we reached more than 71% correct predictions in all six lesion classes. The classification achieved an average accuracy of 95.09% in our dataset. Conclusions: We reported the development of an artificial intelligence model for the automated classification of elementary lesions from oral clinical images, achieving satisfactory performance. Future directions include the study of including trained layers to establish patterns of characteristics that determine benign, potentially malignant and malignant lesions.
Underwater Impact and Intention–Behaviour Gap of Scuba Divers on Coral Communities in Hong Kong SAR, China
Authors: So Jun-Yin , Kwok Ying , Lai Christie , Fong Hei-Wut , Pang Lee-Yan
Published: February 2023

Recreational diving, under the continual growth of the scuba diving industry, may escalate coral reef damage as one of the substantial anthropogenic impacts and is of pressing concern. Besides unregulated and excessive diving activities, accidental contact with corals by inexperienced divers can cause recurring physical damage and heighten the pressure on coral communities. Understanding the ecological impacts of underwater contact with marine biota will thus be crucial to develop more sustainable scuba diving practices in Hong Kong. To probe the scuba diving impacts of divers’ contact with coral communities, WWF-Hong Kong started a citizen science monitoring programme and invited 52 advanced divers to conduct direct underwater observations. Questionnaires were also developed to examine and address the research gap between the associated attitudes and the perceived contact rate of divers. Results from analysing the underwater behaviours of 102 recreational divers showed inconsistent perceived and actual contact rates. It was revealed that recreational divers might often overlook the ecological effects of their activities underwater on coral communities. The questionnaire findings will be utilised to improve the framework of the dive-training programmes and enhance divers’ awareness to minimise their influence on the marine environment.
A Pilot Study of Training Peer Recovery Specialists in Behavioral Activation in the United States: Preliminary Outcomes and Predictors of Competence
Authors: Anvari Morgan , Kleinman Mary , Dean Dwayne , Rose Alexandra , Bradley Valerie , Hines Abigail , Abidogun Tolulope , Felton Julia , Magidson Jessica
Published: February 2023

Background: The peer recovery specialist (PRS) workforce has rapidly expanded to increase access to substance-use disorder services for underserved communities. PRSs are not typically trained in evidence-based interventions (EBIs) outside of motivational interviewing, although evidence demonstrates the feasibility of PRS delivery of certain EBIs, such as a brief behavioral intervention, behavioral activation. However, characteristics that predict PRS competency in delivering EBIs such as behavioral activation remain unknown, and are critical for PRS selection, training, and supervision if the PRS role is expanded. This study aimed to explore the outcomes of a brief PRS training period in behavioral activation and identify predictors of competence. Method: Twenty PRSs in the United States completed a two-hour training on PRS-delivered behavioral activation. Participants completed baseline and post-training assessments, including roleplay and assessments of PRS characteristics, attitudes towards EBIs, and theoretically relevant personality constructs. Roleplays were coded for competence (behavioral activation specific and PRS skills more broadly, i.e., PRS competence) and changes were assessed from baseline to post-training. Linear regression models tested factors predicting post-training competence, controlling for baseline competence. Results: There was a significant pre-post increase in behavioral activation competence (t = −7.02, p < 0.001). Years working as a PRS significantly predicted post-training behavioral activation skills (B = 0.16, p = 0.005). No variables predicted post-training PRS competence. Conclusions: This study provides preliminary evidence that behavioral activation may be appropriate for dissemination to PRSs through brief trainings, particularly for PRSs with more work experience. However, additional research is needed to examine predictors of competence among PRSs.
Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure
Authors: Mrozikiewicz Aleksandra E. , Kurzawińska Grażyna , Ożarowski Marcin , Walczak Michał , Ożegowska Katarzyna , Jędrzejczak Piotr
Published: February 2023

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 120 healthy controls. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A variant of the kinase insertion domain receptor (KDR) gene (rs2071559) was associated with an increased risk of infertility after adjusting for age and BMI (OR = 0.64; 95% CI: 0.45–0.91, p = 0.013 in a log-additive model). Vascular endothelial growth factor A (VEGFA) rs699947 was associated with an increased risk of recurrent implantation failures under a dominant (OR = 2.34; 95% CI: 1.11–4.94, padj. = 0.022) and a log-additive model (OR = 0.65; 95% CI 0.43–0.99, padj. = 0.038). Variants of the KDR gene (rs1870377, rs2071559) in the whole group were in linkage equilibrium (D’ = 0.25, r2 = 0.025). Gene–gene interaction analysis showed the strongest interactions between the KDR gene SNPs rs2071559–rs1870377 (p = 0.004) and KDR rs1870377–VEGFA rs699947 (p = 0.030). Our study revealed that the KDR gene rs2071559 variant may be associated with infertility and rs699947 VEGFA with an increased risk of recurrent implantation failures in infertile ART treated Polish women.
Back to Basics: A Simplified Improvement to Multiple Displacement Amplification for Microbial Single-Cell Genomics
Authors: Sobol Morgan S. , Kaster Anne-Kristin
Published: February 2023

Microbial single-cell genomics (SCG) provides access to the genomes of rare and uncultured microorganisms and is a complementary method to metagenomics. Due to the femtogram-levels of DNA in a single microbial cell, sequencing the genome requires whole genome amplification (WGA) as a preliminary step. However, the most common WGA method, multiple displacement amplification (MDA), is known to be costly and biased against specific genomic regions, preventing high-throughput applications and resulting in uneven genome coverage. Thus, obtaining high-quality genomes from many taxa, especially minority members of microbial communities, becomes difficult. Here, we present a volume reduction approach that significantly reduces costs while improving genome coverage and uniformity of DNA amplification products in standard 384-well plates. Our results demonstrate that further volume reduction in specialized and complex setups (e.g., microfluidic chips) is likely unnecessary to obtain higher-quality microbial genomes. This volume reduction method makes SCG more feasible for future studies, thus helping to broaden our knowledge on the diversity and function of understudied and uncharacterized microorganisms in the environment.
Artificial Intelligence-Based Computational Screening and Functional Assays Identify Candidate Small Molecule Antagonists of PTPmu-Dependent Adhesion
Authors: Molyneaux Kathleen , Laggner Christian , Brady-Kalnay Susann M.
Published: February 2023

PTPmu (PTPµ) is a member of the receptor protein tyrosine phosphatase IIb family that participates in cell-cell adhesion and signaling. PTPmu is proteolytically downregulated in glioblastoma (glioma), and the resulting extracellular and intracellular fragments are believed to stimulate cancer cell growth and/or migration. Therefore, drugs targeting these fragments may have therapeutic potential. Here, we used the AtomNet® platform, the first deep learning neural network for drug design and discovery, to screen a molecular library of several million compounds and identified 76 candidates predicted to interact with a groove between the MAM and Ig extracellular domains required for PTPmu-mediated cell adhesion. These candidates were screened in two cell-based assays: PTPmu-dependent aggregation of Sf9 cells and a tumor growth assay where glioma cells grow in three-dimensional spheres. Four compounds inhibited PTPmu-mediated aggregation of Sf9 cells, six compounds inhibited glioma sphere formation/growth, while two priority compounds were effective in both assays. The stronger of these two compounds inhibited PTPmu aggregation in Sf9 cells and inhibited glioma sphere formation down to 25 micromolar. Additionally, this compound was able to inhibit the aggregation of beads coated with an extracellular fragment of PTPmu, directly demonstrating an interaction. This compound presents an interesting starting point for the development of PTPmu-targeting agents for treating cancer including glioblastoma.
The Association between the Differential Expression of lncRNA and Type 2 Diabetes Mellitus in People with Hypertriglyceridemia
Authors: Yan Shoumeng , Yao Nan , Li Xiaotong , Sun Mengzi , Yang Yixue , Cui Weiwei , Li Bo
Published: February 2023

Compared with diabetic patients with normal blood lipid, diabetic patients with dyslipidemia such as high triglycerides have a higher risk of clinical complications, and the disease is also more serious. For the subjects with hypertriglyceridemia, the lncRNAs affecting type 2 diabetes mellitus (T2DM) and the specific mechanisms remain unclear. Transcriptome sequencing was performed on peripheral blood samples of new-onset T2DM (six subjects) and normal blood control (six subjects) in hypertriglyceridemia patients using gene chip technology, and differentially expressed lncRNA profiles were constructed. Validated by the GEO database and RT-qPCR, lncRNA ENST00000462455.1 was selected. Subsequently, fluorescence in situ hybridization (FISH), real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to observe the effect of ENST00000462455.1 on MIN6. When silencing the ENST00000462455.1 for MIN6 in high glucose and high fat, the relative cell survival rate and insulin secretion decreased, the apoptosis rate increased, and the expression of the transcription factors Ins1, Pdx-1, Glut2, FoxO1, and ETS1 that maintained the function and activity of pancreatic β cells decreased (p < 0.05). In addition, we found that ENST00000462455.1/miR-204-3p/CACNA1C could be the core regulatory axis by using bioinformatics methods. Therefore, ENST00000462455.1 was a potential biomarker for hypertriglyceridemia patients with T2DM.
Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes
Authors: Bertini Luca , Libera Valeria , Ripanti Francesca , Natali Francesca , Paolantoni Marco , Orecchini Andrea , Nucara Alessandro , Petrillo Caterina , Comez Lucia , Paciaroni Alessandro
Published: February 2023

Telomeric G-quadruplexes (G4s) are promising targets in the design and development of anticancer drugs. Their actual topology depends on several factors, resulting in structural polymorphism. In this study, we investigate how the fast dynamics of the telomeric sequence AG3(TTAG3)3 (Tel22) depends on the conformation. By using Fourier transform Infrared spectroscopy, we show that, in the hydrated powder state, Tel22 adopts parallel and mixed antiparallel/parallel topologies in the presence of K+ and Na+ ions, respectively. These conformational differences are reflected in the reduced mobility of Tel22 in Na+ environment in the sub-nanosecond timescale, as probed by elastic incoherent neutron scattering. These findings are consistent with the G4 antiparallel conformation being more stable than the parallel one, possibly due to the presence of ordered hydration water networks. In addition, we study the effect of Tel22 complexation with BRACO19 ligand. Despite the quite similar conformation in the complexed and uncomplexed state, the fast dynamics of Tel22-BRACO19 is enhanced compared to that of Tel22 alone, independently of the ions. We ascribe this effect to the preferential binding of water molecules to Tel22 against the ligand. The present results suggest that the effect of polymorphism and complexation on the G4 fast dynamics is mediated by hydration water.
Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1α
Authors: Fachada Vasco , Silvennoinen Mika , Sahinaho Ulla-Maria , Rahkila Paavo , Kivelä Riikka , Hulmi Juha J. , Kujala Urho , Kainulainen Heikki
Published: February 2023

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1α. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms.
Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review
Authors: Shahini Endrit , Pasculli Giuseppe , Solimando Antonio Giovanni , Tiribelli Claudio , Cozzolongo Raffaele , Giannelli Gianluigi
Published: February 2023

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10–20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients’ survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.
Brassica napus BnaC9.DEWAX1 Negatively Regulates Wax Biosynthesis via Transcriptional Suppression of BnCER1-2
Authors: Wang Saiyu , Bai Chengcheng , Luo Na , Jiang Youwei , Wang Yulu , Liu Yu , Chen Chunjie , Wang Yuxin , Gan Qiaoqiao , Jin Shurong , Ni Yu
Published: February 2023

Very-long-chain alkane plays an important role as an aliphatic barrier. We previously reported that BnCER1-2 was responsible for alkane biosynthesis in Brassica napus and improved plant tolerance to drought. However, how the expression of BnCER1-2 is regulated is still unknown. Through yeast one-hybrid screening, we identified a transcriptional regulator of BnCER1-2, BnaC9.DEWAX1, which encodes AP2\ERF transcription factor. BnaC9.DEWAX1 targets the nucleus and displays transcriptional repression activity. Electrophoretic mobility shift and transient transcriptional assays suggested that BnaC9.DEWAX1 repressed the transcription of BnCER1-2 by directly interacting with its promoter. BnaC9.DEWAX1 was expressed predominantly in leaves and siliques, which was similar to the expression pattern of BnCER1-2. Hormone and major abiotic stresses such as drought and high salinity affected the expression of BnaC9.DEWAX1. Ectopic expression of BnaC9.DEWAX1 in Arabidopsis plants down-regulated CER1 transcription levels and resulted in a reduction in alkanes and total wax loads in leaves and stems when compared with the wild type, whereas the wax depositions in the dewax mutant returned to the wild type level after complementation of BnaC9.DEWAX1 in the mutant. Moreover, both altered cuticular wax composition and structure contribute to increased epidermal permeability in BnaC9.DEWAX1 overexpression lines. Collectively, these results support the notion that BnaC9.DEWAX1 negatively regulates wax biosynthesis by binding directly to the BnCER1-2 promoter, which provides insights into the regulatory mechanism of wax biosynthesis in B. napus.
Evaluation of Anticancer Activity of Zhubech, a New 5-FU Analog Liposomal Formulation, against Pancreatic Cancer
Authors: Ndemazie Nkafu Bechem , Bulusu Raviteja , Zhu Xue You , Frimpong Esther Kesewaah , Inkoom Andriana , Okoro Joy , Ebesoh Dexter , Rogers Sherise , Han Bo , Agyare Edward
Published: February 2023

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP), as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4 °C and 25 °C for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroid (IC50Zhubech = 3.4 ± 1.0 μM vs. IC50MFU = 6.8 ± 1.1 μM) and organoid (IC50Zhubech = 9.8 ± 1.4 μM vs. IC50MFU = 42.3 ± 1.0 μM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 ± 13.5 mm3) compared to 5-FU-treated (1107 ± 116.2 mm3) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.
Bipartite Genomes in Enterobacterales: Independent Origins of Chromids, Elevated Openness and Donors of Horizontally Transferred Genes
Authors: Sonnenberg Cecilie Bækkedal , Haugen Peik
Published: February 2023

Multipartite bacteria have one chromosome and one or more chromid. Chromids are believed to have properties that enhance genomic flexibility, making them a favored integration site for new genes. However, the mechanism by which chromosomes and chromids jointly contribute to this flexibility is not clear. To shed light on this, we analyzed the openness of chromosomes and chromids of the two bacteria, Vibrio and Pseudoalteromonas, both which belong to the Enterobacterales order of Gammaproteobacteria, and compared the genomic openness with that of monopartite genomes in the same order. We applied pangenome analysis, codon usage analysis and the HGTector software to detect horizontally transferred genes. Our findings suggest that the chromids of Vibrio and Pseudoalteromonas originated from two separate plasmid acquisition events. Bipartite genomes were found to be more open compared to monopartite. We found that the shell and cloud pangene categories drive the openness of bipartite genomes in Vibrio and Pseudoalteromonas. Based on this and our two recent studies, we propose a hypothesis that explains how chromids and the chromosome terminus region contribute to the genomic plasticity of bipartite genomes.
Anti-Inflammatory Effects of Flavonoids in Common Neurological Disorders Associated with Aging
Authors: Martínez-Coria Hilda , Arrieta-Cruz Isabel , Gutiérrez-Juárez Roger , López-Valdés Héctor Eduardo
Published: February 2023

Aging reduces homeostasis and contributes to increasing the risk of brain diseases and death. Some of the principal characteristics are chronic and low-grade inflammation, a general increase in the secretion of proinflammatory cytokines, and inflammatory markers. Aging-related diseases include focal ischemic stroke and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Flavonoids are the most common class of polyphenols and are abundantly found in plant-based foods and beverages. A small group of individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, and myricetin) has been used to explore the anti-inflammatory effect in vitro studies and in animal models of focal ischemic stroke and AD and PD, and the results show that these molecules reduce the activated neuroglia and several proinflammatory cytokines, and also, inactivate inflammation and inflammasome-related transcription factors. However, the evidence from human studies has been limited. In this review article, we highlight the evidence that individual natural molecules can modulate neuroinflammation in diverse studies from in vitro to animal models to clinical studies of focal ischemic stroke and AD and PD, and we discuss future areas of research that can help researchers to develop new therapeutic agents.
Genetic Background Influence on Hippocampal Synaptic Plasticity: Frequency-Dependent Variations between an Inbred and an Outbred Mice Strain
Authors: Roux Candice M. , Lecouflet Pierre , Billard Jean-Marie , Esneault Elise , Leger Marianne , Schumann-Bard Pascale , Freret Thomas
Published: February 2023

For almost half a century, acute hippocampal slice preparations have been widely used to investigate anti-amnesic (or promnesic) properties of drug candidates on long-term potentiation (LTP)—a cellular substrate that supports some forms of learning and memory. The large variety of transgenic mice models now available makes the choice of the genetic background when designing experiments crucially important. Furthermore, different behavioral phenotypes were reported between inbred and outbred strains. Notably, some differences in memory performance were emphasized. Despite this, investigations, unfortunately, did not explore electrophysiological properties. In this study, two stimulation paradigms were used to compare LTP in the hippocampal CA1 area of both inbred (C57BL/6) and outbred (NMRI) mice. High-frequency stimulation (HFS) revealed no strain difference, whereas theta-burst stimulation (TBS) resulted in significantly reduced LTP magnitude in NMRI mice. Additionally, we demonstrated that this reduced LTP magnitude (exhibited by NMRI mice) was due to lower responsiveness to theta-frequency during conditioning stimuli. In this paper, we discuss the anatomo-functional correlates that may explain such hippocampal synaptic plasticity divergence, although straightforward evidence is still lacking. Overall, our results support the prime importance of considering the animal model related to the intended electrophysiological experiments and the scientific issues to be addressed.
Molecular Research on Huntington’s Disease
Authors: Valor Luis M.
Published: February 2023

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of CAG triplets in the HTT (Huntingtin) gene [...]
A Review of Biomimetic and Biodegradable Magnetic Scaffolds for Bone Tissue Engineering and Oncology
Authors: Paltanea Gheorghe , Manescu (Paltanea) Veronica , Antoniac Iulian , Antoniac Aurora , Nemoianu Iosif Vasile , Robu Alina , Dura Horatiu
Published: February 2023

Bone defects characterized by limited regenerative properties are considered a priority in surgical practice, as they are associated with reduced quality of life and high costs. In bone tissue engineering, different types of scaffolds are used. These implants represent structures with well-established properties that play an important role as delivery vectors or cellular systems for cells, growth factors, bioactive molecules, chemical compounds, and drugs. The scaffold must provide a microenvironment with increased regenerative potential at the damage site. Magnetic nanoparticles are linked to an intrinsic magnetic field, and when they are incorporated into biomimetic scaffold structures, they can sustain osteoconduction, osteoinduction, and angiogenesis. Some studies have shown that combining ferromagnetic or superparamagnetic nanoparticles and external stimuli such as an electromagnetic field or laser light can enhance osteogenesis and angiogenesis and even lead to cancer cell death. These therapies are based on in vitro and in vivo studies and could be included in clinical trials for large bone defect regeneration and cancer treatments in the near future. We highlight the scaffolds’ main attributes and focus on natural and synthetic polymeric biomaterials combined with magnetic nanoparticles and their production methods. Then, we underline the structural and morphological aspects of the magnetic scaffolds and their mechanical, thermal, and magnetic properties. Great attention is devoted to the magnetic field effects on bone cells, biocompatibility, and osteogenic impact of the polymeric scaffolds reinforced with magnetic nanoparticles. We explain the biological processes activated due to magnetic particles’ presence and underline their possible toxic effects. We present some studies regarding animal tests and potential clinical applications of magnetic polymeric scaffolds.
Small-Molecule-Mediated Suppression of BMP Signaling by Selective Inhibition of BMP1-Dependent Chordin Cleavage
Authors: Mizoguchi Takamasa , Mikami Shohei , Yatou Mari , Kondo Yui , Omaru Shuhei , Kuwabara Shuhei , Okura Wataru , Noda Syouta , Tenno Takeshi , Hiroaki Hidekazu , Itoh Motoyuki
Published: February 2023

BMP signaling is critical for many biological processes. Therefore, small molecules that modulate BMP signaling are useful for elucidating the function of BMP signaling and treating BMP signaling-related diseases. Here, we performed a phenotypic screening in zebrafish to examine the in vivo effects of N-substituted-2-amino-benzoic acid analogs NPL1010 and NPL3008 and found that they affect BMP signaling-dependent dorsal–ventral (D–V) patterning and bone formation in zebrafish embryos. Furthermore, NPL1010 and NPL3008 suppressed BMP signaling upstream of BMP receptors. BMP1 cleaves Chordin, an antagonist of BMP, and negatively regulates BMP signaling. Docking simulations demonstrated that NPL1010 and NPL3008 bind BMP1. We found that NPL1010 and NPL3008 partially rescued the disruptions in the D–V phenotype caused by bmp1 overexpression and selectively inhibited BMP1-dependent Chordin cleavage. Therefore, NPL1010 and NPL3008 are potentially valuable inhibitors of BMP signaling that act through selective inhibition of Chordin cleavage.
Phosphorus-Containing Polybenzoxazine Aerogels with Efficient Flame Retardation and Thermal Insulation
Authors: Que Yusheng , Zhao Chunxia , Wei Jixuan , Yang Fahong , Li Hui , Cheng Jinbo , Xiang Dong , Wu Yuanpeng , Wang Bin
Published: February 2023

Bisphenol A type benzoxazine (Ba) monomers and 10-(2, 5-dihydroxyphenyl)-10- hydrogen-9- oxygen-10- phosphine-10- oxide (DOPO-HQ) were employed to prepare flame retardant and heat insulated polybenzoxazine (PBa) composite aerogels. The successful preparation of PBa composite aerogels was confirmed by Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The thermal degradation behavior and flame-retardant properties of the pristine PBa and PBa composite aerogels were investigated with thermogravimetric analysis (TGA) and cone calorimeter. The initial decomposition temperature of PBa decreased slightly after incorporating DOPO-HQ, increasing the char residue amount. The incorporation of 5% DOPO-HQ into PBa led to a decrease of 33.1% at the peak of the heat-release rate and a decrease of 58.7% in the TSP. The flame-retardant mechanism of PBa composite aerogels was investigated by SEM, Raman spectroscopy, and TGA coupled with infrared spectrometry (TG-FTIR). The aerogel has advantages such as a simple synthesis procedure, easy amplification, lightweight, low thermal conductivity, and good flame retardancy.