bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating High-Intensity Interval Training into a School Setting Improve Body Composition, Cardiorespiratory Fitness and Physical Activity in Children with Obesity: A Randomized Controlled Trial
Authors: Cao Meng , Tang Yucheng , Zou Yu
Published: September 2022

The aim of this study was to examine the effects of school-based high-intensity interval training (HIIT) on cardiorespiratory fitness and visceral adipose tissue (VAT) in children with obesity. A total of 40 students (11.0 ± 0.6 years; 20 boys) were randomized into an intervention group (IG) and control group (CG). The IG group performed a 12-week HIIT intervention with three sessions per week. Each session included 18 min of training (three sets of eight bouts of 15 s run at 100% maximal aerobic speed (MAS) separated by eight bouts of 15 s recovery run at 50% MAS) in PE class; the CG group were instructed to continue their normal behaviors. All subjects had indices of body mass index (BMI), fat mass (FM), body fat percentage (%BF), fat free mass (FFM), VAT, and maximal oxygen uptake (VO2max) measured at baseline and post-intervention. The cooperation of students was high, and all 40 students were included in the final analysis. A significant group–time interaction was determined in body composition (p < 0.05), with a significant decrease in BM (−3.4 ± 1.4 kg, p = 0.001; η2 = 0.63), BMI (−1.7 ± 0.5, p = 0.001; η2 = 0.58), %BF (−3.3 ± 1.4, p = 0.001; η2 = 0.54), and FM (−3.2 ± 1.4 kg, p = 0.001; η2 = 0.69), and VAT (−22.4 ± 9.8 cm2; p = 0.001; η2 = 0.61) in the IG. Furthermore, VO2max exhibited a significant increase in the IG (4.5 ± 1.6 mL/kg/min, p = 0.001; η2 = 0.84) and CG groups (1.7 ± 1.1 mL/kg/min, p = 0.001; η2 = 0.44). Integrating regular school-based HIIT sessions is a suitable method to improve body composition, cardiorespiratory fitness, and physical activity in students with obesity. Trial Registration: ChiCTR2100048737.
Primary Teeth-Derived Demineralized Dentin Matrix Autograft for Unilateral Maxillary Alveolar Cleft during Mixed Dentition
Authors: Matsuzawa Yusuke , Okubo Naoto , Tanaka Soichi , Kashiwazaki Haruhiko , Kitagawa Yoshimasa , Ohiro Yoichi , Mikoya Tadashi , Akazawa Toshiyuki , Murata Masaru
Published: September 2022

This clinical report describes the immediate autograft of primary (milk) teeth-derived demineralized dentin matrix (DDM) granules for a 6-year-old boy with unilateral alveolar cleft. First, four primary teeth were extracted, crushed in an electric mill for 1 min, and the crushed granules were demineralized in 2% HNO3 solution for 20 min. Simultaneously, the nasal mucoperiosteum was pushed upwards above the apices of the permanent central incisor adjacent to the cleft. The nasal and palatal openings were closed by suturing the mucoperiosteum on both sides of the cleft with absorbable threads. The wet DDM granules were grafted into the managed cleft triangle space, and a labial flap was repositioned. The radiographic images at 6 months showed the continuous hard tissues in the cleft area and DDM granules onto lateral incisor (22) and impacted canine (23). The 3D-CT views at 2 years showed impacted tooth (22) blocked by primary canine and the replacement of DDM granules by bone near teeth (22,23). At 4 years, tooth crown (22) was situated just under the mucous membrane, and teeth (22,23) erupted spontaneously until 6 years without a maxillary expansion and a tow guidance of canine. The DDM granules contributed to bone formation without the inhibition of spontaneous tooth eruption. We concluded that autogenous primary teeth DDM graft should become a minimally invasive procedure without bone harvesting and morbidities for unilateral alveolar cleft.
A Novel Discrete Group Teaching Optimization Algorithm for TSP Path Planning with Unmanned Surface Vehicles
Authors: Yang Shaolong , Huang Jin , Li Weichao , Xiang Xianbo
Published: September 2022

A growing number of researchers are interested in deploying unmanned surface vehicles (USVs) in support of ocean environmental monitoring. To accomplish these missions efficiently, multiple-waypoint path planning strategies for survey USVs are still a key challenge. The multiple-waypoint path planning problem, mathematically equivalent to the traveling salesman problem (TSP), is addressed in this paper using a discrete group teaching optimization algorithm (DGTOA). Generally, the algorithm consists of three phases. In the initialization phase, the DGTOA generates the initial sequence for students through greedy initialization. In the crossover phase, a new greedy crossover algorithm is introduced to increase diversity. In the mutation phase, to balance the exploration and exploitation, this paper proposes a dynamic adaptive neighborhood radius based on triangular probability selection to apply in the shift mutation algorithm, the inversion mutation algorithm, and the 3-opt mutation algorithm. To verify the performance of the DGTOA, fifteen benchmark cases from TSPLIB are implemented to compare the DGTOA with the discrete tree seed algorithm, discrete Jaya algorithm, artificial bee colony optimization, particle swarm optimization-ant colony optimization, and discrete shuffled frog-leaping algorithm. The results demonstrate that the DGTOA is a robust and competitive algorithm, especially for large-scale TSP problems. Meanwhile, the USV simulation results indicate that the DGTOA performs well in terms of exploration and exploitation.
Biofilm Formation by Chromoblastomycosis Fungi Fonsecaea pedrosoi and Phialophora verrucosa: Involvement with Antifungal Resistance
Authors: Sousa Ingrid S. , Mello Thaís P. , Pereira Elaine P. , Granato Marcela Q. , Alviano Celuta S. , Santos André L. S. , Kneipp Lucimar F.
Published: September 2022

Patients with chromoblastomycosis (CBM) suffer chronic tissue lesions that are hard to treat. Considering that biofilm is the main growth lifestyle of several pathogens and it is involved with both virulence and resistance to antimicrobial drugs, we have investigated the ability of CBM fungi to produce this complex, organized and multicellular structure. Fonsecaea pedrosoi and Phialophora verrucosa conidial cells were able to adhere on a polystyrene abiotic substrate, differentiate into hyphae and produce a robust viable biomass containing extracellular matrix. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed the tridimensional architecture of the mature biofilms, revealing a dense network of interconnected hyphae, inner channels and amorphous extracellular polymeric material. Interestingly, the co-culture of each fungus with THP-1 macrophage cells, used as a biotic substrate, induced the formation of a mycelial trap covering and damaging the macrophages. In addition, the biofilm-forming cells of F. pedrosoi and P. verrucosa were more resistant to the conventional antifungal drugs than the planktonic-growing conidial cells. The efflux pump activities of P. verrucosa and F. pedrosoi biofilms were significantly higher than those measured in conidia. Taken together, the data pointed out the biofilm formation by CBM fungi and brought up a discussion of the relevance of studies about their antifungal resistance mechanisms.
Assessing the Impact of Digital Alternative News Media in a Hybrid News Environment: Cases from Taiwan and Hong Kong
Authors: Nip Joyce Y. M. , Cheng Yu-Chung
Published: September 2022

As consumption of mainstream news media declines and alternative news media proliferates, in this paper, we seek to assess the impact of digital alternative news media (DANM) in relation to mainstream news media (MNM). We examine the range of DANM, especially public Facebook pages, related to two large-scale social movements neighbouring mainland China as case studies of social movement media exerting maximalist effects. The assessment relies on academic sources, archival materials, descriptive social media metrics, and an original analysis of external content shared on public Facebook pages and groups using data collected from the Facebook Graph API. A six-dimensional scheme is proposed to guide the assessment. Sorting through and piecing together multiple sources, we arrive at a multi-faceted description, comparison, and analysis of the impact of DANM during two social movements.
The Interplay of PR Interval and AV Pacing Delays Used for Cardiac Resynchronization Therapy in Heart Failure Patients: Association with Clinical Response in a Retrospective Analysis of a Large Observational Study
Authors: Gasparini Maurizio , Biffi Mauro , Landolina Maurizio , Cattafi Giuseppe , Rordorf Roberto , Botto Giovanni Luca , Battista Forleo Giovanni , Morani Giovanni , Santini Luca , Dello Russo Antonio , Rossillo Antonio , Meloni Sarah , Grammatico Andrea , Vitolo Marco , Boriani Giuseppe
Published: September 2022

Background. Cardiac resynchronization therapy (CRT) is a treatment for heart failure (HF) patients with prolonged QRS and impaired left ventricular (LV) systolic function. We aim to evaluate how the baseline PR interval is associated with outcomes (all-cause death or HF hospitalizations) and LV reverse remodeling (>15% relative reduction in LV end-systolic volume). Methods. Among 2224 patients with CRT defibrillators, 1718 (77.2%) had a device programmed at out-of-the-box settings (sensed AV delay: 100 ms and paced AV delay: 130 ms). Results. In this cohort of 1718 patients (78.7% men, mean age 66 years, 71.6% in NYHA class III/IV, LVEF = 27 ± 6%), echocardiographic assessment at 6-month follow-up showed that LV reverse remodeling was not constant as a function of the PR interval; in detail, it occurred in 56.4% of all patients but was more frequent (76.6%) in patients with a PR interval of 160 ms. In a median follow-up of 20 months, the endpoint of death or HF hospitalizations occurred in 304/1718 (17.7%) patients; in the multivariable regression analysis it was significantly less frequent when the PR interval was between 150 and 170 ms (hazard ratio = 0.79, 95% confidence interval (CI): 0.63–0.99, p = 0.046). The same PR range was associated with higher probability of CRT response (odds ratio = 2.51, 95% CI: 1.41–4.47, p = 0.002). Conclusions. In a large population of CRT patients, with fixed AV pacing delays, specific PR intervals are associated with significant benefits in terms of LV reverse remodeling and lower morbidity. These observational data suggest the importance of optimizing pacing programming as a function of the PR interval to maximize CRT response and patient outcome.
Muscle-in-Vein Conduits for the Treatment of Symptomatic Neuroma of Sensory Digital Nerves
Authors: Ederer Ines Ana , Kolbenschlag Jonas , Daigeler Adrien , Wahler Theodora
Published: September 2022

Background: Considering the debilitating burden of neuroma resulting in a significant loss of function and excruciating pain, the use of muscle-in-vein conduits (MVCs) for the reconstruction of painful neuroma of sensory nerves of the fingers was assessed. Methods: We retrospectively analyzed 10 patients who underwent secondary digital nerve repair by MVCs. The recovery of sensibility was evaluated by static and moving two-point discrimination (2PDs, 2PDm) and Semmes-Weinstein monofilament testing (SWM). The minimum follow-up was set 12 months after the operation. Results: The median period between trauma and nerve repair was 13.4 weeks (IQR 53.5). After neuroma resection, defects ranged from 10–35 mm (mean 17.7 mm, SD 0.75). The successful recovery of sensibility was achieved in 90% of patients after a median follow-up of 27.0 months (IQR 31.00). The mean 2PDs and 2PDm was 8.1 mm (SD 3.52) and 5.2 mm (SD 2.27), respectively. Assessment by SWM resulted in a mean value of 3.54 (SD 0.69). Reduction in pain was achieved among all patients; eight patients reported the complete relief of neuropathic pain. There was no recurrence of neuroma in any patient. Conclusions: Muscle-in-vein conduits provide an effective treatment for painful neuroma of digital nerves, resulting in satisfactory restoration of sensory function and relief of pain.
Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation
Authors: Sharifi-Rad Javad , Rapposelli Simona , Sestito Simona , Herrera-Bravo Jesús , Arancibia-Diaz Alejandra , Salazar Luis A. , Yeskaliyeva Balakyz , Beyatli Ahmet , Leyva-Gómez Gerardo , González-Contreras Carlos , Gürer Eda Sönmez , Martorell Miquel , Calina Daniela
Published: September 2022

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a tangle-shaped accumulation of beta-amyloid peptide fragments and Tau protein in brain neurons. The pathophysiological mechanism involves the presence of Aβ-amyloid peptide, Tau protein, oxidative stress, and an exacerbated neuro-inflammatory response. This review aims to offer an updated compendium of the most recent and promising advances in AD treatment through the administration of phytochemicals. The literature survey was carried out by electronic search in the following specialized databases PubMed/Medline, Embase, TRIP database, Google Scholar, Wiley, and Web of Science regarding published works that included molecular mechanisms and signaling pathways targeted by phytochemicals in various experimental models of Alzheimer’s disease in vitro and in vivo. The results of the studies showed that the use of phytochemicals against AD has gained relevance due to their antioxidant, anti-neuroinflammatory, anti-amyloid, and anti-hyperphosphorylation properties of Tau protein. Some bioactive compounds from plants have been shown to have the ability to prevent and stop the progression of Alzheimer’s.
Guided Endodontics: Static vs. Dynamic Computer-Aided Techniques—A Literature Review
Authors: Ribeiro Diana , Reis Eva , Marques Joana A. , Falacho Rui I. , Palma Paulo J.
Published: September 2022

(1) Background: access cavity preparation is the first stage of non-surgical endodontic treatment. The inaccuracy of this step may lead to numerous intraoperative complications, which impair the root canal treatment’s prognosis and therefore the tooth’s survival. Guided endodontics, meaning computer-aided static (SN) and dynamic navigation (DN) techniques, has recently emerged as a new approach for root canal location in complex cases. This review aims to compare SN and DN guided endodontics’ techniques in non-surgical endodontic treatment. (2) Methods: an electronic search was performed on PubMed, Scopus, and Cochrane Library databases until October 2021. Studies were restricted by language (English, Spanish and Portuguese) and year of publication (from 2011 to 2021). (3) Results: a total of 449, 168 and 32 articles were identified in PubMed, Scopus, and Cochrane Library databases, respectively, after the initial search. Of the 649 articles, 134 duplicates were discarded. In this case, 67 articles were selected after title and abstract screening, of which 60 were assessed for eligibility through full-text analysis, with one article being excluded. Four cross-references were added. Thus, 63 studies were included. (4) Conclusions: guided endodontics procedures present minimally invasive and accurate techniques which allow for highly predictable root canal location, greater tooth structure preservation and lower risk of iatrogenic damage, mainly when performed by less experienced operators. Both SN and DN approaches exhibit different advantages and disadvantages that make them useful in distinct clinical scenarios.
Impact of Race and Ethnicity on Presentation and Surgical Outcomes of Idiopathic Macular Holes
Authors: Parvus Matthew N. , Louis Abigail M. , Trejo Corona Stephanie , Wong Tien P. , Major James C. , Patel Sagar B. , Wykoff Charles C.
Published: September 2022

There is limited data on the presentation and surgical outcomes of idiopathic macular holes (IMH) for different ethnic and racial groups. Recognition of distinct, clinically-relevant patient subgroups may provide opportunities to identify specific unmet needs including possible barriers to optimal healthcare delivery. Medical records of patients who underwent surgery for IMH (between 2016 and 2022) at a large, urban retina practice were reviewed and self-reported ethnicity (Hispanic and non-Hispanic) and race (Asian, Black, White, and Other) were captured. The primary variables included (1) mean minimum linear diameter (MLD) at presentation and (2) surgical outcome (IMH closure status). Overall, mean MLD for all study eyes (515) was 366.1 μm, and surgical success was achieved in 489 (95.0%) eyes. Hispanic eyes presented with larger mean MLD (p = 0.002) compared to non-Hispanic eyes. Asian, Black, and Other eyes presented with larger mean MLD (p = 0.033, p < 0.001, p < 0.001) when compared to White eyes. The presentation of IMH varied in severity among different ethnic and racial groups. Hispanic patients were found to have worse preoperative visual acuity (VA), longer time to surgery, and larger mean MLD and BD compared to non-Hispanic participants. Black and Other patients were found to have worse VA, time to surgery, and larger mean MLD and BD when compared to White participants.
Computer-Aided Histopathological Characterisation of Endometriosis Lesions
Authors: McKInnon Brett D. , Nirgianakis Konstantinos , Ma Lijuan , Wotzkow Carlos Alvarez , Steiner Selina , Blank Fabian , Mueller Michael D.
Published: September 2022

Endometriosis is a common gynaecological condition characterised by the growth of endometrial tissue outside the uterus and is associated with pain and infertility. Currently, the gold standard for endometriosis diagnosis is laparoscopic excision and histological identification of endometrial epithelial and stromal cells. There is, however, currently no known association between the histological appearance, size, morphology, or subtype of endometriosis and disease prognosis. In this study, we used histopathological software to identify and quantify the number of endometrial epithelial and stromal cells within excised endometriotic lesions and assess the relationship between the cell contents and lesion subtypes. Prior to surgery for suspected endometriosis, patients provided menstrual and abdominal pain and dyspareunia scores. Endometriotic lesions removed during laparoscopic surgery were collected and prepared for immunohistochemistry from 26 patients. Endometrial epithelial and stromal cells were identified with Cytokeratin and CD10 antibodies, respectively. Whole slide sections were digitised and the QuPath software was trained to automatically detect and count epithelial and stromal cells across the whole section. Using this classifier, we identified a significantly larger number of strongly labelled CD10 stromal cells (p = 0.0477) in deeply infiltrating lesions (99,970 ± 2962) compared to superficial lesions (2456 ± 859). We found the ratio of epithelial to stromal cells was inverted in deeply infiltrating endometriosis lesions compared to superficial peritoneal and endometrioma lesions and we subsequently identified a correlation between total endometrial cells and abdominal pain (p = 0.0005) when counted via the automated software. Incorporating histological software into current standard diagnostic pipelines may improve endometriosis diagnosis and provide prognostic information in regards to severity and symptoms and eventually provide the potential to personalise adjuvant treatment decisions.
Research on the Spatial–Temporal Distribution and Morphological Characteristics of Ancient Settlements in the Luzhong Region of China
Authors: Tong Mengfei , Li Baihao , Li Zhao
Published: September 2022

This paper focuses on ancient settlements in the Luzhong region (the centre of Shandong Province) of China and analyses the spatial–temporal distribution and morphological characteristics of ancient settlements with the help of GIS technology and the perspectives of archaeology and cultural geography. Specifically, the 1972 settlements collected were used to establish a database of settlement site attributes. Then, the DEM data were superimposed with the settlement sites, and calculations of the kernel density, elevation, slope, aspect, and buffer zone were further carried out. The distribution and characteristics were refined based on quantitative and qualitative analyses. The study found that the Neolithic period, the Shang–Zhou period, and the Qin–Northern and Southern Dynasties were the three high points of settlement development. In these three periods, the centres of the large-scale distribution of settlements experienced changes from a “single centre” to a “continuous belt” to a “double centre’. In general, the spatial and temporal characteristics of the settlement distribution were continuously developed through time, while the spatial characteristics show that the main body continued to change locally. In different periods, settlements tended to be in the alluvial plains located between 20 and 60 m and with a slope of less than 6°. At the same time, they showed the obvious characteristic of living close to water. The past, present, and future are in the same chain of time; meanwhile, these settlements are the predecessors of today’s cities, towns, and villages. So, this study provides a basis for protecting their heritage value and provides a reference for the coordination of human–land relations, which can help achieve global sustainable development.
Plasticity of Native Intonation in the L1 of English Migrants to Austria
Authors: Mennen Ineke , Reubold Ulrich , Endes Kerstin , Mayr Robert
Published: September 2022

This study examines the plasticity of native language intonation in English-Austrian German sequential bilinguals who have migrated to Austria in adulthood by comparing it to that of monolingual English and monolingual Austrian control speakers. Intonation was analysed along four intonation dimensions proposed by the L2 Intonation Learning theory (LILt): the inventory of categorical phonological elements (‘systemic’ dimension), their phonetic implementation (‘realizational’), the meaning associated with phonological elements (‘semantic’), and their frequency of use (‘frequency’). This allowed us to test whether each intonation dimension is equally permeable to L2-on-L1 influences. The results revealed L2-on-L1 effects on each dimension. These consistently took the form of assimilation. The extent of assimilation appeared to depend on whether the cross-language differences were gradient or categorical, with the former predominantly resulting in intermediate merging and the latter in a complete transfer. The results suggest that native intonation remains plastic in all its dimensions, resulting in pervasive modifications towards the L2. Finally, in this first application of the LILt to the context of L1 attrition, the study confirms the model’s suitability not only to acquisition of L2 intonation but also for predicting where modifications of L1 intonation are likely to occur.
Suppression of OCT-1 in Metastatic Breast Cancer Cells Reduces Tumor Metastatic Potential, Hypoxia Resistance, and Drug Resistance
Authors: Stepchenko Alexander G. , Bulavkina Elizaveta V. , Portseva Tatiana N. , Georgieva Sofia G. , Pankratova Elizaveta V.
Published: September 2022

OCT-1/POU2F1 is a ubiquitously expressed transcription factor. Its expression starts at the earliest stage of embryonic development. OCT-1 controls genes involved in the regulation of differentiation, proliferation, cell metabolism, and aging. High levels of OCT-1 transcription factor in tumor cells correlate with tumor malignancy and resistance to antitumor therapy. Here, we report that suppression of OCT-1 in breast cancer cells reduces their metastatic potential and drug resistance. OCT-1 knockdown in the MDA-MB231 breast cancer cells leads to a fivefold decrease (p < 0.01) in cell migration rates in the Boyden chamber. A decrease in the transcription levels of human invasion signature (HIS) genes (ARHGDIB, CAPZA2, PHACTR2, CDC42, XRCC5, and CAV1) has been also demonstrated by real-time PCR, with high expression of these genes being a hallmark of actively metastasizing breast cancer cells. Transcriptional activity of ATF6 response elements is significantly reduced in the cell lines with decreased OCT-1 expression, which results in lower levels of adaptive EPR stress response. OCT-1 knockdown more than two times increases the MDA-MB231 cell death rate in hypoxia and significantly increases the doxorubicin or docetaxel-treated MDA-MB231 cell death rate. Our findings indicate that OCT-1 may be an important therapeutic target and its selective inhibition may have significant therapeutic effects and may improve prognosis in breast cancer patients.
H2O2/DEM-Promoted Maft Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish
Authors: Chen Ce , He Mingyue , Li Xueting , Yu Lidong , Liu Yi , Yang Yan , Li Li , Jia Jianbo , Li Bingsheng
Published: September 2022

The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli are still poorly understood. In this study, we found that both hydrogen peroxide (H2O2) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H2O2 regulated the demethylation of the maft promoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factor maft, thereby promoting the downstream antioxidant genes. The methylation of the Nrf2/ARE signaling pathway was not significantly regulated by DEM. However, under oxidative stress, the methyltransferase inhibitors (decitabine and azacitidine) demethylated the promoter region of maft. It activated the expression of the maft, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H2O2 and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy.
The Role of MreB, MreC and MreD in the Morphology of the Diazotrophic Filament of Anabaena sp. PCC 7120
Authors: Velázquez-Suárez Cristina , Luque Ignacio , Herrero Antonia
Published: September 2022

The cyanobacterium Anabaena sp. PCC 7120 forms filaments of communicating cells. Under conditions of nitrogen scarcity, some cells differentiate into heterocysts, allowing the oxygen-sensitive N2-reduction system to be expressed and operated in oxic environments. The key to diazotrophic growth is the exchange of molecules with nutritional and signaling functions between the two types of cells of the filament. During heterocyst differentiation, the peptidoglycan sacculus grows to allow cell enlargement, and the intercellular septa are rebuilt to narrow the contact surface with neighboring cells and to hold specific transport systems, including the septal junction complexes for intercellular molecular transfer, which traverse the periplasm between heterocysts and neighboring vegetative cells through peptidoglycan nanopores. Here we have followed the spatiotemporal pattern of peptidoglycan incorporation during heterocyst differentiation by Van-FL labeling and the localization and role of proteins MreB, MreC and MreD. We observed strong transitory incorporation of peptidoglycan in the periphery and septa of proheterocysts and a maintained focal activity in the center of mature septa. During differentiation, MreB, MreC and MreD localized throughout the cell periphery and at the cell poles. In mreB, mreC or mreD mutants, instances of strongly increased peripheral and septal peptidoglycan incorporation were detected, as were also heterocysts with aberrant polar morphology, even producing filament breakage, frequently lacking the septal protein SepJ. These results suggest a role of Mre proteins in the regulation of peptidoglycan growth and the formation of the heterocyst neck during differentiation, as well as in the maintenance of polar structures for intercellular communication in the mature heterocyst. Finally, as previously observed in filaments growing with combined nitrogen, in the vegetative cells of diazotrophic filaments, the lack of MreB, MreC or MreD led to altered localization of septal peptidoglycan-growth bands reproducing an altered localization of FtsZ and ZipN rings during cell division.
Forces Driving a Magic Bullet to Its Target: Revisiting the Role of Thermodynamics in Drug Design, Development, and Optimization
Authors: Minetti Conceição A. , Remeta David P.
Published: September 2022

Drug discovery strategies have advanced significantly towards prioritizing target selectivity to achieve the longstanding goal of identifying “magic bullets” amongst thousands of chemical molecules screened for therapeutic efficacy. A myriad of emerging and existing health threats, including the SARS-CoV-2 pandemic, alarming increase in bacterial resistance, and potentially fatal chronic ailments, such as cancer, cardiovascular disease, and neurodegeneration, have incentivized the discovery of novel therapeutics in treatment regimens. The design, development, and optimization of lead compounds represent an arduous and time-consuming process that necessitates the assessment of specific criteria and metrics derived via multidisciplinary approaches incorporating functional, structural, and energetic properties. The present review focuses on specific methodologies and technologies aimed at advancing drug development with particular emphasis on the role of thermodynamics in elucidating the underlying forces governing ligand–target interaction selectivity and specificity. In the pursuit of novel therapeutics, isothermal titration calorimetry (ITC) has been utilized extensively over the past two decades to bolster drug discovery efforts, yielding information-rich thermodynamic binding signatures. A wealth of studies recognizes the need for mining thermodynamic databases to critically examine and evaluate prospective drug candidates on the basis of available metrics. The ultimate power and utility of thermodynamics within drug discovery strategies reside in the characterization and comparison of intrinsic binding signatures that facilitate the elucidation of structural–energetic correlations which assist in lead compound identification and optimization to improve overall therapeutic efficacy.
MicroRNA: A Linking between Astrocyte Dysfunction, Mild Cognitive Impairment, and Neurodegenerative Diseases
Authors: Ramírez Angelica E. , Gil-Jaramillo Natalia , Tapias María Alejandra , González-Giraldo Yeimy , Pinzón Andrés , Puentes-Rozo Pedro J. , Aristizábal-Pachón Andrés Felipe , González Janneth
Published: September 2022

The importance of miRNAs in cellular processes and their dysregulation has taken significant importance in understanding different pathologies. Due to the constant increase in the prevalence of neurodegenerative diseases (ND) worldwide and their economic impact, mild cognitive impairment (MCI), considered a prodromal phase, is a logical starting point to study this public health problem. Multiple studies have established the importance of miRNAs in MCI, including astrocyte regulation during stressful conditions. Additionally, the protection mechanisms exerted by astrocytes against some damage in the central nervous system (CNS) lead to astrocytic reactivation, in which a differential expression of miRNAs has been shown. Nevertheless, excessive reactivation can cause neurodegeneration, and a clear pattern defining the equilibrium point between a neuroprotective or detrimental astrocytic phenotype is unknown. Therefore, the miRNA expression has gained significant attention to understand the maintenance of brain balance and improve the diagnosis and treatment at earlier stages in the ND. Here, we provide a comprehensive review of the emerging role of miRNAs in cellular processes that contribute to the loss of cognitive function, including lipotoxicity, which can induce chronic inflammation, also considering the fundamental role of astrocytes in brain homeostasis.
An Evaluation of Ireland’s Sustainable Freight Transport Policy
Authors: Zhang Xu , Plant Eoin , Valantasis Kanellos Nikolaos
Published: September 2022

Background: The Irish government has put forth sustainable transport policy measures, yet the emphasis is mainly on the active travel and sustainable mobility for passenger transport. Contrariwise, freight transport has not received equal consideration in policy measures, regulatory frameworks, and support schemes towards the low-carbon transition. This study seeks to address this imbalance. Methods: The paper proposes an adaptation of the ASI framework for freight transport and assesses the applicability of a number of international sustainable transport measures based on their potential sustainability impact if adopted in Ireland. The research applied a Policy Delphi Method to a heterogeneous expert panel. Results: The findings indicate that the current sustainable freight transport policy measures in Ireland are limited, and the paper suggests 38 measures for supply chains, maritime transport, rail transport and urban freight transport. The analysis further suggests that decarbonisation measures in Ireland should first formulate on the decarbonisation stages ‘avoid’ and ‘shift’, and then move to the ‘improve’ stage, thus leading to a greater impact on decarbonising the freight sector. Conclusions: An ‘ASI for freight transport’ framework is proposed as a taxonomy to systematically compare freight decarbonisation policy measures locally and internationally. This updated framework can serve as a new lens to prioritise sustainable freight policy measures. Recommendations are proposed for developing policy measures for sustainable freight transport in Ireland.
Design of a Spiral Double-Cutting Machine for an Automotive Bowden Cable Assembly Line
Authors: Barbosa André F. G. , Campilho Raul D. S. G. , Silva Francisco J. G. , Sánchez-Arce Isidro J. , Prakash Chander , Buddhi Dharam
Published: September 2022

The manufacture of automotive components requires innovative technologies and equipment. Due to the competitiveness in the sector, the implementation of automatic and robotic equipment has been vital in its development to produce the largest number of products in the shortest amount of time. Automation leads to a significant reduction in defects and enables mass production and standardization of the final product. This work was based on the need of an automotive components’ company to increase the rate of spiral cable cutting, used as protection for Bowden (control) cables. Currently, this component, used in automotive systems, is processed with simple cutting machines and cleaning machines. Based on the design science research (DSR) methodology, this work aims to develop a machine capable of performing the cutting and cleaning of two spiral cables simultaneously and automatically. The development of this machine was based on existing machines, and the biggest challenge was the implementation of a double-cutting system. The designed machine met the initial requirements, such as enabling the simultaneous cut of two spirals, being fully automatic, doubling the output over the current solution, and fully complying with the current legislation.
Knowledge and Beliefs on Mathematical Modelling Inferred in the Argumentation of a Prospective Teacher When Reflecting on the Incorporation of This Process in His Lessons
Authors: Ledezma Carlos , Sol Telesforo , Sala-Sebastià Gemma , Font Vicenç
Published: September 2022

Mathematical modelling enjoys affirmed relevance in educational curricula worldwide, and teacher education programs consider that this process should also be experienced during educational internships. The interest of this study focuses on the argumentation of a prospective teacher to justify the incorporation (or not) of mathematical modelling in his lessons. To do this, we analyzed the reflection of a prospective mathematics teacher on the design of a modelling task during his educational internship. Methodologically, it is a case study in which, based on the didactic suitability criteria tool, the study subject structured the reflection on his educational internship in his master’s degree final project (MFP), whose central axis was modelling. We collected data from video recordings of group reflection sessions with the study subject and other prospective teachers of a professionalizing master’s program, and from the analysis of his MFP. The results evidenced the prospective teacher’s arguments to justify the design of a modelling task, his knowledge, and his beliefs about this process, among other aspects. We conclude that the specialized knowledge that is inferred from this argumentation is of different types and is part of a conglomerate formed, in addition, by values, beliefs, and guidelines for action.
The Geometry of the Kiepert Trefoil
Authors: Pulov Vladimir I. , Toda Magdalena D. , Vassilev Vassil M. , Mladenov Ivaïlo M.
Published: September 2022

This article presents a comparative study of Kiepert’s trefoil and its related curves, combining a variety of tools from differential and algebraic geometry, integrable systems, elastica theory, and special functions. While this curve was classically known and well studied in the literature, some related open problems were recently solved, and the goal of this paper is to present and characterize the general solution of the equation that governs this trefoil’s family of curves by involving elliptic functions and elastica theory in the mechanics.
Equivalence of Competitive Equilibria, Fuzzy Cores, and Fuzzy Bargaining Sets in Finite Production Economies
Authors: Liu Jiuqiang
Published: September 2022

For an exchange economy with a continuum of traders and a finite-dimensional commodity space under some standard assumptions, Aumann showed that the core and the set of competitive allocations (two most important solutions) coincide and Mas-Colell proved that the bargaining set and the set of competitive allocations coincide. However, in the case of exchange economies with a finite number of traders, it is well-known that the set of competitive allocations could be a strict subset of the core which can also be a strict subset of the bargaining set. In this paper, we establish the equivalence of the fuzzy core, the fuzzy bargaining set (or Aubin bargaining set), and the set of competitive allocations in a finite coalition production economy with an infinite-dimensional commodity space under some standard assumptions. We first derive a continuous equivalence theorem and then discretize it to obtain the desired equivalence in finite economies.
Hydroxychloroquine Effects on THP-1 Macrophage Cholesterol Handling: Cell Culture Studies Corresponding to the TARGET Cardiovascular Trial
Authors: Ahmed Saba , Konig Justin , Kasselman Lora J. , Renna Heather A. , De Leon Joshua , Carsons Steven E. , Reiss Allison B.
Published: September 2022

Background and Objectives: Cardiovascular (CV) risk is elevated in rheumatoid arthritis (RA). RA patient plasma causes pro-atherogenic derangements in cholesterol transport leading to macrophage foam cell formation (FCF). The TARGET randomized clinical trial compares CV benefits of 2 RA drug regimens. Hydoxychloroquine (HCQ) is a key medication used in TARGET. This study examines effects of HCQ on lipid transport to elucidate mechanisms underlying TARGET outcomes and as an indicator of likely HCQ effects on atherosclerosis in RA. Materials and Methods: THP1 human macrophages were exposed to media alone, IFNγ (atherogenic cytokine), HCQ, or HCQ + IFNγ. Cholesterol efflux protein and scavenger receptor mRNA levels were quantified by qRT-PCR and corresponding protein levels were assessed by Western blot. FCF was evaluated via Oil-Red-O and fluorescent-oxidized LDL. Intracellular cholesterol and efflux were quantified with Amplex Red assay. Results: With the exception of a decrease in the efflux protein cholesterol 27-hydroxylase in the presence IFNγ at all HCQ concentrations, no significant effect on gene or protein expression was observed upon macrophage exposure to HCQ and this was reflected in the lack of change in FCF and oxidized LDL uptake. Conclusions: HCQ did not significantly affect THP1 macrophage cholesterol transport. This is consistent with TARGET, which postulates superior effects of anti-TNF agents over sulfasalazine + HCQ.
Algorithm of Femoropopliteal Endovascular Treatment
Authors: Dubosq Maxime , Raux Maxime , Nasr Bahaa , Gouëffic Yann
Published: September 2022

Background and Objectives: Indications for the endovascular treatment of femoropopliteal lesions have steadily increased over the past decade. Accordingly, the number of devices has also increased, but the choice of the best endovascular treatment remains to be defined. Many devices are now available for physicians. However, in order to obtain a high success rate, it is necessary to respect an algorithm whose choice of device is only one step in the treatment. Materials and Methods: The first step is, therefore, to define the approach according to the lesion to be treated. Anterograde approaches (femoral, radial, or humeral) are distinguished from retrograde approaches depending on the patient’s anatomy and surgical history. Secondarily, the lesion will be crossed intraluminally or subintimally using a catheter or an angioplasty balloon. The third step corresponds to the preparation of the artery, which is essential before the implantation of the device. It has a crucial role in reducing the rate of restenosis. Several tools are available and are chosen according to the lesion requiring treatment (stenosis, occlusion). Among them, we find the angioplasty balloon, the atherectomy probes, or intravascular lithotripsy. Finally, the last step corresponds to the choice of the device to be implanted. This is also based on the nature of the lesion, which is considered short, up to 15 cm and complex beyond that. The choice of device will be between bare stents, covered stents, drug-coated balloons, and drug-eluting stents. Currently, drug-eluting stents appear to be the treatment of choice for short lesions, and active devices seem to be the preferred treatment for more complex lesions, although there is a lack of data. Results: In case of failure to cross the lesion, the retrograde approach is a safe and effective alternative. Balloon angioplasty currently remains the reference method for the preparation of the artery, the aim of which is to ensure the intraoperative technical success of the treatment (residual stenosis < 30%), to limit the risk of dissection and, finally, to limit the occurrence of restenosis. Concerning the treatment, the drug-eluting devices seem to present the best results, whether for simple or complex lesions. Conclusions: Endovascular treatment for femoropopliteal lesions needs to be considered upstream of the intervention in order to anticipate the treatment and the choice of devices for each stage.
Fabrication of Loose Nanofiltration Membranes with High Rejection Selectivity between Natural Organic Matter and Salts for Drinking Water Treatment
Authors: He Zhihai , Wang Kunpeng , Liu Yanling , Zhang Ting , Wang Xiaomao
Published: September 2022

Loose nanofiltration (LNF) membranes with a molecular weight cut-off (MWCO) of about 1000 Da and high surface negative charge density have great application potential for drinking water treatment pursuing high rejection selectivity between natural organic matter (NOM) and mineral salts. This study was conducted to exploit the novel method coupling non-solvent induced phase separation (NIPS) and interfacial polymerization (IP) for the preparation of high-performance LNF membranes. A number of LNF membranes were synthesized by varying the polyethersulfone (PES) and piperazine (PIP) concentrations in the cast solution for the PES support layer preparation. Results showed that these two conditions could greatly affect the membrane water permeance, MWCO and surface charge. One LNF membrane, with a water permeance as high as 23.0 ± 1.8 L/m2/h/bar, when used for the filtration of conventional process-treated natural water, demonstrated a rejection of NOM higher than 70% and a low rejection of mineral salts at about 20%. Both the mineral salts/NOM selectivity and permselectivity were superior to the currently available LNF membranes as far as the authors know. This study demonstrated the great advantage of the NIPS–IP method for the fabrication of LNF membranes, particularly for the advanced treatment of drinking water.
Phase and Microstructure Transition of High Cu Content Cu-W Composite Powder Fabricated by Spray Drying
Authors: Wang Qi , Li Xiuqing , Wei Shizhong , Lou Wenpeng , Xu Liujie , Zhou Yucheng
Published: September 2022

Cu-W composite powder with various W contents (0, 10, 20, and 30 wt%) has been fabricated by spray drying, calcination, and two-stage hydrogen reduction in this work. The microstructures and phase evolution of Cu-W composite powder were studied by FESEM, HRTEM, and XRD. Results show that precursor powder is composed of Cu2(OH)3NO3 and H2WO4·H2O. Spherical CuWO4 with a particle size of about 50 nm and micron-scale flat flake CuO were obtained when the calcination temperature was 500 °C. Through chemical vapor transport (CVT) during the reduction process, volatile WO2(OH)2 continuously migrates to the copper surface and is reduced to W, resulting in a W-coated Cu structure. This coating structure can inhibit the aggregation and growth of copper particles. The particle sizes of Cu-10 wt%W, Cu-20 wt%W, and Cu-30 wt%W composite powders are 9.309 μm, 8.440 μm, and 6.290 μm, reduced by 40.51%, 46.06%, and 59.80%, respectively, compared to the particle size of pure copper powder, 15.648 μm. With increasing W content, the W-coated Cu particles gradually become denser and trend to grow from sphere to flake.
Formation of the Structure and Properties of Deposited Multilayer Specimens from Austenitic Steel under Various Heat Removal Conditions
Authors: Chinakhov Dmitry A. , Akimov Kirill O.
Published: September 2022

The effect of side limiters (shaping blocks) on the formation of the structure and hardness of AISI 308LSi stainless steel workpieces obtained by multilayer build-up welding in an argon environment has been studied. The studies were carried out on specimens deposited using graphite limiters, copper limiters and without limiters. As a result of numerical simulation, it was found that the lowest temperatures of the specimen metal are observed when using copper limiters, and the highest when using graphite limiters (different thermal conductivity of materials) in comparison with the temperatures of the specimen obtained without limiters. With the use of graphite limiters, most of the specimen’s metal is in the temperature range of austenite formation (45%) and a more uniform growth of structural elements is observed, without sharp transitions between the deposited layers, in contrast to the other two types of specimens. The high value of the thermal conductivity of copper leads to an increase in the difference in the size of the dendrites between the central and peripheral side parts of the deposited specimen. The highest values of hardness are observed in the specimen obtained using graphite blocks, due to the more active diffusion of δ-ferrite into austenite by an average of 12%, compared with the other investigated specimens, despite the overall increase in size dendrites. The technology of electric arc multilayer build-up welding with the use of shaping graphite blocks makes it possible to produce a workpiece with a uniform structure and properties. The above makes it a promising direction in electric arc additive manufacturing.