bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Pharmacology of the Low-Impact Ampakine CX717
Authors: Radin Daniel P. , Zhong Sheng , Cerne Rok , Smith Jodi L. , Witkin Jeffrey M. , Lippa Arnold
Published: August 2024

Ampakines are a class of orally available positive allosteric modulators of the AMPA-glutamate receptor (AMPAR) and have therapeutic implications for neurological/neuropsychiatric disorders in which AMPAR signaling is compromised. Low-impact ampakines are a distinct subclass of drugs that only modestly offset receptor desensitization and do not alter agonist binding affinity and thus lack the neurotoxicity and epileptogenic effects associated with other AMPAR modulators. In these studies, we describe the pre-clinical pharmacology of ampakine 1-(benzofurazan-5-ylcarbonyl)morpholine (CX717). CX717 modestly offsets desensitization in hippocampal patches and augments synaptic transmission in vivo. CX717 also enhances long-term potentiation in rats, which is crucial for learning and memory. CX717 enhances performance in the eight-arm radial maze and abrogates amphetamine-induced locomotor activity while being devoid of cataleptic activity in rats. CX717 also ameliorates alfentanil-induced respiratory depression in rats and is not toxic to cultured rat neurons. CX717 is active at doses of 0.3–10 mg/kg and lacked serious adverse events in safety studies in mice up to 2000 mg/kg. CX717 was also previously shown to be safe in humans and effective in reversing opiate-induced respiratory depression and hyperactivity and inattentiveness in adults with ADHD. These findings support the continued clinical investigation of CX717 in the treatment of ADHD, dementia, and opiate-induced respiratory depression.
Genome-Wide Identification, Characterization, and Transcriptional Profile of the HECT E3 Ubiquitin Ligase Gene Family in the Hard-Shelled Mussel Mytilus coruscus Gould
Authors: Guo Feng , Xin Zhenqi , Dong Zhenyu , Ye Yingying
Published: August 2024

The homologous E6-AP carboxy-terminal structural domain (HECT) contained in E3 ubiquitin ligases (E3s) is a key factor in protein degradation and maintenance of cellular homeostasis in animals. However, the functional roles and evolutionary aspects of the HECT gene family in bivalve mussels remain unclear and warrant further investigation. In this study, we identified 22 HECT genes within the genome of Mytilus coruscus Gould, all containing a conserved HECT structural domain derived from dispersed repeats, distributed unevenly across 11 chromosomes. Phylogenetic analysis classified M. coruscus HECT genes into six major classes, with amino acid sequences within the same evolutionary clade displaying similar conserved motifs. Homology analysis with HECT genes of four bivalve species revealed that M. coruscus and Mytilus galloprovincialis possessed the largest number of homologous gene pairs, showing a significant correlation between the two in the evolution of the HECT gene family. Homology analysis with HECT genes of four bivalve species revealed that M. coruscus and M. galloprovincialis possessed the largest number of homologous gene pairs, showing a significant correlation between the two in the evolution of the HECT gene family. M. coruscus exhibited pronounced and specific expression in gills and blood tissues. Notably, Mco_UPL3 gene expression was significantly upregulated after 12 h of acute heat stress (33 °C) and 24 h of Vibrio injection (0.4 OD). Gene ontology analysis of the HECT genes in M. coruscus revealed that it is primarily enriched in protein modification and degradation functions. This suggests that HECT genes may play a key role in protein degradation and immunomodulation in M. coruscus. These findings offer valuable insights for the breeding of stress-tolerant traits in M. coruscus. In summary, our data shed light on the potential functions of HECT E3 ligases in response to heat stress and Vibrio infection, providing practical guidance for enhancing resilience through breeding in M. coruscus.
Studying Intense Convective Rainfall in Turin’s Urban Area for Urban Flooding Early Warning System Implementation
Authors: Cremonini Roberto , Tiranti Davide , Burzio Edoardo , Brussolo Elisa
Published: August 2024

The effects of global warming, coupled with the continuing expansion of urbanization, have significantly increased vulnerability to urban flooding, widespread erosion risks, and related phenomena such as shallow landslides and mudflows. These challenges are particularly evident in both lowland and hill/foothill environments of urbanized regions. Improving resilience to urban flooding has emerged as a top priority at various levels of governance. This paper aims to perform an initial analysis with the goal of developing an early warning system to efficiently manage intense convective rainfall events in urban areas. To address this need, the paper emphasizes the importance of analyzing different hazard scenarios. This involves examining different hydro-meteorological conditions and exploring management alternatives, as a fundamental step in designing and evaluating interventions to improve urban flood resilience. The Turin Metropolitan Area (TMA), located in north-western Italy, represents a unique case due to its complex orography, with a mountainous sector in the west and a flat or hilly part in the east. During the warm season, this urban area is exposed to strong atmospheric convection, resulting in frequent hailstorms and high-intensity rainfall. These weather conditions pose a threat to urban infrastructure, such as drainage systems and road networks, and require effective management strategies to mitigate risks and losses. The TMA’s urban areas are monitored by polarimetric Doppler weather radars and a dense network of rain gauges. By examining various summer precipitation events leading to urban flooding between 2007 and 2021, this study assesses the practicability of deploying a weather-radar early-warning system. The focus is on identifying rainfall thresholds that distinguish urban flooding in lowland areas and runoff erosion phenomena in urbanized hills and foothills.
Interpreting Soft-Sediment Deformation Structures: Insights into Earthquake History and Depositional Processes in the Dead Sea, Jordan
Authors: Al-Saqarat Bety , Abbas Mahmoud , Al Hseinat Mu’ayyad , Qutishat Tala , Shammar Duha , AlShamaileh Ehab
Published: August 2024

Soft-sediment deformation structures (SSDSs) typically form in unconsolidated sedimentary deposits before lithification. Understanding these structures involves evaluating their characteristics, genesis timing, and the dynamics of sediment deformation. SSDSs are essential for deciphering ancient environments, reconstructing depositional processes, and discerning past prevailing conditions. In the Dead Sea region, SSDSs are abundant and well preserved due to unique geological and environmental factors, including rapid sedimentation rates and seismic activity. Influenced by the Dead Sea Transform Fault, the area offers insights into tectonic activity and historical earthquakes predating modern instrumentation. This study extensively examines SSDSs along the Dead Sea area in Jordan, focusing on sediments near the Lisan Peninsula, where the prominent Lisan Formation (71–12 ka) exposes numerous deformations. Mineralogical and geochemical analyses using X-ray diffraction (XRD) and X-ray fluorescence (XRF) were applied on deformed and undeformed layers to test the potential trigger of seismite formation in the Dead Sea area. The XRD and XRF results reveal Aragonite and Halite as the predominant compounds. Field observations, coupled with mineralogical and geochemical data, suggest tectonic activity as the primary driver of SSDSs formation in the Dead Sea region. Other contributing factors, such as high salinity, arid climate, and depositional settings, may also have influenced their formation. These structures offer valuable insights into the region’s geological history, environmental conditions, and tectonic evolution.
Exploring the Relationship between Fundamental Movement Skills and Health-Related Fitness among First and Second Graders in Korea: Implications for Healthy Childhood Development
Authors: Park Se-Won , Yoon Sung-Ho , Lee Seung-Man
Published: August 2024

This study investigated the relationship between fundamental movement skills (FMSs) and health-related fitness (HRF) among first and second graders in South Korean elementary schools. It aimed to provide foundational data for developing physical education programs tailored to the motor development stages and fitness levels of younger elementary school students. This study utilized secondary data from the physical activity competence evaluation conducted by the Health Physical Activity Institute (HPAI). In October 2023, the HPAI evaluated the fundamental movement skills (jumping, running, hopping, static balance, dynamic balance, overhand throwing, and kicking) and health-related fitness (muscular strength, cardiorespiratory endurance, and flexibility) of 291 first and second-grade students. The collected data were analyzed through frequency and multiple regression analyses performed using SPSS software. The results revealed that higher scores in jumping and hopping are associated with greater muscular strength, cardiorespiratory endurance, and flexibility. Running had no significant effect on HRF elements. Higher scores in static balance (i.e., that used in single-leg stance) were associated with increased muscular strength, cardiorespiratory endurance, and flexibility, but dynamic balance (balance beam walking) did not have a significant effect. Higher scores in overhand throwing were associated with greater muscular strength and cardiorespiratory endurance, but kicking did not show a significant association. Overall, these findings emphasize the importance of prioritizing jumping and static balance in physical education for the well-rounded health development of first and second graders. Based on the results derived from this study, it is expected to serve as a theoretical basis for including “jumping” and “static balance” in the first and second grade curriculum of elementary schools, thereby providing essential guidance.
Changes in Substance Use Diagnoses in the Great Plains during the COVID-19 Pandemic
Authors: Nahian Ahmed , McFadden Lisa M.
Published: August 2024

As drug overdose mortality rises in the United States, healthcare visits present critical opportunities to mitigate this trend. This study examines changes in healthcare visits for substance use disorders (SUDs) and remission prior to and during the COVID-19 pandemic in the Great Plains, with a focus on identifying the characteristics of those served. Data were analyzed from 109,671 patient visits (mode = one visit per patient), encompassing diverse demographics, including sex, age, race, ethnicity, and geographic location. Visits analyzed included those for Alcohol Use Disorder (AUD), Opioid Use Disorder (OUD), or Stimulant Use Disorder (StUD) and those in remission of these disorders between March 2019 and March 2021. Patient demographic information and geographic factors, like rurality and Medicaid expansion status, were considered, and logistic regression was utilized. Visits were primarily by White (70.83%) and Native American (21.39%) patients, non-Hispanic (91.70%) patients, and males (54.16%). Various demographic, geographic, and temporal trends were observed. Findings indicated that males were more likely to receive an AUD diagnosis, while females were more likely to receive an OUD or StUD diagnosis. Metropolitan-residing patients were more likely to receive an AUD diagnosis, while non-metropolitan patients were more likely to receive an OUD diagnosis. Remission odds increased for StUD during the pandemic but decreased for AUD and OUD. These findings illuminate the demographic and geographic patterns of SUD-related healthcare visits, suggesting critical touchpoints for intervention. The results emphasize the urgent need for targeted healthcare strategies, especially in rural and underserved areas, to address persistent health disparities.
Infective Endocarditis in Patients with End-Stage Renal Disease on Dialysis: Epidemiology, Risk Factors, Diagnostic Challenges, and Management Approaches
Authors: Issa Rochell , Chaaban Nourhan , Salahie Abdullah , Honnekeri Bianca , Parizher Gary , Xu Bo
Published: August 2024

Infective endocarditis (IE) poses a significant clinical challenge, especially among patients with end-stage renal disease (ESRD) undergoing dialysis, and is associated with high morbidity and mortality rates. This review provides a contemporary discussion of the epidemiology, risk factors, diagnostic challenges, and management strategies for IE among ESRD patients, including a literature review of recent studies focused on this vulnerable population. The review highlights the multifactorial nature of IE risk in ESRD patients, emphasizing the roles of vascular access type, dialysis modality, and comorbid conditions. It also explores the diagnostic utility of different imaging modalities and the importance of a multidisciplinary approach in managing IE, including both medical and surgical interventions. The insights from this review aim to contribute to the improvement of patient outcomes through early recognition, appropriate antimicrobial therapy, and timely surgical intervention when necessary.
Group-Based Trajectory Modeling of N-Terminal Pro-Brain Natriuretic Peptide Levels in Pulmonary Artery Hypertension Associated with Connective Tissue Disease
Authors: Tang Heng , Lu Fengyun , Huang Yingheng , Wang Qiang , Sun Xiaoxuan , Zhang Miaojia , Zhou Lei
Published: August 2024

Group-based trajectory modeling (GBTM) allows the trajectory analyses of repeated N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements during follow-up visits of pulmonary artery hypertension associated with connective tissue disease (CTD-PAH) patients. This study aimed to (1) identify trajectories of NT-proBNP changing over time, (2) explore the association between NT-proBNP trajectories and prognosis, and (3) explore the effects of baseline clinical characteristics on NT-proBNP trajectories. A retrospective, single-centred, observational study was performed on 52 CTD-PAH patients who had undergone at least three follow-up visits within 1 year from baseline. Four NT-proBNP trajectories were identified using GBTM: low stability (n = 15, 28.85%), early remission (remission within 3 months) (n = 20, 38.46%), delayed remission (remission after 6 or 9 months) (n = 11, 21.15%), and high stability (n = 6, 11.54%). The low-stability and early-remission trajectories were related to a similar positive prognosis, while the delayed-remission and high-stability trajectories were associated with a gradually worsening prognosis (p = 0.000). Intensive CTD immunotherapy (corticosteroids plus immunosuppressants) was the only factor that remained significant after least absolute shrinkage and selection operator regression and multivariate logistic regression, and was independently associated with a lower risk NT-proBNP trajectory (p = 0.048, odds ratio = 0.027, 95% confidence interval: 0.001–0.963), which preliminarily indicated a benefit of CTD-PAH patients undergoing intensive CTD immunotherapy.
Relationship between Pain, Physical Activity, Screen Time and Age among Young Children during the COVID-19 Pandemic
Authors: Basuodan Reem M. , Gmmash Afnan , Alghadier Mshari , Albesher Reem A.
Published: August 2024

Introduction: During the COVID-19 pandemic, many countries implemented restrictions, social distancing measures, and lockdowns to limit the spread of the disease. These lockdowns have affected children’s screen time (ST), pain, and physical activity (PA) levels. The present study aimed to explore the relationships between ST, pain, age, and PA before, during, and after the COVID-19 pandemic. Methods: The caregivers of 329 children (median age = 8 years) filled out an online self-reported survey about the children’s PA, ST, and pain before, during, and after the COVID-19 curfew. Spearman’s rank correlation coefficient was used to explore the associations between these variables. Results: After the curfew, pain that existed before the pandemic had a weak negative relationship with PA intensity (−0.11, p = 0.04) and a weak positive relationship with ST (r = +0.12, p = 0.04). There was a strong positive relationship between ST in all time periods (p > 0.01). PA and ST had a weak negative relationship (p > 0.05) during the curfew and after the curfew but not before the COVID-19 pandemic. Age had a weak positive correlation with ST in all time periods (p > 0.01). In addition, ST was affected by the curfew. Conclusion: The study findings indicated that young children had longer ST during the curfew and after the curfew compared with before the curfew. Increasing PA could lessen children’s ST, which could, in turn, increase the probability that their general pain would decrease.
Assessment Study of ChatGPT-3.5’s Performance on the Final Polish Medical Examination: Accuracy in Answering 980 Questions
Authors: Siebielec Julia , Ordak Michal , Oskroba Agata , Dworakowska Anna , Bujalska-Zadrozny Magdalena
Published: August 2024

Background/Objectives: The use of artificial intelligence (AI) in education is dynamically growing, and models such as ChatGPT show potential in enhancing medical education. In Poland, to obtain a medical diploma, candidates must pass the Medical Final Examination, which consists of 200 questions with one correct answer per question, is administered in Polish, and assesses students’ comprehensive medical knowledge and readiness for clinical practice. The aim of this study was to determine how ChatGPT-3.5 handles questions included in this exam. Methods: This study considered 980 questions from five examination sessions of the Medical Final Examination conducted by the Medical Examination Center in the years 2022–2024. The analysis included the field of medicine, the difficulty index of the questions, and their type, namely theoretical versus case-study questions. Results: The average correct answer rate achieved by ChatGPT for the five examination sessions hovered around 60% and was lower (p < 0.001) than the average score achieved by the examinees. The lowest percentage of correct answers was in hematology (42.1%), while the highest was in endocrinology (78.6%). The difficulty index of the questions showed a statistically significant correlation with the correctness of the answers (p = 0.04). Questions for which ChatGPT-3.5 provided incorrect answers had a lower (p < 0.001) percentage of correct responses. The type of questions analyzed did not significantly affect the correctness of the answers (p = 0.46). Conclusions: This study indicates that ChatGPT-3.5 can be an effective tool for assisting in passing the final medical exam, but the results should be interpreted cautiously. It is recommended to further verify the correctness of the answers using various AI tools.
Association between Falls, Fear of Falling and Depressive Symptoms in Community-Dwelling Older Adults
Authors: Pereira Maria Eduarda Armando , Santos Gerson de Souza , Almeida Clara Rabite de , Nunes Kethlyn Cristina Santos , Silva Monalisa Claudia Maria da , José Helena , Sousa Luís , Vitorino Luciano Magalhães
Published: August 2024

Background: Longevity increases pose public health challenges, especially in managing falls and their psychological impacts on older adults. Limited evidence exists on the relationship between a fear of falling (FOF), previous falls, and depressive symptoms among community-dwelling older adults. Objective: To evaluate the association between falls, FOF, and depressive symptoms in community-dwelling older adults. Methods: This cross-sectional study, conducted in 2018, included 400 older adults from a Basic Health Unit in São Paulo, Brazil. The Geriatric Depression Scale (GDS-15) and the International Falls Efficacy Scale (FES-I) were used, along with self-report questionnaires on fall history. Linear and logistic regression were used to analyze the relationships between variables. Results: The mean age was 75.2 (SD = 8.53) years, with 63.2% being female. Depressive symptoms were observed in 18.3% of the participants, while 90.5% reported a fear of falling (FOF). More than half (63.0%) experienced falls, with 49.5% occurring in the last year. Factors such as the female gender, negative health perceptions, and functional dependence were associated with depressive symptoms. Adjusted analyses indicated that both a fear of falling (FOF) (B = 0.043; p = 0.012) and a history of falls (B = 0.725; p = 0.015) were associated with depressive symptoms. Conclusions: Falls, FOF, and depressive symptoms are interlinked among older adults, underscoring the need for targeted interventions to improve their mental and physical health.
Delayed Access to Medical Care and Psychological Distress among Chinese Immigrants in Canada during the Pandemic
Authors: Vo Anh Thu , Yang Lixia , Urquhart Robin , Yi Yanqing , Wang Peizhong Peter
Published: August 2024

The psychological impact of medical care accessibility during the pandemic has been widely studied, but little attention has been given to Asian immigrants in Canada. This study aimed to fill this literature gap by using a cross-sectional survey, which aimed to evaluate the impact of the COVID-19 pandemic on Chinese immigrants in North America during the second wave of the pandemic. The study focused on Chinese immigrants aged 16 or older in Canada. Covariates included sociodemographic variables, delayed access to medical care (i.e., treatment or health assessment), and other COVID-19 related variables. We used logistic LASSO regression for model selection and multivariate logistic regression models to evaluate the association between delayed access to treatment/health assessment and psychological distress outcome, as measured by the COVID-19 Peritraumatic Distress Index (CPDI). Missing data were handled using multiple imputation. Our study included 746 respondents, with 47.18% in the normal CPDI group and 36.82% in the mild-to-severe CPDI group. Most respondents were originally from Mainland China and residing in Ontario. Over half have stayed in Canada for at least 15 years. The multivariate logistic regression models identified significant risk predictors of psychological distress status: delayed access to medical care (OR = 1.362, 95% CI: 1.078–1.720, p = 0.0095), fear of COVID-19 (OR = 1.604, 95% CI: 1.293–1.989, p < 0.0001), and social loneliness (OR = 1.408, 95%CI: 1.314–1.508, p < 0.0001). Sociodemographic variables and other COVID-19-related variates did not significantly impact the study’s outcome. Our findings shed light on the importance of timely medical care access to psychological well-being among Chinese Canadians. Reliable health information, mental health support, and virtual care tailored to immigrants should be considered to mitigate this impact and promote their overall health and well-being.
A Brief History of Social Housing in Spain: Residential Architecture and Housing Policies in the 19th and 20th Centuries
Authors: Hernández Falagán David , Nicolau Maribel Rosselló
Published: August 2024

The history of social housing in Spain over the last two centuries has been influenced by factors of political and economic instability that have affected the entire country. This research examines these factors through the analysis of official legislative documentation and other bibliographic sources. This article covers different study periods, defined by significant historical circumstances, during which housing policies responded to the sociopolitical context of each moment. This study pays special attention to the management instruments that were implemented, as well as the nature of residential architectures and urban solutions that emerged as a consequence. The result is a social housing landscape that presents significant shortcomings and deficiencies, prefiguring a situation of vulnerability in the face of the economic crisis of the early 21st century.
Analysis of Runoff Changes and Their Driving Forces in the Minjiang River Basin (Chengdu Section) in the Last 30 Years
Authors: Liu Jingjing , Yan Kun , Liu Qin , Lin Liyang , Peng Peihao
Published: August 2024

Surface runoff is a key component of the hydrological cycle and is essential for water resource management and water ecological balance in river basins. It is important to accurately reveal the spatial and temporal dynamics of regional surface runoff over long time scales and to quantify the impacts of climate change and human activities on surface runoff changes for sustainable water resources management and utilization. In this study, the Minjiang River Basin (Chengdu section) was selected, which has significant natural and anthropogenic variations, and a comprehensive analysis of runoff and its drivers will help to formulate an effective regional water resource management strategy. We mainly used SWAT to simulate the monthly-scale runoff in the Chengdu section of the Minjiang River Basin from 1990 to 2019 and combined SWAT-CUP to perform sensitivity analysis on the model parameters and Partial Least Squares Structural Equation Modeling (PLS-SEM) to quantitatively analyze the main drivers of the changes in surface runoff. The results show that the average multi-year runoff in the Minjiang River Basin (Chengdu section) ranges from 628.96 to 1088.46 mm, with an average value of 834.13 mm, and that the overall annual runoff in the past 30 years shows a fluctuating tendency. The goodness-of-fit of the PLS-SEM model is 0.507; the validity and reliability assessment indicated that the model was reasonable, and its results showed that economic and landscape factors had significant negative impacts on runoff changes, while natural factors had positive impacts on runoff changes, with path coefficients of −0.210, −0.131, and 0.367, respectively. Meanwhile, this study also identified two potential indirect impact pathways, i.e., the economic factors had an indirect negative impact on runoff by changing the distribution of landscapes, and the natural factors had indirect negative impacts on runoff by influencing economic activities, reflecting the complex interactions among economic activities, landscape distribution, and natural factors in influencing surface runoff. This study provides a research framework and methodology for quantitatively modeling surface runoff and the analysis of influencing factors in watersheds, contributing to a deeper scientific understanding of long-term runoff changes and the contribution of their drivers.
Three-Month Follow-Up of the Post-COVID Syndrome after Admission to a Specialised Post-COVID Centre—A Prospective Study Focusing on Mental Health with Patient Reported Outcome Measures (PROMs)
Authors: Schäfer Isabel Cecil , Krehbiel Johannes , Adler Werner , Borho Andrea , Herold Regina , Greiner Brigitte , Reuner Miriam , Morawa Eva , Erim Yesim
Published: August 2024

Background and objective: The impairments and duration of PASC (post-acute sequelae of COVID-19) symptoms in mental health have, to date, not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course. Methods: The mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID Syndrome Score), depression (Patient Health Questionnaire-9), somatic symptoms (Patient Health Questionnaire-15), anxiety (Generalized Anxiety Disorder-7), fatigue (Fatigue Severity Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional Malaise Screening) was conducted in the home environment. Results: In total, 80% of patients experienced severe PASC at follow-up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% of patients, respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained at an unchanged high level. The risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre. Conclusions: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for the mental health implications of PASC is needed for the planning of health services and disease prevention.
The Governance of Traffic Noise Impacting Pedestrian Amenities in Melbourne Australia: A Critical Policy Review
Authors: O’Reilly David , White Marcus , Langenheim Nano , Alambeigi Pantea
Published: August 2024

By identifying a unified aim of Federal, State, and Local government authorities to deliver healthier, more liveable urban spaces and enable walkable neighbourhoods in Melbourne, Australia, questions emerge regarding noise data collection methods and the policies that aim to protect pedestrian areas from potential increases in urban traffic noise. It highlights a missed opportunity to develop strategies that provide explicit guidance for designing more compact urban forms without diminishing pedestrian amenities. This study investigates the governance of traffic-induced noise pollution and its impact on pedestrian amenities in Melbourne, Australia. It aims to identify the government bodies best positioned to protect pedestrians from noise pollution and evaluate the strategic justification for reducing traffic noise to enhance urban walkability. This research employs a semi-systematic policy selection method and a hybrid critique and review method to evaluate the multidisciplinary governance frameworks engaged in the management and mitigation of traffic noise in Melbourne. Key findings reveal that while traffic noise poses significant health risks, current policies overlook its impact on pedestrian amenities in urban areas. This study emphasises the benefits of qualitative and subjective noise data collection to inform policy-makers of the pedestrian aural experience and impacts. Discussion points include noise management strategies and the value of implementing metropolitan-scale noise-mapping to illustrate the impact of noise rather than quantities of sound. The conclusions demonstrate that there is strategic justification for managing traffic-induced noise pollution to protect pedestrian areas within international, federal, and state government policies and implicit rationale at a local level.
Grid Density Algorithm-Based Second-Hand Housing Transaction Activity and Spatio-Temporal Characterization: The Case of Shenyang City, China
Authors: Ren Jiaqiang , Gao Xiaomeng
Published: August 2024

Second-hand housing transactions constitute a significant segment of the real estate market and are vital for its robust development. The dynamics of these transactions mirror the housing preferences of buyers, and their spatial and temporal analysis elucidates evolving market patterns and buyer behavior. This study introduces an innovative grid density clustering algorithm, dubbed the RScan algorithm, which integrates Bayesian optimization with grid density techniques. This composite methodology is employed to assess clustering outcomes, optimize hyperparameters, and facilitate detailed visualization and analysis of transaction activity across various regions. Focusing on Shenyang, a major urban center in Northeast China, the research spans from 2018 to 2023, exploring the second-hand housing transaction activity and its spatio-temporal attributes. The results reveal temporal fluctuations in transaction intensity across different Shenyang regions, although core areas of high activity remain constant. These regions display a heterogeneous pattern of irregularly stepped and clustered distributions, with a notable absence of uniformly high-activity zones. This study pioneers a novel methodological framework for investigating second-hand housing transactions, offering crucial insights for market development and policy formulation in Shenyang.
Isochrone-Based Accessibility Analysis of Pre-Hospital Emergency Medical Facilities: A Case Study of Central Districts of Beijing
Authors: Zhao Yuan , Zhou Ying
Published: August 2024

Pre-hospital emergency medical service (PHEMS) is critical for the treatment outcomes of life-threatening injuries and time-sensitive illnesses. Response time, influenced by traffic conditions and the site planning of pre-hospital emergency medical facilities (PHEMFs), is the main indicator for evaluating PHEMS. In 2020, the Beijing government released the “Special Plan for Spatial Layout of Pre-hospital Emergency Medical Facilities in Beijing (2020–2022)”. This paper evaluates the functional efficiency and spatial equity of this plan within Beijing’s central six districts using isochrone measures to assess the accessibility of the planned PHEMFs. The isochrone coverages of the area and population were calculated, and the temporal-spatial characteristics of isochrones were concluded. The analysis revealed that while the current planning meets several objectives, challenges in service availability and equity persist. Although 10-min isochrone coverage was high, 8-min coverage was insufficient, particularly during peak hours. This highlights gaps in service accessibility that necessitate additional emergency stations in underserved areas. The current planning approach leads to significant overlap at administrative boundaries, causing service oversupply and increased costs, which calls for a city-wide planning perspective that breaks administrative boundaries to optimize resource allocation. Traffic conditions significantly impact service coverage, with congestion reducing coverage in central areas and better coverage near traffic hubs. Future planning should strategically place stations based on traffic patterns and population distribution to enhance emergency medical service accessibility and equity in urban areas.
Morphographic Changes in the Electrocardiogram of Colossoma macropomum Caused by Exposure to Manganese
Authors: Nascimento Lorena Meirelis do , dos Santos Murilo Farias , Paz Clarissa Araújo da , de Araújo Daniella Bastos , Ferreira Rayllan da Cunha , Deiga Yris da Silva , de Souza Luana Vasconcelos , Câmara Tays Mata , dos Santos Rodrigo Gonçalves , Barbosa Anara de Sousa , Hamoy Maria Klara Otake , do Amaral Anthony Lucas Gurgel , Eiró-Quirino Luciana , Cabral Tárcio dos Santos , da Silva Maria Adrina Paixão de Souza , Muto Nilton Akio , Hamoy Moisés
Published: August 2024

Manganese (Mn2+) is an abundant chemical element in the earth’s crust and is present in soil, water, and industrial environments, including mining, welding, and battery manufacturing. Manganese (Mn) is an essential metal needed as a cofactor for many enzymes to maintain proper biological functions. Excessive exposure to Mn in high doses can result in a condition known as manganism, which results in disorders of the neurological, cardiac, and pulmonary systems. The aim of this study was to assess cardiac susceptibility to manganese intoxication in Colossoma macropomum subjected to a fixed concentration of 4 mg/mL for a period of up to 96 h. This study used 45 Tambaquis (30.38 ± 3.5 g) divided into five groups of 9 animals/treatment. The treated groups were exposed to the manganese concentration for a period of 24, 48, 72, and 96 h, after which the animals’ ECGs were recorded, showing heart rate, R-R interval, P-Q interval, QRS complex duration and S-T interval. The results showed that cardiac activity decreased as the contact time increased, with an increase in the P-Q and S-T intervals. This indicates that the breakdown of circulatory homeostasis in these animals was caused by contact time with manganese.
High-Frequency Imaging Reveals Synchronised Delta- and Theta-Band Ca2+ Oscillations in the Astrocytic Soma In Vivo
Authors: Péter Márton , Héja László
Published: August 2024

One of the major breakthroughs of neurobiology was the identification of distinct ranges of oscillatory activity in the neuronal network that were found to be responsible for specific biological functions, both physiological and pathological in nature. Astrocytes, physically coupled by gap junctions and possessing the ability to simultaneously modulate the functions of a large number of surrounding synapses, are perfectly positioned to introduce synchronised oscillatory activity into the neural network. However, astrocytic somatic calcium signalling has not been investigated to date in the frequency ranges of common neuronal oscillations, since astrocytes are generally considered to be slow responders in terms of Ca2+ signalling. Using high-frequency two-photon imaging, we reveal fast Ca2+ oscillations in the soma of astrocytes in the delta (0.5–4 Hz) and theta (4–8 Hz) frequency bands in vivo in the rat cortex under ketamine–xylazine anaesthesia, which is known to induce permanent slow-wave sleep. The high-frequency astrocytic Ca2+ signals were not observed under fentanyl anaesthesia, excluding the possibility that the signals were introduced by motion artefacts. We also demonstrate that these fast astrocytic Ca2+ signals, previously considered to be exclusive to neurons, are present in a large number of astrocytes and are phase synchronised at the astrocytic network level. We foresee that the disclosure of these high-frequency astrocytic signals may help with understanding the appearance of synchronised oscillatory signals and may open up new avenues of treatment for neurological conditions characterised by altered neuronal oscillations.
Disclosing the Novel Protective Mechanisms of Ocrelizumab in Multiple Sclerosis: The Role of PKC Beta and Its Down-Stream Targets
Authors: Campagnoli Lucrezia Irene Maria , Ahmad Lara , Marchesi Nicoletta , Greco Giacomo , Boschi Federica , Masi Francesco , Mallucci Giulia , Bergamaschi Roberto , Colombo Elena , Pascale Alessia
Published: August 2024

Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCβII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCβII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression.
Loss-of-Function Variants in SUPT5H as Modifying Factors in Beta-Thalassemia
Authors: Harteveld Cornelis L. , Achour Ahlem , Fairuz Mohd Hasan Nik Fatma , Legebeke Jelmer , Arkesteijn Sandra J. G. , Huurne Jeanet ter , Verschuren Maaike , Bhagwandien-Bisoen Sharda , Schaap Rianne , Vijfhuizen Linda , Idrissi Hakima el , Babbs Christian , Higgs Douglas R. , Koopmann Tamara T. , Vrettou Christina , Traeger-Synodinos Joanne , Baas Frank
Published: August 2024

It is well known that modifiers play a role in ameliorating or exacerbating disease phenotypes in patients and carriers of recessively inherited disorders such as sickle cell disease and thalassemia. Here, we give an overview of the literature concerning a recently described association in carriers of SUPT5H Loss-of-Function variants with a beta-thalassemia-like phenotype including the characteristic elevated levels of HbA2. That SUPT5H acts as modifier in beta-thalassemia carriers became evident from three reported cases in whom combined heterozygosity of SUPT5H and HBB gene variants was observed to resemble a mild beta-thalassemia intermedia phenotype. The different SUPT5H variants and hematologic parameters reported are collected and reviewed to provide insight into the possible effects on hematologic expression, as well as potential disease mechanisms in carriers and patients.
Biomarkers Identification in the Microenvironment of Oral Squamous Cell Carcinoma: A Systematic Review of Proteomic Studies
Authors: Pomella Silvia , Melaiu Ombretta , Cifaldi Loredana , Bei Roberto , Gargari Marco , Campanella Vincenzo , Barillari Giovanni
Published: August 2024

An important determinant for oral squamous cell carcinoma (OSCC) onset and outcome is the composition of the tumor microenvironment (TME). Thus, the study of the interactions occurring among cancer cells, immune cells, and cancer-associated fibroblasts within the TME could facilitate the understanding of the mechanisms underlying OSCC development and progression, as well as of its sensitivity or resistance to the therapy. In this context, it must be highlighted that the characterization of TME proteins is enabled by proteomic methodologies, particularly mass spectrometry (MS). Aiming to identify TME protein markers employable for diagnosing and prognosticating OSCC, we have retrieved a total of 119 articles spanning 2001 to 2023, of which 17 have passed the selection process, satisfying all its criteria. We have found a total of 570 proteins detected by MS-based proteomics in the TME of OSCC; among them, 542 are identified by a single study, while 28 are cited by two or more studies. These 28 proteins participate in extracellular matrix remodeling and/or energy metabolism. Here, we propose them as markers that could be used to characterize the TME of OSCC for diagnostic/prognostic purposes. Noteworthy, most of the 28 individuated proteins share one feature: being modulated by the hypoxia that is present in the proliferating OSCC mass.
A Cationic Zn-Phthalocyanine Turns Alzheimer’s Amyloid β Aggregates into Non-Toxic Oligomers and Inhibits Neurotoxicity in Culture
Authors: Sheikh Abdullah Md. , Tabassum Shatera , Yano Shozo , Abdullah Fatema Binte , Wang Ruochen , Ikeue Takahisa , Nagai Atsushi
Published: August 2024

Amyloid β peptide (Aβ) aggregation and deposition are considered the main causes of Alzheimer’s disease. In a previous study, we demonstrated that anionic Zn-phthalocyanine (ZnPc) can interact with the Aβ peptide and inhibit the fibril-formation process. However, due to the inability of anionic ZnPc to cross the intact blood–brain barrier, we decided to explore the interaction of cationic methylated Zn-phthalocyanine (cZnPc) with the peptide. Using a ThT fluorescence assay, we observed that cZnPc dose-dependently and time-dependently inhibited Aβ1-42 fibril levels under in vitro fibril-formation conditions. Electron microscopy revealed that it caused Aβ1-42 peptides to form small aggregates. Western blotting and dot immunoblot oligomer experiments demonstrated that cZnPc increased rather than decreased the levels of oligomers from the very early stages of incubation. A binding assay confirmed that cZnPc could bind with the peptide. Docking simulations indicated that the oligomer species of Aβ1-42 had a higher ability to interact with cZnPc. ANS fluorescence assay results indicated that cZnPc did not affect the hydrophobicity of the peptide. However, cZnPc significantly increased intrinsic tyrosine fluorescence of the peptide after 8 h of incubation in fibril-formation conditions. Importantly, cell culture experiments demonstrated that cZnPc did not exhibit any toxicity up to a concentration of 10 µM. Instead, it protected a neuronal cell line from Aβ1-42-induced toxicity. Thus, our results suggest that cZnPc can affect the aggregation process of Aβ1-42, rendering it non-toxic, which could be crucial for the therapy of Alzheimer’s disease.
Physiological, Metabolome and Gene Expression Analyses Reveal the Accumulation and Biosynthesis Pathways of Soluble Sugars and Amino Acids in Sweet Sorghum under Osmotic Stresses
Authors: Cui Yan-Nong , Yan Shi-Jie , Zhang Yi-Nuo , Wang Rong , Song Le-Ling , Ma Yue , Guo Huan , Yang Pei-Zhi
Published: August 2024

Water scarcity is a major environmental constraint on plant growth in arid regions. Soluble sugars and amino acids are essential osmolytes for plants to cope with osmotic stresses. Sweet sorghum is an important bioenergy crop and forage with strong adaptabilities to adverse environments; however, the accumulation pattern and biosynthesis basis of soluble sugars and amino acids in this species under osmotic stresses remain elusive. Here, we investigated the physiological responses of a sweet sorghum cultivar to PEG-induced osmotic stresses, analyzed differentially accumulated soluble sugars and amino acids after 20% PEG treatment using metabolome profiling, and identified key genes involved in the biosynthesis pathways of soluble sugars and amino acids using transcriptome sequencing. The results showed that the growth and photosynthesis of sweet sorghum seedlings were significantly inhibited by more than 20% PEG. After PEG treatments, the leaf osmotic adjustment ability was strengthened, while the contents of major inorganic osmolytes, including K+ and NO3−, remained stable. After 20% PEG treatment, a total of 119 and 188 differentially accumulated metabolites were identified in the stems and leaves, respectively, and the accumulations of soluble sugars such as raffinose, trehalose, glucose, sucrose, and melibiose, as well as amino acids such as proline, leucine, valine, serine, and arginine were significantly increased, suggesting that these metabolites should play key roles in osmotic adjustment of sweet sorghum. The transcriptome sequencing identified 1711 and 4978 DEGs in the stems, as well as 2061 and 6596 DEGs in the leaves after 20% PEG treatment for 6 and 48 h, respectively, among which the expressions of genes involved in biosynthesis pathways of sucrose (such as SUS1, SUS2, etc.), trehalose (including TPS6), raffinose (such as RAFS2 and GOLS2, etc.), proline (such as P5CS2 and P5CR), leucine and valine (including BCAT2), and arginine (such as ASS and ASL) were significantly upregulated. These genes should be responsible for the large accumulation of soluble sugars and amino acids under osmotic stresses. This study deepens our understanding of the important roles of individual soluble sugars and amino acids in the adaptation of sweet sorghum to water scarcity.