bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Review of Climate Change Impacts on Groundwater Resources: A Focus on the Current Status, Future Possibilities, and Role of Simulation Models
Authors: Davamani Veeraswamy , John Joseph Ezra , Poornachandhra Chidamparam , Gopalakrishnan Boopathi , Arulmani Subramanian , Parameswari Ettiyagounder , Santhosh Anandhi , Srinivasulu Asadi , Lal Alvin , Naidu Ravi
Published: January 2024

The Earth’s water resources, totalling 1.386 billion cubic kilometres, predominantly consist of saltwater in oceans. Groundwater plays a pivotal role, with 99% of usable freshwater supporting 1.5–3 billion people as a drinking water source and 60–70% for irrigation. Climate change, with temperature increases and altered precipitation patterns, directly impacts groundwater systems, affecting recharge, discharge, and temperature. Hydrological models are crucial for assessing climate change effects on groundwater, aiding in management decisions. Advanced hydrological models, incorporating data assimilation and improved process representation, contribute to understanding complex systems. Recent studies employ numerical models to assess climate change impacts on groundwater recharge that could help in the management of groundwater. Groundwater vulnerability assessments vary with the spatial and temporal considerations, as well as assumptions in modelling groundwater susceptibility. This review assesses the vulnerability of groundwater to climate change and stresses the importance of accurate assessments for sustainable water resource management. It highlights challenges in assumptions related to soil and aquifer properties, multiple stressors, adaptive capacity, topography and groundwater contamination processes, gradual sea level rise scenarios, and realistic representations of the region of study. With the advancements in hydrological modelling, including the integration of uncertainty quantification and remote sensing data, artificial intelligence could assist in the efforts to improve models for assessing the impacts of climate change on hydrological modelling.
Objective and Subjective Assessment of Music Perception and Musical Experiences in Young Cochlear Implant Users
Authors: Calvino Miryam , Zuazua-González Alejandro , Gavilán Javier , Lassaletta Luis
Published: January 2024

For many individuals, music has a significant impact on the quality and enjoyability of life. Cochlear implant (CI) users must cope with the constraints that the CI imposes on music perception. Here, we assessed the musical experiences of young CI users and age-matched controls with normal hearing (NH). CI users and NH peers were divided into subgroups according to age: children and adolescents. Participants were tested on their ability to recognize vocal and instrumental music and instruments. A music questionnaire for pediatric populations (MuQPP) was also used. CI users and NH peers identified a similar percentage of vocal music. CI users were significantly worse at recognizing instruments (p < 0.05) and instrumental music (p < 0.05). CI users scored similarly to NH peers on the MuQPP, except for the musical frequency domain, where CI users in the children subgroup scored higher than their NH peers (p = 0.009). For CI users in the children subgroup, the identification of instrumental music was positively correlated with music importance (p = 0.029). Young CI users have significant deficits in some aspects of music perception (instrumental music and instrument identification) but have similar scores to NH peers in terms of interest in music, frequency of music exposure, and importance of music.
Maternal Effects of Habitats Induce Stronger Salt Tolerance in Early-Stage Offspring of Glycyrrhiza uralensis from Salinized Habitats Compared with Those from Non-Salinized Habitats
Authors: Gu Junjun , Yao Shaoxuan , Ma Miao
Published: January 2024

(1) Wild Glycyrrhiza uralensis Fisch (licorice) seeds from different habitats are often mixed for cultivation. However, differences in the responses of seeds from different habitats to salt at the early-stage offspring stage are unclear. (2) Our objective was to evaluate the salt tolerance of G. uralensis germplasms by comparing differences in seed germination and seedling vigor in salinized (abandoned farmland and meadow) and non-salinized (corn farmland edge) soil habitats under different sodium chloride (NaCl) concentrations. (3) The germination rates and germination indexes of seeds from the two salinized habitats with 0–320 mmol·L−1 NaCl were higher and their germination initiation times were earlier. Only seeds from salinized habitats were able to elongate their germs at 240 mmol·L−1 NaCl. Seedlings from salinized habitats had higher fresh weights and relative water contents, while they exhibited lower accumulation of malondialdehyde and less cell electrolyte leakages. Under NaCl treatment, seedlings from the salinized habitats displayed higher superoxide dismutase, catalase, and peroxidase (SOD, CAT, and POD) activities and lower superoxide anion and hydrogen peroxide (O2− and H2O2) contents. Their comprehensive scores showed that the vigor of licorice seeds from salinized habitats was higher. (4) The salt tolerances of different wild G. uralensis seeds were different, and the offspring of licorice from salinized habitats had stronger early-stage salt tolerances.
Emerging Therapeutic Potential of Polyphenols from Geranium sanguineum L. in Viral Infections, Including SARS-CoV-2
Authors: Abarova Silviya , Alexova Ralitza , Dragomanova Stela , Solak Ayten , Fagone Paolo , Mangano Katia , Petralia Maria Cristina , Nicoletti Ferdinando , Kalfin Reni , Tancheva Lyubka
Published: January 2024

The existing literature supports the anti-inflammatory, antioxidant, and antiviral capacities of the polyphenol extracts derived from Geranium sanguineum L. These extracts exhibit potential in hindering viral replication by inhibiting enzymes like DNA polymerase and reverse transcriptase. The antiviral properties of G. sanguineum L. seem to complement its immunomodulatory effects, contributing to infection resolution. While preclinical studies on G. sanguineum L. suggest its potential effectiveness against COVID-19, there is still a lack of clinical evidence. Therefore, the polyphenols extracted from this herb warrant further investigation as a potential alternative for preventing and treating COVID-19 infections.
Meteorin-like Protein and Zonulin in Polycystic Ovary Syndrome: Exploring Associations with Obesity, Metabolic Parameters, and Inflammation
Authors: Kabakchieva Plamena , Gateva Antoaneta , Velikova Tsvetelina , Georgiev Tsvetoslav , Yamanishi Kyosuke , Okamura Haruki , Kamenov Zdravko
Published: January 2024

Objective: Polycystic ovary syndrome (PCOS) is a prevalent hormonal and metabolic disorder, wherein the adipose tissue and gut microbiome have been demonstrated to contribute to its pathogenesis. This study aims to assess the concentrations of the adipokine, meteorin-like protein (Metrnl) and the protein, zonulin, related to intestine permeability, in individuals with PCOS with a particular emphasis on their relationship with obesity, clinical manifestations, hormonal profiles, and metabolic parameters. Methods: A cohort comprising 58 women with PCOS, classified according to the Rotterdam criteria, was enrolled. The study also considered age, body mass index (BMI), and ethnicity-matched controls (n = 30). Comprehensive anthropometric and clinical evaluations, hormonal assays, and biochemical analyses were conducted during the follicular phase. Subsequent subgroup analyses were executed within the PCOS cohort based on waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum concentrations of Metrnl and zonulin were quantified via the enzyme-linked immunosorbent assay (ELISA) technique. Results: The Metrnl and zonulin levels exhibited no significant disparity between PCOS patients and controls. Nevertheless, within the entire participant cohort and the PCOS group exclusively, overweight/obese participants demonstrated higher Metrnl concentrations relative to their normal-weight counterparts (p < 0.001, p = 0.001, respectively). Furthermore, higher Metrnl concentrations were identified in subgroups characterized by high WHtR and IR in comparison to those with low WHtR (p = 0.001) and without IR (p = 0.001), respectively. A correlation emerged between Metrnl levels and various anthropometric and metabolic parameters, as well as sex-hormone-binding globulin (SHBG) and interleukin-18 (IL-18) within the PCOS group. Multiple linear regression analysis identified HOMA-IR as the sole independent predictor of Metrnl levels. Conclusion: While Metrnl and zonulin levels do not serve as diagnostic indicators of PCOS, elevated Metrnl concentrations exhibited robust associations with proinflammatory and metabolic irregularities within the PCOS population.
Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry
Authors: Antza Christina , Rizos Christos V. , Kotsis Vasileios , Liamis George , Skoumas Ioannis , Rallidis Loukianos , Garoufi Anastasia , Kolovou Genovefa , Tziomalos Konstantinos , Skalidis Emmanouil , Sfikas George , Doumas Michalis , Lambadiari Vaia , Anagnostis Panagiotis , Stamatelopoulos Kimon , Anastasiou Georgia , Koutagiar Iosif , Kiouri Estela , Kolovou Vana , Polychronopoulos Georgios , Zacharis Evangelos , Koumaras Charalambos , Boutari Chrysoula , Milionis Haralampos , Liberopoulos Evangelos
Published: January 2024

Background: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. Results: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). Conclusions: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.
Novel Serum Biomarkers for Patients with Allergic Asthma Phenotype
Authors: Palacionyte Jolita , Januskevicius Andrius , Vasyle Egle , Rimkunas Airidas , Bajoriuniene Ieva , Vitkauskiene Astra , Miliauskas Skaidrius , Malakauskas Kestutis
Published: January 2024

In distinguishing the allergic asthma (AA) phenotype, it has been identified that specific biomarkers could assist; however, none of them are considered ideal. This study aimed to analyze three groups of biologically active substances in the serum. Twenty steroid-free AA patients, sensitized to Dermatophagoides pteronyssinus, and sixteen healthy subjects (HSs) were enrolled in this study. Blood samples were collected from all patients. Additionally, all AA patients underwent a bronchial allergen challenge (BAC) with Dermatophagoides pteronyssinus, all of which were positive, and blood samples were collected again 24 h later. The concentrations of ten biologically active substances were measured in the serum samples, using enzyme-linked immunosorbent assay (ELISA) and the Luminex® 100/200™ System technology for bead-based multiplex and singleplex immunoassays. Descriptive and analytical statistical methods were used. A p-value of 0.05 or lower was considered statistically significant. The soluble interleukin 5 receptor subunit alpha (sIL-5Rα) and thioredoxin 1 (TRX1) concentrations were significantly increased, whereas those of tyrosine-protein kinase Met (MET), pentraxin 3 (PTX3), and I C-telopeptide of type I collagen (ICTP) were decreased in the AA group compared with the HS group. A significant positive correlation was noted for sIL-5Rα with fractional exhaled nitric oxide (FeNO), blood eosinophil (EOS) count, and total immunoglobulin E (IgE) levels, and a negative correlation was noted with forced expiratory volume in 1 s (FEV1). Moreover, PTX3 showed negative correlations with blood EOS count and total IgE levels, whereas ICTP exhibited a negative correlation with the blood EOS count. In conclusion, this study demonstrated that the serum concentrations of MET, PTX3, TRX1, ICTP, and particularly sIL-5Rα could potentially serve as biomarkers of the AA phenotype.
Maternal Exposure to Endocrine-Disrupting Chemicals: Analysis of Their Impact on Infant Gut Microbiota Composition
Authors: Vacca Mirco , Calabrese Francesco Maria , Loperfido Federica , Maccarini Beatrice , Cerbo Rosa Maria , Sommella Eduardo , Salviati Emanuela , Voto Luana , De Angelis Maria , Ceccarelli Gabriele , Di Napoli Ilaria , Raspini Benedetta , Porri Debora , Civardi Elisa , Garofoli Francesca , Campiglia Pietro , Cena Hellas , De Giuseppe Rachele
Published: January 2024

Endocrine disruptors (EDCs) are chemicals that interfere with the endocrine system. EDC exposure may contribute to the development of obesity, type 2 diabetes, and cardiovascular diseases by impacting the composition of an infant’s gut microbiota during the first 1000 days of life. To explore the relationship between maternal urinary levels of Bisphenol-A and phthalates (UHPLC-MS/MS), and the composition of the infant gut microbiota (16S rDNA) at age 12 months (T3) and, retrospectively, at birth (T0), 1 month (T1), and 6 months (T2), stool samples from 20 infants breastfed at least once a day were analyzed. Metataxonomic bacteria relative abundances were correlated with EDC values. Based on median Bisphenol-A levels, infants were assigned to the over-exposed group (O, n = 8) and the low-exposed group (B, n = 12). The B-group exhibited higher gut colonization of the Ruminococcus torques group genus and the O-group showed higher abundances of Erysipelatoclostridium and Bifidobacterium breve. Additionally, infants were stratified as high-risk (HR, n = 12) or low-risk (LR, n = 8) exposure to phthalates, based on the presence of at least three phthalates with concentrations exceeding the cohort median values; no differences were observed in gut microbiota composition. A retrospective analysis of gut microbiota (T0–T2) revealed a disparity in β-diversity between the O-group and the B-group. Considering T0–T3, the Linear Discriminant Effect Size indicated differences in certain microbes between the O-group vs. the B-group and the HR-group vs. the LR-group. Our findings support the potential role of microbial communities as biomarkers for high EDC exposure levels. Nevertheless, further investigations are required to deeply investigate this issue.
Neurophysiological Parameters Influencing Sleep–Wake Discrepancy in Insomnia Disorder: A Preliminary Analysis on Alpha Rhythm during Sleep Onset
Authors: Berra Francesca , Fasiello Elisabetta , Zucconi Marco , Casoni Francesca , De Gennaro Luigi , Ferini-Strambi Luigi , Galbiati Andrea
Published: January 2024

Sleep state misperception (SSM) is a common issue in insomnia disorder (ID), causing a discrepancy between objective and subjective sleep/wake time estimation and increased daytime impairments. In this context, the hyperarousal theory assumes that sustained central nervous system activation contributes to the SSM. This study investigates factors influencing SSM during sleep latency (SL) and total sleep time (TST). Objective polysomnographic sleep variables (the alpha density index, latency-to-sleep stages and the first K-complex, and Rapid Eye Movement (REM) arousal density) and subjective sleep indices, taken from sleep diaries, were analyzed in 16 ID patients. Correlation analyses revealed a positive association between the degree of SL misperception (SLm) and the percentage of epochs that contained a visually scored stereotyped alpha rhythm during objective SL. A regression analysis showed that the REM arousal density and alpha density index significantly predicted TST misperception (TSTm). Furthermore, the degree of SLm was associated with an increased probability of transitioning from stage 1 of non-REM sleep to wakefulness during subjective SL. These findings support the role of hyperarousal in SSM and highlight the importance of alpha activity in unravelling the heterogeneous underpinnings of SSM.
Looming Angry Faces: Preliminary Evidence of Differential Electrophysiological Dynamics for Filtered Stimuli via Low and High Spatial Frequencies
Authors: Yu Zhou , Moses Eleanor , Kritikos Ada , Pegna Alan J.
Published: January 2024

Looming motion interacts with threatening emotional cues in the initial stages of visual processing. However, the underlying neural networks are unclear. The current study investigated if the interactive effect of threat elicited by angry and looming faces is favoured by rapid, magnocellular neural pathways and if exogenous or endogenous attention influences such processing. Here, EEG/ERP techniques were used to explore the early ERP responses to moving emotional faces filtered for high spatial frequencies (HSF) and low spatial frequencies (LSF). Experiment 1 applied a passive-viewing paradigm, presenting filtered angry and neutral faces in static, approaching, or receding motions on a depth-cued background. In the second experiment, broadband faces (BSF) were included, and endogenous attention was directed to the expression of faces. Our main results showed that regardless of attentional control, P1 was enhanced by BSF angry faces, but neither HSF nor LSF faces drove the effect of facial expressions. Such findings indicate that looming motion and threatening expressions are integrated rapidly at the P1 level but that this processing relies neither on LSF nor on HSF information in isolation. The N170 was enhanced for BSF angry faces regardless of attention but was enhanced for LSF angry faces during passive viewing. These results suggest the involvement of a neural pathway reliant on LSF information at the N170 level. Taken together with previous reports from the literature, this may indicate the involvement of multiple parallel neural pathways during early visual processing of approaching emotional faces.
Does Leader–Member Exchange (LMX) Ambivalence Influence Employees’ Constructive Deviance?
Authors: Liu Zhen , Liu Qunying
Published: January 2024

The ambivalent experience of superior–subordinate relationships is widespread in organisations and has gradually become an important factor influencing employees to actively engage in extra-role behaviours. However, employees’ constructive deviance is extremely important for organisational development as they are important extra-role behaviours for organisational innovation and change. Owing that academic research on the antecedents of employees’ constructive extra-role behaviours has lacked attention to individual emotional variables such as the leader–member exchange ambivalence, by drawing on self-control resource theory and social cognitive theory, this study examined the effects of leader–member exchange ambivalence on employees’ constructive deviance, as well as the role of ego depletion and role-breadth self-efficacy. Based on a two-point questionnaire survey of 332 employees from different industries in China, the study tested hypotheses with SPSS 27 and AMOS 27 and found that the more leader–member exchange ambivalence, the less likely they were to engage in employees’ constructive deviance, leader–member exchange ambivalence affected employees’ constructive deviance through ego depletion, and when role-breadth self-efficacy is high, the lower the ego depletion of employees with leader–member exchange ambivalence, the more likely they are to engage in employees’ constructive deviance. This study is intended to guide organisations to pay attention to the problem of individual internal conflict arising from superior–subordinate relationships, to remove the barriers to constructive transgression by individuals, and to truly exploit the innovative capacity of individual organisations. The study suggests that managers should pay attention to the negative effects of employees’ perceived ambivalent experiences of supervisor-subordinate relationships, maintain consistency, and build positive social exchange relationships with their employees. Organisations should strengthen the training of leaders and employees to eliminate the serious internal attrition that organisations face from social network relationships. And employees should face the limitations of resources and reduce dependence on the leader–member exchange relationship as the dependence for their work attitudes and behaviours.
Relationship between Athletes’ Big Five Model of Personality and Athletic Performance: Meta-Analysis
Authors: Yang Ji-Hye , Yang Hye Jin , Choi Chulhwan , Bum Chul-Ho
Published: January 2024

Academic interest in athletic performance is ongoing. To examine the correlation between athletic performance and athletes’ personality types, data extraction in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was completed in October 2021, and a meta-analysis was performed using 180 data from 18 selected papers using the “meta” package version 4.8-4 of R Studio 3.3.3. As a result, these selected studies proved to have reliable quality in proceeding with this study via quality assessment. The overall effect of personality on athletic performance (AP) was ESr = 0.124, p < 0.01. Furthermore, only conscientiousness (ESr = 0.178, p < 0.001) and extroversion (ESr = 0.145, p < 0.01), among the five personality types, showed statistically significant results, and these two personality types had a positive correlation with performance. In the publication bias test, this study found that (a) agreeableness had a publication bias; but, with an additional test using trim-and-fill, (b) the effect was not significant enough to be considered. In addition, the analysis of the moderating effects was conducted in four aspects, and all moderating effect analyses showed statistically significant differences between the groups, demonstrating the heterogeneity of this study. Therefore, this study found a significant relationship between personality and athletic performance and showed the importance of conscientiousness and extroversion.
On the Performance of Solar Thermophotovoltaics (STPVs) and Wavelength-Selective Thermophotovoltaics (TPVs): Case Study of a High-Rise Residential Building in a Hot and Semi-Arid Climate
Authors: Safavi Maryam , Khoshbakht Maryam
Published: January 2024

Utilizing integrated solar systems and renewable energy sources has the potential to not only decrease the CO2 emissions of buildings but also provide access to more affordable energy alternatives compared to fossil fuels, especially considering the recent rise in prices. Nevertheless, many designers and project decision makers are hesitant to embrace solar technologies due to the uncertainty surrounding the cost–benefit balance. This paper presents a case study of the design process, highlighting the energy-saving and cost–benefit aspects of a solar façade featuring solar thermophotovoltaics (STPVs) and wavelength-selective thermophotovoltaics (TPVs) in a high-rise residential building situated in the semi-arid climate of Tehran, Iran. The simulation methodology consists of EnergyPlus Engines in Rhino, along with the Ladybug and Honeybee plugins throughout the solar façade design process. The solar façade incorporating STPV yielded energy savings of 25 kWh per square meter, marking a 34% reduction compared to a standard façade. In contrast, the TPV demonstrated energy savings of 35 kWh per square meter, indicating a 48% decrease in energy consumption compared to a regular façade. This research indicates that, particularly in semi-arid climatic conditions, TPV systems exhibit a superior performance when integrated into the façades of high-rise structures; yet, due to the low electricity prices in the region, neither STPVs nor TPVs are financially viable. The study contributes to raising awareness, fostering technological innovations, influencing policy discussions, and promoting the adoption of sustainable practices in the field of energy and architecture.
Assessment of the Historical Gardens and Buildings Lighting Interaction through Virtual Reality: The Case of Casita de Arriba de El Escorial
Authors: Gargiulo Martina , Carleo Davide , Ciampi Giovanni , Masullo Massimiliano , Chìas Navarro Pilar , Maliqari Andrea , Scorpio Michelangelo
Published: January 2024

Green areas and parks are places where people’s quality of life improves, places of recreation and relaxation, in which to carry out various social activities. Among these, the historic gardens represent the union between green areas and historic architecture. Light is considered one of the main factors influencing the perception of such spaces at night; therefore, lighting solutions should be properly balanced. Immersive virtual reality is a tool that allows for lighting design management from different viewpoints. This study investigates how the lighting of a monumental garden affects people’s perception of its architecture at night. With this aim, a detailed 3D model of the western part of Escorial’s monumental complex in Spain was built in DIALux evo 11 and Unreal Engine 4.27 and used to propose six different lighting scenarios. Participants viewed the scenarios through a head-mounted display and provided subjective feedback on the perceived light strength of the environment and architecture. Results highlight that illuminating surrounding areas affects the environment and building perception, as well as the order in which elements capture observer attention. In particular, lit elements between the observer and the façade can reduce façade importance.
Seismic Behavior of Demountable Self-Lock Joint for Middle Column Connection in Modular Steel Construction
Authors: Dai Xiao-Meng , Zong Liang , Ding Yang , Zhang Hao-Wen , Shi Feng-Wei
Published: January 2024

The use of modular steel construction (MSC) achieves a minimum of on-site work and the potential for removability and reuse. In order to realize the overall disassembly of module buildings and the rapid off-site reconstruction after disassembly, special requirements are put forward for the joints of MSCs. The existing joints of MSCs have some problems, such as the difficulty in the erection of the joints for middle column connection and their inability to be reused. In order to solve these key technical problems, an improved version of the demountable self-locking joint is proposed based on the previous plug-in self-locking joint. For this new type of joint, a full-scale test consisting of four specimens was carried out. The results of functional tests verify that the joint has good demountability. The seismic behavior of the joint under seismic load was investigated by cyclic loading tests. Then, finite element (FE) models were developed and validated through the test results. The results of finite element parameter analysis show that joint boxes are very important to the initial stiffness of this kind of joint, but the thickness of the joint box and the diameter of the stud have little influence on the seismic behavior of the joint.
Are We Losing the Final Fight against Cancer?
Authors: Storme Guy
Published: January 2024

Despite our increasing understanding of the biology and evolution of the cancer process, it is indisputable that the natural process of cancer creation has become increasingly difficult to cure, as more mutations are found with age. It is significantly more difficult to challenge the curative method when there is heterogeneity within the tumor, as it hampers clinical and genetic categorization. With advances in diagnostic technologies and screening leading to progressive tumor shrinkage, it becomes more difficult over time to evaluate the effects of treatment on overall survival. New treatments are often authorized based on early evidence, such as tumor response; disease-free, progression-free, meta-static-free, and event-free survival; and, less frequently, based on clinical endpoints, such as overall survival or quality of life, when standard guidelines are not available to approve pharmaceuticals. These clearances usually happen quite rapidly. Although approval takes longer, relative survival demonstrates the genuine worth of a novel medication. Pressure is being applied by pharmaceutical companies and patient groups to approve “new” treatments based on one of the above-listed measures, with results that are frequently insignificantly beneficial and frequently have no impact on quality of life.
The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors
Authors: Evmorfopoulos Konstantinos , Marsitopoulos Konstantinos , Karachalios Raphael , Karathanasis Athanasios , Dimitropoulos Konstantinos , Tzortzis Vassilios , Zachos Ioannis , Vlachostergios Panagiotis J.
Published: January 2024

Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs.
Ensemble Deep Learning Model to Predict Lymphovascular Invasion in Gastric Cancer
Authors: Lee Jonghyun , Cha Seunghyun , Kim Jiwon , Kim Jung Joo , Kim Namkug , Jae Gal Seong Gyu , Kim Ju Han , Lee Jeong Hoon , Choi Yoo-Duk , Kang Sae-Ryung , Song Ga-Young , Yang Deok-Hwan , Lee Jae-Hyuk , Lee Kyung-Hwa , Ahn Sangjeong , Moon Kyoung Min , Noh Myung-Giun
Published: January 2024

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: −0.0094; AUPRC: −0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.
Outcomes in Patients with Spinal Metastases Managed with Surgical Intervention
Authors: Knapp Brendan , Govindan Ashwin , Patel Shalin S. , Pepin Kymberlie , Wu Ningying , Devarakonda Siddhartha , Buchowski Jacob M.
Published: January 2024

Background: Spinal metastases are a significant cause of morbidity in patients with advanced cancer, and management often requires surgical intervention. Although prior studies have identified factors that influence outcomes with surgery, the ability of these factors to predict outcomes remains unclear in the era of contemporary therapies, and there is a need to better identify patients who are likely to benefit from surgery. Methods: We performed a single-center, retrospective analysis to evaluate risk factors for poor outcomes in patients with spinal metastases treated with surgery. The primary outcome was mortality at 180 days. Results: A total of 128 patients were identified. Age ≥ 65 years at surgery (p = 0.0316), presence of extraspinal metastases (p = 0.0110), and ECOG performance scores >1 (p = 0.0397) were associated with mortality at 180 days on multivariate analysis. These factors and BMI ≤ 30 mg/kg2 (p = 0.0008) were also associated with worse overall survival. Conclusions: Age > 65, extraspinal metastases, and performance status scores >1 are factors associated with mortality at 180 days in patients with spinal metastases treated with surgery. Patients with these factors and BMI ≤ 30 mg/kg2 had worse overall survival. Our results support multidisciplinary discussions regarding the benefits and risks associated with surgery in patients with these risk factors.
Heparan Sulfate Modulation Affects Breast Cancer Cell Adhesion and Transmigration across In Vitro Blood–Brain Barrier
Authors: Li Yunfei , Shteyman David B. , Hachem Zeina , Ulay Afaf A. , Fan Jie , Fu Bingmei M.
Published: January 2024

The disruption of endothelial heparan sulfate (HS) is an early event in tumor cell metastasis across vascular barriers, and the reinforcement of endothelial HS reduces tumor cell adhesion to endothelium. Our recent study showed that while vascular endothelial growth factor (VEGF) greatly reduces HS at an in vitro blood–brain barrier (BBB) formed by human cerebral microvascular endothelial cells (hCMECs), it significantly enhances HS on a breast cancer cell, MDA-MB-231 (MB231). Here, we tested that this differential effect of VEGF on the HS favors MB231 adhesion and transmigration. We also tested if agents that enhance endothelial HS may affect the HS of MB231 and reduce its adhesion and transmigration. To test these hypotheses, we generated an in vitro BBB by culturing hCMECs on either a glass-bottom dish or a Transwell filter. We first quantified the HS of the BBB and MB231 after treatment with VEGF and endothelial HS-enhancing agents and then quantified the adhesion and transmigration of MB231 across the BBB after pretreatment with these agents. Our results demonstrated that the reduced/enhanced BBB HS and enhanced/reduced MB231 HS increase/decrease MB231 adhesion to and transmigration across the BBB. Our findings suggest a therapeutic intervention by targeting the HS-mediated breast cancer brain metastasis.
Attrition from Face-to-Face Pediatric Outpatient Chronic Pain Interventions: A Narrative Review and Theoretical Model
Authors: Tiong Kristen , Palmer Greta M. , Jaaniste Tiina
Published: January 2024

There is limited understanding of attrition (premature treatment withdrawal and non-completion) from pediatric chronic pain services. This narrative review aimed to summarize attrition prevalence from face-to-face pediatric outpatient chronic pain interventions, identify associated factors and develop a theoretical model to account for attrition in this setting. A comprehensive search of the published literature revealed massive variability (0–100%) in the reported attrition rates from pediatric chronic pain interventions that varied in type and format (individual vs. group, single discipline vs. interdisciplinary, psychological only vs. multiple combined interventions, of different durations). The factors associated with attrition from pediatric chronic pain programs varied between the studies: some have assessed patient sex, psychological and other comorbidities, avoidance strategies, missed schooling, family composition/tensions, caregiver catastrophizing, scheduling, caregiver leave and clinic access. A theoretical model is presented depicting youth, caregiver and service factors that may impact attrition from pediatric chronic pain interventions. Where available, literature is drawn from the pediatric chronic pain context, but also from adult chronic pain and pediatric weight management fields. The implications for research and clinical practice are discussed, including improved reporting, patient screening and targeted supports to promote intervention completion. This review contributes to a better understanding of attrition, which is crucial for optimizing pediatric chronic pain service outcomes.
Epoxyalcohol Synthase Branch of Lipoxygenase Cascade
Authors: Toporkova Yana Y. , Smirnova Elena O. , Gorina Svetlana S.
Published: January 2024

Oxylipins are one of the most important classes of bioregulators, biosynthesized through the oxidative metabolism of unsaturated fatty acids in various aerobic organisms. Oxylipins are bioregulators that maintain homeostasis at the cellular and organismal levels. The most important oxylipins are mammalian eicosanoids and plant octadecanoids. In plants, the main source of oxylipins is the lipoxygenase cascade, the key enzymes of which are nonclassical cytochromes P450 of the CYP74 family, namely allene oxide synthases (AOSs), hydroperoxide lyases (HPLs), and divinyl ether synthases (DESs). The most well-studied plant oxylipins are jasmonates (AOS products) and traumatin and green leaf volatiles (HPL products), whereas other oxylipins remain outside of the focus of researchers’ attention. Among them, there is a large group of epoxy hydroxy fatty acids (epoxyalcohols), whose biosynthesis has remained unclear for a long time. In 2008, the first epoxyalcohol synthase of lancelet Branchiostoma floridae, BfEAS (CYP440A1), was discovered. The present review collects data on EASs discovered after BfEAS and enzymes exhibiting EAS activity along with other catalytic activities. This review also presents the results of a study on the evolutionary processes possibly occurring within the P450 superfamily as a whole.
Enteral Resuscitation: A Field-Expedient Treatment Strategy for Burn Shock during Wartime and in Other Austere Settings
Authors: Jones Ian F. , Nakarmi Kiran , Wild Hannah B. , Nsaful Kwesi , Mehta Kajal , Shrestha Raslina , Roubik Daniel , Stewart Barclay T.
Published: January 2024

Burn injuries are a constant threat in war. Aspects of the modern battlefield increase the risk of burn injuries and pose challenges for early treatment. The initial resuscitation of a severely burn-injured patient often exceeds the resources available in front-line medical facilities. This stems mostly from the weight and volume of the intravenous fluids required. One promising solution to this problem is enteral resuscitation with an oral rehydration solution. In addition to being logistically easier to manage, enteral resuscitation may be able to mitigate secondary injuries to the gut related to burn shock and systemic immunoinflammatory activation. This has been previously studied in burn patients, primarily using electrolyte solutions, with promising results. Modern ORS containing sodium, potassium, and glucose in ratios that maximize gut absorption may provide additional benefits as a resuscitation strategy, both in terms of plasma volume expansion and protection of the barrier and immune functions of the gut mucosa. While enteral resuscitation is promising and should be used when other options are not available, further research is needed to refine an optimal implementation strategy.
A 12-Bit SAR ADC with Binary Search Calibration Algorithm for a Split Capacitor
Authors: Yang Je-I , Yoon Kwang Sub , Lim Hongki
Published: January 2024

This paper proposes a 12-bit SAR ADC capable of calibrating a split capacitor using a binary search technique for bio-signal processing applications. The proposed SAR ADC employs a calibration logic circuit to calibrate a split capacitor vulnerable to process variations and mismatches. The proposed foreground calibration process involves four iterations through the binary search algorithm. In this manner, the calibration speed can be increased by up to 3.75 times compared with that of the linear search calibration. The proposed SAR ADC was implemented with a CMOS 28 nm 1-poly 8-metal process. The effective layout, excluding bonding pads, occupied 939 × 450 μm. Measurement results illustrated a power consumption of 30.7 μW (analog power: 16.1 μW and digital power: 14.6 μW), INL/DNL of −1.8/1.7 LSB, and −0.7/0.7 LSB, respectively, ENoB of 10.3-bit, and a FoM of 53.7 fJ/step.
Unveiling the Spatial Distribution of Heat Demand in North-West-Europe Compiled with National Heat Consumption Data
Authors: Jüstel Alexander , Humm Elias , Herbst Eileen , Strozyk Frank , Kukla Peter , Bracke Rolf
Published: January 2024

Space and water heating for residential and commercial buildings amount to a third of the European Union’s total final energy consumption. Approximately 75% of the primary energy is still produced by burning fossil fuels, leading to high greenhouse gas emissions in the heating sector. Therefore, policymakers increasingly strive to trigger investments in sustainable and low-emission heating systems. This study forms part of the “Roll-out of Deep Geothermal Energy in North-West-Europe”-project and aims at quantifying the spatial heat demand distribution in the Interreg North-West-Europe region. An open-source geographic information system and selected Python packages for advanced geospatial processing, analysis, and visualization are utilized to constrain the maps. These were combined, streamlined, and optimized within the open-source Python package PyHeatDemand. Based on national and regional heat demand input data, three maps are developed to better constrain heat demand at a high spatial resolution of 100 m × 100 m (=1 ha) for the residential and commercial sectors, and for both together (in total). The developed methodology can not only be applied to transnational heat demand mapping but also on various scales ranging from city district level to states and countries. In addition, the workflow is highly flexible working with raster data, vector data, and tabular data. The results reveal a total heat demand of the Interreg North-West-Europe region of around 1700 TWh. The spatial distribution of the heat demand follows specific patterns, where heat demand peaks are usually in metropolitan regions like for the city of Paris (1400 MWh/ha), the city of Brussels (1300 MWh/ha), the London metropolitan area (520 MWh/ha), and the Rhine-Ruhr region (500 MWh/ha). The developed maps are compared with two international projects, Hotmaps and Heat Roadmap Europe’s Pan European Thermal Atlas. The average total heat demand difference from values obtained in this study to Hotmaps and Heat Roadmap Europe is 24 MWh/ha and 84 MWh/ha, respectively. Assuming the implementation of real consumption data, an enhancement in spatial predictability is expected. The heat demand maps are therefore predestined to provide a conceptual first overview for decision-makers and market investors. The developed methods will further allow for anticipated mandatory municipal heat demand analyses.
Forecast-Based Energy Management for Optimal Energy Dispatch in a Microgrid
Authors: Durán Francisco , Pavón Wilson , Minchala Luis Ismael
Published: January 2024

This article describes the development of an optimal and predictive energy management system (EMS) for a microgrid with a high photovoltaic (PV) power contribution. The EMS utilizes a predictive long-short-term memory (LSTM) neural network trained on real PV power and consumption data. Optimal EMS decisions focus on managing the state of charge (SoC) of the battery energy storage system (BESS) within defined limits and determining the optimal power contributions from the microgrid components. The simulation utilizes MATLAB R2023a to solve a mixed-integer optimization problem and HOMER Pro 3.14 to simulate the microgrid. The EMS solves this optimization problem for the current sampling time (t) and the immediate sampling time (t+1), which implies a prediction of one hour in advance. An upper-layer decision algorithm determines the operating state of the BESS, that is, to charge or discharge the batteries. An economic and technical impact analysis of our approach compared to two EMSs based on a pure economic optimization approach and a peak-shaving algorithm reveals superior BESS integration, achieving 59% in demand satisfaction without compromising the life of the equipment, avoiding inexpedient power delivery, and preventing significant increases in operating costs.
The Atmospheric Stability Dependence of Far Wakes on the Power Output of Downstream Wind Farms
Authors: Foreman Richard J. , Cañadillas Beatriz , Robinson Nick
Published: January 2024

Stability-dependent far-field offshore wind-farm wakes are detected in Supervisory Control and Data Acquisition (SCADA) wind power records from wind farms located in the North Sea. The results are used to assess the strengths and weaknesses of the Openwind engineering model, which in turn enables understanding of the wake signal captured by the SCADA data. Two experimental model set-ups are evaluated, the current standard set-up considering a neutral atmosphere and extended for stable conditions, and the other using a new atmospheric stability implementation called the far-wake atmospheric stability model (ASM) previously reported in Energies. The ASM approach enables the identification within wind power records of wakes of length at least 30 km depending on the atmospheric stability. The ASM approach would be useful for assessing which neighboring wind farms are likely to affect the wind turbine power output and to what extent the power output is affected by stability.
CubeSat Mission Scheduling Method Considering Operational Reliability
Authors: Zhang Jingjing , He Chenyang , Zhang Yan , Qi Xianjun , Yang Xi
Published: January 2024

Mission scheduling is an effective method to increase the value of satellite missions and can greatly improve satellite resource management and quality of service. Based on the priority-based task scheduling model, this paper proposes a CubeSat scheduling method that takes operational reliability into account, considering the impact of scheduling results on reliable operation. In this method, the available energy and the time window are used as scheduling resources, and the average state of charge of the lithium battery and the number of task start-ups are defined as two indices to measure its reliability. To meet the mission requirements and energy availability of photovoltaic (PV) solar panel and battery constraints, the scheduling model is constructed with an objective function that includes mission priority and reliability index. The branch and bound (BB) method and analytical hierarchy process (AHP) method are used to solve the scheduling problem. The example analysis compares different scheduling results and verifies the effectiveness of the proposed scheduling method. Compared with the existing methods, it comprehensively considers the mission value and operational reliability of the CubeSat, improves the energy reserve level of the CubeSat, and reduces the surge current caused by the start-up of tasks.