bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational PK/PD for the Development of Novel Antibiotics—A Drug Developer’s Perspective
Authors: Bissantz Caterina , Zampaloni Claudia , David-Pierson Pascale , Dieppois Guennaelle , Guenther Andreas , Trauner Andrej , Winther Lotte , Stubbings William
Published: January 2024

Antibiotic development traditionally involved large Phase 3 programs, preceded by Phase 2 studies. Recognizing the high unmet medical need for new antibiotics and, in some cases, challenges to conducting large clinical trials, regulators created a streamlined clinical development pathway in which a lean clinical efficacy dataset is complemented by nonclinical data as supportive evidence of efficacy. In this context, translational Pharmacokinetic/Pharmacodynamic (PK/PD) plays a key role and is a major contributor to a “robust” nonclinical package. The classical PK/PD index approach, proven successful for established classes of antibiotics, is at the core of recent antibiotic approvals and the current antibacterial PK/PD guidelines by regulators. Nevertheless, in the case of novel antibiotics with a novel Mechanism of Action (MoA), there is no prior experience with the PK/PD index approach as the basis for translating nonclinical efficacy to clinical outcome, and additional nonclinical studies and PK/PD analyses might be considered to increase confidence. In this review, we discuss the value and limitations of the classical PK/PD approach and present potential risk mitigation activities, including the introduction of a semi-mechanism-based PK/PD modeling approach. We propose a general nonclinical PK/PD package from which drug developers might choose the studies most relevant for each individual candidate in order to build up a “robust” nonclinical PK/PD understanding.
The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease
Authors: Butcko Andrew J. , Putman Ashley K. , Mottillo Emilio P.
Published: January 2024

Cardiometabolic disease (CMD), which encompasses metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD) and cardiovascular disease (CVD), has been increasing considerably in the past 50 years. CMD is a complex disease that can be influenced by genetics and environmental factors such as diet. With the increased reliance on processed foods containing saturated fats, fructose and cholesterol, a mechanistic understanding of how these molecules cause metabolic disease is required. A major pathway by which excessive nutrients contribute to CMD is through oxidative stress. In this review, we discuss how oxidative stress can drive CMD and the role of aberrant nutrient metabolism and genetic risk factors and how they potentially interact to promote progression of MAFLD, CVD and CKD. This review will focus on genetic mutations that are known to alter nutrient metabolism. We discuss the major genetic risk factors for MAFLD, which include Patatin-like phospholipase domain-containing protein 3 (PNPLA3), Membrane Bound O-Acyltransferase Domain Containing 7 (MBOAT7) and Transmembrane 6 Superfamily Member 2 (TM6SF2). In addition, mutations that prevent nutrient uptake cause hypercholesterolemia that contributes to CVD. We also discuss the mechanisms by which MAFLD, CKD and CVD are mutually associated with one another. In addition, some of the genetic risk factors which are associated with MAFLD and CVD are also associated with CKD, while some genetic risk factors seem to dissociate one disease from the other. Through a better understanding of the causative effect of genetic mutations in CMD and how aberrant nutrient metabolism intersects with our genetics, novel therapies and precision approaches can be developed for treating CMD.
Effects of α-Lipoic Acid Supplementation on Growth Performance, Liver Histology, Antioxidant and Related Genes Expression of Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂)
Authors: Huang Weibin , Li Tao , Cai Wenshan , Song Hengyang , Liu Hao , Tan Beiping , Zhang Shuang , Zhou Menglong , Yang Yuanzhi , Dong Xiaohui
Published: January 2024

This study aimed to assess the impact of α-lipoic acid on the growth performance, antioxidant capacity and immunity in hybrid groupers (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) fed with a high-lipid diet. Groupers (8.97 ± 0.01 g) were fed six different diets, with α-lipoic acid content in diets being 0, 400, 800, 1200, 1600, and 2000 mg/kg, named S1, S2, S3, S4, S5, and S6, respectively. The results show that the addition of 2000 mg/kg α-lipoic acid in the diet inhibited the growth, weight gain rate (WGR), and specific growth rate (SGR), which were significantly lower than other groups. In serum, catalase (CAT) and superoxide dismutase (SOD) were significantly higher in the S5 group than in the S1 group. In the liver, CAT, SOD and total antioxidative capacity (T-AOC) levels were significantly increased in α-lipoic acid supplemented groups. α-lipoic acid significantly upregulated liver antioxidant genes sod and cat, anti-inflammatory factor interleukin 10 (il10) and transforming growth factor β (tgfβ) mRNA levels. Conclusion: the addition of 2000 mg/kg of α-lipoic acid inhibits the growth of hybrid groupers. In addition, 400–800 mg/kg α-lipoic acid contents improve the antioxidant capacity of groupers and have a protective effect against high-lipid-diet-induced liver oxidative damage.
Evaluation of Barriers to Deployment of Information and Communication Technologies to Sustain Information and Communication Flow in Floods
Authors: Anwer Izza , Yousuf Muhammad Irfan , Grant-Muller Susan
Published: January 2024

A sustainable information and communication flow (ICF) supports lifelines in floods, especially transport systems. A detailed insight into barriers regarding effective ICF through the implementation of information and communication technologies (ICTs) in the lifecycle of floods was given for evolved and evolving economies, i.e., York and Head-Marala, with sample sizes of 240 and 300 experts, respectively. All experts responded on an ethically approved questionnaire with further information notes that were used whilst discoursing the factors. ICTs were segregated into two groups, ranging from simple to advanced technologies. KMO and Bartlett’s tests confirmed high sampling adequacy with values ranging from 0.679 to 0.823 (≥0.5) with p-values ≤ 0.05. An amended version of Q-Methodology was used to identify nine factors in total. Each factor with an Eigenvalue ≥1 was retained, and all factors were highly reliable with values between 0.89 and 0.96. Factors were explained through communalities, factor loadings, pattern and structure matrices, and notes from experts. Results showed that under-evolved economies have limited technological resources and under-developed flood coping plans compared to evolved economies. Also, the unacknowledged possibility was uncovered that ICF can certainly be sustained if all possibly available ICTs are engaged through a thorough deployment plan of action. Authorities needed to make ICT engagement plans simple and efficient through effective coordination among different institutions. Though authorities were trained and equipped with modern tools, equipment, and technologies, dense and dependent populations overwhelmed the rescue capabilities. Other than VMS, social media pages, and radio, other ICTs were not tried and tested in floods for the exchange of transport–flood ICF. These findings are useful for stakeholders from all communities, transport planning institutions, and flood managers who are not fully benefiting from the extended use of ICTs to manage travel activities in floods.
Partial Parallelism Plots
Authors: Petzold Axel
Published: January 2024

Demonstrating parallelism in quantitative laboratory tests is crucial to ensure accurate reporting of data and minimise risks to patients. Regulatory authorities make the demonstration of parallelism before clinical use approval mandate. However, achieving statistical parallelism can be arduous, especially when parallelism is limited to a subrange of the data. To address potential biases and confounds, I propose a simple graphical method, the Partial Parallelism Plot, to demonstrate partial parallelism. The proposed method offers ease of understanding, intuitiveness, and graphical simplicity. It enables the graphical assessment of quantitative data risk when parallelism is lacking within a defined range. As parallelism may not be consistent across the entire analytical range, the plots focus on partial parallelism. The method can readily be programmed into graphical applications for enhanced interactivity. By providing a clear graphical representation, the method allows researchers to ascertain the presence of parallelism in laboratory tests, thus aiding in the validation process for trials and clinical applications.
Determining Digital Representation and Representative Elementary Volume Size of Broken Rock Mass Using the Discrete Fracture Network–Discrete Element Method Coupling Technique
Authors: Huang Xiao , Li Siyuan , Jin Jionghao , Shi Chong
Published: January 2024

Obtaining the digital characterization and representative elementary volume (REV) of broken rock masses is an important foundation for simulating their mechanical properties and behavior. In this study, utilizing the broken surrounding rock of the main powerhouse at the Liyang pumped storage power station as an engineering background, a three-dimensional fracture network generation program is first developed based on the theories of discrete fracture network (DFN) and discrete element method (DEM). The program is then integrated with a distinct element modelling platform to generate equivalent rock mass models for broken rock masses based on the DFN–DEM coupling technique. Numerical compression tests are conducted on cylindrical rock specimens produced using the proposed modelling approach, aiming to determining the REV size of the target rock masses at the Liyang power station. A comparative validation is also performed to examine the REV result obtained from the proposed approach, which adopted a REV measuring scale index (RMSI) to determine the REV size. Results indicate that the organic integration of DFN simulation techniques and DEM platforms can effectively construct numerical models for actual broken rock masses, with structural surface distributions statistically similar to the real ones. The results also show that the REV size of the investigated rock masses determined by the cylindrical rock models is 5 m × 10 m, which aligns with the size determined by the cubic rock models, as the target cubes show the same height as the cylindrical specimens. This study provides a model and parameter basis for the numerical calculation of the mechanical behavior of broken rock mass.
DSP-KD: Dual-Stage Progressive Knowledge Distillation for Skin Disease Classification
Authors: Zeng Xinyi , Ji Zhanlin , Zhang Haiyang , Chen Rui , Liao Qinping , Wang Jingkun , Lyu Tao , Zhao Li
Published: January 2024

The increasing global demand for skin disease diagnostics emphasizes the urgent need for advancements in AI-assisted diagnostic technologies for dermatoscopic images. In current practical medical systems, the primary challenge is balancing lightweight models with accurate image analysis to address constraints like limited storage and computational costs. While knowledge distillation methods hold immense potential in healthcare applications, related research on multi-class skin disease tasks is scarce. To bridge this gap, our study introduces an enhanced multi-source knowledge fusion distillation framework, termed DSP-KD, which improves knowledge transfer in a dual-stage progressive distillation approach to maximize mutual information between teacher and student representations. The experimental results highlight the superior performance of our distilled ShuffleNetV2 on both the ISIC2019 dataset and our private skin disorders dataset. Compared to other state-of-the-art distillation methods using diverse knowledge sources, the DSP-KD demonstrates remarkable effectiveness with a smaller computational burden.
Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach
Authors: Granata Ilaria , Barboro Paola
Published: January 2024

Prostate cancer (PCa) is characterised by androgen dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate cancer (CRPC) emerges, characterised by heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through the investigation of gene and protein annotations and the integration of published transcriptomic data, we identified two consensus lists to stratify PCa patients’ risk and discriminate CRPC phenotypes based on androgen receptor activity. ROC and Kaplan–Meier survival analyses were used for gene set validation in independent datasets. We further evaluated these genes for their association with cancer dependency. The deregulated expression of the PCa-related genes was associated with overall and disease-specific survival, metastasis and/or high recurrence risk, while the CRPC-related genes clearly discriminated between adeno and neuroendocrine phenotypes. Some of the genes showed context-specific essentiality. We further identified candidate drugs through a computational repositioning approach for targeting these genes and treating lethal variants of PCa. This work provides a proof-of-concept for the use of an integrative approach to identify candidate biomarkers involved in PCa progression and CRPC pathogenesis within the goal of precision medicine.
Are pvcrt-o and pvmdr1 Gene Mutations Associated with Plasmodium vivax Chloroquine-Resistant Parasites?
Authors: Abreu-Fernandes Rebecca de , Almeida-de-Oliveira Natália Ketrin , de Lavigne Mello Aline Rosa , Queiroz Lucas Tavares de , Barros Jacqueline de Aguiar , Baptista Bárbara de Oliveira , Oliveira-Ferreira Joseli , Souza Rodrigo Medeiros de , Pratt-Riccio Lilian Rose , Brasil Patrícia , Daniel-Ribeiro Cláudio Tadeu , Ferreira-da-Cruz Maria de Fátima
Published: January 2024

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum, there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1, T958M and F1076L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976F was not detected. (4) Conclusions: Since K10-pvcrt-o and F1076L/T958M-pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.
Vasodilatory Peripheral Response and Pain Levels following Radiofrequency Stressor Application in Women with Fibromyalgia
Authors: Casas-Barragán Antonio , Muñoz-Revilla Alba , Tapia-Haro Rosa María , Molina Francisco , Correa-Rodríguez María , Aguilar-Ferrándiz María Encarnación
Published: January 2024

Fibromyalgia (FM) is a syndrome of unknown pathogenesis that presents, among other symptoms, chronic widespread musculoskeletal pain. This study aims to analyze the effects of radiofrequency on core body temperature and the peripheral temperature of the dorsal surfaces and palms of the hands and its association with pain levels in patients with FM. A case-control observational study was conducted with a total of twenty-nine women diagnosed with FM and seventeen healthy women. Capacitive monopolar radiofrequency was applied to the palms of the hands using the Biotronic Advance Develops device. Peripheral hand temperature was analyzed using a thermographic camera, and core body temperature was analyzed with an infrared scanner. Pressure pain thresholds (PPTs) and electrical pain were recorded with an algometer and a Pain Matcher device, respectively. A significant decrease was observed in women with FM in pain electrical threshold (95% CI [0.01–3.56], p = 0.049), electrical pain (95% CI [2.87–10.43], p = 0.002), dominant supraspinatus PPT (95% CI [0.04–0.52], p = 0.023), non-dominant supraspinatus PPT (95% CI [0.03–0.60], p = 0.029), and non-dominant tibial PPT (95% CI [0.05–0.89], p = 0.031). Women with FM have increased hypersensitivity to pain as well as increased peripheral temperature after exposure to a thermal stimulus, such as radiofrequency, which could indicate disorders of their neurovascular response.
Advancing Brain Research through Surface-Enhanced Raman Spectroscopy (SERS): Current Applications and Future Prospects
Authors: Elsheikh Suzan , Coles Nathan P. , Achadu Ojodomo J. , Filippou Panagiota S. , Khundakar Ahmad A.
Published: January 2024

Surface-enhanced Raman spectroscopy (SERS) has recently emerged as a potent analytical technique with significant potential in the field of brain research. This review explores the applications and innovations of SERS in understanding the pathophysiological basis and diagnosis of brain disorders. SERS holds significant advantages over conventional Raman spectroscopy, particularly in terms of sensitivity and stability. The integration of label-free SERS presents promising opportunities for the rapid, reliable, and non-invasive diagnosis of brain-associated diseases, particularly when combined with advanced computational methods such as machine learning. SERS has potential to deepen our understanding of brain diseases, enhancing diagnosis, monitoring, and therapeutic interventions. Such advancements could significantly enhance the accuracy of clinical diagnosis and further our understanding of brain-related processes and diseases. This review assesses the utility of SERS in diagnosing and understanding the pathophysiological basis of brain disorders such as Alzheimer’s and Parkinson’s diseases, stroke, and brain cancer. Recent technological advances in SERS instrumentation and techniques are discussed, including innovations in nanoparticle design, substrate materials, and imaging technologies. We also explore prospects and emerging trends, offering insights into new technologies, while also addressing various challenges and limitations associated with SERS in brain research.
Neuralgic Amyotrophy and Hourglass Nerve Constriction/Nerve Torsion: Two Sides of the Same Coin? A Clinical Review
Authors: Granata Giuseppe , Tomasello Fabiola , Sciarrone Maria Ausilia , Stifano Vito , Lauretti Liverana , Luigetti Marco
Published: January 2024

Neuralgic amyotrophy, also called Parsonage–Turner syndrome, in its classic presentation is a brachial plexopathy or a multifocal neuropathy, involving mainly motor nerves of the upper limb with a monophasic course. Recently, a new radiological entity was described, the hourglass constriction, which is characterized by a very focal constriction of a nerve, or part of it, usually associated with nerve thickening proximally and distally to the constriction. Another condition, which is similar from a radiological point of view to hourglass constriction, is nerve torsion. The pathophysiology of neuralgic amyotrophy, hourglass constriction and nerve torsion is still poorly understood, and a generic role of inflammation is proposed for all these conditions. It is now widely accepted that nerve imaging is necessary in identifying hourglass constrictions/nerve torsion pre-surgically in patients with an acute mononeuropathy/plexopathy. Ultrasound and MRI are useful tools for diagnosis, and they are consistent with intraoperative findings. The prognosis is generally favorable after surgery, with a high rate of good motor recovery.
Neurocognitive Assessment of Mathematics-Related Capacities in Neurosurgical Patients
Authors: Castaldi Elisa , Bonaudo Camilla , Maduli Giuseppe , Anobile Giovanni , Pedone Agnese , Capelli Federico , Arrighi Roberto , Della Puppa Alessandro
Published: January 2024

A precise neuropsychological assessment is of the utmost importance for neurosurgical patients undergoing the surgical excision of cerebral lesions. The assessment of mathematical abilities is usually limited to arithmetical operations while other fundamental visuo-spatial aspects closely linked to mathematics proficiency, such as the perception of numerical quantities and geometrical reasoning, are completely neglected. We evaluated these abilities with two objective and reproducible psychophysical tests, measuring numerosity perception and non-symbolic geometry, respectively. We tested sixteen neuro-oncological patients before the operation and six after the operation with classical neuropsychological tests and with two psychophysical tests. The scores of the classical neuropsychological tests were very heterogeneous, possibly due to the distinct location and histology of the tumors that might have spared (or not) brain areas subserving these abilities or allowed for plastic reorganization. Performance in the two non-symbolic tests reflected, on average, the presumed functional role of the lesioned areas, with participants with parietal and frontal lesions performing worse on these tests than patients with occipital and temporal lesions. Single-case analyses not only revealed some interesting exceptions to the group-level results (e.g., patients with parietal lesions performing well in the numerosity test), but also indicated that performance in the two tests was independent of non-verbal reasoning and visuo-spatial working memory. Our results highlight the importance of assessing non-symbolic numerical and geometrical abilities to complement typical neuropsychological batteries. However, they also suggest an avoidance of reliance on an excessively rigid localizationist approach when evaluating the neuropsychological profile of oncological patients.
A Naturalistic Intervention to Promote Executive Functions in Primary School Children: A Pilot Study
Authors: Souza Jonatas B. , Trevisan Bruna T. , Nunes Liana G. , Machado Wagner L. , Seabra Alessandra G.
Published: January 2024

Executive functions are related to the control of cognition, emotion, and behavior. They are essential to lifelong outcomes, including school performance. Naturalistic interventions embedded in children’s daily activities and environments have greater effects. Therefore, this pilot study aimed to develop a naturalistic program suitable for schools, based on Goal Management Training (GMT), and to analyze its effects on executive functions and behavior. The participants consisted of 35 students from 2nd to 5th grade with executive dysfunction complaints. They underwent neuropsychological assessments of working memory, inhibition, cognitive flexibility, and intellectual capacity. Teachers and parents answered questionnaires on executive functions and behavior. Students were randomly assigned to an active control group, who participated in sessions on citizenship, and an experimental group (EG), stimulated through the executive function program, both with 16 sessions conducted by psychologists. After the intervention, all participants were reevaluated. The two-way Wald-type statistic (WTS) revealed greater improvement in executive functions for the EG, including working memory and inhibition. Additionally, parents and teachers, blind to the experimental conditions, reported improvements in some measures of executive functions and behavior. The results are encouraging, but further studies should test the intervention when implemented with larger samples and by teachers.
Effectiveness of Cognitive Behavioral Therapy (CBT) on Psychological Distress among Mothers of Children with Autism Spectrum Disorder: The Role of Problem-Solving Appraisal
Authors: Abdelaziz Enas Mahrous , Alsadaan Nourah , Alqahtani Mohammed , Elsharkawy Nadia Bassuoni , Ouda Marwa Mohamed Ahmed , Ramadan Osama Mohamed Elsayed , Shaban Mostafa , Shokre Evon S.
Published: January 2024

Mothers of children with autism spectrum disorder (ASD) face considerable psychological distress. Cognitive behavioral therapy (CBT) has shown promise in reducing caregiver burden, but evidence in the Arab world is lacking. Problem-solving appraisal training may optimize CBT’s benefits. This study evaluated a tailored CBT program emphasizing the role of problem-solving appraisal in managing distress through the process of CBT. Sixty mothers were randomly allocated in a 1:1 ratio to either the CBT intervention group or the control group. The CBT group received 3-month sessions incorporating problem-solving appraisal training within a CBT curriculum from October 2022 to April 2023. Problem-solving techniques are focused on equipping individuals with the skills to identify, approach, and effectively resolve problems, leading to a reduction in stress levels and an improved capacity to cope with difficult situations. All mothers completed assessments of socio-demographics such as age, level of education, marital status, occupation, and adequacy of family income, the Depression Anxiety Stress Scale (DASS-21) and the Problem-Solving Inventory (PSI) before and after the program. The CBT group showed significant pre-to-post reductions in depression, anxiety, stress, and general psychological distress compared to controls (all p < 0.05). They also exhibited significant improvements in problem-solving confidence, approach-avoidance style and personal control (all p < 0.05). The customized CBT program markedly improved psychological well-being for mothers of children with ASD in Egypt. Incorporating problem-solving techniques may optimize CBT’s benefits cross-culturally. These findings have implications for the implementation of evidence-based support programs for families impacted by ASD worldwide.
Effect of Health and Safety Management Systems in the Construction Sector
Authors: Arévalo Sarrate Carlos , Tarín Martínez Javier , Lara Galera Antonio Lorenzo , Galindo Aires Rubén Ángel
Published: January 2024

Management systems that are recognized as key tools to improve business management and the results associated with it have spread at the business level during the last 50 years. Regarding Safety Management Systems (SMSs), despite having specific international standards, there are no complete studies that analyze the degree of effectiveness of SMS, and even less in construction, a sector that concentrates a large part of registered labor accidents worldwide. The present investigation is an analysis of SMS effectiveness from an empirical study carried out over 48 months in five countries with a total of more than 23 million work hours between 2009 and 2012. Additionally, it is implied that the impact of SMS implementation in a certain organization must be complemented by a statistical qualitative analysis of its effect on the distribution of accidents. Both analyses are developed in the present study, thus contributing relevant implications when assessing both quantitatively and qualitatively the effects of developing and implementing a health and safety management system in this sector. The findings from this research can contribute to understanding how SMS implementation can help reduce accidents in this industry as well as to enhance SMS implementation in a high-risk sector.
Vulnerability of Non-Structural Elements (NSEs) in Buildings and Their Life Cycle Assessment: A Review
Authors: Ahmad Zeeshan , Ahmed Hafiz Asfandyar , Shahzada Khan , Li Yaohan
Published: January 2024

Purpose: This paper conducts a review of the different research carried out recently on the behavior of non-structural elements (NSEs) and the life cycle assessment (LCA) during an earthquake. It focuses on the study conducted recently and identifies the gaps and way forward for future work. Methods: A systematic literature review was carried out among the different research works. The proposed literature review includes (i) identifying the recent research work using the keywords in available search engines, (ii) studying different research papers and selecting the relevant papers only, and (iii) vulnerability and LCA for NSEs and their research gaps. Results and discussions: A summary is given of the importance and type of NSEs under earthquakes, including life cycle cost assessment for NSE, environment life cycle assessment (ELCA) and social life cycle assessment (SLCA) for different facilities and the embodied energies. Conclusions and recommendations: This paper highlights the problems associated with NSEs. For new constructions, modifications to improve the performance of NSEs, particularly infill walls are under research, however for old buildings, their location is also vital. Numerical methods are performed using different tools available; however, implementation is a big challenge to economize the life cycle and its impact on the community.
The Impact of Plasticizers on the Nature of the Alkali-Silicate Corrosion in Cement Composites
Authors: Pustovgar Andrey P. , Krivoborodov Yury R. , Adamtsevich Aleksey O. , Elenova Aurika A. , Butenko Kseniya A. , Kramerov Dmitrii V. , Bugaev Anton M.
Published: January 2024

This research work attempts to reveal the mechanism of alkali corrosion in cement composites in the presence of plasticizers based on polycarboxylates (PCE), naphtha-lene-formaldehydes (SPNF), and lignosulfonates by maintaining a high pH of the liquid phase and additionally containing monovalent alkali earth metals in cement stone, as well as stopping this process by introducing an active mineral additive. ASR is studied by changing the relative strain with time according to ASTM C-1260. Deformation changes were confirmed by SEM and RFA studies of hydration products and ASR in the microstructure. Separate use of PCE plasticizers in the cement composition increases deformation by 50% to the 56th day; the use of SPNF increases deformation by 10% compared with the additive-free composition. The use of PLS reduces the relative deformation by 25%. The introduction of silica fume into cementitious composites containing plasticizers actually stops ASR only for a short time. A reduction in deformation during MC use together with plasticizer based on naphthalene sulfonate and polycarboxylate occurs only when the dosage of MS is increased to 20–30%; at a lower dosage, the effect is negative, which also affects the phase composition of the composites. The introduction of MC increases the value of the relative deformation compared with plasticizer compositions based only on PLS. SEM studies have detected microcracks and dense fine-crystalline silicate gel, which cause deformation changes in cement composite samples. Research has shown that concrete modified with SPNF and PCE at the maximum dosage of MC (30%) has minimal deformation rates and can be used to select optimal concrete compositions. The results of this study could help to minimize risks, prevent unacceptable expansion, and ensure the high quality of concrete and concrete products during their use as part of various nature-modifying additives.
Modeling the Volatility of Daily Listed Real Estate Returns during Economic Crises: Evidence from Generalized Autoregressive Conditional Heteroscedasticity Models
Authors: Zheng Mo , Song Han-Suck , Liang Jian
Published: January 2024

In this paper, we focus on the dynamic volatility behavior of the daily Swedish Real Estate Sector Index and analyze the existence and degree of a long-range dependence or asymmetric news effect since 2003. More specifically, we give extra attention to the 2007–2008 financial crisis, the 2009–2012 European debt crisis, and the first two years of the global COVID-19 pandemic era (2020–2021). We examine changes in volatility during these extreme events. We apply standard GARCH models, asymmetric GARCH models, and long-memory GARCH models with various error distributions to identify the most accurate volatility models of the daily returns of the Swedish Real Estate Sector Index for the full sample period, January 2003 to June 2021. Our results show that the volatility of the Swedish Real Estate Sector Index is time-varying and highly volatile. The impacts of the global financial crisis, European debt crisis, and COVID-19 pandemic are noticeable. Moreover, the volatility pattern during COVID-19 displays significant time-varying long-range dependence and an asymmetrical news impact, which lead to market inefficiency. Finally, the volatility pattern shows a tendency towards increasing leverage effects and less persistent behavior, indicating that the market stakeholders are highly sensitive to negative returns and becoming quicker to respond to market changes.
High-Rise Residential District Morphology Optimization for Enhancing the Green Space Cooling Effect
Authors: Shi Feng , Chen Yuan , Yue Wenru , Wang Yupeng
Published: January 2024

Large-scale urban green spaces exert a cooling effect in cities and have great potential for optimizing the urban climate. In this study, taking the typical green space Xingfulindai in Xi’an as an example, we carried out field measurements and ENVI-met simulations of the area and the surrounding high-rise residential areas to analyze the cooling effect. The results show that the cooling effect is the strongest at night in summer seasons, spreading up to 250 m, and the cooling intensity along the downwind direction can be up to 2 °C. On this basis, a total of 16 ideal models of seven groups of high-rise residential blocks were established to analyze the effect of three morphological indices, namely, building orientation, podium ratio, and otherness with respect to the cooling effect of the green space, and a block morphology design strategy for high-rise residential areas was proposed to enhance the cooling effect of the green space. This study provides climate-adaptive optimization strategies for the construction and renewal of residential blocks.
Comparative Study of the Immune Microenvironment in Heterotopic Tumor Models
Authors: Kienzl Melanie , Maitz Kathrin , Sarsembayeva Arailym , Valadez-Cosmes Paulina , Gruden Eva , Ristic Dusica , Herceg Karolina , Kargl Julia , Schicho Rudolf
Published: January 2024

The tumor microenvironment (TME) is pivotal in cancer progression and the response to immunotherapy. A “hot” tumor typically contains immune cells that promote anti-tumor immunity, predicting positive prognosis. “Cold” tumors lack immune cells, suggesting a poor outlook across various cancers. Recent research has focused on converting “cold” tumors into “hot” tumors to enhance the success of immunotherapy. A prerequisite for the studies of the TME is an accurate knowledge of the cell populations of the TME. This study aimed to describe the immune TME of lung and colorectal cancer and melanoma, focusing on lymphoid and myeloid cell populations. We induced heterotopic immunocompetent tumors in C57BL/6 mice, using KP and LLC (Lewis lung carcinoma) cells for lung cancer, MC38 cells for colorectal cancer, and B16-F10 cells for melanoma. Immune cell infiltration was analyzed using multicolor flow cytometry in single-cell suspensions after tumor excision. KP cell tumors showed an abundance of neutrophils and eosinophils; however, they contained much less adaptive immune cells, while LLC cell tumors predominated in monocytes, neutrophils, and monocyte-derived dendritic cells. Monocytes and neutrophils, along with a significant T cell infiltration, were prevalent in MC38 tumors. Lastly, B16-F10 tumors were enriched in macrophages, while showing only moderate T cell presence. In conclusion, our data provide a detailed overview of the immune TME of various heterotopic tumors, highlighting the variabilities in the immune cell profiles of different tumor entities. Our data may be a helpful basis when investigating new immunotherapies, and thus, this report serves as a helpful tool for preclinical immunotherapy research design.
NAD+ Metabolism-Related Gene Profile Can Be a Relevant Source of Squamous Cell Carcinoma Biomarkers
Authors: Minafò Ylenia Aura , Antonini Dario , Dellambra Elena
Published: January 2024

Poor survival rates of squamous cell carcinomas (SCCs) are associated with high recurrence, metastasis, and late diagnosis, due in part to a limited number of reliable biomarkers. Thus, the identification of signatures improving the diagnosis of different SCC types is mandatory. Considering the relevant role of NAD+ metabolism in SCC chemoprevention and therapy, the study aimed at identifying new biomarkers based on NAD+ metabolism-related gene (NMRG) expression. Gene expression of 18 NMRGs and clinical-pathological information for patients with head and neck SCC (HNSCC), lung SCC (LuSCC), and cervix SCC (CeSCC) from The Cancer Genome Atlas (TCGA) were analyzed by several bioinformatic tools. We identified a 16-NMRG profile discriminating 3 SCCs from 3 non-correlated tumors. We found several genes for HNSCC, LuSCC, and CeSCC with high diagnostic power. Notably, three NMRGs were SCC-type specific biomarkers. Furthermore, specific signatures displayed high diagnostic power for several clinical-pathological characteristics. Analyzing tumor-infiltrating immune cell profiles and PD-1/PD-L1 levels, we found that NMRG expression was associated with suppressive immune microenvironment mainly in HNSCC. Finally, the evaluation of patient survival identified specific genes for HNSCC, LuSCC, and CeSCC with potential prognostic power. Therefore, our analyses indicate NAD+ metabolism as an important source of SCC biomarkers and potential therapeutic targets.
Myeloproliferative Neoplasms: Diseases Mediated by Chronic Activation of Signal Transducer and Activator of Transcription (STAT) Proteins
Authors: Liongue Clifford , Ward Alister C.
Published: January 2024

Myeloproliferative neoplasms (MPNs) are hematopoietic diseases characterized by the clonal expansion of single or multiple lineages of differentiated myeloid cells that accumulate in the blood and bone marrow. MPNs are grouped into distinct categories based on key clinical presentations and distinctive mutational hallmarks. These include chronic myeloid leukemia (CML), which is strongly associated with the signature BCR::ABL1 gene translocation, polycythemia vera (PV), essential thrombocythemia (ET), and primary (idiopathic) myelofibrosis (PMF), typically accompanied by molecular alterations in the JAK2, MPL, or CALR genes. There are also rarer forms such as chronic neutrophilic leukemia (CNL), which involves mutations in the CSF3R gene. However, rather than focusing on the differences between these alternate disease categories, this review aims to present a unifying molecular etiology in which these overlapping diseases are best understood as disruptions of normal hematopoietic signaling: specifically, the chronic activation of signaling pathways, particularly involving signal transducer and activator of transcription (STAT) transcription factors, most notably STAT5B, leading to the sustained stimulation of myelopoiesis, which underpins the various disease sequalae.
Reducing the Risk of Needle Tract Seeding or Tumor Cell Dissemination during Needle Biopsy Procedures
Authors: Holmes Dennis R.
Published: January 2024

Purpose: Many women fear that breast needle biopsies increase the risk of cancer spread. The purpose of this review article is to discuss the breast cancer literature regarding the risk of needle-biopsy-induced cancer cell displacement and its impact on local and regional recurrence and breast cancer survival. Methods: A literature review is performed to discuss the risks and mitigation of needle-biopsy-induced cancer cell displacement. Results: Needle-biopsy-induced cancer cell displacement is a common event. The risk is influenced by the biopsy technique and the breast cancer type. Evidence suggests that the risk of needle-biopsy-induced cancer cell displacement may potentially increase the odds of local recurrence but has no impact on regional recurrence and long-term survival. Conclusions: Technical modifications of needle biopsy procedures can reduce the risk of breast needle-biopsy-induced cancer cell displacement and potentially reduce the risk of local recurrence, especially in patients for whom whole breast radiation is to be omitted.
Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas
Authors: Diez-Feijóo Ramón , Andrade-Campos Marcio , Gibert Joan , Sánchez-González Blanca , Fernández-Ibarrondo Lierni , Fernández-Rodríguez Concepción , Garcia-Gisbert Nieves , Camacho Laura , Lafuente Marta , Vázquez Ivonne , Colomo Luis , Salar Antonio , Bellosillo Beatriz
Published: January 2024

Background: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. Methods: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. Results: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. Conclusions: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients.
Evaluation of Metabolic and Cardiovascular Risk Measured by Laboratory Biomarkers and Cardiopulmonary Exercise Test in Children and Adolescents Recovered from Brain Tumors: The CARMEP Study
Authors: Romano Alberto , Sollazzo Fabrizio , Rivetti Serena , Morra Lorenzo , Servidei Tiziana , Lucchetti Donatella , Attinà Giorgio , Maurizi Palma , Mastrangelo Stefano , Zovatto Isabella Carlotta , Monti Riccardo , Bianco Massimiliano , Palmieri Vincenzo , Ruggiero Antonio
Published: January 2024

In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk.
Can the Epstein–Barr Virus Play a Role in the Development of Prostate Cancer?
Authors: Kiś Jacek , Góralczyk Magdalena , Sikora Dominika , Stępień Ewa , Drop Bartłomiej , Polz-Dacewicz Małgorzata
Published: January 2024

Prostate cancer (PCa) is the fourth most frequently diagnosed cancer worldwide, accounting for 7.3% of all cancers. PCa mortality is the fifth most common cause of cancer death. Despite well-known factors influencing the development of PCa, such as age, race/ethnicity and family history, many researchers have raised the possibility of persistent infections with oncogenic viruses. Therefore, we aimed to assess the frequency of Epstein–Barr virus (EBV) DNA in tissue collected from PCa patients. Next, the frequency and the level of Epstein–Barr virus capsid antigen (EBVCA) and Epstein–Barr nuclear antigen 1 (EBNA1) antibodies in both IgA and IgG classes were measured. The antibody titer was also analyzed depending on the risk group, Gleason score (GS) and tumor, node, metastasis (TNM) classification. Serum samples were analyzed using the Microblot-Array EBV IgM, IgA and IgG test kits. The study group consisted of 115 patients diagnosed and histopathologically confirmed with PCa. In 49% of patients included in the study, EBV DNA was detected in the tumor tissue. The studies showed both higher seroprevalence and higher antibody titers in patients with EBV-positive PCa compared to patients with EBV-negative PCa. We also observed a dependence of antibody titer on pathological features, such as GS, risk group and T stage.