bluuebunny/crossref_metadata_2025 huggingface dataset:
The Forces Associated with Bolus Injection and Continuous Infusion Techniques during Ultrasound-Targeted Nerve Contact: An Ex Vivo Study
Authors: Agweder Ashraf , Zeng Youheng , Liu Jiatao , McLeod Graeme , Huang Zhihong
Published: March 2024

Ultrasound-guided regional anaesthesia with real-time visualization of anatomical structures and needle trajectory has become the standard method for accurately achieving nerve block procedures. Nevertheless, ultrasound is particularly limited in accurately detecting the needle tip in tissues with complex echogenicity. Fat-filled circumneural fascial tissue provides a barrier to local anaesthetic diffusion. Injection during gentle needle nerve contact is more likely to spread under the circumneurium (halo sign). On the other hand, excessive force may cause hematoma or activate the piezo ion channels and intraneural calcium release. Therefore, it is vital to understand the mechanics of needle–tissue interaction for optimizing the procedural outcomes and patients’ safety. We hypothesised that continuous fluid infusion would reduce the needle force applied on the nerve compared to that of bolus injection. Thus, the primary objective of this study was to compare the forces associated with the bolus injection and continuous infusion techniques on the sciatic nerves of fresh lamb legs ex vivo. A needle combining pressure and force was inserted into six legs of lambs ex vivo using a motor stage at a constant velocity and imaged with a linear transducer. Saline injections were block randomised to bolus injection or infusion in the muscle upon gently touching and indenting of the epineurium at nine sites on six sciatic nerves at three angles (30°, 45° and 60°) in each location. The bolus was delivered over 6 s and infused for over 60 s. The result showed less force was generated during the infusion technique when gently touching the epineurium than that of the bolus technique, with p = 0.004, with significant differences observed at a 60° angle (0.49 N, p = 0.001). The injection pressure was also lower when light epineurium touches were applied (9.6 kPa, p = 0.02) and at 60° (8.9 kPa). The time to peak pressure varied across the insertion angles (p < 0.001), with the shortest time at 60° (6.53 s). This study explores future applications by emphasizing the significance of understanding needle–tissue interaction mechanics. This understanding is crucial for optimizing the procedural outcomes and enhancing patients’ safety in ultrasound-guided regional anaesthesia administration. Specifically, continuous infusion demonstrated a notable reduction in needle force compared to that of the bolus injection, especially during gentle epineurium contact.
The Antifungal Effect of Weissella confusa WIKIM51 (Wilac D001) on Vaginal Epithelial Cells Infected by Candida albicans
Authors: Lee Gain , You Young-Ah , Ansari Abuzar , Go Yoon-Young , Park Sunwha , Hur Young Min , Kim Soo-Min , Park Sang Min , Kim Young Ju
Published: March 2024

Vulvovaginal candidiasis (VVC) is a genital infection caused by Candida albicans (C. albicans). Weissella confusa WIKIM51 (Wilac D001) is known to be detected in dandelion kimchi, produce lactic acid, and have an anti−inflammatory ability; however, its diverse antifungal effects have not been studied. Here, we investigated the antifungal effect of Wilac D001 in C. albicans compared to Lactobacillus species on vaginal epithelial cells (VECs). To test the antifungal ability of Wilac D001 against C. albicans on VECs, an adhesion test, pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) analysis, and a disk diffusion test were performed. The acid tolerance test was conducted to investigate the viability of Wilac D001 in various acidic conditions. Lactobacillus reuteri (L. reuteri) and L. rhamnosus were used as positive controls. Wilac D001 showed the capacity to inhibit the colonization of C. albicans by adhering to VECs, with an inhibitory effect similar to that of positive controls. Both pro−inflammatory cytokines including IL−6 and IL−8 concentrations were significantly decreased when Wilac D001 was treated on C. albicans-infected VECs, respectively (p < 0.001). The result of the disk diffusion test indicates that the inhibitory ability of Wilac D001 is comparable to L. reuteri and L. rhamnosus on agar plates infected with C. albicans. Our results demonstrate that Weissella confusa WIKIM51 has antifungal effects against VECs infected by C. albicans.
Mortars with Polypropylene Fibers Modified with Tannic Acid to Increase Their Adhesion to Cement Matrices
Authors: Sokołowska Joanna Julia , Łukowski Paweł , Bączek Alicja
Published: March 2024

The presented research’s main objective was to evaluate the possibility of improving the adhesion between polypropylene fibers and mineral matrices in cementitious composites by modifying the fibers’ surface with tannic acid (TA). This modifier was previously used for polyethylene fibers only. Cement mortar containing modified polypropylene fibers and mortar containing unmodified fibers were tested. The physical and mechanical properties (apparent density, compressive strength, flexural strength and modulus of elasticity) were determined, and the fibers’ morphology after the specimens’ destruction was observed. No adverse effect of the modification was found. The elastic modulus was 6% lower after 28 days, enabling the formation of a less stiff composite material. The integrity of the specimens after mechanical damage was improved, confirming the increased adhesion between the polypropylene fibers and the hardened cement paste. The results of the introductory tests are promising; however, further research is needed in the field.
Breast Cancer Diagnosis Using YOLO-Based Multiscale Parallel CNN and Flattened Threshold Swish
Authors: Mohammed Ahmed Dhahi , Ekmekci Dursun
Published: March 2024

In the field of biomedical imaging, the use of Convolutional Neural Networks (CNNs) has achieved impressive success. Additionally, the detection and pathological classification of breast masses creates significant challenges. Traditional mammogram screening, conducted by healthcare professionals, is often exhausting, costly, and prone to errors. To address these issues, this research proposes an end-to-end Computer-Aided Diagnosis (CAD) system utilizing the ‘You Only Look Once’ (YOLO) architecture. The proposed framework begins by enhancing digital mammograms using the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique. Then, features are extracted using the proposed CNN, leveraging multiscale parallel feature extraction capabilities while incorporating DenseNet and InceptionNet architectures. To combat the ‘dead neuron’ problem, the CNN architecture utilizes the ‘Flatten Threshold Swish’ (FTS) activation function. Additionally, the YOLO loss function has been enhanced to effectively handle lesion scale variation in mammograms. The proposed framework was thoroughly tested on two publicly available benchmarks: INbreast and CBIS-DDSM. It achieved an accuracy of 98.72% for breast cancer classification on the INbreast dataset and a mean Average Precision (mAP) of 91.15% for breast cancer detection on the CBIS-DDSM. The proposed CNN architecture utilized only 11.33 million parameters for training. These results highlight the proposed framework’s ability to revolutionize vision-based breast cancer diagnosis.
Computational Modelling and Biomechanical Analysis of Age-Related Craniocerebral Injuries: Insights into Bridging Veins
Authors: Ratajczak Monika , Ptak Mariusz , Dymek Mateusz , Kubacki Rafał , de Sousa Ricardo J. Alves , Sbriglio Claudia , Kwiatkowski Artur
Published: March 2024

The aim of this study is to explain the higher incidence of subdural haematomas in elderly people compared to young adult. This research addresses the phenomenon by developing two distinct numerical models of the human head, simulating individuals people aged 77 and 28, respectively. These models are methodically constructed based on medical imaging data acquired through collaboration with hospitals and subsequently verified through empirical experimentation. Studies have shown that the main factor that influences the vulnerability to bridging vein rupture in older adults is the degenerative processes of nervous tissue. The most visible structural damage was observed in the outflow cuff segment. This phenomenon can be primarily attributed to specific geometric parameters associated with this anatomical region. The presented research emphasises the importance of computational models in understanding the pathomechanics of brain structures. As a result of the analyses, it was proven that the neurodegenerative processes of the brain that occur with age are crucial in understanding the higher incidence of subdural haematomas in elderly people.
Selection of the Processing Method for Green Banana Chips from Barraganete and Dominico Varieties Using Multivariate Techniques
Authors: Chamorro-Hernandez Liliana M. , Herrera-Granda Erick P. , Rivas-Rosero Carlos
Published: March 2024

Due to their contribution to human health, healthy snacks have garnered the attention of the scientific community and the food industry. This study was conducted to determine the suitability of frying and baking processing methods for producing green banana chips using two varieties: Barraganete and Dominico. The aim was to identify a treatment geared toward producing healthy snacks. Initially, the physicochemical properties of the raw materials were analyzed, revealing significant differences in starch, fat, fiber, and protein content. Subsequently, the bananas were processed into baked and fried chips. Multivariate statistical techniques such as ANCOVA, MANOVA, and post-hoc tests were applied to examine the influence of initial characteristics and detect variations attributable to the cooking method. The main findings show that the initial protein level had a significant covariate effect on the final content in the chips. The Dominico variety generally proved more suitable for making baked chips, retaining higher percentages of protein, starch, and fiber and lower fat content than Barraganete. Baked chips showed significantly lower sodium and fat values than fried ones when differentiated by processing method. The “Dominico + Baked” treatment emerged as the superior alternative, with favorable levels of protein and starch and low levels of sodium and fat, positioning it as the most suitable for producing a healthy snack.
Assessment of Non-Linear Analyses of RC Buildings Retrofitted with Hysteretic Dampers According to the Italian Building Code
Authors: Bruschi Eleonora , Quaglini Virginio
Published: March 2024

While the use of steel hysteretic dampers has spread in the last decade for both new and retrofitted constructions, the Italian Building Code (IBC), as well as the Eurocode 8, does not provide specific recommendations for the design and verification of structures equipped with this technology. Due to their strong non-linear behavior, the effectiveness of the design with these systems must be verified through non-linear analyses. Non-Linear Time-History analyses (NLTHAs) are the most reliable method, but they are computationally expensive. The aim of the study is to investigate the reliability of non-linear static procedures, allowed by the IBC as an alternative to NLTHAs, for the analysis of buildings equipped with hysteretic devices provided with high damping capability. A parametric study is conducted on two reinforced concrete residential buildings, typical of the Italian residential heritage, retrofitted with hysteretic braces characterized by different stiffness and ductility values. The retrofit design is verified using non-linear analyses, both static and dynamic, considering either natural or artificial accelerograms, as the IBC deems them as equivalent. Within this work, reference is made only to the IBC; however, given the significant similarity between the IBC and the European code, the outcomes are expected to have a broader impact and to be not limited to the Italian context. Therefore, although this work is a preliminary study, it is believed to offer some initial insights on the topic and serve as the foundation for a more in-depth study that could lead to a regulatory revision on the subject.
Design and Analysis of a Novel Variable Stiffness Joint Based on Leaf Springs
Authors: Wang Caidong , Gao Yafeng , Xu Yapeng , Wang Xinjie , Wang Liangwen
Published: March 2024

In response to challenges like the complexity and limited scalability of existing variable stiffness joints, a novel variable stiffness joint, based on leaf spring elements, is introduced in this paper. The joint stiffness can be adjusted in real time by changing the effective length of the leaf spring via the use of an Archimedean spiral groove. The stiffness adjustment range and load capacity of the joint can be defined by manually configuring the number of springs involved during offline joint operations. A stiffness model for the joint is established based on the cantilever beam theory of material mechanics. The coupled effects of the design parameters of the variable stiffness mechanism on joint stiffness, elastic torque, and stiffness adjustment resistance torque are analyzed. A dynamic model for the joint is developed, while a PID controller is designed for simulation purposes. The motion characteristics of the joint are analyzed, confirming that this approach has certain advantages in terms of stiffness adjustment speed and accuracy.
Insertion Performance Study of an Inductive Weft Insertion System for Wide Weaving Machines
Authors: Zhang Chengjun , Liu Yue , Peng Yi , Wang Yi , Li Chengyuan , Zuo Xiaoyan , Xu Chuqiao , Zhou Xiangyang
Published: March 2024

Wide weaving machines traditionally enhance the weaving width by increasing the shuttle’s initial velocity. However, this approach introduces challenges like pronounced equipment vibration, elevated noise levels, heightened energy consumption, and a reduced lifespan. Moreover, its efficacy in significantly widening fabric is constrained. Addressing these concerns, this paper proposes a wide-width warp insertion solution that involves driving the high-temperature superconducting shuttle to achieve high-speed horizontal flight through a traveling magnetic field. The inductive weft insertion system structure of wide weaving machines comprises an insertion guideway with an iron core and wound electromagnetic coils. The shuttle consists of a high-temperature superconducting block and a conductive plate, serving as the driving element. By establishing the equivalent circuit of the weft insertion guideway and the suspended shuttle, the calculation formula for the dynamic driving performance of the weft insertion guideway is obtained. Utilizing a transient 3D magnetic field simulation model, the impact of parameters like the current frequency, shuttle conductive plate thickness, and suspension gap on weft insertion performance is explored. Successful wide-width weft insertion motion is achieved by controlling coil input current parameters. Finally, an experimental platform is constructed to validate the correctness of the weft insertion system structure and simulation model through practical experiments.
Quantifying the External Joint Workload and Safety of Latin Dance in Older Adults: Potential Benefits for Musculoskeletal Health
Authors: Loría-Calderón Tyrone M. , Gómez-Carmona Carlos D. , Santamaría-Guzmán Keven G. , Rodríguez-Hernández Mynor , Pino-Ortega José
Published: March 2024

As global aging rises, identifying strategies to mitigate age-related physical decline has become an urgent priority. Dance represents a promising exercise modality for older adults, yet few studies have quantified the external loads older dancers experience. This study aimed to characterize the impacts accumulated across lower limb and spinal locations in older adults during Latin dance. Thirty older Latin dancers (age = 66.56 ± 6.38 years; female = 93.3%) wore inertial sensors on the scapulae, lumbar spine, knees, and ankles during a 1 h class. A distal-to-proximal gradient emerged in the total impacts (F = 429.29; p < 0.01; ωp2 = 0.43) and per intensities (F = 103.94-to-665.55; p < 0.01; ωp2 = 0.07-to-0.54), with the highest impacts sustained in the ankles (≈9000 total impacts) from 2 g to >10 g (p < 0.01; d = 1.03-to-4.95; ankles > knees > lower back > scapulae) and knees (≈12,000 total impacts) when <2 g (p < 0.01, d = 2.73-to-3.25; knees > ankles > lower back > scapulae). The majority of the impacts remained below 6 g across all anatomical locations (>94%). The impacts also increased in lower limb locations with faster tempos (r = 0.10-to-0.52; p < 0.01), while subtly accumulating over successive songs rather than indicating fatigue (r = 0.11-to-0.35; p < 0.01). The mild ankle and knee loads could strengthen the dancers’ lower extremity bones and muscles in a population vulnerable to sarcopenia, osteoporosis, and falls. Quantifying the workload via accelerometry enables creating personalized dance programs to empower healthy aging. With global aging rising, this work addresses a timely public health need regarding sustainable lifelong exercise for older people. Ranging from low to moderate, the measured impact magnitudes suggest that dance lessons may provide enough osteogenic stimulus without overloading structures.
Exploring the Spatio-Temporal Trends of Geomorphological Incidents Induced by Precipitation on Chinese Highways
Authors: Zhang Jie , Tian Hua , Song Jianyang
Published: March 2024

The spatiotemporal distribution of geomorphological incidents was examined in the present study, including the characteristics of obstruction distances and durations, by utilizing nationwide incident mitigation data and precipitation observation records from the period spanning 2019 to 2022. By comparing rainfall features over different temporal scales across various regions, the aim of the present study was to enhance the current comprehension of the patterns through which regional precipitation initiates incidents on highways by comparing rainfall characteristics over distinct temporal scales across diverse geographical areas. The findings indicate that: (1) The spatial distribution of highway incidents in China is significantly correlated with regional natural environments, predominantly concentrated in the southern parts of the country’s second and third topographical terraces. The temporal distribution closely aligns with annual and monthly precipitation patterns, with the majority of occurrences taking place from June to September. Further, notable disparities in the distribution of highway-related incidents were observed among counties across most provinces; (2) National highways experience a notably higher frequency of incidents than expressways and provincial roads, with most obstruction lengths concentrated within 1 km and durations predominantly under 3 days; (3) The probability of daily rainfall inducing highway incidents is distinctly higher than that of short-duration rainfall, with eastern and southern China experiencing significantly greater inducing precipitation volumes than other regions. The majority of areas are susceptible to incidents within a 3-day window following heavy rainfall or within 24 h after intense short-duration rainfall. Moreover, it is observed that incidents are more closely associated with extreme precipitation occurring within a single day; (4) There is a certain lag between the timing of incidents and the occurrence of extreme short-duration heavy rainfall, with the highest frequency of incidents coinciding with continuous rainfall periods of 3 to 6 days.
BioDiffusion: A Versatile Diffusion Model for Biomedical Signal Synthesis
Authors: Li Xiaomin , Sakevych Mykhailo , Atkinson Gentry , Metsis Vangelis
Published: March 2024

Machine learning tasks involving biomedical signals frequently grapple with issues such as limited data availability, imbalanced datasets, labeling complexities, and the interference of measurement noise. These challenges often hinder the optimal training of machine learning algorithms. Addressing these concerns, we introduce BioDiffusion, a diffusion-based probabilistic model optimized for the synthesis of multivariate biomedical signals. BioDiffusion demonstrates excellence in producing high-fidelity, non-stationary, multivariate signals for a range of tasks including unconditional, label-conditional, and signal-conditional generation. Leveraging these synthesized signals offers a notable solution to the aforementioned challenges. Our research encompasses both qualitative and quantitative assessments of the synthesized data quality, underscoring its capacity to bolster accuracy in machine learning tasks tied to biomedical signals. Furthermore, when juxtaposed with current leading time-series generative models, empirical evidence suggests that BioDiffusion outperforms them in biomedical signal generation quality.
Distribution and Genetic Lineages of the Craspedacusta sowerbii Species Complex (Cnidaria, Olindiidae) in Italy
Authors: Morpurgo Massimo , Marrone Federico , Ciutti Francesca , Cappelletti Cristina , Vorhauser Samuel , Alber Renate , Dossena Matteo , Salmaso Nico , Fontaneto Diego , Caputo Luciano , Vecchioni Luca
Published: March 2024

Olindiid freshwater jellyfishes of the genus Craspedacusta Lankester, 1880 are native to eastern Asia; however, some species within the genus have been introduced worldwide and are nowadays present in all continents except Antarctica. To date, there is no consensus regarding the taxonomy within the genus Craspedacusta due to the morphological plasticity of the medusa stages. The species Craspedacusta sowerbii Lankester, 1880 was first recorded in Italy in 1946, and until 2017, sightings of the jellyfish Craspedacusta were reported for 40 water bodies. Here, we shed new light on the presence of the freshwater jellyfishes belonging to the genus Craspedacusta across the Italian peninsula, Sardinia, and Sicily. First, we report 21 new observations of this non-native taxon, of which eighteen refer to medusae sightings, two to environmental DNA sequencing, and one to the finding of polyps. Then, we investigate the molecular diversity of collected Craspedacusta specimens, using a Bayesian analysis of sequences of the mitochondrial gene encoding for Cytochrome c Oxidase Subunit I (mtDNA COI). Our molecular analysis shows the presence of two distinctive genetic lineages: (i) a group that comprises sequences obtained from populations ranging from central to northern Italy; (ii) a group that comprises three populations from northern Italy—i.e., those from the Lake Levico, the Lake Santo of Monte Terlago, and the Lake Endine—and the single known Sicilian population. We also report for the first time a mtDNA COI sequence obtained from a Craspedacusta medusa collected in Spain.
The Effect of Reduced Fibrinogen on Cerebrovascular Permeability during Traumatic Brain Injury in Fibrinogen Gene Heterozygous Knockout Mice
Authors: Sulimai Nurul , Brown Jason , Lominadze David
Published: March 2024

Vascular contribution to cognitive impairment and dementia (VCID) is a term referring to all types of cerebrovascular and cardiovascular disease-related cognitive decline, spanning many neuroinflammatory diseases including traumatic brain injury (TBI). This becomes particularly important during mild-to-moderate TBI (m-mTBI), which is characterized by short-term memory (STM) decline. Enhanced cerebrovascular permeability for proteins is typically observed during m-mTBI. We have previously shown that an increase in the blood content of fibrinogen (Fg) during m-mTBI results in enhanced cerebrovascular permeability. Primarily extravasated via a transcellular pathway, Fg can deposit into the parenchyma and exacerbate inflammatory reactions that can lead to neurodegeneration, resulting in cognitive impairment. In the current study, we investigated the effect of a chronic reduction in Fg concentration in blood on cerebrovascular permeability and the interactions of extravasated Fg with astrocytes and neurons. Cortical contusion injury (CCI) was used to generate m-mTBI in transgenic mice with a deleted Fg γ chain (Fg γ+/−), resulting in a low blood content of Fg, and in control C57BL/6J wild-type (WT) mice. Cerebrovascular permeability was tested in vivo. Interactions of Fg with astrocytes and neurons and the expression of neuronal nuclear factor-кB (NF-кB) were assessed via immunohistochemistry. The results showed that 14 days after CCI, there was less cerebrovascular permeability, lower extravascular deposition of Fg, less activation of astrocytes, less colocalization of Fg with neurons, and lower expression of neuronal pro-inflammatory NF-кB in Fg γ+/− mice compared to that found in WT mice. Combined, our data provide strong evidence that increased Fg extravasation, and its resultant extravascular deposition, triggers astrocyte activation and leads to potential interactions of Fg with neurons, resulting in the overexpression of neuronal NF-кB. These effects suggest that reduced blood levels of Fg can be beneficial in mitigating the STM reduction seen in m-mTBI.
What Are the Economic Arguments for Mandating LGBT+ Health Training for Healthcare Providers? An Economic Evaluation of the Impacts of LGBT+ Health Training on Cervical Screening
Authors: Bashir Saima , Whittaker William , Meads Catherine
Published: March 2024

Background: Equitable access to healthcare is a priority of many healthcare systems, aiming to ensure access is driven by need and not minority groups such as those defined by sexual orientation. However, there are healthcare areas where inequity in access across sexual orientation groups is found that are not justified based on need. Mandated LGBTQ+-specific training of the healthcare workforce may help address some barriers of access for these groups. The study aims to understand the potential economic implications for mandated LGBTQ+-specific healthcare training on the healthcare system in England, UK to inform commissioning of training provision. Methods: Cervical cancer screening was used as an exemplar case where there appears to be inequity in access for different sexual orientation groups. A decision model was developed and analysed that considered the impacts of greater uptake of screening for lesbian and bisexual women due to LGBTQ+ training. Costs took the perspective of the healthcare system and outcomes modelled were cancer cases averted in a timeframe of 5 years. Results: Based on cervical cancer screening alone, where training costs are fully attributed to this service, training would likely result in fewer cancer cases detected in the lesbian and bisexual populations, though this comes at a modest increase in healthcare sector costs, with this increase largely reflecting a greater volume of screens. Training costs do not appear to be a major component of the cost implications. Conclusions: In resource-constrained systems with increasing pressures for efficiency savings, the opportunity cost of delivering training is a realistic component of the commissioning decision. The findings in this paper provide a signal that mandated LGBTQ+ training in healthcare could lead to potentially greater outcomes and in breaking down barriers of access and could also enable the healthcare system to provide more equitable access to healthcare.
Combined Effects of Steel and Glass Fibres on the Fracture Performance of Recycled Rubber Concrete
Authors: Li Xiaohui , Pan Zezhou , Zhen Hao , Luo Wenhua , Chen Zhuangwei , Li Hongming , Wu Zhichao , Liu Feng , Li Lijuan
Published: March 2024

As an environmentally friendly construction material, recycled rubber concrete (RRC) is commonly used as a road material owing to its excellent flexural strength and crack resistance. Previous studies have shown that the addition of fibres is an effective method for improving the crack resistance of concrete. The purpose of this study is to investigate the fracture performance of RRC reinforced with steel fibres (SFs) and glass fibres (GFs). A total of 28 RRC mixtures were prepared. The results of the fracture test showed that the addition of SFs and GFs significantly enhanced the RRC fracture performance. The maximum increases or decreases in flexural strength, brittleness coefficient, fracture energy, initial fracture toughness, and unstable fracture toughness were 64.9, −34.6, 775.6, 92.0, and 118.4%, respectively. The ideal GF content is usually in the range of 0.4–0.6% and decreases with increasing SF content. In addition, scanning electron microscope (SEM) tests were conducted to explore the mechanism of the effect of hybrid fibres on RRC at a microscopic level. The results show that SFs were always pulled out, while GFs were pulled apart at the initial defects. At the same time, excessive GFs caused more initial defects. These results are expected to provide theoretical direction and experimental support for the practical application of hybrid fibre-reinforced recycled rubber concrete (HFRRRC).
Neo-Adjuvant Therapy for Metastatic Melanoma
Authors: Kuijpers Anke M. J. , van Akkooi Alexander C. J.
Published: March 2024

Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient’s immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma.
Prognostic Significance of the Cribriform Pattern in Prostate Cancer: Clinical Outcomes and Genomic Alterations
Authors: Sayan Mutlay , Tuac Yetkin , Akgul Mahmut , Pratt Grace K. , Rowan Mary D. , Akbulut Dilara , Kucukcolak Samet , Tjio Elza , Moningi Shalini , Leeman Jonathan E. , Orio Peter F. , Nguyen Paul L. , D’Amico Anthony V. , Aktan Cagdas
Published: March 2024

Purpose: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. Methods: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher’s exact test. Results: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes—KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63—had significantly lower mRNA expression levels in patients with CP4 compared to those without. Conclusions: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.
Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?
Authors: Riondino Silvia , Rosenfeld Roberto , Formica Vincenzo , Morelli Cristina , Parisi Giusy , Torino Francesco , Mariotti Sabrina , Roselli Mario
Published: March 2024

The interplay between the immune system and chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is complex and multifaceted. In COPD, chronic inflammation and oxidative stress can lead to immune dysfunction that can exacerbate lung damage, further worsening the respiratory symptoms. In NSCLC, immune cells can recognise and attack the cancer cells, which, however, can evade or suppress the immune response by various mechanisms, such as expressing immune checkpoint proteins or secreting immunosuppressive cytokines, thus creating an immunosuppressive tumour microenvironment that promotes cancer progression and metastasis. The interaction between COPD and NSCLC further complicates the immune response. In patients with both diseases, COPD can impair the immune response against cancer cells by reducing or suppressing the activity of immune cells, or altering their cytokine profile. Moreover, anti-cancer treatments can also affect the immune system and worsen COPD symptoms by causing lung inflammation and fibrosis. Immunotherapy itself can also cause immune-related adverse events that could worsen the respiratory symptoms in patients with COPD-compromised lungs. In the present review, we tried to understand the interplay between the two pathologies and how the efficacy of immunotherapy in NSCLC patients with COPD is affected in these patients.
Magnesium Is a Vital Ion in the Body—It Is Time to Consider Its Supplementation on a Routine Basis
Authors: Pethő Ákos Géza , Fülöp Tibor , Orosz Petronella , Tapolyai Mihály
Published: March 2024

The importance of maintaining proper magnesium intake and total body magnesium content in preserving human health remains underappreciated among medical professionals and laymen. This review aimed to show the importance of hypomagnesemia as a modifiable risk factor for developing disease processes. We searched the PubMed database and Google Scholar using the keywords ‘magnesium’, ‘diabetes’, ‘cardiovascular disease’, ‘respiratory disease’, ‘immune system’, ‘inflammation’, ‘autoimmune disease’, ‘neurology’, ‘psychiatry’, ‘cognitive function’, ‘cancer’, and ‘vascular calcification’. In multiple contexts of the search terms, all reviews, animal experiments, and human observational data indicated that magnesium deficiency can lead to or contribute to developing many disease states. The conclusions of several in-depth reviews support our working hypothesis that magnesium and its supplementation are often undervalued and underutilized. Although much research has confirmed the importance of proper magnesium supply and tissue levels, simple and inexpensive magnesium supplementation has not yet been sufficiently recognized or promoted.
Antimicrobial Activity of Dimeric Flavonoids
Authors: Lopes Inês , Campos Carla , Medeiros Rui , Cerqueira Fátima
Published: March 2024

Distributed throughout the environment are various microorganisms such as bacteria, fungi, parasites, and viruses. Although many are part of the human microbiome, many are pathogenic and cause infections ranging from mild to severe. In recent years, the identification of multidrug-resistant microorganisms has become a serious public health problem. The resulting infections call into question the therapeutic capacity of health systems and lead to approximately 70,000 deaths annually worldwide. The progressive resistance to antibiotics and antifungals has been a major challenge for the medical and pharmaceutical community, requiring the search for new compounds with antimicrobial properties. Several studies have demonstrated the potential of natural and synthesized flavonoids, especially the dimers of these molecules. In this review are presented many examples of dimeric flavonoids that have demonstrated antimicrobial activity against viruses, like influenza and Human Immunodeficiency Virus (HIV), protozoal infections, such as Leishmaniasis and Malaria, fungal infections by Candida albicans and Cryptococcus neoformans, and bacterial infections caused, for example, by Staphylococcus aureus and Escherichia coli. In the pursuit to find potential safe agents for therapy in microbial infections, natural dimeric flavonoids are an option not only for the antimicrobial activity, but also for the low toxicity usually associated with these compounds when compared to classic antimicrobials.
Effects of Si Addition on Interfacial Microstructure and Corrosion Resistance of Hot-Dip Zn–Al–Mg–Si Alloy-Coated Steel
Authors: So Seong-Min , Grandhi Srinivasulu , Kwon Eui-Pyo , Oh Min-Suk
Published: March 2024

Alloy coatings protect steel from corrosion in various applications. We investigated the effects of Si addition on the microstructure, electrochemical behavior, and corrosion resistance of steel sheets coated with a hot-dip Zn–Mg–Al–Si alloy using a batch-type galvanization process. Microstructural analysis revealed that the Zn–Al–Mg alloy coating layer contained a significant amount of Fe that diffused from the substrate, leading to delamination due to the formation of brittle Fe–Zn intermetallic compounds. However, the introduction of Si resulted in the formation of a stable Fe2Al3Si inhibition layer at the substrate–coating interface; this layer prevented interdiffusion of Fe as well as enhanced the coating adhesion. Additionally, the formation of acicular Mg2Si phases on the coating surface improved the surface roughness. As the Si content increased, the corrosion resistance of the coating improved. Specifically, the Zn–Al–Mg coating layer with 0.5 wt.% Si exhibited excellent anti-corrosion performance, without red rust formation on its surface even after 2600 h, during a salt spray test.
Ovarian Morphology in Non-Hirsute, Normo-Androgenic, Eumenorrheic Premenopausal Women from a Multi-Ethnic Unselected Siberian Population
Authors: Lazareva Ludmila , Suturina Larisa , Atalyan Alina , Danusevich Irina , Nadelyaeva Iana , Belenkaya Lilia , Egorova Irina , Ievleva Kseniia , Babaeva Natalia , Lizneva Daria , Legro Richard S. , Azziz Ricardo
Published: March 2024

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM). Currently, data on age- and ethnicity-dependent features of PCOM remain insufficient. We aimed to estimate ethnicity- and age-dependent differences in ovarian volume (OV) and follicle number per ovary (FNPO) in a healthy, medically unbiased population of Caucasian and Asian premenopausal women, who participated in the cross-sectional Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384) in 2016–2019. The study population consisted of 408 non-hirsute, normo-androgenic, eumenorrheic premenopausal women aged 18–44 years. All participants underwent a uniform evaluation including a review of their medical history and a physical examination, blood sampling, and pelvic ultrasonography. The statistical analysis included non-parametric tests and the estimation of the upper normal limits (UNLs) by 98th percentiles for OV and FNPO. In the total study population, the upper OV percentiles did not differ by ethnicity or age group. By contrast, the UNL of FNPO was higher in Caucasian women than in Asian women, and women aged <35 years demonstrated a higher UNL of FNPO compared to older women. In summary, these data suggest that the estimation of FNPO, but not OV, should take into account the ethnicity and age of the individual in estimating the presence of PCOM.
A Survey of Offline- and Online-Learning-Based Algorithms for Multirotor Uavs
Authors: Sönmez Serhat , Rutherford Matthew , Valavanis Kimon
Published: March 2024

Multirotor UAVs are used for a wide spectrum of civilian and public domain applications. Their navigation controllers include onboard sensor suites that facilitate safe, autonomous or semi-autonomous multirotor flight, operation, and functionality under nominal and detrimental conditions and external disturbances, even when flying in uncertain and dynamically changing environments. During the last decade, given the available computational power, different learning-based algorithms have been derived, implemented, and tested to navigate and control, among other systems, multirotor UAVs. Learning algorithms have been and are used to derive data-driven based models, to identify parameters, to track objects, to develop navigation controllers, and to learn the environments in which multirotors operate. Learning algorithms combined with model-based control techniques have proven beneficial when applied to multirotors. This survey summarizes the research published since 2015, dividing algorithms, techniques, and methodologies into offline and online learning categories and then further classifying them into machine learning, deep learning, and reinforcement learning sub-categories. An integral part and focus of this survey is on online learning algorithms as applied to multirotors, with the aim to register the type of learning techniques that are either hard or almost hard real-time implementable, as well as to understand what information is learned, why, how, and how fast. The outcome of the survey offers a clear understanding of the recent state of the art and of the type and kind of learning-based algorithms that may be implemented, tested, and executed in real time.
Machine Learning Approaches for Inverse Problems and Optimal Design in Electromagnetism
Authors: Formisano Alessandro , Tucci Mauro
Published: March 2024

The spread of high-performance personal computers, frequently equipped with powerful Graphic Processing Units (GPUs), has raised interest in a set of techniques that are able to extract models of electromagnetic phenomena (and devices) directly from available examples of desired behavior. Such approaches are collectively referred to as Machine Learning (ML). A typical representative ML approach is the so-called “Neural Network” (NN). Using such data-driven models allows the evaluation of the output in a much shorter time when a theoretical model is available, or allows the prediction of the behavior of the systems and devices when no theoretical model is available. With reference to a simple yet representative benchmark electromagnetic problem, some of the possibilities and pitfalls of the use of NNs for the interpretation of measurements (inverse problem) or to obtain required measurements (optimal design problem) are discussed. The investigated aspects include the choice of NN model, the generation of the dataset(s), and the selection of hyper-parameters (hidden layers, training paradigm). Finally, the capabilities in the handling of ill-posed problems are critically revised.
An Efficiency Improvement Strategy for Triple-Active-Bridge-Based DC Energy Routers in DC Microgrids
Authors: Meng Xiaoli , Duan Qing , Sha Guanglin , Zhao Caihong , Wang Haoqing , Wang Xueli , Lan Zheng
Published: March 2024

A triple-active bridge (TAB) can be used as a power conversion unit in a three-port DC energy router (DCER) such as a triple-active bridge-based DC energy router (TAB-DCER). The operational loss of a TAB can be seen as a key factor affecting the efficiency of a TAB-DCER. However, the RMS value of the inductor current of the TAB-DCER increases under single-phase shift (SPS) control, and this greatly increases the system operating losses. The use of phase-shifted plus PWM (PS-PWM) control can reduce the RMS value of the inductor current, but its mathematical model is complex, and involves difficult calculations. To address this problem, in the study reported here, we developed an optimal control strategy for the RMS value of the inductor current based on TAB-DCER. First, the working principle of a TAB-DCER under PS-PWM control was analyzed, and a circuit decomposition model was established. Second, the operating modes under PS-PWM control were analyzed, and corresponding expressions of port power and the RMS value of the inductor current were obtained. Third, an optimized mathematical model of the sum of squares of the RMS value of the inductor current of the TAB-DCER was constructed. Finally, a genetic algorithm was used to solve the mathematical model and derive the optimal phase shift angle; this resulted in a lower RMS value of the inductor current in the TAB-DCER and reduced the system operating losses. The simulation and experimental results show that the TAB-DCER used in the present study can reduce operating losses, improve system efficiency, and deliver coordinated power control.
Lessons in Developing a Behavioral Coding Protocol to Analyze In-the-Wild Child–Robot Interaction Events and Experiments
Authors: Indurkhya Xela , Venture Gentiane
Published: March 2024

Behavioral analyses of in-the-wild HRI studies generally rely on interviews or visual information from videos. This can be very limiting in settings where video recordings are not allowed or limited. We designed and tested a vocalization-based protocol to analyze in-the-wild child–robot interactions based upon a behavioral coding scheme utilized in wildlife biology, specifically in studies of wild dolphin populations. The audio of a video or audio recording is converted into a transcript, which is then analyzed using a behavioral coding protocol consisting of 5–6 categories (one indicating non-robot-related behavior, and 4–5 categories of robot-related behavior). Refining the code categories and training coders resulted in increased agreement between coders, but only to a level of moderate reliability, leading to our recommendation that it be used with three coders to assess where there is majority consensus, and thereby correct for subjectivity. We discuss lessons learned in the design and implementation of this protocol and the potential for future child–robot experiments analyzed through vocalization behavior. We also perform a few observational behavior analyses from vocalizations alone to demonstrate the potential of this field.