bluuebunny/crossref_metadata_2025 huggingface dataset:
Casimersen (AMONDYS 45™): An Antisense Oligonucleotide for Duchenne Muscular Dystrophy
Authors: Assefa Milyard , Gepfert Addison , Zaheer Meesam , Hum Julia M. , Skinner Brian W.
Published: April 2024

Casimersen (AMONDYS 45TM) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass developed by Sarepta therapeutics. It was approved by the Food and Drug Administration (FDA) in February 2021 to treat Duchenne muscular dystrophy (DMD) in patients whose DMD gene mutation is amenable to exon 45 skipping. Administered intravenously, casimersen binds to the pre-mRNA of the DMD gene to skip a mutated region of an exon, thereby producing an internally truncated yet functional dystrophin protein in DMD patients. This is essential in maintaining the structure of a myocyte membrane. While casimersen is currently continuing in phase III of clinical trials in various countries, it was granted approval by the FDA under the accelerated approval program due to its observed increase in dystrophin production. This article discusses the pathophysiology of DMD, summarizes available treatments thus far, and provides a full drug review of casimersen (AMONDYS 45TM).
The Aftermath of COVID-19: Exploring the Long-Term Effects on Organ Systems
Authors: Golzardi Maryam , Hromić-Jahjefendić Altijana , Šutković Jasmin , Aydin Orkun , Ünal-Aydın Pinar , Bećirević Tea , Redwan Elrashdy M. , Rubio-Casillas Alberto , Uversky Vladimir N.
Published: April 2024

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50–70% are hospitalised. It has also been shown that 10–12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC. Conclusions: Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed.
Global DNA Methylation Level in Tumour and Margin Samples in Relation to Human Papilloma Virus and Epstein–Barr Virus in Patients with Oropharyngeal and Oral Squamous Cell Carcinomas
Authors: Gaździcka Jadwiga , Biernacki Krzysztof , Gołąbek Karolina , Miśkiewicz-Orczyk Katarzyna , Zięba Natalia , Misiołek Maciej , Strzelczyk Joanna Katarzyna
Published: April 2024

Background: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. Methods: The enzyme-linked immunosorbent assay (ELISA) was used to analyse global DNA methylation levels in OPSCC and OSCC tumours and the margin samples after DNA isolation. HPV detection was conducted by hybridisation using GenoFlow HPV Array Test Kits (DiagCor Bioscience Inc., Hong Kong, China). EBV detection was performed using real-time PCR with an EBV PCR Kit (EBV/ISEX/100, GeneProof, Brno, Czech Republic). Results: OPSCC tumour samples obtained from women showed lower global DNA methylation levels than those from men (1.3% vs. 3.5%, p = 0.049). The margin samples from OPSCC patients with HPV and EBV coinfection showed global DNA methylation lower than those without coinfection (p = 0.042). G3 tumours from OSCC patients had significantly lower levels of global DNA methylation than G2 tumours (0.98% ± 0.74% vs. 3.77% ± 4.97%, p = 0.010). Additionally, tumours from HPV-positive OSCC patients had significantly lower global DNA methylation levels than those from HPV-negative patients (p = 0.013). In the margin samples, we observed a significant negative correlation between global DNA methylation and the N stage of OSCC patients (rS = −0.33, p = 0.039). HPV-positive OPSCC patients had higher global DNA methylation levels than HPV-positive OSCC patients (p = 0.015). Conclusion: We confirmed that methylation could be changed in relation to viral factors, such as HPV and EBV, as well as clinical and demographical parameters.
The Phenomenon of Antiretroviral Drug Resistance in the Context of Human Immunodeficiency Virus Treatment: Dynamic and Ever Evolving Subject Matter
Authors: Apetroaei Miruna-Maria , Velescu Bruno Ștefan , Nedea Marina Ionela (Ilie) , Dinu-Pîrvu Cristina Elena , Drăgănescu Doina , Fâcă Anca Ionela , Udeanu Denisa Ioana , Arsene Andreea Letiția
Published: April 2024

Human immunodeficiency virus (HIV) is a significant global health issue that affects a substantial number of individuals across the globe, with a total of 39 million individuals living with HIV/AIDS. ART has resulted in a reduction in HIV-related mortality. Nevertheless, the issue of medication resistance is a significant obstacle in the management of HIV/AIDS. The unique genetic composition of HIV enables it to undergo rapid mutations and adapt, leading to the emergence of drug-resistant forms. The development of drug resistance can be attributed to various circumstances, including noncompliance with treatment regimens, insufficient dosage, interactions between drugs, viral mutations, preexposure prophylactics, and transmission from mother to child. It is therefore essential to comprehend the molecular components of HIV and the mechanisms of antiretroviral medications to devise efficacious treatment options for HIV/AIDS.
New Regenerative and Anti-Aging Medicine Approach Based on Single-Stranded Alpha-1 Collagen for Neo-Collagenesis Induction: Clinical and Instrumental Experience of a New Injective Polycomponent Formulation for Dermal Regeneration
Authors: Di Rosa Luigi , De Pasquale Antonino , Baldassano Sara , Marguglio Noemi , Drid Patrik , Proia Patrizia , Vasto Sonya
Published: April 2024

This study explores the efficacy of a novel polycomponent formulation (KARISMA Rh Collagen® FACE, Taumedika Srl, Rome, Italy), containing 200 mg/mL of non-crosslinked high-molecular-weight hyaluronic acid (HMW-HA), 200 μg/mL of a human recombinant polypeptide of collagen-1 alpha chain, and 40 mg/mL of carboxymethyl cellulose (CMC) as a regenerative medicine for skin regeneration and rejuvenation. This formulation combines non-crosslinked high-molecular-weight hyaluronic acid, human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose to stimulate collagen type I production and enhance skin hydration. This study involved 100 subjects with varying skin conditions, divided into three groups based on skin aging, smoking history, and facial scarring, to evaluate the product’s effectiveness in skin regeneration and aesthetic improvement. The methodology included two injections of Karisma (2 mL for each injection) one month apart, with evaluations conducted using FACE-Q questionnaires, the SGAIS Questionnaire, and Antera 3D skin scanner measurements at baseline, 30 days, and 60 days post-treatment. The results demonstrated a significant reduction in skin roughness and an improvement in skin quality across all the groups, with no correlation between the outcomes and the patient’s age. The subjective assessments also indicated high satisfaction with the treatment’s aesthetic results. The analyzed data allow us to conclude that the single-stranded collagen with hyaluronic acid and carboxymethyl-cellulose formulation is able to stimulate the skin’s regenerative response, yielding significant results both in vitro and, through our study, also in vivo. This new polycomponent formulation effectively stimulates skin regeneration, improving skin quality and texture, with significant aesthetic benefits perceived by patients, and a low incidence of adverse events, marking a promising advancement in regenerative medicine.
Associations between the VDR Gene rs731236 (TaqI) Polymorphism and Bone Mineral Density in Postmenopausal Women from the RAC-OST-POL
Authors: Górczyńska-Kosiorz Sylwia , Tabor Elżbieta , Niemiec Paweł , Pluskiewicz Wojciech , Gumprecht Janusz
Published: April 2024

Background: Postmenopausal osteoporosis is not only related to hormonal factors but is also associated with environmental and genetic factors. One of the latter is the polymorphism of vitamin D receptor (VDR). The aim of the reported study was to comprehensively analyze the VDR gene polymorphic variants rs731236 (TaqI), rs1544410 (BsmI) and rs7975232 (ApaI) in the Polish population of postmenopausal women. Methods: The study group consisted of 611 women after menopause (their median age was 65.82 ± 6.29 years). Each of them underwent bone densitometry (DXA) of the non-dominant femoral neck and total hip with a biochemical analysis of vitamin D3 serum concentration and genotyping of the above-mentioned single nucleotide polymorphisms (SNPs); the obtained results were analyzed in the aspect of waist circumference (WC), body mass index (BMI) and past medical history. Results: The genotype prevalence rates of all SNPs were compatible with Hardy–Weinberg equilibrium (p > 0.050). Out of the studied polymorphisms, only rs731236 genotype variants affected DXA, with AG heterozygotes showing the worst bone parameters. Neither patient age nor vitamin D3 concentration, BMI, WC or comorbidities was associated with rs731236 genotype. Conclusions: Out of the polymorphisms studied, only rs731236 genotypes differed among the DXA results, while the AG heterozygotes were characterized by the lowest median bone mineral density.
Artificial Extracellular Vesicles Generated from T Cells Using Different Induction Techniques
Authors: Zmievskaya Ekaterina A. , Mukhametshin Sabir A. , Ganeeva Irina A. , Gilyazova Elvina M. , Siraeva Elvira T. , Kutyreva Marianna P. , Khannanov Artur A. , Yuan Youyong , Bulatov Emil R.
Published: April 2024

Cell therapy is at the forefront of biomedicine in oncology and regenerative medicine. However, there are still significant challenges to their wider clinical application such as limited efficacy, side effects, and logistical difficulties. One of the potential approaches that could overcome these problems is based on extracellular vesicles (EVs) as a cell-free therapy modality. One of the major obstacles in the translation of EVs into practice is their low yield of production, which is insufficient to achieve therapeutic amounts. Here, we evaluated two primary approaches of artificial vesicle induction in primary T cells and the SupT1 cell line—cytochalasin B as a chemical inducer and ultrasonication as a physical inducer. We found that both methods are capable of producing artificial vesicles, but cytochalasin B induction leads to vesicle yield compared to natural secretion, while ultrasonication leads to a three-fold increase in particle yield. Cytochalasin B induces the formation of vesicles full of cytoplasmic compartments without nuclear fraction, while ultrasonication induces the formation of particles rich in membranes and membrane-related components such as CD3 or HLAII proteins. The most effective approach for T-cell induction in terms of the number of vesicles seems to be the combination of anti-CD3/CD28 antibody activation with ultrasonication, which leads to a seven-fold yield increase in particles with a high content of functionally important proteins (CD3, granzyme B, and HLA II).
Circulating Tumour DNA and Its Prognostic Role in Management of Muscle Invasive Bladder Cancer: A Narrative Review of the Literature
Authors: Kapriniotis Konstantinos , Tzelves Lazaros , Lazarou Lazaros , Mitsogianni Maria , Mitsogiannis Iraklis
Published: April 2024

Current management of non-metastatic muscle invasive bladder cancer (MIBC) includes radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC), offers a 5-year survival rate of approximately 50% and is associated with significant toxicities. A growing body of evidence supports the role of liquid biopsies including circulating tumour DNA (ctDNA) as a prognostic and predictive marker that could stratify patients according to individualised risk of progression/recurrence. Detectable ctDNA levels prior to radical cystectomy have been shown to be correlated with higher risk of recurrence and worse overall prognosis after cystectomy. In addition, ctDNA status after NAC/neoadjuvant immunotherapy is predictive of the pathological response to these treatments, with persistently detectable ctDNA being associated with residual bladder tumour at cystectomy. Finally, detectable ctDNA levels post-cystectomy have been associated with disease relapse and worse disease-free (DFS) and overall survival (OS) and might identify a population with survival benefit from adjuvant immunotherapy.
Applications of Hydrogels in Osteoarthritis Treatment
Authors: Gan Xin , Wang Xiaohui , Huang Yiwan , Li Guanghao , Kang Hao
Published: April 2024

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management.
Chemerin in Participants with or without Insulin Resistance and Diabetes
Authors: Zhao Lei , Zhou Jonathan , Abbasi Fahim , Fathzadeh Mohsen , Knowles Joshua W. , Leung Lawrence L. K. , Morser John
Published: April 2024

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92–199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing.
Pleiotropic Action of TGF-Beta in Physiological and Pathological Liver Conditions
Authors: Braczkowski Michał Jakub , Kufel Klaudia Maria , Kulińska Julia , Czyż Daniel Łukasz , Dittmann Aleksander , Wiertelak Michał , Młodzik Marcin Sławomir , Braczkowski Ryszard , Soszyński Dariusz
Published: April 2024

The aim of this study is to review and analyze the pleiotropic effects of TGF-β in physiological and pathological conditions of the liver, with particular emphasis on its role in immune suppression, wound healing, regulation of cell growth and differentiation, and liver cell apoptosis. A literature review was conducted, including 52 studies, comprising review articles, in vitro and in vivo studies, and meta-analyses. Only studies published in peer-reviewed scientific journals were included in the analysis. TGF-β is a pleiotropic growth factor that is crucial for the liver, both in physiology and pathophysiology. Although its functions are complex and diverse, TGF-β plays a constant role in immune suppression, wound healing, and the regulation of cell growth and differentiation. In concentrations exceeding the norm, it can induce the apoptosis of liver cells. Increased TGF-β levels are observed in many liver diseases, such as fibrosis, inflammation, and steatosis. TGF-β has been shown to play a key role in many physiological and pathological processes of the liver, and its concentration may be a potential diagnostic and prognostic marker in liver diseases.
Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases
Authors: Altay Ozlem , Yang Hong , Yildirim Serkan , Bayram Cemil , Bolat Ismail , Oner Sena , Tozlu Ozlem Ozdemir , Arslan Mehmet Enes , Hacimuftuoglu Ahmet , Shoaie Saeed , Zhang Cheng , Borén Jan , Uhlén Mathias , Turkez Hasan , Mardinoglu Adil
Published: April 2024

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.
Irisin and Its Role in Postmenopausal Osteoporosis and Sarcopenia
Authors: Falsetti Irene , Palmini Gaia , Donati Simone , Aurilia Cinzia , Iantomasi Teresa , Brandi Maria
Published: April 2024

Menopause, an extremely delicate phase in a woman’s life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.
Exploring Embodied Intelligence in Soft Robotics: A Review
Authors: Zhao Zikai , Wu Qiuxuan , Wang Jian , Zhang Botao , Zhong Chaoliang , Zhilenkov Anton A.
Published: April 2024

Soft robotics is closely related to embodied intelligence in the joint exploration of the means to achieve more natural and effective robotic behaviors via physical forms and intelligent interactions. Embodied intelligence emphasizes that intelligence is affected by the synergy of the brain, body, and environment, focusing on the interaction between agents and the environment. Under this framework, the design and control strategies of soft robotics depend on their physical forms and material properties, as well as algorithms and data processing, which enable them to interact with the environment in a natural and adaptable manner. At present, embodied intelligence has comprehensively integrated related research results on the evolution, learning, perception, decision making in the field of intelligent algorithms, as well as on the behaviors and controls in the field of robotics. From this perspective, the relevant branches of the embodied intelligence in the context of soft robotics were studied, covering the computation of embodied morphology; the evolution of embodied AI; and the perception, control, and decision making of soft robotics. Moreover, on this basis, important research progress was summarized, and related scientific problems were discussed. This study can provide a reference for the research of embodied intelligence in the context of soft robotics.
Effects of Sodium Alginate and Calcium Chloride on Fungal Growth and Viability in Biomass-Fungi Composite Materials Used for 3D Printing
Authors: Rahman Al Mazedur , Bedsole Caleb Oliver , Akib Yeasir Mohammad , Hamilton Jillian , Rahman Taieba Tuba , Shaw Brian D. , Pei Zhijian
Published: April 2024

To combat climate change, one approach is to manufacture products from biomass-fungi composite materials instead of petroleum-based plastics. These products can be used in packaging, furniture, and construction industries. A 3D printing-based manufacturing method was developed for these biomass-fungi composite materials, eliminating the need for molds, and enabling customized product design. However, previous studies on the 3D printing-based method showed significant shrinkage of printed samples. In this paper, an approach is proposed to reduce the shrinkage by incorporating ionic crosslinking into biomass-fungi composite materials. This paper reports two sets of experiments regarding the effects of sodium alginate (SA) and calcium chloride (CaCl2) on fungal growth and fungal viability. The first set of experiments was conducted using Petri dishes with fungi isolated from colonized biomass-fungi material and different concentrations of SA and CaCl2. Fungal growth was measured by the circumference of fungal colonies. The results showed that concentrations of SA and CaCl2 had significant effects on fungal growth and no fungal growth was observed on Petri dishes with 15% CaCl2. Some of these Petri dishes were also observed under confocal microscopy. The results confirmed the differences obtained by measuring the circumference of fungal colonies. The second set of experiments was conducted using Petri dishes with biomass-fungi mixtures that were treated with different concentrations of SA and exposure times in a CaCl2 (crosslinking) solution. Fungal viability was measured by counting colony-forming units. The results showed that the addition of the SA solution and exposure times in the crosslinking solution had statistically significant effects on fungal viability. The 2SA solution was prepared by dissolving 2 g of SA in 100 mL of water, the 5SA solution was prepared by dissolving 5 g of SA in 100 mL of water, and the crosslinking solution was prepared by dissolving 5 g of CaCl2 in 100 mL of water. The results also showed that fungal viability was not too low in biomass-fungi mixtures that included 2SA solution and were exposed to the crosslinking solution for 1 min.
Differential Cortical and Subcortical Activations during Different Stages of Muscle Control: A Functional Magnetic Resonance Imaging Study
Authors: Peng Yu , Wang Zhaoxin
Published: April 2024

Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical activation across different stages of muscle control using functional magnetic resonance imaging (fMRI). An event-related design was employed. In each trial, participants (n = 10) were instructed to gently press a button with their right index finger, hold it naturally for several seconds, and then relax the finger. Neural activation in these temporally separated stages was analyzed using a General Linear Model. Our findings revealed that a widely distributed cortical network, including the supplementary motor area and insula, was implicated not only in the pressing stage, but also in the relaxation stage, while only parts of the network were involved in the steady holding stage. Moreover, supporting the direct/indirect pathway model of the subcortical basal ganglia, their substructures played distinct roles in different stages of muscle control. The caudate nucleus exhibited greater involvement in muscle contraction, whereas the putamen demonstrated a stronger association with muscle relaxation; both structures were implicated in the pressing stage. Furthermore, the subthalamic nucleus was exclusively engaged during the muscle relaxation stage. We conclude that even the control of simple muscle movements involves intricate automatic higher sensory–motor integration at a neural level, particularly when coordinating relative muscle movements, including both muscle contraction and muscle relaxation; the cortical and subcortical regions assume distinct yet coordinated roles across different stages of muscle control.
What Does It Take to Play the Piano? Cognito-Motor Functions Underlying Motor Learning in Older Adults
Authors: Worschech Florian , Passarotto Edoardo , Losch Hannah , Oku Takanori , Lee André , Altenmüller Eckart
Published: April 2024

The acquisition of skills, such as learning to play a musical instrument, involves various phases that make specific demands on the learner. Knowledge of the cognitive and motor contributions during learning phases can be helpful in developing effective and targeted interventions for healthy aging. Eighty-six healthy older participants underwent an extensive cognitive, motoric, and musical test battery. Within one session, one piano-related and one music-independent movement sequence were both learned. We tested the associations between skill performance and cognito-motor abilities with Bayesian mixed models accounting for individual learning rates. Results showed that performance was positively associated with all cognito-motor abilities. Learning a piano-related task was characterized by relatively strong initial associations between performance and abilities. These associations then weakened considerably before increasing exponentially from the second trial onwards, approaching a plateau. Similar performance–ability relationships were detected in the course of learning a music-unrelated motor task. Positive performance–ability associations emphasize the potential of learning new skills to produce positive cognitive and motor transfer effects. Consistent high-performance tasks that demand maximum effort from the participants could be very effective. However, interventions should be sufficiently long so that the transfer potential can be fully exploited.
Numerical Analysis of the Ultimate Bearing Capacity of Strip Footing Constructed on Sand-over-Clay Sediment
Authors: Banu Shaziya , Attom Mousa , Abed Farid , Vandanapu Ramesh , Astillo Philip Virgil , Al-Lozi Naser , Khalil Ahmed
Published: April 2024

This paper analyzes the bearing capacity of two-layered soil medium using finite element (FE) software ABAQUS/CAE 2023. Although geotechnical engineers design foundations for layered soil, majorly current geotechnical studies emphasize single homogenous soil. So, this research has significant novelty as it focuses on layered soil and adds to the current literature. A nonlinear FE model was prepared and analyzed to determine the ultimate bearing capacity of two-layered soil (sandy soil over clayey soil). The Drucker–Prager and Mohr–Coulomb models were used to represent sandy soil and clayey soil layers, respectively. Strip footing material properties were considered isotropic and linearly elastic. This study performed parametric studies to understand the effects of thickness, unit weight, and the modulus of the elasticity of sandy soil on the ultimate soil bearing capacity. Additionally, it also analyzed the effect of the cohesive strength of clayey soil on layered soil bearing capacity. Results showed that an increase in sandy soil layer thickness strengthens the layered soil, and thus, improves the bearing capacity of soil. Increasing the sandy soil layer thickness over footing width (h1/B) ratio from 0.15 to 2.0 improved the ultimate bearing capacities with elastic settlements of 350 mm and 250 mm by 145.62% and 101.66%, respectively. Additionally, for a thicker sandy soil layer, an increase in the unit weight and modulus of the elasticity of sandy soil led to higher ultimate bearing capacity. Furthermore, it was concluded that an increase in clayey soil’s cohesive strength from 20 kPa to 30 kPa resulted in a 24.31% and 3.47% increase in soil bearing capacity for h1/B = 0.15 and h1/B = 2.0, respectively. So, the effect of cohesion is prevalent in the case of a thicker clayey soil layer.
Volume Stability and Mechanical Properties of Cement Paste Containing Natural Fibers from Phragmites-Australis Plant at Elevated Temperature
Authors: Ghanem Hassan , Ramadan Rawan , Khatib Jamal , Elkordi Adel
Published: April 2024

The utilization of bio-fiber materials in building components has become imperative for improving sustainability, controlling global warming, addressing environmental concerns, and enhancing concrete properties. This study is part of a wide-range investigation on the use of Phragmites-Australis (PhA) fibers in construction and building materials. In this paper, the volume stability and mechanical properties of paste containing PhA fibers and exposed to high temperatures were investigated. Four mixes were made with 0, 0.5, 1, and 2% fibers by volume. To evaluate the volume stability and mechanical properties, the chemical shrinkage, autogenous shrinkage, drying shrinkage, expansion, ultrasonic pulse velocity, compressive strength, and flexural strength were tested. The curing duration and temperature were 180 days and 45 °C, respectively. The results indicated that an addition of PhA fibers of up to 2% resulted in a reduction in all the shrinkage parameters at 180 days. The presence of PhA fibers in the paste tended to reduce the compressive strength, with the lowest value observed at 2%. Apart from the values at 90 days, the optimal flexural strength seemed to be achieved by the paste with 1% PhA fibers. To further elucidate the experimental results, a hyperbolic model was employed to predict the variation in the length change as a function of the curing age with a high accuracy. Based on the results obtained, PhA fibers can play a crucial role in mitigating the shrinkage parameters and enhancing the mechanical properties of cement paste.
Seismic Assessment of Large-Span Spatial Structures Considering Soil–Structure Interaction (SSI): A State-of-the-Art Review
Authors: Zhan Puyu , Xue Suduo , Li Xiongyan , Sun Guojun , Ma Ruisheng
Published: April 2024

Soil–structure interaction (SSI), which characterizes the dynamic interaction between a structure and its surrounding soil, is of great significance to the seismic assessment of structures. Past research endeavors have undertaken analytical, numerical, and experimental studies to gain a thorough understanding of the influences of SSI on the seismic responses of a wide array of structures, including but not limited to nuclear power plants, frame structures, bridges, and spatial structures. Thereinto, large-span spatial structures generally have much more complex configurations, and the influences of SSI may be more pronounced. To this end, this paper aims to provide a state-of-the-art review of the SSI in the seismic assessment of large-span spatial structures. It begins with the modelling of soil medium, followed by the research progress of SSI in terms of numerical simulations and experiments. Subsequently, the focus shifts towards high-lighting advancements in understanding the seismic responses of large-span spatial structures considering SSI. Finally, some discussions are made on the unresolved problems and the possible topics for future studies.
T-Cell Engagers—The Structure and Functional Principle and Application in Hematological Malignancies
Authors: Cech Paweł , Skórka Katarzyna , Dziki Laura , Giannopoulos Krzysztof
Published: April 2024

Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed. T-cell engagers (TCEs) are BsAbs, which simultaneously target tumor-associated antigens on tumor cells and CD3 molecules present on T-cells. This mechanism allows for the direct activation of T-cells and their anti-tumor features, ultimately resulting in the lysis of tumor cells. In 2014, the FDA approved blinatumomab, a TCE directed to CD3 and CD19 for treatment of acute lymphoblastic leukemia. Since then, numerous TCEs have been developed, allowing for treating different hematological malignancies such as acute myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma and Hodgkin lymphoma. As of November 2023, seven clinically approved TCE therapies are on the market. TCE-based therapies still have their limitations; however, improving the properties of TCEs, as well as combining TCE-based therapies with other forms of treatment, give hope to find the cures for currently terminal diseases. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects.
Causes and Risk Factors of Breast Cancer, What Do We Know for Sure? An Evidence Synthesis of Systematic Reviews and Meta-Analyses
Authors: Løyland Borghild , Sandbekken Ida Hellum , Grov Ellen Karine , Utne Inger
Published: April 2024

Breast cancer affected more than 2.3 million women in 2022 and is the most diagnosed cancer among women worldwide. The incidence rates are greater in developed regions and are significantly higher among women with higher education and socioeconomic status. Therefore, it is reasonable to assume that the way women live their lives may impact their risk of being diagnosed with breast cancer. This systematic review aimed to identify what is known about the causes and risk factors of breast cancer, excluding genetic causes. A comprehensive systematic search identified 2387 systematic reviews, 122 were included and six overall themes identified. In our “top list” with the 36 most important findings, a study of breast density had the highest effect size for increasing the risk of breast cancer, and a high sex-hormone-binding globulin level was the most protective factor. Many of the included studies investigating the same topics had conflicting results. The conclusion from this evidence synthesis reveals a lack of consensus of factors associated with the causes and risk of breast cancer. These findings suggest that recommendations about lifestyle and breast cancer should be made with caution.
Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy
Authors: Klotz Laura V. , Zimmermann Julia , Müller Karolina , Kovács Julia , Hassan Mohamed , Koller Michael , Schmid Severin , Huppertz Gunnar , Markowiak Till , Passlick Bernward , Hofmann Hans-Stefan , Winter Hauke , Hatz Rudolf A. , Eichhorn Martin E. , Ried Michael
Published: April 2024

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.
Controlling Fluorescence Wavelength in the Synthesis of TGA-Capped CdTe Quantum Dots
Authors: Martins Catarina S. M. , Silva Ana L. , Gouveia Luís Pleno de , Çaha Ihsan , Bondarchuk Oleksandr , LaGrow Alec P. , Deepak Francis Leonard , Prior João A. V.
Published: April 2024

Quantum dots (QDs) are semiconductor materials, with a size range between 1–10 nm, showcasing unique size-dependent physical and chemical properties. Such properties have potentiated their use in areas like medical imaging and biosensing. Herein, we present an open-air approach for synthesis of QDs, reducing the need for controllable atmospheric conditions. Furthermore, we present a predictive mathematical model for maximum emission wavelength (λmax) control. Through a straightforward microwave-based aqueous synthesis of TGA-CdTe QDs, we investigated the influence of time, temperature, and Te:Cd and TGA:Cd molar ratios on λmax, using a chemometric experimental design approach. CdTe-QDs were characterized by UV-Vis and fluorescence spectroscopies. Additionally, Fourier-Transform Infrared spectroscopy, X-ray photoelectron spectroscopy, Transmission Electron Microscopy, and Energy Dispersive X-ray were conducted. Stable QDs with fluorescence ranging from green to red (527.6 nm to 629.2 nm) were obtained. A statistical analysis of the results revealed that time and temperature were the most significant factors influencing λmax. After fine-tuning the variables, a mathematical model with 97.7% of prediction accurately forecasted experimental conditions for synthesizing TGA-CdTe QDs at predefined λmax. Stability tests demonstrated that the QDs retained their optical characteristics for over a month at 4 °C, facilitating diverse applications.
Gaining Insight into Teenagers’ Experiences of Pain after Laparoscopic Surgeries: A Prospective Study
Authors: Visoiu Mihaela , Chelly Jacques , Sadhasivam Senthilkumar
Published: April 2024

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers’ pain can be complemented by knowledge of patient pain behavior, catastrophizing thoughts about pain, anxiety, and mood level. Two hundred and two patients completed the study—56.4% were female, 89.6% White, 5.4% Black, and 5% were of other races. Patient ages ranged from 11 to 17 years (mean = 13.8; SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r = 0.56) have a high level of agreement, and teenagers and nurses (r = 0.47) have a moderate level of agreement on pain scores (p < 0.05). The correlation between patient APBQ (adolescent pain behavior questionnaire) and teenager VAS (visual analog scale) and between nurse APBQ and teenager VAS, while statistically significant (p < 0.05), is weaker (r range = 0.14–0.17). There is a moderate correlation between teenagers’ pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range = 0.26–0.39; p < 0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.
Development of a Standardized Algorithm for Management of Newly Diagnosed Anorectal Malformations
Authors: Srinivas Shruthi , Gasior Alessandra , Driesbach Sarah , DeBacco Natalie , Pruitt Liese C. C. , Trimble Casey , Zahora Pooja , Mueller Claudia M. , Wood Richard J.
Published: April 2024

Neonates with a new diagnosis of anorectal malformation (ARM) present a unique challenge to the clinical team. ARM is strongly associated with additional midline malformations, such as those observed in the VACTERL sequence, including vertebral, cardiac, and renal malformations. Timely assessment is necessary to identify anomalies requiring intervention and to prevent undue stress and delayed treatment. We utilized a multidisciplinary team to develop an algorithm guiding the midline workup of patients newly diagnosed with ARM. Patients were included if born in or transferred to our neonatal intensive care unit (NICU), or if seen in clinic within one month of life. Complete imaging was defined as an echocardiogram, renal ultrasound, and spinal magnetic resonance imaging or ultrasound within the first month of life. We compared three periods: prior to implementation (2010–2014), adoption period (2015), and delayed implementation (2022); p ≤ 0.05 was considered significant. Rates of complete imaging significantly improved from pre-implementation to delayed implementation (65.2% vs. 50.0% vs. 97.0%, p = 0.0003); the most growth was observed in spinal imaging (71.0% vs. 90.0% vs. 100.0%, p = 0.001). While there were no differences in the rates of identified anomalies, there were fewer missed diagnoses with the algorithm (10.0% vs. 47.6%, p = 0.05). We demonstrate that the implementation of a standardized algorithm can significantly increase appropriate screening for anomalies associated with a new diagnosis of ARM and can decrease delayed diagnosis. Further qualitative studies will help to refine and optimize the algorithm moving forward.
Static Plantar Pressure under Different Conditions in Children with Surgically Treated Unilateral Slipped Capital Femoral Epiphysis
Authors: Negru Marius , Bolovan Andrei Daniel , Amaricai Elena , Catan Liliana , Belei Oana , Lazarescu Adrian Emil , Stanciulescu Corina Maria , Boia Eugen Sorin , Popoiu Calin Marius
Published: April 2024

Background: Slipped capital femoral epiphysis (SCFE) is the most common hip disease during infancy and adolescence. Our study aimed to analyze static plantar pressure in children with surgically treated unilateral SCFE. Methods: Twenty-two children with right SCFE with in situ fixation with one percutaneous screw were assessed by PoData plantar pressure analysis under three different conditions (open eyes, eyes closed, and head retroflexed). Results: The total foot loading was significantly higher on the unaffected limb compared with the affected one for all the three testing conditions (p < 0.05). When assessing the differences between testing conditions, there were no significant differences for the right and left foot loadings, or for the three sites of weight distribution, except for the right fifth metatarsal head (lower loading in eyes-closed condition in comparison to eyes open, p = 0.0068), left fifth metatarsal head (increased loading in head-retroflexed condition in comparison to eyes open, p = 0.0209), and left heel (lower loading in head-retroflexed condition in comparison to eyes open, p = 0.0293). Conclusion: Even after a successful surgical procedure, differences in foot loading can impact the postural static activities in different conditions (natural eyes-open, eyes-closed, or head-retroflexed posture).