bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Evaluation on Thermal Performance of 3D Printed Concrete Walls: The Effects of Lattice Type, Filament Width and Granular Filling Material
Authors: Chamatete Kunda , Yalçınkaya Çağlar
Published: March 2024

Three-dimensional concrete printing (3DCP) is of great interest to scientists and the construction industry to bring automation to structural engineering applications. However, studies on the thermal performance of three-dimensional printed concrete (3DPC) building envelopes are limited, despite their potential to provide a long-term solution to modern construction challenges. This work is a numerical study to examine the impact of infill geometry on 3DPC lattice envelope thermal performance. Three different lattice structures were modeled to have the same thickness and nearly equal contour lengths, voids, and insulation percentages. Additionally, the effects of filament width and the application of granular insulating materials (expanded polystyrene beads and loose-fill perlite) were also studied. Finally, the efficacy of insulation was established. Results show that void area affects the thermal performance of 3DPC envelopes under stagnant air conditions, while web length, filament width, and contact (intersection) area between the webs and face shells affect the thermal behavior when cavities are filled with insulating materials due to thermal bridging. The thermal efficiency of insulation, which shows the effective use of insulation, varies between 26 and 44%, due to thermal bridges.
A Numerical Study of a Soil-Nail-Supported Excavation Pit Subjected to a Vertically Loaded Strip Footing at the Crest
Authors: Gui Meen-Wah , Rajak Ravendra P.
Published: March 2024

Soil nailing is a prevalent and cost-effective technique employed to reinforce and enhance the stability of precarious natural or cut slopes; however, its application as a primary support system to prevent collapses or cave-ins during foundation excavation could be more frequent. To better understand the behavior of such a support system, this study simulated a full-scale nail-supported excavation for the foundation pit of a 20-story building to examine the effect of placing a strip footing with various combinations of configurations on the crest of the excavation pit. The results are discussed in terms of the nail axial force, wall horizontal deflection, basal heave, and safety factor against sliding. The results show that the footing width and setback distance are the two most significant factors dominating the wall horizontal deflection. This study also reveals that the maximum axial force is closely related to the apparent active earth pressure, which accounts for the presence of a tension crack, at nail depth. Such a finding allows engineers to assess and mitigate the risks of structural failure more effectively and optimize the design of nail-retaining structures.
Influence of Staggered Truss on Progressive Collapse-Resistant Behavior of Steel Frame Structures
Authors: Ke Changren , Fan Yihui , Jiang Junling
Published: March 2024

In order to study the effect of the support mode of a staggered truss system on the continuous collapse resistance performance of a steel structure, four finite element models were established based on the bracing arrangement of a five-story steel frame structure. The situations of different columns on the first floor removed were classified into eight scenarios, and five models of each scenario were analyzed with nonlinear dynamic analyses. Finally, a computational metric based on energy robustness was proposed to evaluate the robustness of the structure. The results of nonlinear dynamic analyses indicated that the staggered truss system significantly improved the resistance to progressive collapse of steel frame structures and effectively increased the redundancy of steel frame structures. All four bracing methods effectively reduced the vertical displacement at the point of failure, with the peak displacement at the point of failure reduced by a maximum of 84 percent and a minimum of 41 percent compared to a pure frame structure. Moreover, the staggered truss system can reduce some axial force peaks in the adjacent columns adjacent to the failed columns. The structural robustness coefficients of Model A, Scheme 1, Scheme 2, Scheme 3, and Scheme 4 are 1.144, 1.339, 1.306, 1.584, and 1.176, respectively, according to the proposed robustness calculation method, which shows that the braced steel frame structure has improved robustness over the original structure. The staggered truss system improves the robustness of the steel frame structure so that the steel frame structure has better resistance to progressive collapse.
Model Test on the Collapse Evolution Law of Tunnel Excavation in Composite Strata with a Cavity
Authors: Zhang Changan , Gao Jianlei , Wang Zhengzhong , Liu Chang
Published: March 2024

More complex geological conditions could be encountered with the construction of urban subway projects. At present, many subway tunnels have been built in composite strata with upper soft and lower hard layers, but the presence of a cavity in the strata increases the risk of collapse during construction. In this paper, a series of model experiments and discrete element methods were conducted to investigate the failure behavior of composite strata with a cavity caused by tunnel excavation disturbance. The influence of the distance between the cavity and vault (hd) and the distance between the soil–rock interface and vault (hr) on the collapse of the composite strata are analyzed. The research results indicate that tunnel collapse exhibits progressive failure because of the forming of a collapsed arch in the strata. If the hd is greater than the tunnel span (D), the arch can be stabilized without other disturbances. Additionally, the thickness of the tunnel rock layer affects the height of the collapsed arch significantly, as it is difficult to form a stable arch when the hr is less than 2/3 D. Finally, reasonable construction safety distances are proposed based on the possibility of forming a stable arch collapse in the tunnel and determining the range of the collapse.
Cultivating Sustainable Construction: Stakeholder Insights Driving Circular Economy Innovation for Inclusive Resource Equity
Authors: Karaca Ferhat , Tleuken Aidana , Pineda-Martos Rocío , Ros Cardoso Sara , Orel Daniil , Askar Rand , Agibayeva Akmaral , Güemez Elena Goicolea , Salles Adriana , Varol Huseyin Atakan , Braganca Luis
Published: March 2024

Due to its intricate production processes, complex supply chains, and industry-specific characteristics, the construction industry faces unique challenges in adopting circular economy (CE) principles that promote resource equity. To address this issue, this study aims to delve into identifying stakeholders’ opinions and perceptions regarding key CE strategies across different stages of the building life cycle (BLC). Both European and non-European stakeholders within the “CircularB” COST Action network and beyond participated in this research. Three methods were employed to assess stakeholders’ opinions: an online survey, a structured survey with a semi-guided workshop, and creative thinking round table discussions. Natural language processing (NLP), specifically topic modelling and sentiment analysis, was used to analyse the data collected from the online survey, which gathered text-based opinions from 209 participants on the cost-benefit aspects of circularity strategies. The structured survey, which collected data from 43 workshop participants, evaluated the perceived importance of CE strategies across various BLC phases and assessed the adoption of selected CE strategies in current or past projects. Finally, the Six Thinking Hats® activity, employed in the round table discussions, generated ideas from 25 professionals regarding the broader implementation challenges and opportunities of CE in construction. The research findings highlight the need to bridge the gap between theory and practice by fostering active industry stakeholder involvement in the transition to a CE model. The analyses of the collected stakeholder opinions through the three activities contribute to proactive and collaborative efforts aimed at advancing resource equity in the construction sector and promoting just and inclusive resource use. In summary, this research offers a comprehensive understanding of stakeholders’ opinions on CE strategies and provides guidance for the development of targeted policies and strategies to accelerate the integration of CE principles in the construction industry.
Evaluation of Moisture-Induced Stresses in Wood Cross-Sections Determined with a Time-Dependent, Plastic Material Model during Long-Time Exposure
Authors: Pech Sebastian , Autengruber Maximilian , Lukacevic Markus , Lackner Roman , Füssl Josef
Published: March 2024

In recent years, the use of timber as a building material in larger construction applications such as multi-story buildings and bridges has increased. This requires a better understanding of the material to realize such constructions and design them more economically. However, accurate computational simulations of timber structures are challenging due to the complexity and inhomogeneity of this naturally grown material. It exhibits growth inhomogeneities such as knots and fiber deviations, orthotropic material behavior and moisture dependence of almost all physical parameters. Describing the creep response of wood under real climate conditions is particularly difficult. Changes in moisture content, plasticity and viscoelasticity affect moisture-induced stresses and potentially lead to cracks and structural damage. In this paper, we apply a material model that combines time and moisture-dependent behavior with multisurface plasticity to simulate cross-sections of different dimensions over a 14-month climate period. Our findings indicate that considering this long-term behavior has a minor impact on moisture-induced stresses during the drying period. However, during the wetting period, neglecting the time- and moisture-dependent material behavior of wood leads to a significant overestimation of tensile stresses within the cross-section, resulting in unrealistic predictions of wetting-induced fracture. Therefore, simulations during wetting periods require a sophisticated rheological model to properly reproduce the stress field.
The Mechanical and Self-Sensing Properties of Carbon Fiber- and Polypropylene Fiber-Reinforced Engineered Cementitious Composites Utilizing Environmentally Friendly Glass Aggregate
Authors: Ma Lijun , Sun Meng , Zhang Yunlong
Published: March 2024

In order to facilitate waste glass recycling and enable the monitoring of concrete structures, this study prepares a new type of self-sensing engineered cementitious composite (ECC) via the use of glass sand instead of silica sand. The health monitoring of a concrete structure is achieved through the addition of polypropylene (PP) fibers to enhance the flexural toughness of concrete, and adding carbon fibers (CFs) to make the concrete self aware, enabling it to sense the load changes and structural damage. The fiber dosage of ECC is optimized to analyze the effects of different fiber types and dosages on the mechanical and self-sensing properties of concrete. The results show that the hybrid fibers produce a good synergistic effect on mechanical properties, and the presence of excess fibers causes the mechanical properties of concrete to deteriorate. The critical fiber volume fraction required for the strain hardening of PP ranges from 0.75% vol to 1% vol. At different PP dosages, the CF dosage shows a positive correlation with the initial crack strength. By analyzing the effect of varied curing times and CF doping on the initial resistivity, it is found that the threshold value of CF conductivity is 0.7% vol. The role of CFs in the flexural sensitivity and pressure sensitivity tests is explained from the perspective of fiber distribution, and the fiber distribution theory is verified with scanning electron microscopy (SEM). The optimal level of CF doping for flexural sensitivity and pressure sensitivity is determined to be 1.1% vol and 0.7% vol via the use of self-sensing performance tests, respectively. An increase in PP fiber doping leads to a decrease in the initial resistivity and self-sensing properties of the material. The results of this research provide guidance regarding how to determine the optimal fiber dosage flexibly for different engineering works.
Improving Quality of Life and Psychosocial Health for Penile Cancer Survivors: A Narrative Review
Authors: Torres Irizarry Von Marie , Paster Irasema Concepcion , Ogbuji Vanessa , Gomez D’Andre Marquez , Mccormick Kyle , Chipollini Juan
Published: March 2024

Treatment of penile cancer (PC) focuses on organ preservation, employing various surgical and non-surgical approaches. These interventions may lead to disfigurement, impacting patients’ functional outcomes and psychosocial well-being. We reviewed studies related to penile health and PC up to February 2024, limited to studies published in English. Studies employing health-related quality of life (HRQoL) assessments have identified a detrimental association between aggressive treatment and overall health status, physical functioning, and relationships. In contrast, organ-sparing demonstrates improved measures related to HRQoL and sexual function. Assessment through validated questionnaires reveals diverse voiding outcomes, and varying impacts on QoL and sexual activity, emphasizing the necessity for multidisciplinary personalized care. Studies highlight substantial variations in sexual function, with patients reporting adaptations, reduced satisfaction, and concerns about body image and sexual well-being. Furthermore, unmet needs include challenges in patient–clinician communication, obtaining information, and accessing psychosocial support. Patient experiences underscore the importance of timely diagnosis, treatment access, and addressing psychological consequences. Organ-sparing approaches have higher QoL preservation and sexual function. Individualized support, including sexual therapy, support groups, and family counseling, is essential for post-treatment rehabilitation. Timely diagnosis and comprehensive care are paramount in addressing the multifaceted impact of PC on patients and families.
Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation
Authors: Fleischmann Maximilian , Bechwar Julia , Voigtländer Diana , Fischer Mike , Schnetzke Ulf , Hochhaus Andreas , Scholl Sebastian
Published: March 2024

Inhibition of menin in acute myeloid leukemia (AML) harboring histone-lysine-N-methyltransferase 2A rearrangement (KMT2Ar) or the mutated Nucleophosmin gene (NPM1c) is considered a novel and effective treatment approach in these patients. However, rapid acquisition of resistance mutations can impair treatment success. In patients with elevated retinoic acid receptor alpha (RARA) expression levels, promising effects are demonstrated by the next-generation RARalpha agonist tamibarotene, which restores differentiation or induces apoptosis. In this study, the combination of revumenib and tamibarotene was investigated in various KMT2Ar or NPM1c AML cell lines and patient-derived blasts, focusing on the potential synergistic induction of differentiation or apoptosis. Both effects were analyzed by flow cytometry and validated by Western blot analysis. Synergy calculations were performed using viability assays. Regulation of the relevant key mediators for the MLL complex were quantified by RT-qPCR. In MV4:11 cells characterized by the highest relative mRNA levels of RARA, highly synergistic induction of apoptosis is demonstrated upon combination treatment. Induction of apoptosis by combined treatment of MV4:11 cells is accompanied by pronounced induction of the pro-apoptotic protein BAX and a synergistic reduction in CDK6 mRNA levels. In MOLM13 and OCI-AML3 cells, an increase in differentiation markers like PU.1 or a decreased ratio of phosphorylated to total CEBPA is demonstrated. In parts, corresponding effects were observed in patient-derived AML cells carrying either KMT2Ar or NPM1c. The impact of revumenib on KMT2Ar or NPM1c AML cells was significantly enhanced when combined with tamibarotene, demonstrating synergistic differentiation or apoptosis initiation. These findings propose promising strategies for relapsed/refractory AML patients with defined molecular characteristics.
Radiomodulating Properties of Superparamagnetic Iron Oxide Nanoparticle (SPION) Agent Ferumoxytol on Human Monocytes: Implications for MRI-Guided Liver Radiotherapy
Authors: Shurin Michael R. , Kirichenko Vladimir A. , Shurin Galina V. , Lee Danny , Crane Christopher , Kirichenko Alexander V.
Published: March 2024

Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.
Synergy between BRD9- and IKZF3-Targeting as a Therapeutic Strategy for Multiple Myeloma
Authors: Chowdhury Basudev , Garg Swati , Ni Wei , Sattler Martin , Sanchez Dana , Meng Chengcheng , Akatsu Taisei , Stone Richard , Forrester William , Harrington Edmund , Buhrlage Sara J. , Griffin James D. , Weisberg Ellen
Published: March 2024

Progress in the treatment of multiple myeloma (MM) has resulted in improvement in the survival rate. However, there is still a need for more efficacious and tolerated therapies. We and others have shown that bromodomain-containing protein 9 (BRD9), a member of the non-canonical SWI/SNF chromatin remodeling complex, plays a role in MM cell survival, and targeting BRD9 selectively blocks MM cell proliferation and synergizes with IMiDs. We found that synergy in vitro is associated with the downregulation of MYC and Ikaros proteins, including IKZF3, and overexpression of IKZF3 or MYC could partially reverse synergy. RNA-seq analysis revealed synergy to be associated with the suppression of pathways associated with MYC and E2F target genes and pathways, including cell cycle, cell division, and DNA replication. Stimulated pathways included cell adhesion and immune and inflammatory response. Importantly, combining IMiD treatment and BRD9 targeting, which leads to the downregulation of MYC protein and upregulation of CRBN protein, was able to override IMiD resistance of cells exposed to iberdomide in long-term culture. Taken together, our results support the notion that combination therapy based on agents targeting BRD9 and IKZF3, two established dependencies in MM, represents a promising novel therapeutic strategy for MM and IMiD-resistant disease.
Antineoplastic Drug Synergy of Artesunate with Navitoclax in Models of High-Grade Serous Ovarian Cancer
Authors: McCorkle J. Robert , Ahn Rebecca , Cao Connie D. , Hill Kristen S. , Dietrich Charles S. , Kolesar Jill M.
Published: March 2024

Artesunate belongs to a class of medications derived from the sweet wormwood plant (Artemisia annua) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian cancer. Data suggest that artesunate exacerbates cellular oxidative stress, triggering apoptosis. In the current study, we investigated the ability of navitoclax, an inhibitor of the antiapoptotic Bcl-2 protein family, to enhance artesunate efficacy in ovarian cancer cells. Artesunate and navitoclax both demonstrated antiproliferative effects on 2D and 3D ovarian cancer cell models as single agents. Upon combination of navitoclax with artesunate, antineoplastic drug synergy was also observed in each of the 2D cell lines and ovarian tumor organoid models tested. Further investigation of this drug combination using intraperitoneal CAOV3 xenograft models in BALB/scid mice showed that the artesunate/navitoclax doublet was superior to single-agent artesunate and vehicle control treatment. However, it did not outperform single-agent navitoclax. With optimization, this drug combination could provide a new therapeutic option for ovarian cancer and warrants further preclinical investigation.
Role of SGLT2 Inhibitors, DPP-4 Inhibitors, and Metformin in Pancreatic Cancer Prevention
Authors: Laeeq Tooba , Ahmed Maheen , Sattar Hina , Zeeshan Muhammad Hamayl , Ali Meher Binte
Published: March 2024

Pancreatic carcinoma is a highly aggressive tumor that usually presents when it has already metastasized. Therapeutic options for cure remain scarce and rely on combination chemotherapy with limited sustainability. Diabetes is considered an important risk factor for the development of pancreatic cancer due to the production of proinflammatory cytokines, which result in increased cell proliferation. More than half of patients diagnosed with pancreatic cancer eventually develop diabetes due to the destruction of insulin-producing cells. The interlinkage of both diseases might identify a possible preventative strategy for reducing the incidence of pancreatic carcinoma. This study reviewed the recent literature on the association between pancreatic cancer risk and SGLT2 inhibitors, GLP-1 RA, DPP-4 inhibitors, and biguanides. There are mixed data regarding the relationship between GLP-1 RA and DPP-4 inhibitors and pancreatic cancer, with some trials suggesting that they might increase the risk. In contrast, studies have mostly revealed that SGLT2 inhibitors have an antiproliferative effect on various tumors, such as liver, pancreatic, prostate, bowel, lung, and breast carcinoma, which might be due to their mechanism of blockage of reabsorption of glucose by cells, lowering the amount of available glucose for the growth of tumor cells. Metformin, the first-line agent for diabetes, has also been shown to be associated with decreasing pancreatic cancer risk and improving prognosis in those who already have the disease. Dedicated trials are needed to further delineate the association of antidiabetic drugs with the risk of pancreatic cancer in the general population, as previous studies have mostly focused on diabetic patients.
Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma
Authors: Shirane Yuki , Fujii Yasutoshi , Ono Atsushi , Nakahara Hikaru , Hayes Clair Nelson , Miura Ryoichi , Murakami Serami , Sakamoto Naoya , Uchikawa Shinsuke , Fujino Hatsue , Nakahara Takashi , Murakami Eisuke , Yamauchi Masami , Miki Daiki , Kawaoka Tomokazu , Arihiro Koji , Tsuge Masataka , Oka Shiro
Published: March 2024

The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study aimed to evaluate the status and dynamics of peripheral T cell subpopulations in HCC patients receiving Atez/Bev treatment and to explore biomarkers predictive of a therapeutic response. We enrolled 83 unresectable advanced HCC patients who commenced Atez/Bev treatment at our hospital between October 2020 and June 2022. Peripheral T cell subpopulations in peripheral blood mononuclear cells at baseline and 3 weeks post-treatment were investigated using flow cytometry and compared with those in control samples from 18 healthy individuals. We retrospectively analyzed the association between peripheral T cell subpopulation profiles and clinical outcomes. Baseline peripheral T cell subpopulations could be profiled in 70 patients with sufficient cell counts, among whom 3-week subpopulations could be evaluated in 51 patients. Multivariate analysis showed that a high baseline proportion of CD8+ central memory T (TCM) cells was independently associated with longer progression-free survival (PFS). Further, overall survival (OS) was significantly prolonged in patients with increased CD8+ effector memory T (TEM) cell proportions. In conclusion, TCM proportion at baseline might be a good indicator of the efficacy of Atez/Bev therapy. Furthermore, observation of increasing TEM proportions might be an early predictor of the potential clinical benefits of treatment.
Immune Response and Metastasis—Links between the Metastasis Driver MACC1 and Cancer Immune Escape Strategies
Authors: Torke Sebastian , Walther Wolfgang , Stein Ulrike
Published: March 2024

Metastasis remains the most critical factor limiting patient survival and the most challenging part of cancer-targeted therapy. Identifying the causal drivers of metastasis and characterizing their properties in various key aspects of cancer biology is essential for the development of novel metastasis-targeting approaches. Metastasis-associated in colon cancer 1 (MACC1) is a prognostic and predictive biomarker that is now recognized in more than 20 cancer entities. Although MACC1 can already be linked with many hallmarks of cancer, one key process—the facilitation of immune evasion—remains poorly understood. In this review, we explore the direct and indirect links between MACC1 and the mechanisms of immune escape. Therein, we highlight the signaling pathways and secreted factors influenced by MACC1 as well as their effects on the infiltration and anti-tumor function of immune cells.
Controlling Recombination to Evolve Bacteriophages
Authors: Bull James J. , Wichman Holly A. , Krone Stephen M. , Molineux Ian J.
Published: March 2024

Recombination among different phages sometimes facilitates their ability to grow on new hosts. Protocols to direct the evolution of phage host range, as might be used in the application of phage therapy, would then benefit from including steps to enable recombination. Applying mathematical and computational models, in addition to experiments using phages T3 and T7, we consider ways that a protocol may influence recombination levels. We first address coinfection, which is the first step to enabling recombination. The multiplicity of infection (MOI, the ratio of phage to cell concentration) is insufficient for predicting (co)infection levels. The force of infection (the rate at which cells are infected) is also critical but is more challenging to measure. Using both a high force of infection and high MOI (>1) for the different phages ensures high levels of coinfection. We also apply a four-genetic-locus model to study protocol effects on recombinant levels. Recombinants accumulate over multiple generations of phage growth, less so if one phage outgrows the other. Supplementing the phage pool with the low-fitness phage recovers some of this ‘lost’ recombination. Overall, fine tuning of phage recombination rates will not be practical with wild phages, but qualitative enhancement can be attained with some basic procedures.
Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges
Authors: Prisciandaro Michele , Santinelli Enrico , Tomarchio Valeria , Tafuri Maria Antonietta , Bonchi Cecilia , Palazzo Gloria , Nobile Carolina , Marinucci Alessandra , Mele Marcella , Annibali Ombretta , Rigacci Luigi , Vacca Michele
Published: March 2024

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.
Change in Osmotic Pressure Influences the Absorption Spectrum of Hemoglobin inside Red Blood Cells
Authors: Karabaliev Miroslav , Tacheva Bilyana , Paarvanova Boyana , Georgieva Radostina
Published: March 2024

Absorption spectra of red blood cell (RBC) suspensions are investigated in an osmolarity range in the medium from 200 mOsm to 900 mOsm. Three spectral parameters are used to characterize the process of swelling or shrinkage of RBC—the absorbance at 700 nm, the Soret peak height relative to the spectrum background, and the Soret peak wavelength. We show that with an increase in the osmolarity, the absorbance at 700 nm increases and the Soret peak relative height decreases. These changes are related to the changes in the RBC volume and the resulting increase in the hemoglobin intracellular concentration and index of refraction. Confocal microscopy and flow cytometry measurements supported these conclusions. The maximum wavelength of the Soret peak increases with increasing osmolarity due to changes in the oxygenation state of hemoglobin. Using these spectrum parameters, the process of osmosis in RBCs can be followed in real time, but it can also be applied to various processes, leading to changes in the volume and shape of RBCs. Therefore, we conclude that UV–Vis absorption spectrophotometry offers a convenient, easily accessible, and cost-effective method to monitor changes in RBC, which can find applications in the field of drug discovery and diagnostics of RBC and hemoglobin disorders.
Cockayne Syndrome Patient iPSC-Derived Brain Organoids and Neurospheres Show Early Transcriptional Dysregulation of Biological Processes Associated with Brain Development and Metabolism
Authors: Szepanowski Leon-Phillip , Wruck Wasco , Kapr Julia , Rossi Andrea , Fritsche Ellen , Krutmann Jean , Adjaye James
Published: March 2024

Cockayne syndrome (CS) is a rare hereditary autosomal recessive disorder primarily caused by mutations in Cockayne syndrome protein A (CSA) or B (CSB). While many of the functions of CSB have been at least partially elucidated, little is known about the actual developmental dysregulation in this devasting disorder. Of particular interest is the regulation of cerebral development as the most debilitating symptoms are of neurological nature. We generated neurospheres and cerebral organoids utilizing Cockayne syndrome B protein (CSB)-deficient induced pluripotent stem cells derived from two patients with distinct severity levels of CS and healthy controls. The transcriptome of both developmental timepoints was explored using RNA-Seq and bioinformatic analysis to identify dysregulated biological processes common to both patients with CS in comparison to the control. CSB-deficient neurospheres displayed upregulation of the VEGFA-VEGFR2 signalling pathway, vesicle-mediated transport and head development. CSB-deficient cerebral organoids exhibited downregulation of brain development, neuron projection development and synaptic signalling. We further identified the upregulation of steroid biosynthesis as common to both timepoints, in particular the upregulation of the cholesterol biosynthesis branch. Our results provide insights into the neurodevelopmental dysregulation in patients with CS and strengthen the theory that CS is not only a neurodegenerative but also a neurodevelopmental disorder.
Hypothyroid Myopathy—A Rare Case from Paediatric Practice
Authors: Elkina Stanimira , Stoyanova Ventsislava , Halvadzhiyan Irina , Petrova Chayka
Published: March 2024

Hypothyroid myopathy is uncommon in childhood. Severe hypothyroid myopathy observed in paediatric practice is a part of Kocher–Debré–Semelaigne syndrome (KDSS, OR-PHA:2349), a rare disorder characterised by muscular pseudohypertrophy and long-standing moderate-to-severe hypothyroidism. We present a pubertal girl with KDSS diagnosed with severe myopathy and significantly limited mobility and progressively increasing pains in the lumbar area, hip joints, and the lower limbs. Additionally, the patient presented metabolic syndrome with severe obesity, growth retardation, and educational difficulties. In this case, adequate hormone replacement therapy with Levothyroxine evoked full recovery of the myopathy and a significant reversal in the patient’s general condition. In conclusion, emphasizing the knowledge related to KDSS can improve the diagnosis and prognosis of the condition.
Ultrasound–Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview
Authors: Januś Dominika , Kujdowicz Monika , Kaleta Konrad , Możdżeń Kamil , Radliński Jan , Taczanowska-Niemczuk Anna , Kiszka-Wiłkojć Aleksandra , Maślanka Marcin , Górecki Wojciech , Starzyk Jerzy B.
Published: March 2024

Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic–solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli–Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.
SARS-CoV-2 Seroprevalence in a Berlin Kindergarten Environment: A Cross-Sectional Study, September 2021
Authors: Bernhard Julian , Theuring Stefanie , van Loon Welmoed , Mall Marcus A. , Seybold Joachim , Kurth Tobias , Rubio-Acero Raquel , Wieser Andreas , Mockenhaupt Frank P.
Published: March 2024

SARS-CoV-2 serology may be helpful to retrospectively understand infection dynamics in specific settings including kindergartens. We assessed SARS-CoV-2 seroprevalence in individuals connected to kindergartens in Berlin, Germany in September 2021. Children, staff, and household members from 12 randomly selected kindergartens were interviewed on COVID-19 history and sociodemographic parameters. Blood samples were collected on filter paper. SARS-CoV-2 anti-S and anti-N antibodies were assessed using Roche Elecsys. We assessed seroprevalence and the proportion of so far unrecognized SARS-CoV-2 infections. We included 277 participants, comprising 48 (17.3%) kindergarten children, 37 (13.4%) staff, and 192 (69.3%) household members. SARS-CoV-2 antibodies were present in 65.0%, and 52.7% of all participants were vaccinated. Evidence of previous infection was observed in 16.7% of kindergarten children, 16.2% of staff, and 10.4% of household members. Undiagnosed infections were observed in 12.5%, 5.4%, and 3.6%, respectively. Preceding infections were associated with facemask neglect. In conclusion, two-thirds of our cohort were SARS-CoV-2 seroreactive in September 2021, largely as a result of vaccination in adults. Kindergarten children showed the highest proportion of non-vaccine-induced seropositivity and an increased proportion of previously unrecognized SARS-CoV-2 infection. Silent infections in pre-school children need to be considered when interpreting SARS-CoV-2 infections in the kindergarten context.
Augmenting the Antitumor Efficacy of Natural Killer Cells via SynNotch Receptor Engineering for Targeted IL-12 Secretion
Authors: Ahmadnia Ali , Mohammadi Saeed , Yamchi Ahad , Kalani Mohamad Reza , Farazmandfar Touraj , Khosravi Ayyoub , Memarian Ali
Published: March 2024

Natural killer (NK) cells are crucial components of innate immunity, known for their potent tumor surveillance abilities. Chimeric antigen receptors (CARs) have shown promise in cancer targeting, but optimizing CAR designs for NK cell functionality remains challenging. CAR-NK cells have gained attention for their potential to reduce side effects and enable scalable production in cancer immunotherapy. This study aimed to enhance NK cell anti-tumor activity by incorporating PD1-synthetic Notch (synNotch) receptors. A chimeric receptor was designed using UniProt database sequences, and 3D structure models were generated for optimization. Lentiviral transduction was used to introduce PD1-Syn receptors into NK cells. The expression of PD1-Syn receptors on NK cell surfaces was assessed. Engineered NK cells were co-cultured with PDL1+ breast cancer cells to evaluate their cytotoxic activity and ability to produce interleukin-12 (IL-12) and interferon-gamma (IFNγ) upon interaction with the target cells. This study successfully expressed the PD1-Syn receptors on NK cells. CAR-NK cells secreted IL-12 and exhibited target-dependent IFNγ production when engaging PDL1+ cells. Their cytotoxic activity was significantly enhanced in a target-dependent manner. This study demonstrates the potential of synNotch receptor-engineered NK cells in enhancing anti-tumor responses, especially in breast cancer cases with high PDL1 expression.
Epidemiology of Hepatocellular Carcinoma in Taiwan
Authors: Lai Yu-Wei , Chung Ching-Hu
Published: March 2024

Background: Hepatocellular carcinoma (HCC) is a major contributor to the world’s cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. Methods: From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013–2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. Results: The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77–83.01% with mild liver disease and 29.93–37.30% with diabetes (without complications) in the period 2013–2021. Conclusions: The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.
Can Secondary Adhesive Capsulitis Complicate Calcific Tendinitis of the Rotator Cuff? An Ultrasound Imaging Analysis
Authors: Tuè Giovanni , Masuzzo Oriana , Tucci Francesco , Cavallo Marco , Parmeggiani Anna , Vita Fabio , Patti Alberto , Donati Danilo , Marinelli Alessandro , Miceli Marco , Spinnato Paolo
Published: March 2024

Background: Adhesive capsulitis (AC) of the glenohumeral joint is a recognized cause of pain associated with both active and passive restricted ranges of movement. AC can be subdivided into primary and secondary forms. Trauma, surgery, immobilization, and diabetes mellitus are the leading well-recognized causes of secondary AC. Calcific tendinitis/tendinitis (CT) of the rotator cuff is considered a possible trigger for AC, as reported in a few previous articles. However, there are no original investigations that assess the frequency and characteristics of this association. The aim of our research was to evaluate the presence of AC in a cohort of patients with a known CT condition of the rotator cuff by an ultrasound (US) examination. Materials and methods: We prospectively enrolled all the patients admitted at our single institution (October 2022–June 2023) for the preoperative US evaluation of a known CT condition. In these patients, we searched for parameters related to secondary AC. An axillary pouch (AP) thickness equal to or greater than 4 mm (or greater than 60% of the contralateral AP) was considered diagnostic of AC. Moreover, rotator interval (RI) thickness and the presence of effusion within the long-head biceps tendon (LHBT) sheath was also assessed in all patients. Results: A total of 78 patients (54F, 24M—mean age = 50.0 and range = 31–71 y.o.) were enrolled in the study. In 26 of those patients (26/78—33.3%), US signs of AC were detected. Notably, the mean AP thickness in patients with AC and CT was 3.96 ± 1.37 mm (Group 1) and 2.08 ± 0.40 mm in patients with CT only (Group 2). RI thickness was significantly greater in patients with superimposed AC: 2.54 ± 0.38 mm in Group 1 and 1.81 ± 0.41 mm in Group 2 (p < 0.00001). Moreover, effusion within the LHBT was significantly more frequently detected in patients with AC: 84.61% in Group 1 versus 15.79% in Group 2—p < 0.00001. Conclusion: US signs of AC are found in one-third of patients with CT of the rotator cuff, demonstrating that AC represents a frequent complication that should be routinely evaluated during US investigation to provide more personalized treatment strategies.
A Comprehensive Assessment of Al-Si Coating Growth at Various Heating Rates, Soaking Temperatures, and Times
Authors: Wu Siyu , Bardelcik Alexander , Chiriac Constantin , Shi Cangji
Published: March 2024

In conventional hot stamping, an Al-Si-coated blank is first heated above the austenitization temperature and then soaked for a period of time within a furnace, prior to the stamping operation. In this work, the impacts of furnace heating rate, soaking temperature, and soaking time on the Al-Si coating evolution were investigated for two commercial coating weights, 80 and 150 g/m2. These heat treatment parameters during heating and soaking affect the coating microstructure and the thickness of the interdiffusion layer, which affect the properties of the as-formed coatings. The transformation and growth of binary Fe-Al and ternary Fe-Al-Si intermetallic layers were characterized and quantified for soak times up to 240 s. The results show that the effect of the heating rate on the Al-Si intermetallic distribution and ternary phase morphology was more severe than the soaking time and soaking temperature. The Fe2Al5 (η) phase was the dominant layer at the beginning of the soaking stage with a Fe3Al2Si3 (τ1) layer formed within it, and then the Fe3Al2Si3 layer transformed into FeAl (β2) as the soaking time increased due to the interdiffusion of Fe and Al. The transformation of Fe3Al2Si3 to FeAl occurred at a higher rate for elevated soaking temperatures due to the greater diffusivity of Al and Fe. The interdiffusion layer (IDL) consisted of FeAl,Fe3Al(β1) and α−Fe. Higher soaking temperatures of 1000 °C resulted in a thicker IDL for the same soak time when compared with 900 °C and 950 °C, but when the heating rate was lower, the IDL was thicker than that at the higher heating rate since a longer heating time was required to reach the soaking temperature of 900 °C, which prolonged the diffusion time during the heating stage. The findings were similar for AS80.
Greener Approaches to Combat Biofilm’s Antimicrobial Resistance on 3D-Printed Materials: A Systematic Review
Authors: Sebbar Khaoula , El Aabedy Amal , Ibnsouda Koraichi Saad , Ulag Songul , Gunduz Oguzhan , Elabed Soumya
Published: March 2024

In recent years, Additive Manufacturing (AM), commonly referred to as 3D printing, has garnered the attention of the scientific community due to its capacity to transform ordinary and traditional items into customized materials at an affordable cost through various AM processes. Antimicrobial/antibiofilm 3D printed materials are one of the most trending research topics, owing to the growing concerns over the emergence of complex microbial structures called “biofilms” on various surfaces. The review provides an overview of the evolution of additive manufacturing (AM) technologies and their various derivatives, along with a brief description of their materials and applications. It also introduces how biofilms can represent an advantageous lifestyle for microbial populations. The primary objective of this research was to conduct a systematic review of the development of planctonic or biofilm forms of microorganisms on 3D-printed materials. The article summarizes commonly studied microorganisms on these materials and presents their 3D printing process, materials, as well as the fields covered by each of the analyzed papers. To the best of our knowledge, this is the first all-inclusive systematic review that amalgamates research conducted in diverse fields to assess the development of biofilms on surfaces produced through three-dimensional printing. Most notably, this review presents a comprehensive account of sustainable approaches for producing antimicrobial materials through 3D printing. Additionally, we assess their advancements in various fields such as medicine, environment, agri-food, and other relevant sectors. The findings of our literature review can be used to recommend appropriate microorganisms, 3D printing materials, and technologies for academic and industrial research purposes, focusing on the development of microbial biofilms on 3D-printed surfaces. Furthermore, it highlights the potential of environmentally friendly modified AM technologies to combat biofilms in clinical and non-clinical areas. Our goal with this review is to help readers gain a better understanding of fundamental concepts, inspire new researchers, and provide valuable insights for future empirical studies focused on eradicating biofilms from 3D-printed materials.