bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Resilience Evaluation of Urban Rail Transit Construction Organization Based on the Cloud Matter-Element Model: A Case Study of Nanchang West Station
Authors: Liu Wei , Yuan Xiuxiu
Published: February 2024

In the construction of urban rail transit projects, the disturbance of equipment, sudden failure, rainstorms, and other emergencies may bring serious safety risks. Resilience theory emphasizes the ability of the system to resist, adapt, absorb, and learn from risks in the whole process before, during, and after the occurrence of risks. It is introduced into the safety management of construction organization of urban rail transit projects to describe the ability of urban rail transit projects to cope with risks in the whole process of dealing with construction risks. This study defines the connotation of the resilience of the project construction organization and uses the literature frequency statistics method to determine the resilience evaluation indexes. The game theory combination weighting method is used to determine the index weights, and the cloud matter element model is used to establish the evaluation model of construction organization resilience of urban rail transit projects. Taking Nanchang West Station of Phase 1 Project of Nanchang Line 2 as an example, the validity and accuracy of the model are verified. The results show that the resilience grade of the construction organization of the project is “higher resilience,” which is consistent with the actual survey situation, and the evaluation model is reasonable. In addition, in the evaluation results, the key indexes and risk indexes of the project are determined, and the safety management measures of the construction organization of the project are put forward according to the key indexes and risk indexes.
Construction Simulation and Monitoring of the Jacking Steel Truss and Main Column of a Super High-Rise Building
Authors: Chang Li , Zeng Fankui , Guo Haiying , Zhang Zhenyu , Gao Teng
Published: February 2024

To ensure that the steel truss used in a super high-rise building in Xi’an remains in a safe and reliable state during the construction and jacking process, the jacking steel truss and the main column are studied. A finite element model of the steel truss and the main column is established by using finite element software. The stress values of the steel truss and the main column under various working conditions are simulated, and the stress and perpendicularity of the key points of the structure are monitored via the stress monitoring system under different working conditions. Through the monitoring system, the data on the operation of the steel truss are collected, and the monitoring data are compared with the finite element simulation data to ensure the safe operation of the steel truss. The results indicate that the inclination angle of the main column is easily disturbed by the external environment. The main column is inclined in two directions, but it does not exceed 0.3°, indicating good verticality. The stress monitoring values are generally close to the simulated values. The peak values of the stress at the measuring points during the construction stage are the same as the results obtained from the field test, and the error between the measured maximum stress value and the simulated value is controlled within 10%. In general, the simulated values are in good agreement with the measured values.
The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment
Authors: Marrapodi Ramona , Bellei Barbara
Published: February 2024

Melanoma progression is a multistep evolution from a common melanocytic nevus through a radial superficial growth phase, the invasive vertical growth phase finally leading to metastatic dissemination into distant organs. Melanoma aggressiveness largely depends on the propensity to metastasize, which means the capacity to escape from the physiological microenvironment since tissue damage due to primary melanoma lesions is generally modest. Physiologically, epidermal melanocytes are attached to the basement membrane, and their adhesion/migration is under the control of surrounding keratinocytes. Thus, the epidermal compartment represents the first microenvironment responsible for melanoma spread. This complex process involves cell–cell contact and a broad range of secreted bioactive molecules. Invasion, or at the beginning of the microinvasion, implies the breakdown of the dermo-epidermal basement membrane followed by the migration of neoplastic melanocytic cells in the superficial papillary dermis. Correspondingly, several experimental evidences documented the structural and functional rearrangement of the entire tissue surrounding neoplasm that in some way reflects the atypia of tumor cells. Lastly, the microenvironment must support the proliferation and survival of melanocytes outside the normal epidermal–melanin units. This task presumably is mostly delegated to fibroblasts and ultimately to the self-autonomous capacity of melanoma cells. This review will discuss remodeling that occurs in the epidermis during melanoma formation as well as skin changes that occur independently of melanocytic hyperproliferation having possible pro-tumoral features.
Atypical Endometrial Hyperplasia and Concurrent Cancer: A Comprehensive Overview on a Challenging Clinical Condition
Authors: Giannella Luca , Grelloni Camilla , Bernardi Marco , Cicoli Camilla , Lavezzo Federica , Sartini Gianmarco , Natalini Leonardo , Bordini Mila , Petrini Martina , Petrucci Jessica , Terenzi Tomas , Delli Carpini Giovanni , Di Giuseppe Jacopo , Ciavattini Andrea
Published: February 2024

The present review regarding atypical endometrial hyperplasia (AEH) focused on the main debated factors regarding this challenging clinical condition: (i) predictive variables of occult endometrial cancer (EC); (ii) the rate of EC underestimation according to different endometrial sampling methods; and (iii) the appropriateness of lymph node status assessment. When cancer is detected, approximately 90% of cases include low-risk EC, although intermediate/high-risk cases have been found in 10–13% of women with cancer. Older age, diabetes, high BMI, and increased endometrial thickness are the most recurrent factors in women with EC. However, the predictive power of these independent variables measured on internal validation sets showed disappointing results. Relative to endometrial sampling methods, hysteroscopic endometrial resection (Hys-res) provided the lowest EC underestimation, ranging between 6 and 11%. Further studies, including larger sample sizes of women undergoing Hys-res, are needed to confirm these findings. These data are urgently needed, especially for female candidates for conservative treatment. Finally, the evaluation of lymph node status measured on 660 of over 20,000 women showed a lymph node positivity of 2.3%. Although there has been an increase in the use of this procedure in AEH in recent years, the present data cannot recommend this option in AEH based on a cost/risk/benefit ratio.
Latest Progress in Risk-Adapted Surgery for Medullary Thyroid Cancer
Authors: Machens Andreas , Lorenz Kerstin , Brandenburg Tim , Führer Dagmar , Weber Frank , Dralle Henning
Published: February 2024

(1) Background: The wider adoption of a preoperative ultrasound and calcitonin screening complemented by an intraoperative frozen section has increased the number of patients with occult sporadic medullary thyroid cancer (MTC). These advances offer new opportunities to reduce the extent of the initial operations, minimizing operative morbidity and the risk of postoperative thyroxin supplementation without compromising the cure. (2) Methods: This systematic review of the international literature published in the English language provides a comprehensive update on the latest progress made in the risk-adapted surgery for sporadic and hereditary MTC guided by an intraoperative frozen section. (3) Results: The current evidence confirms the viability of a hemithyroidectomy for desmoplasia-negative sporadic MTC. To add an extra safety margin, the hemithyroidectomy may be complemented by a diagnostic ipsilateral central node dissection. Despite the limited extent of the surgery, all the patients with desmoplasia-negative sporadic tumors achieved a biochemical cure with excellent clinical outcomes. A hemithyroidectomy decreases the need for postoperative thyroxine substitution, but a total thyroidectomy may be required for bilateral nodular thyroid disease. Hereditary MTC is a different issue. Because each residual thyroid C cell carries its own risk of malignant progression, a total thyroidectomy remains mandatory for hereditary MTC. (4) Conclusion: In experienced hands, a hemithyroidectomy, which minimizes morbidity without compromising the cure, is an adequate therapy for desmoplasia-negative sporadic MTC.
Exosomes—Promising Carriers for Regulatory Therapy in Oncology
Authors: Jóźwicka Teresa Maria , Erdmańska Patrycja Maria , Stachowicz-Karpińska Agnieszka , Olkiewicz Magdalena , Jóźwicki Wojciech
Published: February 2024

Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial–mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes.
Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer—Lateralization Concept
Authors: Karwacki Jakub , Gurwin Adam , Jaworski Arkadiusz , Jarocki Michał , Stodolak Marcel , Dłubak Andrzej , Szuba Przemysław , Lemiński Artur , Kaczmarek Krystian , Hałoń Agnieszka , Szydełko Tomasz , Małkiewicz Bartosz
Published: February 2024

Background. Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy’s overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. Methods. Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann–Whitney and Kruskal–Wallis tests, as well as Kendall’s tau-b coefficient, yielding p-values and odds ratios (ORs). Results. Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231–6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525–0.913). Conclusions. Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.
Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA
Authors: Ullah Matti , Mirshahi Shahsoltan , Valinattaj Omran Azadeh , Aldybiat Iman , Crepaux Sullyvan , Soria Jeannette , Contant Geneviève , Pocard Marc , Mirshahi Massoud
Published: February 2024

Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.
Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide
Authors: Hartman-Houstman Hannah , Swenson Steve , Minea Radu O. , Sinha Uttam K. , Chiang Ming-Fu , Chen Thomas C. , Schönthal Axel H.
Published: February 2024

The Epstein–Barr virus (EBV) is accepted as a primary risk factor for certain nasopharyngeal carcinoma (NPC) subtypes, where the virus persists in a latent stage which is thought to contribute to tumorigenesis. Current treatments are sub-optimal, and recurrence occurs in many cases. An alternative therapeutic concept is aimed at triggering the lytic cycle of EBV selectively in tumor cells as a means to add clinical benefit. While compounds able to stimulate the lytic cascade have been identified, their clinical application so far has been limited. We are developing a novel anticancer molecule, NEO212, that was generated by covalent conjugation of the alkylating agent temozolomide (TMZ) to the naturally occurring monoterpene perillyl alcohol (POH). In the current study, we investigated its potential to trigger the lytic cycle of EBV in NPC cells in vitro and in vivo. We used the established C666.1 cell line and primary patient cells derived from the brain metastasis of a patient with NPC, both of which harbored latent EBV. Upon treatment with NEO212, there was an increase in EBV proteins Zta and Ea-D, key markers of the lytic cycle, along with increased levels of CCAAT/enhancer-binding protein homologous protein (CHOP), a marker of endoplasmic reticulum (ER) stress, followed by the activation of caspases. These effects could also be confirmed in tumor tissue from mice implanted with C666.1 cells. Towards a mechanistic understanding of these events, we used siRNA-mediated knockdown of CHOP and inclusion of anti-oxidant compounds. Both approaches blocked lytic cycle induction by NEO212. Therefore, we established a sequence of events, where NEO212 caused reactive oxygen species (ROS) production, which triggered ER stress and elevated the levels of CHOP, which was required to stimulate the lytic cascade of EBV. Inclusion of the antiviral agent ganciclovir synergistically enhanced the cytotoxic impact of NEO212, pointing to a potential combination treatment for EBV-positive cancers which should be explored further. Overall, our study establishes NEO212 as a novel agent able to stimulate EBV’s lytic cycle in NPC tumors, with implications for other virus-associated cancers.
Contemporary Surgical Management of Colorectal Liver Metastases
Authors: Chandra Pratik , Sacks Greg D.
Published: February 2024

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20–30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.
Non-Mutational Key Features in the Biology of Thymomas
Authors: Küffer Stefan , Müller Denise , Marx Alexander , Ströbel Philipp
Published: February 2024

Thymomas (THs) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced THs require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB THs. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through the deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.
Advancing Precision Oncology in Hereditary Paraganglioma-Pheochromocytoma Syndromes: Integrated Interpretation and Data Sharing of the Germline and Tumor Genomes
Authors: Rana Huma Q. , Koeller Diane R. , Walker McKenzie , Unal Busra , Levine Alison Schwartz , Chittenden Anu , Isidro Raymond A. , Hayes Connor P. , Manam Monica D. , Buehler Ryan M. , Manning Danielle K. , Barletta Justine A. , Hornick Jason L. , Garber Judy E. , Ghazani Arezou A. ,   INT2GRATE Oncology Consortium
Published: February 2024

Standard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes. Building on this work, herein, we present the development and application of the INT2GRATE|HPPGL platform. INT2GRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) is a multi-institution oncology consortium that aims to advance the integrated application of constitutional and tumor data and share the integrated variant information in publicly accessible repositories. The INT2GRATE|HPPGL platform enables automated parsing and integrated assessment of germline, tumor, and genetic findings in hereditary paraganglioma–pheochromocytoma syndromes (HPPGLs). Using INT2GRATE|HPPGL, we analyzed 8600 variants in succinate dehydrogenase (SDHx) genes and their associated clinical evidence. The integrated evidence includes germline variants in SDHx genes; clinical genetics evidence: personal and family history of HPPGL-related tumors; tumor-derived evidence: somatic inactivation of SDHx alleles, KIT and PDGFRA status in gastrointestinal stromal tumors (GISTs), multifocal or extra-adrenal tumors, and metastasis status; and immunohistochemistry staining status for SDHA and SDHB genes. After processing, 8600 variants were submitted programmatically from the INT2GRATE|HPPGL platform to ClinVar via a custom-made INT2GRATE|HPPGL variant submission schema and an application programming interface (API). This novel integrated variant assessment and data sharing in hereditary cancers aims to improve the clinical assessment of genomic variants and advance precision oncology.
False Liver Metastasis by Positron Emission Tomography/Computed Tomography Scan after Chemoradiotherapy for Esophageal Cancer—Potential Overstaged Pitfalls of Treatment
Authors: Shai Sen-Ei , Lai Yi-Ling , Chang Chen-I , Hsieh Chi-Wei
Published: February 2024

In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.
Resilient Enzymes through Immobilisation: Stable NDP Polyphosphate Phosphotransferase from Ruegeria pomeroyi for Nucleotide Regeneration
Authors: Hölting Kristin , Götz Sebastian , Aßmann Miriam , Bubenheim Paul , Liese Andreas , Kuballa Jürgen
Published: February 2024

Immobilisation plays an important role in the industrial application of enzymes. The stabilisation and reusability of immobilised enzymes reduce the cost of the catalyst and facilitate their use in continuously operated reactors. For this purpose, an applicable type of immobilisation needs to be identified. In this study, we investigate the conversion of CDP and PolyP to CTP by NDP polyphosphate phosphotransferase 3 from Ruegeria pomeroyi (RpPPK2-3) and describe the covalent immobilisation of RpPPK2-3. In order to select a suitable carrier for the immobilisation of RpPPK2-3, a screening with different amino methacrylate (glutaraldehyde-pre-activated) and epoxy methacrylate carriers was carried out. The epoxy methacrylate carrier ECR8209M (Purolite®) was found to be the most suitable. With a half-life of 462 d when stored at 6 °C and a 50-fold reusability with a 93% residual activity, the immobilised enzyme showed a higher stability compared to the soluble enzyme with a half-life of 0.04 d. Although the half-life of the soluble enzyme could be increased to 32 d by adding PPi, it could not reach the stability of the immobilisate. Due to the resilience of the immobilisate, it is suitable for application in continuous reactor set-ups, e.g., packed-bed reactors.
Enhancing Stability of γ-Al2O3-Supported NiCu Catalysts by Impregnating Basic Oxides in the Hydrodeoxygenation of Anisole
Authors: Vandevyvere Tom , Sabbe Maarten K. , Thybaut Joris W. , Lauwaert Jeroen
Published: February 2024

Basic oxides such as CaO and MgO were added to a γ-Al2O3 support in NiCu-catalyzed hydrodeoxygenation of anisole. A commercial CaO-MgO-γ-Al2O3 was compared to a benchmark γ-Al2O3 and in-house variants with sequential oxide impregnation prior to NiCu impregnation. CaO did not have a significant impact on activity compared to the benchmark, while MgO improved NiCu dispersion, enhancing activity. Co-impregnation of CaO and MgO resulted in intermediate activity. Despite decreased demethoxylation, likely due to moderated support acidity, both CaO-modified and the commercially supported catalysts showed improved stability over 48 h Time On Stream.
Cytochalasins as Modulators of Stem Cell Differentiation
Authors: Pampanella Luca , Petrocelli Giovannamaria , Abruzzo Provvidenza Maria , Zucchini Cinzia , Canaider Silvia , Ventura Carlo , Facchin Federica
Published: February 2024

Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs).
Diet-Induced Obesity Increases Monocyte/Macrophage Proliferation during Skin Wound Healing in Mice
Authors: Pang Jingbo , Urao Norifumi , Koh Timothy J.
Published: February 2024

Obesity is associated with low-grade chronic inflammation and impaired glucose metabolism, both of which are detrimental to wound healing. C-C motif chemokine receptor 2 (CCR2) plays an important role in cell recruitment during healing, and our recent studies revealed the significance of CCR2-CCL2 signaling in promoting the proliferation of pro-inflammatory monocytes/macrophages in wounds. Therefore, we sought to determine whether diet-induced obesity increases monocyte/macrophage proliferation and their accumulation in skin wounds. We first confirmed that wound closure was delayed in obese CCR2RFP/+ mice fed with a high-fat diet (HFD) compared to mice fed with a normal diet (ND). Using in vivo imaging and flow cytometry analysis, we found that HFD mice had significantly increased accumulation of CCR2+ monocytes/macrophages, particularly pro-inflammatory CCR2+Ly6C+ cells in wounds compared to their ND counterparts. Importantly, HFD mice exhibited an increased proliferation of wound CCR2+Ly6C+ compared to ND mice. Together, our data suggest that obesity leads to an increased proliferation and accumulation of pro-inflammatory CCR2+Ly6C+ monocytes/macrophages in skin wounds, which may contribute to delayed healing.
Pronecroptotic Therapy Using Ceramide Nanoliposomes Is Effective for Triple-Negative Breast Cancer Cells
Authors: Ohya Yuki , Ogiso Yuri , Matsuda Masaya , Sakae Harumi , Nishida Kentaro , Miki Yasuhiro , Fox Todd E. , Kester Mark , Sakamoto Wataru , Nabe Takeshi , Kitatani Kazuyuki
Published: February 2024

Regulated necrosis, termed necroptosis, represents a potential therapeutic target for refractory cancer. Ceramide nanoliposomes (CNLs), considered potential chemotherapeutic agents, induce necroptosis by targeting the activating protein mixed lineage kinase domain-like protein (MLKL). In the present study, we examined the potential of pronecroptotic therapy using CNLs for refractory triple-negative breast cancer (TNBC), for which there is a lack of definite and effective therapeutic targets among the various immunohistological subtypes of breast cancer. MLKL mRNA expression in tumor tissues was significantly higher in TNBC patients than in those with non-TNBC subtypes. Similarly, among the 50 breast cancer cell lines examined, MLKL expression was higher in TNBC-classified cell lines. TNBC cell lines were more susceptible to the therapeutic effects of CNLs than the non-TNBC subtypes of breast cancer cell lines. In TNBC-classified MDA-MB-231 cells, the knockdown of MLKL suppressed cell death induced by CNLs or the active substance short-chain C6-ceramide. Accordingly, TNBC cells were prone to CNL-evoked necroptotic cell death. These results will contribute to the development of CNL-based pronecroptotic therapy for TNBC.
PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche
Authors: Liu Hanghang , Liu Linyi , Rosen Clifford J.
Published: February 2024

Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH’s role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH—catabolic and anabolic—on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH’s multifaceted influence on bone health.
Power Analysis for Human Melatonin Suppression Experiments
Authors: Spitschan Manuel , Vidafar Parisa , Cain Sean W. , Phillips Andrew J. K. , Lambert Ben C.
Published: February 2024

In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications.
Investigation of Microstructure, Mechanics, and Corrosion Properties of Ti6Al4V Alloy in Different Solutions
Authors: Ghisheer Mohammed M. M. , Esen Ismail , Ahlatci Hayrettin , Akın Bengü
Published: February 2024

There is a scarcity of research on the characterization of the behaviour of titanium and its alloys in highly corrosive environments. These materials are highly recommended for use in various industries such as aviation, maritime, medical, and chemical, due to their perceived superior corrosion resistance. This research examines the mechanical and corrosion characteristics of Ti6Al4V material when exposed to solutions containing 9% NaCl, 25% HCl, and a mixture of 9% NaCl and 25% HCl. Prior to the corrosion process, the prefabricated Ti6Al4V samples underwent microstructure analysis, hardness assessment, and wear evaluation. The microstructure characterization revealed that the microstructure of the Ti6Al4V alloy is composed of α and modified β phases. The Ti6Al4V sample’s hardness value was determined to be 334.23 HB. The Ti6Al4V sample’s wear rate was determined to be 0.0033 g/Nm, while the friction coefficient was determined to be 0.0326. Corrosion testing was conducted at intervals of 24, 48, 72, 168, and 336 h. Based on the corrosion rate measurements, the sample exhibited the minimum corrosion rate of 1.928519 mg/(dm2·day) in a 9% NaCl environment. The sample with a combination of 9% NaCl and 25% HCl had the maximum corrosion rate, measured at 6.493048 mg per square decimetre per day. The formation of a larger oxide layer in the Ti6Al4V corrosion sample immersed in a 9% NaCl solution serves as a protective barrier on the surface and enhances its resistance to corrosion.
Feasibility Study on Biodegradable Black Paper-Based Film Solidified Using Cooked Tung Oil
Authors: Wu Yi , Shi Yicheng , Zhao Yudie , Yin Yu
Published: February 2024

New biodegradable paper-based films are a hot research topic in the development of green agriculture. In this study, a black paper-based film coated with cooked tung oil with excellent mechanical properties, a hydrophobic surface, high heat transfer and strong weather resistance was prepared by spraying high-pigment carbon black solution on the surface of base paper. The results showed that the surface-solidified oil film had a rough structure produced via the brush coating process using cooked tung oil. The base film of the black paper had a given hydrophobic structure, and the contact angle reached 98.9°. Cooked tung oil permeates into the inside of the paper base, and after curing, it forms a multi-dimensional network film structure. The maximum tensile stress of the black paper base film is about 123% higher than that of the original paper base film. The coloring of carbon black gives the black paper base film a heat conduction effect, and the average heat transfer rate reaches 15.12 °C/s. Cooked tung oil is combined with the paper-based fiber high-toughness layer to form a stable system. The existence of a cured film improves the basic mechanics and hydrophobicity, and the resistance to ultraviolet radiation and hot air is greatly improved. This study provides a feasible scheme for the application of a black paper base film coated with cooked tung oil.
Utilizing High-Capacity Spinel-Structured High-Entropy Oxide (CrMnFeCoCu)3O4 as a Graphite Alternative in Lithium-Ion Batteries
Authors: Oroszová Lenka , Csík Dávid , Baranová Gabriela , Bortel Gábor , Džunda Róbert , Temleitner László , Hagarová Mária , Breitung Ben , Saksl Karel
Published: February 2024

In the realm of advanced anode materials for lithium-ion batteries, this study explores the electrochemical performance of a high-entropy oxide (HEO) with a unique spinel structure. The equiatomic composition of CrMnFeCoCu was synthesized and subjected to a comprehensive materials characterization process, including X-ray diffraction and microscopy techniques. The multicomponent alloy exhibited a multiphase structure, comprising two face-centered cubic (FCC) phases and an oxide phase. Upon oxidation, the material transformed into a spinel oxide with a minor presence of CuO. The resulting high-entropy oxide demonstrated excellent electrochemical behavior when utilized as an anode material. Cyclic voltammetry revealed distinctive reduction peaks attributed to cation reduction and solid electrolyte interphase (SEI) layer formation, while subsequent cycles showcased high reversibility. Electrochemical impedance spectroscopy indicated a decrease in charge transfer resistance during cycling, emphasizing the remarkable electrochemical performance. Galvanostatic charge/discharge tests displayed characteristic voltage profiles, with an initial irreversible capacity attributed to SEI layer formation. The HEO exhibited promising rate capability, surpassing commercial graphite at higher current densities. The battery achieved 80% (275 mAh g−1) of its initial stable capacity at a current density of 500 mA g−1 by the 312th cycle. Post-mortem analysis revealed structural amorphization during cycling, contributing to the observed electrochemical behavior. This research highlights the potential of HEOs as advanced anode materials for lithium-ion batteries, combining unique structural features with favorable electrochemical properties.
Magnesium-Substituted Brushite Cement: Physical and Mechanical Properties
Authors: Fleck Sarah , Vahabzadeh Sahar
Published: February 2024

Brushite cements (BrCs) are calcium phosphate-based materials that are being widely used in hard tissue engineering applications due to their osteoconductivity, injectability, and bioresorbability. Therefore, the goal was to evaluate the effects of Mg concentration on the phase composition, setting time, and strength of BrC. Mg, which plays a vital role in bodily functions and bone health, was added to BrC at concentrations of 0.25, 0.50, 1.00, 1.50, 2.00, and 2.50 wt.%. The results showed that Mg stabilizes the TCP structure and increases the TCP content in final BrC. The initial and final setting times of BrCs increase with higher concentrations of Mg. Although 0.25 wt.% Mg did not change the setting of BrCs significantly, a higher concentration of 1.00 wt.% increased the initial setting time from 4.87 ± 0.38 min to 15.14 ± 0.88 min. Cements with Mg concentrations of 1.5 wt.% and above did not set after 4 h. Mg addition up to 0.5 wt.% did not change the compressive strength; however, higher concentrations decreased it significantly and 2.5 Mg-BrC had the lowest strength of 0.45 ± 0.09 MPs. Together, our results show that Mg can be added up to 1.00 wt.% without any adverse effect on the physical and mechanical properties of BrC.
Modeling 5-FU-Induced Chemotherapy Selection of a Drug-Resistant Cancer Stem Cell Subpopulation
Authors: Ramović Hamzagić Amra , Cvetković Danijela , Gazdić Janković Marina , Milivojević Dimitrijević Nevena , Nikolić Dalibor , Živanović Marko , Kastratović Nikolina , Petrović Ivica , Nikolić Sandra , Jovanović Milena , Šeklić Dragana , Filipović Nenad , Ljujić Biljana
Published: February 2024

(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)–genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.
Haploidentical Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia—Single-Centre Experience
Authors: Stavi Vered , Khaire Niranjan , Lipton Jeffrey H. , Kumar Rajat
Published: February 2024

Severe aplastic anemia (SAA) is a life-threatening type of aplastic anemia for which allogeneic stem cell transplantation or immunosuppressive therapy are the principal treatment modalities. Only about 25–30% of patients have a matched sibling donor, and finding an unrelated donor in ethnic minorities is a challenge. The use of related haploidentical donor transplants in severe aplastic anemia is uncommon. We would like to report our experience with the first four patients who underwent haploidentical transplants for severe aplastic anemia. This is a retrospective study. We collected data from our transplant database of all haploidentical hematopoietic stem cell transplants for SAA from 1 January 2020 to 31 December 2021. The transplant protocol used was the Hopkins’ protocol. There were three patients who underwent haploidentical transplants as primary therapy for SAA. A fourth patient received a haploidentical transplant after immunosuppressive therapy failure. The median age of the patients at transplant was 24 y (range 20–29). All patients were engrafted. Neutrophil engraftment occurred at a median of 21 days (range 17–22). Any active infections resolved with the recovery of blood counts. The median hospitalization time was 27 days (range 22–41). Only one patient had grade 2 acute GVHD involving the skin. There was no chronic GVHD. All patients had complete lymphoid and myeloid donor chimerism on day 60. Based on our experience and the emerging literature, haplo-identical transplantation should be considered for select young patients with SAA who have low chances of responding to immunosuppressive therapy.
Identification and Pathogenicity of Dothiorella sarmentorum Causing Lavender Leaf Blight Disease in Xinjiang, China
Authors: Li Mengyao , Liu Chuli , Shi Wanbin , Wang Aifan , Ma Rong , Su Xiujuan
Published: February 2024

Lavender is an oil-bearing plant, which has long been cultivated for oil, fresh flowers, dried products, and food. Leaf blight disease was observed on ‘Bandera Pink’, which belongs to Lavandula stoechas in Yining County, Xinjiang Uygur Autonomous Region, China. The causal agent of this disease was isolated, and Koch’s postulates were assessed to confirm its pathogenicity. The morphological characteristics of the pathogen were observed, and the LSU, ITS, tef1, and tub2 loci were combined and analyzed. Based on morphological characterization and phylogenetic analyses, the causal agent was identified as a fungal species named Dothiorella sarmentorum. Pathogenicity tests revealed that D. sarmentorum can infect seven varieties of three lavender species. This is the first report of D. sarmentorum causing lavender leaf blight. This study provides a theoretical basis for the diagnosis of disease and the monitoring of disease occurrence and epidemics.
Once Again on the Distribution of Syzygiella (Adelanthaceae, Marchantiophyta) in Indochina
Authors: Bakalin Vadim A. , Klimova Ksenia G. , Choi Seung Se , Nguyen Van Sinh
Published: February 2024

The distribution of known Syzygiella taxa in Indochina was reviewed. Currently, four species are known in Indochina: S. autumnalis, S. elongella, S. nipponica, and S. securifolia. This genus is reported for the first time in the flora of Cambodia, and S. securifolia is newly recorded for Vietnam. Herein, a description of oil bodies for S. securifolia is provided for the first time. A morphological description of the species and intravital photographs, as well as line-art illustrations, are provided along with the identification key to the Syzygiella taxa known in Indochina. A comparison of the climatic parameters of the collection sites for four known species showed that three of them occupy a relatively marginal position in the flora of Indochina as a whole and are known from colder biomes on the very northern edge of the peninsula. The locations of Syzygiella securifolia are scattered not only on the geographical map of Indochina but also on the bioclimatic scatterplot; these locations are likely an underestimation of the distribution of this taxon in Indochina, although it is generally rare worldwide. A comparison of lists of liverworts across the countries of Indochina will help identify groups of taxa for further targeted searches with the purpose of obtaining more comprehensive knowledge of the biodiversity of still poorly studied Indochina countries.