bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating the Effects of COVID-19 Lockdowns in the UK on the O3-NOx-VOC Relationship
Authors: Holland Rayne , Seifert Katya , Saboya Eric , Khan M. Anwar H. , Derwent Richard G. , Shallcross Dudley E.
Published: May 2024

The unprecedented reductions in anthropogenic emissions over the COVID-19 lockdowns were utilised to investigate the response of ozone (O3) concentrations to changes in its precursors across various UK sites. Ozone, volatile organic compounds (VOCs) and NOx (NO+NO2) data were obtained for a 3-year period encompassing the pandemic period (January 2019–December 2021), as well as a pre-pandemic year (2017), to better understand the contribution of precursor emissions to O3 fluctuations. Compared with pre-lockdown levels, NO and NO2 declined by up to 63% and 42%, respectively, over the lockdown periods, with the most significant changes in pollutant concentrations recorded across the urban traffic sites. O3 levels correspondingly increased by up to 30%, consistent with decreases in the [NO]/[NO2] ratio for O3 concentration response. Analysis of the response of O3 concentrations to the NOx reductions suggested that urban traffic, suburban background and suburban industrial sites operate under VOC-limited regimes, while urban background, urban industrial and rural background sites are NOx-limited. This was in agreement with the [VOC]/[NOx] ratios determined for the London Marylebone Road (LMR; urban traffic) site and the Chilbolton Observatory (CO; rural background) site, which produced values below and above 8, respectively. Conversely, [VOC]/[NOx] ratios for the London Eltham (LE; suburban background) site indicated NOx-sensitivity, which may suggest the [VOC]/[NOx] ratio for O3 concentration response may have had a slight NOx-sensitive bias. Furthermore, O3 concentration response with [NO]/[NO2] and [VOC]/[NOx] were also investigated to determine their relevance and accuracy in identifying O3-NOx-VOC relationships across UK sites. While the results obtained via utilisation of these metrics would suggest a shift in photochemical regime, it is likely that variation in O3 during this period was primarily driven by shifts in oxidant (OX; NO2 + O3) equilibrium as a result of decreasing NO2, with increased O3 transported from Europe likely having some influence.
Cyclic Fatigue of Different Ni-Ti Endodontic Rotary File Alloys: A Comprehensive Review
Authors: Abdellatif Dina , Iandolo Alfredo , Scorziello Michela , Sangiovanni Giuseppe , Pisano Massimo
Published: May 2024

Introduction: Modern endodontics aims to decrease the bacterial load from the complex endodontic space. Over the years, improvements in the operative phases have led to a considerable increase in the success rate of endodontic treatments. The shaping phase has seen the development of new techniques supported by technological innovations that have led to higher treatment predictability. Endodontic instruments have experienced a series of changes that have led to modifications in their design, surface treatments, and heat treatments. The clinical use of rotating nickel–titanium instruments has become widespread and consolidated, a success due primarily to the alloy’s mechanical characteristics, which are superior to steel ones, but also to innovations in instrument design. The advent of the Ni-Ti alloy has kept the concepts and requirements of shaping the same but has modified its implementation in endodontics. Aim: The following review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol. The research question focused on Ni-Ti endodontic instruments whose cyclic fatigue was evaluated by analyzing cyclic fatigue strength and the incidence of fracture. Results: At the end of the research, 10 systematic reviews and 1 randomized controlled trial were included in this comprehensive review. The most frequently analysed alloys were M-wire, conventional Ni-Ti, and CM-wire. In seven articles, instruments made of M-wire alloy were used; in eight articles, instruments made of conventional Ni-Ti; and in seven articles, instruments made of CM-wire alloy. Conclusions: The technological evolution of Ni-Ti alloys has led to the development of increasingly high-performance endodontic files that are resistant to cyclic fatigue during clinical practice and have greater resistance to sterilisation practices, making treatment easier and more predictable over time. In particular, heat-treated nickel-titanium root canal instruments present greater resistance to cyclic fatigue than untreated ones and those used with reciprocating kinematics concerning continuous rotation.
Fusion with ARRDC1 or CD63: A Strategy to Enhance p53 Loading into Extracellular Vesicles for Tumor Suppression
Authors: Liu Min , Zhang Yu , He Jianfeng , Liu Wanxi , Li Zhexuan , Zhang Yiti , Gu Ao , Zhao Mingri , Liu Mujun , Liu Xionghao
Published: May 2024

Small extracellular vesicles (sEVs) have emerged as promising therapeutic agents and drug delivery vehicles. Targeted modification of sEVs and their contents using genetic modification strategies is one of the most popular methods. This study investigated the effects of p53 fusion with arrestin domain-containing protein 1 (ARRDC1) and CD63 on the generation of sEVs, p53 loading efficiency, and therapeutic efficacy. Overexpression of either ARRDC1–p53 (ARP) or CD63–p53 (CDP) significantly elevated p53 mRNA and protein levels. The incorporation of ARRDC1 and CD63 significantly enhanced HEK293T-sEV biogenesis, evidenced by significant increases in sEV-associated proteins TSG101 and LAMP1, resulting in a boost in sEV production. Importantly, fusion with ARRDC1 or CD63 substantially increased the efficiency of loading both p53 fusion proteins and its mRNA into sEVs. sEVs equipped with ARP or CDP significantly enhanced the enrichment of p53 fusion proteins and mRNA in p53-null H1299 cells, resulting in a marked increase in apoptosis and a reduction in cell proliferation, with ARP-sEVs demonstrating greater effectiveness than CDP-sEVs. These findings underscore the enhanced functionality of ARRDC1- and CD63-modified sEVs, emphasizing the potential of genetic modifications in sEV-based therapies for targeted cancer treatment.
Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure
Authors: Kozhuharov Nikola , Michou Eleni , Wussler Desiree , Belkin Maria , Heinisch Corinna , Lassus Johan , Siirilä-Waris Krista , Veli-Pekka Harjola , Arenja Nisha , Socrates Thenral , Nowak Albina , Shrestha Samyut , Willi Julie Valerie , Strebel Ivo , Gualandro Danielle M. , Rentsch Katharina , Maeder Micha T. , Münzel Thomas , Tavares de Oliveira Junior Mucio , von Eckardstein Arnold , Breidthardt Tobias , Mueller Christian
Published: May 2024

Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90–140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611–1956) versus 827 (448–1419) pg/mL, and 5890 (2959–12,162) versus 4068 (1986–8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24–71) versus 33 (19–59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31–2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.
Diabetes and Stroke: Impact of Novel Therapies for the Treatment of Type 2 Diabetes Mellitus
Authors: Vieira Inês Henriques , Carvalho Tânia Santos , Saraiva Joana , Gomes Leonor , Paiva Isabel
Published: May 2024

Type 2 diabetes mellitus (T2DM) is a significant risk factor for stroke. Nevertheless, the evidence supporting stringent glycemic control to reduce macrovascular complications, particularly stroke, is not as clear as for microvascular complications. Presently, risk reduction strategies are based on controlling multiple risk factors, including hypertension, dyslipidemia, glycemia, smoking, and weight. Since 2008, new pharmacological therapies for treating T2DM have been required to undergo trials to ensure their cardiovascular safety. Remarkably, several novel therapies have exhibited protective effects against the combined endpoint of major cardiovascular events. Evidence from these trials, with stroke as a secondary endpoint, along with real-world data, suggests potential benefits in stroke prevention, particularly with glucagon-like peptide 1 receptor agonists. Conversely, the data on sodium–glucose cotransporter type 2 inhibitors remains more controversial. Dipeptidyl peptidase 4 inhibitors appear neutral in stroke prevention. More recent pharmacological therapies still lack significant data on this particular outcome. This article provides a comprehensive review of the evidence on the most recent T2DM therapies for stroke prevention and their impact on clinical practice.
Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center
Authors: Abu Arif Jasmin , Knecht Vitus André , Rübsam Anne , Lussac Vanessa , Jami Zohreh , Pohlmann Dominika , Müller Bert , Pleyer Uwe
Published: May 2024

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.
Clinical Outcomes and Molecular Predictors of Pembrolizumab (Keytruda) as a PD-1 Immune Checkpoint Inhibitor in Advanced and Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis
Authors: Balan Lavinia , Cimpean Anca Maria , Nandarge Prashant Sunil , Sorop Bogdan , Balan Catalin , Balica Madalina Alexandra , Bratosin Felix , Brasoveanu Simona , Boruga Madalina , Pirtea Laurentiu
Published: May 2024

This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I2 test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects.
Metastatic Kidney Cancer: Does the Location of the Metastases Matter? Moving towards Personalized Therapy for Metastatic Renal Cell Carcinoma
Authors: Baston Catalin , Parosanu Andreea Ioana , Stanciu Ioana-Miruna , Nitipir Cornelia
Published: May 2024

The management of renal cell carcinoma (RCC) has been revolutionized over the past two decades with several practice-changing treatments. Treatment for RCC often requires a multimodal approach: Local treatment, such as surgery or ablation, is typically recommended for patients with localized tumors, while stage IV cancers often require both local and systemic therapy. The treatment of advanced RCC heavily relies on immunotherapy and targeted therapy, which are highly contingent upon histological subtypes. Despite years of research on biomarkers for RCC, the standard of care is to choose systemic therapy based on the risk profile according to the International Metastatic RCC Database Consortium and Memorial Sloan Kettering Cancer Centre models. However, many questions still need to be answered. Should we consider metastatic sites when deciding on treatment options for metastatic RCC? How do we choose between dual immunotherapy and combinations of immunotherapy and tyrosine kinase inhibitors? This review article aims to answer these unresolved questions surrounding the concept of personalized medicine.
Comparative Analysis on the Mechanical Properties, Transportation Cost, and Carbon Footprint Emission of Cement Mortar with PE and SSRS as Partial Replacement for Aggregates
Authors: Tsai Shen-Lun , Wang Her-Yung , Lin Keng-Ta , Hung Chang-Chi
Published: May 2024

This study presents an innovative approach for the utilization of industrial by-products and municipal waste in the production of sustainable and environmentally friendly cement mortar. We explored stabilized stainless-steel reduced slag (SSRS) and polyethylene (PE) plastic waste as partial replacements for aggregates. Various engineering properties of the resulting cement mortar specimens, including the slump, slump flow, compressive strength, flexural strength, tensile strength, water absorption, and ultrasonic pulse velocity (UPV), were investigated through comprehensive experimental tests. The influence of different water–cement (w/c) or water–binder (w/b) ratios and substitution amounts on the engineering properties of the cement mortar samples was thoroughly examined. The findings revealed that an increase in PE substitution adversely affected the overall workability of the cement mortar mixtures, whereas an increase in the SSRS amount contributed to enhanced workability. As for the hardened properties, a consistent trend was observed in both cases, with higher w/c or w/b ratios and substitution amounts leading to reduced mechanical properties. Water absorption and UPV test results validated the increased formation of porosity with higher w/c or w/b ratios and substitution amounts. This study proposes a promising method to effectively repurpose industrial by-products and municipal waste, transforming them into sustainable construction and building materials. Additionally, a comparative analysis of the transportation costs and carbon footprint emissions between SSRS–cement mortar and PE–cement mortar was conducted to assess their environmental impact and sustainability. Generally, higher w/c or w/b ratios and replacement levels corresponded with a reduced carbon footprint. The geographical location of the source of SSRS and PE remains a challenge and studies to overcome this challenge must be further explored.
Creep Characteristics of Reconstituted Silty Clay under Different Pre-Loading Path Histories
Authors: Xiao Bin , Zhou Peijiao , Wu Shuchong
Published: May 2024

Due to the long-term deformation settlement of foundations, issues such as damage and functional failure of buildings and structures have long been a concern in the engineering field. The creep of soil is one of the primary causes leading to long-term deformation of foundations. In this paper, the consolidation deformation, creep characteristics, and creep model of reconstituted saturated silty clay were studied using the isotropic consolidation creep test and triaxial compression creep test. The results show that for the isotropic consolidation creep test, although the applied load adopted different stages of loading, as long as the final applied confining pressure was the same, the number of stages applied by the confining pressure had little effect on the final isotropic consolidation deformation of the sample and the triaxial undrained shear strength after creep. However, for the triaxial shear creep test, it was found that under the same final deviatoric stress, the final deviatoric strain of the sample was closely related to the number of loading stages of deviatoric stress. The test showed that the more loading stages with the same deviatoric stress, the smaller the final deviatoric strain, and the triaxial undrained shear strength of the sample after creep increased. In addition, it was reasonable to set the pore pressure dissipation of the sample at 95% ((u0 − u)/u0 = 95%) as the time (t100) at which the primary consolidation of the soil sample was completed. The isotropic consolidation creep curves and the triaxial compression creep curves showed certain non-linearity. Then, the logarithmic model and the hyperbolic model were used to fit the creep curves of the samples. It was found that the hyperbolic model had a better fitting effect than the logarithmic model, but for the triaxial compression creep test, the creep parameters of the sample changed greatly. Therefore, studying the creep characteristics of soil under different pre-loading steps is of significant engineering importance for evaluating the long-term deformation of underground structures.
Research on the Design of Recessed Balconies in University Dormitories in Cold Regions Based on Multi-Objective Optimization
Authors: Ji Weidong , Sun Jian , Wang Huiyi , Yu Qiaqing , Liu Chang
Published: May 2024

Thermal comfort and daylighting are vital components of dormitory environments. However, enhancing indoor lighting conditions may lead to increased annual energy consumption and decreased thermal comfort. Therefore, it is crucial to identify methods to reduce buildings’ energy costs while maintaining occupants’ thermal comfort and daylighting. Taking the dormitory building of Songyuan No. 2 at Shandong Jianzhu University of Architecture, which is located in a cold region, as an example, a field measurement analysis was conducted on the recessed balconies within the dormitory. The measured data were analyzed and utilized to simulate the annual energy consumption, thermal comfort predicted mean vote (PMV), and useful daylight illuminance (UDI) values of the dormitory units using the Grasshopper platform with the Ladybug and Honeybee plugins. The different depths of the balconies and window-to-wall ratios have a significant impact on the indoor physical environment and energy consumption, leading to the design of independent variables and the construction of a simplified parametric model. The simulation results underwent multi-objective optimization using genetic algorithm theory through the Octopus platform, resulting in a Pareto optimal solution set. Comparisons between the final-generation data and simulations of the original Song II dormitory unit indicate potential energy savings of up to 2.5%, with a 25% improvement in indoor thermal comfort satisfaction. Although there was no significant improvement in the UDI value, all the solution sets meet the minimum requirement of 300 lux specified by relevant regulations, according to the simulated average illuminance levels on the indoor work plane. Finally, the 60 optimal solution sets were further screened, filtering out sets deviating excessively from certain objectives, to identify 6 optimal solutions that are more balanced and exhibit a higher overall optimization rate. These findings offer detailed data references to assist in the design of dormitory buildings in cold regions.
Influence and Mechanism of the Excavation Width on Excavation Deformations in Shanghai Soft Clay
Authors: Huang Pei , Dang Kexin , Shi Haili , Yang Kun , Wu Jiacheng
Published: May 2024

This study investigated the influence and mechanism of the excavation width on excavation deformations in Shanghai soft clay. Based on three excavations that had different final excavation depths, dissimilar retaining structures and diverse geological conditions, 40 sets of two-dimensional numerical models with different excavation widths were employed to analyze the deformation rules affected by the excavation width. Moreover, a series of simplified models with different excavation widths were employed to analyze the effect of the excavation width on excavation deformations. The results show that under the same excavation depth, both the horizontal displacements of the retaining walls and ground surface settlements increase as the excavation width increases, but the increasing rate gradually decreases. Factors such as the unloading influence depth, the overlap degree of the passive zones, the stress state of the basal soils and the development of the relative shear stress have a significant influence on excavation deformations. With increasing excavation width, the unloading influence depth gradually deepens, the overlap area of the passive zones gradually decreases, the direction of the rotation of the major principal stress gradually reduces and the relative shear stress of the distant and deep soils gradually expands. Therefore, the constraint ability of the passive zones on excavation deformation gradually reduces and excavation deformations gradually increase.
Langerhans Cells in Sentinel Lymph Nodes from Melanoma Patients
Authors: Gerlini Gianni , Susini Pietro , Sestini Serena , Brandani Paola , Giannotti Vanni , Borgognoni Lorenzo
Published: May 2024

Background. Langerhans cells (LCs) are professional Dendritic Cells (DCs) involved in immunoregulatory functions. At the skin level, LCs are immature. In response to tissue injuries, they migrate to regional Lymph Nodes (LNs), reaching a full maturation state. Then, they become effective antigen-presenting cells (APCs) that induce anti-cancer responses. Notably, melanoma patients present several DC alterations in the Sentinel Lymph Node (SLN), where primary antitumoral immunity is generated. LCs are the most represented DCs subset in melanoma SLNs and are expected to play a key role in the anti-melanoma response. With this paper, we aim to review the current knowledge and future perspectives regarding LCs and melanoma. Methods. A systematic review was carried out according to the PRISMA statement using the PubMed (MEDLINE) library from January 2004 to January 2024, searching for original studies discussing LC in melanoma. Results. The final synthesis included 15 articles. Several papers revealed significant LCs–melanoma interactions. Conclusions. Melanoma immune escape mechanisms include SLN LC alterations, favoring LN metastasis arrival/homing and melanoma proliferation. The SLN LCs of melanoma patients are defective but not irreversibly, and their function may be restored by appropriate stimuli. Thus, LCs represent a promising target for future immunotherapeutic strategies and cancer vaccines.
Comparing the Outcomes of Matched and Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation with Different Anti-Thymocyte Globulin Formulations: A Retrospective, Double-Centre Experience on Behalf of the Polish Adult Leukemia Group
Authors: Giordano Ugo , Mordak-Domagała Monika , Sobczyk-Kruszelnicka Małgorzata , Giebel Sebastian , Gil Lidia , Dudek Krzysztof D. , Dybko Jarosław
Published: May 2024

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively).
Studying Outcomes after Steroid-Sparing Immunosuppressive Agent vs. Steroid-Only Treatment for Immune-Related Adverse Events in Non-Small-Cell Lung Cancer (NSCLC) and Melanoma: A Retrospective Case-Control Study
Authors: Syed Sharjeel , Hines Jacobi , Baccile Rachel , Rouhani Sherin , Reid Pankti
Published: May 2024

Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs.
Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports
Authors: Lee Eunso , Jang Jeong Yun , Yang Jinho
Published: May 2024

Background: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). Methods: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. Results: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. Conclusions: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management.
Reimagining Colorectal Cancer Screening: Innovations and Challenges with Dr. Aasma Shaukat
Authors: Cortiana Viviana , Joshi Muskan , Chorya Harshal , Vallabhaneni Harshitha , Kannan Shreevikaa , Coloma Helena S. , Park Chandler H. , Leyfman Yan
Published: May 2024

Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat’s Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm.
Nanosized Tungsten Powder Synthesized Using the Nitridation–Decomposition Method
Authors: He Qing-Yin , Zhao Ben-Li , Sun Shi-Kuan
Published: May 2024

A facile, one-step nitridation–decomposition method was developed for the synthesis of nanosized tungsten powder with a high surface area. This approach involved the nitridation of WO3 in NH3 to form mesoporous tungsten nitride (W2N), followed by in situ decomposition of W2N to directly yield single-phase W particles. The phase and morphology evolution during the synthesis were systematically investigated and compared with the carbothermal reduction of WO3. It was revealed that powdered tungsten product with single-phase particles was obtained after nitridation at 800 °C combined with in situ decomposition at 1000 °C, displaying an average particle size of 15 nm and a large specific surface area of 6.52 m2/g. Furthermore, the proposed method avoided the limitations associated with intermediate phase formation and coarsening observed in carbothermal reduction, which resulted in the growth of W particles up to ~4.4 μm in size. This work demonstrates the potential of the nitridation–decomposition approach for the scalable and efficient synthesis of high-quality, fine-grained tungsten powder.
The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients
Authors: Grigore Liliana-Georgiana , Radoi Viorica-Elena , Serban Alexandra , Mihai Adina Daniela , Stoica Ileana
Published: May 2024

The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania. Germline BRCA1 and BRCA2 mutations were investigated in a cohort of 616 female patients using NGS and/or MLPA methods followed by software-based data analysis and classification according to international guidelines. Out of the 616 female patients included in this study, we found that 482 patients (78.2%) did not have any mutation present in the two genes investigated; 69 patients (11.2%) had a BRCA1 mutation, 34 (5.5%) had a BRCA2 mutation, and 31 (5%) presented different type of mutations with uncertain clinical significance, moderate risk or a large mutation in the BRCA1 gene. Our investigation indicates the most common mutations in the BRCA1 and BRCA2 genes, associated with breast and ovarian cancer in the Romanian population. Our results also bring more data in support of the frequency of the c.5266 mutation in the BRCA1 gene, acknowledged in the literature as a founder mutation in Eastern Europe. We consider that the results of our study will provide necessary data regarding BRCA1 and BRCA2 mutations that would help to create a genetic database for the Romanian population.
Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production
Authors: Bel’skaya Lyudmila V. , Dyachenko Elena I.
Published: May 2024

This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in the human body. The features of the biochemical processes occurring in breast cancer are described, ranging from nonspecific, at first glance, and strictly biochemical to hormone-induced reactions, genetic and epigenetic regulation, which allows for a broader and deeper understanding of the principles of oncogenesis, as well as maintaining the viability of cancer cells in the mammary gland. Specific pathways of the activation of oxidative stress have been studied as a response to the overproduction of stress hormones and estrogens, and specific ways to reduce its negative impact have been described. The diversity of participants that trigger redox reactions from different sides is considered more fully: glycolytic activity in breast cancer, and the nature of consumption of amino acids and metals. The role of metals in oxidative stress is discussed in detail. They can act as both co-factors and direct participants in oxidative stress, since they are either a trigger mechanism for lipid peroxidation or capable of activating signaling pathways that affect tumorigenesis. Special attention has been paid to the genetic and epigenetic regulation of breast tumors. A complex cascade of mechanisms of epigenetic regulation is explained, which made it possible to reconsider the existing opinion about the triggers and pathways for launching the oncological process, the survival of cancer cells and their ability to localize.
Performance of Atmospheric Plasma-Sprayed Thermal Barrier Coatings on Additively Manufactured Super Alloy Substrates
Authors: Bellippady Madhura , Björklund Stefan , Li Xin-Hai , Frykholm Robert , Kjellman Bjorn , Joshi Shrikant , Markocsan Nicolaie
Published: May 2024

This work represents a preliminary study of atmospheric plasma-sprayed (APS) Yttria-Stabilized Zirconia (YSZ)-based thermal barrier coatings (TBCs) deposited on forged and additive manufactured (AM) HAYNES®282® (H282) superalloy substrates. The effect of different feedstock morphologies and spray gun designs with radial and axial injection on APS-deposited YSZ layer characteristics such as microstructure, porosity content, roughness, etc., has been investigated. The performance of TBCs in terms of thermal cycling fatigue (TCF) lifetime and erosion behaviour were also comprehensively investigated. In view of the high surface roughness of as-built AM surfaces compared to forged substrates, two different types of NiCoCrAlY bond coats were examined: one involved high-velocity air fuel (HVAF) spraying of a finer powder, and the other involved APS deposition of a coarser feedstock. Despite the process and feedstock differences, the above two routes yielded comparable bond coat surface roughness on both types of substrates. Variation in porosity level in the APS topcoat was observed when deposited using different YSZ feedstock powders employing axial or radial injection. However, the resultant TBCs on AM-derived substrates were observed to possess similar microstructures and functional properties as TBCs deposited on reference (forged) substrates for any given YSZ deposition process and feedstock.
Recent Advances in the Deposition of Aluminide Coatings on Nickel-Based Superalloys: A Synthetic Review (2019–2023)
Authors: Kopec Mateusz
Published: May 2024

Thermal barrier coatings (TBCs) are widely used to improve the oxidation resistance and high-temperature performance of nickel-based superalloys operating in aggressive environments. Among the TBCs, aluminide coatings (ACs) are commonly utilized to protect the structural parts of jet engines against high-temperature oxidation and corrosion. They can be deposited by different techniques, including pack cementation (PC), slurry aluminizing or chemical vapor deposition (CVD). Although the mentioned deposition techniques have been known for years, the constant developments in materials sciences and processing stimulates progress in terms of ACs. Therefore, this review paper aims to summarize recent advances in the AC field that have been reported between 2019 and 2023. The review focuses on recent advances involving improved corrosion resistance in salty environments as well as against high temperatures ranging between 1000 °C and 1200 °C under both continuous isothermal high-temperature exposure for up to 1000 h and cyclic oxidation resulting from AC application. Additionally, the beneficial effects of enhanced mechanical properties, including hardness, fatigue performance and wear, are discussed.
Effective Promotion of Micro Damping of GO Hybrid PU–PF Copolymer Grinding Wheels on Precision Machining
Authors: Xia Shaoling , Zhang Hongying , Xu Jixian , Liu Yingliang , Liu Cong , Guo Shengdong , Song Xudong , Peng Jin , Jia Yu , Li Jialu
Published: May 2024

The influence of damping and friction performance of grinding wheels on precision grinding was explored for the first time. GO hybrid PU-modified PF copolymers were prepared by in situ synthesis and adopted as a matrix for fabricating grinding wheels. FT-IR, DSC, TG, and mechanical property tests showed the optimal modification when PU content was 10 wt% and GO addition was 0.1 wt%. Damping properties were investigated by DMA, and tribological characteristics were measured by sliding friction and wear experiments. The worn surfaces and fracture morphologies of GO hybrid PU–PF copolymers were observed by SEM. Distribution of components on the worn surfaces was explored by Raman mapping and EDS. The research results revealed that the PU component tended to be dispersed around the edges of corundum abrasives acting as a buffer layer of abrasive particles, which could provide micro-damping characteristics for abrasives, making the grinding force more stable during precision machining and facilitating a smoother surface quality of the workpiece.
Design and Development of an Electronic Controller for Accurate Temperature Management for Storage of Biological and Chemical Samples in Healthcare
Authors: Ilchev Svetozar
Published: May 2024

This paper presents the design and development of an electronic controller for accurate temperature management for the storage of biological and chemical samples in healthcare applications. In the introduction, some important application aspects related to the use of temperature control devices in healthcare are discussed. Keeping these aspects in mind, a brief overview of some related works is presented. The findings are then translated to specific requirements for an electronic controller, which is to be used in a temperature control device. These requirements made necessary the development of a custom controller, as no readily available solutions could be obtained. The paper proceeds with the design of a suitable architecture and discusses some of the design choices. Then, some implementation details are presented and the prototype controller, together with its user interface, is illustrated. Experiments are conducted and several points for improvement are identified. Overall, the main task of keeping accurate, traceable temperature at all times is accomplished successfully, and the electronic controller proves to be a viable solution that conforms to the identified requirements. Future versions will improve the speed of the temperature adaptation and include better user interface and wireless connectivity for remote monitoring and control.
Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada
Authors: Ratiu Claire , Dufresne Simon F. , Thiant Stéphanie , Roy Jean
Published: May 2024

Epstein–Barr virus-related post-transplantation lymphoproliferative disorder (EBV-PTLD) is a serious complication following hematopoietic stem cell transplantation (HSCT). A pre-emptive strategy using rituximab, which aims to manage patients early at the time of EBV reactivation to avoid PTLD, has been recommended by the most recent ECIL-6 guidelines in 2016. However, there is still a great heterogeneity of viral-load monitoring protocols, targeted patient populations, and pre-emptive treatment characteristics between centers, making precise EBV monitoring recommendations difficult. We conducted a literature review from the most recent publications between 1 January 2015 and 1 August 2023, to summarize the emerging data on EBV-PTLD prevention strategies in HSCT recipients, including the EBV-DNA threshold and use of rituximab. We also present the results of a survey of current practices carried out in 12 of the main HSCT centers across Canada. We confirm that pre-emptive rituximab remains an efficient strategy for EBV-PTLD prevention. However, there is an urgent need to perform prospective, randomized, multicentric trials with larger numbers of patients reflecting current practices to determine the best clinical conduct with regards to rituximab dosing, timing of treatment, and criteria to initiate treatments. Longer follow-ups will also be necessary to assess patients’ long-term outcomes.