bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Post-Traumatic Osteoarthritis in the Military: Relevance of OPTIKNEE and Osteoarthritis Action Alliance recommendations
Authors: O'Sullivan Oliver , Bennett A N , Cameron K L , Crossley K , Driban J B , Ladlow P , Macri E , Schmitt L C , Teyhen D S , Wellsandt E , Whittaker J , Rhon D I
Published: October 2024

Musculoskeletal injury (MSKI) is the most common reason for short-term occupational limitation and subsequent medically related early departure from the military. MSKI-related medical discharge/separation occurs when service personnel are unable to perform their roles due to pain or functional limitations associated with long-term conditions, including osteoarthritis (OA). There is a clear link between traumatic knee injuries, such as anterior cruciate ligament or meniscal, and the development of post-traumatic OA (PTOA). Notably, PTOA is the leading cause of disability following combat injury. Primary injury prevention strategies exist within the military, with interventions focused on conditioning, physical health and leadership. However, not every injury can be prevented, and there is a need to develop secondary prevention to mitigate or reduce the risk of PTOA following an MSKI. Two international collaborative groups, OPTIKNEE and OA Action Alliance, recently produced rigorous evidence-based consensus statements for the secondary prevention of OA following a traumatic knee injury, including consensus definitions and clinical and research recommendations. These recommendations focus on patient-centred lifespan interventions to optimise joint health and prevent lost decades of care. This article aims to describe their relevance and applicability to the military population and outline some of the challenges associated with service life that need to be considered for successful integration into military care pathways and research studies.
Association between kidney function, frailty and receipt of invasive management after acute coronary syndrome
Authors: Scott Jemima Kate , Johnson Thomas , Caskey Fergus John , Bailey Pippa , Selman Lucy Ellen , Mulla Abdulrahim , Glampson Ben , Davies Jim , Papdimitriou Dimitri , Woods Kerrie , O'Gallagher Kevin , Williams Bryan , Asselbergs Folkert W , Mayer Erik K , Lee Richard , Herbert Christopher , Grant Stuart W , Curzen Nick , Squire Iain , Kharbanda Rajesh , Shah Ajay , Perera Divaka , Patel Riyaz S , Channon Keith , Mayet Jamil , Kaura Amit , Ben-Shlomo Yoav
Published: October 2024

Background

Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear.

Methods

A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010–2017). Multivariable logistic regression was used to investigate whether eGFR<90 mL/min/1.73 m2was associated with conservative ACS management and test whether (a) differences in care could be related to frailty and (b) associations between eGFR and mortality could be related to variation in revascularisation rates.

Results

Among 10 205 people with ACS, an eGFR of <60 mL/min/1.73m2was found in 25%. Strong inverse linear associations were found between worsening eGFR category and receipt of invasive management, on a relative and absolute scale. People with an eGFR <30 mL compared with ≥90 mL/min/1.73 m2were half as likely to receive coronary angiography (OR 0.50, 95% CI 0.40 to 0.64) after non-ST-elevation (NSTE)-ACS and one-third as likely after STEMI (OR 0.30, 95% CI 0.19 to 0.46), resulting in 15 and 17 per 100 fewer procedures, respectively. Following multivariable adjustment, the ORs for receipt of angiography following NSTE-ACS were 1.05 (95% CI 0.88 to 1.27), 0.98 (95% CI 0.77 to 1.26), 0.76 (95% CI 0.57 to 1.01) and 0.58 (95% CI 0.44 to 0.77) in eGFR categories 60–89, 45–59, 30–44 and <30, respectively. After STEMI, the respective ORs were 1.20 (95% CI 0.84 to 1.71), 0.77 (95% CI 0.47 to 1.24), 0.33 (95% CI 0.20 to 0.56) and 0.28 (95% CI 0.16 to 0.48) (p<0.001 for linear trends). ORs were unchanged following adjustment for frailty. A positive association between the worse eGFR category and 30-day mortality was found (test for trend p<0.001), which was unaffected by adjustment for frailty.

Conclusions

In people with ACS, lower eGFR was associated with reduced receipt of invasive coronary management and increased mortality. Adjustment for frailty failed to change these observations. Further research is required to explain these disparities and determine whether treatment variation reflects optimal care for people with low eGFR.

Trial registration number

NCT03507309.
Increasing rate of non-Candida albicansyeasts and fluconazole resistance in yeast isolates from women with recurrent vulvovaginal candidiasis in Leeds, United Kingdom
Authors: Ratner Jennifer C , Wilson Janet , Roberts Kevin , Armitage Catherine , Barton Richard Christopher
Published: October 2024

Objectives

Azoles have been the mainstay of recurrent vulvovaginal candidiasis (RVVC) for many years. Because of a recent anecdotal increase in non-Candida albicansyeasts (NCAY) and azole-resistantC. albicanscases, their prevalence was calculated from cultures for yeasts in women with complicated/RVVC over 3 years.

Methods

Retrospective data search of vaginal cultures from adult women in Leeds, UK between April 2018 and March 2021 was conducted. Samples with clinical details of complicated/RVVC had full yeast identification and antifungal susceptibility performed. Differences in prevalence between 12-month periods were determined using χ2tests.

Results

Over the 3 years, cultures were performed on 5461 vaginal samples from women with clinical information indicating they had complicated/RVVC, RVVC, with 1828 (33.5%) growing yeasts.

Over 85% of yeasts each year wereC. albicans, however the proportion declined yearly with an increase in NCAY species.Nakaseomyces glabratawas the most frequent NCAY species isolated, increasing from 2.8% in 2018–19 to 6.8% in 2020–21. Total NCAY species increased from 6.0% in 2018–19 to 12.6% in 2020–21. Fluconazole-sensitive dose-dependant (SDD) and resistant isolates increased from 3.5% in 2018–19 to 7.7% in 2019–20 and 9.6% in 2020–21. Most resistance was inC. albicansand the majority of cases were seen in primary care. Most fluconazole non-sensitive isolates were either SDD or resistant to itraconazole (77% and 23%, respectively) and were intermediate or resistant to voriconazole (36.4% and 60%, respectively).

Conclusion

There was a significant increase in the prevalence of NCAY and fluconazole-resistantC. albicansin complicated/RVVC cultures over these 3 years. Successful treatment of such cases can be very challenging. The exact reasons for this increase remain unclear but it follows a policy change that encouraged a clinical diagnosis and empirical treatment of vulvovaginal candidiasis, rather than fungal culture, in primary care.
SYRMEP beamline: state of the art, upgrades and future prospects
Authors: Longo Elena , Contillo Adriano , D’Amico Lorenzo , Prašek Marko , Saccomano Giulia , Sodini Nicola , Dullin Christian , Dreossi Diego , Tromba Giuliana
Published: October 2024

SYRMEP is the hard X-ray imaging beamline of Elettra synchrotron offering X-ray full-field techniques, micro-computed tomography (microCT) and phase-contrast modality in the energy range 10–40 keV. The beamline operates in a multidisciplinary research context spanning from biomedical applications to botany, from zoology to food technology and cultural heritage, from materials engineering to geology and earth science. Thanks to the flexibility of SYRMEP setup, in situ experiments can be performed as well, novel imaging methods can be developed and implemented in a synergical manner with interested users and collaborators. SYRMEP peculiar wide beam together with the long sample-to-detector distance enables multiscale phase-contrast studies with optimized contrast and spatial resolution on rather large specimens, such as human lung phantoms. This is particularly relevant in view of future clinical lung imaging foreseen in the framework of Elettra 2.0 program. Here, the current beamline features and recent upgrades are illustrated, an overview of the imaging methods routinely offered to SYRMEP users’ community is presented, and the outlook for the new beamline SYRMEP-Life Science (SYRMEP-LS) is reported.
Advancing early detection of biological events by digital holographic microscopy and simulation of microorganisms
Authors: Molani Alessandro , Mihalik Béla , Pennati Francesca , Rahi Praveen , Mező Anna , Pálhalmi János , Aliverti Andrea , Bela Györgyi
Published: October 2024

There is a global need to advance bio-aerosol sensing for CBRN (Chemical, Biological, Radiological, and Nuclear) applications by compact and cost-effective devices. Employing digital holographic microscopy (DHM) and deep learning, we developed a system called HoloZcan to automate the analysis of airborne microbial pathogens and particles. DHM provides valuable information, but obtaining data from biological specimens for robust investigations is challenging. This paper introduces a custom simulation approach using the open-source software Meep and the finite-difference time-domain (FDTD) method to overcome limitations of existing Mie-based simulators, especially when dealing with complex microbial shapes. The simulation tool enables the modelling of specific microorganisms, offering a safer and more flexible alternative for CBRN research by bypassing ethical and logistical constraints associated with live pathogens. The study details the simulation workflow, built upon the construction of a database of optical properties of biological materials, for realistic simulations of light-microbe interactions. Evaluations on homogeneous and non-homogeneous objects demonstrate the tool’s limited intrinsic errors and superior sensitivity to refractive index changes compared to traditional Mie-based simulations. This work significantly advances our capability to accurately simulate and analyse CBRN-related scenarios, enhancing comprehensive research in bio-aerosol sensing.

Graphical abstract
Spherical collapse in reconstructed dark energy models
Authors: Mukherjee Ankan
Published: October 2024

This work deals with the spherical collapse of matter overdensity for two reconstructed dark energy models. One of the models is reconstructed from parametrization of effective or total equation of state of energy components in the universe ([Formula: see text] model) and the other model is the constant dark energy equation of state model, namely the wCDM model. The linear evolution and nonlinear evolution of matter density contrast are studied for the present models. It is observed that the linear and even the nonlinear evolutions of density contract are almost indistinguishable in these two models. The critical density contrast at collapse as a function of redshift is also studied. The nature of critical density contrast is also found to be degenerate in the present models. Further, the number count of collapsed objects or dark matter halos along redshift is also studied. Two different halo mass functions, namely the Press–Schechter mass function and the Sheth–Tormen mass function, are adopted in this context. It is observed that for both the mass functions, the [Formula: see text] model has slightly higher number of halos at very low redshift ([Formula: see text]) and at higher redshift the wCDM model has higher number of dark matter halos. On the other hand, it is observed that the Press–Schechter mass function produces slightly higher number of dark matter halos at low redshift compared to Sheth–Tormen mass function and the number of halos is higher for Sheth–Tormen mass function at redshift [Formula: see text] for both the dark energy models. The results clearly show that these two highly degenerate dark energy models are distinguishable in the study of spherical collapse and galaxy cluster number counts.
A Will to Win: The Role of the Public in Taiwan’s Defensive Military Outlook
Authors: BRANDENBARG KAREL , ESAREY ASHLEY , YEH JACKSON
Published: October 2024

Public support is a critical factor in the outcome of interstate conflicts, yet, how it operates, interacts with hard power, or influences the overall military outlook remains surprisingly undertheorized. Public support has been particularly salient for such states as Finland and Ukraine that have faced opponents of vastly greater military size, capability, and sophistication. This paper advances an original theory on the strategic utility of public support for conflict through an analysis of the case of Taiwan, a potential current flashpoint for a great power war. This paper assesses trends in Taiwanese public support for resisting a Chinese invasion over time, identifies a major upswing in the public’s willingness to fight, and argues that further coordination by state and societal actors could deter a Chinese attack or at least greatly increase the costs of an invasion and the likelihood of failure.
Design of Cryptopol: A serious game for teaching cryptocurrency tracing techniques to Law Enforcement
Authors: Hancock Paul John , van Hardeveld Gert Jan , Jakubcek Jarek , Akhgar Babak , Davey Steffi , Amann Philipp
Published: October 2024

Tracing cryptocurrency transactions is a far from trivial process. This likely explains the increasing utilisation by criminal networks for a significant amount of criminal activity, not just cybercrime, but any crime requiring monetary transfers [
1
]. It is, therefore, vitally important that adequate training exists and is readily available for both new and experienced investigators to ensure that they are familiar with the latest techniques, tools and trends. Traditional training methods can be costly and resource-intensive, requiring highly qualified trainers to give their time to conduct training sessions. To address this issue, a training resource, in the form of a serious game, has been created. The game aims at providing a platform to improve the skills and expertise of law enforcement officers whilst reducing the workload of experienced investigators. This article describes the collaborative design and development of the serious game Cryptopol in a partnership between Europol and CENTRIC, which is a multi-disciplinary and end-user focused Center of Excellence, located within Sheffield Hallam University. Cryptopol is the first cryptocurrency-tracing training game of its kind, used by over 1,500 people representing over 550 law enforcement agencies from across the world.
“News has Various Shades”: Quantifying and Analyzing Media Bias at Aspect-level Granularity
Authors: Kuila Alapan , Jena Somnath , Sarkar Sudeshna , Chakrabarti Partha Pratim
Published: October 2024

This research presents a novel approach to dissecting media narratives, with a specific focus on aspect-level granularity and variance in addressing multifaceted news topics. Unlike previous studies, which often concentrate solely on ideological or political biases, our methodology delves deeper, exploring how diverse media outlets navigate the complexities of various news aspects. Through a detailed case study on Indian government policies, we uncover distinctive biases and variations in reporting between Indian and international media. Crucially, our methodology leverages Natural Language Inference (NLI) to identify news aspects and ascertain aspect-level sentiment from news text, enabling scalable and precise quantification of bias across diverse media narratives. Our findings illuminate the multifaceted layers of media coverage, revealing nuanced stances on different aspects of the same topic and the dynamic nature of biases over time. Importantly, our comprehensive framework quantifies media bias through data-driven quantitative evaluation, capturing both selection bias based on news aspect coverage and statement bias based on sentiment polarity. It is relevant to note that in our context, bias is not inherently favorable or unfavorable but rather serves as a quantitative metric to measure divergence in news presentation from the overall average. Thus, our contributions not only enhance understanding of media bias but also introduce a methodology distinguished for its comprehensive and scalable approach to analyzing media narratives, with substantial implications for future research and discussions in this domain.
Management of Insect Pests on Tea Plantations: Safety, Sustainability, and Efficiency
Authors: Chen Zongmao , Luo Zongxiu
Published: October 2024

Tea is the second most consumed beverage after water; thus, tea plants are economically important crops in many countries. The frequent application of chemical pesticides over large plantations of tea monoculture has led to pest outbreaks. In recent years, high amounts of highly water-soluble pesticides have been applied because of the proliferation of piercing-sucking insects; however, this method poses health hazards for humans and has negative environmental effects. This review outlines the effects of pesticide applications on the succession of tea pest populations, the risks posed by the use of highly water-soluble pesticides, and the principles of tea pest management. Various pest control techniques, including physical, biological, chemical-ecological, chemical pesticide, and cultural control methods, have been used in the last few decades. We discuss future prospects and challenges for the integrated pest management of tea plantations.
Effect of Carbon Nanotubes Functionalization on the Chemical Composition and Electrochemical Characteristics of Composites with Layered Potassium Manganese Oxide
Authors: Nesov Sergey N. , Lobov Ivan A. , Matyushenko Sergey A. , Grigoriev E. A.
Published: October 2024

The influence of pretreatment of multiwalled carbon nanotubes (MWCNTs) in oxidizers (solutions of H2O2 and HNO3) on the structure and electrochemical properties of composites with layered potassium-manganese oxide (KxMnO2) was studied. Composites were obtained by soaking carbon nanotubes in an aqueous solution of KMnO4 at 60 °C. The electrochemical performance of the composites was evaluated by cyclic voltammetry and galvanostatic charge‒discharge methods. It has been established that stronger oxidation of the MWCNTs surface at the functionalization stage leads to a noticeable increase in the reaction rate as well as the optimal potassium content in the KxMnO2 composition, which provides higher capacitive characteristics of the composite (a maximum specific capacitance of 150 F g−1 and a rate capability of 43% with increasing density current from 0.1 to 2.0 A g−1). The resulting composites are promising active components for increasing the capacitive characteristics of conductive carbon black (CB). Compared with an electrode based only on CB, electrodes based on a combination of the composite and CB at a mass ratio of 1:1 showed specific capacitance values approximately 1.5 to 3 times greater, as well as a twofold increase in rate capability (from 35 to 70%) in the range of discharge current density 0.1 to 2.0 A g−1.
Using the Objective Key Result Method to Reduce the Rate of Biomedical Waste in Medical Institutions
Authors: Huang Su-Wen , Lai Yuan-Hui , Chiou Shyue-Yow
Published: October 2024

Taiwan has been an active participant in waste recycling for a long period of time due to the need for resource sustainability. The country believes it can one day eventually achieve the goal of zero waste through the effective use of strategies such as source reduction, resource recovery, reuse, and recycling. Despite Taiwan’s long‐standing commitment to waste recycling for purposes of resource sustainability, achieving the goal of zero waste remains an immense challenge. Therefore, putting into effect the previously mentioned strategies will obviously be necessary in order to realize this goal. However, the effective implementation of these strategies requires both comprehensive planning and coordination, particularly in large medical institutions. Here, we have aimed to promote waste reduction throughout the entire hospital system in Taiwan using 3 strategies: (1) standardizing the colors of garbage bags, marking patterns of waste, and reviewing and establishing an internal audit mechanism on a regular basis; (2) the systematic monitoring of individual departments with regard to on waste consumption, brands, and materials while linking departments to the procurement source management team. In addition, any related hardware has been upgraded, precisely controlled, and automatically uploaded to the cloud system for an improved intelligent management system. In addition, the Department of Nutrition has adjusted the handling of ingredients and consumption patterns of hospital employees in order to reduce food waste; and (3) with regard to the disposal of medical waste, medical centers will be consolidating and advancing the knowledge and ability of all hospital personnel through education and training programs established for them. After the implementation of this program to promote awareness, the ratio of biological waste percentage in regard to total hospital waste dropped from 37.3% in 2018 to 33.6% in 2022, with a 49% decrease being seen in food waste, and a 99.32% increase being realized in green designated procurement items. Such an efficient management of medical waste has no doubt been extremely beneficial to the hospital.
Progresses in the NOX Elimination Using Zeolite Under Low‐Temperature Ammonia‐Based Selective Catalytic Reduction—A Review
Authors: Kumar M. Sunil , Srinivasan S. A. , Alphin M. S. , Mustafa B. , Selvaraj Senthil Kumaran
Published: October 2024

The chemical absorption biological reduction process gained profound attention in NOx removal. Treatments for NOx are done popularly using NH3 in selective catalytic reduction (SCR), and deNOx is greatly influenced by catalyst. In recent years, zeolites have been widely explored in ammonia‐selective catalytic reduction (NH3‐SCR) under low‐temperature windows. Different methods were employed to juxtapose the performances of zeolite catalysts with denitrification and NH3‐SCR. In this NH3‐SCR reaction, the zeolite catalyst’s sulfur and water poisoning effects were also investigated. The negatives of the low‐temperature NH3‐SCR reactions were demonstrated by using different methods. Ideally, this audit will set upon essential comprehension of the SCR response on zeolite catalysts and clear the way for future exploration to accomplish reasonable applications. The current review provides a new strategy to enhance the removal of NOx and reveals the fundamental effects of different types of sustainable catalysts for the environment. Further, the perspective of the economic aspects of each catalyst is also examined.
Soil Characteristics, Growth, Yield, Mineral Composition and Proximate Content of Soybeans Under Various Tillage Techniques
Authors: Adekiya Aruna Olasekan , Adedokun Olajire Damilola , Adebiyi Ojo Timothy
Published: October 2024

Different tillage methods can have varying effects on soil properties and crop quality. Therefore, field experiments were conducted at the Teaching and Research Farm of Landmark University, located in Omu‐Aran, Kwara State. The objectives were to investigate the impacts of various tillage methods on soil characteristics and the growth, yield, mineral and proximate content of soybean (Glycine max (L.) Merr.). Based on these objectives, it was hypothesized that soil properties, growth, yield, mineral and proximate contents of soybean would react differently to different tillage methods. Consequently, experiments were conducted to validate this hypothesis. The treatments were four tillage methods: manual clearing (MC), ploughing (P), ploughing plus harrowing (P + H) and manual ridging (MR), replicated three times in a randomized complete block design. Data on the initial soil properties (bulk density, particle size, pH, organic matter, N, P, K, Ca and Mg), along with the chemical properties of the soil on a per‐plot basis at the end of the experiment, were collected. Additionally, data on soil bulk density, porosity, moisture content and temperature were collected during the vegetative growth of the soybean. Soybean plant height and the number of branches were recorded at the midflowering stage, while grain yield and the number of pods were recorded at harvest. Soybean seeds were later analysed for their mineral and proximate contents using standard methods. P + H resulted in lower soil bulk density than other tillage methods and led to higher growth, yield, proximate and mineral contents of soybean. In MC, bulk density, soil moisture content, soil organic matter, N, P, K, Ca and Mg were significantly higher and temperature lower than in other tillage methods; yet, these advantages did not translate into increased yield and quality due to the higher bulk density. The growth, yield and quality of soybean were significantly influenced by soil bulk density rather than by soil chemical properties. Using the mean of the two sites, relative to MC, P and MR, P + H increased the grain yield of soybean by 41.3%, 24.4% and 13.7%, respectively. These findings underscore the importance of appropriate tillage practices for successful soybean cultivation in similar agroecological zones. For small‐scale operations, MR is suggested, while P + H is recommended for large‐scale soybean production in the studied area. Future studies could include additional variables, such as economic analysis, long‐term soil health impacts or the effects of tillage methods under varying climate conditions.
In Vitro Aging and Fracture Tests on Differently Veneered Partially Stabilized Zirconia Anterior Crowns
Authors: Zenthöfer Andreas , Ilani Ali , Rues Stefan
Published: October 2024

Objectives: To evaluate the fracture resistance of veneered incisor crowns made from highly translucent zirconia frameworks.

Materials and Methods: Ninety‐six all‐ceramic single crowns were based on either a coping with minimum wall thickness or a cutback framework fabricated from highly translucent zirconia (5Y‐PSZ). Each one‐third of the specimens was finalized with different veneering ceramics using standardizations and glaze firing. Crowns were luted to cobalt–chromium dies with MDP‐containing composite cement. Half of the entire sample underwent artificial aging (chewing simulation and thermocycling) before fracture load tests were conducted using a 6 mm steel sphere applied in a 90° angle to the oral aspect of the crowns with 1.3 mm distance to the incisal edge. Besides descriptive presentation of recorded forces at first damage (F1d) and fracture (Fu), Kruskal Wallis and Mann–Whitney U tests were used to analyze data at α = 0.05.

Results: Directly after manufacturing, incisor crowns of all test groups showed sufficient mean fracture resistances. After artificial aging, crack formation was observed in a high percentage for fully veneered crowns of all test groups, but only for one veneering ceramics with cutback crowns. Mean test forces of unaged crowns were F1d,mean ≥ 422 N | Fu,mean ≥ 749 N (fully veneered) and F1d,mean ≥ 644 N | Fu,mean ≥ 706 N (cutback) dropped significantly to F1d,mean ≥ 131 N | Fu,mean ≥ 223 N (fully veneered) and F1d,mean ≥ 324 N | Fu,mean ≥ 524 N (cutback) .

Conclusions: Within the limitations of this laboratory study, 5Y‐PSZ based anterior crowns can be a viable treatment option. Framework design, choice of the veneering ceramics and artificial aging show relevant effects on the fracture resistances. Concerted veneering ceramics should be used and partially veneering of the zirconia frameworks should be favored over full veneers.
The Causal Relationship between Immune‐Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two‐Sample Mendelian Randomization Study
Authors: Sun Sijia , Li Jie , Sun Mengxian , He Jie , Tan Songtao , Wang Ge , Zheng Yuan , Fan Xiaoping
Published: October 2024

Background and Objective. Observational studies have frequently linked aortic aneurysm (AA) to immune‐mediated inflammatory diseases (IMIDs) as a cardiovascular complication. However, the presence of confounding factors has cast doubt on the validity of this association and the potential for reverse causality. This study employs a two‐sample bidirectional Mendelian randomization (MR) approach to elucidate the causal relationships between AA and IMIDs. Methods. We sourced genetic association data from public genome‐wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context. Results. The causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01–1.12, P = 0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92–1.02, P = 0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects. Conclusion. Our findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.
Performance Evaluation of Nigeria Railway Track Ballast Under Simulated Operational Conditions
Authors: Alabi Stephen Adeyemi , Ijimdiya Thomas Stephen , Afolayan Joseph Olasehinde , Daramola Oladunni Abosede , Alabi Tolulope Abidemi , Agbede Rahman Tunde , Olowoselu Ayodeji Stanley , Mahachi Jeffrey , Arum Chinwuba
Published: October 2024

Over time, most research on railway track performance has focused mainly on rail and track geometry, with a few considering the damage or degradation occurring at the substructure level. This paper presents a step‐by‐step comprehensive study on the performance evaluation of selected uncontaminated ballast under simulated operational conditions and contaminated ballast (i.e., fouled) based on a series of laboratory tests. Tested parameters included granulometry, strength, durability and drainability and were compared with the recognised railway ballast requirements. The topsoil used as one of the fouling agents is classified into the ML group as inorganic silt with median compressibility. The initial gradation of the ballast indicates that the clean ballast samples are typically uniformly graded and generally strong and suitable for use following relevant recommendations. The abrasion tolerance of the uncontaminated ballast samples from both test locations increased as the cyclic/repeated loading induced by the train increased. The ballast gradation curves for each mix after the fouling process in the worst case of degradation by abrasion and contaminant shifted to broad‐graded classification due to the presence of finer‐sized particles. Generally, the higher the content of the fouling agent as ballast contamination, the lower the hydraulic conductivity. However, the inclusion of diesel as liquid intrusion does not seem to have any significant effect on the hydraulic conductivity. The study further presents an empirical model capable of predicting the hydraulic conductivity of ballast. The study concluded with admissible ballast contamination for cleaning and maintenance works.
Microencapsulation Techniques in HIV Pediatric Formulations: Advances and Future Outlook
Authors: Okafor Nnamdi Ikemefuna
Published: October 2024

The treatment of human immunodeficiency virus (HIV) in children has persistently been complex and tedious on a global scale. This is because adult and pediatric HIV treatments follow a similar therapeutic approach. Due to the dearth of clinically licensed pediatric antiretroviral drug (ARVD) therapy, children with HIV worldwide are prescribed unlicensed drugs each year. This has triggered likelihood of poor drug adherence, therapeutic failure, and even adverse reactions brought on by a variety of factors, including pill size and quantity, which is the main cause of swallowing difficulties, repeated administration of these various ARVDs, many of which have poor solubility and cause severe side effects in children, and unpalatability of the drug, which is one of the criteria for pediatric formulations. Thus, there is a necessity for investigation into several advanced microencapsulation techniques that could curb these challenges. Microencapsulation techniques have explored in drug delivery for encapsulation and manufacture of different nanoparticles that have shown significant potential in mitigating and surmounting different constraints, such as taste masking, enhanced drug solubility and bioavailability, and production of micronized fine powders for treatment of varying diseases. Nevertheless, the usage of these technologies in HIV pediatric formulations has garnered relatively little attention. Thus, this review has paid a keen interest in examining several microencapsulation strategies for potential utilization in the development of HIV pediatric formulations.
Climate Change Adaptation Strategy of the Coastal Indigenous Community of Bangladesh
Authors: Rahman Habibur , Easha Arifa Akter , Fatema Nuzhat , Islam Md. Jahidul , Alam Morshed
Published: October 2024

Climate change has increasingly impacted developing and underdeveloped nations, with Bangladesh’s coastal areas experiencing significant effects such as storm surges, salinity, cyclones, and droughts. These regions, heavily reliant on agriculture, face economic challenges exacerbated by climatic events, making adaptation to climate change a critical concern for coastal inhabitants. This study aims to understand the obstacles and adaptive mechanisms employed by the Munda indigenous people in southeastern coastal Bangladesh to protect their livelihoods. Employing both qualitative and quantitative methodologies, including focus group discussions (FGDs) and thematic analyses, we assessed the community’s challenges and adaptation strategies. FGDs revealed that public life is frequently disrupted, salinity poses a major threat to agriculture and drinking water, and the cropping pattern, fish production, livestock, infrastructure, industry, biodiversity, health, and human settlement are adversely affected. Notably, there is a significant lack of adequate healthcare. Quantitative analysis using the χ2 test showed that 33.2% of participants believe climate change affects their happiness, 85.1% stored 72 h of water and food, and 59.3% had hygiene and sanitation supplies. This research underscores the necessity of adaptive measures such as rainwater harvesting, organic fertilizer usage, community disaster preparedness education, effective communication systems, and social security implementation to mitigate climate change’s adverse effects. The findings offer valuable insights for the government, nongovermental organizations (NGOs), policymakers, civil society, and stakeholders in developing suitable climate adaptation strategies to ensure sustainable livelihoods in coastal Bangladesh.
Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate
Authors: Yurkevicz Annali M. , Liu Yanfeng , Katz Samuel G. , Glazer Peter M.
Published: October 2024

Identifying an optimal antigen for targeted cancer therapy is challenging as the antigen landscape on cancerous tissues mimics that of healthy tissues, with few unique tumor-specific antigens identified in individual patients. pH low insertion peptide (pHLIP) acts as a unique delivery platform that can specifically target the acidic microenvironment of tumors, sparing healthy tissue in the process. We developed a pHLIP-peptide conjugate to deliver the SIINFEKL peptide, an immunogenic fragment of ovalbumin (OVA), to tumor cells in vivo. When processed intracellularly, SIINFEKL is presented for immune recognition through the major histocompatibility complex (MHC) class I pathway. We observed selective delivery of pHLIP-SIINFEKL both in vitro and in vivo using fluorescently labeled constructs. In vitro, treatment of melanoma tumor cells with pHLIP-SIINFEKL resulted in recognition by SIINFEKL-specific T cells (OT1), leading to T-cell activation and effector function. Mechanistically, we show that this recognition by OT1 T cells was abrogated by siRNA/shRNA knockdown of multiple components within the MHC class I pathway in the target tumor cells, indicating that an intact antigen processing pathway in the cancer cells is necessary to mediate the effect of pHLIP-directed SIINFEKL delivery. In vivo, pHLIP-SIINFEKL treatment of tumor-bearing mice resulted in the recruitment of OT1 T cells and suppression of tumor growth in two syngeneic tumor models in immunocompetent mice, with no effect when mutating either the pHLIP or SIINFEKL components of the conjugate. These results suggest that pHLIP-mediated peptide delivery can be used to deliver novel artificial antigens that can be targeted by cell-based therapies.
Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer
Authors: Liang Beiyuan , Khan Misbah , Storts Hayden , Zhang Evan H. , Zheng Xinru , Xing Xuanxuan , Claybon Hazel , Wilson Jenna , Li Chunjie , Jin Ning , Fishel Richard , Miles Wayne O. , Wang Jing J.
Published: October 2024

Colorectal cancer is the second leading cause of cancer mortality in the United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of patients with colorectal cancer, the response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune–competent mice. Riluzole-mediated tumor suppression was dependent on the presence of CD8+ T cells. Riluzole activates the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in colon cancer cells, resulting in increased expression of IFNβ and IFNβ-regulated genes including CXCL10. Inhibition of ataxia telangiectasia mutated (ATM), but not ATM-related, resulted in a synergistic increase in IFNβ expression, suggesting that riluzole induces ATM-mediated damage response that contributes to cGAS/STING activation. Depletion of cGAS or STING significantly attenuated riluzole-induced expression of IFNβ and CXCL10 as well as increase of intratumoral CD8+ T cells and suppression of tumor growth. These results indicate that riluzole-mediated tumor infiltration of CD8+ T cells and attenuation of tumor growth is dependent on tumor cell–intrinsic STING activation. To determine whether riluzole treatment primes the tumor microenvironment for immune checkpoint modulation, riluzole was combined with anti-PD-1 treatment. This combination showed greater efficacy than either single agent and strongly suppressed tumor growth in vivo. Taken together, our studies indicate that riluzole activates cGAS/STING-mediated innate immune responses, which might be exploited to sensitize colorectal tumors to anti-PD-1/PD-L1 therapies.
Supplemental Figure 1 from Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D.
Published: October 2024

Macrophage polarization analysis
A Case of Granulocyte-Colony-Stimulating Factor-Producing Non-Small Cell Lung Cancer under Steroid Treatment and with Poor Performance Status That Responded to Pembrolizumab
Authors: Egusa Hiroki , Masuda Takeshi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Horimasu Yasushi , Kushitani Kei , Nakashima Taku , Iwamoto Hiroshi , Hamada Hironobu , Hattori Noboru
Published: October 2024

Introduction: There have been only a few cases showing the efficacy of pembrolizumab on granulocyte-colony-stimulating factor (G-CSF)-producing non-small-cell lung cancer (NSCLC) with high programmed cell death ligand 1 (PD-L1) expression. Herein, we report the first case showing the efficacy of pembrolizumab for G-CSF-producing NSCLC with high PD-L1 expression, although the patient had factors indicative of poor pembrolizumab efficacy, such as poor performance status (PS) due to the tumor-induced inflammation and corticosteroids administration. Case Presentation: A 77-year-old woman was diagnosed with G-CSF-producing NSCLC-not otherwise specified, classified as clinical stage IVB, T2N3M1c. She had fever and her PS was 3, and her C-reactive protein (CRP) was 6.47 mg/dL due to inflammation by a G-CSF-producing tumor. Thus, we initiated the administration of dexamethasone (3.3 mg/day). Her fever abated the next day, and CRP dropped to 3.22 mg/dL after 4 days. Driver mutations were negative, and PD-L1, tumor proportion score, was highly expressed at 100%. Thus, pembrolizumab was started. Subsequently, the white blood cell count decreased, and the tumor shrank, indicating a partial response. After three cycles of pembrolizumab therapy, the anorexia improved, and she was discharged. The patient developed sclerosing cholangitis after discharge. Therefore, the pembrolizumab treatment was discontinued. The primary lesion was enlarged, indicating progressive disease. However, the patient and her family did not want additional treatment. Finally, her progression-free survival and overall survival were 6 and 7 months, respectively. Conclusion: Pembrolizumab may be effective against G-CSF-producing NSCLC with high PD-L1 expression. Corticosteroids seemed to inhibit inflammation induced by the tumor, and exert the efficacy of pembrolizumab.
Immunotherapy and Tyrosine Kinase Inhibitor as a Bridge to Surgery for Clear Cell Renal Cell Carcinoma Metastases to the Thyroid: A Case Report and Literature Review
Authors: Bränström Robert , Zedenius Jan , Shabo Ivan , Lindskog Magnus , Juhlin C. Christofer
Published: October 2024

Introduction: Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer in adults, presents significant challenges owing to its resistance to conventional therapies. Standard treatment primarily revolves around surgical methods, particularly nephrectomy, which is critical for managing localized diseases. Despite recent advancements, the metastatic potential of ccRCC necessitates ongoing vigilance in postoperative monitoring to manage and detect disease recurrence. Recent shifts in treatment paradigms, especially with the integration of molecular patterns in ccRCC, have enabled the development of targeted therapies. Immune checkpoint and tyrosine kinase inhibitors (TKIs) have become central to managing metastatic ccRCC, offering new hope through improved survival outcomes. Recent studies have corroborated this by demonstrating the benefits of combining these therapies. Case Presentation: This report discusses a case study of a patient with high-grade ccRCC and thyroid metastases initially deemed non-resectable. The combination of immunotherapy and TKIs reduced tumor size, transforming the thyroid metastasis to a resectable state. Conclusion: This case highlights significant advancements in treatment approaches and the critical in the management of ccRCC, underscoring the necessity for continuous adaptation of clinical practices to incorporate new therapeutic developments.
Endothelial Dysfunction Does Not Occur after Acute, Elevated Homocysteine Exposure of the Lumen of the Iliac Artery of the Anaesthetised Pig
Authors: Markos Farouk , O’Leary Andrew J. , Noble Mark I.M. , Ruane-O’Hora Therese
Published: October 2024

Introduction: Elevated luminal homocysteine has been linked with cardiovascular disease; however, whether there is a direct effect of homocysteine on blood vessel endothelium is not clear. In this study, the acute effect of luminal homocysteine on iliac artery endothelial function was assessed in the anaesthetised pig. Methods: Hyperhomocysteinaemic blood was injected into an occluded segment of the iliac in the anaesthetised pig for 20 min, and the effect on atrial diameter during the occlusion and during the reactive hyperaemia assessed. Results: No significant changes in arterial diameter or pressure were observed during the incubation period at homocysteine concentrations of 10, 20, 40 and 100 µM. There was also no difference in the magnitude of the iliac diameter increase in the response to reactive hyperaemia when the incubation period was completed. Conclusion: There is no evidence of endothelial dysfunction in response to an acute 20-min elevation in homocysteine in an intact conduit artery.
Abstract Mo008: Sub-strain Dependent Vulnerability to Psychosocial Stress Exacerbates Doxorubicin-induced Cardiotoxicity in Adult Male Mice
Authors: DANIEL MARY RAPHEL , Grant Marianne , Razzoli Maria , Bartolomucci Alessandro , Zordoky Beshay
Published: October 2024

Introduction:
Psychosocial stress is a significant cardiovascular risk factor and an enormous burden on cancer patients. However, limited knowledge is available on the underlying mechanisms at least in part because of lack of translationally relevant animal models. Previous work from our lab established that adult exposure to social stress can exacerbate the cardiovascular effect of juvenile doxorubicin (DOX) exposure. However, the effect of concomitant DOX and stress exposure in adult mice is unknown.

Methods:
In this study, a ‘two-hit’ mouse model was established, in which chronic subordination stress (CSS) and DOX treatment were given simultaneously. Twelve-week-old male C57BL/6N (6N) and C57BL/6J (6J) mice were subjected to daily episodes of social defeat by dominant CD1 mice with whom they remained in continuous sensory contact with for 28 days, thus establishing social subordination. One week after the start of CSS, mice were administered DOX (8 mg/kg/week) for 3 weeks. Thereafter, cardiac function was assessed by echocardiography and gene expression of inflammatory and pro-fibrotic markers were determined by real-time PCR. Cardiac fibrosis and inflammation were assessed by histopathologic analysis.

Results:
Cardiac dysfunction and significant cardiac fibrosis were observed in 6N but not in 6J mice that were exposed to both DOX and CSS, as evidenced by reduced ejection fraction, cardiac output, and increased trichrome staining, respectively. Additionally, gene expression analysis demonstrated significant upregulation of atrial natriuretic peptide and interleukin-6 in 6N mice exposed to both DOX and CSS compared to 6J mice. Finally, DOX caused cardiac atrophy and abrogated CSS-induced cardiac hypertrophy in 6N but not in 6J mice, as evidenced by measuring left ventricular mass and heart weight/tibia length.

Conclusion:
Exposure to CSS exacerbated the cardiotoxic effects of DOX in a sub-strain dependent manner. These findings highlight psychosocial stress as a risk factor for worse cardiovascular outcome in cancer patients receiving cardiotoxic regimens. The study underscores sub-strain differences in the cardiac responses of 6N and 6J mouse to CSS alone and CSS/DOX treatment that may serve as a discovery platform for the identification of genetic biomarkers of resilience.