bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance
Authors: Wang Liuhao , Yan Xuehao , Wu Hongfen , Wang Feifan , Zhong Ziqi , Zheng Gang , Xiao Qian , Wu Kebang , Na Wei
Published: March 2024

Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their genomic makeup. However, information on the selection signatures of Hainan yellow cattle is scarce. Herein, we compared the genomes of Hainan yellow cattle with those of Zebu, Qinchuan, Nanyang, and Yanbian cattle breeds by the composite likelihood ratio method (CLR), Tajima’s D method, and identifying runs of homozygosity (ROHs), each of which may provide evidence of the genes responsible for heat tolerance in Hainan yellow cattle. The results showed that 5210, 1972, and 1290 single nucleotide polymorphisms (SNPs) were screened by the CLR method, Tajima’s D method, and ROH method, respectively. A total of 453, 450, and 325 genes, respectively, were identified near these SNPs. These genes were significantly enriched in 65 Gene Ontology (GO) functional terms and 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (corrected p < 0.05). Five genes—Adenosylhomocysteinase-like 2, DnaJ heat shock protein family (Hsp40) member C3, heat shock protein family A (Hsp70) member 1A, CD53 molecule, and zinc finger and BTB domain containing 12—were recognized as candidate genes associated with heat tolerance. After further functional verification of these genes, the research results may benefit the understanding of the genetic mechanism of the heat tolerance in Hainan yellow cattle, which lay the foundation for subsequent studies on heat stress in this breed.
Comparison of In Vitro Bacterial Susceptibility to Common and Novel Equine Wound Care Dressings
Authors: Simpson Merrill , Hendrickson Dean A. , Hyatt Doreene R. , Rao Sangeeta
Published: March 2024

Antimicrobial resistance is becoming a problem of concern in the veterinary field, necessitating the use of effective topical treatments to aid the healing of wounds. Honey has been used for thousands of years for its medicinal properties, but in recent years medical-grade Manuka honey has been used to treat infected wounds. The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The pathogens studied include ATCC lab-acclimated Pseudomonas aeruginosa, Escherichia coli, and methicillin-resistant Staphylococcus aureus and one from an equine sample submitted to the Colorado State Veterinary Diagnostic Laboratory (Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus)). An additional goal of the study was to describe the comparison of bactericidal activity of medical-grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings (20% hypertonic saline, silver sulfadiazine cream, PHMB gauze, and PHMB foam). The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting the growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka honey and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab-acclimated. Additional research for in vivo applications needs to be done to see whether differences exist in effective wound management.
Metabolizable Energy and Amino Acid Digestibility of Soybean Meal from Different Sources for Broiler Chickens Supplemented with Protease
Authors: Xavier Junior Maurílio de Lucas , Ferreira Rafael de Sousa , Teixeira Levy do Vale , Valentim Jean Kaique , Gomes Kaique Moreira , Bernandes Romário Duarte , Calderano Arele Arlindo , Albino Luiz Fernando Teixeira
Published: March 2024

This study investigated the effect of the serine protease on metabolizable energy and amino acids’ digestibility of different soybean meal for broilers. A total of 684 broilers chickens form 14 to 23 d age were distributed with nineteen treatments, six replicates, and six birds per replicate. Nine samples of soybean meal from different regions in Brazil were used, with some samples supplemented with the protease enzyme and others without addition. Apparent and corrected-for-nitrogen-balance metabolizable energy were evaluated, as well as the coefficients of amino acid digestibility. All collected data were submitted to ANOVA at a significance level of 5% and Tukey’s test was applied. The results showed that the addition of the protease enzyme significantly increased the values of AME and AMEn in all soybean meal samples. The soybean meal of different origins has significant variations in AME and AMEn. The addition of the protease improved the digestibility of essential amino acids compared to soybean meal without enzyme addition. These results indicate that supplementation with serine protease can improve the metabolizable energy and amino acid digestibility of soybean meal from different regions in the diet of broilers, potentially being an effective strategy to enhance nutrient utilization and animal performance.
Sensitivity Analysis of Influencing Factors of Karst Tunnel Construction Based on Orthogonal Tests and a Random Forest Algorithm
Authors: Wu Bo , Sun Wentao , Meng Guowang
Published: March 2024

To conduct a sensitivity analysis of the relevant parameters that impact the mechanics of tunnel construction in karst areas, firstly, the orthogonal design and range analysis method is applied to sort the 11 kinds of karst-tunnel-influencing factors from high to low according to the sensitivity degree. Secondly, the random forest algorithm based on an orthogonal experimental design is applied to the feature importance ranking of the influencing factors of karst tunnels. Thirdly, according to the results of the sensitivity analysis, the optimum combinations of influencing factors of tunnel construction in karst areas is obtained. The research based on these two methods shows that when taking the vertical displacement as the target variable, the parameters with the highest feature importance are A6 (tunnel diameter) and A10 (tunnel buried depth). When taking the first principal stress as the target variable, the most important influencing factors are A10 (tunnel buried depth) and A9 (location of karst cave). When taking the principal stress difference as the target variable, the most important influencing factors are A10 (tunnel buried depth) and A6 (tunnel diameter). The level combination of the 11 influencing factors obtained by taking the principal stress difference as the target variable was more balanced than the vertical displacement and the principal stress difference as the target variables. The results of this study will provide a theoretical basis to study key parameters in the response of mechanical characteristics to the safe construction of tunnels in karst areas.
Carbon Sequestration Potential of Agroforestry versus Adjoining Forests at Different Altitudes in the Garhwal Himalayas
Authors: Singh Naresh , Riyal Manoj Kumar , Singh Bhupendra , Khanduri Vinod Prasad , Rawat Deepa , Singh Chandramohan , Pinto Marina M. S. Cabral , Kumar Munesh
Published: March 2024

Forests face a variety of threats in the modern era. Agroforestry systems, both traditional and introduced, have a tremendous capacity for providing sustainable resources and combating the impact of global climate change. Indigenous agroforestry and forest land-use systems are important reservoirs for biodiversity conservation and ecosystem services, providing a potential contribution to livelihood security for rural communities. This study aimed to assess the tree diversity and carbon stock of agroforestry and adjoining forests along altitudinal gradients, ranging between 700 and 2200 masl (i.e., lower, middle, and upper altitudes) by laying sample plots randomly of a size of 20 × 20 m2. In the forest land-use system, the maximum Importance Value Index (IVI) included Dalbergia sissoo (71.10), Pyrus pashia (76.78), and Pinus roxburghii (79.69) at the upper, middle, and lower elevations, respectively, whereas, in the agroforestry land-use system, the IVI reported for Ficus semicordata was 43.05 at the upper, while for Grewia optiva it was at 53.82 at the middle and 59.33 at the lower altitudes. The below-ground biomass density (AGBD) was recorded as 1023.48 t ha−1 (lower), 242.92 t ha−1 (middle), and 1099.35 t ha−1(upper), while in the agroforestry land-use system, the AGBD was 353.48 t ha−1 (lower), 404.32 t ha−1 (middle), and 373.23 t ha−1 (upper). The total carbon density (TCD) values recorded were 630.57, 167.32, and 784.00 t ha−1 in forest land-use systems, and 227.46, 343.23, and 252.47 in agroforestry land-use systems for lower, middle, and upper altitudes, respectively. The Margalef’s Index values for agroforestry and forests ranged from 2.39 to 2.85 and 1.12 to 1.30, respectively. Soil organic carbon (SOC) stock recorded 45.32, 58.92, and 51.13 Mg C ha−1 for agroforestry and 61.73, 42.65, and 71.08 Mg C ha−1 for forest in lower, middle and upper elevations, respectively. The study suggests that selecting land use patterns can be an effective management system for tree species at different elevations for carbon storage, helping to mitigate climate change and aiding in sustainable management of ecosystems in the Garhwal Himalayas.
Hydroclimate Changes Based on Testate Amoebae in the Greater Khingan Mountains’ Peatland (NE China) during the Last Millennium
Authors: Li Xiao , Han Dongxue , Cong Jinxin , Gao Chuanyu , Wang Guoping
Published: March 2024

The driving force of climate change in the monsoon margin is complex, making it a key area for regional and global climate change research. Palaeohydrological studies in the monsoon margin have increased the resolution of research in the long term, transitioning from qualitative to quantitative studies to comprehend climate change processes, patterns, and mechanisms. Testate amoebae (TA) in peat sediments are used as a proxy indicator organism for quantitative reconstruction of palaeohydrology. Thus, their community changes are directly related to precipitation, and widely used to reconstruct the patterns of summer precipitation globally. We investigated TA species and reconstructed palaeohydrological changes in the Greater Khingan Mountains’ Hongtu (HT) peatland, located in the East Asian Summer Monsoon (EASM) margin. The result showed that the most abundant TA species were Assulina muscorum (12.4 ± 5.0%) and Nebela tincta (8.9 ± 4.9%) in the HT peat core. The increase in dry indicator species (e.g., A. muscorum and Alabasta militaris) indicated a drying pattern in the HT peatland since 150 cal yr BP. Principal component analysis (PCA) explained 47.6% of the variation in the selected TA assemblages. During 400 to 250 cal yr BP, PCA axis 1 scores ranged from 0.2 to −1.3 (reflecting a drier climate), associating with the Little Ice Age. The paleohydrology of the northern part of the Greater Khingan Mountains was mainly controlled by the EASM, which was associated with changes in North Atlantic Sea surface temperature and solar radiative forcing. The apparent drying pattern may be the result of the gradual intensification of anthropogenic activities and the increase in EASM intensity.
Battery Temperature Prediction Using an Adaptive Neuro-Fuzzy Inference System
Authors: Zhang Hanwen , Fotouhi Abbas , Auger Daniel J. , Lowe Matt
Published: March 2024

Maintaining batteries within a specific temperature range is vital for safety and efficiency, as extreme temperatures can degrade a battery’s performance and lifespan. In addition, battery temperature is the key parameter in battery safety regulations. Battery thermal management systems (BTMSs) are pivotal in regulating battery temperature. While current BTMSs offer real-time temperature monitoring, their lack of predictive capability poses a limitation. This study introduces a novel hybrid system that combines a machine learning-based battery temperature prediction model with an online battery parameter identification unit. The identification unit continuously updates the battery’s electrical parameters in real time, enhancing the prediction model’s accuracy. The prediction model employs an Adaptive Neuro-Fuzzy Inference System (ANFIS) and considers various input parameters, such as ambient temperature, the battery’s current temperature, internal resistance, and open-circuit voltage. The model accurately predicts the battery’s future temperature in a finite time horizon by dynamically adjusting thermal and electrical parameters based on real-time data. Experimental tests are conducted on Li-ion (NCA and LFP) cylindrical cells across a range of ambient temperatures to validate the system’s accuracy under varying conditions, including state of charge and a dynamic load current. The proposed models prioritise simplicity to ensure real-time industrial applicability.
Characterization of the Outer Membrane Vesicles of Pseudomonas aeruginosa Exhibiting Growth Inhibition against Acinetobacter baumannii
Authors: Suh Jin-Woong , Kang Jae-Seong , Kim Jeong-Yeon , Kim Sun-Bean , Yoon Young-Kyung , Sohn Jang-Wook
Published: March 2024

We investigated the Pseudomonas aeruginosa (PA) outer membrane vesicles (OMVs) and their effect on Acinetobacter baumannii (AB) growth in vitro. The inhibitory effects of PA on AB were assessed using a cross-streak assay. The OMVs were extracted through high-speed centrifugation, tangential flow filtration, and ultracentrifugation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs). Proteomic analysis was conducted to compare the OMVs of different PA strains. PA022 exhibited more pronounced inhibition of AB growth compared with PA ATCC 27853. TEM confirmed the presence of OMVs in both PA022 and PA ATCC 27853, revealing phospholipid bilayer structures. The NTA revealed similar sizes and concentrations. Proteomic analysis identified 623 and 538 proteins in PA022 and PA ATCC 27853 OMVs, respectively, with significant proportions of the outer membrane and extracellular proteins, respectively. Importantly, PA022 OMVs contained six known virulence factors and motility-associated proteins. This study revealed the unique characteristics of PA OMVs and their inhibitory effects on AB growth, shedding light on their role in bacterial interactions. Proteomic analysis provides valuable insights into potential pathogenic functions and therapeutic applications against bacterial infections.
Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization
Authors: Germany Morrison Enrique , Danthine Venethia , Santalucia Roberto , Torres Andrés , Cakiroglu Inci , Nonclercq Antoine , El Tahry Riëm
Published: March 2024

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.
Cell Death in Liver Disease and Liver Surgery
Authors: Stoess Christian , Choi Yeon-Kyung , Onyuru Janset , Friess Helmut , Hoffman Hal , Hartmann Daniel , Feldstein Ariel
Published: March 2024

Cell death is crucial for maintaining tissue balance and responding to diseases. However, under pathological conditions, the surge in dying cells results in an overwhelming presence of cell debris and the release of danger signals. In the liver, this gives rise to hepatic inflammation and hepatocellular cell death, which are key factors in various liver diseases caused by viruses, toxins, metabolic issues, or autoimmune factors. Both clinical and in vivo studies strongly affirm that hepatocyte death serves as a catalyst in the progression of liver disease. This advancement is characterized by successive stages of inflammation, fibrosis, and cirrhosis, culminating in a higher risk of tumor development. In this review, we explore pivotal forms of cell death, including apoptosis, pyroptosis, and necroptosis, examining their roles in both acute and chronic liver conditions, including liver cancer. Furthermore, we discuss the significance of cell death in liver surgery and ischemia-reperfusion injury. Our objective is to illuminate the molecular mechanisms governing cell death in liver diseases, as this understanding is crucial for identifying therapeutic opportunities aimed at modulating cell death pathways.
The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma
Authors: Picher Enric Arasanz , Wahajuddin Muhammad , Barth Stefan , Chisholm Julia , Shipley Janet , Pors Klaus
Published: March 2024

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5–8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease. The intensification of chemotherapeutic protocols in advanced-stage RMS has historically induced aggravated toxicity with only very modest therapeutic gain. In this review, we critically analyse what has been achieved so far in RMS therapy and provide insight into how a diverse group of drug-metabolising enzymes (DMEs) possess the capacity to modify the clinical efficacy of chemotherapy. We provide suggestions for new therapeutic strategies that exploit the presence of DMEs for prodrug activation, targeted chemotherapy that does not rely on DMEs, and RMS-molecular-subtype-targeted therapies that have the potential to enter clinical evaluation.
Correction: Liu et al. RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes. Cancers 2021, 13, 3475
Authors: Liu Xiaoming , Chen Xingyu , Xiao Mengqing , Zhu Yuxing , Gong Renjie , Liu Jianye , Zeng Qinghai , Xu Canxia , Chen Xiong , Wang Fen , Cao Ke
Published: March 2024

In the original publication [...]
Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models
Authors: Ye Junjie , Chen Lingjuan , Waltermire Julia , Zhao Jinshun , Ren Jinghua , Guo Zongsheng , Bartlett David L. , Liu Zuqiang
Published: March 2024

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.
Management of Adverse Events Associated with Pomalidomide-Based Combinations in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Nadeem Omar , Ailawadhi Sikander , Khouri Jack , Williams Louis , Catamero Donna , Maples Kathryn , Berdeja Jesús
Published: March 2024

Multi-agent regimens incorporating immunomodulatory (IMiD®) agents such as thalidomide, lenalidomide, and pomalidomide have become the preferred standard of care for the treatment of patients with multiple myeloma (MM), resulting in improved survival outcomes. Currently, there are three IMiD agents approved for the treatment of MM: thalidomide, lenalidomide, and pomalidomide. Lenalidomide is commonly used to treat patients with newly diagnosed MM and as maintenance therapy following stem cell transplant or after disease relapse. Pomalidomide, the focus of this review, is approved in patients with relapsed/refractory MM (RRMM). Despite survival benefits, IMiD agents each have different safety profiles requiring consideration both prior to starting therapy and during treatment. Adverse event (AE) management is essential, not only to ensure treatment adherence and thus ensure optimal efficacy but also to maintain patient quality of life. Here, we discuss AEs associated with pomalidomide and present five clinically relevant hypothetical case studies in patients with RRMM to provide scenario-driven guidance regarding treatment selection and AE prevention and management in the clinical setting. Lastly, as new treatment approaches continue to be explored in MM, we also discuss novel cereblon E3 ligase modulator (CELMoD™) agents including iberdomide (CC-220) and mezigdomide (CC-92480).
Ixazomib, Lenalidomide, and Dexamethasone (IRD) Treatment with Cytogenetic Risk-Based Maintenance in Transplant-Eligible Myeloma: A Phase 2 Multicenter Study by the Nordic Myeloma Study Group
Authors: Partanen Anu , Waage Anders , Peceliunas Valdas , Schjesvold Fredrik , Anttila Pekka , Säily Marjaana , Uttervall Katarina , Putkonen Mervi , Carlson Kristina , Haukas Einar , Sankelo Marja , Szatkowski Damian , Hansson Markus , Marttila Anu , Svensson Ronald , Axelsson Per , Lauri Birgitta , Mikkola Maija , Karlsson Conny , Abelsson Johanna , Ahlstrand Erik , Sikiö Anu , Klimkowska Monika , Matuzeviciene Reda , Fenstad Mona Hoysaeter , Ilveskero Sorella , Pelliniemi Tarja-Terttu , Nahi Hareth , Silvennoinen Raija
Published: March 2024

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib–lenalidomide–dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of <10−5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD < 10−5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD <10−5. Altogether 95% of the patients with sustained MRD <10−5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients.
Preventing and Treating Pain and Anxiety during Needle-Based Procedures in Children with Cancer in Low- and Middle-Income Countries
Authors: McNeil Michael J. , Garcia Quintero Ximena , Gonzalez Miriam , Zheng Yawen , Ugaz Olivares Cecilia , Morales Roxana , Boldrini Erica , Rebollo de Campos Débora , Ferreira Daiane , Coopasamy Kamalina , Caneba Joliza , Padernilla Maria Louisa , Friedrichsdorf Stefan , Baker Justin N. , Friedrich Paola
Published: March 2024

Introduction: Children with cancer experience significant pain and anxiety during needle-based procedures. Undertreated pain in children has long-lasting consequences and reduces the efficacy of subsequent analgesic efforts. A validated quality improvement (QI) intervention, known as the “Children’s Comfort Promise”, includes (1) topical anesthetics, (2) sucrose or breastfeeding for infants, (3) comfort positioning, and (4) distraction techniques, and has been shown to be highly effective in decreasing procedural pain and anxiety in children. However, there is limited data about the adoption, adaptation, and implementation of these interventions in low- and middle-income countries (LMICs). Methods: A QI pilot project utilizing the Model for Improvement of the “Global Comfort Promise” was implemented in four global pediatric cancer hospitals (Lima, Peru; Barretos, Brazil; Pietermaritzburg, South Africa; and Manila, Philippines). Between August 2021 and January 2023, the pilot sites identified a specific aim, co-designed the measurement strategy with St. Jude Children’s Research Hospital, and adopted, adapted, and implemented the project at their individual sites. Results: A total of 2,185 different procedures were recorded in the first year of implementation. Most patients were less than 10 years old (60.5%) and solid tumors (37.9%) were the most common diagnosis. Overall, healthcare professionals (98.3%) were satisfied with the procedures. Parents and patients reported that only 33.7% of patients experienced pain during the procedure. All (100%) parents and patients felt the healthcare teams adequately addressed their child’s pain. Median self-reported adherence to ≥2 interventions was 98.0%. Challenges to the implementation of the QI initiative included lack of training, turnover of the medical staff, maintaining staff enthusiasm, and access to topical anesthetics. Each site had unique change ideas to implement the initiative. Conclusions: This multi-site, multi-country QI initiative was feasible and was successfully adopted, adapted, and implemented in the LMIC context to improve procedural pain in children (Global Comfort Promise). Additionally, this intervention resulted in high satisfaction of both healthcare professionals and patients/families. Further work is needed to overcome the challenges of topical anesthetic access and education of the workforce. Additional plans include modifying the Global Comfort Promise to include high-quality communication and expanding to additional sites with further refinement of the implementation strategy.
Comparison of Immunotherapy versus Targeted Therapy Effectiveness in BRAF-Mutant Melanoma Patients and Use of cGAS Expression and Aneuploidy as Potential Prognostic Biomarkers
Authors: Garrison Zachary , Clister Terri , Bleem Eric , Berry Elizabeth G. , Kulkarni Rajan P.
Published: March 2024

BRAF-mutant melanoma patients can be treated with targeted therapy or immunotherapies, and it is not clear which should be provided first. Targeted treatments do not work in up to one-third of cases, while immunotherapies may only be effective in up to 60% and come with a high risk of immune-related side effects. Determining which treatment to provide first is thus of critical importance. Recent studies suggest that chromosomal instability and aneuploidy and cyclic GMP-AMP synthase (cGAS) can act as biomarkers for cancer severity and patient outcome. Neither potential biomarker has been extensively studied in melanoma. We examined 20 BRAF-mutant melanomas treated with immunotherapy or targeted therapy and measured chromosomal aneuploidy and cGAS expression levels. Treatment type, aneuploidy, and cGAS expression were correlated with progression-free survival (PFS) in these patients. Those treated with immunotherapy first had significantly better outcomes than those treated with targeted therapy, suggesting immunotherapy should be strongly considered as the first-line therapy for patients bearing BRAF-mutant melanoma. We found that there was no correlation of aneuploidy with outcome while there was some positive correlation of cGAS levels with PFS. Further studies are needed to confirm these findings and to test other potential biomarkers.
Recent Advances in Endometrial Cancer Prevention, Early Diagnosis and Treatment
Authors: Baker-Rand Holly , Kitson Sarah J.
Published: March 2024

Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research.
Cutting-Edge Therapies for Lung Cancer
Authors: La’ah Anita Silas , Chiou Shih-Hwa
Published: March 2024

Lung cancer remains a formidable global health challenge that necessitates inventive strategies to improve its therapeutic outcomes. The conventional treatments, including surgery, chemotherapy, and radiation, have demonstrated limitations in achieving sustained responses. Therefore, exploring novel approaches encompasses a range of interventions that show promise in enhancing the outcomes for patients with advanced or refractory cases of lung cancer. These groundbreaking interventions can potentially overcome cancer resistance and offer personalized solutions. Despite the rapid evolution of emerging lung cancer therapies, persistent challenges such as resistance, toxicity, and patient selection underscore the need for continued development. Consequently, the landscape of lung cancer therapy is transforming with the introduction of precision medicine, immunotherapy, and innovative therapeutic modalities. Additionally, a multifaceted approach involving combination therapies integrating targeted agents, immunotherapies, or traditional cytotoxic treatments addresses the heterogeneity of lung cancer while minimizing its adverse effects. This review provides a brief overview of the latest emerging therapies that are reshaping the landscape of lung cancer treatment. As these novel treatments progress through clinical trials are integrated into standard care, the potential for more effective, targeted, and personalized lung cancer therapies comes into focus, instilling renewed hope for patients facing challenging diagnoses.
Parental Attachment and Psychosocial Adjustment in Adolescents Exposed to Marital Conflict
Authors: Maya Jesús , Fuentes Isabel , Arcos-Romero Ana Isabel , Jiménez Lucía
Published: March 2024

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life of the couple but also to the father–child relationship, mother–child relationship, and well-being of adolescents. This study examined the difference in parental attachment and adjustment in adolescents exposed to marital conflict versus those not exposed to parental conflicts in low-income areas. (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father–adolescent attachment in situations of family conflict is recommended.
Medication Adherence Barriers and Their Relationship to Health Determinants for Saudi Pediatric Dialysis Patients
Authors: Baghdadi Leena R. , Alsaiady Manar M.
Published: March 2024

Medication adherence is critical for the treatment and improved outcomes of chronic diseases. However, there is little research on the medication adherence of pediatric dialysis patients in Saudi Arabia. This study examines medication adherence barriers and their relationship to health determinants among Saudi children on dialysis, to enhance treatment success. We conducted a hospital-based, cross-sectional survey of pediatric dialysis patients using a simple random sampling technique. There is a trend of higher medication adherence for peritoneal dialysis patients compared with hemodialysis patients (36.1 ± 12.9 vs. 34.7 ± 8.3, p = 0.07). The leading barriers to medication adherence for all patients included being tired of taking the medication (score = 3.0256), not feeling like taking the medicine sometimes (score = 2.7436), bad taste (score = 2.5513), and forgetfulness (score = 2.41). Determinants of health were associated with medication adherence. Lack of education (56.4%) (some children underage for school) and chronic disease requirements (16.7%) were common barriers. After adjusting for the common confounders, the adherence scores increased significantly with increasing patient age (β = 2.378, p < 0.001), patients with working parents (β = 8.726, p = 0.011), and those living outside Riyadh (β = 19.198, p < 0.001). Medication adherence among pediatric dialysis patients is influenced by sociodemographic factors, health systems, and access to care. Evidence-based targeted interventions can increase medication adherence in this group on frequent dialysis. Future efforts should utilize systematic frameworks and digital health technologies to provide quality alternatives to improve medication adherence.
Trigger Thumb, Trigger Finger and Clasped Thumb
Authors: Carvalho Marcos , Barreto Maria Inês , Alves Cristina , Soldado Francisco
Published: March 2024

Finger deformities are a common reason for medical observation in children. Subtle clinical differences can have a significant impact on the diagnosis and treatment of these patients. Identification of the basic diagnostic and treatment principles of trigger thumb, trigger finger, and clasped thumb is of paramount importance to all general practitioners, pediatricians, and orthopedic surgeons who are involved in the care of children. The purpose of this article is to review the most important concepts regarding these important topics, focusing on etiology, epidemiology, clinical presentation, diagnosis, treatment and prognosis.
NETworking for Health and in Disease: Neutrophil Extracellular Traps in Pediatric Surgical Care
Authors: Dölling Maximilian , Herrmann Martin , Boettcher Michael
Published: March 2024

This comprehensive review examines the role of Neutrophil Extracellular Traps (NETs) in pediatric surgery. Focusing on NET formation, functions, and implications, this study highlights their dual impact in infection control and contribution to tissue damage after surgery. It covers the role of NET formation in a range of pediatric conditions including immunothrombosis, formation of peritoneal adhesions, appendicitis, burns, gallstones, tumors, and necrotizing enterocolitis (NEC). The results underscore the significance of NETs in fighting infections and their association with complications like sepsis and delayed wound healing. The breakdown products of NETs as a diagnostic tool of the clinical course of acute appendicitis will also be discussed. Understanding NET formation in the pathophysiology can potentially help to find new therapeutic approaches such as the application of DNase and elastase inhibitors to change the clinical course of various diseases in pediatric surgery such as improvement of wound healing, adhesion formation, NEC, and many more.
The Effect of La on the Surface Properties of Plasma Nitrided CoCrCuFeNi High-Entropy Alloys at 440 Degrees Celsius
Authors: Wang Yifan , You Yuan , Yan Mufu , Zhang Yanxiang , Sheng Wenping , Wang Yan , Xu Shimiao , Gu Feng , Wang Chaohui , Cheng Weidong
Published: March 2024

This paper investigates the effect of the element La on plasma nitriding of the CoCrCuFeNi high-entropy alloy (HEA) at 440 °C for 8, 16, and 24 h. The phase composition, morphology, and hardness distribution of the nitrided layer are characterized using XRD, optical microscopy, and a microhardness tester. Furthermore, the corrosion resistance is tested using an electrochemical workstation. The study evaluated the friction and wear performance using a testing machine and scanning electron microscope. The thickness of the effective hardening layer after 16 h of treatment with La was similar to that after 24 h of treatment without La. The addition of La significantly increased the growth rate constant of the effective hardening layer from 0.53 × 10−14 m2/s to 0.72 × 10−14 m2/s. In addition, an expanded FCC phase with greater interplanar spacing can be formed on the surface of the sample by introducing La into the plasma nitriding process. This indicates that the expanded FCC phase, with a higher concentration of interstitial nitrogen atoms, can effectively improve the corrosion resistance of the specimen surface. The corrosion rate of the specimen surface was reduced by 27.5% and the wear rate was reduced by 41.7% after 16 h of treatment with the addition of La compared to 24 h of nitriding without the addition of La. It has been shown that the addition of La to the plasma nitriding process results in a higher quality nitrided layer in a shorter time and also demonstrates that La has the potential to optimize the surface properties of plasma nitrided HEAs.
Rapid Growth of Niobium Oxide Nanowires by Joule Resistive Heating
Authors: Calvo-Villoslada Aarón , Fernández Paloma , Sotillo Belén
Published: March 2024

Joule heating of niobium (Nb) metal wires by running a high electric current density through them has been used to grow Nb2O5 nanowires. The formation of a micrometric oxide layer on the Nb wires has also been observed. The size and density of the nanowires are related to the current values applied, as well as the thickness of the oxide layer formed. Characterization of both nanowires and oxide layer has been performed using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray microanalysis, and micro-Raman spectroscopy. It has been observed that this method allows the growth of Nb2O5 nanowires in times as short as tens of seconds.
Uncertainty Quantification of Machine Learning Model Performance via Anomaly-Based Dataset Dissimilarity Measures
Authors: Incorvaia Gabriele , Hond Darryl , Asgari Hamid
Published: March 2024

The use of Machine Learning (ML) models as predictive tools has increased dramatically in recent years. However, data-driven systems (such as ML models) exhibit a degree of uncertainty in their predictions. In other words, they could produce unexpectedly erroneous predictions if the uncertainty stemming from the data, choice of model and model parameters is not taken into account. In this paper, we introduce a novel method for quantifying the uncertainty of the performance levels attained by ML classifiers. In particular, we investigate and characterize the uncertainty of model accuracy when classifying out-of-distribution data that are statistically dissimilar from the data employed during training. A main element of this novel Uncertainty Quantification (UQ) method is a measure of the dissimilarity between two datasets. We introduce an innovative family of data dissimilarity measures based on anomaly detection algorithms, namely the Anomaly-based Dataset Dissimilarity (ADD) measures. These dissimilarity measures process feature representations that are derived from the activation values of neural networks when supplied with dataset items. The proposed UQ method for classification performance employs these dissimilarity measures to estimate the classifier accuracy for unseen, out-of-distribution datasets, and to give an uncertainty band for those estimates. A numerical analysis of the efficacy of the UQ method is conducted using standard Artificial Neural Network (ANN) classifiers and public domain datasets. The results obtained generally demonstrate that the amplitude of the uncertainty band associated with the estimated accuracy values tends to increase as the data dissimilarity measure increases. Overall, this research contributes to the verification and run-time performance prediction of systems composed of ML-based elements.
Advances and Perspectives in Biohydrogen Production from Palm Oil Mill Effluent
Authors: Albuquerque Marcela Moreira , Martinez-Burgos Walter Jose , De Bona Sartor Gabriela , Letti Luiz Alberto Junior , De Carvalho Júlio Cesar , Soccol Carlos Ricardo , Medeiros Adriane Bianchi Pedroni
Published: March 2024

Palm oil, the main vegetable oil produced globally, serves diverse purposes, ranging from cooking to the production of processed foods, cosmetics, and biodiesel. Despite contributing significantly to the economies of major producing nations, the escalating production of palm oil raises serious environmental concerns, including deforestation, biodiversity loss, and various forms of pollution. Palm oil mill effluent (POME), a byproduct of palm oil extraction, poses a severe environmental threat when left untreated. As an eco-friendly alternative, anaerobic digestion in controlled bioreactors has emerged, offering simultaneous POME treatment and biofuel generation, particularly hydrogen, with high energy efficiency. This review explores the challenges and opportunities associated with biohydrogen production from POME. Key considerations involve optimizing parameters through pretreatments, nanoparticle incorporation, defining optimal bioreactor conditions, determining hydraulic retention times, and integrating multi-stage processes like dark fermentation followed by photofermentation. This review also emphasizes the significance of sustainable practices and economic analyses in shaping the future of hydrogen production from POME, positioning it as a pivotal player in the palm oil industry’s circular economy and the global energy transition.
Towards a Hybrid Security Framework for Phishing Awareness Education and Defense
Authors: Loh Peter K. K. , Lee Aloysius Z. Y. , Balachandran Vivek
Published: March 2024

The rise in generative Artificial Intelligence (AI) has led to the development of more sophisticated phishing email attacks, as well as an increase in research on using AI to aid the detection of these advanced attacks. Successful phishing email attacks severely impact businesses, as employees are usually the vulnerable targets. Defense against such attacks, therefore, requires realizing defense along both technological and human vectors. Security hardening research work along the technological vector is few and focuses mainly on the use of machine learning and natural language processing to distinguish between machine- and human-generated text. Common existing approaches to harden security along the human vector consist of third-party organized training programmes, the content of which needs to be updated over time. There is, to date, no reported approach that provides both phishing attack detection and progressive end-user training. In this paper, we present our contribution, which includes the design and development of an integrated approach that employs AI-assisted and generative AI platforms for phishing attack detection and continuous end-user education in a hybrid security framework. This framework supports scenario-customizable and evolving user education in dealing with increasingly advanced phishing email attacks. The technological design and functional details for both platforms are presented and discussed. Performance tests showed that the phishing attack detection sub-system using the Convolutional Neural Network (CNN) deep learning model architecture achieved the best overall results: above 94% accuracy, above 95% precision, and above 94% recall.