bluuebunny/crossref_metadata_2025 huggingface dataset:
Strengthening the policy, implementation, and accountability environment for quality care: experiences from quality of care network countries
Authors: Maliqi Blerta , Cocoman Olive , Dohlsten Martin , Dussey Selina , Hinton Rachael , Mannah Margaret T. , Muzigaba Moise , Rammal Tala , Sabiiti Jesca , Yaqub Nuhu , Banerjee Anshu
Published: January 2024

Despite global commitment to universal health coverage with quality, poor quality of care (QOC) continues to impact health outcomes for mothers and newborns, especially in low-and-middle income countries. Although there is much experience from small-scale projects, without a long-term perspective it is unclear how to implement quality of care effectively and consistently for impact. In 2017, ten countries together with the WHO and a coalition of partners established the Network for Improving Quality of Care for Maternal, Newborn and Child Health (the Network). The Network agreed to pursue four strategic objectives—Leadership, Action, Learning and Accountability (LALA) for QOC. This paper describes, analyses and reflects on what has worked and some of the challenges faced in implementation of the LALA framework. The implementation of the LALA framework has served as a catalyst to develop an enabling environment for QOC in the Network countries through strengthening the policy, implementation, accountability and community engagement for quality care. Developing an enabling health system environment takes time, but it is possible and shows results. The implementation shows that health systems continue to face persistent challenges such as capacities to quickly scale up changes across subnational levels, limited workforce capability to implement quality improvement consistently and gaps in quality of relevant data. The implementation has also highlighted the need to develop new mechanisms for community engagement and learning systems that inform scaling up of good QOC practices across programmes and levels of care. Moving forward, the Network countries will build on the experiences and lessons learned and continue to strengthen the implementation of LALA strategic objectives for impact. We hope the Network experience will encourage other countries and partners to adopt the Network implementation model to enable delivery of quality care for everyone, everywhere, and actively collaborate and contribute to the QOC global learning network.
Lactobacillus johnsonii and host communication: insight into modulatory mechanisms during health and disease
Authors: Arzola-Martínez Llilian , Ravi Keerthikka , Huffnagle Gary B. , Lukacs Nicholas W. , Fonseca Wendy
Published: January 2024

Lactobacillus johnsonii is a commensal bacterium that has been isolated from vaginal and gastrointestinal (GI) tracts of vertebrate hosts, including humans, rodents, swine, and poultry. Lactobacillus-based probiotic supplements are popular because of the health advantages they offer. Species such as L. johnsonii are particularly interesting due to their potential health-promoting properties. Here, we reviewed the research on specific strains of L. johnsonii that have been studied in the context of health and disease and delved into the underlying mechanisms that aid in preserving host homeostasis. The utilization of L. johnsonii strains has been widely linked to numerous health benefits in the host. These include pathogen antagonism, control of mucosal and systemic immune responses, reduction of chronic inflammation, modulation of metabolic disorders, and enhanced epithelial barrier. These findings suggest that L. johnsonii plays a critical role in maintaining host homeostasis, highlighting its potential as a probiotic.
Tour guide robot: a 5G-enabled robot museum guide
Authors: Rosa Stefano , Randazzo Marco , Landini Ettore , Bernagozzi Stefano , Sacco Giancarlo , Piccinino Mara , Natale Lorenzo
Published: January 2024

This paper presents and discusses the development and deployment of a tour guide robot as part of the 5 g-TOURS EU research project, aimed at developing applications enabled by 5G technology in different use cases. The objective is the development of an autonomous robotic application where intelligence is off-loaded to a remote machine via 5G network, so as to lift most of the computational load from the robot itself. The application uses components that have been widely studied in robotics, (i.e., localization, mapping, planning, interaction). However, the characteristics of the network and interactions with visitors in the wild introduce specific problems which must be taken into account. The paper discusses in detail such problems, summarizing the main results achieved both from the methodological and the experimental standpoint, and is completed by the description of the general functional architecture of the whole system, including navigation and operational services. The software implementation is also publicly available.
Forward and back is not enough: applying best practices for translation of pediatric sleep questionnaires
Authors: Thompson Darcy A. , Fineman Melissa S. , Miramontes Valdes Estefania , Tschann Jeanne M. , Meltzer Lisa J.
Published: January 2024

Cultural differences in the experience of sleep warrant consideration in the measurement of sleep across populations. This requires careful attention to both language and culture when translating survey measures. While forward and back translation is the most commonly used approach, it has numerous limitations if used as an isolated method. Best practice guidelines recommend a multi-step team-based approach for translating questionnaires. We present our recent experience applying best practices in a study with both Spanish and English-speaking Mexican American mothers of toddlers. This work is part of a larger project that will measure parental sleep-related beliefs and parenting practices in Mexican American parents of toddlers. We utilized a team-based approach to translation and cultural adaptation, assembling a diverse, bilingual, and bicultural team. The translation process started with items and measures that we had selected, revised as needed, or created. New items were based on constructs identified in semi-structured interviews and focus groups used to explore parental sleep-related beliefs and parenting practices in the target population. Following this, our translation process included forward and back translation, harmonization and decentering, cognitive interviewing, debriefing, adjudication, and proofreading. We outline details of our process and the rationale for each step. We also highlight how each step contributes to ensuring culturally appropriate items with conceptual equivalence across languages. To ensure inclusivity and scientific rigor within the field of sleep research, investigators must utilize best practices for translations and cultural adaptations, building on the foundation of cultural constructs often identified in qualitative work.
Early results of high tibial osteotomy versus combined arthroscopic surgery
Authors: Zhang Zhenbin , Yan Zhaolong , Wang Gongteng , Zhang Wenqi , Li Guangxing , Wang Xufeng , Sun Huaqiang , Li Shufeng
Published: January 2024

Objective

To investigate the early effect of high tibial osteotomy (HTO) compared with combined arthroscopic surgery.

Methods

A retrospective study was conducted on patients who underwent HTO at The First Affiliated Hospital of Shandong First Medical University from January 2018 to January 2022. 138 patients (163 knees) with knee osteoarthritis (KOA) treated with HTO were selected. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA) angle, weight-bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American Knee Society score (KSS), US Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were measured to determine the different effects between HTO and HTO combined with arthroscopic by logistic regression analysis.

Results

Patients with HTO combined with arthroscopic surgery have improved functional scores as well as imaging perspectives compared to preoperative. By multivariate logistic analysis, it was concluded that arthroscopic surgery and gender are influential factors in the outcome of HTO surgery. The postoperative KSS score was 2.702 times more likely to be classified as excellent in the HTO combined with arthroscopy group than in the HTO group [Exp (β) = 2.702, 95% CI (1.049–6.961), P = 0.039]; the postoperative KSS score was 0.349 times more likely to be classified as excellent in women than in men [Exp (β) = 0.349, 95% CI (0.138–0.883), P = 0.026].

Conclusion

Better results with HTO combined with arthroscopic surgery. HTO combined with arthroscopy is a better choice in the surgical treatment of KOA.
Determination of breeding criteria for gait proficiency in leisure riding and racing dromedary camels: a stepwise multivariate analysis of factors predicting overall biomechanical performance
Authors: Iglesias Pastrana Carlos , Navas González Francisco Javier , Ciani Elena , Marín Navas Carmen , Delgado Bermejo Juan Vicente
Published: January 2024

To date, the biomechanical dynamics in camelids have not been addressed, although it might be a factor that can affect selection and breeding in this species. Therefore, the aim of this article is to conduct curve fitting and discriminant canonical analysis to identify the mathematical function that best captures the dynamics of camel locomotion and to study the impact of kinematic, morphometric, physiological, and phaneroptic variables on gait performance in leisure riding and racing activities in dromedaries, respectively. The cubic function emerged as the most suitable mathematical model to represent the locomotive behavior of camels. Various factors were found to play a pivotal role in the athletic performance of leisure riding and racing dromedary camels. Concretely, angular measurements at the distal fore and rear extremity areas, pelvis inclination, relative volume of the hump, impact forces of the front limbs, post-neutering effects, and the kinematic behavior of the scapula, shoulder, carpus, hip, and foot are the factors that greatly impact gait performance in leisure riding and racing camels. The biomechanical performance at these specific body regions has a profound impact on weight absorption and minimization of mechanic impact during camel locomotion, static/dynamic balance, force distribution, energy of propulsion, movement direction and amplitude, and storage of elastic strain in leisure riding and racing dromedaries. In contrast, other animal- and environment-dependent factors do not exert significant influence on camel gait performance, which can be attributed to species-specific, inherited adaptations developed in response to desert conditions, including the pacing gait, broad foot pads, and energy-efficient movements. The outcomes of our functional data analysis can provide valuable insights for making informed breeding decisions aimed at enhancing animal functional performance in camel riding and racing activities. Furthermore, these findings can open avenues for exploring alternative applications, such as camel-assisted therapy.
Do Clean Toilets Help Improve Farmers’ Mental Health? Empirical Evidence from China’s Rural Toilet Revolution
Authors: Zhang Ruohan , Zhang Jialan , Zhang Kuan , Xu Dingde , Qi Yanbin , Deng Xin
Published: January 2024

The mental health crisis poses a major challenge to global sustainable development. In response, the United Nations has launched an ambitious plan to “reshape the environment that affects mental health”. Clean toilets are an important measure of civilization, yet it is unclear whether they are helping to alleviate the global mental health crisis. Therefore, using data from a large sample of rural Chinese households and introducing an instrumental variables approach based on the IV-Tobit model to address endogeneity, this study quantitatively discusses that clean latrines have a positive effect on the mental health of farm households. The results showed the following: (1) 89.8% of Chinese rural households had clean toilets, while the average farm household depression index was 12.568; and (2) clean toilets helped to improve the mental health of farmers, which means that the depression index of farmers with clean toilets decreased by 66.9% compared to farmers without clean toilets. The findings of this study can inform the development of policies to mitigate the global mental health crisis and contribute to the resilience of global development.
Conundrums in the Management of Febrile Infants under Three Months of Age and Future Research
Authors: Wilcox Helena , Umana Etimbuk , Fauteux-Lamarre Emmanuelle , Velasco Roberto , Waterfield Thomas
Published: January 2024

Febrile infants under three months of age pose a diagnostic challenge to clinicians. Unlike in older children, the rates of invasive bacterial infections (IBIs), such as bacteraemia or meningitis, are high. This greater risk of IBI combined with the practical challenges of assessing young infants results in a cautious approach with many febrile infants receiving parenteral antibiotics “just in case”. However, there is a range of validated tailored care guidelines that support targeted investigation and management of febrile infants, with a cohort identified as lower risk suitable for fewer invasive procedures and observation without parenteral antibiotics. This manuscript outlines five common conundrums related to the safe application of tailored-care guidelines for the assessment and management of febrile infants under three months of age. It also explores future research which aims to further refine the management of febrile infants.
Evaluating the Efficacy of Eccentric Half-Squats for Post-Activation Performance Enhancement in Jump Ability in Male Jumpers
Authors: Kannas Theodoros M. , Chalatzoglidis Georgios , Arvanitidou Elli , Babault Nicolas , Paizis Christos , Arabatzi Fotini
Published: January 2024

The purpose of the present study was to investigate effect of post-activation performance enhancement (PAPE) induced by the eccentric half-squat exercise on vertical jump performance in male jumpers. The jumping height, peak power, and work were measured and evaluated in twenty male jumpers (age: 21.2 ± 1.7 years, height: 191.1 ± 3.3 cm, body mass: 81.56 ± 7.3 kg) who participated in the national championship last year. Participants performed five eccentric half-squats at 85% of their one-repetition maximum (1 RM), with a knee angle below 90°, followed by immediate and 2 min delayed jump assessments using the Squat Jump (SJ) and Countermovement Jump (CMJ) tests. Results showed that this specific PAPE protocol did not significantly improve jump performance for the SJ (Height: ES = 0.613, p = 0.462, Work: ES = 0.124, p = 0.231, Power: ES = 0.382, p = 0.125) or CMJ (Height: ES = 0.523, p = 0.368, Work ecc: ES = 0.133, p = 0.505 (only main effect time p < 0.05), Work con: ES = 0.114, p = 0.101, Power ecc: ES = 0.134, p = 0.177, Power con: ES = 0.182, p = 0.195, Leg stiffness: ES = 0.095, p = 0.358) tests. Factors such as stimulus specificity, rest intervals, muscle length, and the balance between potentiation and fatigue may explain these results. This study highlights the complexity of PAPE responses and suggests that a single set of eccentric squats with a short rest may not improve jump performance in male jumpers. Further research is required to optimize the interplay between conditioning stimuli and rest periods to maximize PAPE effects in athletic performance enhancement.
Research on Contactless Detection of Sow Backfat Thickness Based on Segmented Images with Feature Visualization
Authors: Cao Tingjin , Li Xuan , Liu Xiaolei , Liang Hao , Wang Haiyan , Xu Dihong
Published: January 2024

Aiming to address the problem that the existing methods for detecting sow backfat thickness are stressful, costly, and cannot detect in real time, this paper proposes a non-contact detection method for sow backfat with a residual network based on image segmentation using the feature visualization of neural networks. In this paper, removing the irrelevant information of the image to improve the accuracy of the sow backfat thickness detection model is proposed. The irrelevant features in the corresponding image of the feature map are found to have the same high brightness as the relevant feature regions using feature visualization. An image segmentation algorithm is then used to separate the relevant feature image regions, and the model performance before and after image segmentation is compared to verify the feasibility of this method. In order to verify the generalization ability of the model, five datasets were randomly divided, and the test results show that the coefficients of determination (R2) of the five groups were above 0.89, with a mean value of 0.91, and the mean absolute error (MAE) values were below 0.66 mm, with a mean value of 0.54 mm, indicating that the model has high detection accuracy and strong robustness. In order to explain the high accuracy of the backfat thickness detection model and to increase the credibility of the application of the detection model, using feature visualization, the irrelevant features and related features of the sow back images extracted by the residual network were statistically analyzed, which were the characteristics of the hip edge, the area near the body height point, the area near the backfat thickness measurement point (P2), and the lateral contour edge. The first three points align with the previous research on sow backfat, thus explaining the phenomenon of the high accuracy of the detection model. At the same time, the side contour edge features were found to be effective for predicting the thickness of the back. In order to explore the influence of irrelevant features on the accuracy of the model, UNet was used to segment the image area corresponding to the irrelevant features and obtain the sow contour image, which was used to construct a dorsal fat thickness detection model. The R2 results of the model were above 0.91, with a mean value of 0.94, and the MAE was below 0.65 mm, with a mean value of 0.44 mm. Compared to the test results of the model before segmentation, the average R2 of the model after segmentation increased by 3.3%, and the average MAE decreased by 18.5%, indicating that irrelevant features will reduce the detection accuracy of the model, which can provide a reference for farmers to dynamically monitor the backfat of sows and accurately manage their farms.
Effect of Cyclic Loading on Mode I Fracture Toughness of Granite under Real-Time High-Temperature Conditions
Authors: Lv Fei , Zhang Fan , Zhang Subiao , Li Kangwen , Ma Shuangze
Published: January 2024

Under hot dry rock development, rock formations undergo the combined challenges of cyclic loading and high temperatures, stemming from various sources such as cyclic hydraulic fracturing and mechanical excavation. Therefore, a fundamental understanding of how rocks fracture under these demanding conditions is fundamental for cyclic hydraulic fracturing technology. To this end, a series of three-point bending tests were conducted on granite samples. These tests entailed exposing the samples to cyclic loading under varying real-time high-temperature environments, ranging from 25 °C to 400 °C. Furthermore, different upper load limits (75%, 80%, 85%, and 90% of the peak load) obtained in monotonic three-point bending tests were used to explore the behavior of granite under these conditions. The analysis encompassed the study of load–displacement curves, elastic stiffness, and mode I fracture toughness under cyclic loading conditions. In addition, the microscopic features of the fracture surface were examined using a scanning electron microscope (SEM). The findings revealed notable patterns in the behavior of granite. Cumulative vertical displacement in granite increased with the growing number of cycles, especially at 25 °C, 200 °C, and 300 °C. This displacement exhibited a unique trend, initially decreasing before subsequently rising as the cycle count increased. Additionally, the critical damage threshold of granite exhibited a gradual decline as the temperature rose. As the temperature ascended from 25 °C to 200 °C, the damage threshold typically ranged between 80% and 85% of the peak load. At 300 °C, this threshold declined to approximately 75–80% of the peak load, and at 400 °C, it fell below 75% of the peak load. Within the temperature ranging from 25 °C to 300 °C, we noted a significant increase in the incidence of cracks, crystal microfracture zones, and the dislodging of mineral particles within the granite as the number of cycles increased.
Water Flow Boiling in Micro/Mini Channels Using Volume of Fluid Model
Authors: Khan Mughal Muhammad Umer , Waheed Khalid , Sadiq Muhammad Imran , Molla Altaf Hossain , Harun Zambri , Etminan Amin
Published: January 2024

Recent advancements in computational fluid dynamics (CFD) have triggered research in the field of heat exchangers. Driven by the need to decrease the size of heat exchangers, many researchers have exploited the higher heat transfer achieved by replacing single-phase flow systems with boiling counterparts. The concept of using mini-channels to provide compact heat exchangers while maintaining heat transfer performance is relatively new. A minimal number of researchers have reported simulations of water-steam systems in mini-channels. This paper presents a numerical study of the heat transfer performance (HTP) of mini channels in a water-steam system using the volume of fluid (VOF) model coupled with the Lee phase change model on commercial CFD software ANSYS. The numerical model consisted of a 1 mm × 1.5 mm × 52 mm channel with boundary conditions: top adiabatic; constant heat flux at the bottom surface; left/right periodic; mass flow inlet and pressure outlet. A mesh independence study was carried out for the proposed model, and simulations were validated against the experimental results of heat transfer versus vapor quality for a wide range of mass and heat fluxes. The VOF model best predicts experimental HTC at high mass fluxes, although the results at low mass fluxes were predicted with reasonable accuracy. Based on the agreement of numerical and numerical results, the VOF model turned out to be a promising candidate for designing compact micro/mini channel heat exchangers.
Thermal, Multispectral, and RGB Vision Systems Analysis for Victim Detection in SAR Robotics
Authors: Cruz Ulloa Christyan , Orbea David , del Cerro Jaime , Barrientos Antonio
Published: January 2024

Technological advancements have facilitated the development of sophisticated vision systems, integrating optical sensors with artificial vision and machine learning techniques to create applications in different fields of robotics. One such field is Search and Rescue (SAR) robotics, which has historically played a significant role in assisting brigades following post-disaster events, particularly in exploration phases and, crucially, in victim identification. The importance of employing these systems in victim identification lies in their functionality under challenging conditions, enabling the capture of information across different light spectrum ranges (RGB, Thermal, Multispectral). This article proposes an innovative comparative analysis that scrutinizes the advantages and limitations of three sensor types in victim detection. It explores contemporary developments in the state-of-the-art and proposes new metrics addressing critical aspects, such as functionality in specific scenarios and the analysis of environmental disturbances. For the indoor and outdoor testing phase, a quadrupedal robot has been equipped with these cameras. The primary findings highlight the individual contributions of each sensor, particularly emphasizing the efficacy of the infrared spectrum for the thermal camera and the Near Infrared and Red Edge bands for the multispectral camera. Ultimately, following system evaluations, detection precisions exceeding 92% and 86%, respectively, were achieved.
Deep Learning for Neuromuscular Control of Vocal Source for Voice Production
Authors: Palaparthi Anil , Alluri Rishi K. , Titze Ingo R.
Published: January 2024

A computational neuromuscular control system that generates lung pressure and three intrinsic laryngeal muscle activations (cricothyroid, thyroarytenoid, and lateral cricoarytenoid) to control the vocal source was developed. In the current study, LeTalker, a biophysical computational model of the vocal system was used as the physical plant. In the LeTalker, a three-mass vocal fold model was used to simulate self-sustained vocal fold oscillation. A constant /ə/ vowel was used for the vocal tract shape. The trachea was modeled after MRI measurements. The neuromuscular control system generates control parameters to achieve four acoustic targets (fundamental frequency, sound pressure level, normalized spectral centroid, and signal-to-noise ratio) and four somatosensory targets (vocal fold length, and longitudinal fiber stress in the three vocal fold layers). The deep-learning-based control system comprises one acoustic feedforward controller and two feedback (acoustic and somatosensory) controllers. Fifty thousand steady speech signals were generated using the LeTalker for training the control system. The results demonstrated that the control system was able to generate the lung pressure and the three muscle activations such that the four acoustic and four somatosensory targets were reached with high accuracy. After training, the motor command corrections from the feedback controllers were minimal compared to the feedforward controller except for thyroarytenoid muscle activation.
Effect of Pressure and Holding Time during Compression Molding on Mechanical Properties and Microstructure of Coke-Pitch Carbon Blocks
Authors: Gwon Sun-Ung , Lee Sang-Hye , Youn U-Sang , Roh Jae-Seung
Published: January 2024

In this study, isotropic coke and coal tar pitch were subjected to compression molding while varying the compression pressure and holding time. As a result, carbon blocks were fabricated, and their mechanical properties and microstructure were analyzed, with respect to applied pressure and holding time. The compression pressure was set to 70, 100 and 130 MPa, while the holding time was set to 1, 2 and 3 min. Overall, with an increase in compression pressure, bulk density increased while porosity decreased. Increased compression pressure also led to enhanced mechanical and electrical properties. Microstructural analysis confirmed that, after compression molding granules that were larger than existing kneaded particles appeared. The formation of granules is attributed to the tendency of kneaded particles to connect and coalesce with each other under applied pressure during the compression molding process. As the compression pressure increased, the proportion of granules in the microstructure increased while the size of pores decreased. This phenomenon can be attributed to kneaded particles coming closer to each other under applied pressure. At a compression pressure of 130 MPa, both bulk density and porosity increased with a longer holding time. Some pores existed within granules, while others protruded out of granules, thereby forming long channels of connected pores around them. This microstructural change was considered to result in degraded mechanical and electrical properties.
Stalling in Queuing Systems with Heterogeneous Channels
Authors: Sakalauskas Leonidas , Kaklauskas Liudvikas , Macaitiene Renata
Published: January 2024

The present paper considers a model of stalling in a queueing system (QS) with any number of different capacities of heterogeneous servers. The state graph and the corresponding linear system for steady-state probabilities are derived using the standard Markov chain technique. The obtained solution of the steady-state probabilities model is numerically stable; the complexity of the corresponding expressions does not depend on the number of QS states; thus, they enable us to analytically study the QS characteristics. Optimization of a stalling buffer is considered as well, and it is shown that stalling helps us to solve the slow server problem under an appropriate choice of stalling buffer size, making the slow servers usable under various values of system load. The asymptotic conditions of optimal query distribution in channels, when the ratio of the capacities of the fast and slow servers is increasing, are also established. Moreover, some applications of the developed model in heterogeneous server clusters and in work productivity modelling for forest harvesting applications are discussed.
Fractal Analysis Applied to the Diagnosis of Oral Cancer and Oral Potentially Malignant Disorders: A Comprehensive Review
Authors: Contaldo Maria , Di Spirito Federica , Di Palo Maria Pia , Amato Alessandra , Fiori Fausto , Serpico Rosario
Published: January 2024

In nature, everything is regular and orderly arranged. The degree of derailment from geometry is related to the disarrangement of living tissues associated with diseases. In the diagnostic field, fractal analysis calculates the fractal dimension (FD), a numerical measure of the degree of regularity of a tissue or structure. As for oral lesions, fractal analysis has been reported to determine the degree of irregular tissue/vascularization derailment mathematically, and this event has been correlated with the nature of the lesion. The purpose of this paper is to evaluate the scientific literature on the fractal analysis of oral cancer and its precursors (oral potentially malignant disorders, OPMDs) to convey whether the specific fractal dimension may be predictive of cancer or the cancerous progression of OPMDs. For this purpose, three databases (PubMed, Scopus, and ISI Web of Science) were investigated according to the PRISMA checklist to answer the following query: “Is fractal analysis a support method to diagnose oral cancer and distinguish it from its precursors?” The risk of biases was also assessed. All original articles published in English were considered; letters, reviews, editorials, and proceedings were excluded.
Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches
Authors: Musmaker Kendra , Wells Jacob , Tsai Meng-Chia , Comeron Josep M. , Malkova Anna
Published: January 2024

Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10–15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast Saccharomyces cerevisiae and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (RAD51-dependent and RAD51-independent) have been described. Studies in yeast have provided the phenotypic characterization of ALT survivors, descriptions of the proteins involved, and implicated break-induced replication (BIR) as the mechanism responsible for ALT. Nevertheless, many questions have remained, and answering them has required the development of new quantitative methods. In this review we discuss the historic aspects of the ALT investigation in yeast as well as new approaches to investigating ALT, including ultra-long sequencing, computational modeling, and the use of population genetics. We discuss how employing new methods contributes to our current understanding of the ALT mechanism and how they may expand our understanding of ALT in the future.
Molecular Modeling Studies to Probe the Binding Hypothesis of Novel Lead Compounds against Multidrug Resistance Protein ABCB1
Authors: Cheema Yasmeen , Linton Kenneth J. , Jabeen Ishrat
Published: January 2024

The expression of drug efflux pump ABCB1/P-glycoprotein (P-gp), a transmembrane protein belonging to the ATP-binding cassette superfamily, is a leading cause of multidrug resistance (MDR). We previously curated a dataset of structurally diverse and selective inhibitors of ABCB1 to develop a pharmacophore model that was used to identify four novel compounds, which we showed to be potent and efficacious inhibitors of ABCB1. Here, we dock the inhibitors into a model structure of the human transporter and use molecular dynamics (MD) simulations to report the conformational dynamics of human ABCB1 induced by the binding of the inhibitors. The binding hypotheses are compared to the wider curated dataset and those previously reported in the literature. Protein–ligand interactions and MD simulations are in good agreement and, combined with LipE profiling, statistical and pharmacokinetic analyses, are indicative of potent and selective inhibition of ABCB1.
Potential Causal Association between Plasma Metabolites, Immunophenotypes, and Female Reproductive Disorders: A Two-Sample Mendelian Randomization Analysis
Authors: Shen Hui-Hui , Zhang Yang-Yang , Wang Xuan-Yu , Wang Cheng-Jie , Wang Ying , Ye Jiang-Feng , Li Ming-Qing
Published: January 2024

Background: While extensive research highlighted the involvement of metabolism and immune cells in female reproductive diseases, causality remains unestablished. Methods: Instrumental variables for 486 circulating metabolites (N = 7824) and 731 immunophenotypes (N = 3757) were derived from a genome-wide association study (GWAS) meta-analysis. FinnGen contributed data on 14 female reproductive disorders. A bidirectional two-sample Mendelian randomization study was performed to determine the relationships between exposures and outcomes. The robustness of results, potential heterogeneity, and horizontal pleiotropy were examined through sensitivity analysis. Results: High levels of mannose were found to be causally associated with increased risks of gestational diabetes (GDM) (OR [95% CI], 6.02 [2.85–12.73], p = 2.55 × 10−6). A genetically predicted elevation in the relative count of circulating CD28−CD25++CD8+ T cells was causally related to increased female infertility risk (OR [95% CI], 1.26 [1.14–1.40], p = 1.07 × 10−5), whereas a high absolute count of NKT cells reduced the risk of ectopic pregnancy (OR [95% CI], 0.87 [0.82–0.93], p = 5.94 × 10−6). These results remained consistent in sensitivity analyses. Conclusions: Our study supports mannose as a promising GDM biomarker and intervention target by integrating metabolomics and genomics.
The 2.6 Å Structure of a Tulane Virus Variant with Minor Mutations Leading to Receptor Change
Authors: Sun Chen , Huang Pengwei , Xu Xueyong , Vago Frank S. , Li Kunpeng , Klose Thomas , Jiang Xi Jason , Jiang Wen
Published: January 2024

Human noroviruses (HuNoVs) are a major cause of acute gastroenteritis, contributing significantly to annual foodborne illness cases. However, studying these viruses has been challenging due to limitations in tissue culture techniques for over four decades. Tulane virus (TV) has emerged as a crucial surrogate for HuNoVs due to its close resemblance in amino acid composition and the availability of a robust cell culture system. Initially isolated from rhesus macaques in 2008, TV represents a novel Calicivirus belonging to the Recovirus genus. Its significance lies in sharing the same host cell receptor, histo-blood group antigen (HBGA), as HuNoVs. In this study, we introduce, through cryo-electron microscopy (cryo-EM), the structure of a specific TV variant (the 9-6-17 TV) that has notably lost its ability to bind to its receptor, B-type HBGA—a finding confirmed using an enzyme-linked immunosorbent assay (ELISA). These results offer a profound insight into the genetic modifications occurring in TV that are necessary for adaptation to cell culture environments. This research significantly contributes to advancing our understanding of the genetic changes that are pivotal to successful adaptation, shedding light on fundamental aspects of Calicivirus evolution.
Experimental Studies and Finite Element Analysis of Socket-Type Keyway Steel Pipe Scaffolding
Authors: Zhang Chenyang , Yang Jianjun , Jiang Liqiang , He Yanqing
Published: January 2024

Scaffolding is an integral temporary structural system in the field of construction engineering. However, the current scaffolding commonly has the shortcomings of low construction efficiency and high risk. This paper proposes a novel socket-type keyway steel pipe scaffolding, which can well solve the shortcomings of the existing scaffolding. Due to less research related to scaffolding in the past decades, it has resulted in a high number of scaffolding accidents. In order to avoid the occurrence of scaffolding accidents, it is necessary to systematize the study of this novel type of scaffolding. This study is an extremely important reference for the use and design of this novel type of scaffolding. To explore the ultimate load capacity and destabilization mode of the novel socket-type keyway steel pipe scaffolding, full-scale tests were conducted on the socket-type keyway steel pipe scaffolding with cantilever heights of 1.2 m and 0.5 m. The test results indicate that the ultimate load capacity of the scaffolding with a cantilever height of 1.2 m is 196 kN, and the destabilization mode is local instability. The ultimate load capacity with a cantilever height of 0.6 m is 276 kN, and the destabilization mode is half-wave buckling. This phenomenon shows that the different cantilever heights of the scaffolding have a significant effect on the load capacity and destabilization mode. Moreover, the load capacity decreases significantly with increasing cantilever length. The finite element model was established using SAP2000 v21 and compared with the test results. The error between the ultimate load capacity in the finite element linear elastic buckling analysis and the test results is 25%. The error between the calculated ultimate load capacity in the nonlinear buckling analysis considering the initial geometrical defects and the test results is 4%. Therefore, the nonlinear buckling analysis considering the initial geometrical defects is more in line with the force situation of the structure in the real situation.
Failure Probability and Economic Loss Assessment of a High-Rise Frame Structure under Synthetic Multi-Dimensional Long-Period Ground Motions
Authors: Zhang Zheng , Jiang Yunmu
Published: January 2024

Multiple research studies and seismic data analyses have shown that multi-directional long-period ground motion affects crucial and intricate large-scale structures like oil storage containers, long-span bridges, and high-rise buildings. Seismic damage data show a 3–55% chance of long-period ground motion. To clarify, the chance of occurrence is 3% in hard soil and 83% in soft soil. Due of the above characteristics, the aseismic engineering field requires a realistic stochastic model that accounts for long-period multi-directional ground motion. A weighted average seismic amplification coefficient selected NGA database multi-directional long-period ground motion recordings for this study. Due to the significant low-frequency component in the long-period ground motion, this research uses empirical mode decomposition (EMD) to efficiently decompose it into a composite structure with high- and low-frequency components. Given the above, further investigation is needed on the evolutionary power spectrum density (EPSD) functions of high- and low-frequency components. Analyzing the recorded data will reveal these functions and their corresponding parameters. Proper orthogonal decomposition (POD) is needed to simulate samples of high- and low-frequency components in different directions. These samples can be combined to illustrate multi-directional long-period ground motion. Representative samples exhibit the seismic characteristics of long-period multi-directional ground motion, as shown by numerical examples. This proves the method’s engineering accuracy and usefulness. Moreover, this study used incremental dynamic analysis (IDA) to apply seismic vulnerability theory. This study investigated whether long-period ground motions in both x and multi-directional directions could enhance the seismic response of a high-rise frame structure. By using this method, a comprehensive seismic economic loss rate curve was created, making economic loss assessment clearer. This study shows that multi-directional impacts should be included when studying seismic events and calculating structure economic damages.
Prediction of Subclinical and Clinical Multiple Organ Failure Dysfunction in Breast Cancer Patients—A Review Using AI Tools
Authors: Ionescu (Miron) Andreea-Iuliana , Atasiei Dimitrie-Ionut , Ionescu Radu-Tudor , Ultimescu Flavia , Barnonschi Andrei-Alexandru , Anghel Alexandra-Valentina , Anghel Cătălin-Alexandru , Antone-Iordache Ionuț-Lucian , Mitre Ruxandra , Bobolocu Alexandra Maria , Zamfir Andreea , Lișcu Horia-Dan , Coniac Simona , Șandru Florica
Published: January 2024

This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question “Why patients with breast cancer exhibit a tendency to deteriorate”, this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient’s demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as “MODS”, “SIRS”, “sepsis”, “pathophysiology of MODS”, “MODS in cancer patients”, “multiple organ failure”, “risk factors”, “cancer”, “ICU”, “quality of life”, and “breast cancer”. Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process.
Cyclophilin A: An Independent Prognostic Factor for Survival in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab and Chemotherapy
Authors: Moisuc Diana Cornelia , Constantinescu Daniela , Marinca Mihai Vasile , Gafton Bogdan , Pavel-Tanasa Mariana , Cianga Petru
Published: January 2024

Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy. We showed that low levels of CypA at baseline and after one month of treatment were associated with better overall survival (OS) (42 versus 24 months, p = 0.029 at baseline; 42 versus 25 months, p = 0.039 after one month). For copeptin and Tie2, Kaplan–Meier curves showed no correlation between these biomarkers and OS or progression-free survival. When adjusting for baseline and post-treatment factors, a multivariate Cox analysis showed that low values of CypA at baseline and after one month of treatment were independent prognostic factors for OS and correlated with a better prognosis in metastatic CRC patients.
Next-Generation CEA-CAR-NK-92 Cells against Solid Tumors: Overcoming Tumor Microenvironment Challenges in Colorectal Cancer
Authors: Franzén Alexander Sebastian , Boulifa Abdelhadi , Radecke Clarissa , Stintzing Sebastian , Raftery Martin J. , Pecher Gabriele
Published: January 2024

Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A suitable tumor antigen target on CRC is carcinoembryonic antigen (CEA), given its widespread expression and role in tumorigenesis and metastasis. CEA is known to be prolifically shed from tumor cells in a soluble form, thus hindering CAR recognition of tumors and migration through the TME. We have developed a next-generation CAR construct exclusively targeting cell-associated CEA, incorporating a PD1-checkpoint inhibitor and a CCR4 chemokine receptor to enhance homing and infiltration of the CAR-NK-92 cell line through the TME, and which does not induce fratricidal killing of CAR-NK-92-cells. To evaluate this therapeutic approach, we harnessed intricate 3D multicellular tumor spheroid models (MCTS), which emulate key elements of the TME. Our results demonstrate the effective cytotoxicity of CEA-CAR-NK-92 cells against CRC in colorectal cell lines and MCTS models. Importantly, minimal off-target activity against non-cancerous cell lines underscores the precision of this therapy. Furthermore, the integration of the CCR4 migration receptor augments homing by recognizing target ligands, CCL17 and CCL22. Notably, our CAR design results in no significant trogocytosis-induced fratricide. In summary, the proposed CEA-targeting CAR-NK cell therapy could offer a promising solution for CRC treatment, combining precision and efficacy in a tailored approach.
A Potential Role for the Receptor for Advanced Glycation End-Products (RAGE) in the Development of Secondhand Smoke-Induced Chronic Sinusitis
Authors: Robin Hannah , Trudeau Courtney , Robbins Adam , Chung Emily , Rahman Erum , Gangmark-Strickland Olivia , Licari Frank W. , Winden Duane R. , Orr Dan L. , Arroyo Juan A. , Reynolds Paul R.
Published: January 2024

Chronic sinusitis (CS) is characterized by sinonasal inflammation, mucus overproduction, and edematous mucosal tissue. CS impacts one in seven adults and estimates suggest up to 15% of the general U.S. population may be affected. This research sought to assess a potential role for receptors for advanced glycation end-products (RAGE), an inflammatory receptor expressed in tissues exposed to secondhand smoke (SHS). Human sinus tissue sections were stained for RAGE and S100s, common RAGE ligands. Wild-type mice and mice that over-express RAGE in sinonasal epithelium (RAGE TG) were maintained in room air (RA) or exposed to secondhand smoke (SHS) via a nose-only delivery system five days a week for 6 weeks. Mouse sections were stained for RAGE and tissue lysates were assayed for cleaved caspase 3, cytokines, or matrix metalloproteases. We discovered increased RAGE expression in sinus tissue following SHS exposure and in sinuses from RAGE TG mice in the absence of SHS. Cleaved caspase-3, cytokines (IL-1β, IL-3, and TNF-α), and MMPs (-9 and -13) were induced by SHS and in tissues from RAGE TG mice. These results expand the inflammatory role of RAGE signaling, a key axis in disease progression observed in smokers. In this relatively unexplored area, enhanced understanding of RAGE signaling during voluntary and involuntary smoking may help to elucidate potential therapeutic targets that may attenuate the progression of smoke-related CS.