bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalized Calcium Carbonate–Based Microparticles as a Versatile Tool for Targeted Cancer Treatment
Authors: Biny Lara , Gerasimovich Evgeniia , Karaulov Alexander , Sukhanova Alyona , Nabiev Igor
Published: April 2024

Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness of silica-based carriers to spontaneous drug release. Calcium carbonate (CaCO3) is an emerging alternative, being easily available, cost-effective, biocompatible material with high porosity and surface reactivity, which makes it an attractive choice for targeted drug delivery. CaCO3 particles are used in this field in the form of either bare CaCO3 microbeads or core/shell microparticles representing polymer-coated CaCO3 cores. In addition, they serve as removable templates for obtaining hollow polymer microcapsules. Each of these types of particles has its specific advantages in terms of biomedical applications. CaCO3 microbeads are primarily used due to their capacity for carrying pharmaceutics, whereas core/shell systems ensure better protection of the drug-loaded core from the environment. Hollow polymer capsules are particularly attractive because they can encapsulate large amounts of pharmaceutical agents and can be so designed as to release their contents in the target site in response to specific stimuli. This review focuses first on the chemistry of the CaCO3 cores, core/shell microbeads, and polymer microcapsules. Then, systems using these structures for the delivery of therapeutic agents, including drugs, proteins, and DNA, are outlined. The results of systematic analysis of available data are presented. They show that the encapsulation of various therapeutic agents in CaCO3-based microbeads or polymer microcapsules is a promising technique of drug delivery, especially in cancer therapy, enhancing drug bioavailability and specific targeting of cancer cells while reducing side effects. To date, research in CaCO3-based microparticles and polymer microcapsules assembled on CaCO3 templates has mainly dealt with their properties in vitro, whereas their in vivo behavior still remains poorly studied. However, an enormous potential of these highly biocompatible carriers for in vivo applications is undoubted. This last issue is addressed in depth in the Conclusion and Outlook sections of the review.
DEVELOPMENT OF VOLLEYBALL LOWER PASSING SKILL MODEL FOR JUNIOR HIGH SCHOOL EXTRACURRICULARS
Authors: Pangesti Khansa Dwi
Published: April 2024

Abstract

This study aims to obtain empirical data on the effectiveness and results of the volleyball lower passing skills model. This type of research is research and development (R&D) with a pre-test and post-test design. The data analysis technique collects effectiveness test data using the t test with SPSS software. The effectiveness test was conducted on volleyball extracurricular participants at SMPN 15 Depok City, totaling 40 children who were given treatment using a variety of volleyball lower passing skill models for 4 meetings. The volleyball lower passing research instrument was carried out with a 1-minute lower passing test. The results of the study based on expert validation, it can be said that there are 12 models of lower passing skills based on media modifications that are considered feasible. And based on the quality of the model, this model is in the GOOD category, with a score of 88. In addition, after testing the effectiveness of the model, it can be seen that this skill model is effective for improving volleyball lower passing skills with a p value = 0.000 <0.005. so it can be interpreted that there is a significant difference between the average of the experimental group and the control group. So it can be concluded that giving experimental treatment has a significant effect compared to the control group.
The Pengaruh Independensi, Self-Efficacy, dan Tekanan Ketaatan terhadap Audit Judgement dengan Kompleksitas Tugas sebagai Variabel Moderasi
Authors: Jihan Fitriana  , Gurendrawati Etty , Utaminingtyas Tri Hesti
Published: April 2024

Tujuan dari penelitian ini adalah menganalisis pengaruh dari independensi, self-efficacy, dan tekanan ketaatan terhadap audit judgement dengan kompleksitas tugas sebagai variabel moderasi. Penelitian ini menggunakan data primer dengan sampel auditor pada Auditorat Utama Keuangan Negara 1 (AKN 1) pada Badan Pemeriksa Keuangan Republik Indonesia (BPK RI). Penelitian ini menentukan sampel dengan menggunakan metode purposive sampling. Pengujian hipotesis yang dilakukan dalam penelitian ini menggunakan metode analisis regresi linear berganda dan analisis regresi moderasi (Moderated Regression Analysis) dengan program SPSS 25. Berdasarkan hasil dari analisis dapat disimpulkan bahwa independensi, self-efficacy, dan tekanan ketaatan berpengaruh signifikan terhadap audit judgement. Hasil penelitian juga menunjukkan bahwa kompleksitas tugas tidak mampu memoderasi pengaruh independensi, self-efficacy, dan tekanan ketaatan terhadap audit judgement.
The Utility of the Area Deprivation Index in Assessing Complications After Total Joint Arthroplasty
Authors: Dubin Jeremy A. , Bains Sandeep S. , Hameed Daniel , Monárrez Rubén , Gilmor Ruby , Chen Zhongming , Nace James , Delanois Ronald E.
Published: April 2024

Background:

Vulnerable populations, including patients from a lower socioeconomic status, are at an increased risk for infection, revision surgery, mortality, and complications after total joint arthroplasty (TJA). An effective metric to quantify and compare these populations has not yet been established in the literature. The Area Deprivation Index (ADI) provides a composite area-based indicator of socioeconomic disadvantage consisting of 17 U.S. Census indicators, based on education, employment, housing quality, and poverty. We assessed patient risk factor profiles and performed multivariable regressions of total complications at 30 days, 90 days, and 1 year.

Methods:

A prospectively collected database of 3,024 patients who underwent primary elective total knee arthroplasty or total hip arthroplasty performed by 3 fellowship-trained orthopaedic surgeons from January 1, 2015, through December 31, 2021, at a tertiary health-care center was analyzed. Patients were divided into quintiles (ADI ≤20 [n = 555], ADI 21 to 40 [n = 1,001], ADI 41 to 60 [n = 694], ADI 61 to 80 [n = 396], and ADI 81 to 100 [n = 378]) and into groups based on the national median ADI, ≤47 (n = 1,896) and >47 (n = 1,128).

Results:

Higher quintiles had significantly more females (p = 0.002) and higher incidences of diabetes (p < 0.001), congestive heart failure (p < 0.001), chronic obstructive pulmonary disease (p < 0.001), hypertension (p < 0.001), substance abuse (p < 0.001), and tobacco use (p < 0.001). When accounting for several confounding variables, all ADI quintiles were not associated with increased total complications at 30 days, but age (p = 0.023), female sex (p = 0.019), congestive heart failure (p = 0.032), chronic obstructive pulmonary disease (p = 0.001), hypertension (p = 0.003), and chronic kidney disease (p = 0.010) were associated. At 90 days, ADI > 47 (p = 0.040), female sex (p = 0.035), and congestive heart failure (p = 0.001) were associated with increased total complications.

Conclusions:

Balancing intrinsic factors, such as patient demographic characteristics, and extrinsic factors, such as social determinants of health, may minimize postoperative complications following TJA. The ADI is one tool that can account for several extrinsic factors, and can thus serve as a starting point to improving patient education and management in the setting of TJA.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Near-Infrared Light Induces Neurogenesis and Modulates Anxiety-like Behavior
Authors: Qi Xing , Xu Zhiliang , Liu Xingchen , Ren Yanan , Jin Yecheng , Sun Wenjie , Li Jiangxia , Liu Duo , Liu Shuwei , Liu Qiji , Li Xi
Published: April 2024

Background
The hippocampus is associated with mood disorders, and the activation of quiescent neurogenesis has been linked to anxiolytic effects. Near-infrared (NIR) light has shown potential to improve learning and memory in human and animal models. Despite the vast amount of information regarding the effect of visible light, there is a significant gap in our understanding of the response of neural stem cells (NSCs) to NIR stimulation, particularly in anxiety-like behavior. The present study aimed to develop a new optical manipulation approach to stimulate hippocampal neurogenesis and understand the mechanisms underlying its anxiolytic effects.
Methods
We used 940 nm NIR (40 Hz) light exposure to stimulate hippocampal stem cells in C57BL/6 mice. The enhanced proliferation and astrocyte differentiation of NIR-treated NSCs were assessed using 5-Ethynyl-2’-deoxyuridine (EdU) incorporation and immunofluorescence assays. Additionally, we evaluated calcium activity of NIR light-treated astrocytes using GCaMP6f recording through fluorescence fiber photometry. The effects of NIR illumination of the hippocampus on anxiety-like behaviors were evaluated using elevated plus maze and open-field test.
Results
In vitro, the NIR light effectively promoted the NSC proliferation and astrocyte differentiation via the Opn4 photoreceptor. In vivo, the NIR stimulation significantly enhanced neurogenesis and calcium-dependent astrocytic activity. Moreover, activating hippocampal astrocytes with 40-Hz NIR light substantially improved anxiety-like behaviors in mice.
Conclusions
We found that flickering NIR (940 nm/40Hz) light illumination improved neurogenesis in the hippocampus with anxiolytic effects. This innovative approach holds promise as a novel preventive treatment for depression.
General Anesthesia Versus Conscious Sedation with Locoregional Anesthesia in S-ICD Implantation: A Monocentric Retrospective Analysis
Authors: Marco Corrado , Lebon Jean-Sébastien , Rousseau-Saine Nicolas , Dubuc Marc , Thibault Bernard , Cadrin-Tourigny Julia , Raymond-Paquin Alexandre , Chabot-Blanchet Malorie , Fortier Annik , Mondésert Blandine
Published: April 2024

Background
The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a safe and effective alternative to the transvenous ICD (TV-ICD). Historically, S-ICD implantations have been performed under general anesthesia (GA). This study examines whether conscious sedation with locoregional anesthesia (CS-LA) is a safe and effective alternative to GA in S-ICD implantation.
Methods
138 S-ICD implantations (90 CS-LA) at our institution between 2013-2020 were studied. Analgesic efficacy in the 24 post-operative hours was evaluated by Numerical Pain Rating Scale (NPRS) score and by total analgesic medication received. Safety was evaluated by comparing the incidence of significant adverse events (AE): hypotension <80 mmHg or requiring vasopressors, bradycardia <40 bpm, or desaturation <90% or requiring non-invasive ventilation maneuvers.
Results
Post-procedural pain at 15 minutes and 24 hours was significantly less in CS-LA (-0.90 (p=0.04) and -1.21 (p=0.004), respectively). Post-procedural opioid consumption was 10.64mg of per osmorphine equivalents (p=0.046) lower in CS-LA. No significant difference in the likelihood ≥1 adverse event was noted (CS-LA OR 1.95 (95% CI [0.86, 4.40], p=0.11)).
Conclusion
S-ICD implantation under CS-LA was at least equivalent to GA in terms of analgesic efficacy and demonstrated a comparable safety profile. CS-LA represents a possible alternative to GA during S-ICD implantation in sites without readily available anesthesiologists.
SPAJoint: A Multivariate Saddlepoint Approximation for Time-to- Event and Response Joint Analysis
Authors: Lai Xin , An Mengke , Zhang Xuanping , Zhu Xiaoyan , Liu Yuqian , Shao Yang , Wang Jiayin , Wang Yixuan
Published: April 2024

Time-to-event and response endpoints are typical phenotypes in association studies that often exhibit stochastic correlation within the same individual. However, current analytic methods do not take the inherent correlation into account. Separate or fixed-connected endpoints assumptions can yield unreliable and prejudiced outcomes. Saddlepoint approximation is commonly used in association analysis to calibrate the type I error rate, but it is mostly applied in the univariate domain. Applying binary saddlepoint approximation to analyze joint models poses significant technical challenges. The bivariate saddlepoint approximation, considering natural correlations, necessitates intricate mathematical derivations. Therefore, we propose the a multivariate saddlepoint approximation method SPAJoint for time-to-event and response joint analysis, which constructs a joint model and applies binary saddlepoint approximation to calibrate test statistics, and the experimental results demonstrate that SPAJoint can control the type I error rate and more accurately identify genomic variants associated with multiple endpoints. The SPAJoint method incorporates random effects using the generalized linear mixed model to account for the correlation between time-to-event and tumour response. Bivariate saddlepoint approximation is utilized to calibrate test statistics for improved accuracy. By examining bladder cancer, kidney cancer, and lung cancer, we demonstrate that SPAJoint effectively manages type I error rates.
Investigating the Papain Enzyme's Potential for Sheepskin Unhairing
Authors: Ahmed Seid , Birlie Alehegn , Admasu Kelemiwork
Published: April 2024

Sheepskin is a natural resource that finds wide applications in various industries, including leather production. Traditionally, unhairing has been achieved through harsh chemicals and mechanical methods, which can be detrimental to the environment and compromise the quality of the final product. The primary objective of this research is to investigate the Papain Enzyme's Potential for Sheepskin Unhairing. The main factors involved in the experiment with their respective levels were the enzyme concentration in percent (1, 1.5, 2), temperature in degrees Celsius (25, 32.5, 40), and incubation time in minutes (60, 80, 120). The dependent variables studied were the unhairing efficiency of papain enzyme in percent. The results of the study demonstrated that papain enzyme exhibited significant unhairing potential for sheepskin. Increasing the temperature during the unhairing process can enhance enzyme activity, speeding up the breakdown of proteins in the hair and making it easier to remove. However, excessively high temperatures can also damage the skin, leading to reduced quality. However, as the incubation time increases the unhairing efficiency decreases, and as time goes on the strength of the skin decreases. The findings of this research contribute to the development of eco-friendly approaches in the leather industry.
Association of systemic inflammatory response index with the cardiometabolic multimorbidity among US adults: a population- based study
Authors: Li Jing , Ma Nan , Zhao Songfeng , Zhang Xiaowen , Fan Mengyan , Wan Jiaxin , Lin Rijin , Fan Feng , Liu Guo , Guan Sheng , Liu Aihua
Published: April 2024

Background
Chronic inflammation plays an essential role in the occurrence and progression of cardiometabolic diseases (CMDs). We aim to examine the association between a novel inflammatory biomarker systemic inflammatory response index (SIRI) and different cardiometabolic multimorbidity (CMM) status.
Methods
This is a cross-sectional study that include general participants of National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018. SIRI was calculated as neutrophil count × lymphocyte count/monocyte count. The cardiometabolic diseases were defined as a series of diseases including diabetes mellitus (DM), heart disease, and stroke. We explored the association of SIRI with outcomes with weighted multivariable logistic regression models weighted restricted cubic spline (RCS). The diagnostic value of SIRI was evaluated using weighted receiver operating curves (ROCs).
Results
A total of 43,345 participants were enrolled with a mean age of 45.86 years. The weighted prevalence of CMD and CMM was 17.14% and 2.94%, respectively. Compared to those without cardiometabolic disease, the adjusted odds ratios (ORs) (95% confidence interval, CI) for each unit increase in SIRI index were 1.14 (1.09, 1.19) for diabetes mellitus (DM), 1.13 (1.07, 1.19) for heart disease, 1.11 (1.04, 1.19) for stroke, 1.17 (1.12, 1.22) for CMD, and 1.16 (1.10, 1.23) for CMM, according to the weighted multivariable logistic regression. Elevated SIRI level was independently associated with increased cardiometabolic multimorbidity. There was no interaction found in subgroup analysis. According to the ROC analysis, SIRI had a superior diagnostic ability to NLR, PLR, and MLR for CMD (AUC = 0.581) and CMM (AUC = 0.633)
Conclusions
Elevated level of SIRI was positively associated with the prevalence of DM, coronary artery disease, stroke, CMD, and CMM, suggesting that SIRI could be a potential non-invasive biomarker for CMD and CMM.
Application of Morphogo based on convolutional neural network for morphological identification of bone marrow nucleated cells
Authors: Zhang Qiufang , Zhang Xiaofeng , Hua Changhui , Kong Tingting , Li Jingyuan , Peng Yuan , Wu Jingyan , Chen Yan
Published: April 2024

Introduction:
The morphological examination of bone marrow (BM) cells, commonly used for diagnosing hematological diseases, heavily relies on the expertise of pathologists. This approach is time-consuming, labor-intensive, subjective, and lacks objectivity. Therefore, it is crucial to develop automated analysis systems to aid in the diagnosis of hematological diseases.
Methods
The BM smears from patients with hematological diseases were collected from Dian Diagnostics between September 2021 and December 2021. These smears were classified into five groups based on varying degrees of cell morphological alterations. Images of the BM nucleated cells were captured using the Morphogo system, and its performance in cell identification was compared with that of pathologists.
Results
The Morphogo system demonstrated a high performance in identifying BM nucleated cells, with a sensitivity of 0.9362, specificity of 0.9977, PPV of 0.8354, NPV of 0.9974, and accuracy of 0.9954. Comparison between the percentage of BM nucleated cells identified by the Morphogo system and pathologists showed almost perfect agreement, with an average Kappa value of 0.8695 for 25 cell classes. The practical utility of the Morphogo system was evaluated in hematological diseases, with pathologists achieving averaged sensitivity, specificity, PPV, NPV and accuracy ranging from 0.9098 to 0.9868 when using the system for disease diagnosis. The diagnostic results were consistent with those made by pathologists using a microscope, with an average Kappa value of 0.9096.
Conclusion
Morphogo system had the potential to assist pathologists in diagnosis of hematological diseases by improving the efficiency of identification of BM nucleated cells.
Wood density of 38 Dalbergia and 29 Diospyros malagasy species and its relationship with climate and tree diameter
Authors: Raobelina Andry Clarel , Leban Jean Michel , Jaozandry Caroline Christina , Ramananantoandro Tahiana
Published: April 2024

Several Malagasy Dalbergia and Diospyros species are highly valued, especially in the furniture industry due to their desirable wood properties. However, there remains a lack of understanding regarding the wood technological properties of many species within these genera, hindering their effective utilization. This study aimed to adress this gap by assessing the wood density of 38 Dalbergia and 29 Diospyros species, their radial wood density variation, and the influence of climate and tree size. Wood density measurements were conducted on 297 wood cores using X-ray computed tomography. One-way analysis of variance was used to evaluate between-genus, between-species, and between-trees density variations. To compare the radial density profile of cores of different length, each analyzed core was divided into 10 segments of equal length. For species that show significant differences in mean density along the segments, the radial density trend was evaluated through correlation tests between the average density of each segment and its distance from the pith. Correlation test was also conducted to evaluate the relationship between tree diameter, climatic data, and density. Diospyros genus (1.070 ± 0.165 g∙cm-3) have significantly denser heartwood compared to Dalbergia (0.961 ± 0.142 g∙cm-3). Furthermore, eleven groups of Dalbergia and seven groups of Diospyros, each with significantly different heartwood density value ranges, were identified. While the radial wood density profile varied among species, a decreasing trend was observed in most analyzed species. Wood density increases with rising temperature and decreasing precipitation at the tree's growth site. Tree diameter does not influence the wood density.
Clinical Significance of LncRNAs SOX2-OT and NEAT1 in Esophageal Squamous Cell Carcinoma
Authors: Kumar Rajiv Ranjan , Mohanta Adrija , Rana Manjit Kaur , uttam Vivek , Tuli Hardeep Singh , Jain Aklank
Published: April 2024

Despite strides in diagnostic and therapeutic approaches for ESCC, patient survival rates remain relatively low. Recent studies highlight the pivotal role of long non-coding RNAs (lncRNAs) in regulating diverse cellular activities in humans. Dysregulated lncRNAs have emerged as potential diagnostic indicators across various cancers, including ESCC. However, further research is necessary to effectively leverage ESCC-associated lncRNAs in clinical settings. Understanding their clinical significance for ESCC diagnosis and their mechanisms can pave the way for more effective therapeutic strategies. Our qRT-PCR observations indicated significant downregulation of SOX2-OT and NEAT1 in ESCC blood samples (SOX2-OT down by ~ 2.02-fold and NEAT1 down by ~ 1.53-fold). The decreased expression of SOX2-OT and NEAT1 shows promise in differentiating ESCC patients from healthy individuals, as demonstrated by Receiver Operating Characteristics (ROC) curves and Area Under the Curve (AUC) values (AUC: SOX2-OT = 0.736, NEAT1 = 0.621) for ESCC diagnosis. Subsequent investigations explored the relationship between aberrant SOX2-OT and NEAT1 expression in ESCC patients and various clinicopathological features, including age, gender, smoking habits, alcohol consumption, hot beverage intake, tumor grade, and TNM stages. In-depth in-silico analysis unveiled the involvement of SOX2-OT and NEAT1 in miRNA sponging through the mTOR and MAPK pathways. In contrast, co-expression network analysis identified genes co-expressed with these lncRNA targets. This groundwork lays the foundation for future endeavours aimed at identifying and predicting ESCC prognosis by leveraging SOX2-OT and NEAT1. By thoroughly investigating the functions of these lncRNAs, we aim to deepen our understanding of their potential as diagnostic markers and their role in facilitating effective therapeutic interventions for esophageal squamous cell carcinoma (ESCC) within clinical contexts.
The Impact of Relaxing the Requirements for Dyspeptic Symptom Onset Frequency or Duration in Rome IV Criteria on the Symptom Pattern and Diagnosis of Functional Dyspepsia
Authors: Wang Jinsheng , Wu Junhao , Hou Xiaohua , Zhang Lei
Published: April 2024

Background
The Rome IV criteriafor functional dyspepsia (FD) has strict requirements for symptom frequency and onset duration, making it challenging to identify patients with broadly defined FD in clinical practice. This study aimed to investigate the impact of relaxing the Rome IV criteria on the diagnosis and symptom pattern of FD.
Methods
A cross-sectional, multi-center study was conducted involving 2935 consecutive broadly defined FD patients with no positive findings on upper gastrointestinal endoscopy and routine examinations. Questionnaires were used to collect demographic and upper gastrointestinal symptom data. Symptom pattern was compared between Rome IV criteria defined FD patients and those defined by relaxed Rome IV criteria.
Results
Only 22.2% of broadly defined FD patients rigorously fulfilled Rome IV criteria. No significant difference was found for proportion of patients with dyspeptic symptoms, dysmotility-like symptoms, reflux-like symptoms, as well as severity and onset frequency of dyspeptic symptoms (all P>0.05), between broadly defined FD who fulfilled Rome IV criteria but had a duration of 3-6 months and Rome IV criteria defined FD. Broadly defined Postprandial Distress Syndrome (PDS) patients who fulfilled the Rome IV criteria but had a symptom frequency of 1-2 days per week had significantly lower symptom severity (P<0.001), but similar postprandial symptom characteristics compared to those defined by the Rome IV criteria.
Conclusions
A symptom duration criterion of 3 months may be sufficient for diagnosing FD. Reducing the symptom onset frequency to no less than 1 day per week in the Rome IV criteria for PDS does not affect its postprandial symptom characteristics.
Leveraging AI Hyperparameters for Enhanced Security in Triplestore Databases: A Comprehensive Analysis of Deployment and Delivery Models
Authors: Henchiri Mourad , Wani Sharyar
Published: April 2024

Leveraging ameliorated AI hyperparameters introduces a multifaceted research landscape that enhances the fundamental principles of optimization and security in triplestore databases. Yet, the implementation should align with the characteristics and requirements of triplestore technology. xVelocity and .NET Security can be implemented in Triplestore Databases to optimize performance and ensure security. The integration of xVelocity technology, which is known for its in-memory data compression and columnstore indexing capabilities, can enhance query performance in Triplestore Databases. Additionally, .NET Security measures can be applied to safeguard the database environment, ensuring secure data access and preventing potential vulnerabilities. Combining these technologies contributes to a robust and efficient Triplestore Database system. This research addresses key challenges associated with dynamic optimization strategies optimizing query performance, enhancing security measures, and integrating machine learning models within triplestore environments. Security considerations involve AI-driven access controls, anomaly detection, and ethical AI usage, ensuring dynamic and context-aware security policies. The research delves into machine learning model integration, focusing on model explainability, real-time updates, and the seamless interoperability of AI modules with triplestore databases.
A countermovement jump with an arm swing is defined by four functional degrees of freedom and an enhanced proximal-to-distal delay.
Authors: Cefai Christina M. , Shaw Joseph W. , Cushion Emily J. , Cleather Daniel J.
Published: April 2024

An abundance of degrees of freedom (DOF) exist when executing a countermovement jump (CMJ). This research aims to simplify the understanding of this complex system by comparing jump performance and independent functional DOF (fDOF) present in CMJs without (CMJNoArms) and with (CMJArms) an arm swing. Principal component analysis was used on 39 muscle forces and 15 3-dimensional joint contact forces obtained from kinematic and kinetic data, analyzed in FreeBody (a segment-based musculoskeletal model). Jump performance was greater in CMJArms with the increased ground contact time resulting in higher external (p = .012), hip (p < .001) and ankle (p = .009) vertical impulses, and slower hip extension enhancing the proximal-to-distal joint extension strategy. This allowed the hip muscles to generate higher forces and greater time-normalized hip vertical impulse (p = .006). Three fDOF were found for the muscle forces and 3-dimensional joint contact forces during CMJNoArms, while four fDOF were present for CMJArms. This suggests that the underlying anatomy provides mechanical constraints during a CMJ, reducing the demand on the control system. The additional fDOF present in CMJArms suggests that the arms are not mechanically coupled with the lower extremity, resulting in additional variation within individual motor strategies.
Morphometric analysis of the sperm midpiece during capacitation
Authors: Skowronek Maria Fernanda , Pietroroia Santiago , Silvera Diego , Ford Mariana , Cassina Adriana , Lecumberry Federico , Sapiro Rossana
Published: April 2024

Background
In mammalian sperm, mitochondria are very densely packed and form a helical sheath located in the midpiece of the flagellum. Mitochondria play multiple roles in the cell and can rapidly change shape to adapt to environmental conditions. During capacitation, mammalian spermatozoa undergo morphological and physiological changes to acquire fertilization ability. This is evidenced by changes in sperm motility patterns (hyperactivation) and the ability to perform the acrosome reaction. Whether there are changes in sperm mitochondrial shape or dimensions during capacitation is unknown. This work aimed to quantify morphometric changes in the sperm midpiece during capacitation based on computational analysis and image processing.
Results
Using mitochondrial fluorescent probes and a combination of freely available software, we quantified the dimensions and fluorescence intensity of the midpiece of the sperm flagellum. After capacitation, the area occupied by the mitochondria decreased. This decrease was due to a reduction in the width but not the length of the midpiece. A reduction in the area and width of the midpiece occurred in spermatozoa that underwent the acrosome reaction, suggesting a shrinkage of the mitochondria during the process of capacitation.
Conclusion
These results suggest that the flagellar structure is remodeled during sperm capacitation and the acrosome reaction, which is consistent with the observed changes in mitochondrial organization. The application of image processing to fluorescence microscopy images may help to identify morphological changes during capacitation.
Decomposition of a complex motor skill in learning improves experts' expertise
Authors: Kimoto Yudai , Hirano Masato , Furuya Shinichi
Published: April 2024

Complex motor skills involve intricate sequences of movements that require precise temporal coordination across multiple body parts, posing challenges to mastery based on perceived error or reward. One approach that has been widely used is to decompose such skills into simpler, constituent movement elements during the learning process, thereby aligning the task complexity with the learners' capacity for accurate execution. Despite common belief and prevalent adoption, the effectiveness of this method remains elusive. Here we addressed this issue by decomposing a sequence of precisely timed coordination of movements across multiple fingers into individual constituent elements separately during piano practice. The results demonstrated that the decomposition training enhanced the accuracy of the original motor skill, a benefit not achieved through mere repetition of movements alone, specifically when skilled pianists received explicit visual feedback on timing error in the order of milliseconds during training. During the training, the patterns of multi-finger movements changed significantly, suggesting exploration of movements to refine the skill. By contrast, neither unskilled pianists who underwent the same training nor skilled pianists who performed the decomposition training without receiving visual feedback on the error showed improved skill through training. These findings offer novel evidences suggesting that decomposing a complex motor skill, coupled with receiving feedback on subtle movement error during training, further enhances motor expertise of skilled individuals by facilitating exploratory refinement of movements.
Parameter identification of solar cell model based on improved northern goshawk optimization algorithm
Authors: Xiao Wenbo , Zhou Heng , Wu Huaming , Li Yongbo
Published: April 2024

In this study, an improved northern goshawk optimization algorithm called SR-NGO is developed to solve the parameter identification problem of the Single Diode Model (SDM), Double Diode Model (DDM), and Triple Diode Model (TDM). Compared to the NGO algorithm, the SR-NGO algorithm reduces the minimum, maximum, mean, and standard deviation values of the root mean square error between experimental I-V data and the SDM(DDM, TDM) fitting data by 0.0004284% (0.2542%, 0.2034%), 1.1094% (3.7313%, 6.0740%), 0.05106% (0.6901%, 1.0699%), and 99.9999% (88.1540%, 94.0600%), respectively. Furthermore, the SR-NGO algorithm exhibits higher accuracy, faster convergence speed, and stronger stability compared to other existing algorithms. These results demonstrate that the SR-NGO algorithm, which combines the sine cosine guiding mechanism and random learning mechanism, enhances both local and global search capabilities, thereby improving the ability to escape local optima.
A multimodal cross-species comparison of pancreas development
Authors: Lickert Heiko , Yang Kaiyuan , Spitzer Hannah , Sterr Michael , Hrovatin Karin , O Sean de la , Zhang Xinghao , Setyono Eunike , Ud-Dean Minhaz , Walzthoeni Thomas , Flisikowski Krzysztof , Flisikowska Tatiana , Schnieke Angelika , Scheibner Katharina , Wells James , Sneddon Julie , Kessler Barbara , Wolf Eckhard , Kemter Elisabeth , Theis Fabian
Published: April 2024

Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in pancreas development more closely than rodents, and as such, offer a valuable alternative large-animal model. As pig pancreas organogenesis is unexplored, we first annotated developmental hallmarks and lineage markers of pancreas differentiation and morphogenesis throughout the 114-day gestation. Building on this detailed roadmap, we further constructed a pig single-cell multiome pancreas atlas capturing temporal resolution across all three trimesters. Cross-species comparisons with human and mouse time-resolved integrated pancreas atlases accentuated that pig closely resembled human in developmental tempo, epigenetic and transcriptional regulation, gene expression patterns and gene regulatory networks (GRNs). Specifically, pig mimicked the dynamics of progenitor status, differentiation trajectories and GRNs governing endocrine fate acquisition in human. In pig multiome GRN, over 40% of transcription factors targeted by NEUROG3, the endocrine master regulator, were confirmed in human stem cell models. Most notably, we uncovered beta-cell heterogeneity arising during embryonic development, owing to endocrine induction in pancreatic progenitors with temporally altered epigenetic and transcriptional identity. Overall, our work lays the foundation for using pigs to model human pancreas biology and provides unprecedented insights into developmental principles and mechanisms across species.
Lassa virus persistence with high viral titers following experimental infection in its natural reservoir host, Mastomys natalensis
Authors: Hoffmann Chris , Krasemann Susanne , Wurr Stephanie , Hartmann Kristin , Pallasch Elisa , Bockholt Sabrina , Müller Jonas , Günther Stephan , Oestereich Lisa
Published: April 2024

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis. Viral RNA levels in body fluids, virus titers in organs and antibody presence in blood were analyzed. In adults and 2-week-old animals, LASV caused transient infections with subsequent seroconversion. However, neonates and younger juveniles exhibited persistent infections lasting up to 16 months despite antibody presence. LASV was detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs were observed. Infected individuals efficiently transmitted the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population.
Sex differences in brain cell-type specific chromatin accessibility in schizophrenia
Authors: Roussos Panos , Ma Yixuan , Girdhar Kiran , Hoffman Gabriel , Fullard John , Bendl Jaroslav
Published: April 2024

Our understanding of the sex-specific role of the non-coding genome in serious mental illness remains largely incomplete. To address this gap, we explored sex differences in 1,393 chromatin accessibility profiles, derived from neuronal and non-neuronal nuclei of two distinct cortical regions from 234 cases with serious mental illness and 235 controls. We identified sex-specific enhancer-promoter interactions and showed that they regulate genes involved in X-chromosome inactivation (XCI). Examining chromosomal conformation allowed us to identify sex-specific cis- and trans-regulatory domains (CRDs and TRDs). Co-localization of sex-specific TRDs with schizophrenia common risk variants pinpointed male-specific regulatory regions controlling a number of metabolic pathways. Additionally, enhancers from female-specific TRDs were found to regulate two genes known to escape XCI, (XIST and JPX), underlying the importance of TRDs in deciphering sex differences in schizophrenia. Overall, these findings provide extensive characterization of sex differences in the brain epigenome and disease-associated regulomes.
Multiple-Stimuli Fluorescent Responsive Metallo-Organic Helicated Cage Arising from Monomer and Excimer Emission
Authors: Wang Pingshan , zhang zhe , Bai Qixia , Zhai Zirui , Long Qingwu , Han Ermeng , Zhao He , Zhou Chuang-Wei , Lin Haobo , Zhang Wei , Ning Guo-Hong , Xie Ting-Zheng , Wu Tun
Published: April 2024

Effectively controlling monomer and excimer emission in a singular luminous platform is challenging due to their highly stable structures in solution, solid, or doped states when subjected to external stimuli. This study presents a metallo-cage (MTH) featuring a triple helical motif that displays a unique dual emission. This emission arises from both intramolecular monomer and intermolecular excimer, respectively. The distorted molecular conformation of MTH and the staggered stacking mode for MTH excimer were verified through single crystal X-ray diffraction analysis. These structural features facilitate the switch between monomer and excimer emission, which is induced by changes in concentration and temperature. Significantly, adjusting the equilibrium between these two states in MTH enables the production of vibrant white light emission in both solution and solid state. Moreover, when combined with a PMMA (polymethyl methacrylate) solution, the resulting thin films can serve as straightforward fluorescence thermometer and materials for thermally activated information encryption.
Combined titanium-steel structures formation by directed energy deposition using vanadium and nickel interlayers
Authors: Terentyev Egor V. , Borodavkina Ksenia T. , Kozyrev Khariton M. , Shishkin Dmitriy V. , Sliva Andrey P. , Goncharov Aleksey L. , Gudenko Aleksandr V. , Zhgut Daria A.
Published: April 2024

The possibility of obtaining a combined titanium-steel construction by directed energy deposition using vanadium or vanadium/nickel interlayers. Vanadium wire VnPr-1, nickel wire NP1 grade and welding wires Sv-08G2S, 316L, MSG NiFe-1 grades were used for deposition on the end of the titanium plate VT1-0. The use of vanadium as an interlayer deposited on titanium makes it possible to provide a joining with a stable structure, steady hardness distribution and acceptable manufacturability. The content of dissolved titanium in the vanadium layer negatively influence on the subsequent deposition of steel, nickel or iron-nickel alloy. Therefore, the titanium content was reduced to the level of ˂0.5% by deposition at least 4 vanadium beads. The results of tensile tests showed that all specimens failed in the elastic section mostly along the interlayers between vanadium and subsequent layers of low-carbon steel, nickel and iron-nickel alloys deposited on it. The only specimen was destroyed along the titanium-vanadium interlayer probably due to brittle ω–phase formation.
Assessing the antitumor effects of metformin on ovarian clear cell carcinoma
Authors: Takemori Satoshi , Morisada Tohru , Osaka Makoto , Watanabe Momoe , Tajima Atsushi , Tanigaki Shinji , Kobayashi Yoichi
Published: April 2024

Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase and suppressed phosphorylation of the mammalian target of rapamycin. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin.
Competencies Required to Make Use of Information Science and Technology among Japanese Medical Students: A Cross-sectional Study
Authors: Ota Yuma , Asada Yoshikazu , Mieno Makiko , Matsuyama Yasushi
Published: April 2024

Background
Medical students have emphasized the importance of acquiring competencies that allow the use of information science and technology (IST) related to digital health. This study identified learning objectives and competencies that correspond with low self-assessment and factors that improve self-assessment among medical students.
Methods
A questionnaire was administered to sixth-year medical students across 82 medical schools in Japan between November 2022 and February 2023.
Results
Three academic goals were difficult to achieve: (1) provide an overview of the regulations, laws, and guidelines related to IST in medicine; (2) discuss ethical issues, such as social disparities caused by the digital divide that may arise in the use of IST in medicine; and (3) understand IST related to medical care. Further, problem-based learning, engaging with IST beyond class, and learning approach impacted medical students’ acquisition of competencies related to IST. However, the competencies required by medical students may change over the course of an updated medical school curriculum.
Conclusions
It is equally important for medical students to recognize the significance of learning, establish active learning methods, and gain experience in practically applying these competencies.
A Comprehensive Allele Specific Expression Resource for the Equine Transcriptome
Authors: Heath Harrison , Peng Sichong , Szmatola Tomasz , Ryan Stephanie , Bellone Rebecca , Kalbfleisch Theodore , Petersen Jessica , Finno Carrie
Published: April 2024

Background: Allele-specific expression (ASE) analysis provides a nuanced view of cis-regulatory mechanisms affecting gene expression.
Results: An equine ASE analysis was performed, using integrated Iso-seq and short-read RNA sequencing data from four healthy Thoroughbreds (2 mares and 2 stallions) across 9 tissues from the Functional Annotation of Animal Genomes (FAANG) project. Allele expression was quantified by haplotypes from long-read data, with 42,900 allele expression events compared. Within these events, 635 (1.48%) demonstrated ASE, with liver tissue containing the highest proportion. Genetic variants within ASE events were in histone modified regions 64.2% of the time. Validation of allele-specific variants, using a set of 66 equine liver samples from multiple breeds, confirmed that 97% of variants demonstrated ASE.
Conclusions: This valuable publicly accessible resource is poised to facilitate investigations into regulatory variation in equine tissues. Our results highlight the tissue-specific nature of allelic imbalance in the equine genome.
Experiences of family and community care physicians and nurse residents in Madrid regarding their training during the COVID-19 pandemic: A Photovoice study
Authors: Elena Polentinos-Castro , Raquel Sanchez- Ruano , Paloma Conde-Espejo , Miguel López-MIguel , Lucia Nuevo-Coello , María Minué-Estirado , Elena Valera-Bermejo , Isabel Del Cura-González
Published: April 2024

Background: The COVID-19 pandemic brought about sudden changes in healthcare demands, necessitating additional healthcare professionals and altering the educational landscape for medical and nursing residents. This study aimed to explore the experiences and impact of the pandemic on the training of family and community medicine as well as family and community nursing residents.
Method: A participatory qualitative study was conducted using the Photovoice methodology. Seven residents in family and community medicine and nursing in the Madrid region were purposively sampled. Participants took photographs and engaged in weekly sessions over five weeks to discuss and analyse their photos, which were grouped into themes and further categorized. Recommendations for institutions and program leaders were developed using an adapted logical framework approach.
Results: The average age was 27 years, with 86% being female. Participants captured 96 photographs categorized into five themes (physical and emotional impact; impact on primary care system; hospital care ; social and environmental impact ; and impact on training). Through critical discussions on impact on training-related photos, seven emergent themes were identified: 1) COVID-19 monograph, buried knowledge; 2) Changing roles ; 3) Transition from face-to-face to online delivery format ; 4) Supervision; 5) Tutor as educator and caregiver ; 6) Advocacy ; 7) Family and nursing residents as agents of change. Subsequently, participants formulated seven recommendations that should be considered in similar situations.
Conclusion: The COVID-19 pandemic has posed significant challenges in implementing medical education programs. It has had both formative and professional impacts on medical and nursing residents. These findings can aid in designing coping and educational strategies to navigate exceptional situations such as the one experienced during the pandemic.
An Integrated Group Signature and Chameleon Hash Framework for Effective, Secure, and Private VANET Communication
Authors: MV Ranjith Kumar , N Bhalaji
Published: April 2024

VANET (Vehicular Ad hoc Networks) enable on-road wireless communication using vehicular and road-based electronic infrastructure. The services provided include routine traffic information dissemination aimed at ensuring safe driving while offering payment systems, and entertainment services are also part of VANET services. Ensuring secure, cost-effective VANET communication is a key research focus. A mechanism for unidentified message transmission, reciprocal vehicular and road base verification, as well as highly secure authentication by a trusted party, preservation of confidentiality of messages, recovery of the identity of vehicle by a trusted authority in unfortunate events, and low set up cost, is the prerequisite for trusted vehicular communication in VANET. The technique of Chameleon hashing signature provides message security with frequent changing of keys. The validation of vehicular identity in group-based communication is centralized using group signature and time stamping. This study proposes a framework combining chameleon hash signatures with group signatures to enhance VANET communication privacy, security, and cost-effectiveness.