bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Studies of Embryogenic Callus Induction Rate in Peanut (Arachis hypogaea L.)
Authors: Luo Dandan , Shi Lei , Sun Ziqi , Qi Feiyan , Liu Hongfei , Xue Lulu , Li Xiaona , Liu Han , Qu Pengyu , Zhao Huanhuan , Dai Xiaodong , Dong Wenzhao , Zheng Zheng , Huang Bingyan , Fu Liuyang , Zhang Xinyou
Published: January 2024

The capability of embryogenic callus induction is a prerequisite for in vitro plant regeneration. However, embryogenic callus induction is strongly genotype-dependent, thus hindering the development of in vitro plant genetic engineering technology. In this study, to examine the genetic variation in embryogenic callus induction rate (CIR) in peanut (Arachis hypogaea L.) at the seventh, eighth, and ninth subcultures (T7, T8, and T9, respectively), we performed genome-wide association studies (GWAS) for CIR in a population of 353 peanut accessions. The coefficient of variation of CIR among the genotypes was high in the T7, T8, and T9 subcultures (33.06%, 34.18%, and 35.54%, respectively), and the average CIR ranged from 1.58 to 1.66. A total of 53 significant single-nucleotide polymorphisms (SNPs) were detected (based on the threshold value −log10(p) = 4.5). Among these SNPs, SNPB03-83801701 showed high phenotypic variance and neared a gene that encodes a peroxisomal ABC transporter 1. SNPA05-94095749, representing a nonsynonymous mutation, was located in the Arahy.MIX90M locus (encoding an auxin response factor 19 protein) at T8, which was associated with callus formation. These results provide guidance for future elucidation of the regulatory mechanism of embryogenic callus induction in peanut.
The Importance of Aquatic Fauna on Ancient Mesopotamian Healing Practices—An Environmental Humanities Approach to Human Dependency of Non-Human World
Authors: Satiro Ana , Gomes de Almeida Isabel , Brito Cristina
Published: January 2024

Diachronically, Mesopotamian data pertaining to the religious spheres point to a transversal notion that deities were considered responsible for every cause–effect event observed/experienced by humans in their natural/cosmic surroundings. Such notion is especially visible on texts pertaining to the restoration of human health, where such an aspect was ultimately considered as a divine prerogative. Yet, these textual data also show how natural elements were basilar to the success of healing practices when thoroughly manipulated by specialists. Their examination through a perspective that intertwines the apparatus of History of Religions and Environmental History thus reveals great potential for contributing to the topic of human/nonhuman entanglements in the longue durée. With this paper, we propose to revisit the uses of aquatic fauna as displayed in Babylonian and Assyrian healing texts dated to the second half of the 2nd millennium and the first half of the 1st millennium BC. Although at a preliminary stage, our research has been guided by the combined theoretical-methodological perspective above-mentioned, aiming at highlighting the great importance conferred to these animals. Ultimately, we aim at stressing the importance of addressing the dependence of Mesopotamian specialists and patients on such elements of Nature to better understand this ancient context.
Differences in Functional Capacity between Oncologic and Non-Oncologic Populations: Reference Values
Authors: Mojas Egoitz , Santisteban Aitor , Muñoz-Pérez Iker , Larrinaga-Undabarrena Arkaitz , Arietaleanizbeaskoa Maria Soledad , Mendizabal-Gallastegui Nere , Grandes Gonzalo , Cacicedo Jon , Río Xabier
Published: January 2024

This study is focused on the fact that in the context of increasing global aging and cancer diagnoses, additional challenges arise in clinical care. Adequate functionality and body composition are key to coping with antineoplastic treatment, which can lead to better treatment tolerance, survival, and quality of life. This is a cross-sectional comparative study focused on the assessment and comparison of body composition and functionality between cancer patients and a reference population, with the aim of establishing meaningful baseline values. Techniques such as manual dynamometry, the Five-Times Sit-to-Stand test, and bioimpedance were used to collect data from 374 oncologic patients and 1244 reference individuals. The results reveal significant disparities in functionality and body composition among participants, and provide age group-specific adjusted baseline values for those diagnosed with cancer. These findings may have crucial clinical implications for applying particular cut-off points designed for this population group, which makes the assessment process faster and more accurate, enhances the capacity of medical personnel to act quickly, and improves the management of frailty in cancer patients.
Workplace Violence Experienced by Personal Care Workers in a District in Seoul, Republic of Korea: A Comparison Study with Office and Service Workers
Authors: Cho Mi-Suk , Min Kyoung-Bok , Min Jin-Young
Published: January 2024

This study compared the level of workplace violence experienced by personal healthcare workers in a district in Seoul, Republic of Korea, with those experienced by workers in office or service jobs. We matched 150 personal care workers with 150 office workers and 150 service workers using a propensity score. Workplace violence was categorized into psychological violence and physical violence. Of the surveyed personal care workers, 53.3% reported experiencing psychological violence, and 42.0% reported experiencing physical violence. After adjusting for self-reported work-related symptoms, personal care workers had significantly higher odds of experiencing psychological violence than office workers (OR = 5.01; 95% CI: 2.80–8.97) or service workers (OR = 7.54; 95% CI: 3.93–14.47). The adjusted odds for physical violence were also significantly higher for personal care workers compared with those for office workers (OR = 5.83; 95% CI: 2.96–11.50) and service workers (OR = 6.00; 95% CI: 2.88–12.49). In terms of specific types of workplace violence, personal care workers were 7–10 times more likely to experience unwanted sexual attention, sexual harassment, and physical violence than office or service workers. We found that personal care workers were more prone to workplace violence than office or service workers, with gender-based or physical violence being the most common types. Considering the negative impact of workplace violence on workers’ well-being and health services, policy updates and interventions focusing on personal care workers are needed to reduce workplace violence, safeguard workers’ rights, and establish a secure working environment.
Validation of the Korean Version of the Health Care Climate Questionnaire among Cancer Survivors
Authors: Yeom Hyun-E , Lee Jungmin , Kim Young-Joo
Published: January 2024

Healthcare professionals should support autonomy in their patients in order for them to maintain the motivation to cope actively with their conditions. The Health Care Climate Questionnaire (HCCQ) is useful for assessing patients’ perceptions of the autonomy support provided to them. We aimed to validate the psychometric properties of the Korean version of the HCCQ (HCCQ-K) among Korean cancer survivors. This study evaluated the factor structure, concurrent validity, and internal consistency. Data from 367 cancer survivors were analyzed using confirmatory factor analysis (CFA), Pearson’s correlations, and Cronbach’s α values. The CFA validated that the single-factor structure of the HCCQ-K had an excellent fit that was consistent with that of the original English version. Concurrent validity was confirmed by moderate correlations between the HCCQ-K and both psychological well-being and self-management. Reliability was verified by satisfactory internal consistency, with a Cronbach’s α value of 0.91 and strong item-total and inter-item correlations. The HCCQ-K is therefore a valid and reliable tool for assessing autonomy support provided by healthcare professionals to Korean cancer survivors. The HCCQ-K may help healthcare professionals understand their patients’ needs for autonomy support and develop strategies to motivate active coping behaviors.
Is There Somebody Looking out for Me? A Qualitative Analysis of Bullying Experiences of Individuals Diagnosed with Bipolar Disorder
Authors: Özer Gülüm , Işık İdil , Escartín Jordi
Published: January 2024

According to the World Health Organisation, there are globally 40 million individuals with bipolar disorder (BD), and they experience stigma and discrimination, as many people with mental illness do. Work bullying (WB) is a common organisational problem, deteriorating the well-being and performance of employees and organisations. Although WB experiences have been researched for over three decades, we do not know much about the experiences of this group and what they need to extend their work-life. The current research aims to understand the workplace bullying experiences of individuals with BD and factors that may foster or hinder their participation in the labour force. The research methodology was based on in-depth interviews with 19 employees diagnosed with BD. Bullying experiences were mapped onto the Negative Acts Questionnaire. The data were analysed using the deductive qualitative content analysis on MAXQDA. Results showed that individuals with BD were exposed to bullying in work settings. Perceived reasons for the negative behaviours were mainly the undesirable individual characteristics of the bully, prejudices toward bipolar disorder, and already-existing toxic behaviours within the organisation. To reduce bullying, participants suggested that, among others, top management include equal and fair treatment of disadvantaged employees as performance criteria for supervisors and that organisations provide training against bullying, investigate complaints, apply sanctions, and establish an inclusive environment. If organisations set a stable and enduring vision, enhance a common identity for all employees, work on team building, and emphasise team efforts and goals, the organisational environment would be more inclusive, and individuals with BD would have longer work lives.
In Vitro Growth of Human Follicles: Current and Future Perspectives
Authors: Malo Clara , Oliván Sara , Ochoa Ignacio , Shikanov Ariella
Published: January 2024

Ovarian tissue cryopreservation is gaining importance as a successful method to restore fertility to girls and young women at high risk of sterility. However, there are concerns regarding the safety of transplantation after ovarian tissue cryopreservation due to the high risk of reintroducing cancer cells and causing disease recurrence. In these cases, the development of culture systems that support oocyte development from the primordial follicle stage is required. Notable achievements have been reached in human follicle in vitro growth in the past decade. Currently, systems for the in vitro culture of ovarian tissue are based on two-dimensional substrates that do not support the survival of follicles or recapitulate the mechanical heterogenicity in the mammalian ovary. Recognition of the importance of special arrangements between cells has spurred research in three-dimensional culture systems, and the provision of a precise culture system that maximizes the diffusion of nutrients and gases through the follicles has raised interest in advanced biomimetic models. The current review critically examines various culture systems employed for the in vitro development of follicles, with a particular focus on solutions utilizing Organ-on-a-Chip (OOC) technology. The emphasis on OOC technology underscores its role as a promising avenue in ensuring the successful cultivation and maintenance of follicular structures during the culture period.
Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo
Authors: Barbier Martin A. , Ferland Karel , De Koninck Henri , Doucet Emilie J. , Dubourget Ludivine , Kim MinJoon , Cattier Bettina , Morissette Amélie , Bchetnia Mbarka , Larouche Danielle , Kim Dong Hyun , St-Jean Guillaume , Germain Lucie
Published: January 2024

Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method requires many animals and several months to obtain useful results. In previous studies, we showed the potential of tissue-engineered skin substitutes (TESs) as a model for normal skin in which cancer cells can be included in vitro. Herein, we showed a new method to study tumorigenicity, using cancer spheroids that were embedded in TESs (cTES) and grafted onto athymic mice, and compared it with the commonly used cell injection assay. Tumors developed in both models, cancer cell injection and cTES grafting, but metastases were not detected at the time of sacrifice. Interestingly, the rate of tumor development was faster in cTESs than with the injection method. In conclusion, grafting TESs is a sensitive method to detect tumor cell growth with and could be developed as an alternative test for tumorigenicity.
Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma
Authors: Teixeira Elisabete , Fernandes Cláudia , Bungărdean Maria , Paula Arnaud Da Cruz , Lima Raquel T. , Batista Rui , Vinagre João , Sobrinho-Simões Manuel , Máximo Valdemar , Soares Paula
Published: January 2024

In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline USP42 mutation [p.(Gly486Arg)]. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a USP13 missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the USP42 mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The USP42 gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated USP42 downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of USP42 mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.
Attenphos: General Phosphorylation Site Prediction Model Based on Attention Mechanism
Authors: Song Tao , Yang Qing , Qu Peng , Qiao Lian , Wang Xun
Published: January 2024

Phosphorylation site prediction has important application value in the field of bioinformatics. It can act as an important reference and help with protein function research, protein structure research, and drug discovery. So, it is of great significance to propose scientific and effective calculation methods to accurately predict phosphorylation sites. In this study, we propose a new method, Attenphos, based on the self-attention mechanism for predicting general phosphorylation sites in proteins. The method not only captures the long-range dependence information of proteins but also better represents the correlation between amino acids through feature vector encoding transformation. Attenphos takes advantage of the one-dimensional convolutional layer to reduce the number of model parameters, improve model efficiency and prediction accuracy, and enhance model generalization. Comparisons between our method and existing state-of-the-art prediction tools were made using balanced datasets from human proteins and unbalanced datasets from mouse proteins. We performed prediction comparisons using independent test sets. The results showed that Attenphos demonstrated the best overall performance in the prediction of Serine (S), Threonine (T), and Tyrosine (Y) sites on both balanced and unbalanced datasets. Compared to current state-of-the-art methods, Attenphos has significantly higher prediction accuracy. This proves the potential of Attenphos in accelerating the identification and functional analysis of protein phosphorylation sites and provides new tools and ideas for biological research and drug discovery.
Overexpression of a ‘Beta’ MYB Factor Gene, VhMYB15, Increases Salinity and Drought Tolerance in Arabidopsis thaliana
Authors: Han Jiaxin , Dai Jing , Chen Zhe , Li Wenhui , Li Xingguo , Zhang Lihua , Yao Anqi , Zhang Bingxiu , Han Deguo
Published: January 2024

‘Beta’ is a hybrid of Vitis riparia L. and V. labrusca and has a strong ability to adapt to adverse growth environments and is mainly cultivated and used as a resistant rootstock. At present, the most extensively studied MYB TFs are R2R3-type, which have been found to be involved in plant growth, development, and stress response processes. In the present research, VhMYB15, a key transcription factor for abiotic stress tolerance, was screened by bioinformatics in ‘Beta’ rootstock, and its function under salinity and drought stresses was investigated. VhMYB15 was highly expressed in roots and mature leave under salinity and drought stresses. Observing the phenotype and calculating the survival rate of plants, it was found that VhMYB15-overexpressing plants exhibited relatively less yellowing and wilting of leaves and a higher survival rate under salinity and drought stresses. Consistent with the above results, through the determination of stress-related physiological indicators and the expression analysis of stress-related genes (AtSOS2, AtSOS3, AtSOS1, AtNHX1, AtSnRK2.6, AtNCED3, AtP5CS1, and AtCAT1), it was found that transgenic Arabidopsis showed better stress tolerance and stronger adaptability under salinity and drought stresses. Based on the above data, it was preliminarily indicated that VhMYB15 may be a key factor in salinity and drought regulation networks, enhancing the adaptability of ‘Beta’ to adverse environments.
Attention Deficit Hyperactivity Disorder (ADHD) and Polyphenols: A Systematic Review
Authors: Turiaco Fabrizio , Cullotta Chiara , Mannino Federica , Bruno Antonio , Squadrito Francesco , Pallio Giovanni , Irrera Natasha
Published: January 2024

Polyphenols are natural compounds also contained in daily consumed foods that show their efficacy in different clinical fields. Both pre-clinical and clinical studies demonstrated that polyphenols may manage neuroinflammation and oxidative stress processes tightly connected to neurodegenerative diseases and mental disorders. Thus, a neuroinflammatory state may influence the neurotransmitters pathways, such as the noradrenergic, glutamatergic, serotoninergic, and, in particular, dopaminergic ones, whose impairment is strongly associated with attention deficit hyperactivity disorder (ADHD). Therefore, the aim of the present systematic review is to provide an overview of the clinical outcomes’ changes following ADHD treatment with polyphenols alone and in combination with the traditional drugs. This review was conducted according to PRISMA guidelines and recorded on PROSPERO with the number CRD42023438491; PubMed, Scopus, and Web of Science were used as search-engines to lead our research until June 2023. The inclusion criteria were articles written in English, including clinical, placebo-controlled, and case-control trials. We excluded reviews, metanalyses, background articles, and papers published in other languages. To avoid any bias, Rayyan software (COPYRIGHT © 2022 RAYYAN) was used to organize the work and manage the literature review. After screening, 10 studies were included, with a total of 556 patients that met the established inclusion criteria. The data obtained from these studies showed that polyphenols rebalanced oxidative stress pathways through different mechanisms, are effective for the treatment of ADHD both alone and in combination with traditional drugs, and are able to reduce symptoms as well as the side effects related to the use of conventional therapies. Finally, a positive effect of using polyphenols for ADHD prevention could be hypothesized.
Exploring the Impact of BKCa Channel Function in Cellular Membranes on Cardiac Electrical Activity
Authors: Chen Yin-Chia , Shih Chia-Lung , Wu Chao-Liang , Fang Yi-Hsien , So Edmund Cheung , Wu Sheng-Nan
Published: January 2024

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels’ conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo.
Maternal–Infant Factors in Relation to Extracellular Vesicle and Particle miRNA in Prenatal Plasma and in Postpartum Human Milk
Authors: Muse Meghan E. , Armstrong David A. , Hoen Anne G. , Gilbert-Diamond Diane , Gui Jiang , Palys Thomas J. , Kolling Frederick W. , Christensen Brock C. , Karagas Margaret R. , Howe Caitlin G.
Published: January 2024

MicroRNAs (miRNA) in extracellular vesicles and particles (EVPs) in maternal circulation during pregnancy and in human milk postpartum are hypothesized to facilitate maternal–offspring communication via epigenetic regulation. However, factors influencing maternal EVP miRNA profiles during these two critical developmental windows remain largely unknown. In a pilot study of 54 mother–child dyads in the New Hampshire Birth Cohort Study, we profiled 798 EVP miRNAs, using the NanoString nCounter platform, in paired maternal second-trimester plasma and mature (6-week) milk samples. In adjusted models, total EVP miRNA counts were lower for plasma samples collected in the afternoon compared with the morning (p = 0.024). Infant age at sample collection was inversely associated with total miRNA counts in human milk EVPs (p = 0.040). Milk EVP miRNA counts were also lower among participants who were multiparous after delivery (p = 0.047), had a pre-pregnancy BMI > 25 kg/m2 (p = 0.037), or delivered their baby via cesarean section (p = 0.021). In post hoc analyses, we also identified 22 specific EVP miRNA that were lower among participants who delivered their baby via cesarean section (Q < 0.05). Target genes of delivery mode-associated miRNAs were over-represented in pathways related to satiety signaling in infants (e.g., CCKR signaling) and mammary gland development and lactation (e.g., FGF signaling, EGF receptor signaling). In conclusion, we identified several key factors that may influence maternal EVP miRNA composition during two critical developmental windows, which should be considered in future studies investigating EVP miRNA roles in maternal and child health.
Does Hypertension Affect the Recovery of Renal Functions after Reversal of Unilateral Ureteric Obstruction?
Authors: Hammad Fayez T. , Lubbad Loay , Al-Salam Suhail , Hammad Waheed F. , Yasin Javed , Meeran Mohamed Fizur Nagoor , Ojha Shreesh , Arunachalam Seenipandi , Hammad Awwab F.
Published: January 2024

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.
E3 Ubiquitin Ligase Uhrf2 Knockout Reveals a Critical Role in Social Behavior and Synaptic Plasticity in the Hippocampus
Authors: Zhuang Yinghan , Li Chuhan , Zhao Fang , Yan Yan , Pan Hongjie , Zhan Jianmin , Behnisch Thomas
Published: January 2024

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity—a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin–proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation.
Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine
Authors: Yang Daiyu , Lyu Chengzhen , He Kun , Pang Ke , Guo Ziqi , Wu Dong
Published: January 2024

Bile acid diarrhea (BAD) is a multifaceted intestinal disorder involving intricate molecular mechanisms, including farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and Takeda G protein–coupled receptor 5 (TGR5). Current diagnostic methods encompass bile acid sequestrants (BAS), 48-h fecal bile acid tests, serum 7α-hydroxy-4-cholesten-3-one (C4), fibroblast growth factor 19 (FGF19) testing, and 75Selenium HomotauroCholic acid test (75SeHCAT). Treatment primarily involves BAS and FXR agonists. However, due to the limited sensitivity and specificity of current diagnostic methods, as well as suboptimal treatment efficacy and the presence of side effects, there is an urgent need to establish new diagnostic and treatment methods. While prior literature has summarized various diagnostic and treatment methods and the pathogenesis of BAD, no previous work has linked the two. This review offers a molecular perspective on the clinical diagnosis and treatment of BAD, with a focus on FXR, FGFR4, and TGR5, emphasizing the potential for identifying additional molecular mechanisms as treatment targets and bridging the gap between diagnostic and treatment methods and molecular mechanisms for a novel approach to the clinical management of BAD.
Computation of X-ray and Neutron Scattering Patterns to Benchmark Atomistic Simulations against Experiments
Authors: Majumdar Arnab , Müller Martin , Busch Sebastian
Published: January 2024

Molecular Dynamics simulations study material structure and dynamics at the atomic level. X-ray and neutron scattering experiments probe exactly the same time- and length scales as the simulations. In order to benchmark simulations against measured scattering data, a program is required that computes scattering patterns from simulations with good single-core performance and support for parallelization. In this work, the existing program Sassena is used as a potent solution to this requirement for a range of scattering methods, covering pico- to nanosecond dynamics, as well as the structure from some Ångströms to hundreds of nanometers. In the case of nanometer-level structures, the finite size of the simulation box, which is referred to as the finite size effect, has to be factored into the computations for which a method is described and implemented into Sassena. Additionally, the single-core and parallelization performance of Sassena is investigated, and several improvements are introduced.
The Molecular Landscape of Thymic Epithelial Tumors: A Comprehensive Review
Authors: Elm Lisa , Levidou Georgia
Published: January 2024

Thymic epithelial tumors (TETs) are characterized by their extreme rarity and variable clinical presentation, with the inadequacy of the use of histological classification alone to distinguish biologically indolent from aggressive cases. The utilization of Next Generation Sequencing (NGS) to unravel the intricate genetic landscape of TETs could offer us a comprehensive understanding that is crucial for precise diagnoses, prognoses, and potential therapeutic strategies. Despite the low tumor mutational burden of TETS, NGS allows for exploration of specific genetic signatures contributing to TET onset and progression. Thymomas exhibit a limited mutational load, with prevalent GTF2I and HRAS mutations. On the other hand, thymic carcinomas (TCs) exhibit an elevated mutational burden, marked by frequent mutations in TP53 and genes associated with epigenetic regulation. Moreover, signaling pathway analyses highlight dysregulation in crucial cellular functions and pathways. Targeted therapies, and ongoing clinical trials show promising results, addressing challenges rooted in the scarcity of actionable mutations and limited genomic understanding. International collaborations and data-sharing initiatives are crucial for breakthroughs in TETs research.
Sources of Variance in Human Tear Proteomic Samples: Statistical Evaluation, Quality Control, Normalization, and Biological Insight
Authors: Bruszel Bella , Tóth-Molnár Edit , Janáky Tamás , Szabó Zoltán
Published: January 2024

Human tear fluid contains numerous compounds, which are present in highly variable amounts owing to the dynamic and multipurpose functions of tears. A better understanding of the level and sources of variance is essential for determining the functions of the different tear components and the limitations of tear samples as a potential biomarker source. In this study, a quantitative proteomic method was used to analyze variations in the tear protein profiles of healthy volunteers. High day-to-day and inter-eye personal variances were observed in the tear volumes, protein content, and composition of the tear samples. Several normalization and outlier exclusion approaches were evaluated to decrease variances. Despite the intrapersonal variances, statistically significant differences and cluster analysis revealed that proteome profile and immunoglobulin composition of tear fluid present personal characteristics. Using correlation analysis, we could identify several correlating protein clusters, mainly related to the source of the proteins. Our study is the first attempt to achieve more insight into the biochemical background of human tears by statistical evaluation of the experimentally observed dynamic behavior of the tear proteome. As a pilot study for determination of personal protein profiles of the tear fluids of individual patients, it contributes to the application of this noninvasively collectible body fluid in personal medicine.
Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs
Authors: Gwozdzinski Lukasz , Pieniazek Anna , Gwozdzinski Krzysztof
Published: January 2024

One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.
Antifibrotic Drugs against Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis Induced by COVID-19: Therapeutic Approaches and Potential Diagnostic Biomarkers
Authors: Perez-Favila Aurelio , Garza-Veloz Idalia , Hernandez-Marquez Lucia del Socorro , Gutierrez-Vela Edgar Fernando , Flores-Morales Virginia , Martinez-Fierro Margarita L.
Published: January 2024

The COVID-19 pandemic has had a significant impact on the health and economy of the global population. Even after recovery from the disease, post-COVID-19 symptoms, such as pulmonary fibrosis, continue to be a concern. This narrative review aims to address pulmonary fibrosis (PF) from various perspectives, including the fibrotic mechanisms involved in idiopathic and COVID-19-induced pulmonary fibrosis. On the other hand, we also discuss the current therapeutic drugs in use, as well as those undergoing clinical or preclinical evaluation. Additionally, this article will address various biomarkers with usefulness for PF prediction, diagnosis, treatment, prognosis, and severity assessment in order to provide better treatment strategies for patients with this disease.
The Lectin Pathway of the Complement System—Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems
Authors: Dobó József , Kocsis Andrea , Farkas Bence , Demeter Flóra , Cervenak László , Gál Péter
Published: January 2024

The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation–fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Mannose-binding lectin (MBL), other collectins, and ficolins are collectively termed as the pattern recognition molecules (PRMs) of the LP, and they are responsible for targeting LP activation to molecular patterns, e.g., on bacteria. MBL-associated serine proteases (MASPs) are the effectors, while MBL-associated proteins (MAps) have regulatory functions. Two serine protease components, MASP-1 and MASP-2, trigger the LP activation, while the third component, MASP-3, is involved in the function of the alternative pathway (AP) of complement. Besides their functions within the complement system, certain LP components have secondary (“moonlighting”) functions, e.g., in embryonic development. They also contribute to blood coagulation, and some might have tumor suppressing roles. Uncontrolled complement activation can contribute to the progression of many diseases (e.g., stroke, kidney diseases, thrombotic complications, and COVID-19). In most cases, the lectin pathway has also been implicated. In this review, we summarize the history of the lectin pathway, introduce their components, describe its activation and regulation, its roles within the complement cascade, its connections to blood coagulation, and its direct cellular effects. Special emphasis is placed on disease connections and the non-canonical functions of LP components.
Cellular Distribution of Aquaporin 3, 7 and 9 in the Male Reproductive System: A Lesson from Bovine Study (Bos taurus)
Authors: Oberska Patrycja , Grabowska Marta , Marynowska Marta , Murawski Maciej , Gączarzewicz Dariusz , Syczewski Andrzej , Michałek Katarzyna
Published: January 2024

The increasing incidence of male infertility in humans and animals creates the need to search for new factors that significantly affect the course of reproductive processes. Therefore, the aim of this study was to determine the temporospatial expression of aquaglyceroporins (AQP3, AQP7 and AQP9) in the bovine (Bos taurus) reproductive system using immunohistochemistry and Western blotting. The study also included morphological analysis and identification of GATA-4. In brief, in immature individuals, AQP3 and AQP7 were found in gonocytes. In reproductive bulls, AQP3 was observed in spermatocytes and spermatogonia, while AQP7 was visible in all germ cells and the Sertoli cells. AQP7 and AQP9 were detected in the Leydig cells. Along the entire epididymis of reproductive bulls, aquaglyceroporins were visible, among others, in basal cells (AQP3 and AQP7), in epididymal sperm (AQP7) and in the stereocilia of the principal cells (AQP9). In males of all ages, aquaglyceroporins were identified in the principal and basal cells of the vas deferens. An increase in the expression of AQP3 in the testis and cauda epididymis and a decrease in the abundance of AQP7 in the vas deferens with age were found. In conclusion, age-related changes in the expression and/or distribution patterns of AQP3, AQP7 and AQP9 indicate the involvement of these proteins in the normal development and course of male reproductive processes in cattle.
Machine Learning-Based Classification of Transcriptome Signatures of Non-Ulcerative Bladder Pain Syndrome
Authors: Akshay Akshay , Besic Mustafa , Kuhn Annette , Burkhard Fiona C. , Bigger-Allen Alex , Adam Rosalyn M. , Monastyrskaya Katia , Hashemi Gheinani Ali
Published: January 2024

Lower urinary tract dysfunction (LUTD) presents a global health challenge with symptoms impacting a substantial percentage of the population. The absence of reliable biomarkers complicates the accurate classification of LUTD subtypes with shared symptoms such as non-ulcerative Bladder Pain Syndrome (BPS) and overactive bladder caused by bladder outlet obstruction with Detrusor Overactivity (DO). This study introduces a machine learning (ML)-based approach for the identification of mRNA signatures specific to non-ulcerative BPS. Using next-generation sequencing (NGS) transcriptome data from bladder biopsies of patients with BPS, benign prostatic obstruction with DO, and controls, our statistical approach successfully identified 13 candidate genes capable of discerning BPS from control and DO patients. This set was validated using Quantitative Polymerase Chain Reaction (QPCR) in a larger patient cohort. To confirm our findings, we applied both supervised and unsupervised ML approaches to the QPCR dataset. A three-mRNA signature TPPP3, FAT1, and NCALD, emerged as a robust classifier for non-ulcerative BPS. The ML-based framework used to define BPS classifiers establishes a solid foundation for comprehending the gene expression changes in the bladder during BPS and serves as a valuable resource and methodology for advancing signature identification in other fields. The proposed ML pipeline demonstrates its efficacy in handling challenges associated with limited sample sizes, offering a promising avenue for applications in similar domains.
Chronic Morphine Treatment and Antiretroviral Therapy Exacerbate HIV-Distal Sensory Peripheral Neuropathy and Induce Distinct Microbial Alterations in the HIV Tg26 Mouse Model
Authors: Antoine Danielle , Chupikova Irina , Jalodia Richa , Singh Praveen Kumar , Roy Sabita
Published: January 2024

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individuals, leading to chronic pain and reduced quality of life. Even with antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16S rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain pathways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine- and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mouse model to be a relevant system that can help elucidate the pathogenic mechanisms of the opioid- and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate interplay between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.
Compressive Sensing in Image/Video Compression: Sampling, Coding, Reconstruction, and Codec Optimization
Authors: Zhou Jinjia , Yang Jian
Published: January 2024

Compressive Sensing (CS) has emerged as a transformative technique in image compression, offering innovative solutions to challenges in efficient signal representation and acquisition. This paper provides a comprehensive exploration of the key components within the domain of CS applied to image and video compression. We delve into the fundamental principles of CS, highlighting its ability to efficiently capture and represent sparse signals. The sampling strategies employed in image compression applications are examined, emphasizing the role of CS in optimizing the acquisition of visual data. The measurement coding techniques leveraging the sparsity of signals are discussed, showcasing their impact on reducing data redundancy and storage requirements. Reconstruction algorithms play a pivotal role in CS, and this article reviews state-of-the-art methods, ensuring a high-fidelity reconstruction of visual information. Additionally, we explore the intricate optimization between the CS encoder and decoder, shedding light on advancements that enhance the efficiency and performance of compression techniques in different scenarios. Through a comprehensive analysis of these components, this review aims to provide a holistic understanding of the applications, challenges, and potential optimizations in employing CS for image and video compression tasks.
Peripartum Takotsubo Cardiomyopathy: A Review and Insights from a National Registry
Authors: Vazirani Ravi , Blanco-Ponce Emilia , Almendro Delia Manuel , Martín-Garcia Agustín C. , Fernández-Cordón Clara , Uribarri Aitor , Vedia Oscar , Sionis Alessandro , Salamanca Jorge , Corbí-Pascual Miguel , Pérez-Castellanos Alberto , Martínez-Selles Manuel , Manuel-Becerra Víctor , Raposeiras-Roubín Sergio , Aritza-Conty David , Lopez-País Javier , Guillén-Marzo Marta , Lluch-Requerey Carmen , Núñez-Gil Iván J.
Published: January 2024

Takotsubo syndrome (TTS) during the peripartum period is a relevant cause of morbidity in this population; its clinical course and prognosis, compared to the general TTS population, is yet to be elucidated. Our aim was to analyze the clinical features and prognosis of peripartum TTS in a nationwide prospective specifically oriented registry database and consider the published literature. Peripartum TTS patients from the prospective nationwide RETAKO registry—as well as peripartum TTS patients from the published literature—were included, and multiple comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between the groups. Patients with peripartum TTS exhibit a higher prevalence of secondary forms, dyspnea, atypical symptoms, and echocardiographic patterns, as well as less ST-segment elevation than the general TTS population. In the literature, patients with peripartum TTS had a higher Killip status on admission. TTS during the peripartum period has a higher prevalence of angina and dyspnea, as well as physical triggers, neither of which are related to a worse prognosis. Killip status on admission was higher in the literature for patients with TTS but with excellent mid- and long-term prognoses after the acute phase, despite mostly being secondary forms.
Management of Advanced Peri-Implantitis by Guided Bone Regeneration in Combination with Trabecular Metal Fixtures, Two Months after Removal of the Failed Implants: Two-Year Results of a Single-Cohort Clinical Study
Authors: Bianconi Stefano , Romanos Georgios , Testori Tiziano , Del Fabbro Massimo
Published: January 2024

Background: Implant replacement is among the treatment options for severe peri-implantitis. The aim of this single-cohort study was to evaluate the feasibility of replacing compromised implants affected by advanced peri-implantitis with new implants with a porous trabecular metal (TM) structure. Materials and Methods: Patients with one or more implants in the posterior region showing a defect depth >50% of implant length, measured from the residual crest, were consecutively included. Two months after implant removal, patients received a TM implant combined with a xenograft and a resorbable membrane. The implant stability quotient (ISQ) was measured at placement and re-assessed five months later (at uncovering), then after 6, 12, and 24 months of function. Marginal bone loss was radiographically evaluated. Results: Twenty consecutive cases were included. One patient dropped out due to COVID-19 infection, and nineteen cases were evaluated up to 24 months. At placement, the mean ISQ was 53.08 ± 13.65 (standard deviation), which increased significantly to 69.74 ± 9.01 after five months of healing (p < 0.001) and to 78.00 ± 7.29 after six months of loading (p < 0.001). Thereafter, the ISQ remained stable for up to 24 months (80.55 ± 4.73). All implants successfully osseointegrated and were restored as planned. After two years, the average marginal bone level change was −0.41 ± 0.38 mm (95% confidence interval −0.60, −0.21), which was limited yet significantly different from the baseline (p < 0.05). Conclusions: The treatment of advanced peri-implant defects using TM implants inserted two months after explantation in combination with guided bone regeneration may achieve successful outcomes up to two years follow-up, even in the presence of low primary stability.