Miracle-dz/UniFAR-FTUs huggingface dataset:
Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

The systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell transcriptome atlas of adult pigs encompassing 229,268 high-quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.
Majorization-based convergence rate bounds for subspace iterations and the block Lanczos method

The Rayleigh-Ritz method finds the stationary values, called Ritz values, of the Rayleigh quotient on a given trial subspace as approximations to eigenvalues of a Hermitian operator A. If the trial subspace is A-invariant, the Ritz values are some of the eigenvalues of A. Given two subspaces X and Y of the same finite dimension, such that X is A-invariant, the absolute changes in the Ritz values of A with respect to X compared to the Ritz values with respect to Y represent the absolute eigenvalue approximation error. A recent paper by M. Argentati et al. bounds the error in terms of the principal angles between X and Y using weak majorization. In this talk we derive a new majorization-type convergence rate bound for subspace iterations and combine it with the previous result to obtain a similar bound for the block Lanczos method. These majorization results imply a very general set of inequalities that involve all of the principal angles, not just the largest principal angle.
Impact of cell-free supernatant of lactic acid bacteria on Staphylococcus aureus biofilm and its metabolites

Introduction A safe bio-preservative agent, lactic acid bacteria (LAB) can inhibit the growth of pathogenic bacteria and spoilage organisms. Its cell-free supernatant (LAB-CFS), which is rich in bioactive compounds, is what makes LAB antibacterial work. Methods This study focused on the changes in biofilm activity and related metabolic pathways of S. aureus treated with lactic acid bacteria planktonic CFS (LAB-pk-CFS) and biofilm state (LAB-bf-CFS). Results The findings demonstrated that the LAB-CFS treatment considerably slowed Staphylococcus aureus (S. aureus) growth and prevented it from forming biofilms. Additionally, it inhibits the physiological traits of the S. aureus biofilm, including hydrophobicity, motility, eDNA, and PIA associated to the biofilm. The metabolites of S. aureus biofilm treated with LAB-CFS were greater in the LAB-bf-CFS than they were in the LAB-pk-CFS, according to metabolomics studies. Important metabolic pathways such amino acids and carbohydrates metabolism were among the most noticeably altered metabolic pathways. Discussion These findings show that LAB-CFS has a strong potential to combat S. aureus infections.
Identification of bacterial pathogens in sudden unexpected death in infancy and childhood using 16S rRNA gene sequencing

Background Sudden unexpected death in infancy (SUDI) is the most common cause of post-neonatal death in the developed world. Following an extensive investigation, the cause of ~40% of deaths remains unknown. It is hypothesized that a proportion of deaths are due to an infection that remains undetected due to limitations in routine techniques. This study aimed to apply 16S rRNA gene sequencing to post-mortem (PM) tissues collected from cases of SUDI, as well as those from the childhood equivalent (collectively known as sudden unexpected death in infancy and childhood or SUDIC), to investigate whether this molecular approach could help identify potential infection-causing bacteria to enhance the diagnosis of infection. Methods In this study, 16S rRNA gene sequencing was applied to de-identified frozen post-mortem (PM) tissues from the diagnostic archive of Great Ormond Street Hospital. The cases were grouped depending on the cause of death: (i) explained non-infectious, (ii) infectious, and (iii) unknown. Results and conclusions In the cases of known bacterial infection, the likely causative pathogen was identified in 3/5 cases using bacterial culture at PM compared to 5/5 cases using 16S rRNA gene sequencing. Where a bacterial infection was identified at routine investigation, the same organism was identified by 16S rRNA gene sequencing. Using these findings, we defined criteria based on sequencing reads and alpha diversity to identify PM tissues with likely infection. Using these criteria, 4/20 (20%) cases of unexplained SUDIC were identified which may be due to bacterial infection that was previously undetected. This study demonstrates the potential feasibility and effectiveness of 16S rRNA gene sequencing in PM tissue investigation to improve the diagnosis of infection, potentially reducing the number of unexplained deaths and improving the understanding of the mechanisms involved.
YAP at the progression of inflammation

Yes-associated protein (YAP) is a transcriptional regulator that affects cell proliferation, organ size and tissue development and regeneration, and has therefore, been an important object of study. In recent years, there has been an increasing research focus on YAP in inflammation and immunology, and the role of YAP in the development of inflammation and in immune escape by tumors has been progressively elucidated. Because YAP signaling involves a variety of different signal transduction cascades, the full range of functions in diverse cells and microenvironments remains incompletely understood. In this article, we discuss the complex involvement of YAP in inflammation, the molecular mechanisms through which it exercises pro- and anti-inflammatory effects under different conditions, and the progress achieved in elucidating the functions of YAP in inflammatory diseases. A thorough understanding of YAP signaling in inflammation will provide a foundation for its use as a therapeutic target in inflammatory diseases.
Metagenomic-based pathogen surveillance for children with severe pneumonia in pediatric intensive care unit

Background Pneumonia is a significant cause of morbidity and mortality in children. Metagenomic next-generation sequencing (mNGS) has the potential to assess the landscape of pathogens responsible for severe pulmonary infection. Methods Bronchoalveolar lavage fluid (BALF) samples of 262 children with suspected pulmonary infections were collected from April 2019 to October 2021 in the Pediatric Intensive Care Unit (PICU) of Guangdong Women and Children Hospital. Both mNGS and conventional tests were utilized for pathogen detection. Results A total of 80 underlying pathogens were identified using both mNGS and conventional tests. Respiratory syncytial virus (RSV), Staphylococcus aureus and rhinovirus were the most frequently detected pathogens in this cohort. The incidence rate of co-infection was high (58.96%, 148/251), with bacterial-viral agents most co-detected. RSV was the main pathogen in children younger than 6 months of age, and was also commonly found in older pediatric patients. Rhinovirus was prevalent in children older than 6 months. Adenovirus and Mycoplasma pneumoniae were more prevalent in children older than 3 years than in other age groups. Pneumocystis jirovecii was detected in nearly 15% of children younger than 6 months. Besides, influenza virus and adenovirus were rarely found in 2020 and 2021. Conclusions Our study highlights the importance of using advanced diagnostic techniques like mNGS to improve our understanding of the microbial epidemiology of severe pneumonia in pediatric patients.
Heterotypic and homotypic continuity in psychopathology: a narrative review

Psychopathology is a process: it unfolds over time and involves several different factors. To extend our knowledge of such process, it is vital to understand the trajectories that lead to developing and maintaining a specific disorder. The construct of continuity appears very useful to this aim. It refers to the consistency, similarity, and predictability of behaviors or internal states across different developmental phases. This paper aims to present a narrative review of the literature on homotypic and heterotypic continuity of psychopathology across the lifespan. A detailed search of the published literature was conducted using the PsycINFO Record and Medline (PubMed) databases. Articles were included in the review based on the following criteria: (1) publication dates ranging from January 1970 to October 2022; and (2) articles being written in the English language. To ensure a thorough investigation, multiple combinations of keywords such as “continuity,” “psychopathology,” “infancy,” “childhood,” “adolescence,” “adulthood,” “homotypic,” and “heterotypic” were used. Articles were excluded if exclusively focused on epidemiologic data and if not specifically addressing the topic of psychopathology continuity. The literature yielded a total of 36 longitudinal studies and an additional 190 articles, spanning the research published between 1970 and 2022. Studies on continuity focus on the etiology of different forms of mental disorders and may represent a fundamental resource from both a theoretical and clinical perspective. Enhancing our understanding of the different trajectories beneath psychopathology may allow clinicians to implement more effective strategies, focusing both on prevention and intervention. Since literature highlights the importance of early detection of clinical signs of psychopathology, future research should focus more on infancy and pre-scholar age.
Mentalising and depression: a mini-review on behavior, neural substrates, and treatment options

Major depression is one of the most common mental disorders, affecting millions of people around the globe. In recent years, researchers increasingly investigated social cognition in depression and discovered pronounced alterations. A special focus has been put on mentalising or Theory of Mind, the ability to recognize and understand another person’s thoughts and feelings. While there is behavioral evidence for deficits in this ability in patients with depression as well as specialized therapeutic interventions, the neuroscientific substrates are only beginning to be understood. In this mini-review, we take a social neuroscience perspective to analyse the importance of altered mentalising in depression and whether it can help to understand the origins and perpetuation of the disorder. We will put a special focus on treatment options and corresponding neural changes to identify relevant paths for future (neuroscientific) research.
Cognitive-motor interventions based on virtual reality and instrumental activities of daily living (iADL): an overview

Non-invasive, non-pharmacological interventions utilizing virtual reality (VR) represent a promising approach to enhancing cognitive function in patients with degenerative cognitive disorders. Traditional “pen and paper” therapies often lack the practical engagement in everyday activities that older individuals encounter in their environment. These activities pose both cognitive and motor challenges, underscoring the necessity of understanding the outcomes of such combined interventions. This review aimed to assess the advantages of VR applications that integrate cognitive-motor tasks, simulating instrumental activities of daily living (iADLs). We systematically searched five databases–Scopus, Web of Science, Springer Link, IEEE Xplore, and PubMed, from their inception until January 31, 2023. Our review revealed that motor movements, coupled with VR-based cognitive-motor interventions, activate specific brain areas and foster improvements in general cognition, executive function, attention, and memory. VR applications that meld cognitive-motor tasks and simulate iADLs can offer significant benefits to older adults. Enhanced cognitive and motor performance can promote increased independence in daily activities, thereby contributing to improved quality of life.
A scoping review of different monitoring-technology devices in caring for older adults with cognitive impairment

Various monitoring technologies are being developed to prevent potential complications among older adults with cognitive impairment and improve their cognitive function. This scoping review identified gaps in the development of monitoring-technology devices for cognitive health status and highlights areas that require further inquiry. This study used the Joanna Briggs Institute (JBI) and the PRISMA extension for the checklist for scoping reviews using the eligibility criteria recommended by Population, Concept, and Context (PCC) framework. The study population included adults aged 65 years and above, while the concept and context are monitoring-technology devices utilized in detecting and caring for an older adult with cognitive impairment. Three electronic databases (Medline, Scopus, and Web of Science) were searched, and a total of 21 articles met the selection criteria. Several innovative technology-based devices for screening, assessing, detecting, and monitoring the interventions for older adult cognitive impairment and for family caregivers to ensure the continuity of care were established. Monitoring devices are useful in promoting older adult safety, improving their quality of life by enabling them to live independently for a longer period, and improving their mental wellbeing to help reduce the burden on caregivers by providing them with information concerning the activities of older adults. Moreover, studies have shown that older adults and their caregivers can learn to use these devices effectively and comfortably with proper education and training. The results of this study provide crucial insights into innovative technologies that can be used to assess cognitive health among older adults, which could substantially improve their mental health, and this baseline information can be used for supporting public health policy and enhancing their quality of life.
Evolution of human language: duetting as part of prosociality and cognition

The evolution of human language is a topic that has received undiminished attention. Numerous hypotheses for the origin of human language have been proposed, including gestural communication found specifically among apes. This study advances the hypothesis that human evolution, including human language development, is three-pronged: prosocial, cognitive, and collaborative. Duetting and turn-taking in primates are used as pivotal examples of how bonding leads to joint action and collaboration. It points out that such vocal behavior itself may be a crucial precursor of language evolution in the sense that it is explicitly focused on a conspecific. Some current hypotheses have acknowledged duetting as an important perceptual and behavioral example of synchronicity. Some forms of synchronized behavior, as found in duetting, synchronized dance, or even shared song, were perhaps crucial evolutionary steps preceding the evolution of human language. Duetting signifies more than that, however, because it is an observable and significant cognitive investment that signals attention toward a partner. This study also advances the hypothesis that affect and cognition would have needed to precede any form of duetting or signs of affiliation such as grooming. Hence, this study, asking what duetting in primates signifies in evolutionary terms, takes a multidisciplinary and multimodal approach to suggest important affective and cognitive steps in the evolution of human language and speech, the chief of which is prosociality. Prosociality, as an attitude and awareness of another, be this as a friend or partner for whom one can do favors or whom one can help, is a model for collaboration and cooperation, and also increased cognition.
Function of Akkermansia muciniphila in type 2 diabetes and related diseases

The prevalence of type 2 diabetes (T2D) is increasing worldwide, with many patients developing long-term complications that affect their cardiovascular, urinary, alimentary, and other systems. A growing body of literature has reported the crucial role of gut microbiota in metabolic diseases, one of which, Akkermansia muciniphila, is considered the “next-generation probiotic” for alleviating metabolic disorders and the inflammatory response. Although extensive research has been conducted on A. muciniphila, none has summarized its regulation in T2D. Hence, this review provides an overview of the effects and multifaceted mechanisms of A. muciniphila on T2D and related diseases, including improving metabolism, alleviating inflammation, enhancing intestinal barrier function, and maintaining microbiota homeostasis. Furthermore, this review summarizes dietary strategies for increasing intestinal A. muciniphila abundance and effective gastrointestinal delivery.
HSV-1 selectively packs the transcription factor Oct-1 into EVs to facilitate its infection

HSV-1 hijacks the cellular vesicular secretion system and promotes the secretion of extracellular vesicles (EVs) from infected cells. This is believed to facilitate the maturation, secretion, intracellular transportation and immune evasion of the virus. Intriguingly, previous studies have shown that noninfectious EVs from HSV-1-infected cells exert antiviral effects on HSV-1 and have identified host restrictive factors, such as STING, CD63, and Sp100 packed in these lipid bilayer-enclosed vesicles. Octamer-binding transcription factor-1 (Oct-1) is shown here to be a pro-viral cargo in non-virion-containing EVs during HSV-1 infection and serves to facilitate virus dissemination. Specifically, during HSV-1 infection, the nuclear localized transcription factor Oct-1 displayed punctate cytosolic staining that frequently colocalized with VP16 and was increasingly secreted into the extracellular space. HSV-1 grown in cells bereft of Oct-1 (Oct-1 KO) was significantly less efficient at transcribing viral genes during the next round of infection. In fact, HSV-1 promoted increased exportation of Oct-1 in non-virion-containing EVs, but not the other VP16-induced complex (VIC) component HCF-1, and EV-associated Oct-1 was promptly imported into the nucleus of recipient cells to facilitate the next round of HSV-1 infection. Interestingly, we also found that EVs from HSV-1-infected cells primed cells for infection by another RNA virus, vesicular stomatitis virus. In summary, this investigation reports one of the first pro-viral host proteins packed into EVs during HSV-1 infection and underlines the heterogenetic nature and complexity of these noninfectious double-lipid particles.
The relationship between dominant follicle development and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study

Research question Hormone replacement therapy (HRT) is one of the most used endometrial preparation protocols for frozen embryo transfer (FET) due to the convenience of its administration and stability of pregnancy outcomes. There are several HRT cycles accompanied by the development of dominant follicles. However, the relationship between dominant follicle development and clinical outcomes in HRT-FET cycles remains unclear. Design We carried out a retrospective cohort study of 13251 cycles at our reproductive medicine center from 2012 to 2019. Total cycles were divided into two groups according to whether there was dominant follicular development. In addition, we conducted a secondary analysis that used propensity-score matching to reduce confounding variables. A univariate and multivariable logistic regression model was further employed to analyze the effect of dominant follicle development in HRT cycles on clinical pregnancy outcomes. Results There was no significant correlation between dominant follicle development in HRT-FET cycles and the clinical pregnancy rate (adjusted OR = 1.162, 95% CI: 0.737-1.832, P = 0.52). In addition, there was a positive correlation between the basic follicle-stimulating hormone (FSH) level and the development of dominant follicles, while there was a negative correlation between antral follicle count (AFC), menstrual cycle length and the development of dominant follicles in HRT cycles. Conclusions The development of dominant follicles in HRT-FET cycles does not affect the clinical pregnancy rate, early miscarriage rate and live birth rate. Therefore, it is not necessary to immediately cancel the FET cycle immediately when dominant follicle development is monitored in the HRT-FET cycle.
Impacts of gender and age on meibomian gland in aged people using artificial intelligence

Purpose: To evaluate the effects of age and gender on meibomian gland (MG) parameters and the associations among MG parameters in aged people using a deep-learning based artificial intelligence (AI). Methods: A total of 119 subjects aged ≥60 were enrolled. Subjects completed an ocular surface disease index (OSDI) questionnaire, received ocular surface examinations including Meibography images captured by Keratograph 5M, diagnosis of meibomian gland dysfunction (MGD) and assessment of lid margin and meibum. Images were analyzed using an AI system to evaluate the MG area, density, number, height, width and tortuosity. Results: The mean age of the subjects was 71.61 ± 7.36 years. The prevalence of severe MGD and meibomian gland loss (MGL) increased with age, as well as the lid margin abnormities. Gender differences of MG morphological parameters were most significant in subjects less than 70 years old. The MG morphological parameters detected by AI system had strong relationship with the traditional manual evaluation of MGL and lid margin parameters. Lid margin abnormities were significantly correlated with MG height and MGL. OSDI was related to MGL, MG area, MG height, plugging and lipid extrusion test (LET). Male subjects, especially the ones who smoke or drink, had severe lid margin abnormities, and significantly decreased MG number, height, and area than the females. Conclusion: The AI system is a reliable and high-efficient method for evaluating MG morphology and function. MG morphological abnormities developed with age and were worse in the aging males, and smoking and drinking were risk factors.