Miracle-dz/UniFAR-FTUs huggingface dataset:
Trafficking of Mononuclear Phagocytes in Healthy Arteries and Atherosclerosis

Monocytes and macrophages play essential roles in all stages of atherosclerosis – from early precursor lesions to advanced stages of the disease. Intima-resident macrophages are among the first cells to be confronted with the influx and retention of apolipoprotein B-containing lipoproteins at the onset of hypercholesterolemia and atherosclerosis development. In this review, we outline the trafficking of monocytes and macrophages in and out of the healthy aorta, as well as the adaptation of their migratory behaviour during hypercholesterolemia. Furthermore, we discuss the functional and ontogenetic composition of the aortic pool of mononuclear phagocytes and its link to the atherosclerotic disease process. The development of mouse models of atherosclerosis regression in recent years, has enabled scientists to investigate the behaviour of monocytes and macrophages during the resolution of atherosclerosis. Herein, we describe the dynamics of these mononuclear phagocytes upon cessation of hypercholesterolemia and how they contribute to the restoration of tissue homeostasis. The aim of this review is to provide an insight into the trafficking, fate and disease-relevant dynamics of monocytes and macrophages during atherosclerosis, and to highlight remaining questions. We focus on the results of rodent studies, as analysis of cellular fates requires experimental manipulations that cannot be performed in humans but point out findings that could be replicated in human tissues. Understanding of the biology of macrophages in atherosclerosis provides an important basis for the development of therapeutic strategies to limit lesion formation and promote plaque regression.
Juvenile Neuromuscular Systems Show Amplified Disturbance to Muscle Unloading

Muscle unloading results in severe disturbance in neuromuscular function. During juvenile stages of natural development, the neuromuscular system experiences a high degree of plasticity in function and structure. This study aimed to determine whether muscle unloading imposed during juvenile development would elicit more severe disruption in neuromuscular function than when imposed on fully developed, mature neuromuscular systems. Twenty juvenile (3 months old) and 20 mature (8 months old) rats were equally divided into unloaded and control groups yielding a total of four groups (N = 10/each). Following the 2 week intervention period, soleus muscles were surgically extracted and using an ex vivo muscle stimulation and recording system, were examined for neuromuscular function. The unloading protocol was found to have elicited significant (P ≤ 0.05) declines in whole muscle wet weight in both juvenile and mature muscles, but of a similar degree (P = 0.286). Results also showed that juvenile muscles displayed significantly greater decay in peak force due to unloading than mature muscles, such a finding was also made for specific tension or force/muscle mass. When examining neuromuscular efficiency, i.e., function of the neuromuscular junction, it again was noted that juvenile systems were more negatively affected by muscle unloading than mature systems. These results indicate that juvenile neuromuscular systems are more sensitive to the effects of unloading than mature ones, and that the primary locus of this developmental related difference is likely the neuromuscular junction as indicated by age-related differences in neuromuscular transmission efficiency.
Examining Distinctive Working Memory Profiles in Chinese Children With Predominantly Inattentive Subtype of Attention-Deficit/Hyperactivity Disorder and/or Reading Difficulties

Although evidence has shown that both RD and ADHD-I children suffer from working memory problems, inconsistencies in impaired modalities have been reported. This study aimed to (1) compare the three WM domains (i.e., verbal WM, visual-spatial WM, and behavioral WM) among pure ADHD-I, pure RD, comorbid ADHD-I+RD, and typical control groups and (2) examine the impact of comorbidity on the three WM domains. A Chinese sample of participants from Hong Kong included 29 children in the ADHD-I group, 78 children in the RD group, 31 children in the comorbid group (ADHD-I+RD), and 64 children in the TD control group. All participants completed the assessments individually. The findings showed that the children with ADHD-I and/or RD exhibited diverse cognitive profiles. In particular, RD was associated with verbal and visual-spatial working memory deficits, while ADHD-I was associated with behavioral working memory deficits. Interestingly, the comorbid condition demonstrated additive deficits of the two disorders but with greater deficits in behavioral working memory. These findings support the cognitive subtype hypothesis and provide a clearer picture of the distinctive working memory profiles of different groups, allowing for the development of intervention programs in the future.
Clinical Predictors of Abnormal Head Computed Tomography Findings in Non-trauma Patients Presenting to a South African Emergency Department

Background: Head computed tomography (head CT) examinations conducted at emergency departments (EDs) for non-trauma patients are expensive and expose patients to ionizing radiation. Identification of symptoms likely to yield abnormal head CT scans can reduce costs and prevent unnecessary patient irradiation. There is limited comprehensive data in the literature concerning the utilization of head CT in low- and middle-income countries (LMICs) EDs. Methods: A retrospective study of successive non-contrasted head CT scans from February 2017 through January 2018 performed on non-trauma ED patients aged 18 years and above without known pre-existing intracranial pathology was conducted. Univariate and multivariate logistic models were used to determine which presenting clinical features were likely to yield abnormal head CT findings. Clinical information was obtained from the history and physical examination findings entered on the requisition form by the ED clinicians and from previous head CT reports if present on the picture archiving and communication system (PACS). Results: A total of 396 consecutive patients who received head CT examinations had a median age of 49 years (IQR: 36–53), and 53.3% were male (n = 211/396). Of the head CT scans included, 73.5% of head CTs included were abnormal (n = 291/396). Age >61 years (aOR:1.54; 95%CI: 1.12–2.10), focal neurologic deficit (aOR: 2.46; 95%CI: 1.42–4.26), and loss of consciousness (aOR 2.82; 95%CI: 1.21–6.57) were the predictors of abnormal head CT findings. Conclusion: A head CT scan in a non-trauma patient presenting to an emergency department in a low–middle income country like South Africa is likely to yield abnormal findings if a patient presented with age above 61 years, loss of consciousness, or focal neurological deficit.
Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10–15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.
Imagine, Sing, Play- Combined Mental, Vocal and Physical Practice Improves Musical Performance

Classical musicians face a high demand for flawless and expressive performance, leading to highly intensified practice activity. Whereas the advantage of using mental strategies is well documented in sports research, few studies have explored the efficacy of mental imagery and overt singing on musical instrumental learning. In this study, 50 classically trained trumpet students performed short unfamiliar pieces. Performances were recorded before and after applying four prescribed practice strategies which were (1) physical practice, (2) mental imagery, (3) overt singing with optional use of solfege, (4) a combination of 1, 2 and 3 or a control condition, no practice. Three experts independently assessed pitch and rhythm accuracy, sound quality, intonation, and musical expression in all recordings. We found higher gains in the overall performance, as well as in pitch accuracy for the physical practice, and the combined practice strategies, compared to no practice. Furthermore, only the combined strategy yielded a significant improvement in musical expression. Pitch performance improvement was positively correlated with previous solfege training and frequent use of random practice strategies. The findings highlight benefits from applying practice strategies that complement physical practice in music instrument practice in short term early stages of learning a new piece. The study may generalize to other forms of learning, involving cognitive processes and motor skills.
Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV

Background Cervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses. Methods The 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay. Results Overall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p < 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses. Discussion Depletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.
The Therapeutic Intervention of Sex Steroid Hormones for Sarcopenia

Sarcopenia, characterized by the excessive loss of skeletal muscle mass, strength, and function, is associated with the overall poor muscle performance status of the elderly, and occurs more frequently in those with chronic diseases. The causes of sarcopenia are multifactorial due to the inherent relationship between muscles and molecular mechanisms, such as mitochondrial function, inflammatory pathways, and circulating hormones. Age-related changes in sex steroid hormone concentrations, including testosterone, estrogen, progesterone, and their precursors and derivatives, are an important aspect of the pathogenesis of sarcopenia. In this review, we provide an understanding of the treatment of sarcopenia through the regulation of sex steroid hormones. The potential benefits and future research emphasis of each sex steroid hormone therapeutic intervention (testosterone, SARMs, estrogen, SERMs, DHEA, and progesterone) for sarcopenia are discussed. Enhanced understanding of the role of sex steroid hormones in the treatment for sarcopenia could lead to the development of hormone therapeutic approaches in combination with specific exercise and nutrition regimens.
Comparison of CRISPR–Cas Immune Systems in Healthcare-Related Pathogens

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridium difficile have been identified as the leading global cause of multidrug-resistant bacterial infections in hospitals. CRISPR–Cas systems are bacterial immune systems, empowering the bacteria with defense against invasive mobile genetic elements that may carry the antimicrobial resistance (AMR) genes, among others. On the other hand, the CRISPR–Cas systems are themselves mobile. In this study, we annotated and compared the CRISPR–Cas systems in these pathogens, utilizing their publicly available large numbers of sequenced genomes (e.g., there are more than 12 thousands of S. aureus genomes). The presence of CRISPR–Cas systems showed a very broad spectrum in these pathogens: S. aureus has the least tendency of obtaining the CRISPR–Cas systems with only 0.55% of its isolates containing CRISPR–Cas systems, whereas isolates of C. difficile we analyzed have CRISPR–Cas systems each having multiple CRISPRs. Statistical tests show that CRISPR–Cas containing isolates tend to have more AMRs for four of the pathogens (A. baumannii, E. faecium, P. aeruginosa, and S. aureus). We made available all the annotated CRISPR–Cas systems in these pathogens with visualization at a website (https://omics.informatics.indiana.edu/CRISPRone/pathogen), which we believe will be an important resource for studying the pathogens and their arms-race with invaders mediated through the CRISPR–Cas systems, and for developing potential clinical applications of the CRISPR–Cas systems for battles against the antibiotic resistant pathogens.
Acceptance of a COVID-19 Vaccine Before it is Available in China During the Pandemic

Objectives: China was believed to be the country with the world’s highest acceptance rate of the COVID-19 vaccine following several investigations. This study aims to explore the Chinese acceptance of a COVID-19 vaccine before it is made available, including its determinants. Methods: A cross-national online survey was conducted covering all 31 provinces of mainland China. The survey consists of the demographic variables, acceptance of a self-paid COVID-19 vaccine as the dependent variable, and the 3Cs factors (i.e., confidence, convenience, and complacency) as the independent variables. Results: Among the 1,532 participants, 57.9% accepted to get a self-paid COVID-19 vaccine. COVID-19 vaccine acceptors were more likely to be concerned about the effectiveness of the vaccines, believe that they were at risk of COVID-19 infection, have a high perceived susceptibility of COVID-19, and trust in the health care system. Conclusion: Findings indicate that the critical task in the early stage of the COVID-19 vaccine development in China is to increase the tolerance to some intuitive concerns about the vaccines, put more emphasis on the communication of the saliency of the disease threats, and effectively translate people’s trust in the government into vaccine acceptance.
Single-Cell Transcriptome Profiling Identifies Phagocytosis-Related Dual-Feature Cells in A Model of Acute Otitis Media in Rats

Background The molecular mechanisms of acute otitis media (AOM) development, and the intercellular crosstalk within the multicellular ecosystem of AOM, are not clear. Methods We established a model of AOM in rats (with normal rats as controls) and undertook single-cell RNA sequencing (scRNA-seq) for the middle-ear mucosa (MEM). Cell clustering and trajectory analyses were undertaken using Seurat and Monocle 2 packages in R software. Pathway analyses were done by gene set enrichment analysis (GSEA). Cell–cell interactions were inferred by CellChat. Cell scores were calculated to identify cells with dual-feature. Results A total of 7023 cells from three samples of inflamed MEM and 5258 cells from three samples of healthy MEM underwent scRNA-seq, which identified 20 cell clusters belonging to eight major cell types. After exposure to lipopolysaccharide, the MEM underwent significant conversion of cell types characterized by rapid infiltration of macrophages and neutrophils. M2 macrophages seemed to play a key part in inflammatory intercellular crosstalk, which facilitated the maintenance and proliferation of macrophages, cell chemotaxis, and regulation of the proinflammatory activities of cytokines. Three rare cell clusters with phagocytosis-related dual-feature were also identified. They coexisted with professional phagocytes in the MEM, and displayed distinct immunoregulatory functions by maintaining a normal immune microenvironment or influencing inflammation progression. Conclusions Macrophages might be the “master” initiators and regulators of the inflammatory response of the MEM to external stimuli. And their functions are fulfilled by a specific polarization status (M2) and sophisticated intercellular crosstalk via certain signaling pathways. Besides, the coexistence of professional phagocytes and non-professional phagocytes as well as their interplay in the MEM provides new clues for deciphering the underlying pathogenic mechanisms of AOM.
Structure-Based Primer Design Minimizes the Risk of PCR Failure Caused by SARS-CoV-2 Mutations

The coronavirus disease 2019 (COVID-19) has caused and is still causing tremendous damage to the global economy and human health. Qualitative reverse transcription-PCR (RT-qPCR) is the golden standard for COVID-19 test. However, the SARS-CoV-2 variants may not only make vaccine less effective but also evade RT-qPCR test. Here we suggest an innovative primer design strategy for the RT-qPCR test of SARS-CoV-2. The principle is that the primers should be designed based on both the nucleic acid sequence and the structure of the protein encoded. The three nucleotides closest to the 3′ end of the primer should be the codon which encodes the tryptophan in the structure core. Based on this principle, we designed a pair of primers targeting the nucleocapsid (N) gene. Since tryptophan is encoded by only one codon, any mutation that occurs at this position would change the amino acid residue, resulting in an unstable N protein. This means that this kind of SARS-CoV-2 variant could not survive. In addition, both our data and previous reports all indicate that the mutations occurring at other places in the primers do not significantly affect the RT-qPCR result. Consequently, no SARS-CoV-2 variant can escape detection by the RT-qPCR kit containing the primers designed based on our strategy.
Anxiety and Perceived Risk in Red Cross Volunteer Personnel Facing the Coronavirus Disease 2019 Pandemic

In the current situation of sanitary emergencies, humanitarian organizations and their volunteers are playing an important role in the coronavirus disease 2019 (COVID-19) pandemic. A study is proposed that includes a network of volunteers who perform humanitarian activities during the COVID-19 pandemic to assess anxiety, perceived risk, and response behaviors and to explore their relationship with sociodemographic variables. For data collection, an online questionnaire was developed through the Google Forms® platform, where the perceived risk, anxiety, and behavioral responses of the general population to the Influenza A (H1N1) pandemic were assessed. The survey presented is a modified version of that survey adapted for COVID-19. This adaptation was endorsed by an experts committee made up of the health chief of the Ecuadorian Red Cross, the focus point of operations from the International Federation of the Red Cross in Ecuador, and a member from the Health Unit of the Americas Regional Office of the International Federation of the Red Cross. A significant relationship has been shown between the job situation and perceived risk and anxiety, being the staff who worked full time away from home, which was exposed to greater risk and anxiety. Both perceived risk and perceived anxiety are very high (according to a 5-point Likert scale). Knowing these data from this first-line personnel will allow adopting measures that could be beneficial for stress management and, therefore, contribute to the well-being and support of these humanitarian and volunteer organizations in the worldwide response to COVID-1 9.