Miracle-dz/UniFAR-FTUs huggingface dataset:
Ethnic Differences in the Frequency of CFTR Gene Mutations in Populations of the European and North Caucasian Part of the Russian Federation

Cystic fibrosis (CF) is a common monogenic disease caused by pathogenic variants in the CFTR gene. The distribution and frequency of CFTR variants vary in different countries and ethnic groups. The spectrum of pathogenic variants of the CFTR gene was previously studied in more than 1,500 CF patients from different regions of the European and North Caucasian region of Russia and the spectrum of the most frequent pathogenic variants of the CFTR gene and ethnic features of their distribution were determined. To assess the population frequency of CFTR gene mutations some of the common variants were analyzed in the samples of healthy unrelated individuals from the populations of the European part of the Russian Federation: 1,324 Russians from four European regions (Pskov, Tver, Rostov, and Kirov regions), representatives of five indigenous ethnic groups of the Volga-Ural region [Mari (n = 505), Udmurts (n = 613), Chuvash (n = 780), Tatars (n = 704), Bashkirs (n = 517)], and six ethnic groups of the North Caucasus [Karachay (n = 324), Nogais (n = 118), Circassians (n = 102), Abazins (n = 128), Ossetians (n = 310), and Chechens (n = 100)]. The frequency of common CFTR mutations was established in studied ethnic groups. The frequency of F508del mutation in Russians was found to be 0.0056 on average, varying between four regions, from 0.0027 in the Pskov region to 0.0069 in the Rostov region. Three variants W1282X, 1677delTA, and F508del were identified in the samples from the North Caucasian populations: in Karachay, the frequency of W1282X mutation was 0.0092, 1677delTA mutation – 0.0032; W1282X mutation in the Nogais sample – 0.0127, the frequency of F508del mutations was 0.0098 and 1677delTA – 0.0098 in Circassians; in Abazins F508del (0.0039), W1282X (0.0039) and 1677delTA (0.0117) mutations were found. In the indigenous peoples of the Volga-Ural region, the maximum frequency of the F508del mutation was detected in the Tatar population (0.099), while this mutation was never detected in the Mari and Bashkir populations. The E92K variant was found in Chuvash and Tatar populations. Thus, interethnic differences in the spectra of CFTR gene variants were shown both in CF patients and in healthy population of the European and North Caucasian part of Russia.
Correlation Between Maternal Smoking During Pregnancy and Dental Caries in Children: A Systematic Review and Meta-Analysis

Background: Dental caries is a long-standing oral health problem for children all over the world. The available evidence shows that the association between maternal smoking during pregnancy and childhood caries is still controversial. Therefore, the aim of this systematic review and meta-analysis was to determine whether there was a correlation of prenatal smoking and dental caries in children. Methods: PubMed, EMBASE, Cochrane, Web of Science, and Scopus databases were searched for observational studies assessing the relationship between maternal smoking during the pregnancy and childhood caries. According to the predesigned eligibility criteria and items, studies selection, and data extraction were conducted, respectively. The effect estimates were pooled using a fixed-effect model or a random-effect model. Newcastle-Ottawa Scale (NOS) was adopted to evaluate the methodological quality of the included studies. All analyses were carried out through Stata 12.0 software. Results: Our systematic review included a total of 11 studies, of which 6 cross-sectional studies and 3 longitudinal studies were included in the final meta-analysis. The pooled estimates indicated maternal smoking during pregnancy was significantly associated with dental caries in children both in cross-sectional studies (OR = 1.57, 95% CI = 1.47–1.67) and longitudinal studies (RR = 1.26, 95% CI = 1.07–1.48). Sensitivity analyses confirmed the overall effect estimates were robust. Conclusions: There is a significant correlation of maternal smoking during pregnancy and childhood caries. However, the causal relationship between them cannot be determined. More prospective and extensive studies on this theme is needed for verification. Even so, it is necessary for pregnant women and women of reproductive age to quit smoking. Strategies must be developed to raise public awareness about the impact of prenatal smoking on children's oral health.
The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury

Acute kidney injury (AKI) is a common clinical complication with an incidence of up to 8–18% in hospitalized patients. AKI is also a complication of COVID-19 patients and is associated with an increased risk of death. In recent years, numerous studies have suggested that epigenetic regulation is critically involved in the pathophysiological process and prognosis of AKI. Histone acetylation, one of the epigenetic regulations, is negatively regulated by histone deacetylases (HDACs). Increasing evidence indicates that HDACs play an important role in the pathophysiological development of AKI by regulation of apoptosis, inflammation, oxidative stress, fibrosis, cell survival, autophagy, ATP production, and mitochondrial biogenesis (MB). In this review, we summarize and discuss the role and mechanism of HDACs in the pathogenesis of AKI.
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences

Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.
Making the Most of the Host; Targeting the Autophagy Pathway Facilitates Staphylococcus aureus Intracellular Survival in Neutrophils

The success of Staphylococcus aureus as a human commensal and an opportunistic pathogen relies on its ability to adapt to several niches within the host. The innate immune response plays a key role in protecting the host against S. aureus infection; however, S. aureus adeptness at evading the innate immune system is indisputably evident. The “Trojan horse” theory has been postulated to describe a mechanism by which S. aureus takes advantage of phagocytes as a survival niche within the host to facilitate dissemination of S. aureus to secondary sites during systemic infection. Several studies have determined that S. aureus can parasitize both professional and non-professional phagocytes by manipulating the host autophagy pathway in order to create an intracellular survival niche. Neutrophils represent a critical cell type in S. aureus infection as demonstrated by the increased risk of infection among patients with congenital neutrophil disorders. However, S. aureus has been repeatedly shown to survive intracellularly within neutrophils with evidence now supporting a pathogenic role of host autophagy. By manipulating this pathway, S. aureus can also alter the apoptotic fate of the neutrophil and potentially skew other important signalling pathways for its own gain. Understanding these critical host-pathogen interactions could lead to the development of new host directed therapeutics for the treatment of S. aureus infection by removing its intracellular niche and restoring host bactericidal functions. This review discusses the current findings surrounding intracellular survival of S. aureus within neutrophils, the pathogenic role autophagy plays in this process and considers the therapeutic potential for targeting this immune evasion mechanism.
HearMeVirtual Reality: Using Virtual Reality to Facilitate Empathy Between Hearing Impaired Children and Their Parents

Cochlear implants (CI) enable hearing in individuals with sensorineural hearing loss, albeit with difficulties in speech perception and sound localization. In noisy environments, these difficulties are disproportionately greater for CI users than for children with no reported hearing loss. Parents of children with CIs are motivated to experience what CIs sound like, but options to do so are limited. This study proposes using virtual reality to simulate having CIs in a school setting with two contrasting settings: a noisy playground and a quiet classroom. To investigate differences between hearing conditions, an evaluation utilized a between-subjects design with 15 parents (10 female, 5 male; age M = 38.5, SD = 6.6) of children with CIs with no reported hearing loss. In the virtual environment, a word recognition and sound localization test using an open-set speech corpus compared differences between simulated unilateral CI, simulated bilateral CI, and normal hearing conditions in both settings. Results of both tests indicate that noise influences word recognition more than it influences sound localization, but ultimately affects both. Furthermore, bilateral CIs are equally to or significantly beneficial over having a simulated unilateral CI in both tests. A follow-up qualitative evaluation showed that the simulation enabled users to achieve a better understanding of what it means to be an hearing impaired child.
Cetacean Research and Citizen Science in Kenya

In 2011, several non-governmental and government agencies established the Kenya Marine Mammal Network (KMMN) to provide a platform for the consistent collection of data on marine mammals along the Kenyan coast, identify areas of importance and engage marine users and the general public in marine mammal conservation. Prior to the KMMN, relatively little was known about marine mammals in Kenya, limiting conservation strategies. The KMMN collects data nationwide through dedicated surveys, opportunistic sightings and participative citizen science, currently involving more than 100 contributors. This paper reviews data on sightings and strandings for small cetaceans in Kenya collated by the KMMN. From 2011 to 2019, 792 records of 11 species of small cetaceans were documented. The most frequently reported inshore species were the Indo-Pacific bottlenose dolphin and Indian Ocean humpback dolphin. Offshore species, included killer whales, short-finned pilot whale and long-snouted spinner dolphin. Indo-Pacific bottlenose dolphins, long-snouted spinner dolphins, striped dolphins and Risso’s dolphins were recorded through stranding reports. The efforts of the KMMN were disseminated through international meetings (International Whaling Commission, World Marine Mammal Conference), national status reports, outreach and social media. Data has also supported the identification of three IUCN Important Marine Mammal Areas and one Area of Interest in Kenya. Further research is needed to improve estimates of cetacean abundance and distribution, particularly in unstudied coastal areas, and to assess the extent of anthropogenic threats associated with fisheries, coastal and port development, seismic exercises and unregulated tourism. The expansion of the network should benefit from the participation of remote coastal fishing communities, government research agencies, tourism and seismic operations, among others. The KMMN demonstrated the value of dedicated and citizen science data to enhance marine mammal conservation strategies to boost awareness and eco-tourism and to bring the public and science closer together, promoting research and effective conservation efforts.
Social Value and Urban Sustainability in Food Markets

Urban food markets can promote sustainable development through the generation of social value in the spaces where they are located and contribute to sustainability on a global scale. To measure this, indicators are required to evaluate and monitor these markets. Studies in this regard are scarce and often developed according to top-down schemes. This study seeks to remedy this relative deficiency and aims to design specific social sustainability metrics for these organizations from a bottom-up perspective. The Integrated Social Value model is used. This social accounting system is considered appropriate in this study due to the phenomenological approach on which it is based and is applied to a service cooperative located in the Canary Islands. The main contribution of this work is that new social sustainability indicators are obtained and applied to the analysis of an entity, and they are relevant and understandable to stakeholders. This would provide, in future developments, a system of sustainability indicators for similar organizations in Spain.
Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

In nature, animals need to adapt to constant changes in their environment. Learning and memory are cognitive capabilities that allow this to happen. Extinction, the reduction of a certain behavior or learning previously established, refers to a very particular and interesting type of learning that has been the basis of a series of therapies to diminish non-adaptive behaviors. In recent years, the exploration of the cellular and molecular mechanisms underlying this type of learning has received increasing attention. Hebbian plasticity (the activity-dependent modification of the strength or efficacy of synaptic transmission), and homeostatic plasticity (the homeostatic regulation of plasticity) constitute processes intimately associated with memory formation and maintenance. Particularly, long-term depression (LTD) has been proposed as the underlying mechanism of extinction, while the protein phosphatase calcineurin (CaN) has been widely related to both the extinction process and LTD. In this review, we focus on the available evidence that sustains CaN modulation of LTD and its association with extinction. Beyond the classic view, we also examine the interconnection among extinction, Hebbian and homeostatic plasticity, as well as emergent evidence of the participation of kinases and long-term potentiation (LTP) on extinction learning, highlighting the importance of the balance between kinases and phosphatases in the expression of extinction. Finally, we also integrate data that shows the association between extinction and less-studied phenomena, such as synaptic silencing and engram formation that open new perspectives in the field.
Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

Background Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative. Aims To identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD. Methods Three groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4+ T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (Tregs, Foxp3+), CD45RA-Foxp3+ Tregs and subpopulation naive Tregs (CD45RA+Foxp3int), effector Tregs (CD45RA-Foxp3high) and non-suppressive Tregs (CD45RA-Foxp3int) proportions were determined. Results The mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4+ Tregs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA-Foxp3+ Tregs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector Tregs/non suppressive-Tregs, which was significantly higher than in MOGNR. Conclusions Our findings suggest that CD4+ Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of Tregs to rh-MOG in MOGNR, where CD4+ Tregs increased, and in MOGR, where CD45RA-Foxp3+ Tregs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease.
Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer

Background Several oncogenic drivers in non-small cell lung cancer (NSCLC) are considered actionable with available or promising targeted therapies. Although targetable drivers rarely overlap with each other, there were a minority of patients harboring co-occurring actionable oncogenic targets, whose clinical characteristics and prognosis are not yet clear. Methods A total of 3,077 patients with NSCLC who underwent molecular analysis by NGS were included, and their demographic and clinical data were retrospectively collected. Results Our study found that the frequency of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with EGFR-undetermined mutations, the incidence was 1.3% (40/3077); 80% (37/46) harbored both EGFR mutations and other potentially actionable drivers such as MET amplification (21.6%; 8/37) and alterations in ERBB2 including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in ERBB2, KRAS, MET, ALK, and RET were also identified. Additionally, de novo MET/ERBB2 amplification in patients harboring EGFR-mutant NSCLC treated with first-generation EGFR tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p < 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes. Conclusions Approximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.
Recent Advances in Molecular Biology of Human Bocavirus 1 and Its Applications

Human bocavirus 1 (HBoV1) was discovered in human nasopharyngeal specimens in 2005. It is an autonomous human parvovirus and causes acute respiratory tract infections in young children. HBoV1 infects well differentiated or polarized human airway epithelial cells in vitro. Unique among all parvoviruses, HBoV1 expresses 6 non-structural proteins, NS1, NS1-70, NS2, NS3, NS4, and NP1, and a viral non-coding RNA (BocaSR), and three structural proteins VP1, VP2, and VP3. The BocaSR is the first identified RNA polymerase III (Pol III) transcribed viral non-coding RNA in small DNA viruses. It plays an important role in regulation of viral gene expression and a direct role in viral DNA replication in the nucleus. HBoV1 genome replication in the polarized/non-dividing airway epithelial cells depends on the DNA damage and DNA repair pathways and involves error-free Y-family DNA repair DNA polymerase (Pol) η and Pol κ. Importantly, HBoV1 is a helper virus for the replication of dependoparvovirus, adeno-associated virus (AAV), in polarized human airway epithelial cells, and HBoV1 gene products support wild-type AAV replication and recombinant AAV (rAAV) production in human embryonic kidney (HEK) 293 cells. More importantly, the HBoV1 capsid is able to pseudopackage an rAAV2 or rHBoV1 genome, producing the rAAV2/HBoV1 or rHBoV1 vector. The HBoV1 capsid based rAAV vector has a high tropism for human airway epithelia. A deeper understanding in HBoV1 replication and gene expression will help find a better way to produce the rAAV vector and to increase the efficacy of gene delivery using the rAAV2/HBoV1 or rHBoV1 vector, in particular, to human airways. This review summarizes the recent advances in gene expression and replication of HBoV1, as well as the use of HBoV1 as a parvoviral vector for gene delivery.
The Safety and Immunogenicity of the mRNA-BNT162b2 SARS-CoV-2 Vaccine in Hemodialysis Patients

Background Hemodialysis patients are at high risk for severe COVID-19. SARS-CoV-2 vaccination related safety and immunogenicity data in these patients are rare. Methods In this observational study SARS-CoV-2-seronegative hemodialysis patients were vaccinated with two doses of the Pfizer/BioNTech mRNA-BNT162b2 vaccine (COMIRNATY® 30 µg) and followed for 90 days. Local and systemic side effects were assessed at every dialysis session during the first post-vaccination week after the first and second vaccine dose. Immunogenicity was determined four weeks after vaccination by quantifying anti-SARS-CoV-2 spike protein IgG antibodies (LIAISON® SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay) expressed in binding activity units per milliliter (BAU/mL) adapted to the WHO International standard. Results Fifty patients (32% women, 68% men) with a mean (SD) age of 67.6 (14.8) years were included. Mild local reactions occurred in 38% after the first injection, and in 29.2% with mild, in 2.1% with moderate and in 2.1% with severe degree after the second injection. Systemic reactive events occurred less often, with diarrhea (4% mild, 4% moderate) and fatigue (8% mild) being the most frequent ones. After the first injection 42% of the patients developed a positive response using the assay specific cut-off value of 33.8 binding activity units per milliliter (BAU/mL) with a median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentration of 20.0 (11.7, 51.0) BAU/mL. After the second injection the percentage of seropositive patients increased to 97.9% with an anti-SARS-CoV-2 spike IgG concentration of 1075 (290.8, 1735) BAU/mL. Higher age and immunosuppression were associated with lower, calcitriol treatment and prior seroconversion to hepatitis B vaccination with significantly higher antibody concentration. Conclusions The mRNA-BNT162b2 SARS-CoV-2 vaccine appears to be safe and well-tolerated and shows a high immunogenicity in hemodialysis patients.