Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children. Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival. Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation. Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.
Barriers, facilitators and motivators of electronic community health information system use among health workers in Ethiopia

Background The electronic community health information system (eCHIS) has been implemented in Ethiopia to support health services delivered by community health workers. Despite the many benefits of digitizing community health information systems, the implementation of the eCHIS is challenged by many barriers resulting in low uptake. This study assessed the barriers, facilitators, and motivators of eCHIS use among health workers with focus on health extension workers (HEWs) in Ethiopia. Methods Phenomenological approach was used to assess the barriers, facilitators and motivators of eCHIS use in Amhara, Harari, Oromia, Sidama, South West Ethiopia and Southern Nation Nationalities and People's regions of Ethiopia. Data were collected from 15–29 May 2022. A total of 54 face-to-face in-depth interviews were conducted among HEWs, HEW supervisors, health information technicians and managers. The interviews were audiotaped using Open Data Kit, transcribed verbatim and translated into English. OpenCode 4.03 software was used for coding and categorizing the data. Thematic analysis was used to analyze the data. Results The HEWs and other eCHIS users reported lack of infrastructure and resources; poor quality of training, follow-up, and supervision; parallel recording using the manual and electronic system; and HEWs' workload as barriers hindering eCHIS use. Data quality, retrievability, and traceability; tablet portability; encouragement from supervisors; and positive image in the community resulting from HEWs using tablets in their routine activities were the main facilitators of eCHIS use. Conclusion The study identified various barriers that adversely affect the use of eCHIS. An integrated and coordinated approach to eCHIS implementation that encompasses removing the barriers, and reinforcing facilitators is required.
Editorial: Brain serotonergic system

COPYRIGHT © 2023 Mouradian and Cooper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Brain serotonergic system
Genome-wide association identifies key loci controlling blackberry postharvest quality

Introduction Blackberry (Rubus subgenus Rubus) is a soft-fruited specialty crop that often suffers economic losses due to degradation in the shipping process. During transportation, fresh-market blackberries commonly leak, decay, deform, or become discolored through a disorder known as red drupelet reversion (RDR). Over the past 50 years, breeding programs have achieved better fruit firmness and postharvest quality through traditional selection methods, but the underlying genetic variation is poorly understood. Methods We conducted a genome-wide association of fruit firmness and RDR measured in 300 tetraploid fresh-market blackberry genotypes from 2019-2021 with 65,995 SNPs concentrated in genic regions of the R. argutus reference genome. Results Fruit firmness and RDR had entry-mean broad sense heritabilities of 68% and 34%, respectively. Three variants on homologs of polygalacturonase (PG), pectin methylesterase (PME), and glucan endo-1,3-β-glucosidase explained 27% of variance in fruit firmness and were located on chromosomes Ra06, Ra01, and Ra02, respectively. Another PG homolog variant on chromosome Ra02 explained 8% of variance in RDR, but it was in strong linkage disequilibrium with 212 other RDR-associated SNPs across a 23 Mb region. A large cluster of six PME and PME inhibitor homologs was located near the fruit firmness quantitative trait locus (QTL) identified on Ra01. RDR and fruit firmness shared a significant negative correlation (r = -0.28) and overlapping QTL regions on Ra02 in this study. Discussion Our work demonstrates the complex nature of postharvest quality traits in blackberry, which are likely controlled by many small-effect QTLs. This study is the first large-scale effort to map the genetic control of quantitative traits in blackberry and provides a strong framework for future GWAS. Phenotypic and genotypic datasets may be used to train genomic selection models that target the improvement of postharvest quality.
Novel mechanisms for the synthesis of important secondary metabolites in Ginkgo biloba seed revealed by multi-omics data

Although the detailed biosynthetic mechanism is still unclear, the unique secondary metabolites of Ginkgo biloba, including ginkgolic acids (GAs) and terpene trilactones, have attracted increasing attention for their potent medicinal, physiological and biochemical properties. In particular, GAs have shown great potential in the fields of antibacterial and insecticidal activities, making it urgent to elucidate their biosynthetic mechanism. In this study, we systematically revealed the landscape of metabolic-transcriptional regulation across continuous growth stages of G. biloba seeds (GBS) based on multi-omics mining and experimental verification, and successfully identified all major types of GAs and terpene trilactones along with more than a thousand kinds of other metabolites. The phenological changes and the essential gene families associated with these unique metabolites were analyzed in detail, and several potential regulatory factors were successfully identified based on co-expression association analysis. In addition, we unexpectedly found the close relationship between large introns and the biosynthesis of these secondary metabolites. These genes with large introns related to the synthesis of secondary metabolites showed higher gene expression and expression stability in different tissues or growth stages. Our results may provide a new perspective for the study of the regulatory mechanism of these unique secondary metabolites in GBS.
A multiethnic genome-wide analysis of 19,420 individuals identifies novel loci associated with axial length and shared genetic influences with refractive error and myopia

Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci. Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample. Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = −0.83; SE, 0.04; p = 1.95 × 10−89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10−55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04). Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk.
Decreased inpatient psychiatric admissions with telepsychiatry use during the COVID-19 pandemic

Objective This study examines the quality of care provided through telepsychiatry by comparing psychiatric hospitalization rates among patients receiving in-person psychiatric care prior to the COVID-19 pandemic with rates among patients receiving virtual psychiatric care during the COVID-19 pandemic. Methods Mental health-related hospitalization rates among patients enrolled in a large academic hospital’s outpatient psychiatry programs between March 1, 2018 and February 28, 2022 were retrospectively analyzed. Four time periods were created, spanning March 1 to February 28 of the following year. Demographic and clinical data were collected from the electronic health record, and descriptive statistics were calculated. Change in hospitalization rate between time periods was evaluated using McNemar’s test. Results In the 2018 time period, 7.38% of all enrolled patients were hospitalized, compared to 7.70% hospitalized in the 2019 period, 5.74% in the 2020 period, and 5.38% in the 2021 period. Patients enrolled in both the 2018 and the 2019 periods saw no difference in hospitalization rate between the 2 years (2.93% in 2018, 2.83% in 2019; p = 0.830); patients enrolled in both 2019 and 2020 saw significantly lower hospitalization rates in 2020 (5.47% in 2019, 4.58% in 2020; p = 0.022); and patients enrolled in both 2020 and 2021 saw no difference (3.34% in 2020, 3.23% in 2021; p = 0.777). Conclusion Psychiatric hospitalization rates significantly decreased between the 2019 and the 2020 periods, suggesting a decrease in admissions associated with adoption of telepsychiatry. Future research should differentiate the roles played by telepsychiatry and COVID-19-related factors in reducing hospitalization rates during the pandemic.
Solvated interaction energy: from small-molecule to antibody drug design

Scoring functions are ubiquitous in structure-based drug design as an aid to predicting binding modes and estimating binding affinities. Ideally, a scoring function should be broadly applicable, obviating the need to recalibrate and refit its parameters for every new target and class of ligands. Traditionally, drugs have been small molecules, but in recent years biologics, particularly antibodies, have become an increasingly important if not dominant class of therapeutics. This makes the goal of having a transferable scoring function, i.e., one that spans the range of small-molecule to protein ligands, even more challenging. One such broadly applicable scoring function is the Solvated Interaction Energy (SIE), which has been developed and applied in our lab for the last 15 years, leading to several important applications. This physics-based method arose from efforts to understand the physics governing binding events, with particular care given to the role played by solvation. SIE has been used by us and many independent labs worldwide for virtual screening and discovery of novel small-molecule binders or optimization of known drugs. Moreover, without any retraining, it is found to be transferrable to predictions of antibody-antigen relative binding affinities and as accurate as functions trained on protein-protein binding affinities. SIE has been incorporated in conjunction with other scoring functions into ADAPT (Assisted Design of Antibody and Protein Therapeutics), our platform for affinity modulation of antibodies. Application of ADAPT resulted in the optimization of several antibodies with 10-to-100-fold improvements in binding affinity. Further applications included broadening the specificity of a single-domain antibody to be cross-reactive with virus variants of both SARS-CoV-1 and SARS-CoV-2, and the design of safer antibodies by engineering of a pH switch to make them more selective towards acidic tumors while sparing normal tissues at physiological pH.
A COVID-19 isolation facility for people experiencing homelessness in Berlin, Germany: a retrospective patient record study

Introduction People experiencing homelessness (PEH) are disproportionately affected by the COVID-19 pandemic. For many PEH it is impossible to isolate due to the lack of permanent housing. Therefore, an isolation facility for SARS-CoV-2 positive PEH was opened in Berlin, Germany, in May 2020, offering medical care, opioid and alcohol substitution therapy and social services. This study aimed to assess the needs of the admitted patients and requirements of the facility. Materials and methods This was a retrospective patient record study carried out in the isolation facility for PEH in Berlin, from December 2020 to June 2021. We extracted demographic and clinical data including observed psychological distress from records of all PEH tested positive for SARS-CoV-2 by RT-PCR. Data on duration and completion of isolation and the use of the facilities’ services were analyzed. The association of patients’ characteristics with the completion of isolation was assessed by Student’s t-test or Fisher’s exact test. Results A total of 139 patients were included in the study (89% male, mean age 45 years, 41% with comorbidities, 41% non-German speakers). 81% of patients were symptomatic (median duration 5 days, range 1–26). The median length of stay at the facility was 14 days (range 2–41). Among the patients, 80% had non-COVID-19 related medical conditions, 46% required alcohol substitution and 17% opioid substitution therapy. Three patients were hospitalized due to low oxygen saturation. No deaths occurred. Psychological distress was observed in 20%, and social support services were used by 65% of PEH. The majority (82%) completed the required isolation period according to the health authority’s order. We did not observe a statistically significant association between completion of the isolation period and sociodemographic characteristics. Conclusion The specialized facility allowed PEH a high compliance with completion of the isolation period. Medical care, opioid and alcohol substitution, psychological care, language mediation and social support are essential components to address the specific needs of PEH. Besides contributing to infection prevention and control, isolation facilities may allow better access to medical care for SARS-CoV-2 infected PEH with possibly positive effects on the disease course.
The effect of reading literary fiction on the theory of mind skills among persons with schizophrenia and normal controls

Introduction Recent research data suggest that theory of mind (ToM) skills may improve after reading literary fiction. However, beside this short term favorable effect, regular long-term reading of literary fiction may also support ToM development or may improve ToM performance. The presence of impaired ToM abilities is well-documented in schizophrenia; however, the role of reading in these deficits is unknown. In the present study our aim was to assess the effect of prior reading experiences on theory of mind performance in patients with schizophrenia, and in healthy controls. Materials and methods ToM assessment was done with the Short Story Task, which is based on the interpretation of a Hemingway short story. After reading the short story, questions were asked in an interview format regarding comprehension, explicit and implicit ToM skills, then comparative analysis of schizophrenia patients was performed (n = 47) and matched to a normal control (n = 48) group concerning deficits of ToM abilities. Participants were also stratified according to their prior reading experiences. Results Previous reading experience was associated with better comprehension and explicit ToM performance both in patients with schizophrenia, and in healthy controls. However, the explicit ToM performance of patients with prior reading was still weaker compared to healthy controls with reading experiences. Path model analysis revealed that reading had a direct positive effect on ToM, and an indirect effect through improving comprehension. Conclusions Prior reading experience is associated with better ToM performance not just in healthy controls but also in patients living with schizophrenia. Previous reading experience also improves comprehension, which in turn has a favorable impact on ToM. Our results support the idea that literary fiction reading may have a therapeutic potential in the rehabilitation of schizophrenia.
The oral bacteriomes of patients with allergic rhinitis and asthma differ from that of healthy controls

Allergic rhinitis and asthma are two of the most common chronic respiratory diseases in developed countries and have become a major public health concern. Substantial evidence has suggested a strong link between respiratory allergy and upper airway dysbacteriosis, but the role of the oral bacteriota is still poorly understood. Here we used 16S rRNA massive parallel sequencing to characterize the oral bacteriome of 344 individuals with allergic rhinitis (AR), allergic rhinitis with asthma (ARAS), asthma (AS) and healthy controls (CT). Four of the most abundant (>2%) phyla (Actinobacteriota, Firmicutes, Fusobacteriota, and Proteobacteria) and 10 of the dominant genera (Actinomyces, Fusobacterium, Gemella, Haemophilus, Leptotrichia, Neisseria, Porphyromonas, Prevotella, Streptococcus, and Veillonella) in the oral cavity differed significantly (p ≤ 0.03) between AR, ARAS or AS and CT groups. The oral bacteriome of ARAS patients showed the highest intra-group diversity, while CT showed the lowest. All alpha-diversity indices of microbial richness and evenness varied significantly (p ≤ 0.022) in ARAS vs. CT and ARAS vs. AR, but they were not significantly different in AR vs. CT. All beta-diversity indices of microbial structure (Unifrac, Bray-Curtis, and Jaccard distances) differed significantly (p ≤ 0.049) between each respiratory disease group and controls. Bacteriomes of AR and ARAS patients showed 15 and 28 upregulated metabolic pathways (PICRUSt2) mainly related to degradation and biosynthesis (p < 0.05). A network analysis (SPIEC-EASI) of AR and ARAS bacteriomes depicted simpler webs of interactions among their members than those observed in the bacteriome of CT, suggesting chronic respiratory allergic diseases may disrupt bacterial connectivity in the oral cavity. This study, therefore, expands our understanding of the relationships between the oral bacteriome and allergy-related conditions. It demonstrates for the first time that the mouth harbors distinct bacteriotas during health and allergic rhinitis (with and without comorbid asthma) and identifies potential taxonomic and functional microbial biomarkers of chronic airway disease.
The ‘Matthew effect’ in Chinese kindergarten principals’ professional development: a mixed-methods study

Principals play a leading role in kindergarten quality improvement, and thus their needs for professional development (PD) should be understood and met. This national study adopted a mixed-methods approach to survey 3,065 kindergarten principals in China and interviewed 16 of them. First, the latent profile analysis of survey data yielded three profiles of PD needs: (1) low (7.5%), (2) medium (22.2%), and (3) high profiles (70.3%), indicating 70.3% of Chinese principals need PD badly. The high-profile group features ‘inexperienced principals working at newly established private kindergartens’, the most disadvantaged among the three groups. Second, ANOVA tests revealed significant rural–urban and public-private differences in Chinese principals’ professional backgrounds and PD needs. In particular, significant public-private and rural–urban differences were observed in the principals’ ‘current degree’ (Fs > 63, ps < 0.001) and ‘desired degree’ (Fs > 39, ps < 0.001). The rural principals aspired more than their urban counterparts to obtain ‘a higher degree” or ‘a certificate’ (ps < 0.05). Third, the follow-up interviews confirmed remarkable rural–urban and public-private gaps in PD needs, indicating a noticeable ‘Matthew effect’: the poor got less, whereas the rich got more. The implications for future PD policy and program development are discussed.