Miracle-dz/UniFAR-FTUs huggingface dataset:
SLC44A2 Frequency, a New TaqMan Real-Time Polymerase Chain Reaction Method for HNA-3A/3B Genotyping, and a New Application of Droplet Digital PCR

Background: Human neutrophil antigen-3A (HNA-3A) and human neutrophil antigen-3B (HNA-3B) are generated by a single-nucleotide polymorphism (rs2288904, c.461G > A) in exon 7 of the choline transporter-like protein-2 gene (CTL2, also known as SLC44A2). Antibodies to HNA-3 can be generated following blood transfusion or other factors resulting in exposure to HNA-3 antigens. These antibodies can cause transfusion-related acute lung injury (TRALI) or neonatal alloimmune neutropenia (NAIN). This study describes a sensitive and specific TaqMan real-time polymerase chain reaction (PCR) method to screen for the HNA-3 genotype using specific primers and probes designed to detect allelic polymorphisms. Considering the high sensitivity and accuracy of droplet digital PCR (ddPCR) in the identification of the rare SLC44A2*2 allele, we used this technique to identify blood donors with the rare HNA-3B antigen and calculate the allele frequency of SLC44A2 in mixed populations with different proportions. Methods: DNA samples purified from 208 donors in northwest China were subjected to TaqMan real-time PCR to detect allelic polymorphisms in SLC44A2. The results were confirmed by Sanger sequencing. The rare HNA-3B antigen was detected by ddPCR. SLC44A2 frequency was determined by two-channel ddPCR. Results: The genotypes of all DNA samples were detected by the TaqMan real-time PCR using specific probes for HNA-3, and the results were consistent with the Sanger sequencing results in respect to the HNA-3A and HNA-3B polymorphisms. The allele frequencies of SLC44A2*1 and SLC44A2*2 in the 208 donors in northwest China were 64.9% (95% confidence interval [CI], 59%–70.8%) and 35.1% (95% CI, 29.2%–41%), respectively. The ratio of SLC44A2*2 alleles was accurately detected in all blood pools by ddPCR but not by TaqMan real-time PCR. This allowed for the SLC44A2 frequency in the population to be accurately inferred. Conclusion: This new method of detecting SLC44A2 alleles was highly sensitive and specific, as confirmed by Sanger sequencing. ddPCR using the designed probes resulted in successful detection of the rare HNA-3B antigen. Furthermore, we successfully detected the rare HNA-3B antigen and inferred the SLC44A2 frequency by ddPCR using the probes that we designed.
Citizen Coherence and Cultivated Cleanliness: Using Technology-Induced Social Norms to Strengthen Sustainable Household Bonds

Social identity and social capital are critical to human well-being and sustainable development. However, existing research on sustainable behavior typically treats these factors merely as taken-for-granted preconditions to environmental protection. This paper argues that they can also be direct outcomes of environment-oriented efforts, thus becoming drivers of sustainable societies. As part of a larger research project on household recycling and waste behavior, the authors assess and compare perceived social identity and social capital of residents in a multi-family residential dwelling in Sweden before (N = 66) and after (N = 18) exposure to a social norm-based intervention delivered through a smartphone app. Reported levels of social identity and social capital were higher after (vs. before) the intervention, both compared to participants' own previous measurement and a control group. Together, the current research offers a novel perspective on technology-enabled social norms. Specifically, such norms may not only create sustainable responses immediately, but may also play a pivotal role in shaping more sustainable communities in the long run. Future studies are needed to elucidate the specific psychological mechanisms driving the observed effects and shed further light on whether, when, and why social norms may foster sustainable responses with a clear social connotation.
Risk Factors of Readmission to Pediatric Intensive Care Unit Within 1 Year: A Case-Control Study

Background Research on pediatric intensive care unit (PICU) readmission is lacking in China. This study was conducted to describe the risk factors associated with PICU readmission within 1 year after PICU discharge. Methods This retrospective case-control study included patients aged from 1 month to 16 years who were discharged between January 2018 and May 2020. The case group included readmitted patients with two or more PICU admissions within 1 year during the study period. The control group included survivors with only one PICU admission during the same study period, and the controls were matched on age and sex. Demographic and clinical variables were collected from the electronic administrative database. Risk factors were analyzed by univariate and multivariate analyses. Results From January 2018 to May 2020, 2,529 patients were discharged from the PICU, and 103 (4.07%) were readmitted within 1 year. In the univariate analysis, PICU readmission within 1 year was associated with lower weight, the presence of chronic conditions, a higher StrongKids score on admission, length of PICU stay of more than 2 weeks, the presence of dysfunction at discharge, sedation medications use, vasopressor use, and invasive mechanical ventilation in the first PICU stay. Patients had a higher StrongKids score as a surrogate for increased risk of malnutrition. In the multivariate analysis, the factors most significantly associated with PICU readmission within 1 year were the presence of chronic conditions, a higher StrongKids score on admission, and length of PICU stay of more than 2 weeks in the first PICU stay. In the subgroup analysis, compared with the control group, the factors most significantly associated with readmission within 48 h of discharge were the presence of chronic conditions, a higher StrongKids score on admission, and vasopressor use during the first PICU stay. The mortality rate was 8.74% (9/103) in patients with PICU readmission. The overall PICU mortality rate was 7.39% (201/2,721) during the study period. Conclusions Patients with chronic conditions, a higher StrongKids score on admission, and length of PICU stay of more than 2 weeks were at much higher risk for PICU readmission within 1 year. Patients with vasopressor use during the first PICU hospitalization were more likely to be readmitted within 48 h of discharge.
Fortunella venosa (Champ. ex Benth.) C. C. Huang and F. hindsii (Champ. ex Benth.) Swingle as Independent Species: Evidence From Morphology and Molecular Systematics and Taxonomic Revision of Fortunella (Rutaceae)

Recently, the systematic status of Fortunella Swingle and its taxonomy has attracted much attention. Flora of China incorporates Fortunella into Citrus Linn. and treats all species of the traditional Fortunella as one species, namely Citrus japonica (Thunb.) Swingle. Furthermore, F. venosa (Champ. ex Benth.) C. C. Huang and F. hindsii (Champ. ex Benth.) Swingle are currently considered as synonyms of C. japonica. In this paper, morphological, palynological, and phylogenetic analyses were used to systematically explore the taxonomic status of traditional Fortunella. The key morphological features that differed among the Fortunella species were the leaf and the petiole hence could be key in its taxonomic classification of the species. Additionally, pollen morphological analysis based on the pollen size, germination grooves, polar, and equatorial axes also supported the separation of the species. The results of the phylogenetic analysis showed that each of the three species clustered separately, hence strongly supporting the conclusion of independent species. In addition, the phylogenetic analysis showed that the two genera clustered closely together hence our results support the incorporation of Fortunella into Citrus. Based on the above, this article has revised the classification of the traditional Fortunella and determined that this genus has three species, namely; F. venosa, F. hindsii, and F. japonica. F. venosa and F. hindsii are placed in the Citrus as separate species, and their species names still use the previous specific epithet. The revised scientific names of the new combinations of F. venosa and F. hindsii are as follows: Citrus venosa (Champ. ex Benth.) K. M. Liu, X. Z. Cai, and G. W. Hu, comb. nov. and Citrus hindsii (Champ. ex Benth.) K. M. Liu, G. W. Hu, and X. Z. Cai, comb. nov. F. venosa is the original species of Fortunella, F. venosa and F. hindsii are both listed as the second-class key protected wild plants in China. Therefore, the establishment of the taxonomic status of F. venosa and F. hindsii not only deepens our understanding, importance, and the complexity of the systematic classification of Fortunella, but is also significant for global biodiversity conservation, genetic resources for breeding purposes, and population genetics.
Mental Health, Burnout, and Job Stressors Among Healthcare Workers During the COVID-19 Pandemic in Iran: A Cross-Sectional Survey

Introduction The COVID-19 pandemic has caused increasing levels of mental health problems such as anxiety and depression among doctors, nurses and other healthcare workers in hospitals or health centers. The main objective of this study was to assess the mental health, job stressors, and burnout among healthcare workers in Iran. Materials and Methods A cross-sectional study was performed in the primary healthcare centers and hospitals affiliated with six of the medical universities in Iran. The selection of participants was done using multi-center convenient sampling. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Copenhagen Burnout Inventory were used for gathering data through an online platform. Data related to job stressors were obtained using a validated checklist. Data analysis was performed using Chi-square and multiple regression tests and the phi coefficient. Results The results of our study showed that 53% of the healthcare workers of the hospitals and primary healthcare centers enrolled in our study either had generalized anxiety disorder or major depressive disorder or both disorders. Moderate and high levels of burnout were seen among 48.9% of the study participants. The prevalence of mental disorders and burnout were significantly higher among the female healthcare workers compared to the male (p = 0.0001) and a higher rate of mental disorder and burnout was also seen among healthcare workers of hospitals compared to those working in primary healthcare centers (p = 0.024). “Worry about children and old members of family,” “family worries for my health condition” and “lack of specific effective treatment for COVID-19” were found to be predictive of mental disorder and burnout. The most prevalent job stressor among the total sample was “low payment or income during the COVID-19 period”. Conclusion The results of our study revealed high psychological distress and burnout among healthcare workers of the hospitals during the fourth peak of the COVID-19 pandemic in Iran. This study highlights the need for health officials to pay attention to the job stressors of healthcare workers and obliges them to perform effective interventions to address their needs and concerns.
The Effects of Leader Emotional Intelligence, Leadership Styles, Organizational Commitment, and Trust on Job Performance in the Real Estate Brokerage Industry

This study examines the effects of leader emotional intelligence, leadership styles (transformational and transactional), organizational commitment, and trust on job performance. A questionnaire was administered to the participants, who were real estate brokers in Kaohsiung City. Of the 980 questionnaires administered, 348 valid responses were received, indicating an effective response rate of 35.5%. Structural equation modeling was used for the analysis. The results show that leader emotional intelligence has a significant and positive effect on trust in supervisors, and transformational leadership and trust within a team have significant and positive effects on job performance. In addition, organizational commitment has a significant and positive effect on job performance. Trust within a team mediates the significant and positive effect of leader emotional intelligence on job performance. Although transactional leadership has no direct, positive, and significant effects on employee job performance, trust in the workplace shaped by a leader’s leadership style will empower a team’s spirit and boost their morale, thereby indirectly affecting their job performance in a positive manner.
Regularized Functional Connectivity in Schizophrenia

Regularization may be used as an alternative to dimensionality reduction when the number of variables in a model is much larger than the number of available observations. In a recent study from our group regularized regression was employed to quantify brain functional connectivity in a sample of healthy controls using a brain parcellation and resting state fMRI images. Here regularization is applied to evaluate resting state connectivity abnormalities at the voxel level in a sample of patients with schizophrenia. Specifically, ridge regression is implemented with different degrees of regularization. Results are compared to those delivered by the weighted global brain connectivity method (GBC), which is based on averaged bivariate correlations and from the non-redundant connectivity method (NRC), a dimensionality reduction approach that applies supervised principal component regressions. Ridge regression is able to detect a larger set of abnormally connected regions than both GBC and NRC methods, including schizophrenia related connectivity reductions in fronto-medial, somatosensory and occipital structures. Due to its multivariate nature, the proposed method is much more sensitive to group abnormalities than the GBC, but it also outperforms the NRC, which is multivariate too. Voxel based regularized regression is a simple and sensitive alternative for quantifying brain functional connectivity.
Circulating Tumor DNA in Pediatric Cancer

The measurement of circulating tumor DNA (ctDNA) has gained increasing prominence as a minimally invasive tool for the detection of cancer-specific markers in plasma. In adult cancers, ctDNA detection has shown value for disease-monitoring applications including tumor mutation profiling, risk stratification, relapse prediction, and treatment response evaluation. To date, there are ctDNA tests used as companion diagnostics for adult cancers and it is not understood why the same cannot be said about childhood cancer, despite the marked differences between adult and pediatric oncology. In this review, we discuss the current understanding of ctDNA as a disease monitoring biomarker in the context of pediatric malignancies, including the challenges associated with ctDNA detection in liquid biopsies. The data and conclusions from pediatric cancer studies of ctDNA are summarized, highlighting treatment response, disease monitoring and the detection of subclonal disease as applications of ctDNA. While the data from retrospective studies highlight the potential of ctDNA, large clinical trials are required for ctDNA analysis for routine clinical use in pediatric cancers. We outline the requirements for the standardization of ctDNA detection in pediatric cancers, including sample handling and reproducibility of results. With better understanding of the advantages and limitations of ctDNA and improved detection methods, ctDNA analysis may become the standard of care for patient monitoring in childhood cancers.
Age, Sex, and Race/Ethnicity in Clinical Outcomes Among Patients Hospitalized With COVID-19, 2020

The COVID-19 pandemic revealed the disproportionate risk of poor clinical outcomes among population subgroups. The study investigates length of stay (LOS), intensive care unit (ICU) admission, and in-hospital death across age, sex, and race among patients hospitalized with COVID-19. A pooled cross-sectional study analyzed hospital discharge data of state-licensed hospitals in Texas from April to December 2020. Of 98,879 patients, males accounted for 52.3%. The age distribution was 31.9% for the 65–79 age group, 29.6% for those aged 50–64, and 16.3% for those older than 79. Whites constituted the largest proportion (42.6%), followed by Hispanics (36.2%) and Blacks (13.1%). Higher in-hospital death rates were found among patients aged 80 and over (Adjusted Risk Ratio (aRR) 1.12, 95%CI 1.11–1.13) and patients aged 65–79 (aRR 1.08, 95%CI 1.07–1.09) compared to patients aged 19 and below. Hispanics (aRR 1.03, 95%CI 1.02–1.03) and other minorities (aRR 1.02, 95%CI 1.02–1.03) exhibited higher in-hospital death rates than whites, and these patients also had longer LOS and higher ICU admission rates. Patients aged 65–79, 50–64, and 80 and over all had longer hospital stays and higher ICU admission rates. Males experienced poor health outcomes in all assessed outcomes. Findings showed that disparities in clinical outcomes among population subgroups existed and remained throughout 2020. While the nation has to continue practicing public health measures to minimize the harm caused by the novel virus, serious consideration must be given to improving the health of marginalized populations during and beyond the pandemic.
The Effects of Interacting With a Paro Robot After a Stressor in Patients With Psoriasis: A Randomised Pilot Study

Objective Stress can play a role in the onset and exacerbation of psoriasis. Psychological interventions to reduce stress have been shown to improve psychological and psoriasis-related outcomes. This pilot randomised study investigated the feasibility of a brief interaction with a Paro robot to reduce stress and improve skin parameters, after a stressor, in patients with psoriasis. Methods Around 25 patients with psoriasis participated in a laboratory stress task, before being randomised to either interact with a Paro robot or sit quietly (control condition) for 30 min. Raman spectroscopy and trans-epidermal water loss were measured at baseline, after the stressor and after the intervention as indexes of acute skin changes. Psychological variables, including self-reported stress and affect, were also measured at the three time-points. Results No statistically significant differences between the two conditions were found for any of the outcomes measured. However, effect sizes suggest significance could be possible with a larger sample size. Changes in the psychological and Raman spectroscopy outcomes across the experimental session were found, indicating the feasibility of the procedures. Conclusion This pilot study showed that a brief interaction with a Paro robot was a feasible intervention for patients with psoriasis, but future trials should broaden the inclusion criteria to try to increase recruitment rates. Studying people who are highly stressed, depressed or who are stress-responders may increase the power of the intervention to show effects using a longer-term intervention.
Alcohol Impairs Immunometabolism and Promotes Naïve T Cell Differentiation to Pro-Inflammatory Th1 CD4+ T Cells

CD4+ T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4+ subsets rely on glycolysis, while immunosuppressive Treg cells require functional mitochondria for their differentiation and function. Previous pre-clinical studies have shown that ethanol (EtOH) administration increases pro-inflammatory CD4+ T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4+ T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4+ immunometabolism, and whether this affects CD4+ T cell differentiation. Naïve human CD4+ T cells were plated on anti-CD3 coated plates with soluble anti-CD28, and differentiated with IL-12 in the presence of ethanol (0 and 50 mM) for 3 days. Both Tbet-expressing (Th1) and FOXP3-expressing (Treg) CD4+ T cells increased after differentiation. Ethanol dysregulated CD4+ T cell differentiation by increasing Th1 and decreasing Treg CD4+ T cell subsets. Ethanol increased glycolysis and impaired oxidative phosphorylation in differentiated CD4+ T cells. Moreover, the glycolytic inhibitor 2-deoxyglucose (2-DG) prevented the ethanol-mediated increase in Tbet-expressing CD4+ T cells but did not attenuate the decrease in FOXP3 expression in differentiated CD4+ T cells. Ethanol increased Treg mitochondrial volume and altered expression of genes implicated in mitophagy and autophagosome formation (PINK1 and ATG7). These results suggest that ethanol impairs CD4+ T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4+ T cell differentiation to a pro-inflammatory phenotype.
Macrophage Cx43 Is Necessary for Fibroblast Cytosolic Calcium and Lung Fibrosis After Injury

Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown to mediate efflux of ATP by macrophages, with resulting cytosolic calcium responses in adjacent cells. Here we report that lung macrophages with deletion of connexin 43 (MacΔCx43) had decreased ATP efflux into the extracellular space and induced a decreased cytosolic calcium response in co-cultured fibroblasts compared to WT macrophages. Furthermore, MacΔCx43 mice had decreased lung fibrosis after bleomycin-induced injury. Interrogating single cell data for human and mouse, we found that P2rx4 was the most highly expressed ATP receptor and calcium channel in lung fibroblasts and that its expression was increased in the setting of fibrosis. Fibroblast-specific deletion of P2rx4 in mice decreased lung fibrosis and collagen expression in lung fibroblasts in the bleomycin model. Taken together, these studies reveal a Cx43-dependent profibrotic effect of lung macrophages and support development of fibroblast P2rx4 as a therapeutic target for lung fibrosis.
Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans

Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.