Miracle-dz/UniFAR-FTUs huggingface dataset:
Connectome Analysis in an Individual with SETD1B-Related Neurodevelopmental Disorder and Epilepsy

This article has supplementary material on the web site: www.jdbp. org. ABSTRACT: Objective: Causative variants in SETD1B, encoding a lysine-specific methyltransferase, have recently been associated with a neurodevelopmental phenotype encompassing intellectual disability, autistic features, pronounced language delay, and epilepsy. It has been noted that long-term and deep phenotype data are needed to further delineate this rare condition. Methods: In this study, we provide an in-depth clinical characterization with long-term follow-up and trio exome sequencing findings to describe one additional individual affected by SETD1B-related disorder. The diagnostic workup was complemented by a functional magnetic resonance imaging (fMRI) study. Results: We report a 24-year-old male individual with an early-onset neurodevelopmental disorder with epilepsy due to the de novo missense variant c.5699A>G, p.(Tyr1900Cys) in SETD1B (NM_015048.1). He exhibited delayed speech development, autism spectrum disorder, and early-onset epilepsy with absence and generalized tonic-clonic seizures. Despite profoundly impaired communication skills, ongoing improvements regarding language production have been noted in adulthood. fMRI findings demonstrate abnormal language activation and resting-state connectivity structure. Conclusion: Our report expands the previously delineated phenotype of SETD1B-related disorder and provides novel insights into underlying disease mechanisms.
Birth Experiences, Breastfeeding, and the Mother-Child Relationship: Evidence from a Large Sample of Mothers

Background It is a priority for public health professionals to improve global breastfeeding rates, which have remained low in Western countries for more than a decade. Few researchers have addressed how maternal perceptions of birth experiences affect infant feeding methods. Furthermore, mixed results have been shown in research regarding breastfeeding and mother-child bonding, and many studies are limited by small sample sizes, representing a need for further investigation. Purpose We aimed to examine the relationship between subjective birth experiences and breastfeeding outcomes, and explored whether breastfeeding affected mother-infant bonding. Methods 3,080 mothers up to three years postpartum completed a cross – sectional survey. Results Mothers who had more positive birth experiences were more likely to report breastfeeding their babies. Moreover, mothers who perceived their birth as more positive were more likely to breastfeed their child for a longer period (over 9 months) than those who had more negative experiences. In line with recent research, breastfeeding behaviours were not associated with reported mother-infant bonding. Conclusions Mothers who reported better birth experiences were most likely to breastfeed, and breastfeed for longer. We find no evidence to suggest that feeding methods are associated with bonding outcomes.
Association between Recurrence or Exacerbation at Time of Disaster and Allergic Symptoms Several Years Later in Schoolchildren with Asthma or Atopic Dermatitis: The ToMMo Child Health Study.

25 Asthma and atopic dermatitis are common among schoolchildren. The Great 26 East Japan Earthquake of 2011 caused serious damage to buildings and 27 infrastructure as well as the total or partial collapse of many hospitals and 28 medical clinics. The aim of this study was to examine the association between 29 recurrence or exacerbation (recurrence/exacerbation) of asthma or atopic 30 dermatitis at the time of disaster and allergic symptoms several years later in 31 schoolchildren. A cross-sectional survey was conducted via a parent- 32 administered questionnaire between 2013 and 2015 in Miyagi Prefecture, 33 northeast Japan. We analysed the data of 2,399 schoolchildren with a 34 diagnosis of asthma and 2,107 with a diagnosis of atopic dermatitis. Among 35 those who had experienced recurrence/exacerbation of their symptoms soon 36 after the disaster, the prevalence of later wheezing and eczema was 71.2% (N 37 = 195) and 81.9% (N = 379), respectively. Recurrence/exacerbation of allergic 38 symptoms just after the disaster was positively associated with wheezing (odds 39 ratio, OR 6.54, 95% confidence interval, 95% CI 4.94–8.67) and eczema (OR 40 8.12, 95% CI 6.25–10.55) several years later. Disasters might have long-term 41 effects on the allergy symptoms of children. It is necessary to prepare for 42 prevention of recurrence/exacerbation, to treat allergic symptoms, and to 43 support children to continue their allergy treatments and daily care when a 44 disaster strikes. 45
Deep SED‐Net with interactive learning for multiple testicular cell types segmentation and cell composition analysis in mouse seminiferous tubules

The development of mouse spermatozoa is a continuous process from spermatogonia, spermatocytes, spermatids to mature sperm. Those developing germ cells (spermatogonia, spermatocyte, and spermatids) together with supporting sertoli cells are all enclosed inside seminiferous tubules of the testis, their identification is key to testis histology and pathology analysis. Automated segmentation of all these cells is a challenging task because of their dynamical changes in different stages. The accurate segmentation of testicular cells is critical in developing computerized spermatogenesis staging. In this paper, we present a novel segmentation model, SED‐Net, which incorporates a squeeze‐and‐excitation (SE) module and a dense unit. The SE module optimizes and obtains features from different channels, whereas the dense unit uses fewer parameters to enhance the use of features. A human‐in‐the‐loop strategy, named deep interactive learning, is developed to achieve better segmentation performance while reducing the workload of manual annotation and time consumption. Across a cohort of 274 seminiferous tubules from stages VI to VIII, the SED‐Net achieved a pixel accuracy of 0.930, a mean pixel accuracy of 0.866, a mean intersection over union of 0.710, and a frequency weighted intersection over union of 0.878, respectively, in terms of four types of testicular cell segmentation. There is no significant difference between manual annotated tubules and segmentation results by SED‐Net in cell composition analysis for tubules from stages VI to VIII. In addition, we performed cell composition analysis on 2346 segmented seminiferous tubule images from 12 segmented testicular section results. The results provided quantitation of cells of various testicular cell types across 12 stages. The rule reflects the cell variation tendency across 12 stages during development of mouse spermatozoa. The method could enable us to not only analyze cell morphology and staging during the development of mouse spermatozoa but also potentially could be applied to the study of reproductive diseases such as infertility.
Examining the role of language competency in genetic testing awareness among adults in the United States

English language competency, as a component of health literacy, is associated with increased awareness and uptake of health‐related genetic testing. The relationship between language competency and genetic testing awareness has not yet been explored in the wider U.S. population yet has significant implications for the practice of genetic counselors and in the promotion of genomic medicine for public health. We analyzed data from the 2017 Health Information National Trends Survey 5 Cycle 1 using weighted logistic regression to model the relationship between self‐reported English competency, genetic testing awareness, and race and explore adjusted odds ratios and average marginal effects for levels of English competency. Compared to respondents with high English competency, the probability of genetic testing awareness was 20 percentage points lower for White participants reporting moderate English competency (p = .029) and 37 percentage points lower for non‐White participants reporting low English competency (p < .001). Future research is needed to understand the mechanisms through which English competency affects awareness and uptake of genetic testing in the United States and to develop strategies to overcome language barriers for the practice of genetic counselors and the implementation of genetics services.
Great ape health watch: Enhancing surveillance for emerging infectious diseases in great apes

Infectious diseases have the potential to extirpate populations of great apes. As the interface between humans and great apes expands, zoonoses pose an increasingly severe threat to already endangered great ape populations. Despite recognition of the threat posed by human pathogens to great apes, health monitoring is only conducted for a small fraction of the world's wild great apes (and mostly those that are habituated) meaning that outbreaks of disease often go unrecognized and therefore unmitigated. This lack of surveillance (even in sites where capacity to conduct surveillance is present) is the most significant limiting factor in our ability to quickly detect and respond to emerging infectious diseases in great apes when they first appear. Accordingly, we must create a surveillance system that links disease outbreaks in humans and great apes in time and space, and enables veterinarians, clinicians, conservation managers, national decision makers, and the global health community to respond quickly to these events. Here, we review existing great ape health surveillance programs in African range habitats to identify successes, gaps, and challenges. We use these findings to argue that standardization of surveillance across sites and geographic scales, that monitors primate health in real‐time and generates early warnings of disease outbreaks, is an efficient, low‐cost step to conserve great ape populations. Such a surveillance program, which we call “Great Ape Health Watch” would lead to long‐term improvements in outbreak preparedness, prevention, detection, and response, while generating valuable data for epidemiological research and sustainable conservation planning. Standardized monitoring of great apes would also make it easier to integrate with human surveillance activities. This approach would empower local stakeholders to link wildlife and human health, allowing for near real‐time, bidirectional surveillance at the great ape‐human interface.
Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients. Description Longitudinal studies of human and murine T cell phenotypes reveal a potential role for type 2 immune polarization in neonatal cardiopulmonary disease. Characterizing cardiopulmonary disease Bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (BPD-PH) cause substantial morbidity and mortality in preterm infants. However, the drivers of BPD and BPD-PH are not well understood. Here, Lao and colleagues characterized immune polarization in blood samples from preterm infants and in a mouse model of BPD and BPD-PH. In both cases, BPD was associated with type 2 immune polarization, characterized by interleukin-4 (IL-4), IL-5, and IL-13, as well as activation of signal transducer and activator of transcription 6 (STAT6). STAT6 deficiency or blockade of type 2 immune mediators partially reversed evidence of alveolar and pulmonary vascular disease in mice, suggesting that this signaling axis could be targeted for preterm infants with BPD.
Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians

ABSTRACT Introduction The unprecedented success of chimeric antigen receptor (CAR)-T-cell therapy in the management of B-cell malignancies comes with a price of specific side effects. Healthy B-cell depletion is an anticipated ‘on-target’ ‘off-tumor’ side effect and can contribute to severe and prolonged hypogammaglobulinemia. Evidence-based guidelines for the use of immunoglobulin replacement therapy (IGRT) for infection prevention are lacking in this population. Areas Covered This article reviews the mechanisms and epidemiology of hypogammaglobulinemia and antibody deficiency, association with infections, and strategies to address these issues in CD19- and BCMA-CAR-T-cell recipients. Expert Opinion CD19 and BCMA CAR-T-cell therapy result in unique immune deficits due to depletion of specific B-lineage cells and may require different infection prevention strategies. Hypogammaglobulinemia before and after CAR-T-cell therapy is frequent, but data on the efficacy and cost-effectiveness of IGRT are lacking. Monthly IGRT should be prioritized for patients with severe or recurrent bacterial infections. IGRT may be more broadly necessary to prevent infections in BCMA-CAR-T-cell recipients and children with severe hypogammaglobulinemia irrespective of infection history. Vaccinations are indicated to augment humoral immunity and can be immunogenic despite cytopenias; re-vaccination(s) may be required. Controlled trials are needed to better understand the role of IGRT and vaccines in this population.
Recombinant expression and biophysical characterization of Mrt4 protein that involved in mRNA turnover and ribosome assembly from Saccharomyces cerevisiae

ABSTRACT The mRNA turnover and ribosome assembly are facilitated by Mrt4 protein from Saccharomyces cerevisiae. In present study, we are reporting the cloning, expression and homogeneous purification of recombinant Mrt4. Mrt4 is a 236-amino-acid-long nuclear protein that plays a very crucial role in mRNA turnover and ribosome assembly during the translation process. mrt4 gene was amplified by polymerase chain reaction and cloned in expression vector pET23a (+) under the bacteriophage T7-inducible promoter and lac operator. Furthermore, protein was purified to homogeneity using immobilized metal affinity chromatography (IMAC) and its homogeneous purification was further validated by immunoblotting with anti-His antibody. The far-UV CD spectra represent that Mrt4 has a typical α helix with characteristic negative minima at 222 and 208 nm. At physiological pH, the fluorescence spectra and CD spectra showed properly folded tertiary and secondary structures of Mrt4, respectively. Saccharomyces Mrt4 protein possesses putative bipartite NLS (nuclear localization signal) at the N-terminal part followed by two well-conserved domains, rRNA-binding domains and translation factor (TF) binding domain. PIPSA analysis evaluates electrostatic interaction properties of proteins and concluded that Mrt4 protein can be used as a fingerprint for classifying Mrt4-like mRNA turnover protein from various species. The availability of an ample amount of protein may help in its biochemical and biophysical characterization, crystallization and identification of new interacting partners of Mrt4.
Transition Metal Dichalcogenide Dimer Nanoantennas for Tailored Light–Matter Interactions

Transition metal dichalcogenides have emerged as promising materials for nanophotonic resonators because of their large refractive index, low absorption within a large portion of the visible spectrum, and compatibility with a wide range of substrates. Herein, we use these properties to fabricate WS2 double-pillar nanoantennas in a variety of geometries enabled by the anisotropy in the crystal structure. Using dark-field spectroscopy, we reveal multiple Mie resonances, to which we couple WSe2 monolayer photoluminescence and achieve Purcell enhancement and an increased fluorescence by factors up to 240 for dimer gaps of 150 nm. We introduce postfabrication atomic force microscope repositioning and rotation of dimer nanoantennas, achieving gaps as small as 10 ± 5 nm, which enables a host of potential applications, including strong Purcell enhancement of single-photon emitters and optical trapping, which we study in simulations. Our findings highlight the advantages of using transition metal dichalcogenides for nanophotonics by exploring applications enabled by their properties.
Lung Transplantation Advanced Prediction Tool: Determining Recipient’s Outcome for a Certain Donor

Background. Many risk-prediction models for lung transplantation are centered on recipient characteristics and do not account for impact of donor and transplant-related factors or only examine short-term outcomes (eg, predicted 1-y survival). We sought to develop a comprehensive model guiding recipient-donor matching. Methods. We identified double lung transplant recipients (≥12 y old) in the United Network for Organ Sharing Registry (2005–2020) to develop a risk scoring tool. Cohort was divided into derivation and validation sets. A total of 42 recipient, donor, and transplant factors were included in the analysis. Lasso method was used for variable selection. Survival was estimated using Cox-proportional hazard models. An interactive web-based tool was developed for clinical use. Results. A derivation cohort (n = 10 660) informed the model with 13-recipient, 4-donor, and 2-transplant variables. Adjusted risk scores were computed for every transplant and grouped into 3 clusters. Model-estimated survival probabilities were similar to the observed in the validation cohort (n = 4464) for all clusters. The mortality increases for medium- and high-risk groups was similar in both derivation and validation cohorts (C statistics for 1-, 5-, and 10-y survival were 0.67, 0.64, and 0.72, respectively). The web-based application estimated 1-, 5-, 10-y survival and half-life for low- (92%, 73%, 52%; 10.5 y), medium- (89%, 62%, 38%; 7.3 y), and high-risk clusters (85%, 52%, 26%; 5.2 y). Conclusions. Advanced methods incorporating machine/deep learning led to a risk scoring model (including recipient, donor, and transplant factors) and a web-based clinical tool providing short- and long-term survival probabilities for recipient-donor matches. This will enable risk-based matching that could improve utilization of and benefit from a limited donor pool.
Monomerization of abscisic acid receptors through CARKs-mediated phosphorylation.

Cytosolic ABA Receptor Kinases (CARKs) play a pivotal role in abscisic acid (ABA)-dependent pathway in response to dehydration, but their regulatory mechanism in ABA signaling remains unexplored. In this study, we showed that CARK4/5 of CARK family physically interacted with ABA receptors (RCARs/PYR1/PYLs), including RCAR3, RCAR11~RCAR14, while CARK2/7/11 only interacted with RCAR11~RCAR14, but not RCAR3. It indicates that the members in CARK family function redundantly and differentially in ABA signaling. RCAR12 can form heterodimer with RCAR3 in vitro and in vivo. Moreover, the members of CARK family can form homo- or heterodimer in a kinase activity dependent manner. ITC (isothermal titration calorimetry) analysis demonstrated that the phosphorylation of RCAR12 by CARK1 enhanced the ABA binding affinity. The phosphor-mimic RCAR12T105D significantly displayed ABA-induced inhibition of the phosphatase ABI1 (ABA insensitive 1) activity, leading to up-regulation of ABA-responsive genes RD29A and RD29B in cark157:RCAR12T105D transgenic plants, which exhibited ABA hypersensitive phenotype. The transcription factor ABI5 (ABA insensitive 5) activates the transcriptions of CARK1 and CARK3 by binding to ABRE elements of their promoters. Collectively, our data imply that the dimeric CARKs phosphorylate homo- or heterodimer ABA receptors, leading to monomerization for triggering ABA responses in Arabidopsis.
Enzyme Trafficking and Co-Clustering Precede and Accurately Predict Human Breast Cancer Recurrences: An Interdisciplinary Review.

Although great effort has been expended to understand cancer's origins, less attention has been given to the primary cause of cancer deaths - cancer recurrences and their sequelae. This interdisciplinary review addresses mechanistic features of aggressive cancer by studying metabolic enzyme patterns within ductal carcinoma in situ (DCIS) of the breast lesions. DCIS lesions from patients who did or did not experience a breast cancer recurrence were compared. Several proteins, including phospho-Ser226-glucose transporter type 1, phosphofructokinase type L and phosphofructokinase/fructose 2,6-bisphosphatase type 4 are found in nucleoli of ductal epithelial cells in samples from patients who will not subsequently recur, but traffic to the cell periphery in samples from patients who will experience a cancer recurrence. Large co-clusters of enzymes near plasmalemmata will enhance product formation because enzyme concentrations in clusters are very high while solvent molecules and solutes diffuse through small channels. These structural changes will accelerate aerobic glycolysis. Agglomerations of pentose phosphate pathway and glutathione synthesis enzymes enhance GSH formation. As aggressive cancer lesions are incomplete at early stages, they may be unrecognizable. We have found that machine learning provides superior analyses of tissue images and may be used to identify biomarker patterns associated with recurrent and non-recurrent patients with high accuracy. This suggests a new prognostic test to predict DCIS patients who are likely to recur and those who are at low risk for recurrence. Mechanistic interpretations provide a deeper understanding of anti-cancer drug action and suggest that aggressive metastatic cancer cells are sensitive to reductive chemotherapy.