Miracle-dz/UniFAR-FTUs huggingface dataset:
TCP and MADS-Box Transcription Factor Networks Regulate Heteromorphic Flower Type Identity in Gerbera hybrida.

The large sunflower family, Asteraceae, is characterized by compressed, flower-like inflorescences that may bear phenotypically distinct flower types. The CYCLOIDEA (CYC)/TEOSINTE BRANCHED1-like transcription factors (TFs) belonging to the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) protein family are known to regulate bilateral symmetry in single flowers. In Asteraceae, they function at the inflorescence level, and were recruited to define differential flower type identities. Here, we identified upstream regulators of GhCYC3, a gene that specifies ray flower identity at the flower head margin in the model plant Gerbera hybrida. We discovered a previously unidentified expression domain and functional role for the paralogous CINCINNATA-like TCP proteins. They function upstream of GhCYC3 and affect the developmental delay of marginal ray primordia during their early ontogeny. At the level of single flowers, the Asteraceae CYC genes show a unique function in regulating the elongation of showy ventral ligules that play a major role in pollinator attraction. We discovered that during ligule development, the E class MADS-box TF GRCD5 activates GhCYC3 expression. We propose that the C class MADS-box TF GAGA1 contributes to stamen development upstream of GhCYC3. Our data demonstrate how interactions among and between the conserved floral regulators, TCP and MADS-box TFs, contribute to the evolution of the elaborate inflorescence architecture of Asteraceae.
Breaking Neural Reasoning Architectures With Metamorphic Relation-Based Adversarial Examples

The ability to read, reason, and infer lies at the heart of neural reasoning architectures. After all, the ability to perform logical reasoning over language remains a coveted goal of Artificial Intelligence. To this end, models such as the Turing-complete differentiable neural computer (DNC) boast of real logical reasoning capabilities, along with the ability to reason beyond simple surface-level matching. In this brief, we propose the first probe into DNC’s logical reasoning capabilities with a focus on text-based question answering (QA). More concretely, we propose a conceptually simple but effective adversarial attack based on metamorphic relations. Our proposed adversarial attack reduces DNCs’ state-of-the-art accuracy from 100% to 1.5% in the worst case, exposing weaknesses and susceptibilities in modern neural reasoning architectures. We further empirically explore possibilities to defend against such attacks and demonstrate the utility of our adversarial framework as a simple scalable method to improve model adversarial robustness.
An assessment of potential biomarkers of environment enteropathy and its association with age and microbial infections among children in Bangladesh

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.
COVID-19 infection in solid organ transplant recipients after SARS-CoV-2 vaccination

The prevalence and mortality of COVID-19 are higher in solid organ transplant recipients (SOTs) compared to the general population (1-3). Two SARS-CoV-2 messenger RNA (mRNA) vaccines have been approved by the FDA, both are 95% efficient in preventing COVID-19 in the general population. The efficacy of these vaccines in SOTs remains to be unknown as immunocompromised patients have been excluded from the vaccine studies.
Structure-Function Relationship of the Ligand-Binding Domain of the Fibroblast Growth Factor Receptor

The interactions between FGF and fibroblast growth factor receptors are responsible for the regulation of key cellular processes. FGF is important in both germ cell and embryonic developments. FGF continues to play important roles during adulthood by regulating embryogenesis, cell differentiation, and wound healing (1-7). The regulations of these cellular events are initiated through FGF binding to the fibroblast growth factor receptors. The complex formed by FGF and the receptor involves a key interaction with heparin. Through interactions with heparin, the FGF, FGFR and Heparin form a 2:2:2 complex (8). This complex formation results in autophosphorylation in the tyrosine kinase domain in the cytoplasm. The autophosphorylation events lead to downstream signaling that result in the regulation of previously mentioned cellular processes (9, 10). Mutations within the FGF or FGFR may interfere with signaling or protein stability. Changes in the signaling efficiency by FGF or the FGFR are shown to lead to disease states There exist many point mutations in the FGF receptor that result in craniofacial, hypogonadotropic hypogonadism, anosmia, and tumor development. Using site-directed mutagenesis we have shown non-covalent interactions formed by Kallmann syndrome linked mutations result in a loss-of-binding between FGF and the FGF receptor. This evidence has shown that the non-covalent ligand binding interactions lost are due to changes in the D2 structure or binding site. Additionally, the R203C mutation, linked to breast cancer, was tested and determined to break a D2 stabilizing cation-π bond. The cation-π stabilized the binding interaction with heparin and provides stability to the D2 domain. Although the decreased stability of the D2 domain supports a loss-of-function, we are currently investigating intermolecular disulfide bond formation between adjacent receptor. This is a known mechanism among FGF receptors that may lead to signaling in the absence of a ligand.
The OsABCI7 Transporter Interacts with OsHCF222 to Stabilize the Thylakoid Membrane in Rice.

The thylakoid membrane is a highly complex membrane system in plants and plays crucial roles in the biogenesis of the photosynthetic apparatus and plant development. However, the genetic factors involved in chloroplast development and its relationship with intracellular metabolites are largely unknown. Here, a rice (Oryza sativa) chlorotic and necrotic leaf1 (cnl1) mutant was identified and map-based cloning revealed that a single base substitution followed by a 6-bp deletion in the ATP-binding cassette transporter I family member7 (OsABCI7) resulted in chlorotic and necrotic leaves with thylakoid membrane degradation, chlorophyll breakdown, photosynthesis impairment, and cell death in cnl1. Furthermore, the expression of OsABCI7 was inducible under lower temperatures, which severely affected cnl1 chloroplast development, and etiolated cnl1 seedlings were unable to recover to a normal green state under light conditions. Functional complementation and overexpression showed that OsABCI7 could rescue the cnl1 chlorotic and necrotic phenotype. OsABCI7 interacted with HIGH CHLOROPHYLL FLUORESCENCE222 (OsHCF222) to regulate cellular reactive oxygen species (ROS) homeostasis for thylakoid membrane stability. OsABCI7 localized to thylakoid membranes, while OsHCF222 targeted to endoplasmic reticulum and chloroplasts. Exogenous application of ascorbic acid eased the yellowish leaf phenotype by increasing chlorophyll content and alleviating ROS stress in cnl1. Unlike cnl1, the CRISPR/Cas9-mediated OsHCF222 knockout lines showed chlorotic leaves but were seedling lethal. Our results provide insight into the functions of ABC transporters in rice, especially within the relationship between ROS homeostasis and stability of thylakoid membranes.
A Physiological-Based Pharmacokinetic Model For The Broad Spectrum Antimicrobial Zinc Pyrithione: II. Dermal Absorption And Dosimetry In The Rat

ABSTRACT The broad spectrum antimicrobial/antifungal zinc pyrithione (ZnPT) is used in products ranging from antifouling paint to antidandruff shampoo. The hazard profile of ZnPT was established based upon comprehensive toxicological testing, and products containing this biocide have been safely used for years. The purpose of this study was to create a dermal physiologically based pharmacokinetic (PBPK) model for ZnPT in the rat for improving dose–response analysis of ZnPT-induced toxicity where reversible hindlimb weakness was the endpoint used as the basis for ZnPT risk assessments. Previously, we developed a PBPK model which simulated the kinetics of pyrithione (PT) and its major metabolites 2-(methylsulfonyl)pyridine and S-glucuronide conjugates in blood and tissues of rats following oral ZnPT administration. The dermal model was optimized utilizing in vitro dermal penetration investigations conducted with rat skin and with historical data from a dermal repeat dose study using rats. The model replicated the observed temporal patterns and elimination kinetics of [14C]PT equivalents in blood and urine during and following repeated dermal dosing and replicated the observed dose-dependencies of absorption, blood [14C]PT equivalents and plasma PT concentrations. The model provided internal dosimetry predictions for a benchmark dose analysis of hindlimb weakness in rats that combined dermal, gavage and dietary studies into a single internal dose–response model with area-under-the-curve (AUC) for plasma PT, the toxic moiety in the rat, as the internal dose metric. This PBPK model has predictive validity for calculating internal doses of PT and/or [14C]PT equivalents from different routes of exposure in the rat.
Inhaled corticosteroids and risk of lung cancer among chronic obstructive pulmonary disease patients: a comprehensive analysis of nine prospective cohorts

Background It remains uncertain whether there is a protective effect of inhaled corticosteroids (ICs) against lung cancer in chronic obstructive pulmonary disease (COPD) patients. Methods Databases including PubMed, Web of Science, EMBASE, and Medline were comprehensively searched. Random-effects model meta-analysis was conducted to calculate the hazard ratios (HRs) for lung cancer incidence among ICs users versus non-ICs users in patients with COPD. Stratified analysis was performed based on region and age of each study. This review was registered on PROSPERO (registration number CRD42020159082). Results Based on data from 181,859 COPD patients with a total follow-up duration of 1,109,339.9 person-years, we identified that the use of ICs in COPD patients was associated with a decreased risk of lung cancer [HR: 0.73, 95% confidence interval (CI): 0.62–0.86; P<0.001]. The region-specific HRs for lung cancer incidence were 0.62 (95% CI: 0.62–0.86; P=0.004), 0.77 (95% CI: 0.60–0.97; P=0.028) and 0.81 (95% CI: 0.61–1.08; P=0.155) among European, Asian and North American COPD patients, respectively. Additionally, we found the consistent outcome among age groups (≥70 years old: HR: 0.73, 95% CI: 0.65–0.99, P=0.043; <70 years old: HR: 0.74, 95% CI: 0.56–0.99, P=0.040). Conclusions This study demonstrates that ICs have a protective effect against lung cancer in COPD patients. It could provide guidance for clinicians in the prevention of lung cancer among patients with COPD.
Expression Profiles Reveal Involvement of VEGF, IGF1, BIRC5, and MMP1 in Vulvar Carcinogenesis

Objective: The objective of this study was to identify key genes and shed light on the underlying molecular mechanisms of vulvar squamous cell carcinoma (VSCC). Methods: Bioinformatic software was utilized for the identification and characterization of key differentially expressed genes (DEGs) from microarrays GSE63678 and GSE38228, which contain VSCC and normal vulvar tissue data. These microarrays were obtained from Gene Expression Omnibus (GEO). Immunohistochemical assays (55 VSCC and 50 normal vulvar tissues) were utilized to validate the expression of VEGF, IGF1, BIRC5, and MMP1 screened from the identified DEGs. SPSS 18.0 software was used for statistical analyses of the relationships between IGF1, BIRC5, VEGF, MMP1 expression levels and patient clinicopathological characteristics. Results: A total of 141 DEGs were identified, among which 18 genes were closely correlated with the biological characteristics of VSCC. Four of the 18 genes (VEGF, IGF1, BIRC5, and MMP1) screened from the GEO database were markedly enriched in pathways in cancer (P < 0.05), and could be considered key genes in VSCC based on KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis in DAVID (Database for Annotation, Visualization and Integrated Discovery). The expression levels of these 4 hub genes, determined by immunohistochemical assays, were consistent with the bioinformatics results. Higher expression of IGF1 showed significant association with well-differentiated carcinomas (P = 0.017). BIRC5 expression levels showed a positive correlation with clinical stage (P = 0.039); compared with those in menopause for over 10 years, patients in menopause for less than 10 years at the time of diagnosis tended to have significantly higher expression of BIRC5 (P = 0.003). VEGF and MMP1 expression levels were not correlated with any of the tested clinicopathological characteristics. Conclusion: VEGF, IGF1, BIRC5, and MMP1 were identified as being associated with VSCC using integrated bioinformatic methods, which may provide important insights into the pathogenesis of this disease and help to identify new biomarkers.
SCA7 Mouse Cerebellar Pathology Reveals Preferential Downregulation of Key Purkinje Cell-Identity Genes and Shared Disease Signature with SCA1 and SCA2

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease mainly characterized by motor incoordination because of progressive cerebellar degeneration. SCA7 is caused by polyglutamine expansion in ATXN7, a subunit of the transcriptional coactivator SAGA, which harbors histone modification activities. Polyglutamine expansions in specific proteins are also responsible for SCA1-SCA3, SCA6, and SCA17; however, the converging and diverging pathomechanisms remain poorly understood. Using a new SCA7 knock-in mouse, SCA7140Q/5Q, we analyzed gene expression in the cerebellum and assigned gene deregulation to specific cell types using published datasets. Gene deregulation affects all cerebellar cell types, although at variable degree, and correlates with alterations of SAGA-dependent epigenetic marks. Purkinje cells (PCs) are by far the most affected neurons and show reduced expression of 83 cell-type identity genes, including these critical for their spontaneous firing activity and synaptic functions. PC gene downregulation precedes morphologic alterations, pacemaker dysfunction, and motor incoordination. Strikingly, most PC genes downregulated in SCA7 have also decreased expression in SCA1 and SCA2 mice, revealing converging pathomechanisms and a common disease signature involving cGMP-PKG and phosphatidylinositol signaling pathways and LTD. Our study thus points out molecular targets for therapeutic development, which may prove beneficial for several SCAs. Furthermore, we show that SCA7140Q/5Q males and females exhibit the major disease features observed in patients, including cerebellar damage, cerebral atrophy, peripheral nerves pathology, and photoreceptor dystrophy, which account for progressive impairment of behavior, motor, and visual functions. SCA7140Q/5Q mice represent an accurate model for the investigation of different aspects of SCA7 pathogenesis. SIGNIFICANCE STATEMENT Spinocerebellar ataxia 7 (SCA7) is one of the several forms of inherited SCAs characterized by cerebellar degeneration because of polyglutamine expansion in specific proteins. The ATXN7 involved in SCA7 is a subunit of SAGA transcriptional coactivator complex. To understand the pathomechanisms of SCA7, we determined the cell type-specific gene deregulation in SCA7 mouse cerebellum. We found that the Purkinje cells are the most affected cerebellar cell type and show downregulation of a large subset of neuronal identity genes, critical for their spontaneous firing and synaptic functions. Strikingly, the same Purkinje cell genes are downregulated in mouse models of two other SCAs. Thus, our work reveals a disease signature shared among several SCAs and uncovers potential molecular targets for their treatment.
An Initial Review of the Status of Electrode Materials for Potassium‐Ion Batteries

The status of room‐temperature potassium‐ion batteries is reviewed in light of recent concerns regarding the rising cost of lithium and the fact that room‐temperature sodium‐ion batteries have yet to be commercialised thus far. Initial reports of potassium‐ion cells appear promising given the infancy of the research area. This review presents not only an overview of the current potassium‐ion battery literature, but also attempts to provide context by describing previous developments in lithium‐ion and sodium‐ion batteries and the electrochemical reaction mechanisms discovered thus far. Perspectives and directions on the techniques available to characterize newly developed battery materials are also provided based on our experience and knowledge from the literature. It is hoped that through this review, the potential of potassium‐ion batteries as a competitive energy‐storage technology will be realised, and the accessibility and available knowledge of the techniques required to develop the technology will be made apparent.
Nalbuphine for spinal anesthesia: A systematic review and meta‐analysis

Various adjuvants for prolongation of intra‐operative and postoperative analgesia have been clinically studied, but the safety and efficiency of nalbuphine as an adjuvant to local anesthetics in spinal anesthesia remains unconfirmed. Therefore, we conducted a meta‐analysis about the effect of nalbuphine as an adjuvant to local anesthetics in spinal anesthesia in regard to time of onset of sensory blockade and motor blockade, duration of motor blockade, 2‐segment sensory regression time, the duration of analgesia, and incidence of side effects to provide a reliable basis for clinical application.
Is the p-value properly interpreted by critical care professionals? Online survey

Objective To determine the prevalence of and risk factors for insufficient knowledge related to p-values among critical care physicians and respiratory therapists in Argentina. Methods This cross-sectional online survey contained 25 questions about respondents’ characteristics, self-perception and p-value knowledge (theory and practice). Descriptive and multivariable logistic regression analyses were conducted. Results Three hundred seventy-six respondents were analyzed. Two hundred thirty-seven respondents (63.1%) did not know about p-values. According to the multivariable logistic regression analysis, a lack of training on scientific research methodology (adjusted OR 2.50; 95%CI 1.37 - 4.53; p = 0.003) and the amount of reading (< 6 scientific articles per year; adjusted OR 3.27; 95%CI 1.67 - 6.40; p = 0.001) were found to be independently associated with the respondents’ lack of p-value knowledge. Conclusion The prevalence of insufficient knowledge regarding p-values among critical care physicians and respiratory therapists in Argentina was 63%. A lack of training on scientific research methodology and the amount of reading (< 6 scientific articles per year) were found to be independently associated with the respondents’ lack of p-value knowledge.
From the Andes to the desert: 16S rRNA metabarcoding characterization of aquatic bacterial communities in the Rimac river, the main source of water for Lima, Peru

The Rimac river is the main source of water for Lima, Peru’s capital megacity. The river is constantly affected by different types of contamination including mine tailings in the Andes and urban sewage in the metropolitan area. In this work, we aim to produce the first characterization of aquatic bacterial communities in the Rimac river using a 16S rRNA metabarcoding approach which would be useful to identify bacterial diversity and potential understudied pathogens. We report a lower diversity in bacterial communities from the Lower Rimac (Metropolitan zone) in comparison to other sub-basins. Samples were generally grouped according to their geographical location. Bacterial classes Alphaproteobacteria, Bacteroidia, Campylobacteria, Fusobacteriia, and Gammaproteobacteria were the most frequent along the river. Arcobacter cryaerophilus (Campylobacteria) was the most frequent species in the Lower Rimac while Flavobacterium succinicans (Bacteroidia) and Hypnocyclicus (Fusobacteriia) were the most predominant in the Upper Rimac. Predicted metabolic functions in the microbiota include bacterial motility and quorum sensing. Additional metabolomic analyses showed the presence of some insecticides and herbicides in the Parac-Upper Rimac and Santa Eulalia-Parac sub-basins. The dominance in the Metropolitan area of Arcobacter cryaerophilus, an emergent pathogen associated with fecal contamination and antibiotic multiresistance, that is not usually reported in traditional microbiological quality assessments, highlights the necessity to apply next-generation sequencing tools to improve pathogen surveillance. We believe that our study will encourage the integration of omics sciences in Peru and its application on current environmental and public health issues.
‘I knew it wasn’t normal, I just didn’t know what to do about it’: adversity and caregiver support when growing up in a family with Huntington’s disease

Abstract Objective Excessive adversity in childhood can have long-term consequences on health and well-being. One group of children that may be at risk are those who grow up with a parent with Huntington’s disease (HD). Despite this, there is little knowledge about how these children are impacted by adversity. We aimed to explore adverse childhood experiences (ACEs) of individuals who grew up with a parent with HD and their perceptions of caregiver support. Design Semi-structured qualitative interviews of 36 adults and adolescents were analysed using interpretative phenomenological analysis (IPA). Results First, the analysis revealed a range of frequent adverse events during participants’ childhoods, leading to feelings of uncertainty, loss, fear, and a lack of care. Next, how the presence or absence of support had impacted participants’ perceptions of these experiences was analysed. Results showed that participants without support were often overwhelmed by feelings of stress, whereas participants with support tolerated adversity better. Conclusion Findings suggest that children in families with HD can be exposed to a range of adverse experiences. Findings also suggest that sufficient support from a caregiver without HD can buffer or protect against negative consequences of these experiences.