Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypothyroidism and Adverse Endpoints in Diabetic Patients: A Systematic Review and Meta-Analysis

Background: This study investigated the relationship strength between hypothyroidism and cardiovascular and renal outcomes in diabetic patients. Methods: The electronic databases PubMed, EmBase, and Cochrane library were screened for relevant studies published before November 2018. The outcomes included major cardiovascular events (MACEs), all-cause mortality, cardiac death, stroke, diabetic nephropathy (DN), diabetic retinopathy (DR), and chronic kidney disease (CKD). The pooled results for all outcomes were calculated using random-effects models. Results: A total of eight studies met the inclusion criteria. The summary results indicated that hypothyroidism was not associated with the risk of MACEs (OR:1.21; 95%CI:0.68–2.16; P = 0.514), all-cause mortality (OR:1.27; 95%CI:0.93–1.74; P = 0.136), cardiac death (OR:1.16; 95%CI:0.89–1.52; P = 0.271), stroke (OR:0.96; 95%CI: 0.49–1.88; P = 0.915), and DN (OR:1.71; 95%CI:0.37–7.90; P = 0.490). There was a significant association between hypothyroidism and the risk of DR (OR:1.73; 95%CI:1.08–2.77; P = 0.023) and CKD (OR:1.22; 95%CI:1.10–1.36; P < 0.001). Conclusions: These findings indicate that diabetic patients with hypothyroidism have an increased risk of DR and CKD. Additional large-scale prospective studies should be carried out to verify the prognosis of patients with diabetes and hypothyroidism.
Contact Heat Evoked Potentials Are Responsive to Peripheral Sensitization: Requisite Stimulation Parameters

The sensitizing effect of capsaicin has been previously characterized using laser and contact heat evoked potentials (LEPs and CHEPs) by stimulating in the primary area of hyperalgesia. Interestingly, only CHEPs reveal changes consistent with notion of peripheral sensitization (i.e., reduced latencies). The aim of this study was to investigate contact heat stimulation parameters necessary to detect peripheral sensitization related to the topical application of capsaicin, and therefore significantly improve the current method of measuring peripheral sensitization via CHEPs. Rapid contact heat stimulation (70°C/s) was applied from three different baseline temperatures (35, 38.5, and 42°C) to a 52°C peak temperature, before and after the topical application of capsaicin on the hand dorsum. Increased pain ratings in the primary area of hyperalgesia were accompanied by reduced N2 latency. Changes in N2 latency were, however, only significant following stimulation from 35 and 38.5°C baseline temperatures. These findings suggest that earlier recruitment of capsaicin-sensitized afferents occurs between 35 and 42°C, as stimulations from 42°C baseline were unchanged by capsaicin. This is in line with reduced thresholds of type II A-delta mechanoheat (AMH) nociceptors following sensitization. Conventional CHEP stimulation, with a baseline temperature below 42°C, is well suited to objectively detect evidence of peripheral sensitization.
Hunting and Forest Modification Have Distinct Defaunation Impacts on Tropical Mammals and Birds

The mammalian and avian assemblages of intact tropical forests are among the most diverse vertebrate communities on Earth and influence the structure, composition, and functioning of these forests in myriad ways. Over recent centuries, however, increasing human domination of the tropics has led to widespread defaunation, or the decline, local-, or global extinction of tropical animal species. Defaunation is one of the defining features of the Anthropocene and is best documented for vertebrate species, especially mammals and birds. Defaunation is driven by several direct (e.g., hunting) and indirect (e.g., habitat alteration) anthropogenic threats, but how these threats differ in the nature and magnitude of their impacts on tropical mammal and bird species remains unclear. Using a meta-analysis of 82 studies on 254 mammal and 1,640 bird species from across the tropics, we assess the effects of three major regional-scale drivers of tropical defaunation, namely hunting, forest degradation and forest conversion, on measures of abundance for tropical mammal and bird species belonging to different dietary guilds and IUCN conservation status groups. Mammal species across dietary guilds either declined or did not change, on average, in response to the three drivers, with hunting having the most consistent negative impacts on abundances of carnivores, frugivores, herbivores/granivores, large-bodied species, and species of high conservation importance. By contrast, bird species declined most strongly in response to forest conversion, with responses varying widely across different dietary and conservation importance groups, and not consistently related to body size. Our results reveal that hunting, forest degradation and conversion are associated with distinct types of defaunation of mammal and bird species, and are therefore likely to have distinct implications for animal-mediated interactions and processes, ecosystem functions, and conservation of tropical forests. Addressing major gaps in our empirical understanding of defaunation effects—e.g., hunting impacts on smaller-bodied mammals and birds, and responses of species in southeast Asian forests—is key to better understanding, predicting, and mitigating the impacts of this pervasive global threat.
Three Transcription Activators of ABA Signaling Positively Regulate Suberin Monomer Synthesis by Activating Cytochrome P450 CYP86A1 in Kiwifruit

Wound attack stimulates accumulation of abscisic acid (ABA) that activates a number of genes associated with wound suberization of plants. Cytochrome P450 fatty acid ω-hydroxylase CYP86A1 catalyzes ω-hydroxylation of fatty acids to form the ω-functionalized monomers that play a pivotal role in suberin synthesis. However, the transcriptional regulation of ABA signaling on AchnCYP86A1 has not been characterized in kiwifruit. In this study, AchnCYP86A1, a kiwifruit homolog of Arabidopsis AtCYP86A1, was isolated. AchnCYP86A1-overexpressed N. benthamiana leaves displayed that the AchnCYP86A1 functioned as a fatty acid ω-hydroxylase associated with synthesis of suberin monomer. The regulatory function of three transcription factors (TFs, including AchnMYC2, AchnMYB41 and AchnMYB107) on AchnCYP86A1 was identified. All the three TFs were localized in nucleus and could individually interact with AchnCYP86A1 promoter to activate gene expression in yeast one-hybrid and dual-luciferase assays. The findings were further demonstrated in transient overexpressed N. benthamiana, in which all TFs notably elevated the expression of aliphatic synthesis genes including CYP86A1 and the accumulation of ω-hydroxyacids, α, ω-diacids, fatty acids and primary alcohols. Moreover, exogenous ABA induced the expression of AchnMYC2, AchnMYB41 and AchnMYB107 that promoted AchnCYP86A1 involving in suberin monomer formation. Contrary to the inductive effects of ABA, however, fluridone (an inhibitor of ABA biosynthesis) inhibited the three TFs expression and suberin monomer formation. These results indicate that AchnMYC2, AchnMYB41 and AchnMYB107 positively regulate suberin monomer synthesis by activating AchnCYP86A1 promoter in response to ABA.
“An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process

Endogenously-arising DNA double-strand breaks (DSBs) rarely harbor canonical 5′-phosphate, 3′-hydroxyl moieties at the ends, which are, regardless of the pathway used, ultimately required for their repair. Cells are therefore endowed with a wide variety of enzymes that can deal with these chemical and structural variations and guarantee the formation of ligatable termini. An important distinction is whether the ends are directly “unblocked” by specific enzymatic activities without affecting the integrity of the DNA molecule and its sequence, or whether they are “processed” by unspecific nucleases that remove nucleotides from the termini. DNA end structure and configuration, therefore, shape the repair process, its requirements, and, importantly, its final outcome. Thus, the molecular mechanisms that coordinate and integrate the cellular response to blocked DSBs, although still largely unexplored, can be particularly relevant for maintaining genome integrity and avoiding malignant transformation and cancer.
Microarray Strategies for Exploring Bacterial Surface Glycans and Their Interactions With Glycan-Binding Proteins

Bacterial surfaces are decorated with distinct carbohydrate structures that may substantially differ among species and strains. These structures can be recognized by a variety of glycan-binding proteins, playing an important role in the bacteria cross-talk with the host and invading bacteriophages, and also in the formation of bacterial microcolonies and biofilms. In recent years, different microarray approaches for exploring bacterial surface glycans and their recognition by proteins have been developed. A main advantage of the microarray format is the inherent miniaturization of the method, which allows sensitive and high-throughput analyses with very small amounts of sample. Antibody and lectin microarrays have been used for examining bacterial glycosignatures, enabling bacteria identification and differentiation among strains. In addition, microarrays incorporating bacterial carbohydrate structures have served to evaluate their recognition by diverse host/phage/bacterial glycan-binding proteins, such as lectins, effectors of the immune system, or bacterial and phagic cell wall lysins, and to identify antigenic determinants for vaccine development. The list of samples printed in the arrays includes polysaccharides, lipopoly/lipooligosaccharides, (lipo)teichoic acids, and peptidoglycans, as well as sequence-defined oligosaccharide fragments. Moreover, microarrays of cell wall fragments and entire bacterial cells have been developed, which also allow to study bacterial glycosylation patterns. In this review, examples of the different microarray platforms and applications are presented with a view to give the current state-of-the-art and future prospects in this field.
Electrically-Driven Soft Fluidic Actuators Combining Stretchable Pumps With Thin McKibben Muscles

Soft wearable robots could provide support for lower and upper limbs, increase weight lifting ability, decrease energy required for walking and running, and even provide haptic feedback. However, to date most of wearable robots are based on electromagnetic motors or fluidic actuators, the former being rigid and bulky, the latter requiring external pumps or compressors, greatly limiting integration and portability. Here we describe a new class of electrically-driven soft fluidic muscles combining thin, fiber-like McKibben actuators with fully Stretchable Pumps. These pumps rely on ElectroHydroDynamics, a solid-state pumping mechanism that directly accelerates liquid molecules by means of an electric field. Requiring no moving parts, these pumps are silent and can be bent and stretched while operating. Each electrically-driven fluidic muscle consists of one Stretchable Pump and one thin McKibben actuator, resulting in a slender soft device weighing 2 g. We characterized the response of these devices, obtaining a blocked force of 0.84 N and a maximum stroke of 4 mm. Future work will focus on decreasing the response time and increasing the energy efficiency. Modular and straightforward to integrate in textiles, these electrically-driven fluidic muscles will enable soft smart clothing with multi-functional capabilities for human assistance and augmentation.
Tools for Assessing the Protective Efficacy of TB Vaccines in Humans: in vitro Mycobacterial Growth Inhibition Predicts Outcome of in vivo Mycobacterial Infection

Tuberculosis (TB) remains a leading global cause of morbidity and mortality and an effective new vaccine is urgently needed. A major barrier to the rational development of novel TB vaccines is the lack of a validated immune correlate or biomarker of protection. Mycobacterial Growth Inhibition Assays (MGIAs) provide an unbiased measure of ability to control mycobacterial growth in vitro, and may represent a functional correlate of protection. However, the biological relevance of any potential correlate can only be assessed by determining the association with in vivo protection from either a controlled mycobacterial infection or natural development of TB disease. Our data demonstrate that the direct MGIA using peripheral blood mononuclear cells (PBMC) is measuring a biologically relevant response that correlates with protection from in vivo human BCG infection across two independent cohorts. This is the first report of an MGIA correlating with in vivo protection in the species-of-interest, humans, and furthermore on a per-individual as well as per-group basis. Control of mycobacterial growth in the MGIA is associated with a range of immune parameters measured post-BCG infection in vivo including the IFN-γ ELISpot response, frequency of PPD-specific IFN-γ or TNF-α producing CD4+ T cells and frequency of specific sub-populations of polyfunctional CD4+ T cells. Distinct transcriptomic profiles are associated with good vs. poor mycobacterial control in the MGIA, with good controllers showing enrichment for gene sets associated with antigen processing/presentation and the IL-23 pathway, and poor controllers showing enrichment for hypoxia-related pathways. This study represents an important step toward biologically validating the direct PBMC MGIA for use in TB vaccine development and furthermore demonstrates the utility of this assay in determining relevant immune mechanisms and pathways of protection.
Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer’s Disease

Alzheimer’s disease (AD) is a type of incurable neurodegenerative disease that is characterized by the accumulation of amyloid-β (Aβ; plaques) and tau hyperphosphorylation as neurofibrillary tangles (NFTs) in the brain followed by neuronal death, cognitive decline, and memory loss. The high prevalence of AD in the developed world has become a major public health challenge associated with social and economic burdens on individuals and society. Due to there being limited options for early diagnosis and determining the exact pathophysiology of AD, finding effective therapeutic strategies has become a great challenge. Several possible risk factors associated with AD pathology have been identified; however, their roles are still inconclusive. Recent clinical trials of the drugs targeting Aβ and tau have failed to find a cure for the AD pathology. Therefore, effective preventive strategies should be followed to reduce the exponential increase in the prevalence of cognitive decline and dementia, especially AD. Although the search for new therapeutic targets is a great challenge for the scientific community, the roles of lifestyle interventions and nutraceuticals in the prevention of many metabolic and neurodegenerative diseases are highly appreciated in the literature. In this article, we summarize the molecular mechanisms involved in AD pathology and the possible ameliorative action of lifestyle and nutritional interventions including diet, exercise, Calorie restriction (CR), and various bioactive compounds on cognitive decline and dementia. This article will provide insights into the role of non-pharmacologic interventions in the modulation of AD pathology, which may offer the benefit of improving quality of life by reducing cognitive decline and incident AD.
The Fungal-Specific Transcription Factor VpFSTF1 Is Required for Virulence in Valsa pyri

Valsa pyri is the causal agent of pear canker disease, which leads to enormous losses of pear production in eastern Asian, especially China. In this study, we identified a fungal-specific transcription factor 1 (termed as VpFSTF1) from V. pyri, which is highly conserved in fungi. To characterize its functions, we generated mutant and complementation strains in V. pyri and found that ΔVpFSTF1 mutants lost the ability to form fruiting bodies along with the reduced virulence. The radial growth of ΔVpFSTF1 mutant was sensitive to increasing concentrations of hydrogen peroxide (H2O2) and salicylic acid (SA). Moreover, RNA-sequencing (RNA-Seq) analysis of wild-type (WT) and ΔVpFSTF1 mutant strains was performed, and the results revealed 1,993 upregulated, and 2006 downregulated differentially expressed genes (DEGs) in the mutant. The DEGs were corresponding to the genes that are involved in amino acid metabolism, starch, and sucrose metabolism, gluconeogenesis, citrate cycle, and carbon metabolism. Interestingly, pathogen host interaction (PHI) analysis showed that 69 downregulated genes were related to virulence, suggesting that they might function downstream of VpFSTF1. Nine DEGs were further validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the results were consistent with RNA-seq analysis. Furthermore, promoter regions were predicted, and VpFSTF1 binding activity was assessed. We demonstrated that five promoters are directly or indirectly targeted by VpFSTF1, including catalase-related peroxidase (VPIG_01209) and P450 family genes. Taken together, these findings indicate that VpFSTF1 is crucial for the virulence of V. pyri via direct or indirect regulation of downstream genes expression and lay an important foundation for understanding the molecular mechanism of V. pyri infection.
Low Testosterone in Adolescents & Young Adults

Male hypogonadism, the clinical syndrome with variable symptoms associated with gonadal dysfunction, can affect men of all ages. In older males, physiologic changes of the aging testis, account for the majority of decreased testosterone levels in this population. For younger males and adolescents, the etiology of hypogonadism is commonly due to congenital or acquired conditions that disrupt the testis production of testosterone or signaling from the hypothalamic-pituitary-gonadal axis. Diagnosis of hypogonadism in younger males can be a challenge, as symptoms such as decreased libido or erectile dysfunction, common in the older men, are not usually present, and young men instead commonly complain of low energy. While an underlying congenital cause should always be considered in young men with hypogonadism, acquired conditions such as obesity, diabetes, anabolic steroid or illicit drug use have all been associated with low testosterone levels. Outside of modifying identifiable risk factors for hypogonadism, pharmacologic testosterone therapy can also lead to therapeutic dilemmas in young men who desire paternity. Topical or injectable administration of testosterone, through negative feedback on the hypothalamus and pituitary, can decrease spermatogenesis, posing an infertility risk. Other agents that can replace testosterone or increase the body's natural production of testosterone without decreasing spermatogenesis are preferred, such as intranasal testosterone, selective estrogen modulators, aromatase inhibitors or human-chorionic gonadotrophin, often used in combination. Clinicians must maintain a high level of suspicion to properly diagnose young men with hypogonadism and tailor treatment based on both the underlying etiology and fertility goals.
Executive Functions, Pragmatic Skills, and Mental Health in Children With Congenital Cytomegalovirus (CMV) Infection With Cochlear Implants: A Pilot Study

Congenital cytomegalovirus (cCMV) infection is the most common cause of progressive hearing impairment. In our previous study around 90% of children with a cCMV infection and CI had severely damaged balance functions (Karltorp et al., 2014). Around 20% had vision impairment, 15% were diagnosed with Autism-Spectrum-Disorder, and 20% with ADHD. One clinical observation was that children with cCMV infection had problems with executive functioning (EF), while controls with a genetic cause of deafness (Connexin 26 mutations; Cx26) did not have similar difficulties. A follow-up study was therefore initiated with the main objective to examine EF and pragmatic skills in relation to mental health in children with a cCMV infection and to draw a comparison with matched controls with Cx26 mutations (age, sex, hearing, non-verbal cognitive ability, vocabulary, and socioeconomic status level). Ten children with a cCMV infection and CI (4.8–12:9 years) and seven children with CI (4:8–12:8 years) participated in the study, which had a multidisciplinary approach. Executive functioning was assessed both with formal tests targeting working memory and attention, parent and teacher questionnaires, and a systematic observation by a blinded psychologist during one test situation. Pragmatics and mental health were investigated with parent and teacher reports. In addition, the early language outcome was considered in non-parametric correlation analyses examining the possible relationships between later EF skills, pragmatics, and mental health. Children with cCMV had a statistically significant worse pragmatic outcome and phonological working memory than controls despite their groups having similar non-verbal cognitive ability and vocabulary. However, there were no statistical differences between the groups regarding their EF skills in everyday settings and mental health. There were associations between early language outcomes and later EF skills and pragmatics in the whole sample. Conclusion: Children with a cCMV infection are at risk of developing learning difficulties in school due to difficulties with phonological working memory and pragmatic skills in social interactions.
New Insights on the Role of Lipid Metabolism in the Metabolic Reprogramming of Macrophages

Macrophage activation is intimately linked to metabolic reprogramming. Inflammatory (M1) macrophages are able to sustain inflammatory responses and to kill pathogens, mostly by relying on aerobic glycolysis and fatty acid biosynthesis. Glycolysis is a fast way of producing ATP, and fatty acids serve as precursors for the synthesis of inflammatory mediators. On the opposite side, anti-inflammatory (M2) macrophages mediate the resolution of inflammation and tissue repair, switching their metabolism to fatty acid oxidation and oxidative phosphorylation. Over the years, this classical view has been challenged by recent discoveries pointing to a more complex metabolic network during macrophage activation. Lipid metabolism plays a critical role in the activation of both M1 and M2 macrophages. Recent evidence shows that fatty acid oxidation is also essential for inflammasome activation in M1 macrophages, and glycolysis is now known to fuel fatty acid oxidation in M2 macrophages. Ultimately, targeting lipid metabolism in macrophages can improve the outcome of metabolic diseases. Here, we review the main aspects of macrophage immunometabolism from the perspective of the metabolism of lipids. Building a reliable metabolic network during macrophage activation will bring us closer to targeting macrophages for improving human health.