Miracle-dz/UniFAR-FTUs huggingface dataset:
Repetitive DNA Restructuring Across Multiple Nicotiana Allopolyploidisation Events Shows a Lack of Strong Cytoplasmic Bias in Influencing Repeat Turnover

Allopolyploidy is acknowledged as an important force in plant evolution. Frequent allopolyploidy in Nicotiana across different timescales permits the evaluation of genome restructuring and repeat dynamics through time. Here we use a clustering approach on high-throughput sequence reads to identify the main classes of repetitive elements following three allotetraploid events, and how these are inherited from the closest extant relatives of the maternal and paternal subgenome donors. In all three cases, there was a lack of clear maternal, cytoplasmic bias in repeat evolution, i.e., lack of a predicted bias towards maternal subgenome-derived repeats, with roughly equal contributions from both parental subgenomes. Different overall repeat dynamics were found across timescales of <0.5 (N. rustica L.), 4 (N. repanda Willd.) and 6 (N. benthamiana Domin) Ma, with nearly additive, genome upsizing, and genome downsizing, respectively. Lower copy repeats were inherited in similar abundance to the parental subgenomes, whereas higher copy repeats contributed the most to genome size change in N. repanda and N. benthamiana. Genome downsizing post-polyploidisation may be a general long-term trend across angiosperms, but at more recent timescales there is species-specific variance as found in Nicotiana.
Effects of Sensorineural Hearing Loss on Cortical Synchronization to Competing Speech during Selective Attention

When selectively attending to a speech stream in multi-talker scenarios, low-frequency cortical activity is known to synchronize selectively to fluctuations in the attended speech signal. Older listeners with age-related sensorineural hearing loss (presbycusis) often struggle to understand speech in such situations, even when wearing a hearing aid. Yet, it is unclear whether a peripheral hearing loss degrades the attentional modulation of cortical speech tracking. Here, we used psychoacoustics and electroencephalography (EEG) in male and female human listeners to examine potential effects of hearing loss on EEG correlates of speech envelope synchronization in cortex. Behaviorally, older hearing-impaired (HI) listeners showed degraded speech-in-noise recognition and reduced temporal acuity compared with age-matched normal-hearing (NH) controls. During EEG recordings, we used a selective attention task with two spatially separated simultaneous speech streams where NH and HI listeners both showed high speech recognition performance. Low-frequency (<10 Hz) envelope-entrained EEG responses were enhanced in the HI listeners, both for the attended speech, but also for tone sequences modulated at slow rates (4 Hz) during passive listening. Compared with the attended speech, responses to the ignored stream were found to be reduced in both HI and NH listeners, allowing for the attended target to be classified from single-trial EEG data with similar high accuracy in the two groups. However, despite robust attention-modulated speech entrainment, the HI listeners rated the competing speech task to be more difficult. These results suggest that speech-in-noise problems experienced by older HI listeners are not necessarily associated with degraded attentional selection. SIGNIFICANCE STATEMENT People with age-related sensorineural hearing loss often struggle to follow speech in the presence of competing talkers. It is currently unclear whether hearing impairment may impair the ability to use selective attention to suppress distracting speech in situations when the distractor is well segregated from the target. Here, we report amplified envelope-entrained cortical EEG responses to attended speech and to simple tones modulated at speech rates (4 Hz) in listeners with age-related hearing loss. Critically, despite increased self-reported listening difficulties, cortical synchronization to speech mixtures was robustly modulated by selective attention in listeners with hearing loss. This allowed the attended talker to be classified from single-trial EEG responses with high accuracy in both older hearing-impaired listeners and age-matched normal-hearing controls.
Impact of Dietary Interventions during Pregnancy on Maternal, Neonatal, and Child Outcomes in Low- and Middle-Income Countries

Optimal nutrition plays a crucial role in pregnancy. Maternal malnutrition is a risk factor for maternal, fetal, and neonatal complications and is more prevalent in low and middle-income countries (LMICs). This review aims to study the effectiveness of antenatal macronutrient nutritional interventions on maternal, neonatal, and child outcomes. We searched the CENTRAL, PubMed, Embase, and other databases for randomized controlled trials and quasi-experimental designs on healthy pregnant women in LMICs. We also searched grey literature and reports from Google Scholar, Web of Science, and websites of different organizations. Title/abstract screening, full-text screening, and data extraction filtered 15 studies for inclusion. Balanced energy protein (BEP) supplementation (n = 8) studies showed a reduced incidence of perinatal mortality, stillbirths, low birth weight (LBW) infants, small for gestational age (SGA) babies and increased birth weight. Food distribution programs (FDPs) (n =5) witnessed reduced rates of SGA, stunting, wasting, and increased birth weight and birth length. Studies on intervention for obesity prevention (n = 2) showed reductions in birth weight. Other findings were statistically insignificant. Subgroup analyses were conducted to study the effectiveness of supplementation between regions, location, the timing of supplementation and nutritional status; however, there were a limited number of studies in each subgroup. Data from our review supports the antenatal supplementation of BEP and FDP for the prevention of adverse maternal, neonatal, and child outcomes that can be utilized for future policymaking. However, more research is required before recommending obesity prevention programs.
Chlamydia: what is on the outside does matter

Abstract This review summarises major highlights on the structural biology of the chlamydial envelope. Chlamydiae are obligate intracellular bacteria, characterised by a unique biphasic developmental cycle. Depending on the stage of their lifecycle, they appear in the form of elementary or reticulate bodies. Since these particles have distinctive functions, it is not surprising that their envelope differs in lipid as well as in protein content. Vice versa, by identifying surface proteins, specific characteristics of the particles such as rigidity or immunogenicity may be deduced. Detailed information on the bacterial membranes will increase our understanding on the host–pathogen interactions chlamydiae employ to survive and grow and might lead to new strategies to battle chlamydial infections.
Stress and Psychiatric Disorders: The Role of Mitochondria.

In seeking to understand mental health and disease, it is fundamental to identify the biological substrates that draw together the experiences and physiological processes that underlie observed psychological changes. Mitochondria are subcellular organelles best known for their central role in energetics, producing adenosine triphosphate to power most cellular processes. Converging lines of evidence indicate that mitochondria play a key role in the biological embedding of adversity. Preclinical research documents the effects of stress exposure on mitochondrial structure and function, and recent human research suggests alterations constituting recalibrations, both adaptive and nonadaptive. Current research suggests dynamic relationships among stress exposure, neuroendocrine signaling, inflammation, and mitochondrial function. These complex relationships are implicated in disease risk, and their elucidation may inform prevention and treatment of stress- and trauma-related disorders. We review and evaluate the evidence for mitochondrial dysfunction as a consequence of stress exposure and as a contributing factor to psychiatric disease. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 16 is May 7, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

Interstitial lung disease (ILD) induced by immune checkpoint inhibitors (ICIs) is a potentially life‐threatening adverse event. The purpose of this study was to evaluate whether the development of immune‐related adverse events (irAEs), especially ILD, was associated with treatment efficacy and to research the features and risk factors of ILD in advanced non‐small cell lung cancer (NSCLC).
Effect of cytokines on NK cell activity and activating receptor expression in high-risk cutaneous melanoma patients

Objective: Stage II melanoma patients have high risk for regional and distant metastases and may benefit from novel therapeutic strategies. To clarify the role of NK cells in Stage II melanoma, we characterized the cytotoxic activity of NK cells and the expression of various activating and inhibitory receptors in high-risk cutaneous melanoma patients (Stages IIB and IIC) compared to low-risk patients (Stage IA). Materials and Methods: Native and cytokine-treated peripheral blood mononuclear cells were used for functional and phenotypical analyses. Results: Compared to Stage IA-B patients, Stage IIB-C patients showed significantly decreased NK cell activity, as well as decreased expression of the activating NKG2D and CD161 receptors, most likely due to increased serum levels of the immunosuppressive cytokine TGF-β1 in these patients. Interestingly, treatment of periperal blood mononuclear cells with IFN-α, IL-2, IL-12 or the combination of IL-12 and IL-18 significantly induced NK cell activity for both groups of melanoma patients. However, only low-risk patients had a significant increase in the expression of the NKG2D receptor after in vitro treatment with IFN-α, as well as an significant increase in the expression of CD161 after treatment with IFN-α or IL-12. Although IL-2 induced the expression of NKG2D in both groups of patients, this increase was significantly lower in high-risk melanoma. Conclusion: NK cell parameters may be useful as biomarkers of disease progression in localized melanoma patients. Our results further suggest that the use of NK cell-activating cytokines in combination with inhibitors of immunosuppressive factors like TGF-β1 could be a therapeutic option for the treatment of high-risk cutaneous melanoma patients.
Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders

Transplantation of stem cells, in particular mesenchymal stem cells (MSCs), stands as a promising therapy for trauma, stroke or neurodegenerative conditions such as spinal cord or traumatic brain injuries (SCI or TBI), ischemic stroke (IS), or Parkinson’s disease (PD). Over the last few years, cell transplantation-based approaches have started to focus on the use of cell byproducts, with a strong emphasis on cell secretome. Having this in mind, the present review discusses the current state of the art of secretome-based therapy applications in different central nervous system (CNS) pathologies. For this purpose, the following topics are discussed: (1) What are the main cell secretome sources, composition, and associated collection techniques; (2) Possible differences of the therapeutic potential of the protein and vesicular fraction of the secretome; and (3) Impact of the cell secretome on CNS-related problems such as SCI, TBI, IS, and PD. With this, we aim to clarify some of the main questions that currently exist in the field of secretome-based therapies and consequently gain new knowledge that may help in the clinical application of secretome in CNS disorders.
Visible near infrared reflectance molecular chemical imaging of human ex vivo carcinomas and murine in vivo carcinomas

Abstract. Significance: A key risk faced by oncological surgeons continues to be complete removal of tumor. Currently, there is no intraoperative imaging device to detect kidney tumors during excision. Aim: We are evaluating molecular chemical imaging (MCI) as a technology for real-time tumor detection and margin assessment during tumor removal surgeries. Approach: In exploratory studies, we evaluate visible near infrared (Vis-NIR) MCI for differentiating tumor from adjacent tissue in ex vivo human kidney specimens, and in anaesthetized mice with breast or lung tumor xenografts. Differentiation of tumor from nontumor tissues is made possible with diffuse reflectance spectroscopic signatures and hyperspectral imaging technology. Tumor detection is achieved by score image generation to localize the tumor, followed by application of computer vision algorithms to define tumor border. Results: Performance of a partial least squares discriminant analysis (PLS-DA) model for kidney tumor in a 22-patient study is 0.96 for area under the receiver operating characteristic curve. A PLS-DA model for in vivo breast and lung tumor xenografts performs with 100% sensitivity, 83% specificity, and 89% accuracy. Conclusion: Detection of cancer in surgically resected human kidney tissues is demonstrated ex vivo with Vis-NIR MCI, and in vivo on mice with breast or lung xenografts.
Microneedle-Facilitated Intradermal Proretinal Nanoparticle Delivery

Topical retinoid treatments stimulate biological activities in the skin. The main physical barrier, which limits the efficacy of transdermal drug delivery, is the stratum corneum. Proretinal nanoparticles (PRN) have already been proven to efficiently deliver retinal into the epidermis. In the present study, two transdermal drug delivery systems, microneedles (MN) and PRN, were combined to directly target the dermis. The microchannels induced by the MN, the PRN localization in the microchannels and the skin closure kinetics were investigated by non-invasive imaging techniques, such as dermoscopy, optical coherence tomography and multiphoton tomography. Additionally, the amount of retinal in the epidermis and dermis after application in three different forms (PRN-Loaded microneedles, PRN suspension or conventional retinal solution) was compared. All imaging techniques confirmed the formation of microchannels in the skin, which were partly still detectable after 24 h. Multiphoton tomography showed the release of PRN from the MN within the microchannels. The recovered retinal concentration in the dermis was significantly higher when applied via PRN-loaded microneedles. We hypothesized that this platform of PRN-loaded microneedles can provide a rapid and efficient administration of retinal in the dermis and could be of benefit in some skin conditions such as atrophic scar or photo-aged skin.
Neuron–glia interaction in the Drosophila nervous system

Animals are able to move and react in manifold ways to external stimuli. Thus, environmental stimuli need to be detected, information must be processed, and, finally, an output decision must be transmitted to the musculature to get the animal moving. All these processes depend on the nervous system which comprises an intricate neuronal network and many glial cells. Glial cells have an equally important contribution in nervous system function as their neuronal counterpart. Manifold roles are attributed to glia ranging from controlling neuronal cell number and axonal pathfinding to regulation of synapse formation, function, and plasticity. Glial cells metabolically support neurons and contribute to the blood–brain barrier. All of the aforementioned aspects require extensive cell–cell interactions between neurons and glial cells. Not surprisingly, many of these processes are found in all phyla executed by evolutionarily conserved molecules. Here, we review the recent advance in understanding neuron–glia interaction in Drosophila melanogaster to suggest that work in simple model organisms will shed light on the function of mammalian glial cells, too.
Comprehensive Evaluation of Hepatitis E Serology and Molecular Testing in a Large Cohort

Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.
Absolute Quantification of the Central Carbon Metabolome in Eight Commonly Applied Prokaryotic and Eukaryotic Model Systems

Absolute quantification of intracellular metabolite pools is a prerequisite for modeling and in-depth biological interpretation of metabolomics data. It is the final step of an elaborate metabolomics workflow, with challenges associated with all steps—from sampling to quantifying the physicochemically diverse metabolite pool. Chromatographic separation combined with mass spectrometric (MS) detection is the superior platform for high coverage, selective, and sensitive detection of metabolites. Herein, we apply our quantitative MS-metabolomics workflow to measure and present the central carbon metabolome of a panel of commonly applied biological model systems. The workflow includes three chromatographic methods combined with isotope dilution tandem mass spectrometry to allow for absolute quantification of 68 metabolites of glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle, and the amino acid and (deoxy) nucleoside pools. The biological model systems; Bacillus subtilis, Saccharomyces cerevisiae, two microalgal species, and four human cell lines were all cultured in commonly applied culture media and sampled in exponential growth phase. Both literature and databases are scarce with comprehensive metabolite datasets, and existing entries range over several orders of magnitude. The workflow and metabolite panel presented herein can be employed to expand the list of reference metabolomes, as encouraged by the metabolomics community, in a continued effort to develop and refine high-quality quantitative metabolomics workflows.
Characterization of Sheep Milk Extracellular Vesicle-miRNA by Sequencing and Comparison with Cow Milk

Simple Summary Milk provides significant health benefits for mammals, especially as the primary nutrient sources of neonates. Milk was recognized as the epigenetic “doping system” during mammalian development in recent research due to the bioactive component extracellular vesicles, which can act as mediators of intercellular communication, and even as signal carriers between different individuals, especially mothers and babies, by the containing regulatory miRNAs. It is widely accepted that although cow milk is generally more consumed by humans, sheep milk is more suitable for infants. However, compared with cow milk, few studies have focused on the sheep milk extracellular vesicles, which select specific types of miRNA to encapsulate. This study clarified the sheep milk extracellular vesicle-miRNA profiling by sequencing and made a comparison with that of cow milk. The results of this study provide more documents for the milk bioactive components in different species. Abstract Milk can mediate maternal-neonatal signal transmission by the bioactive component extracellular vesicles (EVs), which select specific types of miRNA to encapsulate. The miRNA profiling of sheep milk EVs was characterized by sequencing and compared with that of cow milk. Nanoparticle tracking analysis revealed that the concentration of sheep milk EVs was 1.3 ± 0.09 × 1012 particles/mL and the diameter was peaked at 131.2 ± 0.84 nm. Sheep milk EVs contained various small RNAs, including tRNA, Cis-regulatory element, rRNA, snRNA, other Rfam RNA, and miRNA, which held about 36% of all the small RNAs. In total, 84 types of miRNA were annotated with Ovis aries by miRBase (version 22.0) in sheep milk EVs, with 75 shared types of miRNAs in all samples. The miR-26a, miR-191, let-7f, let-7b and miR-10b were highly expressed both in cow and sheep milk EVs, and 14 sheep milk EV-miRNAs in the top 20, occupying 98% of the total expression, were immune-related. Although pathway analysis showed different potential functions of cow and sheep milk EV-miRNAs, there were still some shared points: lipid metabolism (phospholipase D, glycerophospholipid and glycosylphosphatidylinositol), calcium metabolism, and nerve conduction (axon guidance and synapse). This study provides reference for the bioactive components in the milk of different species.
Screening for Cognitive Impairment in Older Adults: US Preventive Services Task Force Recommendation Statement.

Importance Dementia (also known as major neurocognitive disorder) is defined by a significant decline in 1 or more cognitive domains that interferes with a person's independence in daily activities. Dementia affects an estimated 2.4 to 5.5 million individuals in the United States, and its prevalence increases with age. Objective To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on screening for cognitive impairment, including mild cognitive impairment and mild to moderate dementia, in community-dwelling adults, including those 65 years or older residing in independent living facilities. Population This recommendation applies to community-dwelling older adults 65 years or older, without recognized signs or symptoms of cognitive impairment. Evidence Assessment The USPSTF concludes that the evidence is lacking, and the balance of benefits and harms of screening for cognitive impairment cannot be determined. Recommendation The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults. (I statement).