Miracle-dz/UniFAR-FTUs huggingface dataset:
How consistent are associations between stunting and child development? Evidence from a meta-analysis of associations between stunting and multidimensional child development in fifteen low- and middle-income countries

Abstract Objective Despite documented associations between stunting and cognitive development, few population-level studies have measured both indicators in individual children or assessed stunting’s associations with other developmental domains. Design Meta-analysis using publicly available data from fifteen Multiple Indicator Cluster Surveys (MICS-4) to assess the association between stunting and development, controlling for maternal education, family wealth, books in the home, developmentally supportive parenting and sex of the child, stratified by country prevalence of breast-feeding (‘low BF’<90 %, ‘high BF’ ≥90 %). Ten-item Early Childhood Development Index (ECDI) scores assessed physical, learning, literacy/numeracy and socio-emotional developmental domains. Children on track in three or four domains were considered ‘on-track’ overall. Setting Fifteen low- and middle-income countries. Subjects Publically available data from 58 513 children aged 36–59 months. Results Severe stunting (height-for-age Z-score <−3) was negatively associated with on-track development (OR=0·75; 95 % CI 0·67, 0·83). Any stunting (Z-score <−2) was negatively associated with on-track development in countries with high BF prevalence (OR=0·82; 95 % CI 0·75, 0·89). Severe and any stunting were negatively associated with physical development (OR=0·77; 95 % CI 0·66, 0·89 and OR=0·82; 95 % CI 0·74, 0·91, respectively) and literacy/numeracy development in high BF countries (OR=0·45; 95 % CI 0·38, 0·53 and OR=0·59, 95 % CI 0·51, 0·68, respectively), but not low BF countries (OR=0·93; 95 % CI 0·70, 1·23 and OR=0·95, 95 % CI 0·79, 1·12, respectively). Any stunting was negatively associated with learning (OR=0·79; 95 % CI 0·72, 0·88). There was no clear association between stunting and socio-emotional development. Conclusions Stunting is associated with many but not all developmental domains across a diversity of countries and cultures. However, associations varied by country breast-feeding prevalence and developmental domain.
Testing Phylogenetic Hypotheses of the Subgenera of the Freshwater Crayfish Genus Cambarus (Decapoda: Cambaridae)

Background The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression. Methodology/Principal Findings We use three mitochondrial and one nuclear gene regions to estimate the phylogenetic relationships for species within the genus Cambarus and test evolutionary hypotheses of relationships and associated morphological and biogeographical hypotheses. Our resulting phylogeny indicates that the genus Cambarus is polyphyletic, however we fail to reject the monophyly of Cambarus with a topology test. The majority of the Cambarus subgenera are rejected as monophyletic, suggesting the morphological characters used to define those taxa are subject to convergent evolution. While we found incongruence between taxonomy and estimated phylogenetic relationships, a multiple model regression analysis indicates that taxonomy had more explanatory power of genetic relationships than either habitat or geographic distance. Conclusions We find convergent evolution has impacted the morphological features used to delimit Cambarus subgenera. Studies of the crayfish genus Orconectes have shown gonopod morphology used to delimit subgenera is also affected by convergent evolution. This suggests that morphological diagnoses based on traditional crayfish taxonomy might be confounded by convergent evolution across the cambarids and has little utility in diagnosing relationships or defining natural groups. We further suggest that convergent morphological evolution appears to be a common occurrence in invertebrates suggesting the need for careful phylogenetically based interpretations of morphological evolution in invertebrate systematics.
Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene

Lycopene (LP), an important functional compound in tomatoes, and gold nanoparticles (AN), have received considerable attention as potential candidates for cancer therapy. However, the extreme instability and poor bioavailability of LP limits its in vivo application. This study intends to develop a nanoemulsion system incorporating both LP and AN, and to study the possible synergistic effects on the inhibition of the HT-29 colon cancer cell line. LP–nanogold nanoemulsion containing Tween 80 as an emulsifier was prepared, followed by characterization using transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, ultraviolet spectroscopy, and zeta potential analysis. The particle size as determined by TEM and DLS was 21.3±3.7 nm and 25.0±4.2 nm for nanoemulsion and 4.7±1.1 nm and 3.3±0.6 nm for AN, while the zeta potential of nanoemulsion and AN was −32.2±1.8 mV and −48.5±2.7 mV, respectively. Compared with the control treatment, both the combo (AN 10 ppm plus LP 12 μM) and nanoemulsion (AN 0.16 ppm plus LP 0.4 μM) treatments resulted in a five- and 15-fold rise in early apoptotic cells of HT-29, respectively. Also, the nanoemulsion significantly reduced the expressions of procaspases 8, 3, and 9, as well as PARP-1 and Bcl-2, while Bax expression was enhanced. A fivefold decline in the migration capability of HT-29 cells was observed for this nanoemulsion when compared to control, with the invasion-associated markers being significantly reversed through the upregulation of the epithelial marker E-cadherin and downregulation of Akt, nuclear factor kappa B, pro-matrix metalloproteinase (MMP)-2, and active MMP-9 expressions. The TEM images revealed that numerous nanoemulsion-filled vacuoles invaded cytosol and converged into the mitochondria, resulting in an abnormally elongated morphology with reduced cristae and matrix contents, demonstrating a possible passive targeting effect. The nanoemulsion containing vacuoles were engulfed and internalized by the nuclear membrane envelop for subsequent invasion into the nucleoli. Taken together, LP–nanogold nanoemulsion could provide synergistic effects at AN and LP doses 250 and 120 times lower than that in the combo treatment, respectively, demonstrating the potential of nanoemulsion developed in this study for a possible application in colon cancer therapy.
Molecular size and charge as dimensions to identify and characterize circulating glycoforms of human FSH, LH and TSH

Abstract Background: FSH, LH, and TSH are glycoprotein hormones secreted from the pituitary as fully and low-asparagine-glycosylated hormones. These glycoforms of the hormones exist as a large number of isoforms varying in their glycan contents of terminal anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU). Due to the immense heterogeneity and the low concentrations in serum it has been a challenge to develop reliable analytical methods to measure and characterize the circulating glycoforms of these hormones. Methods: The hormones were separated with respect to AMS content per molecule by calibrated 0.1% agarose suspension electrophoreses. Glycoforms in separated fractions were then analyzed with respect to size by 180 calibrated Sephadex G-100 gel filtrations. The hormones were measured with time-resolved sandwich fluoroimmunoassays. All separations and assays were performed in veronal buffer at pH 8.7. Sera and fractions were also analyzed after removal of terminal SA. Results: In addition to the fully glycosylated FSH, LH, and TSH, also tri-glycosylated FSH and di-glycosylated LH and TSH forms could be identified in serum samples. The low- and fully glycosylated hormones differed both with respect to size and to median number of AMS per molecule. Algorithms, based on the distributions by electrophoreses, were developed for each hormone to estimate percent low-glycosylated forms in serum. The median numbers of SA and SU per glycoform molecule were estimated using results obtained after desialylation. Conclusion: The methods can be used for identification and characterization of glycoforms of circulating FSH, LH, and TSH in physiological and clinical studies.
Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease.

Purpose The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method Participants were tested under permutations of low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each session, participants recited a sentence. Acoustic characteristics of vowel production were extracted, and naive listeners provided estimates of speech intelligibility. Results Overall, lower-frequency STN-DBS stimulation (60 Hz) was found to lead to improvements in intelligibility and acoustic vowel expansion. An interaction between speaker sex and STN-DBS stimulation was found for vowel measures. The combination of low frequency, mid to high voltage, and low to mid pulse width led to optimal speech outcomes; however, these settings did not demonstrate significant speech outcome differences compared with the standard clinical STN-DBS settings, likely due to substantial individual variability. Conclusions Although lower-frequency STN-DBS stimulation was found to yield consistent improvements in speech outcomes, it was not found to necessarily lead to the best speech outcomes for all participants. Nevertheless, frequency may serve as a starting point to explore settings that will optimize an individual's speech outcomes following STN-DBS surgery. Supplemental Material https://doi.org/10.23641/asha.5899228.
Efficacy of limited fluid resuscitation in patients with hemorrhagic shock: a meta-analysis.

BACKGROUNDS The objective of this meta-analysis was to evaluate the efficacy of limited fluid resuscitation during active hemorrhage compared with regular fluid resuscitation and provide strong evidences for the improvement of fluid resuscitation strategies in uncontrolled hemorrhagic shock. METHODS Electronic searches were performed using PubMed, Medline, Embase and CNKI in accordance with pre-set guidelines. Clinical trials and observation studies were included or excluded according to the criteria. The endpoints examined were mortality, hemoglobin (Hb), platelets (PLT), hematocrit (Hct), prothrombin Time (PT), activated partial thromboplastin time (APTT), base excess (BE), blood lactic acid (BLA) and the main complications, such as multiple organ dysfunction syndrome (MODS) and acute Respiratory Distress Syndrome (ARDS). Risk ratios (RR), mean differences (MDs) and 95% confidence intervals (95% Cl) were calculated using fixed/random effect model. RESULTS The search indentified 11 studies including 1482 subjects. 725 hemorrhagic patients were treated with limited fluid resuscitation while 757 patients undertook regular fluid resuscitation during active hemorrhage. Limited fluid resuscitation had its advantage to reduce the mortality in hemorrhagic shock (RR = 0.67; 95% CI = 0.56-0.81; P < 0.0001) and easily controlled the blood routine index close to normal compared with regular fluid resuscitation (Hb: MD = 13.04; 95% CI = 2.69-23.38; P = 0.01. PLT: MD = 23.16; 95% CI = 6.41-39.91; P = 0.007. Hct: MD = 0.02; 95% CI = 0.02-0.03; P < 0.00001). LFR also had shorter PT and APTT compared with RFR (PT: MD = -2.81; 95% CI = -3.44--2.17; P < 0.00001 and APTT: MD = -5.14; 95% CI = -6.16--4.12; P < 0.00001). As for blood gas analysis, LFR reduced the decrease of BE (MD = 2.48; 95% CI = 1.11-3.85; P = 0.0004) and increase of BLA (MD = -0.65; 95% CI = -0.85--0.44; P < 0.00001). Besides, LFR may also reduce the occurrence of postoperative complications (MODS: RR= 0.37; 95% CI = 0.21-0.66; P = 0.0008. ARDS: RR = 0.35; 95% CI = 0.21-0.60; P < 0.0001). CONCLUSION The results provide convincing evidence that support the continued investigation and use of limited fluid resuscitation during active hemorrhage in the trauma setting.
Intricate but tight coupling of spiracular activity and abdominal ventilation during locust discontinuous gas exchange cycles

ABSTRACT Discontinuous gas exchange (DGE) is the best studied among insect gas exchange patterns. DGE cycles comprise three phases, which are defined by their spiracular state: closed, flutter and open. However, spiracle status has rarely been monitored directly; rather, it is often assumed based on CO2 emission traces. In this study, we directly recorded electromyogram (EMG) signals from the closer muscle of the second thoracic spiracle and from abdominal ventilation muscles in a fully intact locust during DGE. Muscular activity was monitored simultaneously with CO2 emission, under normoxia and under various experimental oxic conditions. Our findings indicate that locust DGE does not correspond well with the commonly described three-phase cycle. We describe unique DGE-related ventilation motor patterns, coupled to spiracular activity. During the open phase, when CO2 emission rate is highest, the thoracic spiracles do not remain open; rather, they open and close rapidly. This fast spiracle activity coincides with in-phase abdominal ventilation, while alternating with the abdominal spiracle and thus facilitating a unidirectional air flow along the main trachea. A change in the frequency of rhythmic ventilation during the open phase suggests modulation by intra-tracheal CO2 levels. A second, slow ventilatory movement pattern probably serves to facilitate gas diffusion during spiracle closure. Two flutter-like patterns are described in association with the different types of ventilatory activity. We offer a modified mechanistic model for DGE in actively ventilating insects, incorporating ventilatory behavior and changes in spiracle state. Editors' Choice: Direct monitoring of ventilation/spiracle muscle activity, simultaneously with respirometry, reveals two different ventilation motor patterns that could explain the mechanistic basis of discontinuous gas exchange cycles in locusts.
Morphological and Functional Characterization of Non-fast-Spiking GABAergic Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex

Abstract GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons, 2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons, 4) intra-columnar projecting VIP-like interneurons, and 5) locally projecting neurogliaform-like interneurons. Trans-columnar projecting interneurons are one of the most striking interneuron types, which have not been described so far in Layer 4. They feature extensive axonal collateralization not only in their home barrel but also in adjacent barrels. Furthermore, we identified that most of the L4 nFS interneurons express somatostatin, while few are positive for the transcription factor Prox1. The morphological and electrophysiological characterization of different L4 nFS interneuron types presented here provides insights into their synaptic connectivity and functional role in cortical information processing.
Extracellular Nucleotide Hydrolysis in Dermal and Limbal Mesenchymal Stem Cells: A Source of Adenosine Production

Human Limbal (L‐MSCs) and Dermal Mesenchymal Stem Cell (D‐MSCs) possess many properties that increase their therapeutic potential in ophthalmology and dermatology. It is known that purinergic signaling plays a role in many aspects of mesenchymal stem cells physiology. They release and respond to purinergic ligands, altering proliferation, migration, differentiation, and apoptosis. Therefore, more information on these processes would be crucial for establishing future clinical applications using their differentiation potential, but without undesirable side effects. This study evaluated and compared the expression of ecto‐nucleotidases, the enzymatic activity of degradation of extracellular nucleotides and the metabolism of extracellular ATP in D‐MSCs and L‐MSCs, isolated from discard tissues of human skin and sclerocorneal rims. The D‐MSCs and L‐MSCs showed a differentiation potential into osteogenic, adipogenic, and chondrogenic lineages and the expression of markers CD105+, CD44+, CD14−, CD34−, CD45−, as expected. Both cells hydrolyzed low levels of extracellular ATP and high levels of AMP, leading to adenosine accumulation that can regulate inflammation and tissue repair. These cells expressed mRNA for ENTPD1, 2, 3, 5 and 6, and CD73 that corresponded to the observed enzymatic activities. Thus, considering the degradation of ATP and adenosine production, limbal MSCs are very similar to dermal MSCs, indicating that from the aspect of extracellular nucleotide metabolism L‐MSCs are very similar to the characterized D‐MSCs. J. Cell. Biochem. 118: 2430–2442, 2017. © 2017 Wiley Periodicals, Inc.
Effects of flexibility and aspect ratio on the aerodynamic performance of flapping wings

In the current study, we experimentally investigated the flexibility effects on the aerodynamic performance of flapping wings and the correlation with aspect ratio at angle of attack α = 45°. The Reynolds number based on the chord length and the wing tip velocity is maintained at Re = 5.3 × 103. Our result for compliant wings with an aspect ratio of 4 shows that wing flexibility can offer improved aerodynamic performance compared to that of a rigid wing. Flexible wings are found to offer higher lift-to-drag ratios; in particular, there is significant reduction in drag with little compromise in lift. The mechanism of the flexibility effects on the aerodynamic performance is addressed by quantifying the aerodynamic lift and drag forces, the transverse displacement on the wings and the flow field around the wings. The regime of the effective stiffness that offers improved aerodynamic performance is quantified in a range of about 0.5–10 and it matches the stiffness of insect wings with similar aspect ratios. Furthermore, we find that the aspect ratio of the wing is the predominant parameter determining the flexibility effects of compliant wings. Compliant wings with an aspect ratio of two do not demonstrate improved performance compared to their rigid counterparts throughout the entire stiffness regime investigated. The correlation between wing flexibility effects and the aspect ratio is supported by the stiffness of real insect wings.
Positive Regulation of Hepatitis E Virus Replication by MicroRNA-122

ABSTRACT The molecular mechanisms of liver pathology and clinical disease in hepatitis E virus (HEV) infection remain unclear. MicroRNAs (miRNAs) are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using HEV genotype 1 (HEV-1), HEV-2, HEV-3, and HEV-4 sequences showed that the majority of genomes (203/222) harbor at least one miR-122/microRNA-122-3p (miR-122*) target site. Interestingly, HEV-1 genomes showed a highly (97%) conserved miR-122 target site in the RNA-dependent RNA polymerase (RdRp) region (RdRpc). We analyzed the significance of miR-122 target sites in HEV-1/HEV-3 (HEV-1/3) genomes by using a replicon-based cell culture system. HEV infection did not change the basal levels of miR-122 in hepatoma cells. However, transfection of these cells with miR-122 mimics enhanced HEV-1/3 replication and depletion of miR-122 with inhibitors led to suppression of HEV-1/3 replication. Mutant HEV-1 replicons with an altered target RdRpc sequence (CACTCC) showed a drastic decrease in virus replication, whereas introduction of alternative miR-122 target sites in mutant replicons rescued viral replication. There was enrichment of HEV-1 RNA and miR-122 molecules in RNA-induced silencing complexes in HEV-infected cells. Furthermore, pulldown of miR-122 molecules from HEV-infected cells resulted in pulldown of HEV genomic RNA along with miR-122 molecules. These observations indicate that miR-122 facilitates HEV-1 replication, probably via direct interaction with a target site in the viral genome. The positive role of miR-122 in viral replication presents novel opportunities for antiviral therapy and management of hepatitis E. IMPORTANCE Hepatitis E is a problem in both developing and developed countries. HEV infection in most patients follows a self-limited course; however, 20% to 30% mortality is seen in infected pregnant women. HEV superinfections in patients with chronic hepatitis B or hepatitis C virus infections are associated with adverse clinical outcomes, and both conditions warrant therapy. Chronic HEV infections in immunocompromised transplant recipients are known to rapidly progress into cirrhosis. Currently, off-label use of ribavirin (RBV) and polyethylene glycol-interferon (PEG-IFN) as antiviral therapy has shown promising results in both acute and chronic hepatitis E patients; however, the teratogenicity of RBV limits its use during pregnancy, while alpha IFN (IFN-α) increases the risk of transplant rejections. Experimental data determined with genotype 1 virus in the current study show that miR-122 facilitates HEV replication. These observations present novel opportunities for antiviral therapy and management of hepatitis E.