Miracle-dz/UniFAR-FTUs huggingface dataset:
Daidzein alleviates cisplatin‐induced muscle atrophy by regulating Glut4/AMPK/FoxO pathway

Cisplatin (DDP) is widely used in cancer treatment, but DDP can cause skeletal muscle atrophy and cachexia. This study explored the effect and mechanism of daidzein (DAI) in reducing DDP‐induced skeletal muscle atrophy and cachexia in vivo and in vitro. DAI alleviated the weight, food intake, muscle, adipose tissue, kidney weight and forelimb grip of LLC tumour‐bearing mice after DDP treatment, and did not affect the antitumour effect of DDP. DAI can reduce the decrease of the cross‐sectional area of skeletal muscle fibre‐induced by DDP and prevent the change of fibre type proportion. In skeletal muscle, it can inhibit Glut4/AMPK/FoxO pathway, down‐regulate the expression of atrogin1 and MuRF1, and inhibit skeletal muscle protein degradation. In DDP treated C2C12 myotubes, DAI could inhibit Glut4/AMPK/FoxO pathway to reduce myotubes atrophy, while AMPK agonist MK‐3903 could reverse the protective effect of DAI. These results suggest that DAI can alleviate DDP‐induced skeletal muscle atrophy by downregulating the expression of Atrogin1 and MuRF1 through the regulation of Glut4/AMPK/FoxO pathway.
Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals

Abstract Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. Magnetic resonance images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage × sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis. We observed a significant APOE ε4 dosage × sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P < 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage × sex interaction effect on tau deposition after adjusting for global cortical amyloid-β (P < 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P > 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all 12 regions of interest (P < 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P < 0.05). Results from voxel-wise analysis were similar to the ones obtained from regions of interest analysis. Our findings indicate that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer’s disease and uncovers a potential explanation underlying differential APOE ε4-associated Alzheimer’s risk in males and females.
Efficacy of dialectical behavior therapy for adolescent self-harm and suicidal ideation: a systematic review and meta-analysis

Abstract Background Given the widespread nature and clinical consequences of self-harm and suicidal ideation among adolescents, establishing the efficacy of developmentally appropriate treatments that reduce both self-harm and suicidal ideation in the context of broader adolescent psychopathology is critical. Methods We conducted a systematic review and meta-analysis of the Dialectical Behaviour Therapy for Adolescents (DBT-A) literature on treating self-injury in adolescents (12–19 years). We searched for eligible trials and treatment evaluations published prior to July 2020 in MEDLINE/PubMed, Scopus, Google Scholar, EMBASE, and the Cochrane Library databases for clinical trials. Twenty-one studies were identified [five randomized-controlled trials (RCTs), three controlled clinical trials (CCTs), and 13 pre-post evaluations]. We extracted data for predefined primary (self-harm, suicidal ideation) and secondary outcomes (borderline personality symptoms; BPD) and calculated treatment effects for RCTs/CCTs and pre-post evaluations. This meta-analysis was pre-registered with OSF: osf.io/v83e7. Results Overall, the studies comprised 1673 adolescents. Compared to control groups, DBT-A showed small to moderate effects for reducing self-harm (g = −0.44; 95% CI −0.81 to −0.07) and suicidal ideation (g = −0.31, 95% CI −0.52 to −0.09). Pre-post evaluations suggested large effects for all outcomes (self-harm: g = −0.98, 95% CI −1.15 to −0.81; suicidal ideation: g = −1.16, 95% CI −1.51 to −0.80; BPD symptoms: g = −0.97, 95% CI −1.31 to −0.63). Conclusions DBT-A appears to be a valuable treatment in reducing both adolescent self-harm and suicidal ideation. However, evidence that DBT-A reduces BPD symptoms was only found in pre-post evaluations.
Evaluation of Potential Application of Wharton’s Jelly-Derived Human Mesenchymal Stromal Cells and its Conditioned Media for Dermal Regeneration using Rat Wound Healing Model

Mesenchymal stromal cells and the derived conditioned media represent an area of tremendous medical interest and, among other clinical applications, are currently being extensively explored for wound healing. The aim of this study was to comparatively evaluate the wound healing potential of xeno-free human umbilical cord-derived mesenchymal stromal cells (MSCs) and the conditioned media (CM) in a full-thickness excision wound model in rats. The evaluation parameters included rate of wound healing, serum cytokine analyses, collagen content, histopathology, and hyperspectral imaging as an independent qualitative and quantitative tool. Both the cell-based and cell-free approaches scored better in lower inflammation, as evidenced in lower IL-10 and stable IL-6 levels, and improved rate of wound healing (p < 0.0001). More importantly, no adverse reaction or rejection was observed although human MSCs and CM were used in a xenogeneic model. The presence of hFGF, hHGF, hGCSF, hIL-1Ra, hVEGF, and hIL-6 in the secretome may elucidate the regenerative potential of the xeno-free cell-based and cell-free approaches which have translational value for advanced wound care. The results revealed the therapeutic potential of both the cell-based and cell-free approaches for wound healing.
People have shaped most of terrestrial nature for at least 12,000 years

Significance The current biodiversity crisis is often depicted as a struggle to preserve untouched habitats. Here, we combine global maps of human populations and land use over the past 12,000 y with current biodiversity data to show that nearly three quarters of terrestrial nature has long been shaped by diverse histories of human habitation and use by Indigenous and traditional peoples. With rare exceptions, current biodiversity losses are caused not by human conversion or degradation of untouched ecosystems, but rather by the appropriation, colonization, and intensification of use in lands inhabited and used by prior societies. Global land use history confirms that empowering the environmental stewardship of Indigenous peoples and local communities will be critical to conserving biodiversity across the planet. Archaeological and paleoecological evidence shows that by 10,000 BCE, all human societies employed varying degrees of ecologically transformative land use practices, including burning, hunting, species propagation, domestication, cultivation, and others that have left long-term legacies across the terrestrial biosphere. Yet, a lingering paradigm among natural scientists, conservationists, and policymakers is that human transformation of terrestrial nature is mostly recent and inherently destructive. Here, we use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong. Even 12,000 y ago, nearly three quarters of Earth’s land was inhabited and therefore shaped by human societies, including more than 95% of temperate and 90% of tropical woodlands. Lands now characterized as “natural,” “intact,” and “wild” generally exhibit long histories of use, as do protected areas and Indigenous lands, and current global patterns of vertebrate species richness and key biodiversity areas are more strongly associated with past patterns of land use than with present ones in regional landscapes now characterized as natural. The current biodiversity crisis can seldom be explained by the loss of uninhabited wildlands, resulting instead from the appropriation, colonization, and intensifying use of the biodiverse cultural landscapes long shaped and sustained by prior societies. Recognizing this deep cultural connection with biodiversity will therefore be essential to resolve the crisis.
A single‐centre real‐life experience on effectiveness and safety of dupilumab in adolescents with severe atopic dermatitis in treatment with cyclosporine A

Dupilumab, a fully human monoclonal antibody that inhibits the IL-4 receptor α subunit, has been recently approved for adolescents with inadequately controlled moderate-to-severe atopic dermatitis (AD). Although large clinical trials in adolescents have demonstrated its safety and efficacy1,2, few real life data are still available3. Studies carried out required a 4-week washout period for any systemic immunosuppressants prior to starting dupilumab. However in clinical practice this procedure is not often performed.
Stream tracer breakthrough curve decomposition into mass fractions: A simple framework to analyze and compare conservative solute transport processes

Ecological functions are coupled to the physical transport of water and solutes in streams. Transport of conservative tracers in lotic systems is subject to the processes of advection, dispersion, transient storage, and mass loss to groundwater. Stream tracer experiments and the simulation of observed tracer breakthrough curve (BTC) data with 1‐D numerical transient storage models (TSMs) are commonly used to quantify these processes. Results from TSMs can be useful, but issues related to model appropriateness and parameter identifiability suggest a need for conceptually simpler approaches to BTC analyses. We present a new approach to analyze BTCs to quantify the amount of stream water transported by each dominant process. BTCs are analyzed to parse the total quantity of injected tracer mass into three dominant process domains: advection and dispersion, transient storage, and gross loss of tracer. This method can be used to quantify the relative influence of transport processes within, and among streams, and estimate the proportion of stream water associated with each mode of transport. As proof of concept, we apply this approach to conservative tracer injections on two streams of contrasting morphology. Application of this method indicates that transport of injected solute mass in an alluvial stream is dominated by advection and dispersion, relative to a beaded, peat‐bottomed stream, where more tracer mass transport was found to be associated with longer timescale transient storage processes. This approach provides a simple, inexpensive, and useful quantification of dominant transport processes and provides an additional tool for analyzing experimental BTC data.
Inclusion Membrane Growth and Composition Are Altered by Overexpression of Specific Inclusion Membrane Proteins in Chlamydia trachomatis L2

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections. This obligate intracellular bacterium develops within a membrane-bound vacuole called an inclusion, which sequesters the chlamydiae from the host cytoplasm. Host-pathogen interactions at this interface are mediated by chlamydial inclusion membrane proteins (Incs). ABSTRACT Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections. This obligate intracellular bacterium develops within a membrane-bound vacuole called an inclusion, which sequesters the chlamydiae from the host cytoplasm. Host-pathogen interactions at this interface are mediated by chlamydial inclusion membrane proteins (Incs). However, the specific functions of most Incs are poorly characterized. Previous work from our laboratories indicated that expressing an IncF fusion protein at high levels in C. trachomatis L2 negatively impacted inclusion expansion and progeny production. We hypothesize that some Incs function in the structure and organization of the inclusion membrane and that overexpression of those Incs will alter the composition of endogenous Incs within the inclusion membrane. Consequently, inclusion biogenesis and chlamydial development are negatively impacted. To investigate this, C. trachomatis L2 was transformed with inducible expression plasmids encoding IncF-, CT813-, or CT226-FLAG. Overexpression of IncF-FLAG or CT813-FLAG, but not CT226-FLAG, altered chlamydial development, as demonstrated by smaller inclusions, fewer progeny, and increased plasmid loss. The overexpression of CT813-FLAG reduced the detectable levels of endogenous IncE and IncG in the inclusion membrane. Notably, recruitment of sorting nexin-6, a eukaryotic protein binding partner of IncE, was also reduced after CT813 overexpression. Gene expression studies and ultrastructural analysis of chlamydial organisms demonstrated that chlamydial development was altered when CT813-FLAG was overexpressed. Overall, these data indicate that disrupting the expression of specific Incs changed the composition of Incs within the inclusion membrane and the recruitment of associated host cell proteins, which negatively impacted C. trachomatis development.
A Systematic Review of Cognitive Function in Adults with Spina Bifida

ABSTRACT Background: Though much research has been done on the cognitive profiles of children, the abilities of patients with SBM as they age into adulthood are not well understood. Objective: Determine if adults with SBM have impairments in overall cognition, attention, executive function, and memory compared to typically developing adults or a standardized population mean. Methods: A medical librarian composed a search of spina bifida, adults, and cognitive function. 549 results were screened using title and abstract. Data were extracted using Covidence review software, including risk of bias assessments. 24 studies were included. Results: Memory impairments, notably working and prospective, have been reported. Results in other domains varied. Average VIQ or PIQ did not imply lack of impairment in other specific domains. Conclusion: Memory impairments should be accounted for and neuropsychological testing should be considered when providing care to adults with SBM. Future longitudinal cognitive aging and interventional studies are needed.
Double burden of underweight and overweight among Indian adults: spatial patterns and social determinants

Abstract Objective: The current study explores the spatial patterns of underweight and overweight among adult men and women in districts of India and identifies the micro-geographical locations where the risks of underweight and overweight are simultaneously prevalent, after accounting for demographic and socio-economic factors. Design: We relied on BMI (weight (kg)/height squared (m2)), a measure of nutritional status among adult individuals, from the 2015–2016 National Family and Health Survey. Underweight was defined as <18·5 kg/m2 and overweight as ≥25·0 kg/m2. Setting: We adopted Bayesian structured additive quantile regression to model the underlying spatial structure in underweight and overweight burden. Participants: Men aged 15–54 years (sample size: 108 092) and women aged 15–49 years (sample size: 642 002). Results: About 19·7 % of men and 22·9 % of women were underweight, and 19·6 % of men and 20·6 % of women were overweight. Results indicate that malnutrition burden in adults exhibits geographical divides across the country. Districts located in the central, western and eastern regions show higher risks of underweight. There is evidence of substantial spatial clustering of districts with higher risk of overweight in southern and northern India. While finding a little evidence on double burden of malnutrition among population groups, we identified a total of sixty-six double burden districts. Conclusions: The current study demonstrates that the geographical burden of overweight in Indian adults is yet to surpass that of underweight, but the coexistence of double burden of underweight and overweight in selected regions presents a new challenge for improving nutritional status and necessitates specialised policy initiatives.
Kinematic and Temporospatial Changes in Children with Cerebral Palsy during the Initial Stages of Gait Development

ABSTRACT Purpose To identify changes in the gait kinematics and temporospatial parameters of children with bilateral Cerebral Palsy (CP) at 8 months after the onset of independent walking and identify differences to Typical Development (TD) children at the onset of independent walking and at 8 months follow up. Method Sixteen children with bilateral CP, GMFCS levels I and II, and 15 TD children were recruited. Gait kinematics and temporospatial parameters were recorded using a 3-D gait analysis system; the sagittal plane of the lower limb joints was analyzed. Baseline measurements were recorded at the individual’s onset of independent walking and follow up was after 8 months. Results Compared to baseline, children with bilateral CP demonstrated increased (mean difference ± SE) plantar flexion (11.79 ± 2.96), single support (0.04 ± 0.01), step length (0.2 ± 0.05) and stride length (0.4 ± 0.09), at follow up; all p < . 05. Compared to TD children, they also had lower gait speed (0.16 ± 0.05), higher single support (0.02 ± 0.01) and lower maximum knee extension (9.14 ± 4.49) during the swing phase, at baseline and follow up (0.1 ± 0.04, 0.05 ± 0.01, 23.04 ± 4.17, respectively); all p < . 05. Conclusion There are changes in the sagittal plane kinematics and temporospatial parameters of the gait during the first 8 months of independent walking. These indicate gait maturation changes and highlight the impact of walking experience on the gait characteristics of children with bilateral CP.
Lynch syndrome screening in colorectal cancer: results of a prospective 2‐year regional programme validating the NICE diagnostics guidance pathway throughout a 5.2‐million population

Screening all patients newly diagnosed with colorectal cancer (CRC) for possible Lynch syndrome (LS) has been recommended in the United Kingdom since the National Institute for Health and Care Excellence (NICE) released new diagnostics guidance in February 2017. We sought to validate the NICE screening pathway through a prospective regional programme throughout a 5.2‐million population during a 2‐year period.
Fuzzy SMC for Quantized Nonlinear Stochastic Switching Systems With Semi-Markovian Process and Application

This article is concerned with the issue of quantized sliding-mode control (SMC) design methodology for nonlinear stochastic switching systems subject to semi-Markovian switching parameters, T–S fuzzy strategy, uncertainty, signal quantization, and nonlinearity. Compared with the previous literature, the quantized control input is first considered in studying T–S fuzzy stochastic switching systems with a semi-Markovian process. A mode-independent sliding surface is adopted to avoid the potential repetitive jumping effects. Then, by means of the Lyapunov function, stochastic stability criteria are proposed to be dependent of sojourn time for the corresponding sliding-mode dynamics. Furthermore, the fuzzy-model-based SMC law is proposed to ensure the finite-time reachability of the sliding-mode dynamics. Finally, an application example of a modified series dc motor model is provided to demonstrate the effectiveness of the theoretical findings.
Does getting defensive get you anywhere?—Seasonal balancing selection, temperature, and parasitoids shape real‐world, protective endosymbiont dynamics in the pea aphid

Facultative, heritable endosymbionts are found at intermediate prevalence within most insect species, playing frequent roles in their hosts’ defence against environmental pressures. Focusing on Hamiltonella defensa, a common bacterial endosymbiont of aphids, we tested the hypothesis that such pressures impose seasonal balancing selection, shaping a widespread infection polymorphism. In our studied pea aphid (Acyrthosiphon pisum) population, Hamiltonella frequencies ranged from 23.2% to 68.1% across a six‐month longitudinal survey. Rapid spikes and declines were often consistent across fields, and we estimated that selection coefficients for Hamiltonella‐infected aphids changed sign within this field season. Prior laboratory research suggested antiparasitoid defence as the major Hamiltonella benefit, and costs under parasitoid absence. While a prior field study suggested these forces can sometimes act as counter‐weights in a regime of seasonal balancing selection, our present survey showed no significant relationship between parasitoid wasps and Hamiltonella prevalence. Field cage experiments provided some explanation: parasitoids drove modest ~10% boosts to Hamiltonella frequencies that would be hard to detect under less controlled conditions. They also showed that Hamiltonella was not always costly under parasitoid exclusion, contradicting another prediction. Instead, our longitudinal survey – and two overwintering studies – showed temperature to be the strongest predictor of Hamiltonella prevalence. Matching some prior lab discoveries, this suggested that thermally sensitive costs and benefits, unrelated to parasitism, can shape Hamiltonella dynamics. These results add to a growing body of evidence for rapid, seasonal adaptation in multivoltine organisms, suggesting that such adaptation can be mediated through the diverse impacts of heritable bacterial endosymbionts.