julilili42/papers huggingface dataset:
Multicenter evaluation of blood‐based biomarkers for the detection of endometriosis and adenomyosis: A prospective non‐interventional study
2023-08-28

Abstract Objective To evaluate blood‐based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014–April 2018). Methods This prospective, non‐interventional study assessed the diagnostic accuracy of 54 blood‐based biomarker immunoassays in samples from 919 women (aged 18–45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were “pathologic symptomatic controls” or “pathology‐free symptomatic controls”. The main outcome measure was receiver operating characteristic‐area under the curve (ROC‐AUC) and Wilcoxon P values corrected for multiple testing ( q values). Results CA‐125 performed best in “all endometriosis cases” versus “all symptomatic controls” (AUC 0.645, 95% confidence interval [CI] 0.600–0.690, q &lt; 0.001) and increased ( P &lt; 0.001) with disease stage. In “all endometriosis cases” versus “pathology‐free symptomatic controls”, S100‐A12 performed best (AUC 0.692, 95% CI 0.614–0.769, q = 0.001) followed by CA‐125 (AUC 0.649, 95% CI 0.569–0.729, q = 0.021). In “adenomyosis only cases” versus “symptomatic controls” or “pathology‐free symptomatic controls”, respectively, the top‐performing biomarkers were sFRP‐4 (AUC 0.615, 95% CI 0.551–0.678, q = 0.045) and S100‐A12 (AUC 0.701, 95% CI 0.611–0.792, q = 0.004). Conclusion This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.
Global reorganization of atmospheric circulation during Dansgaard–Oeschger cycles
2023-08-28

Ice core records from Greenland provide evidence for multiple abrupt cold–warm–cold events recurring at millennial time scales during the last glacial interval. Although climate variations resembling Dansgaard–Oeschger (DO) oscillations have been identified in climate archives across the globe, our understanding of the climate and ecosystem impacts of the Greenland warming events in lower latitudes remains incomplete. Here, we investigate the influence of DO-cold-to-warm transitions on the global atmospheric circulation pattern. We comprehensively analyze δ 18 O changes during DO transitions in a globally distributed dataset of speleothems and set those in context with simulations of a comprehensive high-resolution climate model featuring internal millennial-scale variations of similar magnitude. Across the globe, speleothem δ 18 O signals and model results indicate consistent large-scale changes in precipitation amount, moisture source, or seasonality of precipitation associated with the DO transitions, in agreement with northward shifts of the Hadley circulation. Furthermore, we identify a decreasing trend in the amplitude of DO transitions with increasing distances from the North Atlantic region. This provides quantitative observational evidence for previous suggestions of the North Atlantic region being the focal point for these archetypes of past abrupt climate changes.
Efficacy, safety, and tolerability of albendazole and ivermectin based regimens for the treatment of microfilaraemic loiasis in adult patients in Gabon: A randomized controlled assessor blinded clinical trial
2023-08-28

Background There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon. Methods Eligible adult patients with L . loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L . loa microfilaraemia ≤ 100 mf/ml at Day 168. Results In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80–90% reduction of microfilaraemia was observed in the active treatment groups. Conclusion The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe. Trial registration Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027 .
Hillslope Morphology Drives Variability of Detrital 10Be Erosion Rates in Steep Landscapes
2023-08-28

Abstract The connection between topography and erosion rate is central to understanding landscape evolution and sediment hazards. However, investigation of this relationship in steep landscapes has been limited due to expectations of: (a) decoupling between erosion rate and “threshold” hillslope morphology; and (b) bias in detrital cosmogenic nuclide erosion rates due to deep‐seated landslides. Here we compile 120 new and published 10 Be erosion rates from catchments in the San Gabriel Mountains, California, and show that hillslope morphology and erosion rate are coupled for slopes approaching 50° due to progressive exposure of bare bedrock with increasing erosion rate. We find no evidence for drainage area dependence in 10 Be erosion rates in catchments as small as 0.09 km 2 , and we show that landslide deposits influence erosion rate estimates mainly by adding scatter. Our results highlight the potential and importance of sampling small catchments to better understand steep hillslope processes.
The Rhabdodontidae (Dinosauria, Ornithischia), an enigmatic dinosaur group endemic to the Late Cretaceous European Archipelago
2023-08-28

The Rhabdodontidae was one of the most important dinosaur groups inhabiting the Late Cretaceous European Archipelago. Currently, the clade comprises nine species within six genera, which have been found in southern France, northern Spain, eastern Austria, western Hungary and western Romania, ranging from the Santonian to the late Maastrichtian. Phylogenetic analyses consistently place the Rhabdodontidae at the very base of the iguanodontian radiation, whereas the in-group relationships of rhabdodontids are relatively poorly understood; nevertheless, the clade seems to have had a rather complicated biogeographical history. Generally, rhabdodontids were small- to medium-sized, probably habitually bipedal herbivores, characterised by a rather stocky build and a comparatively large, triangular skull. Several lines of evidence suggest that they were presumably gregarious animals, as well as selective browsers that fed on fibrous plants and occupied different ecological niches than sympatric herbivorous dinosaur clades. Moreover, the sympatry of at least two rhabdodontid taxa was rather common and can be explained, at least in some instances, by niche partitioning. While rhabdodontids disappeared prior to the K/Pg extinction event in Western Europe, they survived close to the end of the Cretaceous in Eastern Europe, where they were amongst the last non-avian dinosaurs still present before the end of the Cretaceous. In this paper, we provide an overview of the rhabdodontid taxonomic history, diversity, phylogenetic relationships and palaeobiogeographic history, as well as palaeoecology and extinction. In addition, we also highlight still open questions on each of these topics and suggest potential future research directions.
Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset
2023-08-28

Abstract Background The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA). Methods To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical‐onset FA (&lt;25 years) participating in the 4‐year prospective European FA Consortium for Translational Studies (EFACTS). Pattern of disease progression was determined using linear mixed‐effects regression models. The chosen statistical model was re‐fitted in order to estimate parameters and predict disease progression. Median time‐to‐change and rate of score progression were estimated using the Kaplan–Meier method and weighted linear regression models, respectively. Results SARA score at study enrollment and age at onset were the major predictive factors of total score progression during the 4‐year follow‐up. To a less extent, age at evaluation also influenced the speed of SARA progression, while disease duration did not improve the prediction of the statistical model. Temporal dynamics of total SARA and items showed a great variability in the speed of score increase during disease progression. Gait item had the highest annual progression rate, with median time for one‐point score increase of 1 to 2 years. Interpretation Analyses of statistical properties of SARA suggest a variable sensitivity of the scale at different disease stages, and provide important information for population selection and result interpretation in future clinical trials.
Exploring the potential of automated speech recognition for scoring the Korean Elicited Imitation Test
2023-08-28

Elicited Imitation Tests (EITs) are often used as a practical tool for measuring L2 proficiency. In this study, we explore the potential of applying three commercial automated speech recognition (ASR) tools—Amazon, Google, and Naver—in combination with several transcription scoring metrics to automate Korean EIT scoring. Two hundred and four participants' previously human-scored EITs (Isbell & Lee, 2022) were compared with automated EIT scores based on ASR transcriptions. Nearly all combinations of ASR platforms and transcription metrics correlated with original human EIT total scores above .90, with the Naver and Google transcriptions yielding the strongest correlations (r = .94-.96). Moreover, examining the item-level relationships between transcription metrics and original EIT scores yielded moderate-to-large correlations near .80 for the Google and Naver transcriptions, thereby providing additional support for the validity of automated EIT scoring. We conclude with implications for prospective users and developers of machine-scored EITs.
Long-term environmental enrichment is associated with better fornix microstructure in older adults
2023-08-28

Background Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer’s disease. This cross-sectional cohort study investigated the association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults. Methods N = 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher ( n = 104) or lower ( n = 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status. Results Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized β = 0.117, p = 0.033) and lower MD (β = −0.147, p = 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized B = 0.619, p = 0.038; MD: B = −0.035, p = 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts. Conclusion Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption.
Distinct impacts of alpha-synuclein overexpression on the hippocampal epigenome of mice in standard and enriched environments
2023-08-28

Elevated alpha-synuclein (SNCA) gene expression is associated with transcriptional deregulation and increased risk of Parkinson's disease, which may be partially ameliorated by environmental enrichment. At the molecular level, there is emerging evidence that excess alpha-synuclein protein (aSyn) impacts the epigenome through direct and/or indirect mechanisms. However, the extents to which the effects of both aSyn and the environment converge at the epigenome and whether epigenetic alterations underpin the preventive effects of environmental factors on transcription remain to be elucidated. Here, we profiled five DNA and histone modifications in the hippocampus of wild-type and transgenic mice overexpressing human SNCA. Mice of each genotype were housed under either standard conditions or in an enriched environment (EE) for 12 months. SNCA overexpression induced hippocampal CpG hydroxymethylation and histone H3K27 acetylation changes that associated with genotype more than environment. Excess aSyn was also associated with genotype- and environment-dependent changes in non-CpG (CpH) DNA methylation and H3K4 methylation. These H3K4 methylation changes included loci where the EE ameliorated the impacts of the transgene as well as loci resistant to the effects of environmental enrichment in transgenic mice. In addition, select H3K4 monomethylation alterations were associated with changes in mRNA expression. Our results suggested an environment-dependent impact of excess aSyn on some functionally relevant parts of the epigenome, and will ultimately enhance our understanding of the molecular etiology of Parkinson's disease and other synucleinopathies.
Hippocampal volume and affect in response to fluctuating estrogens in menstrual cycle irregularity: A longitudinal single-subject study
2023-08-28

Abstract Background The menstrual cycle is a critical indicator of women's reproductive, physical, and mental health, influenced by neuromodulatory sex steroid hormones, including estrogens like 17β-estradiol, and estrone. Irregular menstrual cycles can lead to various health conditions. Understanding the relationship between endogenous hormone fluctuations and brain function across the menstrual cycle is essential for comprehending mental health disorders prevalent in women. Here, we investigated the impact of hormonal variations on hippocampal morphology and affect in a participant with an irregular menstrual cycle. Methods In this dense-sampling longitudinal study, a healthy female with an irregular menstrual cycle underwent testing for five consecutive weeks, covering mostly the follicular phase and ovulation. Daily blood draws provided measurements of estradiol, estrone, and progesterone. T 1 -weighted MRI scans assessed bilateral hippocampal volumes. Psychological measures of positive and negative affect were collected each session. Statistical analyses included cubic regression curves, Spearman correlations, and mediation regression models to explore hormonal associations with hippocampal morphology and affect. Results Fluctuations were observed in hormonal concentrations, hippocampal volume, and affect across the 25 testing days. Estradiol and estrone correlated significantly with hippocampal volume, while progesterone did not show any significant association. Increased estrogen levels were linked to decreased positive affect, mediated by hippocampal volume fluctuations. Increased estrogen levels were further associated with increased negative affect, however, independently of hippocampal changes. Conclusion This study sheds light on the complex relationship between endogenous hormone fluctuations, hippocampal morphology, and affect in a participant with an irregular menstrual cycle. The findings suggest potential roles of estrogens and estrone in affect regulation, with implications for women's mental health and brain function. Further research is warranted to explore these associations in larger samples and various menstrual cycle patterns.
Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway
2023-08-29

Abstract Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&amp;E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a “notable marker” after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.
Donor–Acceptor–Donor Triads with Flexible Spacers: Deciphering Complex Photophysics for Targeted Materials Design
2023-08-29

Abstract The complex photokinetics of donor–acceptor–donor triads with varying flexible spacer lengths ( n = 4–10 carbon atoms) are investigated in liquid and solid solution, as well as in crystals, by steady‐state and transient fluorescence spectroscopy combined with computational studies. For the short spacer ( n = 4) in a liquid solution, dynamic charge‐transfer (CT) state formation with subsequent, efficient exciplex emission is observed, effectively competing with quenching through electron transfer (eT) via a radical ion pair. In a solid solution, a fluorescent CT static complex is formed upon freezing for all spacer lengths. This allows the observations of a former seminal report on stimuli‐responsive high‐contrast fluorescence on/off switching in films of the triads to be reassigned (Adv. Mater. 2012, 24, 5487), now providing a holistic picture on varying spacer length. In fact, external stimuli of the film by modulating the geometry of the CT complex, which results in on/off fluorescence switching (for n &gt; 4) or in a change of the emission color ( n = 4). The work thus demonstrates how in‐depth analysis of complex photophysics can be put to practical use in materials science.
Foxo3 Knockdown Mediates Decline of Myod1 and Myog Reducing Myoblast Conversion to Myotubes
2023-08-29

Sarcopenia has a high prevalence among the aging population. Sarcopenia is of tremendous socioeconomic importance because it can lead to falls and hospitalization, subsequently increasing healthcare costs while limiting quality of life. In sarcopenic muscle fibers, the E3 ubiquitin ligase F-Box Protein 32 (Fbxo32) is expressed at substantially higher levels, driving ubiquitin-proteasomal muscle protein degradation. As one of the key regulators of muscular equilibrium, the transcription factor Forkhead Box O3 (FOXO3) can increase the expression of Fbxo32, making it a possible target for the regulation of this detrimental pathway. To test this hypothesis, murine C2C12 myoblasts were transduced with AAVs carrying a plasmid for four specific siRNAs against Foxo3. Successfully transduced myoblasts were selected via FACS cell sorting to establish single clone cell lines. Sorted myoblasts were further differentiated into myotubes and stained for myosin heavy chain (MHC) by immunofluorescence. The resulting area was calculated. Myotube contractions were induced by electrical stimulation and quantified. We found an increased Foxo3 expression in satellite cells in human skeletal muscle and an age-related increase in Foxo3 expression in older mice in silico. We established an in vitro AAV-mediated FOXO3 knockdown on protein level. Surprisingly, the myotubes with FOXO3 knockdown displayed a smaller myotube size and a lower number of nuclei per myotube compared to the control myotubes (AAV-transduced with a functionless control plasmid). During differentiation, a lower level of FOXO3 reduced the expression Fbxo32 within the first three days. Moreover, the expression of Myod1 and Myog via ATM and Tp53 was reduced. Functionally, the Foxo3 knockdown myotubes showed a higher contraction duration and time to peak. Early Foxo3 knockdown seems to terminate the initiation of differentiation due to lack of Myod1 expression, and mediates the inhibition of Myog. Subsequently, the myotube size is reduced and the excitability to electrical stimulation is altered.
Benefitting Nonhuman Animals with AI: Why Going Beyond “Do No Harm” Is Important
2023-08-29

Abstract AI technologies affect not only humans in many ways but also sentient animals. When investigating the impact of AI on other animals, it is important to consider how these technologies can harm them. However, it is equally important to explore how they can be used to enable animals to live good lives and improve their wellbeing. In this article, I present the rationale for this claim (Section 1), highlight applications through which AI systems are or can be used to benefit nonhuman animals, and show how these benefits can be classified in terms of the harm framework proposed by Coghlan and Parker (Philosophy &amp; Technology 36:25, 2023; Section 2). Finally, I identify open research questions that need to be addressed next (Section 3).