Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

ABSTRACT Introduction The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results. Aim of Study The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects. Material and Methods MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran’s Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively. Results A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects. Conclusions Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.
A new theoretical study for head‐on collisions of solitary waves

Abstract A new and simple theoretical method is presented to investigate the classical problem of head‐on collisions of solitary waves. The interaction term, assumed to be composed of both the right‐going and the left‐going factors, can be solved easily. Due to our results, the run‐up phenomenon and the phase lag of each soliton can be well explained.
Time-dependent process of M/G/1 vacation models with exhaustive service

Generalized M/G/1 vacation systems with exhaustive service include multiple and single vacation models and a setup time model possibly combined with an N-policy. In these models with given initial conditions, the time-dependent joint distribution of the server's state, the queue size, and the remaining vacation or service time is known (Takagi (1990)). In this paper, capitalizing on the above results, we obtain the Laplace transforms (with respect to time) for the distributions of the virtual waiting time, the unfinished work (backlog), and the depletion time. The steady-state limits of those transforms are also derived. An erroneous expression for the steady-state distribution of the depletion time in a multiple vacation model given by Keilson and Ramaswamy (1988) is corrected.
Physicochemical and prebiotic properties of waxy rice flour modified by pullulanase

ABSTRACT The purpose of this study was to elucidate the structural, physicochemical, prebiotic, and in-vitro digestibility properties of enzymatically modified waxy rice flour (EM_WRF). Waxy rice flour (WRF) was enzymatically modified with different concentrations of pullulanase (25, 50, and 75 NPUN per g of dry basis WRF). According to XRD analysis, the A-type XRD pattern of WRF was changed to a B+V-type XRD pattern by pullulanase treatment. In the in-vitro starch digestibility study, it was found that resistant starch content (30.12–34.53%) of EM_WRF were significantly higher than that of WRF (17.34%). After fermentation of EM_WRF for 24 h, the total viable counts of L. acidophilus ATCC 4356 and L. rhamnosus ATCC 7469 on all EM_WRF was significantly higher than those on inulin. The results indicated that EM_WRF has a great prebiotic potential for the functional food industry.
A Novel Dataset and Deep Learning Benchmark for Classical Music Form Recognition and Analysis

Automated computational analysis schemes for Western classical music analysis based on form and hierarchical structure have not received much attention in the literature so far. One reason, of course, is the paucity of labeled datasets Ð which, if available, could be used to train machine learning approaches. Dataset curation cannot be crowdsourced; one needs trained musicians to devote sizable effort to carry out such annotations. Further, such an analysis is not simple for beginners; obtaining labeled data that can capture the nuances of a musician’s reasoning acquired over years of practice is fraught with challenges. To this end, we provide a system for computational analysis of classical music, both for machine learning and music researchers. First, we introduce a labeled dataset containing 200 classical music pieces annotated by form and phrases. Then, by leveraging this dataset, we show that deep learning-based methods can be used to learn Form Classification as well as Phrase Analysis and Classification, for which few (if any) results have been reported yet. Taken together, we provide the community with a unique dataset as well as a toolkit needed to analyze classical music structure, which can be used or extended to drive applications in both commercial and educational settings.
Rule-based NLP vs ChatGPT in ambiguity detection, a preliminary study

With the rapid advances of AI-based tools, the question of whether to use such tools or conventional rule-based tools often arises in many application domains. In this paper, we address this question when considering the issue of ambiguity in requirements documents. For this purpose, we consider GPT-3 that is the third-generation of the Generative Pretrained Transformer language model, developed by OpenAI and we compare its ambiguity detection capability with that of a publicly available rule-based NLP tool on a few example requirements documents
Mitochondrial Sodium/Calcium Exchanger (NCLX) Regulates Basal and Starvation-Induced Autophagy Through Calcium Signaling

Mitochondria shape intracellular Ca2+ signaling through the concerted activity of Ca2+ uptake via mitochondrial calcium uniporter, and efflux from by Na+/Ca2+ exchangers (NCLX). Here, we describe a novel relationship between NCLX, intracellular Ca2+, and autophagic activity. Conditions that stimulate autophagy in vivo and in vitro, such as caloric restriction and nutrient deprivation, upregulate NCLX expression in hepatic tissue and cells. Conversely, knockdown of NCLX impairs basal and starvation-induced autophagy. Similarly, acute inhibition of NCLX activity by CGP 37157 affects bulk and endoplasmic reticulum autophagy (ER-phagy) without significant impacts on mitophagy. Mechanistically, CGP 37157 inhibited the formation of FIP200 puncta and downstream autophagosome biogenesis. Inhibition of NCLX caused decreased cytosolic Ca2+ levels, and intracellular Ca2+ chelation similarly suppressed autophagy. Furthermore, chelation did not exhibit an additive effect on NCLX inhibition of autophagy, demonstrating that mitochondrial Ca2+ efflux regulates autophagy through the modulation of Ca2+ signaling. Collectively, our results show that the mitochondrial Ca2+ extrusion pathway through NCLX is an important regulatory node linking nutrient restriction and autophagy regulation.
FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1

Aging is characterized by changes in gene expression that drive deleterious cellular phenotypes leading to senescence. The transcriptional activation of senescence genes has been mainly attributed to epigenetic shifts, but the changes in chromatin accessibility and its underling mechanisms remain largely elusive in natural aging. Here, we profiled chromatin accessibility in human dermal fibroblasts (HDFs) from neonatal and octogenarian individuals. We found that AP-1 binding motifs are prevalent in elderly specific accessible regions of the chromatin while neonatal-specific regions are highly enriched for TEAD binding motifs. We further show that TEAD4 and FOXM1 share a conserved transcriptional regulatory landscape controlled by an age-dependent enhancer that closes with aging and drives senescence when deleted. Finally, we demonstrate that FOXM1 ectopic expression in elderly cells partially resets chromatin accessibility to a youthful state due to FOXM1 repressive function in the promoters of several members of the AP-1 complex. These results place FOXM1 at a top hierarchical level in chromatin remodeling required to prevent senescence.
The microbiota of Amblyomma americanum reflects known westward expansion

Amblyomma americanum, a known vector of multiple tick-borne pathogens, has expanded its geographic distribution across the United States in the past decades. Tick microbiomes may play a role shaping their host’s life history and vectorial capacity. Bacterial communities associated with A. americanum may reflect, or enable, geographic expansion and studying the microbiota will improve understanding of tick- borne disease ecology. We examined the microbiota structure of 189 adult ticks collected in four regions encompassing their historical and current geographic distribution. Both geographic region of origin and sex were significant predictors of alpha diversity. As in other tick models, within-sample diversity was low and uneven given the presence of dominant endosymbionts. Beta diversity analyses revealed that bacterial profiles of ticks of both sexes collected in the West were significantly different from those of the Historic range. Biomarkers were identified for all regions except the historical range. In addition, Bray-Curtis dissimilarities overall increased with distance between sites. Relative quantification of ecological processes showed that, for females and males, respectively, drift and dispersal limitation were the primary drivers of community assembly. Collectively, our findings highlight how microbiota structural variance discriminates the western-expanded populations of A. americanum ticks from the Historical range. Spatial autocorrelation, and particularly the detection of non- selective ecological processes, are indicative of geographic isolation. Our conclusions demonstrate the value of synergistic analysis of biogeographic and microbial ecology data in investigating range expansion in A. americanum and potentially other tick vectors as well. Importance The incidence of tick-borne diseases is on the rise worldwide, including in the United States. This increase in cases is in large part due to the geographic expansion of tick vectors. Among them is the Lone Star tick, Amblyomma americanum, and understanding the factors driving its recent expansion is important for risk assessment and tick population control. Climate change and human activities have previously been posited to be main driving forces for their expansion. New sources of relevant biological data can further our understanding of this phenomenon. Microbial communities associated with ticks include bacteria that affect pathogen transmission and tick behaviors. Here, we investigated whether bacterial community and geographic location data could be combined to better understand the expansion of A. americanum populations. It’s not clear whether differences in the microbiota are reflective of or facilitating expansion, but our findings suggest this approach is promising and warrants further investigation.
Evaluation of three sets of advanced backcrosses of eggplant with wild relatives from different gene pools under low N fertilization conditions

The development of new cultivars with improved nitrogen use efficiency (NUE) is key for implementing sustainable agriculture practices. Crop wild relatives (CWRs) provide valuable genetic resources for breeding programs aimed at achieving this goal. In this study, three eggplant (Solanum melongena) accessions together with their advanced backcrosses (ABs; BC3 to BC5 generations) with introgressions from the wild relatives S. insanum, S. dasyphyllum, and S. elaeagnifolium were evaluated for 22 morpho-agronomic, physiological, and N use efficiency (NUE) traits under low nitrogen fertilization conditions. The three S. melongena recurrent parents were also evaluated under control (normal) N fertilization. Reduction of N fertilization in the parents resulted in decreased chlorophyll content-related traits, aerial biomass, stem diameter and yield, and increased NUE, nitrogen uptake efficiency (NUpE), and nitrogen utilization efficiency (NUtE). However, the decrease in yield was moderate, ranging between 62.6% and 72.6%. A high phenotypic variation was observed within each of the three sets of ABs under low nitrogen conditions, with some individuals displaying improved transgressive characteristics over the recurrent parents. Genotyping with the SPET 5k probes platform revealed a high, although variable, degree of recovery of the recurrent parent genome in the ABs and allowed the identification of 16 QTLs. Different allelic effects were observed for the introgressed QTL alleles. Several candidate genes were identified in the QTL regions associated with plant growth, yield, fruit size, and NUE-related parameters. Our results show that eggplant materials with introgressions from CWRs can result in a dramatic impact in eggplant breeding for a more sustainable agriculture.
MskAge - An Epigenetic Biomarker of Musculoskeletal Age Derived from a Genetic Algorithm Islands Model

Background Age is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model. Results We developed a highly accurate epigenetic clock, Msk-Age, that is specific to tissues and cells of the musculoskeletal system. MskAge was built using a penalised genetic algorithm islands model that addresses multi-tissue clock bias. The final model was trained on the transformed principal components of CpGs selected by the genetic algorithm, which are significantly enriched for pathways terms related to the skeletal system and mesenchyme development. We show that MskAge tracks epigenetic ageing ex vivo and in vitro. Epigenetic age estimates are rejuvenated to zero with cellular reprogramming and are accelerated at a rate of 0.45 years per population doubling. Remarkably, MskAge explains more variance associated with in vitro ageing of fibroblasts than the purpose-developed skin and blood clock. Conclusion The precision of MskAge and its ability to capture perturbations in biological ageing make it a promising research tool for musculoskeletal and ageing biologists.
Nuclear export is a limiting factor in eukaryotic mRNA metabolism

The eukaryotic mRNA life cycle includes transcription, nuclear mRNA export and degradation. To quantify all these processes simultaneously, we perform thiol-linked alkylation after metabolic labeling of RNA with 4-thiouridine (4sU), followed by sequencing of RNA (SLAM-seq) in the nuclear and cytosolic compartments. We develop a model that reliably quantifies mRNA synthesis, nuclear export, and nuclear and cytosolic degradation rates on a genome-wide scale. We find that nuclear degradation of polyadenylated mRNA is negligible and nuclear mRNA export is slow, while cytosolic mRNA degradation is comparatively fast. Consequently, an mRNA molecule generally spends most of its life in the nucleus. We also observe large differences in the nuclear export rates of different 3’UTR transcript isoforms. Furthermore, we identify genes whose expression is abruptly induced upon metabolic labeling. These transcripts are exported substantially faster than average mRNAs, suggesting the existence of alternative export pathways. Our results highlight nuclear mRNA export as a limiting factor in mRNA metabolism and gene regulation.
Genetic control of the error-prone repair of a chromosomal double-strand break with 5’ overhangs in yeast

A targeted double-strand break introduced into the genome of Saccharomyces cerevisiae is repaired by the relatively error-prone nonhomologous-end joining (NHEJ) pathway when homologous recombination is not an option. A ZFN cleavage site was inserted out-of-frame into the LYS2 locus of a haploid yeast strain to study the genetic control of NHEJ when the ends contain 5′ overhangs. Repair events that destroyed the cleavage site were identified either as Lys+ colonies on selective medium or as surviving colonies on rich medium. Junction sequences in Lys+ events solely reflected NHEJ and were influenced by the nuclease activity of Mre11 as well as by the presence/absence of the NHEJ-specific polymerase Pol4 and the translesion-synthesis DNA polymerases Pol σ and Pol 11. Although most NHEJ events were dependent on Pol4, a 29-bp deletion with endpoints in 3-bp repeats was an exception. The Pol4-independent deletion required TLS polymerases as well as the exonuclease activity of the replicative Pol DNA polymerase. Survivors were equally split between NHEJ events and 1 kb or 11 kb deletions that reflected microhomology-mediated end joining (MMEJ). MMEJ events required the processive resection activity of Exo1/Sgs1, but there unexpectedly was no dependence on the Rad1-Rad10 endonuclease for the removal of presumptive 3′ tails. Finally, NHEJ was more efficient in non-growing than in growing cells and was most efficient in G0 cells. These studies provide novel insight into the flexibility and complexity of error-prone DSB repair in yeast.
Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity

Alzheimer’s disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to altered visual experience in vivo in the visual cortex. We show that the baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, visual deprivation fails to induce inhibitory synapse loss in amyloidosis, a phenomenon observed in nonpathological conditions. Intriguingly, inhibitory synapse loss associated with visual deprivation in nonpathological mice is accompanied by the broadening of spontaneous but not visually evoked calcium transients. However, such broadening does not manifest in the context of amyloidosis. We also show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state. In contrast, a fraction of synapse loss is not locally clustered in amyloidosis, indicating an impairment in inhibitory synapse adaptation to changes in excitatory synaptic activity.
Glycan strand cleavage by a lytic transglycosylase, MltD contributes to the expansion of peptidoglycan in Escherichia coli

Peptidoglycan (PG) is a protective sac-like exoskeleton present in most bacterial cell walls. It is a large, covalently cross-linked mesh-like polymer made up of several glycan strands cross-bridged to each other by short peptide chains. Because PG forms a continuous mesh around the bacterial cytoplasmic membrane, opening the mesh is critical to generate space for the incorporation of new material during its expansion. In Escherichia coli, the ‘space-making activity’ is known to be achieved by cleavage of cross-links between the glycan strands by a set of redundant PG endopeptidases whose absence leads to rapid lysis and cell death. Here, we demonstrate a hitherto unknown role of glycan strand cleavage in making space for cell wall expansion in E. coli. We find that overexpression of a membrane-bound lytic transglycosylase, MltD that cuts the glycan polymers of the PG sacculus rescues the cell lysis caused by the absence of essential cross-link specific endopeptidases, MepS, MepM and MepH. Further detailed genetic and biochemical analysis revealed that MltD works in conjunction with cross-link specific endopeptidases to expand the PG sacculus. Interestingly, we find that cellular MltD levels are stringently controlled by two independent regulatory pathways. MltD undergoes regulated proteolysis by NlpI-Prc, a periplasmic adaptor-protease complex that specifically degrades two of the elongation-specific endopeptidases, MepS and MepH. In addition, MltD levels are post-transcriptionally controlled by RpoS, a stationary-phase specific sigma factor. Overall, our results show that coordinated cleavage of the glycan strands and the peptide cross-bridges facilitates the opening of the PG mesh for successful expansion of the cell wall during growth of a bacterium. AUTHOR SUMMARY Most bacteria are protected by a cell wall made up of peptidoglycan (PG), a mesh-like large polymer. PG consists of several linear glycan strands interlinked through short peptide chains to form a continuous meshwork around the bacterial cytoplasmic membrane. Because PG tightly encases the cytoplasmic membrane, the growth of a bacterial cell is coupled to the expansion of PG requiring the activity of hydrolytic enzymes that cleave PG cross-links to make space for incorporation of new PG material. ln E. coli, a set of redundant cross-link specific endopeptidases are known to be crucial for expansion of PG. In this study, we show that cleavage of the glycan polymers by MltD, a glycan cleaving enzyme compensates the absence of cross-link cleavage and contributes to the expansion of PG. Overall, our work shows a previously unknown role of glycan hydrolases in cell wall expansion identifying these as potential targets for development of cell wall-specific antimicrobial agents.
Existence of positive almost periodic or ergodic solutions for some neutral nonlinear integral equations

E.Ait Dads Université Cadi Ayyad, Département de Mathématiques, Faculté des Sciences, B.P. 2390 Marrakech, Morocco e-mail: aitdads@ucam.ac. ma P. Cieutat Laboratoire de Mathématiques de Versailles, Université de Versailles Saint-Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France e-mail: Philippe.Cieutat@math.uvsq. fr L. Lhachimi Université Cadi Ayyad, Département de Mathématiques, Faculté des Sciences, B.P. 2390 Marrakech, Morocco e-mail: lhachimi@voila.fr