Miracle-dz/UniFAR-FTUs huggingface dataset:
Processing of Hippocampal Network Activity in the Receiver Network of the Medial Entorhinal Cortex Layer V

The interplay between hippocampus and medial entorhinal cortex (mEC) is of key importance for forming spatial representations. Within the hippocampal–entorhinal loop, the hippocampus receives context-specific signals from layers II/III of the mEC and feeds memory-associated activity back into layer V (LV). The processing of this output signal within the mEC, however, is largely unknown. The interplay between hippocampus and medial entorhinal cortex (mEC) is of key importance for forming spatial representations. Within the hippocampal–entorhinal loop, the hippocampus receives context-specific signals from layers II/III of the mEC and feeds memory-associated activity back into layer V (LV). The processing of this output signal within the mEC, however, is largely unknown. We characterized the activation of the receiving mEC network by evoked and naturally occurring output patterns in mouse hippocampal-entorhinal cortex slices. Both types of glutamatergic neurons (mEC LVa and LVb) as well as fast-spiking inhibitory interneurons receive direct excitatory input from the intermediate/ventral hippocampus. Connections between the two types of excitatory neurons are sparse, and local processing of hippocampal output signals within mEC LV is asymmetric, favoring excitation of far projecting LVa neurons over locally projecting LVb neurons. These findings suggest a new role for mEC LV as a bifurcation gate for feedforward (telencephalic) and feedback (entorhinal–hippocampal) signal propagation. SIGNIFICANCE STATEMENT Patterned network activity in hippocampal networks plays a key role in the formation and consolidation of spatial memories. It is, however, largely unclear how information is transferred to the neocortex for long-term engrams. Here, we elucidate the propagation of network activity from the hippocampus to the medial entorhinal cortex. We show that patterned output from the hippocampus reaches both major cell types of deep entorhinal layers. These cells are, however, only weakly connected, giving rise to two parallel streams of activity for local and remote signal propagation, respectively. The relative weight of both pathways is regulated by local inhibitory interneurons. Our data reveal important insights into the hippocampal–neocortical dialogue, which is of key importance for memory consolidation in the mammalian brain.
Genome-wide dynamics of RNA synthesis, processing, and degradation without RNA metabolic labeling

The quantification of the kinetic rates of RNA synthesis, processing, and degradation are largely based on the integrative analysis of total and nascent transcription, the latter being quantified through RNA metabolic labeling. We developed INSPEcT−, a computational method based on the mathematical modeling of premature and mature RNA expression that is able to quantify kinetic rates from steady-state or time course total RNA-seq data without requiring any information on nascent transcripts. Our approach outperforms available solutions, closely recapitulates the kinetic rates obtained through RNA metabolic labeling, improves the ability to detect changes in transcript half-lives, reduces the cost and complexity of the experiments, and can be adopted to study experimental conditions in which nascent transcription cannot be readily profiled. Finally, we applied INSPEcT− to the characterization of post-transcriptional regulation landscapes in dozens of physiological and disease conditions. This approach was included in the INSPEcT Bioconductor package, which can now unveil RNA dynamics from steady-state or time course data, with or without the profiling of nascent RNA.
Androgen receptor DNA methylation is an independent determinant of glucose metabolic disorders in women; testosterone plays a moderating effect

We have previously shown that serum testosterone was associated with impaired fasting glucose (IFG) and type 2 diabetes (T2D). Testosterone can be acting through binding the androgen receptor (AR). Therefore, we aimed to explore the independent associations of AR DNA methylation (ARm) with IFG and T2D and the moderation effects of serum testosterone on the associations.
Plasmodium berghei sporozoites in nonreplicative vacuole are eliminated by a PI3P‐mediated autophagy‐independent pathway

The protozoan parasite Plasmodium, causative agent of malaria, invades hepatocytes by invaginating the host cell plasma membrane and forming a parasitophorous vacuole membrane (PVM). Surrounded by this PVM, the parasite undergoes extensive replication. Parasites inside a PVM provoke the Plasmodium‐associated autophagy‐related (PAAR) response. This is characterised by a long‐lasting association of the autophagy marker protein LC3 with the PVM, which is not preceded by phosphatidylinositol 3‐phosphate (PI3P)‐labelling. Prior to productive invasion, sporozoites transmigrate several cells and here we describe that a proportion of traversing sporozoites become trapped in a transient traversal vacuole, provoking a host cell response that clearly differs from the PAAR response. These trapped sporozoites provoke PI3P‐labelling of the surrounding vacuolar membrane immediately after cell entry, followed by transient LC3‐labelling and elimination of the parasite by lysosomal acidification. Our data suggest that this PI3P response is not only restricted to sporozoites trapped during transmigration but also affects invaded parasites residing in a compromised vacuole. Thus, host cells can employ a pathway distinct from the previously described PAAR response to efficiently recognise and eliminate Plasmodium parasites.
Delivery Approaches for Therapeutic Genome Editing and Challenges

Impressive therapeutic advances have been possible through the advent of zinc-finger nucleases and transcription activator-like effector nucleases. However, discovery of the more efficient and highly tailorable clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas9) has provided unprecedented gene-editing capabilities for treatment of various inherited and acquired diseases. Despite recent clinical trials, a major barrier for therapeutic gene editing is the absence of safe and effective methods for local and systemic delivery of gene-editing reagents. In this review, we elaborate on the challenges and provide practical considerations for improving gene editing. Specifically, we highlight issues associated with delivery of gene-editing tools into clinically relevant cells.
Sociodemographic data and APOE-ε4 augmentation for MRI-based detection of amnestic mild cognitive impairment using deep learning systems

Detection and diagnosis of early and subclinical stages of Alzheimer’s Disease (AD) play an essential role in the implementation of intervention and prevention strategies. Neuroimaging techniques predominantly provide insight into anatomic structure changes associated with AD. Deep learning methods have been extensively applied towards creating and evaluating models capable of differentiating between cognitively unimpaired, patients with Mild Cognitive Impairment (MCI) and AD dementia. Several published approaches apply information fusion techniques, providing ways of combining several input sources in the medical domain, which contributes to knowledge of broader and enriched quality. The aim of this paper is to fuse sociodemographic data such as age, marital status, education and gender, and genetic data (presence of an apolipoprotein E (APOE)-ε4 allele) with Magnetic Resonance Imaging (MRI) scans. This enables enriched multi-modal features, that adequately represent the MRI scan visually and is adopted for creating and modeling classification systems capable of detecting amnestic MCI (aMCI). To fully utilize the potential of deep convolutional neural networks, two extra color layers denoting contrast intensified and blurred image adaptations are virtually augmented to each MRI scan, completing the Red-Green-Blue (RGB) color channels. Deep convolutional activation features (DeCAF) are extracted from the average pooling layer of the deep learning system Inception_v3. These features from the fused MRI scans are used as visual representation for the Long Short-Term Memory (LSTM) based Recurrent Neural Network (RNN) classification model. The proposed approach is evaluated on a sub-study containing 120 participants (aMCI = 61 and cognitively unimpaired = 59) of the Heinz Nixdorf Recall (HNR) Study with a baseline model accuracy of 76%. Further evaluation was conducted on the ADNI Phase 1 dataset with 624 participants (aMCI = 397 and cognitively unimpaired = 227) with a baseline model accuracy of 66.27%. Experimental results show that the proposed approach achieves 90% accuracy and 0.90 F1-Score at classification of aMCI vs. cognitively unimpaired participants on the HNR Study dataset, and 77% accuracy and 0.83 F1-Score on the ADNI dataset.
RELIABLE: Resource Allocation Mechanism for 5G Network using Mobile Edge Computing

Technological advancement is currently focused on the miniaturization of devices, and integrated circuits allow us to observe the increase in the number of Internet of Things (IoT) devices. Most IoT services and devices require an Internet connection, which needs to provide the minimum processing, storage and networking requirements to best serve a requested service. One of the main goals of 5G networks is to comply with the user’s various Quality of Service (QoS) requirements in different application scenarios. Fifth-generation networks use Network Function Virtualization (NFV) and Mobile Edge Computing (MEC) concepts to achieve these QoS requirements. However, the computational resource allocation mechanisms required by the services are considered very complex. Thus, in this paper, we propose an allocation and management resources mechanism for 5G networks that uses MEC and simple mathematical methods to reduce the model complexity. The mechanism decides to allocate the resource in MEC to meet the requirements requested by the user. The simulation results show that the proposed mechanism provides a larger amount of services, leading to a reduction in the service lock number and as a reduction in the blocking ratio of services due to the accuracy of the approach and its load balancing in the process of resource allocation.
BP4RNAseq: a babysitter package for retrospective and newly generated RNA-seq data analyses using both alignment-based and alignment-free quantification method

SUMMARY Processing raw reads of RNA sequencing (RNA-seq) data, no matter public or newly sequenced data, involves a lot of specialized tools and technical configurations that are often unfamiliar and time-consuming to learn for non-bioinformatics researchers. Here, we develop the R package BP4RNAseq, which integrates the state-of-art tools from both alignment-based and alignment-free quantification workflows. The BP4RNAseq package is a highly automated tool by using an optimized pipeline to improve the sensitivity and accuracy of RNA-seq analyses. It can take only two nontechnical parameters and output six formatted gene expression quantification at gene and transcript levels. The package applies to both retrospective and newly generated bulk RNA-seq data analyses and is also applicable for single-cell RNA-seq analyses. It, therefore, greatly facilitates the application of RNA-seq. AVAILABILITY The BP4RNAseq package for R and its documentation are freely available at https://github.com/sunshanwen/BP4RNAseq. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Recovery and variation of the coastal fish community following a cold intrusion event in the Penghu Islands, Taiwan

Knowledge of community resilience aids the development of strategies to mitigate the impacts of a disturbance. An extreme low-seawater temperature event in late January and February 2008 resulted in high fish mortality in the coastal waters of the Penghu Islands, Taiwan. In this study, we used underwater diving visual censuses to analyze fish communities at eight sampling stations along the coast of the Penghu Islands for seven years after the 2008 event. We evaluated community metrics, including species richness, abundance-weighted diversity, average thermal affinity, and average trophic level, and described the temporal variation in select dominant species abundances. Species richness and diversity of the communities required 53 months to reach a steady-state at the sampling stations following the cold water intrusion. The cold event initially reduced community thermal affinity, which then increased throughout the study period, reflecting the recovery of the community to baseline thermal conditions. The increased average trophic level after the cold event implied that the temperature shock decreased the proportion of lower trophic-level fishes. Average trophic level declined as the communities recovered from the disturbance, reflecting the recovery of the community to baseline species composition in terms of feeding habit. Our results suggest that functional diversity may require longer to recover than taxonomic diversity for communities in the Penghu Islands.
Perceived discrimination and mental health among African American and Caribbean Black adolescents: ethnic differences in processes and effects

ABSTRACT Objectives: Although the relationship between perceived discrimination and mental health among Black youth is well-documented, the mechanisms underlying this association remain unclear. Drawing from the stress process model, this study examines two psychosocial mediators – self-esteem and self-efficacy – in the association between perceived discrimination and mental health among African American and Caribbean Black adolescents. This research addresses three primary research questions: First, how is perceived discrimination associated with mental health? Second, to what extent do self-esteem and self-efficacy mediate the relationship between perceived discrimination and mental health? Finally, do these relationships and processes differ between African American and Caribbean Black adolescents? Design: Data for these analyses come from the National Survey of American Life – Adolescent Supplement. We use generalized structural equation modeling to examine relationships among perceived discrimination, psychosocial resources, and mental health. Results: For both African American and Caribbean Black adolescents, more frequent perceptions of discriminatory events were associated with greater depressive symptoms and a higher likelihood of having an anxiety disorder diagnosis. However, the association between perceived discrimination and depressive symptoms was significantly stronger for Caribbean Black adolescents. Generally, self-esteem and self-efficacy were found to be significant mediators in the association between perceived discrimination and mental health, although mechanisms varied between African American and Caribbean Black youth. Conclusion: African American and Caribbean Black adolescents are highly susceptible to experiences of discrimination that negatively affect their mental health. Heterogeneity among Black youth populations must be considered when developing interventions to reduce exposure to and the effects of discrimination among these adolescents.
LncRNA Profiling Reveals That the Deregulation of H19, WT1-AS, TCL6, and LEF1-AS1 Is Associated with Higher-Risk Myelodysplastic Syndrome

Simple Summary Although lncRNAs have been increasingly recognized as regulators of hematopoiesis, only several studies addressed their role in myelodysplastic syndrome (MDS). By genome-wide profiling, we identified lncRNAs deregulated in various groups of MDS patients. We computationally constructed lncRNA-protein coding gene networks to associate deregulated lncRNAs with cellular processes involved in MDS. We showed that expression of H19, WT1-AS, TCL6, and LEF1-AS1 lncRNAs associate with higher-risk MDS and proposed processes related with these transcripts. Abstract Background: myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder with an incompletely known pathogenesis. Long noncoding RNAs (lncRNAs) play multiple roles in hematopoiesis and represent a new class of biomarkers and therapeutic targets, but information on their roles in MDS is limited. Aims: here, we aimed to characterize lncRNAs deregulated in MDS that may function in disease pathogenesis. In particular, we focused on the identification of lncRNAs that could serve as novel potential biomarkers of adverse outcomes in MDS. Methods: we performed microarray expression profiling of lncRNAs and protein-coding genes (PCGs) in the CD34+ bone marrow cells of MDS patients. Expression profiles were analyzed in relation to different aspects of the disease (i.e., diagnosis, disease subtypes, cytogenetic and mutational aberrations, and risk of progression). LncRNA-PCG networks were constructed to link deregulated lncRNAs with regulatory mechanisms associated with MDS. Results: we found several lncRNAs strongly associated with disease pathogenesis (e.g., H19, WT1-AS, TCL6, LEF1-AS1, EPB41L4A-AS1, PVT1, GAS5, and ZFAS1). Of these, downregulation of LEF1-AS1 and TCL6 and upregulation of H19 and WT1-AS were associated with adverse outcomes in MDS patients. Multivariate analysis revealed that the predominant variables predictive of survival are blast count, H19 level, and TP53 mutation. Coexpression network data suggested that prognosis-related lncRNAs are predominantly related to cell adhesion and differentiation processes (H19 and WT1-AS) and mechanisms such as chromatin modification, cytokine response, and cell proliferation and death (LEF1-AS1 and TCL6). In addition, we observed that transcriptional regulation in the H19/IGF2 region is disrupted in higher-risk MDS, and discordant expression in this locus is associated with worse outcomes. Conclusions: we identified specific lncRNAs contributing to MDS pathogenesis and proposed cellular processes associated with these transcripts. Of the lncRNAs associated with patient prognosis, the level of H19 transcript might serve as a robust marker comparable to the clinical variables currently used for patient stratification.
Redox and apoptotic potential of novel ruthenium complexes in the rat blood and heart.

Ruthenium(II) complexes offer the potential for lower toxicity compared to platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received intraperitoneally single dose of complexes (4 mg/kg/week) for 4-weeks period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometrically determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by RT-PCR. Our results showed that systemic and cardiac pro-oxidative markers (TBARS and NO2-) were significantly lower in ruthenium groups compared to cisplatin group, while concentrations of antioxidative parameters (CAT, SOD, and GSSG) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared to cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared to cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.
Time to recovery and predictors of severe community-acquired pneumonia among pediatric patients in Debre Markos referral hospital, North West Ethiopia: A retrospective follow-up study

Introduction Globally, pneumonia is a major cause of morbidity and mortality among children which leads to over 156 million episodes and 14.9 million hospitalizations each year. Besides this fact, the recovery time and predictors of children’s hospitalization related to severe community-acquired pneumonia is not well known. Therefore, the aim of this study was to estimate the median time to recovery and its predictors among severe community-acquired pneumonia patients admitted to the pediatric ward, Debre Markos referral hospital, North West Ethiopia. Methods An institution-based retrospective follow-up study was employed among 352 records of children who were admitted starting from January 2016 to December 2018. Patients' charts were retrieved using a structured data extraction tool. Cox proportional hazard model assumption and model fitness was checked. Stratified Cox regression was fitted as a final model. Hazard ratio with its 95% confidence interval was used and P-value < 0.05 was considered as a statistically significant association. Result The overall median recovery time was 4 days IQR (3–7). Recovery rate from severe community acquired pneumonia was 16.25 (95% CI: 14.54–18.15) per 100 person day observation. Age (AHR; 0.94 95% CI (0.90–0.98)), being stunted (AHR; 0.62 95% CI (0.43–0.91)), presence of danger sign at admission (AHR; 0.61 95% CI (0.40–0.94)), late presentation to seek care(AHR; 0.64 95% CI (0.47–0.88)) and co-morbidity (AHR; 0.45 95% CI (0.35–0.58)) were significant predictors of recovery time. Conclusion The median recovery time from severe community-acquired pneumonia was long so that measures to reduce recovery time should be strengthened.
Protein Intake and Frailty: A Matter of Quantity, Quality, and Timing

Frailty is a geriatric syndrome that refers to a state of reduced resiliency to stressful events that occurs in response to physiological and/or psychosocial detriments. Frailty is a predictor of poor prognosis, given that frail older adults are at higher risk of many adverse health-related events. Hence, the identification of potential strategies to prevent the development and progression of frailty is of extreme importance for avoiding its negative outcomes. An adequate protein consumption is advocated as a possible intervention for the management of frailty in older adults due to its effects on muscle mass and physical function. However, empirical evidence is still needed to support this proposition. On the other hand, substantial evidence from observational studies has provided important information on the association between frailty and dietary protein-related parameters. Here, we provide a narrative review of the current literature regarding the association between protein intake (amount (how much? ), quality (what type? ), and distribution across meals (when? )) and frailty-related parameters. The ultimate aim of this work is to offer practical, evidence-based indications to healthcare professionals responsible for the care of frail older adults.
Host Selection and Feeding Behavior by the Tarnished Plant Bug, Lygus lineolaris (Hemiptera: Miridae)

Tarnished plant bugs spent more time feeding than non-locomotion, locomotion, tapping, or probing on mustard, alfalfa, and cotton plants. More time was spent feeding on mustard than on any other host plant. Frequency and duration of rostral tapping and time to initiate feeding were inversely related to duration of feeding. There was no significant difference in the mean number of stylet probes on any host plant. Ingestion of sucrose was decreased from significantly greater amounts ( P = 0.05) to amounts not significant from that of water, by allowing the insects to contact a P -mercuribenzoate (PMB)-saturated disc placed over a feeding container. Ingestion was decreased to amounts significantly lower than that of water when PMB was added to sucrose below parafilm-covered feeding containers. It is suggested that differential inhibition of rostral tip and epipharyngeal chemosensilla by PMB is responsible for this reduction in ingestion. A model of the sequence of events, with sensory input involved in host selection and feeding of the tarnished plant bug, is proposed.