Miracle-dz/UniFAR-FTUs huggingface dataset:
Master Harold And The Boys

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A Cache Replication Strategy Based on Betweenness and Edge Popularity in Named Data Networking

Caching content in routers is the most significant feature of Named Data Networking (NDN) and therefore the cache performance is increasingly being concerned for NDN deployment. The default cache policy of NDN is Leave Copy Everywhere (LCE) that leaves the copies in each node the data packet passed, and most of the copies will not be requested again, which leads to the waste of cache resources. The Betweenness Strategy caches data in the node with the maximal betweenness value, which causes a high replacement rate. Considering the betweenness of nodes and the popularity of content, as well as the filter effect of cache, we propose Betweenness and Edge Popularity strategy (BEP) which caches the most popular content in the most important nodes. We also conduct comprehensive simulations based on ndnSIM. By evaluating BEP and other cache replication strategies on a virtual topology, it is indicated that BEP can achieve higher performance in terms of the cache hit ratio, server load and average delay.
Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy.
Speech-Language Disorders in 22q11.2 Deletion Syndrome: Best Practices for Diagnosis and Management

Purpose Speech and language disorders are hallmark features of 22q11.2 deletion syndrome (22qDS). Learning disabilities, cognitive deficits, palate abnormalities, velopharyngeal dysfunction, behavioral differences, and various medical and psychiatric conditions are also major features of this syndrome. The goal of this document is to summarize the state of the art of current clinical and scientific knowledge regarding 22qDS for speech-language pathologists (SLPs) and provide recommendations for clinical management. Method Best practices for management of individuals with 22qDS were developed by consensus of an expert international group of SLPs and researchers with expertise in 22qDS. These care recommendations are based on the authors' research, clinical experience, and literature review. Results This document describes the features of 22qDS as well as evaluation procedures, treatment protocols, and associated management recommendations for SLPs for the often complex communication disorders present in this population. Conclusion Early diagnosis and appropriate management of speech-language disorders in 22qDS is essential to optimize outcomes and to minimize the long-term effects of communication impairments. Knowledge of this diagnosis also allows anticipatory care and guidance regarding associated features for families, health care, and educational professionals.
Validating the theoretical bases of sleep reactivation during sharp‐wave ripples and their association with emotional valence

Sleep is important for memory consolidation, and an abundant literature suggests that reactivation in the hippocampus during sleep is instrumental to this process. Yet, the current interpretation of activity during sharp‐waves ripples (SWRs), as replay of wake experiences, relies on hypotheses that, while widely accepted, have only recently begun to be tested directly. Moreover, this theory has been mainly studied in the context of pure spatial learning, and it is still not clear how emotional valence can fit into this conceptual framework when considering reward‐ or punishment‐based learning. In this review, we will present recent experimental arguments validating the interpretation of sleep replay as reactivation of awake experiences and examine the evidence showing that the emotional valence is also replayed during sleep in a coordinated fashion with hippocampal SWRs. Finally, we will detail recent experiments showing that brain–computer interfaces can be used to modify the emotional valence associated with sleep replay.
Community Participation in and Perception of Community-Directed Treatment with Ivermectin in Kinshasa, DRC

The success of community-directed treatment with Ivermectin (CDTI) depends on active community participation. We conducted a case study nested in a cross-sectional study in the Binza Ozone Health Zone (ZS) in Kinshasa, Democratic Republic of Congo, in order to investigate community’s knowledges and perceptions of onchocerciasis and on all CDTI’s aspects. We interviewed 106 people aged 20 and over, purposively selected, through eight individual interviews and 12 focus groups. Themes used for collecting data were drawn for the Health Belief Model and data were analyzed using a deductive thematic approach. The term onchocerciasis was unknown to participants who called it “Mbitiri”, the little black fly, in their local language. This disease is seen as curse put on the sufferer by a witch and perceived as a threat because of the “Mbitiri” bites. The afflicted participants were reluctant to seek treatment and preferred traditional practitioners or healers. CDTI is considered devastating because of adverse effects of ivermectin as well as inefficient after occurrence of deaths. This explains the low level of community adhesion and participation to this strategy. Recruitment procedures for community distributors are poorly understood and awareness and health education campaigns are either non-existent or rarely carried out. Nevertheless, the latter should be regularly done.
An early Myc‐dependent transcriptional program orchestrates cell growth during B‐cell activation

Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy‐producing and anabolic pathways, widespread chromatin decompaction, and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains unclear. We addressed this issue by profiling the response to LPS stimulation in wild‐type and c‐myc‐deleted primary mouse B‐cells. Myc is rapidly induced, becomes detectable on virtually all active promoters and enhancers, but has no direct impact on global transcriptional activity. Instead, Myc contributes to the swift up‐ and down‐regulation of several hundred genes, including many known regulators of the aforementioned cellular processes. Myc‐activated promoters are enriched for E‐box consensus motifs, bind Myc at the highest levels, and show enhanced RNA Polymerase II recruitment, the opposite being true at down‐regulated loci. Remarkably, the Myc‐dependent signature identified in activated B‐cells is also enriched in Myc‐driven B‐cell lymphomas: hence, besides modulation of new cancer‐specific programs, the oncogenic action of Myc may largely rely on sustained deregulation of its normal physiological targets.
Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.
Differential Stimulation of Post-Exercise Myofibrillar Protein Synthesis in Humans Following Isonitrogenous, Isocaloric Pre-Exercise Feeding

The aim of this study was to test the effects of two disparate isonitrogenous, isocaloric pre-exercise feeds on deuterium-oxide (D2O) derived measures of myofibrillar protein synthesis (myoPS) in humans. Methods: In a double-blind parallel group design, 22 resistance-trained men aged 18 to 35 years ingested a meal (6 kcal·kg−1, 0.8 g·kg−1 carbohydrate, 0.2 g·kg−1 fat) with 0.33 g·kg−1 nonessential amino acids blend (NEAA) or whey protein (WHEY), prior to resistance exercise (70% 1RM back-squats, 10 reps per set to failure, 25% duty cycle). Biopsies of M. vastus lateralis were obtained pre-ingestion (PRE) and +3 h post-exercise (POST). The myofibrillar fractional synthetic rate (myoFSR) was calculated via deuterium labelling of myofibrillar-bound alanine, measured by gas chromatography–pyrolysis–isotope ratio mass spectrometry (GC-Pyr-IRMS). Data are a mean percentage change (95% CI). Results: There was no discernable change in myoFSR following NEAA (10(−5, 25) %, p = 0.235), whereas an increase in myoFSR was observed after WHEY (28 (13, 43) %, p = 0.003). Conclusions: Measured by a D2O tracer technique, a disparate myoPS response was observed between NEAA and WHEY. Pre-exercise ingestion of whey protein increased post-exercise myoPS, whereas a NEAA blend did not, supporting the use of NEAA as a viable isonitrogenous negative control.
Five-Year Follow-up of SWOG S0816: Limitations and Values of a PET-Adapted Approach for Stage III/IV Hodgkin Lymphoma.

Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on S0816 (NCT00822120). Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete remission (CR) on PET2 (Deauville Score{less than or equal to}3) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 (Deauville Score>3) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. We report the 5-year follow-up of S0816. A subset of 336 eligible patients were analyzed (331 had central review of PET2). PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS was 74% (95%CI:69%-79%). For patients with PET2-, the 5-year PFS was 76% (95%CI:70-81%). For patients with PET2+, the 5-year PFS was 66% (95% CI:52-76%). For all patients, the estimated 5-year overall survival (OS) was 94% (95%CI:91%-96%). There were 7 (14%) reported cases of second cancers in patients treated with eBEACOPP and 6 (2%) in patients treated with ABVD (P=0.001). The long-term OS of HL patients treated on S0816 remains high. However, nearly 25% of patients with PET2- experienced relapse events, demonstrating limitations of frontline ABVD therapy and in the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients.
Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling

Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.
Effect of screening mammography on breast cancer mortality: Quasi‐experimental evidence from rollout of the Dutch population‐based program with 17‐year follow‐up of a cohort

There is uncertainty about the magnitude of the effect of screening mammography on breast cancer mortality. The relevance and validity of evidence from dated randomized controlled trials has been questioned, whereas observational studies often lack a valid comparison group. There is no estimate of the effect of one screening invitation only. We exploited the geographic rollout of the Dutch screening mammography program across municipalities to estimate the effects of one additional biennial screening invitation on breast cancer and all‐cause mortality. Population administrative data provided vital status and cause of death of a cohort of women aged 49–63 in 1995 over 17 years. Linear probability models were used to estimate the mortality effects. We estimated 154 fewer breast cancer deaths (95% confidence interval: 40–267; p = 0.01) over 17 years in a population of 100,000 women aged 49–63 who received one additional biennial screening invitation, which corresponds to an 9.6% risk reduction for a woman of age 56. The estimated effect on all‐cause mortality was negative but not close to statistical significance. Our study shows that one single invitation for breast cancer screening is effective in reducing breast cancer mortality, which is important for health policy. The effect is smaller than previous estimates of the effect of invitation for multiple screens, which further emphasizes the importance of achieving regular participation.
Seeing‐good‐gene‐based mate choice: From genes to behavioural preferences

Abstract Although vertebrates have been reported to gain higher reproductive outputs by choosing mates, few studies have been conducted on threatened species. However, species recovery should benefit if natural mate choice could improve reproductive output (i.e. pair performance related to offspring number, such as increased clutch size, numbers of fertilized egg and fledglings). We assessed the evidence for major histocompatibility complex (MHC)‐based mate preference in the endangered crested ibis (Nipponia nippon) and quantified the impacts of such choice on reproductive output. We tested the hypothesis that crested ibis advertise “good genes” through external traits, by testing whether nuptial plumage characteristics and body morphology mediate mate choice for underlying genetic MHC variation. We found differences between males and females in preferred MHC genotypes, external traits used in mate choice and contributions to reproductive outputs. Females preferred MHC‐heterozygous males, which had darker [i.e. lower total reflectance and ultraviolet (UV) reflectance] nuptial plumage. Males preferred females lacking the DAB*d allele at the MHC class II DAB locus, which had higher average body mass. DAB*d‐free females yielded heavier eggs and more fledglings, while MHC‐heterozygous males contributed to more fertilized eggs and fledglings. Fledging rate was highest when both parents had the preferred MHC genotypes (i.e. MHC‐heterozygous father and DAB*d‐free mother). Comparisons showed that free‐mating wild and semi‐natural pairs yielded more fertilized eggs and more fledglings, with a higher fledging rate, than captive pairs matched artificially based on pedigree. Conservation programmes seldom apply modern research results to population management, which could hinder recovery of threatened species. Our results show that mate choice can play an important role in improving reproductive output, with an example in which an endangered bird selects mates using UV visual capability. Despite the undoubted importance of pedigree‐based matching of mates in conservation programmes, we show that free mating can be a better alternative strategy.
Evaluation of the synergistic antioxidant effect of resveratrol and Zataria multiflora Boiss essential oil in sodium alginate bioactive films.

Biodegradable films are the appropriate alternatives to synthetic polymers due to their potential to enhance food safety and their function as carrier for wide range of food additives especially natural antioxidants. The aim of this study was to compare the potential antioxidant activities of sodium alginate films containing resveratrol (RES) alone and in combination with Zataria multiflora essential oil (ZEO) using an in vitro model. At first, the major chemical compositions of ZEO were evaluated by GC/MS. Then, the amount of phenolic compounds of sodium alginate films were evaluated by total phenolic contents assay and antioxidant activities of films were evaluated by DPPH and ABTS assays. Finally, the concentrations of ZEO and RES which showed better antioxidant activities in sodium alginate films, were incorporated to films in combination forms, in order to evaluate their synergistic effects. According to GC/MS analysis, 35 compounds of ZEO were identified and the most important constituent compounds were Thymol (37.94%), p-Cymene (9.50%) and 3-Carene (4.98%), respectively. The results of the radical scavenging evaluations, showed better antioxidant activities of the films containing RES than the films containing ZEO and BHT. Also, the combination use of ZEO and RES into alginate films had the synergistic effects (P<0.05). Therefore, it can be concluded that alginate films incorporated with the combination of ZEO and RES is the appropriate option to postpone the oxidative reactions and can be used as natural antioxidant in food packaging industry.
Investigation of the allosteric coupling mechanism in a glutamate transporter homolog via unnatural amino acid mutagenesis

Significance Glutamate transporters harness ionic gradients for the concentrative uptake of glutamate. Normal function of glutamate transporters is required for rapid removal of glutamate from the synaptic space, which is required for efficient neurotransmission and preventing excitotoxicity. A key question in glutamate transporters is the mechanism by which the ionic gradient is coupled to glutamate uptake. Previous studies have proposed a role for hairpin-2 (HP2) in this coupling mechanism. Here, we use unnatural amino-acid mutagenesis to develop a fluorescence assay for HP2 movement in the archaeal homolog, GltPh. Using this assay, we show how key residues in the substrate binding site modulate movement of HP2 and thereby identify the sequence of events involved in the coupled binding of sodium and substrate. Glutamate transporters harness the ionic gradients across cell membranes for the concentrative uptake of glutamate. The sodium-coupled Asp symporter, GltPh is an archaeal homolog of glutamate transporters and has been extensively used to understand the transport mechanism. A critical aspect of the transport cycle in GltPh is the coupled binding of sodium and aspartate. Previous studies have suggested a major role for hairpin-2 (HP2), which functions as the extracellular gate for the aspartate binding site, in the coupled binding of sodium and aspartate to GltPh. In this study, we develop a fluorescence assay for monitoring HP2 movement by incorporating tryptophan and the unnatural amino acid, p-cyanophenylalanine into GltPh. We use the HP2 assays to show that HP2 opening with Na+ follows an induced-fit mechanism. We also determine how residues in the substrate binding site affect the opening and closing of HP2. Our data, combined with previous studies, provide the molecular sequence of events in the coupled binding of sodium and aspartate to GltPh.