Miracle-dz/UniFAR-FTUs huggingface dataset:
Abrogation of Plasminogen Activator Inhibitor-1-Vitronectin Interaction Ameliorates Acute Kidney Injury in Murine Endotoxemia

Sepsis-induced acute kidney injury (AKI) contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1) and vitronectin (Vn) are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1−/−) or expressing a PAI-1-mutant (PAI-1R101A/Q123K) in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1−/− and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT) mice after LPS challenge. Also, PAI-1−/− mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC) in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.
Global Effects of Kinase Inhibitors on Signaling Networks Revealed by Quantitative Phosphoproteomics*

Aberrant signaling causes many diseases, and manipulating signaling pathways with kinase inhibitors has emerged as a promising area of drug research. Most kinase inhibitors target the conserved ATP-binding pocket; therefore specificity is a major concern. Proteomics has previously been used to identify the direct targets of kinase inhibitors upon affinity purification from cellular extracts. Here we introduce a complementary approach to evaluate the effects of kinase inhibitors on the entire cell signaling network. We used triple labeling SILAC (stable isotope labeling by amino acids in cell culture) to compare cellular phosphorylation levels for control, epidermal growth factor stimulus, and growth factor combined with kinase inhibitors. Of thousands of phosphopeptides, less than 10% had a response pattern indicative of targets of U0126 and SB202190, two widely used MAPK inhibitors. Interestingly, 83% of the growth factor-induced phosphorylation events were affected by either or both inhibitors, showing quantitatively that early signaling processes are predominantly transmitted through the MAPK cascades. In contrast to MAPK inhibitors, dasatinib, a clinical drug directed against BCR-ABL, which is the cause of chronic myelogenous leukemia, affected nearly 1,000 phosphopeptides. In addition to the proximal effects on ABL and its immediate targets, dasatinib broadly affected the downstream MAPK pathways. Pathway mapping of regulated sites implicated a variety of cellular functions, such as chromosome remodeling, RNA splicing, and cytoskeletal organization, some of which have been described in the literature before. Our assay is streamlined and generic and could become a useful tool in kinase drug development.
Dietary Inflammatory Index, Sleep Duration, and Sleep Quality: A Systematic Review

The inflammatory potential of the diet, as measured by the Dietary Inflammatory Index (DII®), has been repeatedly shown to be associated with various inflammatory markers and mental and physical health outcomes. Of specific importance, several cross-sectional studies revealed mixed results regarding the correlations between the DII and sleep outcomes. Hence, in the current paper, a systematic review that examines the associations between the DII, sleep duration, and sleep quality was performed. The PubMed database was systematically searched for studies published up to November 2023 following PRISMA guidelines. Only cross-sectional studies that assessed the DII, sleep duration, and sleep quality across healthy and unhealthy cohorts were included. Eleven and seven studies were included in the systematic review for sleep quality and duration, respectively. The results of the present systematic review show that pro-inflammatory diets may be associated with poor sleep outcomes (duration and quality); however, as the current literature is inconsistent and limited, further cross-sectional studies in larger cohorts are necessary to (i) explore this relationship to address this heterogeneity and (ii) explore populations that are more sensitive to diet-induced inflammation.
Effects of Dantrolene Treatment on Ventricular Electrophysiology and Arrhythmogenesis in Rats With Chronic β-Adrenergic Receptor Activation

Dantrolene, which is primarily used to treat malignant hyperthermia, has recently been suggested for the prevention of arrhythmogenesis in various animal models. In this study, the effects of dantrolene treatment on electrophysiological properties and ventricular arrhythmias (VAs) in rats with chronic β-adrenergic receptor (β-AR) activation were investigated. Rats were randomized to treatment with saline (control group), isoproterenol (ISO; ISO group), or ISO + dantrolene (ID group) for 2 weeks. An electrophysiological study was performed to assess action potential duration restitution (APDR) and induce action potential duration (APD) alternans or VA in vitro. The protein levels of Cav1.2, sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and ryanodine receptor 2 (RyR2) were detected by Western blot. Compared with the control group, chronic administration of ISO significantly increased APD, the maximum slope (Smax) of APDR curve, and the spatial dispersions of Smax and APD (all P < .01), and all effects were attenuated by dantrolene treatment (all P < .05). Additionally, chronic ISO administration significantly reduced the protein levels of SERCA2 and RyR2, but increased the Cav1.2 protein expression (all P < .05). However, compared with the ISO group, dantrolene treatment preserved SERCA2a and RyR2 protein levels and decreased Cav1.2 protein levels in the ID group (all P < .05). The intracellular Ca2+ ([Ca2+]i) levels measured by incubating isolated cardiomyocytes with Fluo-3/alveolar macrophages were significantly increased in the ISO group compared with the control group (P < .01). Dantrolene treatment markedly reduced the rise of [Ca2+]i levels caused by chronic administration of ISO (P < .05). Dantrolene treatment also prevented the reductions in the APD alternans and VA thresholds induced by chronic ISO stimulation (all P < .05). These data suggest that dantrolene stabilizes ventricular electrophysiological characteristics and increases the expression of key sarcoplasmic reticulum calcium cycling proteins to reduce vulnerability to VA in rats with chronic β-AR activation.
Impression Formation in Computer-Mediated Communication Revisited

Following either a text-based, synchronous computer-mediated conversation (CMC) or a face-to-face dyadic interaction, 80 participants rated their partners' personality profile. Impressions were assessed in terms of both their breadth (the comprehensiveness of the impression) and intensity (the magnitude of the attributions). Results indicated that impressions formed in the CMC environment were less detailed but more intense than those formed face-to-face. These data provide support for theories that, in addition to acknowledging the unique constraints and characteristics of CMC, consider the cognitive strategies and heuristics involved in the impression formation process. The differential impact of a text-based medium on trait-specific impressions (e.g., extraversion, neuroticism) is also discussed in the context of a cross-modal approach to impression formation.
Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group.

PURPOSE This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. PATIENTS AND METHODS Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent. RESULTS A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. CONCLUSION GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine.

In mice, the mdr1a and mdr1b genes encode drug-transporting proteins that can cause multidrug resistance in tumor cells by lowering intracellular drug levels. These P-glycoproteins are also found in various normal tissues such as the intestine. Because mdr1b P-glycoprotein is not detectable in the intestine, mice with a homozygously disrupted mdr1a gene [mdr1a(-/-) mice] do not contain functional P-glycoprotein in this organ. We have used these mdr1a(-/-) mice to study the effect of gut P-glycoprotein on the pharmacokinetics of paclitaxel. The area under the plasma concentration-time curves was 2- and 6-fold higher in mdr1a(-/-) mice than in wild-type (wt) mice after i.v. and oral drug administration, respectively. Consequently, the oral bioavailability in mice receiving 10 mg paclitaxel per kg body weight increased from only 11% in wt mice to 35% in mdr1a(-/-) mice. The cumulative fecal excretion (0-96 hr) was markedly reduced from 40% (after i.v. administration) and 87% (after oral administration) of the administered dose in wt mice to below 3% in mdr1a(-/-) mice. Biliary excretion was not significantly different in wt and mdr1a(-/-) mice. Interestingly, after i.v. drug administration of paclitaxel (10 mg/kg) to mice with a cannulated gall bladder, 11% of the dose was recovered within 90 min in the intestinal contents of wt mice vs. <3% in mdr1a(-/-) mice. We conclude that P-glycoprotein limits the oral uptake of paclitaxel and mediates direct excretion of the drug from the systemic circulation into the intestinal lumen.
The complete mitochondrial genome of Meriones meridianus (Rodentia: Cricetidae) and its phylogenetic analysis

Abstract Meriones meridianus belongs to the genus Meriones in Gerbillinae. Total length of complete mitochondrial genome of M. meridianus is 16,376 bp and the heavy strand contains 32.8% A, 13.1% G, 25.3% C and 28.8% T. Sequences of protein-coding genes are 11,341 bp in length, accounting for 69.25%, approximately. Results of phylogenetic analysis shown that M. meridianus and Meriones unguiculatus were clustered in a single branch. This conclusion would be an important data for relevant studies about the genus Meriones, and mitochondrial genome would be an important supplement for the gene pool of Rodentia. It would play a pivotal role in researches about phylogeography and proteomics involving M. meridianus as well.
Phytochemical and Biological Investigation of Clivia nobilis Flowers Cultivated in Egypt

Amaryllidaceae is a well-known family for its high alkaloidal content. These alkaloids comprise a unique group of bases that have been found to occur in this family. The Amaryllidaceae alkaloids represent a large and still expanding group of isoquinoline alkaloids, the majority of which are not known to occur in any other family of plants. This article reports on the phytochemical investigation of the alkaloidal content of the flowers of clivia nobilis cultivated in Egypt which resulted in the isolation of four alkaloids; lycorine with pyrrolo{de}phenanthridine nucleus (lycorine-type) which is the common alkaloid of the amaryllidaceae family, clivatine and nobilisine, both with [2]benzopyrano (3,4-g) indole nucleus (lycorenine-type) and (+) 8-O-demethylmaritidine with 5,10b-ethanophenanthridine nucleus (crinine-type). Furthermore, the antimicrobial activity of the chloroform extract of the flowers of c. nobilis along with some of the isolated alkaloids has been studied.
Bioinformatics Analysis of MAPKKK Family Genes in Medicago truncatula

Mitogen-activated protein kinase kinase kinase (MAPKKK) is a component of the MAPK cascade pathway that plays an important role in plant growth, development, and response to abiotic stress, the functions of which have been well characterized in several plant species, such as Arabidopsis, rice, and maize. In this study, we performed genome-wide and systemic bioinformatics analysis of MAPKKK family genes in Medicago truncatula. In total, there were 73 MAPKKK family members identified by search of homologs, and they were classified into three subfamilies, MEKK, ZIK, and RAF. Based on the genomic duplication function, 72 MtMAPKKK genes were located throughout all chromosomes, but they cluster in different chromosomes. Using microarray data and high-throughput sequencing-data, we assessed their expression profiles in growth and development processes; these results provided evidence for exploring their important functions in developmental regulation, especially in the nodulation process. Furthermore, we investigated their expression in abiotic stresses by RNA-seq, which confirmed their critical roles in signal transduction and regulation processes under stress. In summary, our genome-wide, systemic characterization and expressional analysis of MtMAPKKK genes will provide insights that will be useful for characterizing the molecular functions of these genes in M. truncatula.
A QoS-Aware Intelligent Replica Management Architecture for Content Distribution in Peer-to-Peer Overlay Networks

The large scale content distribution systems were improved broadly using the replication techniques. The demanded contents can be brought closer to the clients by multiplying the source of information geographically, which in turn reduce both the access latency and the network traffic. The system scalability can be improved by distributing the load across multiple servers which is proposed by replication. If a copy of the requested object (e.g., a web page or an image) is located in its closer proximity then the clients would feel low access latency. Depending on the position of the replicas, the effectiveness of replication tends to a large extent. A QoS based overlay network architecture involving an intelligent replica placement algorithm is proposed in this paper. Its main goal is to improve the network utilization and fault tolerance of the P2P system. In addition to the replica placement, it also has a caching technique, to reduce the search latency. We are able to show that our proposed architecture attains less latency and better throughput with reduced bandwidth usage, through the simulation results. Keywords-Clusters, Content, Overlay, QoS, Replica, Routing
Myc Enforces Overexpression of EZH2 in Early Prostatic Neoplasia via Transcriptional and Post-transcriptional Mechanisms

EZH2 is part of the PRC2 polycomb repressive complex that is overexpressed in multiple cancer types and has been implicated in prostate cancer initiation and progression. Here, we identify EZH2 as a target of the MYC oncogene in prostate cancer and show that MYC coordinately regulates EZH2 through transcriptional and post-transcriptional means. Although prior studies in prostate cancer have revealed a number of possible mechanisms of EZH2 upregulation, these changes cannot account for the overexpression EZH2 in many primary prostate cancers, nor in most cases of high grade PIN. We report that upregulation of Myc in the mouse prostate results in overexpression of EZH2 mRNA and protein which coincides with reductions in miR-26a and miR-26b, known regulators of EZH2 in some non-prostate cell types, albeit not in others. Further, in human prostate cancer cells, Myc negatively regulates miR-26a and miR-26b via direct binding to their parental Pol II gene promoters, and forced overexpression of miR-26a and miR-26b in prostate cancer cells results in decreased EZH2 levels and suppressed proliferation. In human clinical samples, miR-26a and miR-26b are downregulated in most primary prostate cancers. As a separate mechanism of EZH2 mRNA upregulation, we find that Myc binds directly to and activates the transcription of the EZH2 promoter. These results link two major pathways in prostate cancer by providing two additional and complementary Myc-regulated mechanisms by which EZH2 upregulation occurs and is enforced during prostatic carcinogenesis. Further, the results implicate EZH2-driven mechanisms by which Myc may stimulate prostate tumor initiation and disease progression.
Fast Higher-Order MR Image Reconstruction Using Singular-Vector Separation

Medical resonance imaging (MRI) conventionally relies on spatially linear gradient fields for image encoding. However, in practice various sources of nonlinear fields can perturb the encoding process and give rise to artifacts unless they are suitably addressed at the reconstruction level. Accounting for field perturbations that are neither linear in space nor constant over time, i.e., dynamic higher-order fields, is particularly challenging. It was previously shown to be feasible with conjugate-gradient iteration. However, so far this approach has been relatively slow due to the need to carry out explicit matrix-vector multiplications in each cycle. In this work, it is proposed to accelerate higher-order reconstruction by expanding the encoding matrix such that fast Fourier transform can be employed for more efficient matrix-vector computation. The underlying principle is to represent the perturbing terms as sums of separable functions of space and time. Compact representations with this property are found by singular-vector analysis of the perturbing matrix. Guidelines for balancing the accuracy and speed of the resulting algorithm are derived by error propagation analysis. The proposed technique is demonstrated for the case of higher-order field perturbations due to eddy currents caused by diffusion weighting. In this example, image reconstruction was accelerated by two orders of magnitude.
The Diagnosis of Polycystic Ovary Syndrome during Adolescence

Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological features used in adult women may be normal pubertal physiological events. Hence, international pediatric and adolescent specialty societies have defined criteria that have sufficient evidence to be used for the diagnosis of PCOS in adolescents. Methods: The literature has been reviewed and evidence graded to address a series of questions regarding the diagnosis of PCOS during adolescence including the following: clinical and biochemical evidence of hyperandrogenism, criteria for oligo-anovulation and polycystic ovary morphology, diagnostic criteria to exclude other causes of hyperandrogenism and amenorrhea, role of insulin resistance, and intervention. Results and Conclusion: Features of PCOS overlap normal pubertal development. Hence, caution should be taken before diagnosing PCOS without longitudinal evaluation. However, treatment may be indicated even in the absence of a definitive diagnosis. While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.
Does very advanced maternal age, with or without egg donation, really increase obstetric risk in a large tertiary center?

Abstract Objective: To assess complications of very advanced maternal age (VAMA) pregnancies ≥45 years with and without egg donation (ED). Study design: Obstetric and neonatal complications were studied in 20,659 singleton pregnancies according to three maternal age groups: 20–39, 40–44 [advanced maternal age (AMA)] and ≥45 years (VAMA). Twenty pregnancies within the AMA/LAMA group that were achieved with ED were compared with age-matched controls. Results: AMA mothers were more likely to have higher rates of preterm deliveries (OR 1.25), cesarean sections (OR 1.84) hypertension (OR 1.71) and diabetes (OR 2.45). Their newborns were more frequently small for gestational age (OR 1.30), and were more likely to have high rates of respiratory distress syndrome (OR 1.66), neonatal intensive care admission (OR 1.40) and perinatal/neonatal mortality (OR 1.83). VAMA pregnancies had >50% cesarean section rate and a high rate of diabetes (OR 2.29), hypertension (OR 1.54) and postpartum hemorrhage (OR 5.38). Congenital anomalies were more common among ED pregnancies. Conclusions: The higher rate of pregnancy complications for women ≥40 years is not further increased after 45 years of age.
Physical layer authentication in OFDM systems based on hypothesis testing of CFO estimates

Information security is becoming a critical challenge in wireless communications due to the open nature of wireless channels and the transparency of standardized transmission schemes. Among the various wireless security techniques, user authentication is one essential measure to identify legitimate users and protect the integrity of transmissions. In this paper, a novel physical layer authentication scheme is proposed to enhance the communication security by exploiting the unique characteristics of oscillator in each communication device. In realistic scenarios, radio frequency (RF) oscillators in each transmitter and receiver pair always present some bias to the nominal carrier frequency due to manufacturing limitations and operating conditions. This bias is characterized by a device-dependent carrier frequency offset (CFO), which can be used to identify a specific wireless transmitter. In the proposed authentication scheme, the CFO at different time of the received signal is first estimated. It is then examined by a hypothesis testing to determine whether the signal has the consistent CFO for authentication purpose. Adaptive thresholds of CFO variation are derived for user discrimination based on the received signal-to-noise ratio (SNR). Simulation results further confirm the effectiveness of the proposed scheme in multipath fading environments.