Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria

Calcium and apatite granulations are demonstrated here to form in both human and fetal bovine serum in response to the simple addition of either calcium or phosphate, or a combination of both. These granulations are shown to represent precipitating complexes of protein and hydroxyapatite (HAP) that display marked pleomorphism, appearing as round, laminated particles, spindles, and films. These same complexes can be found in normal untreated serum, albeit at much lower amounts, and appear to result from the progressive binding of serum proteins with apatite until reaching saturation, upon which the mineralo-protein complexes precipitate. Chemically and morphologically, these complexes are virtually identical to the so-called nanobacteria (NB) implicated in numerous diseases and considered unusual for their small size, pleomorphism, and the presence of HAP. Like NB, serum granulations can seed particles upon transfer to serum-free medium, and their main protein constituents include albumin, complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as well as other calcium and apatite binding proteins found in the serum. However, these serum mineralo-protein complexes are formed from the direct chemical binding of inorganic and organic phases, bypassing the need for any biological processes, including the long cultivation in cell culture conditions deemed necessary for the demonstration of NB. Thus, these serum granulations may result from physiologically inherent processes that become amplified with calcium phosphate loading or when subjected to culturing in medium. They may be viewed as simple mineralo-protein complexes formed from the deployment of calcification-inhibitory pathways used by the body to cope with excess calcium phosphate so as to prevent unwarranted calcification. Rather than representing novel pathophysiological mechanisms or exotic lifeforms, these results indicate that the entities described earlier as NB most likely originate from calcium and apatite binding factors in the serum, presumably calcification inhibitors, that upon saturation, form seeds for HAP deposition and growth. These calcium granulations are similar to those found in organisms throughout nature and may represent the products of more general calcium regulation pathways involved in the control of calcium storage, retrieval, tissue deposition, and disposal.
Sketch Acceleration on FPGA and its Applications in Network Anomaly Detection

Sketch, a highly accurate data stream summarization technique, has gained much interest in the research community in recent years. Because of its sub-linear memory complexity, Sketch-based techniques consume significantly less memory than the traditional per-item-state techniques for processing high throughput data streams. One of the major applications of Sketch is in network anomaly detection, which is critical for network management and security in both Internet and data centers. In these applications, throughput is a key performance metric. Due to the low memory complexity, Sketch-based techniques can be supported by the fast on-chip storage of the state-of-the-art computing platforms to achieve high throughput. In this work, we first propose a generic architecture on FPGA to accelerate Sketch and adopt it to 2 widely used Sketches: Count-min Sketch and K-ary Sketch. We propose online Sketch-based algorithms for 2 key network anomaly detection tasks: heavy hitter detection and heavy change detection. We adopt the proposed generic architecture for Sketch to accelerate these online algorithms. The post place-and-route results on a state-of-the-art FPGA show that our generic architecture can accelerate both Count-min Sketch and K-ary Sketch to over 150 Gbps, demonstrating significant throughput performance improvements compared with other Sketch acceleration techniques. Our architectures for online anomaly detection tasks sustain 100-150 Gbps throughput for various system configurations.
Evaluation of Prognostic Factors and Proposed Changes to the Modified Tokuhashi Score in Patients With Spinal Metastases From Breast Cancer

Study Design. A retrospective study of all patients with histologically confirmed breast cancer spinal metastases presenting to a single institution between May 2001 and April 2012. Objectives. The aim of this study was to investigate whether the 2014mT is more accurate than the 2005mT. Summary of Background Data. The commonly used 2005 modified Tokuhashi score (2005mT) has become more inaccurate as oncologists move toward treating tumors according to their molecular and genomic profile, rather than their tissue-of-origin. In attempts to improve the accuracy of the 2005mT, a revised score (2014mT) was published, suggesting that hormone receptor negative and triple-negative breast cancer patients be given a modified Tokuhashi histological score of 3 rather than 5. Methods. Demographic characteristics, tumor receptor status, clinical findings in relation to the primary tumor and its metastases, and actual survival time were collated. The 2005mT was compared with the 2014mT. Univariate and multivariate Cox regression analyses were used to evaluate the influence of each parameter on survival, and receiver operating characteristic curves were used to determine predictive values of each score version. Results. Of the 185 patients included, 32 underwent operative treatment, while 153 were managed nonoperatively for their spinal metastases. The overall cohort had a median survival time of 24 months following the diagnosis of spinal metastases, with a 6-month survival rate of 90%. Hormone, HER2 and triple-negative receptor statuses were significant predictors of poorer survival upon multivariate analysis (P = 0.004, P = 0.007, P < 0.001, and P < 0.001, respectively). Age, the original Tokuhashi score components, previous breast surgery for cancer, previous radiotherapy to the breast, previous radiotherapy to the spine, previous chemotherapy, and previous immunotherapy were not significant. At 6 months, the 2005mT AUROC was 0.62, while that of the 2014mT was 0.64 (P = 0.5394). Conclusion. Tumor histological subtype is crucial when prognosticating the survival of patients with breast cancer spinal metastases. Although the 2014mT was marginally more accurate than the 2005mT, its predictive ability remains poor. Level of Evidence: 3
Ice slurry ingestion does not enhance self‐paced intermittent exercise in the heat

This study aimed to determine if ice slurry ingestion improved self‐paced intermittent exercise in the heat. After a familiarisation session, 12 moderately trained males (30.4 ± 3.4 year, 1.8 ± 0.1 cm, 73.5 ± 14.3 kg, V˙ O2max 58.5 ± 8.1 mL/kg/min) completed two separate 31 min self‐paced intermittent protocols on a non‐motorised treadmill in 30.9 ± 0.9 °C, 41.1 ± 4.0% RH. Thirty minutes prior to exercise, participants consumed either 7.5 g/kg ice slurry (0.1 ± 0.1 °C) (ICE) or 7.5 g/kg water (23.4 ± 0.9 °C) (CONTROL). Despite reductions in Tc (ΔTc: −0.51 ± 0.3 °C, P < 0.05) and thermal sensation prior to exercise, ICE did not enhance self‐paced intermittent exercise compared to CONTROL. The average speed during the walk (CONTROL: 5.90 ± 1.0 km, ICE: 5.90 ± 1.0 km), jog (CONTROL: 8.89 ± 1.7 km, ICE: 9.11 ± 1.5 km), run (CONTROL: 12.15 ± 1.7 km, ICE: 12.54 ± 1.5 km) and sprint (CONTROL: 17.32 ± 1.3 km, ICE: 17.18 ± 1.4 km) was similar between conditions (P > 0.05). Mean Tsk, Tb, blood lactate, heart rate and RPE were similar between conditions (P > 0.05). The findings suggest that lowering Tc prior to self‐paced intermittent exercise does not translate into an improved performance.
Coding communications across time: Documenting changes in interaction patterns across adopter categories

Abstract GLOBALink, a large online network of tobacco control professionals, was active in the promotion of the World Health Organization's Framework Convention on Tobacco Control treaty, an international treaty aimed at reducing the global burden of tobacco-related death and disease. We examined and compared the roles that different countries served in the GLOBALink community during FCTC negotiation and ratification. Previous studies of FCTC ratification found the process adhered to a diffusion of innovation model (Valente et al., 2015). We followed that work by conducting content analyses of discussion messages posted by GLOBALink members representing different countries. Based on the time when they ratified the FCTC, each country was labeled by one of the four adoption stages of the diffusion model and we investigated the amount of shared word use between the different stages. A goodness-of-fit chi-squared test indicated that content was not shared in an expected manner between stages (χ2 = 11,856.45, N = 51,447, p < 0.001). A deeper look at the specific words shared between countries within and between adoption stages provided insight into how interactions between certain countries might have served to support the ratification process.
Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+ T-Lymphocyte-Depleted Mice

ABSTRACT Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+ T lymphocytes are critical for host defense against this infection, but in the absence of CD4+ T lymphocytes, CD8+ T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against Pneumocystis and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with Pneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to Pneumocystis murina and that administration of rhIL-7 markedly enhanced clearance of Pneumocystis in CD4-depleted mice. Additionally, we observed increased recruitment of CD8+ T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+ T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+ central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine Pneumocystis pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+ T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+ T lymphocytes.
Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

ABSTRACT Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.
Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.
Ewing sarcoma during follow-up

Summary Aim: To evaluate the performance of a prospectively defined follow-up imaging protocol that includes FDG-PET(/CT) to detect tumour recurrence in Ewing sarcoma (EwS) before becoming symptomatic. Methods: Imaging results and clinical data during follow-up were retrospectively analysed from all patients treated successfully within the EURO E.W. I.N. G. 99 trial at the University Hospital Münster, Germany. All patients received follow-up imaging according to a comprehensive protocol that included regular X-ray, CT, MRI, bone scan and PET(/CT), albeit not all on the same day and with varying intervals for the different modalities. Results: 80 of 105 patients underwent follow-up at our institution after complete remission. 30 patients had recurrent tumour during the follow-up period of 3.6 years on average. 19 recurrences (63%) were detected by scheduled imaging before the advent of clinical symptoms. The majority of these recurrences (8 out of 19; 42%) was detected first by PET/ CT (and confirmed with additional imaging thereafter), even though the total number of PET/CTs was comparatively low (138) and PET/CT was not systematically scheduled before other imaging techniques. Recurrences detected by bone scan were also detectable by PET. Conclusions: The implemented follow-up protocol was effective in the detection of EwS recurrence before the advent of symptoms. Most cases of those detected before onset of symptoms were detected by PET/CT first. This hybrid imaging modality should therefore be considered in the routine follow-up of EwS patients, as is standard in our hospital. In combination with PET, low-dose chest CT seems to be sufficient in the detection of small pulmonary nodules.
Dopamine/noradrenaline reuptake inhibition in women improves endurance exercise performance in the heat

Catecholamine reuptake inhibition improves the performance of male volunteers exercising in warm conditions, but sex differences in thermoregulation, circulating hormones, and central neurotransmission may alter this response. With local ethics committee approval, nine physically active women (mean ± SD age 21 ± 2 years; height 1.68 ± 0.08 m; body mass 64.1 ± 6.0 kg; VO2peak 51 ± 7 mL/kg/min) were recruited to examine the effect of pre‐exercise administration of Bupropion (BUP; 4 × 150 mg) on prolonged exercise performance in a warm environment. Participants completed a VO2peak test, two familiarization trials, and two randomized, double‐blind experimental trials. All trials took place during the first 10 days of the follicular phase of the menstrual cycle. Participants cycled for 1 h at 60% VO2peak followed by a 30‐min performance test. Total work done was greater during the BUP trial (291 ± 48 kJ) than the placebo trial (269 ± 46 kJ, P = 0.042, d = 0.497). At the end of the performance test, core temperature was higher on the BUP trial (39.5 ± 0.4 °C) than on the placebo trial (39.2 ± 0.6 °C, P = 0.021; d = 0.588), as was heart rate (185 ± 9 vs 179 ± 13, P = 0.043; d = 0.537). The results indicate that during the follicular phase of the menstrual cycle, an acute dosing protocol of BUP can improve self‐regulated performance in warm conditions.
Characterization of six PHT1 members in Lycium barbarum and their response to arbuscular mycorrhiza and water stress

Phosphorus (P) is vitally important for most plant processes. However, the P available to plants is present in the soil in the form of inorganic phosphate (Pi), and is often present in only limited amounts. Water stress further reduces Pi availability. Previous studies have highlighted the important roles of members of the PHOSPHATE TRANSPORTER 1 (PHT1) family and arbuscular mycorrhizal (AM) associations for Pi acquisition by plants growing in various environments. In order to understand the Pi uptake of Lycium barbarumL. , a drought-tolerant ligneous species belonging to the Solanaceae family, we cloned and characterized six L. barbarum genes encoding transporter proteins belonging to the PHT1 family, and investigated their transcriptional response to AM associations and water stress. The six cloned PHT1 genes of L. barbarum had a similar evolutionary history to that of PHT1 genes found in other Solanaceae species. Three of these genes (LbPT3, LbPT4 and LbPT5) were AM-induced; the other three genes (LbPT1, LbPT2 and LbPT7) played distinct roles in Pi acquisition, translocation and remobilization in roots and leaves. AM-induced PHT1 genes maintained their function under water stress, while moderate and severe water stress upregulated non-AM-induced PHT1 genes in roots and leaves, respectively. Moreover, although LbPT1 was upregulated in AM roots under water stress, LbPT2 and LbPT7 were inhibited in AM roots, which suggested that an AM association satisfied the demand for Pi in roots under water stress and that LbPT1 may play a role in translocating Pi from roots to shoots in this situation.
A Comparative Study of Standardized Infinity Reference and Average Reference for EEG of Three Typical Brain States

The choice of different reference electrodes plays an important role in deciphering the functional meaning of electroencephalography (EEG) signals. In recent years, the infinity zero reference using the reference electrode standard technique (REST) has been increasingly applied, while the average reference (AR) was generally advocated as the best available reference option in previous classical EEG studies. Here, we designed EEG experiments and performed a direct comparison between the influences of REST and AR on EEG-revealed brain activity features for three typical brain behavior states (eyes-closed, eyes-open and music-listening). The analysis results revealed the following observations: (1) there is no significant difference in the alpha-wave-blocking effect during the eyes-open state compared with the eyes-closed state for both REST and AR references; (2) there was clear frontal EEG asymmetry during the resting state, and the degree of lateralization under REST was higher than that under AR; (3) the global brain functional connectivity density (FCD) and local FCD have higher values for REST than for AR under different behavior states; and (4) the value of the small-world network characteristic in the eyes-closed state is significantly (in full, alpha, beta and gamma frequency bands) higher than that in the eyes-open state, and the small-world effect under the REST reference is higher than that under AR. In addition, the music-listening state has a higher small-world network effect than the eyes-closed state. The above results suggest that typical EEG features might be more clearly presented by applying the REST reference than by applying AR when using a 64-channel recording.
Comprehension of Generalized Conversational Implicatures by Children With and Without Autism Spectrum Disorder

This study evaluates the comprehension of generalized conversational implicatures (GCI) in children with and without autism spectrum disorder (ASD), using a GCI test constructed based on the Levinson model, which distinguishes between three types of implicatures: type Q (or scalar: “what is not referred to does not occur”); type I (“by default, it is not necessary to say what can be assumed”); and type M (“if someone is expressing something in a not very simple or marked way, it is because s/he is describing a situation that is not very typical, frequent, or prototypical”). In addition to the ASD group (n = 22), two comparison groups were utilized: a group matched on chronological age with the ASD group, but with a higher linguistic age (TCD group, n = 22), and a group matched on linguistic age with the ASD group, but with a lower chronological age (TLD group, n = 22). In all cases, linguistic age was assessed with the Peabody test. The performance of the three groups on the GCI test was compared (overall and on each type of implicature), and performance on the three types of implicature was compared within each group. The ASD group obtained worse performance than the other two groups, both overall and for each implicature type, without also obtaining differences in performance on the three implicature types. The TCD group obtained better performance than the TLD group on overall performance, but not on each implicature type, and both groups obtained lower performance on the type M heuristics than on the type I. Based on these results, the children with ASD in our study presented limitations in the comprehension of the three types of GCI, but it was not possible to obtain evidence for an inferential continuum of the three types of GCI. However, in the two typical development groups, this evidence was obtained, leading us to propose an inferential continuum model based on the different levels of dependence on the context of each of the three types of implicatures, with type M implicatures being more contextually dependent.