Miracle-dz/UniFAR-FTUs huggingface dataset:
Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Gemcitabine Effects Against Pancreatic Cancer

Pancreatic cancer is one of the most lethal malignancies with very limited treatment option. In the effort of enhancing the effect of the conventional chemotherapeutic drug gemcitabine against pancreatic cancer, we investigated in vitro and in vivo the anticancer effect of a β-carboline-enriched extract from the plant Rauwolfia vomitoria (Rau), either alone or in combination with gemcitabine, in preclinical pancreatic cancer models. Rau induced apoptosis in pancreatic cancer cells in a concentration-dependent manner, and completely inhibited colony formation of PANC-1 cells in soft agar. The combination of Rau and gemcitabine had synergistic effect in inhibiting cell growth with dose reduction effect for gemcitabine. In an orthotopic pancreatic cancer mouse model, PANC-1 tumor growth was significantly suppressed by Rau treatment. Metastasis was inhibited by Rau. Adding Rau to gemcitabine treatment reduced tumor burden and metastatic potential in the gemcitabine non-responsive tumor. These data suggest that Rau possesses anti–pancreatic cancer activity and could improve effect of gemcitabine.
Modeling and Pre-Treatment of Photon-Starved CT Data for Iterative Reconstruction

An increasing number of X-ray CT procedures are being conducted with drastically reduced dosage, due at least in part to advances in statistical reconstruction methods that can deal more effectively with noise than can traditional techniques. As data become photon-limited, more detailed models are necessary to deal with count rates that drop to the levels of system electronic noise. We present two options for sinogram pre-treatment that can improve the performance of photon-starved measurements, with the intent of following with model-based image reconstruction. Both the local linear minimum mean-squared error (LLMMSE) filter and pointwise Bayesian restoration (PBR) show promise in extracting useful, quantitative information from very low-count data by reducing local bias while maintaining the lower noise variance of statistical methods. Results from clinical data demonstrate the potential of both techniques.
Pé doloroso do idoso associado à incapacidade funcional

BACKGROUND AND OBJECTIVES: Foot pain in elderly people may interfere with gait balance and cycle and may contribute for functional incapacity in the geriatric population. This study aimed at evaluating the frequency of functional incapacity associated to foot pain in elderly people. METHOD: Participated in this study 100 elderly people aged 60 years, with foot pain intensity of 30 mm by the pain visual analog scale (VAS). Types of feet and their injuries, types of shoes, falls, their circumstances and consequences were evaluated. Manchester Foot Pain Disability Index (MFPDI) and VAS at rest and movement, dynamic gait index and instrumental activity of daily life scale (IADL) were applied. Sperman and multiple regression tests were used for statistical analysis with significance level of 5% (p < 0.05). RESULTS: There has been prevalence of functional incapacity associated to foot pain above 50%. Univariate analysis has shown significant correlations of functional incapacity associated to foot pain and foot pain intensity at movement (p < 0.002), with the level of functional independence for IADL (p < 0.001), and with gait functionality, balance and risk for falls (p < 0.003), with significant association with the latter. The same correlations were significant in the multivariate analysis (p < 0.005). CONCLUSION: Functional incapacity associated to foot pain was highly prevalent in the elderly and was significantly correlated to foot pain intensity at movement, to the level of functional independence for IADL and to gait / balance functionality and risk for falls.
Do Yoga and Aerobic Exercise Training Have Impact on Functional Capacity, Fatigue, Peripheral Muscle Strength, and Quality of Life in Breast Cancer Survivors?

Aim. The aim of the study was to compare the effects of aerobic exercise training and yoga on the functional capacity, peripheral muscle strength, quality of life (QOL), and fatigue in breast cancer survivors. Material and methods. A total of 52 patients with a diagnosis of breast cancer were included in the study. The patients were randomly assigned to 2 groups: aerobic exercise (n = 28) and yoga added to aerobic exercise (n = 24). Both groups participated in submaximal exercise 30 minutes/d, 3 d/wk for 6 weeks. The second group participated in a 1-hour yoga program in addition to aerobic exercise training. Functional capacity was assessed by the 6-Minute Walk Test (6MWT). Peripheral muscle strength was evaluated with a hand-held dynamometer. The fatigue severity level was assessed with the Fatigue Severity Scale (FSS). The QOL was determined by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire. Results. There were statistically significant increases in peripheral muscle strength, the 6MWT distance, and the perception of QOL in both groups (P < .05). Additionally, the group with aerobic exercise and yoga showed marked improvement compared with the aerobic exercise group in fatigue perception (P < .05). Conclusion. According to the data from this study, aerobic exercise training and yoga improved the functional capacity and QOL of breast cancer patients. Aerobic exercise programs can be supported by body mind techniques, such as yoga, in the rehabilitation of cancer patients for improving functional recovery and psychosocial wellness.
An Adaptive Non-Local-Means Filter for Real-Time MR-Thermometry

Proton resonance frequency shift-based magnetic resonance thermometry is a currently used technique for monitoring temperature during targeted thermal therapies. However, in order to provide temperature updates with very short latency times, fast MR acquisition schemes are usually employed, which in turn might lead to noisy temperature measurements. This will, in general, have a direct impact on therapy control and endpoint detection. In this paper, we address this problem through an improved non-local filtering technique applied on the temperature images. Compared with previous non-local filtering methods, the proposed approach considers not only spatial information but also exploits temporal redundancies. The method is fully automatic and designed to improve the precision of the temperature measurements while at the same time maintaining output accuracy. In addition, the implementation was optimized in order to ensure real-time availability of the temperature measurements while having a minimal impact on latency. The method was validated in three complementary experiments: a simulation, an ex-vivo and an in-vivo study. Compared to the original non-local means filter and two other previously employed temperature filtering methods, the proposed approach shows considerable improvement in both accuracy and precision of the filtered data. Together with the low computational demands of the numerical scheme, the proposed filtering technique shows great potential for improving temperature measurements during real-time MR thermometry dedicated to targeted thermal therapies.
Reintroduction of Two Deleted Virulence Loci Restores Full Virulence to the Live Vaccine Strain of Francisella tularensis

ABSTRACT A disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. In the 1950s, a live vaccine strain, LVS, was developed from a type B strain of Francisella tularensis, the causative agent of tularemia. LVS, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. The efforts to improve biopreparedness have identified a demand for a vaccine against tularemia. Recently the rapid progress in genomics of different Francisella strains has led to identification of several regions of differences (RDs). Two genes carried within RDs, pilA, encoding a putative type IV pilin, and FTT0918, encoding an outer membrane protein, have been linked to virulence. Interestingly, LVS has lost these two genes via direct repeat-mediated deletions. Here we show that reintroduction of the two deleted regions restores virulence of LVS in a mouse infection model to a level indistinguishable from that of virulent type B strains. The identification of the two attenuating deletion events could facilitate the licensing of LVS for use in humans.
Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide

ABSTRACT Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression.
Understanding Barriers to Borrelia burgdorferi Dissemination during Infection Using Massively Parallel Sequencing

ABSTRACT Borrelia burgdorferi is an invasive spirochete that can cause acute and chronic infections in the skin, heart, joints, and central nervous system of infected mammalian hosts. Little is understood about where the bacteria encounter the strongest barriers to infection and how different components of the host immune system influence the population as the infection progresses. To identify population bottlenecks in a murine host, we utilized Tn-seq to monitor the composition of mixed populations of B. burgdorferi during infection. Both wild-type mice and mice lacking the Toll-like receptor adapter molecule MyD88 were infected with a pool of infectious B. burgdorferi transposon mutants with insertions in the same gene. At multiple time points postinfection, bacteria were isolated from the mice and the compositions of the B. burgdorferi populations at the injection site and in distal tissues determined. We identified a population bottleneck at the site of infection that significantly altered the composition of the population. The magnitude of this bottleneck was reduced in MyD88−/− mice, indicating a role for innate immunity in limiting early establishment of B. burgdorferi infection. There is not a significant bottleneck during the colonization of distal tissues, suggesting that founder effects are limited and there is not a strict limitation on the number of organisms able to initiate populations at distal sites. These findings further our understanding of the interactions between B. burgdorferi and its murine host in the establishment of infection and dissemination of the organism.
Cancer-Related Fatigue and Muscle Quality in Hodgkin’s Lymphoma Survivors

The purpose of this study was to compare fatigue, strength, body composition, muscle thickness, and muscle quality between Hodgkin’s lymphoma survivors (HLS) and apparently healthy subjects matched by age, gender, and physical activity levels (CON). Twelve HLS (32.16 ± 8.06) and 36 CON (32.42 ± 7.64) were enrolled in the study. Fatigue was assessed using the 20-item Multidimensional Fatigue Inventory, muscle strength using an isokinetic dynamometer, body composition using dual-energy X-ray absorptiometry, and thickness and muscle quality using B-mode ultrasound. Differences between HLS and CON were analyzed using independent samples t tests. No significant differences were observed between groups for any demographic characteristics: age (P = .922), weight (P = .943), height (P = .511), body mass index (P = .796), fat mass (P = .688), fat-free mass (P = .520), and percent body fat (P = .446). No significant differences were observed for strength (peak torque; P = .552), relative peak torque (P = .200), muscle thickness (P > .05) and muscle quality (P > .05). However, self-perceived fatigue was significantly higher in HLS than in CON (P = .009). It appears that when HLS are matched by age and physical activity levels to CON, no significant difference in body composition, muscle thickness, muscle quality, or strength is observed. Self-perceived fatigue, as predicted, is higher in HLS, which may have implications and should be considered when prescribing exercise training to this cancer population.
Plasmonic Nanolasers Enhanced by Hybrid Graphene-Insulator-Metal Structures.

Graphene is a two-dimensional (2D) structure that creates linear relationship between energy and momentum that not only forms massless Dirac fermions with extremely high group velocity but also exhibits a broadband transmission from 300 to 2500 nm that can be applied to many optoelectronic applications, such as solar cells, light-emitting devices, touchscreens, ultrafast photodetectors, and lasers. Although the plasmonic resonance of graphene occurs in the terahertz band, graphene can be combined with a noble metal to provide a versatile platform for supporting surface plasmon waves. In this study, we propose a hybrid graphene-insulator-metal (GIM) structure that can modulate the surface plasmon polariton (SPP) dispersion characteristics and thus influence the performance of plasmonic nanolasers. Compared with values obtained when graphene is not used on an Al template, the propagation length of SPP waves can be increased to twice and the threshold of nanolasers is reduced by 50% when graphene is incorporated on the template. The GIM structure can be further applied in the future to realize electrical control or electrical injection of plasmonic devices through graphene.
Effects of a Translational Community-Based Multimodal Exercise Program on Quality of Life and the Influence of Start Delay on Physical Function and Quality of Life in Breast Cancer Survivors: A Pilot Study

The purpose of this investigation was 2-fold: (1) to investigate the effects of a translational 12-week community-based multimodal exercise program on quality of life (QoL) in breast cancer survivors (BCS) and (2) to examine the influence of a start delay on physical function and QoL in BCS. Fifty-two female BCS completed a 12-week program consisting of 90-minute supervised exercise sessions at a frequency of 2 supervised sessions per week. Exercise sessions consisted of three 30-minute components: (1) aerobic conditioning, (2) resistance exercise training, and (3) balance and flexibility training. Significant (P < .05) improvements in QoL were identified post-program completion. Cohort stratification comparison between the early start (<1 year since completion of oncologic treatment) and late start (>1 year since completion of oncologic treatment) revealed no significant (P > .05) differences between the early start and late start groups on improvements in physical function. Regarding the influence of start delay on QoL, the early start group showed significant (P < .05) improvement in emotional well-being. No other significant differences in improvement in QoL were detected between the early start and late start groups. Regardless of start delay, meaningful improvements in physical function and QoL were found after completing the community-based multimodal exercise program. Early participation in community-based exercise programming may benefit BCS’ emotional well-being compared to later participation.
Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

ABSTRACT Granzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.
Investigating the strengths and difficulties of children from families with a parental mental illness

Abstract This study investigated whether two groups of children from families with a parent with a mental illness were different to a normative group of children (no parental illness) on the Strengths and Difficulties Questionnaire (SDQ). Of the total 833 children aged 8-12 years, there were 101 children of parents with a mental illness from the general community, 134 children of parents with a mental illness who attended an intervention program and a normative sample of 598. The intervention group scored significantly higher than the other groups on all difficulties. In addition, the general community group with a parental illness scored significantly higher than those without a parental mental illness on the Total Difficulties, Emotional Symptoms and Hyperactivity subscales. These were important findings as the community and intervention children with a parent with a mental illness scored at two and three times respectively the normative level of risk to their mental health. Combined with previous risk estimates, children with a parent who attend mental health services are between two to five times more likely than the norm to be scoring in the clinical range on the SDQ. Recommendations are made regarding child morbidity, mental health policy, programs, workforce and future research.
Neisseria Prophage Repressor Implicated in Gonococcal Pathogenesis

ABSTRACT Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus NgoΦ4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the −10 and −35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis.
Unidirectional Spin-orbit Interaction Induced by Line Defect in Monolayer Transition Metal Dichalcogenides for High Performance Devices.

Spin-orbit (SO) interaction is an indispensable element in the field of spintronics for effectively manipulating spin of carriers. However, in crystalline solids, the momentum-dependent SO effective magnetic field generally results in spin randomization by a process known as the Dyakonov-Perel spin relaxation, leading to the loss of spin information. To overcome this obstacle, the persistent spin helix (PSH) state with a unidirectional SO field was proposed, but difficult to achieve in real materials. Here, based on first-principles calculations and tight-binding model analysis, we report for the first time a unidirectional SO field in monolayer transition metal dichalcogenides (TMDs, MX2, M = Mo, W and X = S, Se) induced by two parallel chalcogen vacancy lines. By changing the relative positions of the two vacancy lines, the direction of the SO field can be tuned from x to y. Moreover, using k · p perturbation theory and group theory analysis, we demonstrate that the emerging unidirectional SO field is subject to both the structural symmetry and 1D nature of such defects engineered in 2D TMDs. In particular, through transport calculations, we confirm that the predicted SO states carry highly coherent spin current. Our findings shed new light on creating PSH states for high performance spintronic devices.
Actin Dynamics and Rho GTPases Regulate the Size and Formation of Parasitophorous Vacuoles Containing Coxiella burnetii

ABSTRACT Q fever is a disease caused by Coxiella burnetii. In the host cell, this pathogen generates a large parasitophorous vacuole (PV) with lysosomal characteristics. Here we show that F-actin not only is recruited to but also is involved in the formation of the typical PV. Treatment of infected cells with F-actin-depolymerizing agents alters PV development. The small PVs formed in latrunculin B-treated cells were loaded with transferrin and Lysotracker and labeled with an antibody against cathepsin D, suggesting that latrunculin B did not affect vacuole cargo and its lysosomal characteristics. Nevertheless, the vacuoles were unable to fuse with latex bead phagosomes. It is known that actin dynamics are regulated by the Rho family GTPases. To assess the role of these GTPases in PV formation, infected cells were transfected with pEGFP expressing wild-type and mutant Rac1, Cdc42, and RhoA proteins. Rac1 did not show significant PV association. In contrast, PVs were decorated by both the wild types and constitutively active mutants of Cdc42 and RhoA. This association was inhibited by treatment of infected cells with chloramphenicol, suggesting a role for bacterial protein synthesis in the recruitment of these proteins. Interestingly, a decrease in vacuole size was observed in cells expressing dominant-negative RhoA; however, these small vacuoles accumulated transferrin, Lysotracker, and DQ-BSA. In summary, these results suggest that actin, likely modulated by the GTPases RhoA and Cdc42 and by bacterial proteins, is involved in the formation of the typical PV.