Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Imprecise Small Photon Beam Modeling by Two Treatment Planning System Algorithms

Background: Dosimetric accuracy in intensity-modulated radiation therapy (IMRT) is the main part of quality assurance program. Improper beam modeling of small fields by treatment planning system (TPS) can lead to inaccuracy in treatment delivery. This study aimed to evaluate of the dose delivery accuracy at small segments of IMRT technique using two-dimensional (2D) array as well as evaluate the capability of two TPSs algorithm in modeling of small fields. Methods: Irradiation were performed using 6 MV photon beam of Siemens Artiste linear accelerator. Dosimetric behaviors of two dose calculation algorithms, namely, collapsed cone convolution/superposition (CCCS) and full scatter convolution (FSC) in small segments of IMRT plans were analyzed using a 2D diode array and gamma evaluation. Results: Comparisons of measurements against TPSs calculations showed that percentage difference of output factors of small fields were 2% and 15% for CCCS and FSC algorithm, respectively. Gamma analysis of calculated dose distributions by TPSs against those measured by 2D array showed that in passing criteria of 3 mm/3%, the mean pass rate for all segment sizes is higher than 95% except for segment sizes below 3 cm × 3 cm optimized by TiGRT TPS. Conclusions: High pass rate of gamma index (95%) achieved in planned small segments by Prowess relative to results obtained with TiGRT. This study showed that the accuracy of small field modeling differs between two dose calculation algorithms.
Continuous Online Sequence Learning with an Unsupervised Neural Network Model

Abstract The ability to recognize and predict temporal sequences of sensory inputs is vital for survival in natural environments. Based on many known properties of cortical neurons, hierarchical temporal memory (HTM) sequence memory recently has been proposed as a theoretical framework for sequence learning in the cortex. In this letter, we analyze properties of HTM sequence memory and apply it to sequence learning and prediction problems with streaming data. We show the model is able to continuously learn a large number of variable order temporal sequences using an unsupervised Hebbian-like learning rule. The sparse temporal codes formed by the model can robustly handle branching temporal sequences by maintaining multiple predictions until there is sufficient disambiguating evidence. We compare the HTM sequence memory with other sequence learning algorithms, including statistical methods—autoregressive integrated moving average; feedforward neural networks—time delay neural network and online sequential extreme learning machine; and recurrent neural networks—long short-term memory and echo-state networks on sequence prediction problems with both artificial and real-world data. The HTM model achieves comparable accuracy to other state-of-the-art algorithms. The model also exhibits properties that are critical for sequence learning, including continuous online learning, the ability to handle multiple predictions and branching sequences with high-order statistics, robustness to sensor noise and fault tolerance, and good performance without task-specific hyperparameter tuning. Therefore, the HTM sequence memory not only advances our understanding of how the brain may solve the sequence learning problem but is also applicable to real-world sequence learning problems from continuous data streams.
DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signalling.

AIMS Dual Ig domain-containing adhesion molecule (DICAM), a protein with homology to the junctional adhesion molecule family, has been demonstrated to interact with integrin αVβ3 that plays a critical role in angiogenesis. Here, we determined the role of DICAM during angiogenesis and the molecular mechanisms involved in the inhibition of angiogenesis. METHODS AND RESULTS DICAM was expressed on the endothelial cells of large vessels to small capillaries. In human umbilical vein endothelial cells (HUVECs), DICAM was up-regulated by vascular endothelial growth factor (VEGF) through the MEK/ERK and PI3K/AKT pathways. Furthermore, the exogenous expression of DICAM in HUVECs suppressed angiogenesis in vitro Matrigel and in vivo plug assays, and conversely, DICAM knockdown enhanced angiogenesis. In addition, DICAM inhibited HUVEC migration and accelerated apoptosis via down-regulation of Bcl-2, but did not affect viability or proliferation of HUVEC. Mechanistically, the exogenous expression of DICAM suppressed VEGF-induced phosphorylarion of AKT and p38 MAP kinase. When integrin signalling was activated by vitronectin, a forced expression of DICAM attenuated integrin β3/FAK signalling and downstream AKT and p38 MAP kinase signalling in HUVECs. CONCLUSION Collectively, DICAM suppressed angiogenesis by attenuating AKT and p38 MAP kinase signalling, which suggests that DICAM may be a novel negative regulator of angiogenesis.
Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system. Results: The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment. Conclusion: Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI.
Structural integrity of frontostriatal connections predicts longitudinal changes in self-esteem

ABSTRACT Diverse neurological and psychiatric conditions are marked by a diminished sense of positive self-regard, and reductions in self-esteem are associated with risk for these disorders. Recent evidence has shown that the connectivity of frontostriatal circuitry reflects individual differences in self-esteem. However, it remains an open question as to whether the integrity of these connections can predict self-esteem changes over larger timescales. Using diffusion magnetic resonance imaging and probabilistic tractography, we demonstrate that the integrity of white matter pathways linking the medial prefrontal cortex to the ventral striatum predicts changes in self-esteem 8 months after initial scanning in a sample of 30 young adults. Individuals with greater integrity of this pathway during the scanning session at Time 1 showed increased levels of self-esteem at follow-up, whereas individuals with lower integrity showed stifled or decreased levels of self-esteem. These results provide evidence that frontostriatal white matter integrity predicts the trajectory of self-esteem development in early adulthood, which may contribute to blunted levels of positive self-regard seen in multiple psychiatric conditions, including depression and anxiety.
Capping Agent-Dependent Toxicity and Antimicrobial Activity of Silver Nanoparticles: An In Vitro Study. Concerns about Potential Application in Dental Practice

Objectives: In dentistry, silver nanoparticles (AgNPs) have drawn particular attention because of their wide antimicrobial activity spectrum. However, controversial information on AgNPs toxicity limited their use in oral infections. Therefore, the aim of the present study was to evaluate the antibacterial activities against a panel of oral pathogenic bacteria and bacterial biofilms together with potential cytotoxic effects on human gingival fibroblasts of 10 nm AgNPs: non-functionalized - uncapped (AgNPs-UC) as well as surface-functionalized with capping agent: lipoic acid (AgNPs-LA), polyethylene glycol (AgNPs-PEG) or tannic acid (AgNPs-TA) using silver nitrate (AgNO3) as control. Methods: The interaction of AgNPs with human gingival fibroblast cells (HGF-1) was evaluated using the mitochondrial metabolic potential assay (MTT). Antimicrobial activity of AgNPs was tested against anaerobic Gram-positive and Gram-negative bacteria isolated from patients with oral cavity and respiratory tract infections, and selected aerobic Staphylococci strains. Minimal inhibitory concentration (MIC) values were determined by the agar dilution method for anaerobic bacteria or broth microdilution method for reference Staphylococci strains and Streptococcus mutans. These strains were also used for antibiofilm activity of AgNPs. Results: The highest antimicrobial activities at nontoxic concentrations were observed for the uncapped AgNPs and the AgNPs capped with LA. It was found that AgNPs-LA and AgNPs-PEG demonstrated lower cytotoxicity as compared with the AgNPs-TA or AgNPs-UC in the gingival fibroblast model. All of the tested nanoparticles proved less toxic and demonstrated wider spectrum of antimicrobial activities than AgNO3 solution. Additionally, AgNPs-LA eradicated Staphylococcus epidermidis and Streptococcus mutans 1-day biofilm at concentration nontoxic to oral cells. Conclusions: Our results proved that a capping agent had significant influence on the antibacterial, antibiofilm activity and cytotoxicity of AgNPs. Clinical significance: This study highlighted potential usefulness of AgNPs against oral anaerobic Gram-positive and Gram-negative bacterial infections and aerobic Staphylococci strains provided that pharmacological activity and risk assessment are carefully performed.
Ecological requirements, antioxidant activity and new chemotype essential oil from Achillea millefolium L. and Achillea micrantha Wild. in North of Iran (Golestan province).

In many field observation, ecological equipment, phenology and ethnopharmacological data of Achillea millefolium L. and A. micrantha Wild. were studied. The inflorescences of plants were collected in different locations of Golestan province: Chaharbagh (2000 m) and Dozan (2200 m) respectively. Essential oils were obtained by steam distillation (Clevenger) and analyzed by gas chromatography-mass spectrometry and (GCMS). Total phenol (TP) and total flavonoid (TF) were determined with spectro photo meteri. Antioxidant properties were obtained by three radical scavenging activity methods: reducing power (RP), total antioxidant capacity (TAC) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH). Field observation showed that both species of Achillea are perennial aromatic plants which can grow 30 to 70 cm tall, flowers appeared in mid to late of May where the annual average rainfall were 399-345 mm, in sandy loam to silty clay loam soil. These plants has been used in traditional medicine as antibacterial, anti infection ,anti spasm, sedative, astringent, anti nociceptive and wound healing. Flowers essential oils of A. millefoilum and A. micrantha were characterized by higher amounts of similar constituents: binapacryle (63.82% 83.63%), 1-8 cineol (14.97% 3.76%) and α-selinene (4.81% 4.49%) respectively. TP content (12.34±0.264 to 18.44±0.085 mgGAEgr) and TF contents (61.003±2.38 to 80.30±5.793 mgQUE g) were measured in A. micrantha and A. millefolium, respectively. A. micrantha had more antioxidant activity with IC50 )0.184±0.0475 μg/ml in dry weight in DPPH method) than A. millefolium (IC50 0.178±0.178 μg/ml in dry weight in RP method). According to the results, there is a positive correlation between antioxidant activity and important secondary metabolites (TP, TF), this could help to study more about the application of these plants in traditional medicine as an antiseptic, anti spasm and antibacterial agent.
LoRea: A Backscatter Architecture that Achieves a Long Communication Range

There is the long-standing assumption that radio communication in the range of hundreds of meters needs to consume mWs of power at the transmitting device. In this paper, we demonstrate that this is not necessarily the case for some devices equipped with backscatter radios. We present LOREA an architecture consisting of a tag, a reader and multiple carrier generators that overcomes the power, cost and range limitations of existing systems such as Computational Radio Frequency Identification (CRFID). LOREA achieves this by: First, generating narrow-band backscatter transmissions that improve receiver sensitivity. Second, mitigating self-interference without the complex designs employed on RFID readers by keeping carrier signal and backscattered signal apart in frequency. Finally, decoupling carrier generation from the reader and using devices such as WiFi routers and sensor nodes as a source of the carrier signal. An off-the-shelf implementation of LOREA costs 70 USD, a drastic reduction in price considering commercial RFID readers cost 2000 USD. LOREA's range scales with the carrier strength, and proximity to the carrier source and achieves a maximum range of 3.4 km when the tag is located at 1 m distance from a 28 dBm carrier source while consuming 70 μW at the tag. When the tag is equidistant from the carrier source and the receiver, we can communicate upto 75 m, a significant improvement over existing RFID readers.
The Use of CRISPR/Cas9 Gene Editing to Confirm Congenic Contaminations in Host-Pathogen Interaction Studies

Murine models of Salmonella enterica serovar Typhimurium infection are one of the commonest tools to study host-pathogen interactions during bacterial infections. Critically, the outcome of S. Typhimurium infection is impacted by the genetic background of the mouse strain used, with macrophages from C57BL/6 and BALB/c mice lacking the capacity to control intracellular bacterial replication. For this reason, the use of congenic strains, which mix the genetic backgrounds of naturally protected mouse strains with those of susceptible strains, has the capacity to significantly alter results and interpretation of S. Typhimurium infection studies. Here, we describe how macrophage knockout cell lines generated by CRISPR/Cas9 gene editing can help determine the contribution of background contaminations in the phenotypes of primary macrophages from congenic mice, on the outcome of S. Typhimurium infection studies. Our own experience illustrates how the CRISPR/Cas9 technology can be used to complement pre-existing knockout models, and shows that there is great merit in performing concurrent studies with both genetic models, to exclude unanticipated side-effects on host-pathogen interactions.
AIR QUALITY MODELLING IN

The levels of air pollution in Chiang Mai city, Thailand, are higher than in most western cities and are a cause of concern. Within the city, air pollution monitoring stations are few and modelling is potentially an important planning aid. For the present study the use of the ADMSUrban model was tested using data for Chiang Mai – a tropical city. Pollutant concentrations calculated by ADMS-Urban were compared with concentrations recorded at two monitoring stations. Source information on emission rates, street canyons and meteorological data were inputs to the model. Good correlations were only obtained when corrections were made for the high levels of imported ambient background pollution. The reasons for the limitations in applying the existing ADMS-Urban model to a tropical city are being explored and recommendations for modifications will be made. The model was used to identify ‘hot-spots’ within the city (along Highways 106 and 108). The results produced are influencing the selection of sites for investigating the potential impacts of air pollution on respiratory health. Schools were located in the hot spot areas and a preliminary respiratory health survey using a standardised questionnaire was later conducted in 4 urban schools in identified "hot spots", and 2 rural schools. The results showed that the prevalence of asthma was similar in all the schools (approximately 5.5%) but the prevalence of rhinitis and atopic dermatitis was higher in the urban schools (24.4% and 12.2%, respectively) than in rural schools (15.7% and 7.2%, respectively).
The effect of fermented wheat germ extract on production parameters and immune status of growing pigs

Model experiment was conducted with growing pigs fed diets containing zero or two levels (1 or 2 g/kg) of fermented wheat germ extract (FWGE). In the first part of the experiment (19 days between 49 and 68 days of age) weight gain and feed conversion were tested. The 2 nd part of the experiment (21 days between 68 and 89 days of age) served to measure the effect of FWGE on some compartments of the immune system. In the first part of the experiment supplementation of the starters’ diet with FWGE yielded 7.8 and 14.2% additional daily weight gain in the 1 st and 2 nd experimental groups, respectively (P<0.05). Humoral immune response to purified horse globulin (PHG) antigen was unaffected by the treatment. The blastogenic response of lymphocytes to non specific mitogens (PHA, Con-A, PWM), phagocytic activity and phagocytic index as well as the intradermal PHA test was consistently and significantly enhanced by the treatments.
Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD+ and NADH) rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses. The Wallerian degeneration slow allele, WldS, decreases the vulnerability of retinal ganglion cells in eyes with elevated IOP, but the exact mechanism(s) of protection from glaucoma are not determined. Here, we demonstrate that WldS increases retinal NAD levels. Coupled with nicotinamide administration (an NAD precursor), it robustly protects from glaucomatous neurodegeneration in a mouse model of glaucoma (94% of eyes having no glaucoma, more than WldS or nicotinamide alone). Importantly, nicotinamide and WldS protect somal, synaptic, and axonal compartments, prevent loss of anterograde axoplasmic transport, and protect from visual dysfunction as assessed by pattern electroretinogram. Boosting NAD production generally benefits major compartments of retinal ganglion cells, and may be of value in other complex, age-related, axonopathies where multiple neuronal compartments are ultimately affected.
Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: clinical evidences.

OBJECTIVE Alpha Lipoic Acid (ALA) is a safe natural molecule that exerts a selective immunomodulating activity with antioxidant and anti-inflammatory properties. This randomized controlled clinical trial (RCT) tested the effect of the vaginal administration with ALA or Progesterone, in subchorionic hematoma resorption in women with threatened miscarriage. PATIENTS AND METHODS 400 mg of vaginal Progesterone or 10 mg of vaginal ALA were administered to sixty-two pregnant women, in the first trimester of gestation with threatened miscarriage and subchorionic hematoma. Controls were patients who chose not to receive any treatment. RESULTS In the ALA group the subchorionic hematoma was reabsorbed more quickly in comparison with the progression detected in Progesterone group (p ≤ 0.05). The other parameters checked (pelvic pain and vaginal bleeding) did not show any significant difference and a smaller number of miscarriages was recorded in the ALA group, compared to Progesterone group. CONCLUSIONS Our data provides the first evidence of the efficacy of ALA, administered by vaginal route, in the healing process of patients with threatened miscarriage, thus supporting the normal course of pregnancy. CLINICAL TRIAL REGISTRATION NUMBER NCT02601898 (ClinicalTrials.gov registry).
Dual ALK and CDK4/6 Inhibition Demonstrates Synergy against Neuroblastoma

Purpose: Anaplastic lymphoma kinase (ALK) is the most frequently mutated oncogene in the pediatric cancer neuroblastoma. We performed an in vitro screen for synergistic drug combinations that target neuroblastomas with mutations in ALK to determine whether drug combinations could enhance antitumor efficacy. Experimental Design: We screened combinations of eight molecularly targeted agents against 17 comprehensively characterized human neuroblastoma-derived cell lines. We investigated the combination of ceritinib and ribociclib on in vitro proliferation, cell cycle, viability, caspase activation, and the cyclin D/CDK4/CDK6/RB and pALK signaling networks in cell lines with representative ALK status. We performed in vivo trials in CB17 SCID mice bearing conventional and patient-derived xenograft models comparing ceritinib alone, ribociclib alone, and the combination, with plasma pharmacokinetics to evaluate for drug–drug interactions. Results: The combination of ribociclib, a dual inhibitor of cyclin-dependent kinase (CDK) 4 and 6, and the ALK inhibitor ceritinib demonstrated higher cytotoxicity (P = 0.008) and synergy scores (P = 0.006) in cell lines with ALK mutations as compared with cell lines lacking mutations or alterations in ALK. Compared with either drug alone, combination therapy enhanced growth inhibition, cell-cycle arrest, and caspase-independent cell death. Combination therapy achieved complete regressions in neuroblastoma xenografts with ALK-F1174L and F1245C de novo resistance mutations and prevented the emergence of resistance. Murine ribociclib and ceritinib plasma concentrations were unaltered by combination therapy. Conclusions: This preclinical combination drug screen with in vivo validation has provided the rationale for a first-in-children trial of combination ceritinib and ribociclib in a molecularly selected pediatric population. Clin Cancer Res; 23(11); 2856–68. ©2016 AACR.