Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition

Abstract Background Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. By modeling ponatinib resistance and testing samples from these CML patients, it is hoped that an alternative drug target can be identified and inhibited with a novel compound. Methods Two CML cell lines with acquired BCR-ABL-independent resistance were generated following culture in ponatinib. RNA sequencing and gene ontology (GO) enrichment were used to detect aberrant transcriptional response in ponatinib-resistant cells. A validated oncogene drug library was used to identify US Food and Drug Administration–approved drugs with activity against TKI-resistant cells. Validation was performed using bone marrow (BM)–derived cells from TKI-resistant patients (n = 4) and a human xenograft mouse model (n = 4–6 mice per group). All statistical tests were two-sided. Results We show that ponatinib-resistant CML cells can acquire BCR-ABL-independent resistance mediated through alternative activation of mTOR. Following transcriptomic analysis and drug screening, we highlight mTOR inhibition as an alternative therapeutic approach in TKI-resistant CML cells. Additionally, we show that catalytic mTOR inhibitors induce autophagy and demonstrate that genetic or pharmacological inhibition of autophagy sensitizes ponatinib-resistant CML cells to death induced by mTOR inhibition in vitro (% number of colonies of control[SD], NVP-BEZ235 vs NVP-BEZ235+HCQ: 45.0[17.9]% vs 24.0[8.4]%, P = .002) and in vivo (median survival of NVP-BEZ235- vs NVP-BEZ235+HCQ-treated mice: 38.5 days vs 47.0 days, P = .04). Conclusion Combined mTOR and autophagy inhibition may provide an attractive approach to target BCR-ABL-independent mechanism of resistance.
Using MALDI-TOF-MS to test Staphylococcus aureus–infected vitreous

Purpose This study aimed to establish a method for testing Staphylococcus aureus in the vitreous of endophthalmitis with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), which is simple, fast, and sensitive. Methods S. aureus at different numbers was either mixed with homogenized vitreous or inoculated in porcine eyes for culturing, followed by homogenization. The homogenized vitreous samples, with or without centrifugation, were stained with Gram and Coomassie Blue (CBB) dyes and cultured with blood agar. The pellet of the vitreous mixture was analyzed with MALDI-TOF-MS. Results The minimum detectable levels of S. aureus in H2O and in the pellet of homogenized vitreous were 9.0 × 103 (positive rate, 22.2%) and 1.0 × 104 CFU/μl (positive rate, 11.1%), respectively. In the vitreous samples inoculated with S. aureus and cultured for 12 h, the number of S. aureus increased in a dose-dependent manner to the number of bacteria in the inoculate. In the supernatant of the homogenized vitreous, there were traces of bacteria identified with Gram staining. On the blood agar plates, the supernatant grew a few colonies, while the pellet grew intensive colonies. The vitreous fragments that were stained with CBB were displayed in the supernatants, in small numbers, and in the pellets. When the inoculated number was 1.0 × 104 CFU/μl or higher, the bacteria in the vitreous pellets could be identified in all samples (100%, n = 9). However, bacteria could be detected in only two out of nine spots of pellets (22.2%) if the number of inoculated S. aureus was 1.0 × 103 CFU/μl. Conclusions A method for testing S. aureus directly from vitreous samples of endophthalmitis by the combination of easy extraction methods and a MALDI-TOF- MS assay was provided. This rapid identification method is easily adaptable for use in clinical routine and can help reduce the delay in diagnosis, allowing for earlier therapeutic intervention in patients.
Clinical Outcomes of Standard Triple Therapy Plus Probiotics or Concomitant Therapy for Helicobacter pylori Infection

Background/Aims The efficacy of standard triple therapy (STT) in treating Helicobacter pylori infection has decreased. Many investigators have attempted to increase the eradication rate. We investigated the outcomes of concomitant therapy (CT) and STT combined with probiotics (STP) as a first-line treatment for H. pylori infection. Methods We reviewed the medical records of 361 patients who received either STP (n=286) or CT (n=75). The STP group received STT combined with a probiotic preparation for 1 week. The CT group received STT and metronidazole for 1 week. Results The intention-to-treat and per-protocol eradication rates were 83.6% (95% confidence interval [CI], 79.0 to 87.7) and 87.1% (95% CI, 81.2 to 89.7) in the STP group and 86.7% (95% CI, 78.7 to 93.3) and 91.4% (95% CI, 83.6 to 97.1) in the CT group (p=0.512 and p=0.324), respectively. The frequency of adverse effects was higher in the CT group (28.2%) than in the STP group (12.8%) (p=0.002). Conclusions STP and CT are encouragingly efficacious as first-line treatments for H. pylori infection. Therefore, adding probiotics to STT may be a feasible option to avoid side effects.
Impact of roll compaction design, process parameters, and material deformation behaviour on ribbon relative density

Abstract Ribbons from microcrystalline cellulose (MCC), mannitol, and their 50:50% mixture were produced using the roll compactors AlexanderWerk BT120, Hosokawa Alpine Pharmapaktor C250, L.B. Bohle BRC 25, and Gerteis Mini-Pactor in the frame of multilevel full factorial experimental plans. The specific compaction force (SCF)/hydraulic pressure (HP), gap width (GW), roll speed, and fraction of MCC were analyzed as quantitative factors, whereas the roll surface and sealing system were examined as qualitative factors. Ribbon relative density was investigated as response of the models. The SCF/HP is found to be the most significant factor in each model. A significant inverse effect of the GW is obtained in the models of AlexanderWerk BT120, Pharmapaktor C250, and BRC 25 roll compactors, using smooth rolls. The principle of the establishment of a conversion factor (cf) is introduced based on the obtained data sets of AlexanderWerk BT120 and Mini-Pactor. This can facilitate the transfer of a roll compaction process between different types of roll compactors.
Skin microneedling for acne scars associated with pigmentation in patients with dark skin

Acne is very common skin condition. Most patients with acne will have a degree of scarring as a result of their acne. In patients with darker skin color the scarring can be further complicated by hyperpigmentation. Several treatment options can be used to improve acne scarring, however the problem of post acne hyperpigmentation is not often addressed. This study especially focus on the treatment of pigmented post acne scarring using skin microneedling.
AHNS Series: Do you know your guidelines? Principles of treatment for locally advanced or unresectable head and neck squamous cell carcinoma

This article is a continuation of the “Do You Know Your Guidelines” series, initiated by the Education committee of the American Head and Neck Society. Treatment guidelines for advanced head and neck squamous cell carcinoma are reviewed here, including the critical roles of radiotherapy, chemotherapy, and the recent application of immunotherapy agents. We will be limiting this discussion to include cancers of the oral cavity, oropharynx, hypopharynx, and larynx. It should be noted that much of the article pertains to human papillomavirus (HPV)‐negative oropharyngeal cancer where applicable, as HPV‐positive oropharyngeal squamous cell carcinoma carries a different natural history, different prognosis, and now different staging criteria. Additionally, the article will not include information on nasopharyngeal or sinus cancers, as these latter topics are covered in separate “Do you know your guidelines? ” installments and these diagnoses carry somewhat different approaches to diagnosis and management that diverge from the focus of this article.
Survey of Extended LEACH-Based Clustering Routing Protocols for Wireless Sensor Networks

An energy efficient routing protocol is the major concern in Wireless Sensor Networks (WSNs). In this survey paper, we present energy efficient hierarchical routing protocols, developed from conventional LEACH routing protocol. Main focus of our study is how these extended protocols work in order to increase the life time and how quality routing protocol are improved for WSNs. Furthermore, this paper also highlights some of the issues faced by LEACH and also explains how these issues are tackled by extended versions of LEACH. We compare the features and performance issues of the selected hierarchical routing protocols.
Chondrogenesis of Embryonic Stem Cell‐Derived Mesenchymal Stem Cells Induced by TGFβ1 and BMP7 Through Increased TGFβ Receptor Expression and Endogenous TGFβ1 Production

For decades stem cells have proven to be invaluable to the study of tissue development. More recently, mesenchymal stem cells (MSCs) derived from embryonic stem cells (ESCs) (ESC‐MSCs) have emerged as a cell source with great potential for the future of biomedical research due to their enhanced proliferative capability compared to adult tissue‐derived MSCs and effectiveness of musculoskeletal lineage‐specific cell differentiation compared to ESCs. We have previously compared the properties and differentiation potential of ESC‐MSCs to bone marrow‐derived MSCs. In this study, we evaluated the potential of TGFβ1 and BMP7 to induce chondrogenic differentiation of ESC‐MSCs compared to that of TGFβ1 alone and further investigated the cellular phenotype and intracellular signaling in response to these induction conditions. Our results showed that the expression of cartilage‐associated markers in ESC‐MSCs induced by the TGFβ1 and BMP7 combination was increased compared to induction with TGFβ1 alone. The TGFβ1 and BMP7 combination upregulated the expression of TGFβ receptor and the production of endogenous TGFβs compared to TGFβ1 induction. The growth factor combination also increasingly activated both of the TGF and BMP signaling pathways, and inhibition of the signaling pathways led to reduced chondrogenesis of ESC‐MSCs. Our findings suggest that by adding BMP7 to TGFβ1‐supplemented induction medium, ESC‐MSC chondrogenesis is upregulated through increased production of endogenous TGFβ and activities of TGFβ and BMP signaling. J. Cell. Biochem. 118: 172–181, 2017. © 2016 Wiley Periodicals, Inc.
Erythrocyte membrane fatty acids and breast cancer risk: a prospective analysis in the nurses' health study II

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case‐control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd‐chain saturated (SFA, e.g. 17:0, ORQ4vsQ1(95% CI) =1.85 (1.18–2.88), ptrend=0.006 pint<0.001), trans (TFA, e.g. 18:1, ORQ4vsQ1(95% CI) =2.33 (1.45–3.77), ptrend<0.001, pint=0.007) and dairy‐derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n‐7t; ORQ4vsQ1(95% CI) =1.83(1.16–2.89), ptrend=0.005, pint<0.001) were positively associated, and n‐3 polyunsaturated fatty acids (n‐3 PUFA, e.g. alpha‐linolenic acid; ORQ4vsQ1(95% CI) =0.57 (0.36–0.89), ptrend=0.017, pint=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (ORQ4vsQ1(95% CI) =0.68 (0.46–0.98), ptrend=0.05, pint=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy‐derived fatty acids and inverse associations of n‐3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.
Which one is better?: information navigation techniques for spatially aware handheld displays

Information navigation techniques for handheld devices support interacting with large virtual spaces on small displays, for example finding targets on a large-scale map. Since only a small part of the virtual space can be shown on the screen at once, typical interfaces allow for scrolling and panning to reach off-screen content. Spatially aware handheld displays sense their position and orientation in physical space in order to provide a corresponding view in virtual space. We implemented various one-handed navigation techniques for camera-tracked spatially aware displays. The techniques are compared in a series of abstract selection tasks that require the investigation of different levels of detail. The tasks are relevant for interfaces that enable navigating large scale maps and finding contextual information on them. The results show that halo is significantly faster than other techniques. In complex situations zoom and halo show comparable performance. Surprisingly, the combination of halo and zooming is detrimental to user performance.
Population genetics and phylogeography of sea turtles

The seven species of sea turtles occupy a diversity of niches, and have a history tracing back over 100 million years, yet all share basic life‐history features, including exceptional navigation skills and periodic migrations from feeding to breeding habitats. Here, we review the biogeographic, behavioural, and ecological factors that shape the distribution of genetic diversity in sea turtles. Natal homing, wherein turtles return to their region of origin for mating and nesting, has been demonstrated with mtDNA sequences. These maternally inherited markers show strong population structure among nesting colonies while nuclear loci reveal a contrasting pattern of male‐mediated gene flow, a phenomenon termed ‘complex population structure’. Mixed‐stock analyses indicate that multiple nesting colonies can contribute to feeding aggregates, such that exploitation of turtles in these habitats can reduce breeding populations across the region. The mtDNA data also demonstrate migrations across entire ocean basins, some of the longest movements of marine vertebrates. Multiple paternity occurs at reported rates of 0–100%, and can vary by as much as 9–100% within species. Hybridization in almost every combination among members of the Cheloniidae has been documented but the frequency and ultimate ramifications of hybridization are not clear. The global phylogeography of sea turtles reveals a gradient based on habitat preference and thermal regime. The cold‐tolerant leatherback turtle (Dermochelys coriacea) shows no evolutionary partitions between Indo‐Pacific and Atlantic populations, while the tropical green (Chelonia mydas), hawksbill (Eretmochelys imbricata), and ridleys (Lepidochelys olivacea vs. L. kempi) have ancient separations between oceans. Ridleys and loggerhead (Caretta caretta) also show more recent colonization between ocean basins, probably mediated by warm‐water gyres that occasionally traverse the frigid upwelling zone in southern Africa. These rare events may be sufficient to prevent allopatric speciation under contemporary geographic and climatic conditions. Genetic studies have advanced our understanding of marine turtle biology and evolution, but significant gaps persist and provide challenges for the next generation of sea turtle geneticists.
A Collaborative Framework for 3 D Mapping Using Unmanned Aerial Vehicles

This paper describes an overview of a generic framework for collaboration among humans and multiple heterogeneous robotic systems based on the use of a formal characterization of delegation as a speech act. The system used contains a complex set of integrated software modules that include delegation managers for each platform, a task specification language for characterizing distributed tasks, a task planner, a multiagent scan trajectory generation and region partitioning module, and a system infrastructure used to distributively instantiate any number of robotic systems and user interfaces in a collaborative team. The application focusses on 3D reconstruction in alpine environments intended to be used by alpine rescue teams. Two complex UAV systems used in the experiments are described. A fully autonomous collaborative mission executed in the Italian Alps using the framework is also described.
Summarising the points made in online political debates

Online communities host growing numbers of discussions amongst large groups of participants on all manner of topics. This user-generated content contains millions of statements of opinions and ideas. We propose an abstractive approach to summarize such argumentative discussions, making key content accessible through ‘point’ extraction, where a point is a verb and its syntactic arguments. Our approach uses both dependency parse information and verb case frames to identify and extract valid points, and generates an abstractive summary that discusses the key points being made in the debate. We performed a human evaluation of our approach using a corpus of online political debates and report significant improvements over a high-performing extractive summarizer.
Semiquantitation of Axonal Injury in Traumatically Damaged Brains Using Color Deconvolution

Introduction: In traumatic brain injury biomechanics, macroscale biomechanical events need to be correlated with microscale neuropathologic changes and improved quantitation of microscopic axonal injury is an essential component of lesion evaluation. Objectives: To develop a novel technique for automatically identifying injured amyloid precursor protein immunopositive axons and aggregating these observations over a macroscopic brain dissection. Methods: A color deconvolution method was adapted into Matlab to identify clusters of pixels with colors typical of amyloid precursor protein positive tissue from large-scale brain dissection. Results: The methodology is demonstrated in the brain of a sheep subjected to a controlled cortical indentation. Conclusions: The technique will be of interest to pathologists and bioengineers seeking to quantitate brain injury over macroscales.
Video partitioning by segmenting moving object trajectories

Video partitioning may be involve in a number of applications and present solutions for monitoring and tracking particular person trajectory and also helps in to generate semantic analysis of single entity or of entire video. Many recent advances in object detection and tracking concern about motion structure and data association used to be assigned a label to trajectories and analyze them independently. In this work we propose an approach for video portioning and a structure is given to store motion structure of target set to monitor in video. Spatio-temporal tubes separate individual objects that help to generate semantic analysis report for each object individually. The semantic analysis system for video based on this framework provides not only efficient synopsis generation but also spatial collision where the temporal consistency can be resolved for representation of semantic knowledge of each object. For keeping low computational complexity trajectories are generated online and classification, knowledge representation and arrangement over spatial domain are suggested to perform in offline manner.
Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge

In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid‐morning of simulated proestrus, and compared to vehicle‐treated or intact rats. In both simulated and intact rats, CA1‐evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain‐derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1‐evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus.