Miracle-dz/UniFAR-FTUs huggingface dataset:
Stable disease in a patient with metastatic leiomyosarcoma treated with trabectedin

Leiomyosarcomas represent the most common variant of uterine sarcomas, and are also considered to be the least chemosensitive. To date, adriamycin and ifosfamide are believed to be the most effective drugs for its treatment, in addition to docetaxel and gemcitabine. Recently, the introduction of trabectedin has provided clinicians with another treatment option, and the drug may have some benefits for patients as it may allow for long-term treatment. We present the case of a patient who previously failed multiple cycles of chemotherapy and who was subsequently treated with 30 cycles of trabectedin as third-line therapy for multiple metastases of uterine leiomyosarcoma. During the treatment period, the dosage and dose interval of trabectedin were optimized because of the appearance of grade 4 hematological and gastrointestinal toxicity. Dose adjustments led to acceptable tolerability. Trabectedin was associated with a very good partial response, especially at the pulmonary and pancreatic levels, and stable disease was achieved at all metastatic sites. The patient is currently continuing treatment with trabectedin and has clinically stable disease after 2 years of therapy. This case report provides further evidence that trabectedin is a valid and well-tolerated therapeutic option that can be used in the long term in uterine leiomyosarcoma.
Comparative analyses of simple sequence repeats (SSRs) in 23 mosquito species genomes: Identification, characterization and distribution (Diptera: Culicidae)

Simple sequence repeats (SSRs) exist in both eukaryotic and prokaryotic genomes and are the most popular genetic markers, but the SSRs of mosquito genomes are still not well understood. In this study, we identified and analyzed the SSRs in 23 mosquito species using Drosophila melanogaster as reference at the whole‐genome level. The results show that SSR numbers (33 076–560 175/genome) and genome sizes (574.57–1342.21 Mb) are significantly positively correlated (R2 = 0.8992, P < 0.01), but the correlation in individual species varies in these mosquito species. In six types of SSR, mono‐ to trinucleotide SSRs are dominant with cumulative percentages of 95.14%–99.00% and densities of 195.65/Mb–787.51/Mb, whereas tetra‐ to hexanucleotide SSRs are rare with 1.12%–4.22% and 3.76/Mb–40.23/Mb. The (A/T)n, (AC/GT)n and (AGC/GCT)n are the most frequent motifs in mononucleotide, dinucleotide and trinucleotide SSRs, respectively, and the motif frequencies of tetra‐ to hexanucleotide SSRs appear to be species‐specific. The 10–20 bp length of SSRs are dominant with the number of 110 561 ± 93 482 and the frequency of 87.25% ± 5.73% on average, and the number and frequency decline with the increase of length. Most SSRs (83.34% ± 7.72%) are located in intergenic regions, followed by intron regions (11.59% ± 5.59%), exon regions (3.74% ± 1.95%), and untranslated regions (1.32% ± 1.39%). The mono‐, di‐ and trinucleotide SSRs are the main SSRs in both gene regions (98.55% ± 0.85%) and exon regions (99.27% ± 0.52%). An average of 42.52% of total genes contains SSRs, and the preference for SSR occurrence in different gene subcategories are species‐specific. The study provides useful insights into the SSR diversity, characteristics and distribution in 23 mosquito species of genomes.
A mixed integer programming formulation for the three-dimensional bin packing problem deriving from an air cargo application

The present paper discusses the problem of optimizing the loading of boxes into containers. The goal is to minimize the unused volume. This type of problem belongs to the family of multiple bin size bin packing problems (MBSBPP). The approach includes an extensive set of constraints encountered in real-world applications in the three-dimensional case: the stability, the fragility of the items, the weight distribution, and the possibility to rotate the boxes. It also includes the specific situation in which containers are truncated parallelepipeds. This is typical in the field of air transportation. While most papers on cutting and packing problems describe ad hoc procedures, this paper proposes a mixed integer linear program. The validity of this model is tested on small instances.
Identifying the bacteria causing ovine gangrenous mastitis and detection of Staphylococcus aureus in gangrenous milk by PCR.

Summary The objective of this study was to identify bacteria causing gangrenous ovine mastitis as well as to detect and genotype Staphylococcus aureus in milk samples by using polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) of coagulase gene. A total of 264 milk samples were collected from Awassi sheep with gangrenous mastitis raised in Sanliurfa province of Turkey. By using bacteriological examination Staphylococcus aureus (75%), Mannheimia haemolytica (7.2%), coagulase negative staphylococci (6.43%), Escherichia coli (4.55%), Corynebacterium spp. (0.76%) and Actinomyces pyogenes (0.76%) were identified. Bacterial DNA was isolated from 155 randomly selected milk sample. By PCR amplification of coagulase gene S. aureus was detected in 91.6% of the milk samples. Three different amplicons of 420 (0.7%), 580 (65.3%) and 780 (34%) bp band sizes, each showing a specific RFLP profile were observed. In conclusion, S. aureus was found to be mostly responsible for gangrenous mastitis in sheep raised in this region. S. aureus in milk samples could be more rapidly detected by PCR method. Two coa genotype of S. aureus were found to be common suggesting that limited number of strains were responsible for most cases of gangrenous mastitis in the region under the study.
Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma.

BACKGROUND BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAFV600E assay was reported. The objective of this study was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment. METHODS Circulating BRAFV600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy. RESULTS In a murine model of anaplastic thyroid carcinoma with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAFV600E levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. CONCLUSIONS This study shows the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes

Background: Bolus calculators help patients with type 1 diabetes to mitigate the effect of meals on their blood glucose by administering a large amount of insulin at mealtime. Intraindividual changes in patients physiology and nonlinearity in insulin-glucose dynamics pose a challenge to the accuracy of such calculators. Method: We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal size. Following meal announcements, the meal compartment and the meal time constant are estimated, otherwise insulin sensitivity is estimated. Results: We compare the performance of a conventional linear bolus calculator with the proposed bolus calculator. The proposed basal-bolus calculator significantly improves the time spent in glucose target (P < .01) compared to the conventional bolus calculator. Conclusion: An adaptive nonlinear basal-bolus calculator can efficiently compensate for physiological changes. Further clinical studies will be needed to validate the results.
Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment

The solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)-coated CPT nanocomposite by means of a simple heat-treatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid cross-membrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.
Ultrashort echo time magnetization transfer (UTE‐MT) imaging and modeling: magic angle independent biomarkers of tissue properties

MRI biomarkers such as T2, T2* and T1rho have been widely used, but are confounded by the magic angle effect. The purpose of this study is to investigate the use of the two‐dimensional ultrashort echo time magnetization transfer (UTE‐MT) sequence for potential magic angle independent MR biomarkers. Magnetization transfer was investigated in cadaveric Achilles tendon samples using the UTE‐MT sequence at five MT powers and five frequency offsets ranging from 2 to 50 kHz. The protocol was applied at five sample orientations ranging from 0 to 90° relative to the B0 field. The results were analyzed with a two‐pool quantitative MT model. Multiple TE data were also acquired and mono‐exponential T2* was calculated for each orientation. Macromolecular proton fractions and exchange rates derived from UTE‐MT modeling did not appreciably change between the various orientations, whereas the T2* relaxation time demonstrated up to a sixfold increase from 0° to 55°. The UTE‐MT technique with two‐pool modeling shows promise as a clinically compatible technique that is resistant to the magic angle effect. This method provides information on the macromolecular proton pool that cannot be directly obtained by other methods, including regular UTE techniques.
Anticoagulants inhibit proteolytic clearance of plasma amyloid beta

We recently discovered a plasma proteolysis pathway, termed the FXII-FVII pathway which is composed of coagulation proteases, and found it to be mainly responsible for the clearance of Aβ42 in the plasma in mice. Aβ42 and Aβ40 are the main Aβ forms in Alzheimer’s disease (AD). In the present study, in vitro assays, wild type (WT) mice and J20 mice (a transgenic AD model) are used to assess the degradation of Aβ40 and Aβ42 by the FXII-FVII pathway and the impact of anticoagulants on such degradation. Four clinically available and mechanistically distinct anticoagulants are evaluated, including dabigatran, enoxaparin (EP), rivaroxaban and warfarin. Each anticoagulant significantly elevates plasma level of synthetic Aβ42 in WT mice, among which EP is the most effective. The differential efficacies of the anticoagulants in elevating plasma Aβ42 level match closely with their inhibitory mechanisms towards the FXII-FVII pathway. Plasma Aβ40 is also degraded by the FXII-FVII pathway and is protected by EP. Moreover, the FXII-FVII pathway is significantly activated in J20 mice, but EP inhibits the activation and significantly elevates plasma levels of both Aβ40 and Aβ42. Taken together, our results shed new light on Aβ metabolism, reveal a novel function of anticoagulants, and suggest a novel approach to potentially developing plasma Aβ as an AD biomarker.
Local host specialization, host-switching, and dispersal shape the regional distributions of avian haemosporidian parasites

Significance Within eastern North America, distributions of vector-transmitted haemosporidian blood parasites of birds, commonly known as “avian malaria parasites,” are associated with the distributions of their host species independently of direct effects of climate on potential vectors. Spatial analyses additionally indicated an absence of dispersal limitation for these parasites. Finally, host-breadth, ranging continuously from specialist to generalist, varies among parasite lineages and is dynamic within parasite assemblages over space and time. The distributions of avian haemosporidian parasites emphasize the ability of parasites to disperse across broad regions and to switch readily between hosts to become emerging infectious diseases. The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily.
Combustion and Emissions Performance of Syngas Fuels Derived from Palm Kernel Shell and Polyethylene (PE) Waste via Catalytic Steam Gasification

Computational fluid dynamics analysis of the burning of syngas fuels derived from biomass and plastic solid waste mixture through gasification process is presented in this paper. The syngas fuel is burned in gas turbine can combustor. Gas turbine can combustor with swirl is designed to burn the fuel efficiently and reduce the emissions. The main objective is to test the impact of the alternative syngas fuel compositions and lower heating value on the combustion performance and emissions. The syngas fuel is produced by blending palm kernel shell (PKS) with polyethylene (PE) waste via catalytic steam gasification (fluidized bed reactor). High hydrogen content syngas fuel was obtained by mixing 30% PE waste with PKS. The syngas composition obtained through the gasification process is 76.2% H2, 8.53% CO, 4.39% CO2 and 10.90% CH4. The lower heating value of the syngas fuel is LHV = 15.98 MJ/m. Three fuels were tested in this study natural gas (100%CH4), syngas fuel and pure hydrogen (100% H2). The power from the combustor was kept constant for all the fuels tested in this study. The effect of syngas fuel composition and lower heating value on the flame shape, gas temperature, mass of carbon dioxide (CO2) and nitrogen oxides (NOX) per unit of energy generation is presented in this paper. The results show an increase of the peak flame temperature and NO mass fractions for the syngas and hydrogen fuels compared to natural gas fuel combustion. Lower average CO2 emissions at the exit of the combustor are obtained for the syngas compared to the natural gas fuel. Keywords—CFD, Combustion, Emissions, Gas Turbine Combustor, Gasification, Solid Waste, Syngas and Waste to Energy.
Synthesis and characterization of nano-CuO and CuO/TiO2 photocatalysts

CuO nanocrystals were prepared by thermal decomposition of Cu-oxalate at 400 °C; then CuO/TiO2 core/shell nanocrystals were formed via the hydrolysis of titanium isopropoxide (TIP) on the surface of CuO nanocrystals. The characteristics of the synthesized nanocrystals were systematically studied using appropriate techniques, namely the morphology by using scanning electron microscopy (SEM), and the crystalline structure by x-ray powder diffraction (XRD) and Raman spectroscopy. The structure, shape and size of the CuO and CuO/TiO2 nanocrystals could be tuned by changing various technological parameters: (i) the reaction/growth time (from several minutes to several hours), (ii) reaction temperature (from room temperature to 90 °C) and (iii) the molar ratios of the precursors. The results showed that the reaction temperature and the molar ratio of the precursors play important roles in controlling the morphology and size of both CuO and CuO/TiO2 nanocrystals. With increasing reaction temperature, nano-CuO evolved from spherical shaped nanoparticles to microspheres. By shelling the large-bandgap TiO2 layers on CuO nanocrystals, the core/shell structure is formed and the narrow-bandgap nano-CuO core is expected to be resistant to photocorrosion.
Do current quality measures truly reflect the quality of dialysis?

The US End Stage Renal Disease (ESRD) Program, which came into existence in 1973, was initially envisioned to provide needed financial coverage for about 50 000 patients through Medicare. Over the past 45 years the evolution of the ESRD program has been quite different, and it now serves over one half million dialysis and transplant patients. The Medicare Improvements for Patients and Providers Act (MIPPA) of 2008 Section 153(c) requires the Centers for Medicare and Medicaid Services (CMS) to develop and implement quality measures for dialysis patients as part of the ESRD Quality Incentive Program (QIP) beginning in payment year (PY) 2012. The annual ESRD Prospective Payment System (PPS) rulemaking process allows CMS to create ESRD QIP rules that specify the measures, scoring methods, and payment reduction ranges applicable to the respective PY. CMS assesses each facility's performance and calculates a score for each measure, according to the method detailed for that PY. Scores for each measure are combined to create the Total Performance Score (TPS) for each facility. If a facility's TPS does not meet or exceed the performance standards established during the earlier comparison period, the facility will incur a payment reduction of up to 2% for the entire PY. The QIP program has evolved over the several years since its inception. There have been deletions and additions of various measures. CMS uses additional measures in its Dialysis Facility Compare (DFC) website which is available to the public and forms the basis of the 5‐star rating system for dialysis facilities. The evidence underlying inclusion many of these measures in the QIP and DFC remains an area of debate. In this review, we discuss the evolution of these measures and their appropriateness. We recommend that some of the current QIP and DFC measures should not be used for public reporting and/or payment as unintended consequences may occur. Nonetheless, all the current QIP and DFC measures and others are suitable for internal quality review.
A Simple Method for the Cross-Section Area Determination of Single Profiled Fibers and Its Application

Abstract One of the critical prerequisites for accurately measuring the mechanical properties of profiled fibers is the precise determination of their cross-sectional areas (CSAs). In this study, a new method is established for determining a single profiled fibers’ CSA based on the frozen section method and digital photo, pixel-ratio method (FS-DP). FS-DP is used to obtain a transverse section of a fiber, by acquiring an image of the cross section using optical microscopy or scanning electron microscopy, and then calculating the CSA using Photoshop. Using FS-DP, it was found that the shape of a fiber of silk changes little in a range of 50 μm, but varies considerably over a range of 1 m, while the CSA of cocoon silk (900 m) first increases and then decreases. Mechanical property tests showed that the elongation, strength, elastic modulus, and toughness values of the cocoon silk are consistent with those reported previously. Additionally, FS-DP was also used to observe other profiled fibers. The application tests indicated that FS-DP can be used to quickly and accurately obtain the CSA of a single profiled fiber, and that it is suitable for the large-scale determination and analysis of the mechanical properties of profiled fibers.
Proteomics-based investigation of multiple stages of OSCC development indicates that the inhibition of Trx-1 delays oral malignant transformation

The majority of cases of oral squamous cell carcinoma (OSCC) develop from oral potentially malignant disorders, which have been confirmed to be involved in chronic oxidative stimulation. However, no effective treatment approaches have been used to prevent the development of dysplasia into cancerous lesions thus far. In the present study, a well-established OSCC model was used to detect proteomics profiles at different stages during oral malignant transformation. Of the 15 proteins that were found to be upregulated in both the dysplasia and carcinoma stages, the oxidative stress-associated proteins, thioredoxin-1 (Trx-1), glutaredoxin-1 and peroxiredoxin-2 were note as the proteins with significant changes in expression Trx-1 was identified to be the most significantly upregulated protein in the precancerous stage. Validation experiments confirmed that Trx-1 was overex-pressed both in dysplasia and cancerous tissue samples, and the inhibition of Trx-1 was able to promote the apoptosis of OSCC cells under hypoxic conditions. Furthermore, the experimental application of a Trx-1-specific inhibitory agent in an animal model led to a lower cancerization rate and a delay in tumor formation. The possible mechanisms were associated with the increased apoptosis via a reactive oxygen species (ROS)-dependent pathway. Taken together, our findings indicate that Trx-1 may be an important target for delaying oral malignant transformation, which provides a novel therapeutic strategy for the prevention and treatment of OSCC.