Miracle-dz/UniFAR-FTUs huggingface dataset:
Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
Scaffold surface modifications and culture conditions as key parameters to develop cartilage and bone tissue engineering implants

This thesis is focused on the development and evaluation of different hybrid scaffolds for the treatment of injuries in cartilage or bone. These hybrid materials were three-dimensional polycaprolactone macroporous scaffolds obtained through freeze extraction and particle leaching combined method and modified with hyaluronic acid or mineral particles. In order to facilitate the description of the obtained results, the thesis is divided in two sections dedicated to bone and cartilage tissue engineering respectively. In the case of bone tissue engineering we addressed the treatment of disorders associated with the spine that require spinal immobilization. This Thesis proposes the development of a synthetic macroporous support for intervertebral fusion as an alternative to commercial bone substitutes. Macroporous scaffolds were developed with bare polycaprolactone or its blends with polylactic acid in order to increase its mechanical properties and degradation rate. Furthermore, the scaffolds obtained were reinforced with hydroxyapatite or Bioglass®45S5 to improve their mechanical properties and turn them in bioactive scaffolds. The supports were characterized physicochemically and biologically to determine if they met the requirements of the project. Finally, materials were tested in vivo in a bone critical size defect preformed in a rabbit model against a commercial support. Cartilage engineering has been extensively studied in the last years due to the inherent limited self repair ability of this tissue. The second part of the thesis was focused in developing a construct composed by in vitro differentiated chondrocyte like cells in a hybrid scaffold for cartilage tissue engineering. Polycaprolactone hybrid substrates coated with hyaluronic acid scaffold were developed obtaining a substrate with positive influence over the development of chondrocyte phenotype in culture and able to protect the cells from excessive mechanical loading in the joint. Cell-scaffolds constructs were obtained combining hybrid scaffolds with mesenchymal stem cells and differentiating them to chondrocytes using chondrogenic culture medium combined with hypoxia, mechanical stimulus or co-culture. Finally the cellularized scaffolds were mechanically, biochemically and histologically characterized to determine the production of extracellular matrix and expression of chondrogenic markers.
Surface morphology, bioactivity, and antibacterial studies of pulsed laser deposited hydroxyapatite coatings on Stainless Steel 254 for orthopedic implant applications

Coating of hydroxyapatite using the pulsed laser deposition technique, on medical grade UNS S31254 stainless steel (254SS), to yield a biomaterial for potential orthopedic implant applications, is unreported so far in the literature. In this paper, the pulsed laser deposition process was used to improve the physiological response of 254SS. The surface morphology of the deposited hydroxyapatite coatings was characterized using scanning electron microscopy and atomic force microscopy, while the phase composition of the deposited hydroxyapatite coatings was determined using the X-ray diffraction method. The thickness and adhesive strength of the hydroxyapatite coatings were determined using an ellipsometer and a tensometer, respectively. The antibacterial efficacy of the deposited hydroxyapatite coatings was confirmed using the modern technique of fluorescence-activated cell sorting. Finally, the bioactivity of hydroxyapatite coatings was investigated by conducting immersion test in simulated body fluid environment. The scanning electron microscopy and atomic force microscopy results revealed higher (∼8 nm) average surface roughness, which is likely to facilitate better osseointegration. X-ray diffraction analysis confirmed that postdeposition annealing is essential to achieve the desired crystallinity and uniformity of coatings. Tensile pull-out tests confirmed adhesive strength of hydroxyapatite coatings beyond the standard expected values. Immersion tests inferred high bioactivity of pulsed laser deposition hydroxyapatite coatings. The promising results obtained in this research signify the potential application of hydroxyapatite coatings in orthopedic implants.
Determination of Johnson-Cook model constants by measurement of strain rate by optical method

The goal of the research program implemented by the authors was to develop methodology to be used for determination of constants for Johnson-Cook material model using Charpy impact test. This model is used in programs for modeling by the FEM method in order to account for the influence of strain rate on the strength properties. The method we propose involves selection of the material constants by comparing behavior of a specimen during Charpy test with results of simulation using the FEM method, in LS-DYNA program. Measurement of strain on the specimen surface involved recording Charpy test by means of a fast video camera and time –lapse measurement of changes in the distance of markers.
Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.
Cognition, quality‐of‐life, and symptom clusters in breast cancer: Using Bayesian networks to elucidate complex relationships

Breast cancer patients frequently complain of cognitive dysfunction during chemotherapy. Patients also report experiencing a cluster of sleep problems, fatigue, and depressive symptoms during chemotherapy. We aimed to understand the complex dynamic interrelationships of depression, fatigue, and sleep to ultimately elucidate their role in cognitive performance and quality of life amongst breast cancer survivors undergoing chemotherapy treatment.
Nasogastric Tube Feeding for Individuals With Anorexia Nervosa

BACKGROUND: The use of nasogastric (NG) feeding in individuals with anorexia nervosa (AN) is endorsed by national professional organizations; however, no guidelines currently exist. OBJECTIVES: The objectives of this review were to identify and evaluate outcomes of NG feedings for individuals with AN and to develop recommendations for future research, policy, and practice. DESIGN: An integrative review of the research literature was conducted. RESULTS: Of the 19 studies reviewed, all indicated short-term weight gain following NG feeding. Four studies examined adherence; nearly 30% of subjects were nonadherent as evidenced by tube manipulation. Seven studies reported psychiatric outcomes, suggesting NG feeding reduces eating disorder behaviors but not overall symptomology. CONCLUSIONS: NG feeding promotes short-term weight gain; however, long-term outcomes are poorly understood. Future research, using rigorous methods, is still needed to inform practice.
Use of a physiologically based pharmacokinetic model to simulate drug–drug interactions between antineoplastic and antiretroviral drugs

Background: Co-administration of antineoplastics with ART is challenging due to potential drug–drug interactions (DDIs). However, trials specifically assessing such DDIs are lacking. Our objective was to simulate DDIs between the antineoplastics erlotinib and gefitinib with key antiretroviral drugs and to predict dose adjustments using a physiologically based pharmacokinetic (PBPK) model. Methods: In vitro data describing chemical properties and pharmacokinetic processes of each drug and their effect on cytochrome P450 isoforms were obtained from the literature. Plasma drug–concentration profiles were simulated in a virtual population of 50 individuals receiving erlotinib or gefitinib alone or with darunavir/ritonavir, efavirenz or etravirine. Simulated pharmacokinetic parameters and the magnitude of DDIs with probe drugs (midazolam, maraviroc) were compared with literature values. Erlotinib and gefitinib pharmacokinetics with and without antiretrovirals were compared and dose-adjustment strategies were evaluated. Results: Simulated parameters of each drug and the magnitude of DDIs with probe drugs were in agreement with reference values. Darunavir/ritonavir increased erlotinib and gefitinib exposure, while efavirenz and etravirine decreased erlotinib and gefitinib concentrations. Based on our predictions, dose-adjustment strategies may consist of once-daily dosing erlotinib at 25 mg and gefitinib at 125 mg with darunavir/ritonavir; or erlotinib at 200 mg and gefitinib at 375 mg with etravirine. The interaction with efavirenz was not overcome even after doubling erlotinib or gefitinib doses. Conclusions: PBPK models predicted the in vivo pharmacokinetics of erlotinib, gefitinib and the antiretrovirals darunavir/ritonavir, efavirenz and etravirine, and the DDIs between them. The simulated dose-adjustments may represent valuable strategies to optimize antineoplastic therapy in HIV-infected patients.
A stochastic resampling based selective particle filter for visual object tracking

In this work, a particle filter based algorithm has been proposed for visual object tracking. The key idea of the tracking algorithm is to combine a modified particle filter with bat algorithm to reduce sample degeneracy, sample impoverishments, memory requirement and number of particles and to increase tracking accuracy. The proposed particle filter includes a new resampling algorithm which has been proposed by modifying meta-heuristic bat search algorithm. A four dimensional color histogram based model is used which suppresses background color present inside the foreground template, boosting the foreground histogram, when size of the object shrinks, but the template size remains intact. The motion dynamics model further reduces the chance of sample degeneracy among the particles by adaptively shifting mean of the process noise. The proposed algorithm has been compared with other particle filter based visual object tracking algorithms and has been found to be working satisfactorily.
Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis

Aims To review maternal and foetal outcomes in women with mechanical heart valves (MHVs) treated with vitamin-K antagonists (VKAs), first-trimester heparin followed by VKAs (sequential treatment), low molecular weight heparin (LMWH) and unfractionated heparin (UFH) during pregnancy, in order to inform practice. Methods and results Medline, Embase and Central were searched from inception until February 2016. Two reviewers independently screened 1786 titles, reviewed 110 full-texts and extracted data and assessed risk-of-bias from 46 articles. Pooled incidence (95% confidence intervals) was calculated for maternal and foetal outcomes. Included studies had a moderate or high risk-of-bias. With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4–1.4), 2.0% (0.8–3.1) and 2.9% (0.2–5.7), thromboembolic complications in 2.7% (1.4–4.0), 5.8% (3.8–7.7) and 8.7% (3.9–13.4), livebirths in 64.5% (48.8–80.2), 79.9% (74.3–85.6) and 92.0% (86.1–98.0) and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3–3.7), 1.4% (0.3–2.5) and 0%, respectively. When UFH is used throughout pregnancy, 11.2% (2.8–19.6) suffered thromboembolic complications. Foetal loss and adverse events occurred with first-trimester warfarin doses ⩽ 5 mg/day, although there were more livebirths [83.6% (75.8–91.4) vs. 43.9% (32.8–55.0)] and fewer foetal anomalies [2.3% (0.7–4.0) vs. 12.4% (3.3–21.6)] with lower doses than with warfarin > 5 mg/day. Conclusions VKAs are associated with fewest maternal complications but also with fewest livebirths. Sequential treatment does not eliminate anticoagulant-related foetal/neonatal adverse events. LMWH is associated with the highest number of livebirths. The safety of UFH throughout pregnancy and first-trimester warfarin ⩽ 5 mg/day remains unconfirmed.
Centriole Overduplication is the Predominant Mechanism Leading to Centrosome Amplification in Melanoma

Centrosome amplification (CA) is common in cancer and can arise by centriole overduplication or by cell doubling events, including the failure of cell division and cell–cell fusion. To assess the relative contributions of these two mechanisms, the number of centrosomes with mature/mother centrioles was examined by immunofluorescence in a tissue microarray of human melanomas and benign nevi (n = 79 and 17, respectively). The centrosomal protein 170 (CEP170) was used to identify centrosomes with mature centrioles; this is expected to be present in most centrosomes with cell doubling, but on fewer centrosomes with overduplication. Using this method, it was determined that the majority of CA in melanoma can be attributed to centriole overduplication rather than cell doubling events. As Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication, the hypothesis that PLK4 overexpression contributes to centriole overduplication was evaluated. PLK4 is significantly overexpressed in melanoma compared with benign nevi and in a panel of human melanoma cell lines (A375, Hs294T, G361, WM35, WM115, 451Lu, and SK-MEL-28) compared with normal human melanocytes. Interestingly, although PLK4 expression did not correlate with CA in most cases, treatment of melanoma cells with a selective small-molecule PLK4 inhibitor (centrinone B) significantly decreased cell proliferation. The antiproliferative effects of centrinone B were also accompanied by induction of apoptosis. Implications: This study demonstrates that centriole overduplication is the predominant mechanism leading to centrosome amplification in melanoma and that PLK4 should be further evaluated as a potential therapeutic target for melanoma treatment. Mol Cancer Res; 16(3); 517–27. ©2018 AACR.
Umbilical Cord Blood Platelet Lysate as Serum Substitute in Expansion of Human Mesenchymal Stem Cells

Objective The diverse clinical applications for human mesenchymal stem cells (hM- SCs) in cellular therapy and regenerative medicine warrant increased focus on developing adequate culture supplements devoid of animal-derived products. In the present study, we have investigated the feasibility of umbilical cord blood-platelet lysate (UCB-PL) as a standard substitute for fetal bovine serum (FBS) and human peripheral blood-PL (PB-PL). Materials and Methods In this experimental study, platelet concentrates (PC) from UCB and human PB donors were frozen, melted, and sterilized to obtain PL. Quality control included platelet cell counts, sterility testing (viral and microbial), total protein concentrations, growth factor levels, and PL stability. The effects of UCB-PL and PB-PL on hMSCs proliferation and differentiation into osteocytes, chondrocytes, and adipocytes were studied and the results compared with FBS. Results UCB-PL contained high levels of protein content, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor (TGF) compared to PB-PL. All growth factors were stable for at least nine months post-storage at -70˚C. hMSCs proliferation enhanced following treatment with UCB-PL. With all three supplements, hMSCs could differentiate into all three lineages. Conclusion PB-PL and UCB-PL both were potent in hMSCs proliferation. However, PB promoted osteoblastic differentiation and UCB-PL induced chondrogenic differentiation. Because of availability, ease of use and feasible standardization of UCB-PL, we have suggested that UCB-PL be used as an alternative to FBS and PB-PL for the cultivation and expansion of hMSCs in cellular therapy.
Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory.

BACKGROUND Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. OBJECTIVE To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. METHODS Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. RESULTS In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. CONCLUSION Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA.
A Coordinated Frequency Regulation Framework Based on Hybrid Battery-Ultracapacitor Energy Storage Technologies

The replacement of conventional electricity generators by wind turbines and solar photovoltaic panels results in reduced system inertia, which jeopardizes the electric power system frequency. Frequency variation is critical as it may cause equipment damage and blackouts. Frequency regulation (FR) plays a crucial role in sustaining the stability of electric power grids by minimizing the instantaneous mismatches between electric power generation and load demand. Regulation service (RS) providers dynamically inject/absorb electric power to/from the grid, in response to regulation signals provided by independent system operators (ISOs), in order to keep the frequency within the permissible limits. The regulation signals are highly transient and hence require quick responding resources in order to provide FR effectively. This paper proposes innovative design and operation frameworks for state-of-the-art battery-energy storage system (BESS) and ultracapacitor (UC)-based hybrid energy storage system (HESS) employed for FR in electricity market. The proposed system design framework is based upon the initial investment cost, replacement cost, maintenance cost, and financial penalty imposed by ISO on RS provider for not supplying the required RS. The proposed system operation framework allocates power to both BESS and UC based upon their maximum power ratings while fulfilling their constraints at the same time. The frequent partial charge–discharge transitions, which are detrimental for BESS, are reduced by using two battery banks instead of one large battery bank. The charging and discharging of two battery banks are controlled innovatively to reduce the transitions between the partial charge–discharge transitions. Moreover, a comparison based upon cost per unit between two cases, that is: 1) HESS employed for FR and 2) BESS employed for FR, is presented, which shows that the HESS is more economical.
Dexamethasone Modulates Nonvisual Opsins, Glucocorticoid Receptor, and Clock Genes in Danio rerio ZEM-2S Cells

Here we report, for the first time, the differential cellular distribution of two melanopsins (Opn4m1 and Opn4m2) and the effects of GR agonist, dexamethasone, on the expression of these opsins and clock genes, in the photosensitive D. rerio ZEM-2S embryonic cells. Immunopositive labeling for Opn4m1 was detected in the cell membrane whereas Opn4m2 labeling shows nuclear localization, which did not change in response to light. opn4m1, opn4m2, gr, per1b, and cry1b presented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression of per1b and cry1b transcripts to ZT16, which corresponds to the highest opn4m1 expression. Interestingly, DEX promoted an increase of per1b expression when applied in LD condition but a decrease when the cells were kept under DD condition. Although DEX effects are divergent with different light conditions, the response resulted in clock synchronization in all cases. Taken together, these data demonstrate that D. rerio ZEM-2S cells possess a photosensitive system due to melanopsin expression which results in an oscillatory profile of clock genes in response to LD cycle. Moreover, we provide evidence that glucocorticoid acts as a circadian regulator of D. rerio peripheral clocks.