Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired Fibrillin-1 Function Promotes Features of Plaque Instability in Apolipoprotein E–Deficient Mice

Background— Arterial stiffness has been associated with an increased cardiovascular risk. The aim of this study was to investigate the interaction between arterial stiffness and atherosclerosis. Methods and Results— Mice with a mutation (C1039G+/−) in the fibrillin-1 gene leading to fragmentation of the elastic fibers were crossbred with apolipoprotein E–deficient (ApoE−/−) mice. Subsequently, ApoE−/− and ApoE−/−C1039G+/− mice were fed a Western-type diet for 10 or 20 weeks. Our results show that the interaction between arterial stiffness and atherosclerosis is bidirectional. On the one hand, arterial stiffness in ApoE−/−C1039G+/− mice increased more rapidly in the presence of atherosclerotic plaques. On the other hand, arterial stiffness promoted the development of larger and more unstable plaques in ApoE−/−C1039G+/− mice. The plaque area at the aortic root was increased 1.5- and 2.1-fold in ApoE−/−C1039G+/− mice after 10 and 20 weeks of Western-type diet, respectively. After 10 weeks of Western-type diet, plaques of ApoE−/−C1039G+/− mice showed increased apoptosis of smooth muscle cells, which was associated with a decrease in collagen content, an enlargement of the necrotic core, and an increase in macrophages. After 20 weeks of Western-type diet, the number of buried fibrous caps was increased in atherosclerotic lesions of ApoE−/−C1039G+/− mice, not only at the level of the aortic valves but also in the brachiocephalic artery and in the upper, middle, and lower thoracic aorta. Furthermore, acute plaque rupture was observed. Conclusion— These results indicate that fragmentation of the elastic fibers leads to increased vascular stiffness, which promotes features of multifocal plaque instability.
Genetic diversity and drug resistance of Mycobacterium tuberculosis in Ecuador.

BACKGROUND The genetic diversity of Mycobacterium tuberculosis in Quito, Ecuador is not well known. OBJECTIVE To investigate mutations related to drug resistance and bacterial genotypes in M. tuberculosis strains in Ecuador. DESIGN This was a retrospective study of M. tuberculosis isolates from 104 patients. Isolates were phenotypically resistant to rifampicin (RMP) and/or isoniazid (INH). The genotype was determined using 24-locus mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). RESULTS Isolates showed mutations in the rpoB and katG genes, and the inhA promoter. In rpoB, we found 13 genetic alterations at codons 511, 513, 514, 515, 516, 526 and 531. Forty-six (44.2%) RMP-resistant isolates belonged to codon 531. In katG, there were nine genetic alterations at codons 296, 312, 314, 315, 322, 324 and 351. Fifty-three (51%) INH-resistant isolates belonged to codon 315. Five mutations not previously described were identified in katG: Thr324Ser, Thr314Ala, Ala312Pro, Trp351Stop and deleted G at 296 codon. The Latin American Mediterranean (LAM) (33.7%) and Ghana (30.8%) lineages presented most of the main mutations observed. CONCLUSION This is the first report from Ecuador; it describes five new mutations in katG and indicates that LAM is the most prevalent lineage.
Simple fabrication of inner chitosan-coated alginate hollow microfiber with higher stability.

Sodium alginate (NaA) has been widely used as microfiber-based scaffold material. However, Ca-alginate microfiber might disintegrate in the physiological environment due to the loss of calcium ions, which will limit its long-term application in tissue engineering. In this work, to enhance the stability of Ca-alginate microfiber in the physiological environment, an inner chitosan coating was introduced to Ca-alginate hollow microfiber by one step via a microfluidic device. A more stable composite microfiber with double cross-linking layers was generated. The stability of the microfiber was studied in the PBS solution (pH 7.4) to identify the coating effect on the hollow structure. The results revealed that chitosan component bonded an NaA layer to form a stable polyelectrolyte complex membrane in the inner wall of the microfiber, which stabilized the hollow region even though the Ca-alginate shell was disintegrated by PBS solution. In addition, the introduction of chitosan coating improved the inner environment of the low affinity of alginate to cell surfaces and facilitated the cell adhesion and culture in the microfiber. HepG2 cells in the microfibers displayed favorable cell viability and proliferation ability. We believe that this work will lead to the development of innovative methodologies and materials for both cell culture and tissue engineering application. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2019.
Vertebral evolution and ontogenetic allometry: The developmental basis of extreme body shape divergence in microcephalic sea snakes

Snakes exhibit a diverse array of body shapes despite their characteristically simplified morphology. The most extreme shape changes along the precloacal axis are seen in fully aquatic sea snakes (Hydrophiinae): “microcephalic” sea snakes have tiny heads and dramatically reduced forebody girths that can be less than a third of the hindbody girth. This morphology has evolved repeatedly in sea snakes that specialize in hunting eels in burrows, but its developmental basis has not previously been examined. Here, we infer the developmental mechanisms underlying body shape changes in sea snakes by examining evolutionary patterns of changes in vertebral number and postnatal ontogenetic growth. Our results show that microcephalic species develop their characteristic shape via changes in both the embryonic and postnatal stages. Ontogenetic changes cause the hindbodies of microcephalic species to reach greater sizes relative to their forebodies in adulthood, suggesting heterochronic shifts that may be linked to homeotic effects (axial regionalization). However, microcephalic species also have greater numbers of vertebrae, especially in their forebodies, indicating that somitogenetic effects also contribute to evolutionary changes in body shape. Our findings highlight sea snakes as an excellent system for studying the development of segment number and regional identity in the snake precloacal axial skeleton.
Green light‐emitting diode phototherapy for neonatal hyperbilirubinemia: Randomized controlled trial

The main photochemical pathway in phototherapy for neonatal hyperbilirubinemia is the production and elimination (in bile or urine) of cyclobilirubin, which is a structural photoisomer of bilirubin, and which is most efficiently produced by green light. Green light‐emitting diode (LED) phototherapy, however, has not been evaluated in the clinical setting because it is not recommended in American Academy of Pediatrics guidelines. We therefore compared the efficacy of green LED phototherapy and blue LED phototherapy in patients with neonatal hyperbilirubinemia.
And Remember the Truth That Once Was Spoken: Knowledge of Having Disclosed Private Information to a Stranger Is Retrieved Automatically

Whenever individuals reveal personally relevant information to a stranger, they have to remember their self-disclosure for future interactions. Relying on instance-based theories of automaticity, we hypothesized that knowledge about having revealed private information to someone unfamiliar is retrieved automatically whenever this person is encountered again. In two studies, participants were orally interviewed by two different persons and instructed to be honest to one of them and to lie to the other. This instruction was either related to the identity of the interviewers (Experiment 1) or their gender (Experiment 2). Afterward, the target words honest and dishonest had to be identified in a categorization task in which pictures of the interviewers and of unknown persons served as task-irrelevant prime stimuli. In line with the hypothesis, results revealed congruence effects, indicating faster identification of the target word honest following the picture of a person whom one had told the truth.
Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

Significance Populations living in remote rural communities would benefit from rapid, highly sensitive molecular, DNA-based diagnostics to inform the correct and timely treatment of infectious diseases. Such information is also becoming increasingly relevant in global efforts for disease elimination, where the testing of asymptomatic patients is now seen as being important for the identification of disease reservoirs. However, healthcare workers face practical and logistical problems in the implementation of such tests, which often involve complex instrumentation and centralized laboratories. Here we describe innovations in paper microfluidics that enable low-cost, multiplexed DNA-based diagnostics for malaria, delivered, in a first-in-human study, in schools in rural Uganda. Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.
Bioactive poly(ε-caprolactone) microspheres with tunable open pores as microcarriers for tissue regeneration

Microparticles with porous structure can be applied as microcarriers for both cell culture and tissue regeneration. While well-controlled pore structure represents a critical challenge to be achieved. In the present study, in order to develop microcarriers for cell culture, a series of poly(ε-caprolactone) microspheres were fabricated with varied macroporous structures. Poly(ε-caprolactone) microspheres were prepared via the integration of the emulsion/solvent evaporation and particle leaching mechanisms. Particularly, by adjusting poly(ε-caprolactone) concentration and the ratio between the porogen paraffin and poly(ε-caprolactone), the microspheres with the pore size of 25.6–84.0 μm and the porosity of 57.4–75.5% were obtained. Further, the microspheres were subjected to alkaline hydrolysis, followed by surface coating with hydroxyapatite. These porous poly(ε-caprolactone) microspheres with surface modification well supported the adhesion and growth of human fibroblasts. Together, bioactive poly(ε-caprolactone) microspheres with controlled pore structure are potential to be applied in cell culture and tissue regeneration.
In vivo localization of human acetylcholinesterase-derived species in a β-sheet conformation at the core of senile plaques in Alzheimer's disease

Many neurodegenerative diseases are characterized by amyloid deposition. In Alzheimer's disease (AD), β-amyloid (Aβ) peptides accumulate extracellularly in senile plaques. The AD amyloid cascade hypothesis proposes that Aβ production or reduced clearance leads to toxicity. In contrast, the cholinergic hypothesis argues for a specific pathology of brain cholinergic pathways. However, neither hypothesis in isolation explains the pattern of AD pathogenesis. Evidence suggests that a connection exists between these two scenarios: the synaptic form of human acetylcholinesterase (hAChE-S) associates with plaques in AD brains; among hAChE variants, only hAChE-S enhances Aβ fibrillization in vitro and Aβ deposition and toxicity in vivo. Only hAChE-S contains an amphiphilic C-terminal domain (T40, AChE575–614), with AChE586–599 homologous to Aβ and forming amyloid fibrils, which implicates T40 in AD pathology. We previously showed that the amyloid scavenger, insulin-degrading enzyme (IDE), generates T40-derived amyloidogenic species that, as a peptide mixture, seed Aβ fibrillization. Here, we characterized 11 peptides from a T40–IDE digest for β-sheet conformation, surfactant activity, fibrillization, and seeding capability. We identified residues important for amyloidogenicity and raised polyclonal antibodies against the most amyloidogenic peptide. These new antisera, alongside other specific antibodies, labeled sections from control, hAChE-S, hAPPswe, and hAChE-S/hAPPswe transgenic mice. We observed that hAChE-S β-sheet species co-localized with Aβ in mature plaque cores, surrounded by hAChE-S α-helical species. This observation provides the first in vivo evidence of the conformation of hAChE-S species within plaques. Our results may explain the role of hAChE-S in Aβ deposition and aggregation, as amyloidogenic hAChE-S β-sheet species might seed Aβ aggregation.
Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non-Hodgkin's Lymphoma.

INTRODUCTION To reduce health care costs and improve care, payers and physician groups are switching to quality-based and episodic or bundled-care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression. METHODS This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, accounting for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs. CONCLUSION Progression of CLL, AML, and NHL was associated with higher health care costs over a 12-month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types. IMPLICATIONS FOR PRACTICE Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.
Study on inactivation of porcine epidemic diarrhoea virus, porcine sapelovirus 1 and adenovirus in the production and storage of laboratory spray‐dried porcine plasma

Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray‐dried porcine plasma (SDPP).
Is co-location of services with HIV care associated with improved HIV care outcomes? A systematic review

ABSTRACT This systematic review identifies models of service co-location, a structural intervention strategy to remove barriers to HIV care and services, and examines their associations with HIV care outcomes. A cumulative database (e.g., MEDLINE, EMBASE) of HIV, AIDS, and STI literature was systematically searched and manual searches were conducted to identify relevant studies. Thirty-six studies were classified into six models of co-location: HIV care co-located with multiple ancillary services, tuberculosis (TB) care, non-HIV specific primary care, drug abuse treatment, prevention of mother to child transmission programs (PMTCT), and mental health care. More evidence of a positive association was seen for linkage to care and antiretroviral therapy (ART) uptake than for retention and viral suppression. Models of co-location that addressed HIV and non-HIV medical care issues (i.e., co-location with non-HIV specific primary care, PMTCT, and TB) had more positive associations, particularly for linkage to care and ART uptake, than other co-location models. While some findings are encouraging, more research with rigorous study designs is needed to strengthen the evaluation of, and evidence for, service co-location.
UV LEDs based on p–i–n core–shell AlGaN/GaN nanowire heterostructures grown by N-polar selective area epitaxy

Ultraviolet light-emitting diodes fabricated from N-polar AlGaN/GaN core–shell nanowires (NWs) with p–i–n structure produced electroluminescence at 365 nm with ∼5× higher intensities than similar GaN homojunction LEDs. The improved characteristics were attributed to localization of spontaneous recombination to the NW core, reduction of carrier overflow losses through the NW shell, and elimination of current shunting. Poisson-drift-diffusion modeling indicated that a shell Al mole fraction of x = 0.1 in AlxGa1−xN effectively confines electrons and injected holes to the GaN core region. AlGaN overcoat layers targeting this approximate Al mole fraction were found to possess a low-Al-content tip and high-Al-content shell, as determined by scanning transmission electron microscopy. Photoluminescence spectroscopy further revealed the actual Al mole fraction to be NW diameter-dependent, where the tip and shell compositions converged towards the nominal flux ratio for large diameter NWs.
Network-based methods for predicting essential genes or proteins: a survey

Genes that are thought to be critical for the survival of organisms or cells are called essential genes. The prediction of essential genes and their products (essential proteins) is of great value in exploring the mechanism of complex diseases, the study of the minimal required genome for living cells and the development of new drug targets. As laboratory methods are often complicated, costly and time-consuming, a great many of computational methods have been proposed to identify essential genes/proteins from the perspective of the network level with the in-depth understanding of network biology and the rapid development of biotechnologies. Through analyzing the topological characteristics of essential genes/proteins in protein-protein interaction networks (PINs), integrating biological information and considering the dynamic features of PINs, network-based methods have been proved to be effective in the identification of essential genes/proteins. In this paper, we survey the advanced methods for network-based prediction of essential genes/proteins and present the challenges and directions for future research.
The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases

Purpose: Previous studies have shown that the PI3K/Akt/mTOR pathway is activated in up to 70% of breast cancer brain metastases, but there are no approved agents for affected patients. GDC-0084 is a brain penetrant, dual PI3K/mTOR inhibitor that has shown promising activity in a preclinical model of glioblastoma. The aim of this study was to analyze the efficacy of PI3K/mTOR blockade in breast cancer brain metastases models. Experimental Design: The efficacy of GDC-0084 was evaluated in PIK3CA-mutant and PIK3CA wild-type breast cancer cell lines and the isogenic pairs of PIK3CA wild-type and mutant (H1047R/+) MCF10A cells in vitro. In vitro studies included cell viability and apoptosis assays, cell-cycle analysis, and Western blots. In vivo, the effect of GDC-0084 was investigated in breast cancer brain metastasis xenograft mouse models and assessed by bioluminescent imaging and IHC. Results: In vitro, GDC-0084 considerably decreased cell viability, induced apoptosis, and inhibited phosphorylation of Akt and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines. In contrast, GDC-0084 led only to growth inhibition in PIK3CA wild-type cell lines in vitro. In vivo, treatment with GDC-0084 markedly inhibited the growth of PIK3CA-mutant, with accompanying signaling changes, and not PIK3CA wild-type brain tumors. Conclusions: The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating PIK3CA mutations. A national clinical trial is planned to further investigate the role of this compound in patients with brain metastases.