Miracle-dz/UniFAR-FTUs huggingface dataset:
The Pulmonary Circulation and Exercise Responses in the Elderly

Aging is associated with a progressive deterioration in the structure and function of the pulmonary circulation. Remodeling of the pulmonary vasculature occurs from maturity to senescence that is characterized by an increase in pulmonary vascular stiffness, pulmonary vascular pressures, and pulmonary vascular resistance along with increased heterogeneity of alveolar ventilation and pulmonary perfusion and decreased pulmonary capillary blood volume and membrane diffusing capacity that is consistent with a reduction in alveolar-capillary surface area. In theory, the aforementioned age-related changes in the pulmonary circulation may conspire to make elderly individuals more susceptible to gas exchange abnormalities during exercise. However, despite the erosion in ventilatory reserve with aging, the healthy older adult appears able to maintain alveolar ventilation at a level that allows maintenance of arterial blood gases within normal limits, even during heavy exercise. This ability to maintain adequate gas exchange likely occurs because age-related reductions in the maximal metabolic demand of exercise occur at a rate equal to or greater than the rate of deterioration in ventilatory reserve. A more prominent aspect of aging is the loss of lung elastic recoil that is associated with a modest reduction in the expiratory boundary of the maximal ﬂow-volume envelope. This in turn increases the severity of expiratory airﬂow limitation and induces dynamic lung hyperinﬂation during exercise. The consequences of this age-associated decrease in elastic recoil on the pulmonary circulation are speculative, but an age-associated decline in elastic recoil may inﬂuence pulmonary vascular resistance and cardiac output, in addition to its impact on the work and oxygen cost of breathing.
Targeted Therapy in Advanced Non-Small-Cell Lung Cancer

Molecularly targeted therapies have recently expanded the options available for patients with advanced non-small-cell lung cancer (NSCLC). Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathway. The former has emerged as a key regulator of cancer cell proliferation and invasion, and several EGFR inhibitors have been developed. Erlotinib, a small-molecule inhibitor of the EGFR intracellular tyrosine kinase, has been found to improve survival compared with placebo in previously treated patients with advanced NSCLC and is Food and Drug Administration (FDA)-approved in this setting. Clinical and molecular predictors of response to erlotinib, such as a history of never smoking and EGFR gene mutation or ampliﬁcation, are presently being evaluated to select patients for earlier therapy with erlotinib. Additional EGFR inhibitors are also being examined in randomized trials. The VEGF pathway, a key mediator of angiogenesis, has become an attractive target in multiple malignancies, including lung cancer. Bevacizumab, a monoclonal antibody to VEGF, received FDA approval for use in advanced non-squamous-cell NSCLC in 2006 after a phase III trial reported a signiﬁcant survival advantage when bevacizumab was added to standard ﬁrst-line chemotherapy. Small-molecule inhibitors of the VEGF receptor tyrosine kinase, such as sunitinib and sorafenib, have also shown promise in phase II trials and are being further investigated in phase III studies. Because preclinical data suggest a synergistic effect when VEGF and EGFR inhibitors are combined, the concurrent use of erlotinib and bevacizumab has additionally been evaluated in a phase II trial, with encouraging early results suggesting at least equivalent activity to standard salvage chemotherapy, with less toxicity. Several other novel agents are being examined, including inhibitors of histone deacteylases and the 26S proteosome. Research efforts are currently focusing on tailoring such therapies according to predictive clinical and molecular markers.
Adaptive asymptotic stabilization of a class of unknown nonlinear systems with specified convergence rate

This paper focuses on the asymptotic stabilization problem for a class of multivariable nonlinear systems with relative degree one, practical examples of which incorporate the liquid level control of water tanks, and the speed control of interconnected carts. The presence of the unknown (other than uncertain) additive and multiplicative nonlinearities renders asymptotic stability difficult to be achieved by the existing robust control methods. To conquer this obstacle, a novel adaptive control strategy is proposed. In the control design, the state constraint technique is newly introduced to the adaptive design to generate a proper control gain to compensate for unknown nonlinearities, instead of the use of extra approximating structures. By this means, both the prescribed transient performance regarding the convergence rate and the expected asymptotic stability are preserved. Finally, simulation results are given to illustrate the established theoretical findings.
Reliability computing method combined with compressed storage and Krylov subspace for phased-mission system

ABSTRACT Application of the Markov approach in the reliability analysis of phased-mission systems (PMS) may encounter the problem of state space explosion. In this paper, a relationship is derived to compute the non-zero elements of the transition rate matrix (TRM) of a Markov model on the basis of the states binary description. Moreover, a TRM compressed storage scheme (TRMCS) is proposed, and an algorithm for matrix vector multiplication under TRMCS is presented. A method to solve the state probability vector using the Krylov subspace is proposed. The performance and the effectiveness of the proposed methods are demonstrated through a typical example.
Working with Linguistically Diverse Families in Early Intervention: Misconceptions and Missed Opportunities

Traditionally, speech-language pathologists (SLPs) and other professionals have held the belief that children with speech and language disabilities are unable to successfully learn more than one language. It is often automatically assumed that exposing young children to two languages will cause confusion and signiﬁcant delays in the learning of any language. Because of this belief, many families have been inﬂuenced to give up their home language in their efforts to ensure their child’s successful learning of English. Yet it has been documented that children who are learning two languages simultaneously can succeed and often become balanced bilinguals, if the exposure and learning opportunities to both languages are maintained. However, the ongoing beliefs and practice of many SLPs as they provide guidance and recommendations about language learning to parents and other professionals are not consistent with implications from current research about bilingualism, especially as it pertains to young children with learning challenges. This article discusses the inconsistencies regarding these myths about early language learning. It summarizes research and literature within the context of evidenced-based practice that question the idea that young children with disabilities cannot learn more than one language. In this article, perspectives from parents as well as researchers support an ‘‘additive’’ approach to language learning that values diversity, engages in information sharing with families, and supports decisions that are made by families regarding their child’s language(s). In this way, parents are empowered and enabled to make decisions about what language(s) their children will learn.
The Genetics of Mitochondrial Disease

The discovery that defects in mitochondria and mitochondrial DNA could cause human disease has led to the development of a rapidly expanding group of disorders known as mitochondrial disease. Mitochondrial disease is so named because of the common feature of impaired mitochondrial function. The main function of the mitochondrion is to produce energy for the cell in the form of ATP. ATP is generated by the respiratory chain, a series of complex proteins that are located in the mitochondrial membrane, and are encoded for by both the mitochondrial and nuclear genomes. Consequently, mitochondrial disease can be caused by mutations in either mitochondrial or nuclear DNA. Given the distribution of mitochondria throughout the body, the speciﬁc properties of mitochondrial DNA, and the mitochondrion’s dependence on nuclear genes for its normal function, the clinical presentation of mitochondrial disease can be highly variable. Thus, familiarity with typical clinical presentations and knowledge of the genes that contribute to mitochondrial function will aid the clinician in the recognition, diagnosis, and management of patients with this group of diverse disorders.
Imprinting Disorders and Assisted Reproductive Technology

Worldwide use of assisted reproductive technology (ART) accounts for an estimated 1 to 3% of births. Since 2002, a series of reports have suggested an increased risk of imprinting disorders (Beckwith-Wiedemann syndrome and Angelman syndrome) in children conceived by ART. Deﬁnitive conclusions are difﬁcult to substantiate due to the rarity of imprinting disorders and the variability in ART protocols. Despite these limitations, there is biological plausibility for alteration in nongenomic inheritance caused by ART. Animal studies have shown that ART procedures can alter normal imprinting, speciﬁcally DNA methylation patterns. Collectively, studies suggest an association between ART and loss of maternal methylation. More recent reports examined a possible association between ART and global hypomethylation of DNA. Three other imprinting disorders (Silver-Russell syndrome, maternal hypomethylation syndrome, and retinoblastoma) have also been implicated, but there is insufﬁcient evidence to establish an association of these syndromes with ART. Based on current evidence, the absolute risk of imprinting disorders after ART remains small and does not warrant routine screening. Large prospective studies are needed to better understand the risks associated with imprinting disorders, imprinting defects, and ART.
Risk during Pregnancy and Birth after Assisted Reproductive Technologies: An Integral View of the Problem

Pregnancy and obstetric outcome are the ﬁnal steps in infertility treatment. Additional data from recent studies demonstrate an increased risk for pregnancy course and obstetric outcome. These risks include an increased risk for intrauterine growth retardation, preeclampsia, and premature birth. Children born after in vitro fertilization and intra-cytoplasmic sperm injection (ICSI) have an increased risk for major malformations compared with spontaneously conceived pregnancies. Patients have to be counseled about these risks. The question is where these increased risks originate. At present, there are insufﬁcient data available from pregnancies established following hormonal treatment or intrauterine insemination cycles. Therefore, the question is still open for debate, whether either in vitro culture or infertility per se or perhaps other components of the treatment cycle contribute to this risk. There is some evidence that at least the ICSI technique or the in vitro culture technique is not the only or most prominent factor. A long time to pregnancy with subsequent spontaneous pregnancy results in a similar risk proﬁle as pregnancies following infertility treatment. This article discusses a possible pathogenetic model for these observations.
Error estimates for the postprocessing approach applied to Neumann boundary control problems in polyhedral domains

This paper deals with error estimates for the finite element approximation of Neumann boundary control problems in polyhedral domains. Special emphasis is put on singularities contained in the solution as the computational domain has edges and corners. Thus, we use tailored regularity results in weighted Sobolev spaces which allow to derive sharp convergence results for locally refined meshes. The first main result is an optimal error estimate for linear finite element approximations on the boundary in the L( )-norm for both quasi-uniform and isotropically refined meshes. Later, the approximations of Neumann control problems using the postprocessing approach are investigated, that is, first a fully discrete solution with piecewise linear state and co-state, and piecewise constant controls, is computed and afterwards, an improved control by a pointwise evaluation of the discrete optimality condition is obtained. It is shown that quadratic convergence up to logarithmic factors is achieved for this control approximation if either the singularities are weak enough or the sequence of meshes is refined appropriately.
MRI of Knee Joint Injury

Most knee injuries are the result of rotational, varus, valgus, hyperextension, or translational forces or a combination of these. The pattern of abnormalities seen on magnetic resonance imaging depends on the mechanism of trauma and the position of the joint at the time of injury. Knee injuries can be classiﬁed under two broad categories of direct and indirect injuries.
Social and Ethical Controversies in Thrombophilia Testing and Update on Genetic Risk Factors for Venous Thromboembolism

Over the past 20 years, the landscape with respect to evaluation of thrombophilia, the inherited or acquired tendency to develop venous thromboembolism, has changed dramatically. Increased knowledge regarding the contribution of genetic predisposition to thrombosis has raised several questions regarding screening, diagnosis, and management. In this review, we will examine these issues while providing an update on genetic testing for inherited thrombotic disorders.
Medical Treatment of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a sinister condition that is often diagnosed late and is associated with a progressive clinical deterioration and premature death. However, over the past 10 years the ﬁeld has seen a dramatic increase in the number of effective therapies underpinned by advances in our understanding of the pathobiology of this illness. Identiﬁcation of dysfunctional signaling pathways in the pulmonary circulation provided novel therapeutic targets with the goal of reducing pulmonary vascular resistance and prevention of death from right ventricular failure. Treatment algorithms have now become more complex, with therapeutic options deﬁned by pulmonary artery vasoreactivity, functional class, and response to treatment. Combination therapies are increasingly considered as clinical trials demonstrating the efﬁcacy of this approach are emerging. Monitoring and measuring the response to treatment in clinical trials and clinical practice are evolving from the historical dependence on functional class and 6-minute walk test to include estimates of the delay in the time to clinical worsening and the response of emerging biomarkers.
The Platelet P2 Receptors in Thrombosis

Adenosine diphosphate (ADP) and adenosine triphosphate (ATP) play a crucial role in hemostasis and thrombosis, and their receptors are potential targets for antith-rombotic drugs. The ATP-gated channel P2X 1 and the two G protein–coupled P2Y 1 and P2Y 12 ADP receptors selectively contribute to platelet aggregation. Because of its central role in the formation and stabilization of a thrombus, the P2Y 12 receptor is a well-established target of antithrombotic drugs such as clopidogrel, which has proven efﬁcacy in many clinical trials and experimental models of thrombosis. Competitive P2Y 12 antagonists have also been shown to be effective in experimental thrombosis as well as in several clinical trials. Studies in P2Y 1 and P2X 1 knockout mice and experimental thrombosis models using selective P2Y 1 and P2X 1 antagonists have shown that, depending on the conditions, these receptors could also be potential targets for new antithrombotic drugs. Because both P2X 1 and P2Y 1 receptor inhibition result in milder prolongation of the bleeding time as compared with P2Y 12 inhibition, the idea is put forward that combinations of P2 receptor antagonists could improve efﬁcacy with diminished hemorrhagic risk. However, further studies with stronger and more selective P2 receptor antagonists are required to validate such a point of view.
The Intrauterine Growth Restriction Phenotype: Fetal Adaptations and Potential Implications for Later Life Insulin Resistance and Diabetes

The intrauterine growth restricted (IUGR) fetus develops unique metabolic adaptations in response to exposure to reduced nutrient supply. These adaptations provide survival value for the fetus by enhancing the capacity of the fetus to take up and use nutrients, thereby reducing the need for nutrient supply. Each organ and tissue in the fetus adapts differently, with the brain showing the greatest capacity for maintaining nutrient supply and growth. Such adaptations, if persistent, also have the potential in later life to promote nutrient uptake and storage, which directly lead to complications of obesity
Semen Analysis and Sperm Function Assays: What Do They Mean?

Appropriate laboratory testing is an integral component of the proper evaluation of the male presenting with infertility. This article reviews the semen analysis and sperm function assays. Sperm function testing is used to determine if the sperm have the biologic capacity to perform the tasks necessary to reach and fertilize ova and ultimately result in live births. For a sperm to be fertile in vivo, it must be able to traverse the cervical mucus and reach the ova. The sperm must undergo capacitation and the acrosome reaction, fuse with the oolemma, and incorporate into the ooplasm. Proper embryo development requires that functional DNA be delivered to the ooplasm. Defects in any of these steps may result in infertility. A variety of tests are available to evaluate different aspects of these functions. To accurately use these functional assays, the clinician must understand what the tests measure, what the indications are for the assays, and how to interpret the results to direct further testing or patient management.
An Examination of Nonspeech Oral Motor Exercises for Children with Velopharyngeal Inadequacy

The velopharyngeal closure mechanism is the articulator that separates the oral and nasal cavities during speech and swallowing. Articulation and resonance may be adversely affected if velopharyngeal inadequacy (VPI) is present. VPI is generally corrected through surgery or speech prosthetics. There is, however, a small subset of clients who may improve with treatment using muscle rehabilitation procedures that are task speciﬁc to speech. Nonspeech oral motor exercise treat-ment has been used but found ineffective.
Morphological Changes of Early Human Hepatocarcinogenesis

Recent advances in liver imaging, surgery, and transplantation have drawn attention to a variety of lesions that are found in chronically diseased, usually cirrhotic, livers. Several studies have established the precancerous nature of dysplastic foci and dysplastic nodules and have delineated the morphological features of small hepatocellular carcinoma. Dysplastic foci represent incidental ﬁndings on microscopic examination of hepatic specimens, whereas dysplastic nodules are detected grossly, and often radiologically. Dysplastic foci commonly consist of proliferating hepatocytes with small cell change, which is cytologically reminiscent of well-differentiated hepatocellular carcinoma. Dys-plastic nodules may show evidence of cytological or structural atypia, or both, that is insufﬁcient for the diagnosis of hepatocellular carcinoma. The evolution of dysplastic nodules to hepatocellular carcinoma within several months to a few years of follow-up is well-documented. Small hepatocellular carcinoma with indistinct margins has been identiﬁed as an early, well-differentiated neoplasm that usually measures less than 15 mm in greatest dimension. As this lesion grows larger, it may transform into nodular hepatocellular carcinoma with distinct margins.
Estrogen and Cognition, with a Focus on Alzheimer's Disease

Cognitive aging is associated with decreases in memory, attention, and visual/ motor performance and skills. Dementia consists of loss of memory and other cognitive abilities, associated with social or occupational impairment. Potential neuroprotective effects of estrogen include lowering b -amyloid, enhancing cholinergic function, promoting synaptic plasticity and nerve process growth, reducing oxidative stress, and enhancing brain glucose transport. Observational and longitudinal studies suggest that hormone therapy may attenuate age-associated cognitive impairment or decrease Alzheimer’s disease but this has not been conﬁrmed by randomized clinical trials. A critical window of time may exist around the menopause when hormone therapy may delay or decrease cognitive changes; however, hormone therapy initiated in the late postmenopause does not improve global cognition and may increase dementia risk.
Platelet Receptors for Adenine Nucleotides and Thromboxane A2

Adenosine diphosphate (ADP) and thromboxane A 2 (TXA 2 ) are important physiological activators of platelets and exert their effects by acting on cell surface receptors. Platelet nucleotide receptors can be distinguished as three separate subtypes of the P2 receptor family. The P2X 1 receptor is a ligand-gated adenosine triphosphate (ATP) receptor that was originally mistaken for an ADP receptor. This calcium-inﬂux-causing receptor mediates platelet shape change and plays an important role in thrombus formation in small arterioles. The P2Y 1 receptor, through activation of G q and phospholipase C, is required for ADP-induced platelet shape change, ﬁbrinogen receptor activation, and TXA 2 generation. The G i -coupled P2Y 12 receptor plays an important role in platelet aggregation, potentiation of dense granule release, and TXA 2 generation. Both the P2Y receptors are crucial for in vivo thrombus formation. TXA 2 stimulates two subtypes of G protein-coupled TP receptor, TP a and TP b , but its effects in platelets are mediated predominantly through the a isoform. Although interference with the activation of G protein-coupled ADP or TP receptors results in increased bleeding times and protection from thromboembolism, TP receptor antagonists did not translate into effective antiplatelet drugs. Blockade of ADP receptor is a mode of newer classes of antithrombotic drugs in the coming era. This review focuses on the contribution of different nucleotide receptors and TP receptors to platelet function and their potential as antithrombotic agents.
Antiphospholipid Syndrome and Pre-Eclampsia

Antiphospholipid syndrome (APS) is deﬁned as an autoimmune disorder characterized by recurrent thrombosis or obstetrical morbidity. These features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospho-lipid-binding proteins. Obstetric morbidity includes recurrent abortion (early and late) and severe pre-eclampsia (P-EC)/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and/or severe placental insufﬁciency. Criteria that deﬁne the major clinical and laboratory events were published in revised forms in the Sydney recommendations in 2006. We analyzed the blood of patients with severe P-EC according to the subgroups based on the 2006 revised criteria deﬁnition and compared these results with women after uncomplicated pregnancy and delivery. We found 20% elevated antiphospholipid antibodies (APAs) in women with severe P-EC (group I, 7.5%; group IIa, 5.0%; group IIb, 5.0%; group IIc, 2.5%). The increased APAs were observed only in women with severe P-EC (odds ratio: 2.45; 95% conﬁdence interval, 1.01 to 4.3) and not in patients with severe P-EC at > 34 weeks of gestation. According to our retrospective observation, we recommend the determination of anticardiolipin antibodies, lupus anticoagulant, and b -2 glycoprotein-1 antibodies in patients with severe P-EC at < 34 weeks of gestation.