Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroimaging Advances and the Transformation of Acute Stroke Care

Neuroimaging techniques have transformed the delivery of stroke care. Multi-modal computed tomography and magnetic resonance imaging rapidly illustrate the vascular and parenchymal correlates in acute ischemic and hemorrhagic stroke. Optimal selection of thrombolytic candidates and the characterization of ischemic sequelae may be achieved with imaging. The nature and topography of intracerebral hemorrhage may also be deﬁned. Increasing use of multimodal imaging in acute stroke has expanded our current understanding of stroke pathophysiology and streamlined the care of stroke patients from the hyperacute to chronic phases. The integration of neuroimaging techniques in research studies has elucidated pitfalls in the translation of novel therapy into clinical practice. This review explores the impact of neuroimaging advances in stroke and emphasizes the critical role of these modalities in the care of patients with ischemic and hemorrhagic events.
Evaluation of Clinical Intervention: Accountability

Reprint requests: Dr. Vetter, Dept. of Communicative Disorders, University of WisconsinMadison, 1975 Willow Dr., Madison, WI 53706 Assessment and remediation of communication disorders are expensive both in terms of the time involved and money invested. Speech and language therapy and auditory rehabilitation may be lengthy processes. Since professional persons who have been highly trained provide the expertise, someone pays for the time and knowledge of the experts. With the rising costs of all health care, professional persons are either initiating accountability in their treatment of clients, or it is being forced on them by third parties. An additional impetus toward accountability comes from the fact that these same professionals are attempting to share information with one another about the effectiveness of treatment plans that they have devised. All of these factors have led to a need to provide a systematic accounting of the effects of treatment. Unfortunately, a belief has persisted for many years that clinical practice and rigorous experimental research are discrete endeavors. Various articles and books have been written to dispel this belief and to provide a framework for conceptualizing the evaluation of clinical endeavors (Ringel, 1972; Bloom and Fischer, 1982; McReynolds and Kearns, 1983; McNeil and Kennedy, 1984). This article focuses on a single general approach to the rigorous evaluation of treatment effects and on a few specific procedures that seem especially appropriate for the clinical practitioner in communicative disorders. For some persons, the idea of a systematic approach to clinical treatment means inflexibility, lack of spontaneity, and dullness. They may even believe that it would increase the time taken to effect a change in the client. A systematic approach to treatment does not have to mean any of these things. In fact, one could hypothesize that treatment length would be decreased if objectives were clarified and there were awareness and focus to the approach and techniques employed by the clinician. A central concern of an accountable professional undoubtedly is to provide the best treatment to accomplish the desired behav55
Preclinical Animal Models for Hemophilia Gene Therapy: Predictive Value and Limitations

Hemophilia A and B are excellent candidate disorders for the application of somatic cell gene therapy. One of the major advantages in the preclinical development of hemophilia gene therapy strategies has been the availability of several animal models for both hemophilia A and B. These models recapitulate many of the phenotypic aspects of human hemophilia and have proven to be very informative in exploring the efﬁcacy and safety of gene therapy. Considerable progress has been made in the design of gene therapy protocols, and over the last 5 years it has been shown that long-term phenotypic correction, with sustained therapeutic levels of factor VIII (FVIII) and factor IX (FIX), can be attained in FVIII-and FIX-deﬁcient mice and dogs using various viral vector-mediated gene therapy approaches. These animal models also have elucidated potential complications of gene therapy protocols, including acute vector-associated toxicities and the induction of neutralizing antibodies to the FVIII and FIX transgene products. Nevertheless, although the preclinical paradigm of hemophilic mouse followed by hemophilic dog studies has proven to be extremely helpful in evaluating the efﬁcacy and safety of potential clinical gene therapy protocols, several limitations to these animal models still exist. This review presents a summary of the animal models available for hemophilia gene therapy, and highlights the various strengths and weaknesses of these models.
Single-Chain Antibodies as New Antithrombotic Drugs

Antibodies are the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. At present, several antibodies are approved for therapeutic use in diverse clinical settings, including oncology, chronic inﬂammatory diseases, transplantation, infectious diseases, and cardiovascular medicine. These approved antibody therapeutics include unmodiﬁed immunoglobulin G molecules, radioimmuno-conjugates, antibody–drug conjugates, and fragment antigen-binding molecules. At least 150 additional antibodies are in clinical development. A major strength of therapeutic antibodies is their established properties as a drug class with high success rates from clinical trials to regulatory approvals. Much of the experience gained from the generation and optimization of one antibody is applicable to other antibodies. Antibody fragments are a subclass with growing clinical importance. This review focuses on single-chain antibodies as the smallest possible format for recombinant antibodies, and their use as antithrombotic drugs. We describe different antibody formats, the current applications of antibody fragments, and their generation by cloning from hybridoma cell lines as well as their selection from antibody libraries. We review the use of antibody fragments for thrombus targeting using ﬁbrin and platelet-speciﬁc single-chain antibodies in combination with anticoagulants and thrombolytic agents as antithrombotic drugs.
Bayesian Subset Selection for Inverse Gauss Regression Models

Inspired by the idea of Kuo and Mallick, Bayesian subset selection for inverse Gauss regression models is studied by Gibbs sampler and Metropolis-Hastings algorithm in this paper. Simulation study and the aerobic fitness data example are employed to demonstrate the proposed methodology. Keywords—Bayesian subset selection; Gibbs sampler; Metropolis-Hastings algorithm; Inverse Gauss regression models
Lower Doses of Oral Estrogen and Progestogens as Treatment for Postmenopausal Women

Estrogen, with or without a progestin, is effective for the treatment of menopausal symptoms. Larger doses of estrogen/progestin have been used than required for the amelioration of menopausal symptoms. Both positive and negative outcomes of hormone therapy are reported in postmenopausal women. The positive aspects have been those associated with a reduction in menopausal symptoms such as hot ﬂashes, and improvement in vulvovaginal atrophy with maintenance of bone mineral density. The problems have included an increased risk of venous thrombosis and breast cancer. The anticipation is that as the dose of oral estrogen and progestins is lowered, the beneﬁts can be maintained and the side effects reduced. Recent clinical trials have found that lower doses of estrogen and/ or progestin reduce or improve menopausal symptoms and maintain bone mineral density. The impact of lower doses of hormones on heart disease, and venous thromboembolism and stroke remain to be determined in future studies.
Nutrition and Gastrointestinal Tract Assessment and Management of Children with Dysphagia

Limited ability to take in nutrients places young patients with dysphagia at risk for malnutrition and failure to gain weight. These children require careful evaluation and ongoing monitoring of growth and nutritional status. Gastroesophageal reﬂux and recurrent vomiting may contribute to dysphagia when the reﬂuxate causes laryngopharyngeal irritation and can increase the morbidity in patients prone to aspiration. A paucity of evidence-based literature on relevant topics demands both clinical judgment and an interdisciplinary approach for management decisions for these issues. Advances in nutrition and management of aerodigestive conditions related to dysphagia will be reviewed.
First Order Hadamard Variation of the Harmonic Navigation Function on a Sphere World

Planning conflict-free trajectories is a long-standing problem in Air Traffic Management. Navigation functions designed specifically to produce flyable trajectories have been previously considered, but lack the robustness to uncertain weather conditions needed for use in an operational context. These uncertainties can be taken into account be modifying the boundary of the domain on which the navigation function is computed. In the following work, we present a method for efficiently taking into account boundary variations, using the Hadamard variation.
Targeted Contrast Agents—an Adjunct to Whole-Body Imaging: Current Concepts

This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-speciﬁc contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.
Noninvasive Detection of Pulmonary Hypertension

There continues to be a nationally recognized need for noninvasive methods to diagnose pulmonary hypertension. The pulmonary arterial pressure becomes elevated at some point in the natural history of nearly every form of heart or lung disease. Furthermore, pulmonary hypertension and some of the frequent complications, such as low cardiac output, right heart failure, and systemic venous congestion, lead to multisystem failure or sudden death. Thus, the development of pulmonary hypertension has an important impact on the patient. It seems possible that early detection of pulmonary hypertension could allow for early treatment. One problem is that steps toward early detection have been uncertain. The reason, in part, is that pulmonary hypertensive symptoms are insidious and patients often come late to the physician. Also, the diagnostic methods most available to the physician, the history, physical examination, electrocardiogram, and chest radiograph, are not sensitive enough to diagnose mild pulmonary hypertension. The newer noninvasive methods, such as echocardiography, Doppler, and radionuclide angiography, are only now currently being evaluated in the assessment of pulmonary hypertension. Cardiac catheterization, at present, the gold standard for diagnosing abnormal pulmonary circulatory states, is too invasive and costly for screening purposes. Thus, although pulmonary hypertension is an important clinical problem, physicians need noninvasive methods for its early detection. Newer technology has brought fresh approaches to the problem and have reawakened interest in older ideas. Our purposes are to review the field, to determine what the state of knowledge is, and to examine possible future directions. Our approach is to examine the pathophysiologic consequences of elevated pulmonary arterial pressure and to evaluate noninvasive methods that measure these consequences. Specifically, pulmonary hypertension effects the pulmonary vascular bed itself, the right ventricle, and right atrium and the systemic veins. We will examine the effects in this order, considering that the order represents the approximate pathophysiologic sequence of events. As such, measurements most likely to be useful for early detection relate to the pulmonary vascular bed itself and those least likely relate to the right atrium and systemic veins.
Modelling the suppression of autoimmunity after pathogen infection

We study a mathematical model of immune response by T cells where the regulatory T cells (Treg) inhibit interleukin 2 (IL‐2) secretion. We model the suppression of the autoimmune line of T cells after a different line of T cells responded to a pathogen infection. In this paper, we show that if the population of the pathogen responding line of T cells becomes large enough, the competition for IL‐2 and the increase in the death rates may lead to a depletion in the concentration of autoimmune T cells. Provided this lasts for a sufficiently long time, the concentration of autoimmune T cells can be brought down to values inside the basin of attraction of the controlled state, and autoimmunity can be suppressed.
Respiratory Support for the Severely Handicapped Child with Neuromuscular Disease: Ethics and Practicality

Recent respiratory developments have altered the management of children with severe neuromuscular disease, and in some cases changed the natural history of the conditions. These developments include improvements in diagnosis; a greater availability of ventilatory support techniques, including noninvasive modes; and better functional scoring systems that enable global muscle function and the impact of treatment to be evaluated. Greater choices can make for more difﬁcult decision making, and the ability to prolong survival brings with it opportunities, but also ethical dilemmas. Clearer outcome information and assessment of the beneﬁts and burdens of ventilatory support for the child and family should aid decision making. In many conditions there is no relationship between functional ability, the need for ventilatory support, and quality of life. Noninvasive ventilation combined with cough assistance is usually preferred to invasive ventilation and is likely to reduce respiratory morbidity. In situations where noninvasive ventilation does not extend survival, it may have a role in palliating symptoms and allowing the child to be cared for at home.
Owning Up to Complexity: A Sociocultural Orientation to Attention Deficit Hyperactivity Disorder

To enrich our conception of attention deﬁcit hyperactivity disorder (ADHD), it is necessary to take a wider orientation to this disability category than has been advocated traditionally. Over the past decade, there has been an emerging conception of ADHD from a sociocultural perspective, and this orientation, when linked to the traditional biomedical perspective, provides a more accurate and authentic construct of ADHD. In this article, we advocate that speech-language pathologists approach ADHD with a mindset that is open to the complexities of context-bound human functioning at all levels. Four sources of data demonstrating the richness of the sociocultural orientation are presented and clinical implications are detailed
Diagnosis and Hemodynamic Assessment of Pulmonary Arterial Hypertension

Pulmonary hypertension (PH) can occur as either a primary or a secondary process, and in general, its presence increases overall morbidity and mortality. Importantly, the majority of prior studies have been in the setting of idiopathic pulmonary arterial hypertension (IPAH); thus the following discussion focuses on IPAH. Because the majority of available diagnostic strategies lack sensitivity and speciﬁcity, the physician must maintain a high index of suspicion in considering PAH. This article provides an overview of the available diagnostic studies for PAH with a particular focus on hemodynamic assessment. Novel approaches to the often delayed diagnosis of PAH are being studied and are also discussed here.
Affine Laumon spaces and integrable systems

In this paper we formalize and prove a conjecture of Braverman concerning integrals of the Chern polynomial of the tangent bundle to affine Laumon spaces. This provides the computation of the Nekrasov partition function of N = 2 gauge theory with adjoint matter on C^2 in the Omega background, in the presence of a full surface operator insertion
The Role of Cytokines during the Pathogenesis of Ventilator-Associated and Ventilator-Induced Lung Injury

Mortality rates from acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) range from 30 to 65%. Although mechanical ventilation (MV) may delay mortality in critically ill patients with ALI/ARDS, it may also cause a lung injury that further promotes and perpetuates ALI/ARDS and multiorgan dysfunction syndrome (MODS). Recent studies have demonstrated that lung protective strategies of MV, as compared with the injurious strategy of conventional MV (CMV) can reduce absolute mortality rates during ALI/ARDS. The protective strategies limit tidal volumes and peak/plateau pressures while maximizing positive end-expiratory pressure. The injury to the lung by CMV is characterized histologically by edema, leukocyte extravasation, and endothelial and epithelial damage. Both human and animal studies suggest that alveolar cell deformation from CMV leads to the release of cytokines/chemokines which orchestrate the extravasation, activation, and recruitment of leukocytes, causing ventilator-associated lung injury (VALI) and ventilator-induced lung injury (VILI). Moreover, VALI/VILI can perpetuate the chronic inﬂammatory response during ALI/ARDS and MODS. This article explores the role of cytokines/chemokines during the pathogenesis of VALI/VILI.
KCNQ5 controls perivascular adipose tissue-mediated vasodilation

Background Small arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells (SMCs), potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels. However, the mechanisms by which PVAT signals small arteries, and their relevance, remain largely unknown. We aimed to uncover key molecular components in adipose-vascular coupling. Methods A wide-spectrum of genetic mouse models targeting Kcnq3, Kcnq4 and Kcnq5 genes (Kcnq3−/−, Kcnq4−/−, Kcnq5−/−, Kcnq5dn/dn, Kcnq4−/−/Kcnq5dn/dn, Kcnq4−/−/Kcnq5−/−), telemetry blood pressure measurements, targeted lipidomics, and RNA-Seq profiling, wire-myography, patch-clamp, and sharp-electrode membrane potential measurements were used. Results We show that PVAT causes SMC KCNQ5 (KV7.5) channels to hyperpolarize the membrane potential. This effect relaxes small arteries and regulates blood pressure. Oxygenation of polyunsaturated fats generates oxylipins, a superclass of lipid mediators. We identified numerous oxylipins released by PVAT that potentiate vasodilatory action in small arteries by opening SMC KCNQ5 channels. Conclusions Our results reveal a key molecular function of KCNQ5 channels in adipose-vascular coupling, translating PVAT signals, particularly oxylipins, to the central physiological function of vasoregulation. This novel pathway opens new therapeutic perspectives.
Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds, which involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited opposing dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model. This model predicted that disrupting either D2-MSN or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also increased response times, shifted MSN dynamics, and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs make complementary contributions to interval timing despite opposing dynamics, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for a broad range of human striatal diseases and for therapies targeting striatal pathways.
Pressure fluctuations and Lagrangian accelerations in two-dimensional incompressible isotropic turbulence

The pressure field is studied by applying Quasi-Normal and Eddy Damped Quasi-Normal Markovian (EDQNM) closure approximations. We first show that these two closure methods provide the same closure equation for the pressure spectrum. Then we derive the closure equation satisfied by this spectrum; we determine the structure functions, characteristic length scales and spectra associated with the pressure and pressure gradient fluctuations; we also inspect the influence of the Reynolds number upon the difference between the pressure gradient fluctuation correlation and the Lagrangian acceleration correlation