Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury

ABSTRACT Introduction: Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation. Areas covered: In this review, we discuss the potential mechanisms by which GH-based therapies act on the multiple tissue types involved in peripheral nerve regeneration to ultimately enhance outcomes, and review the pertinent mechanistic and translational studies that have been performed. We also address potential secondary benefits of GH-based therapies pertaining to improved bone, tendon and wound healing in the setting of peripheral nerve injury. Expert opinion: GH-based therapies carry great promise for the treatment of peripheral nerve injuries, given the multi-modal mechanism of action not seen with other experimental therapies. A number of FDA-approved drugs that augment the GH axis are currently available, which may facilitate clinical translation.
Expression of epidermal growth factor receptor and human epidermal growth factor receptor 2 in periocular squamous cell carcinomas of horses.

OBJECTIVE To determine whether epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are expressed in periocular squamous cell carcinomas (SCCs) of horses. SAMPLE Biopsy specimens of SCCs from 46 horses. PROCEDURES Pathology records were searched retrospectively for biopsy specimens of periocular SCCs obtained from horses. Slides of the specimens were reviewed histologically to confirm the SCC diagnosis and stained for EGFR and HER2 by immunohistochemical methods. For both EGFR and HER2, the immunohistochemical staining intensity and percentage of stain-positive cells on the slides were determined. RESULTS 43 of 46 (93%) SCCs were immunoreactive for EGFR. The median score for EGFR staining intensity was 4 (range, 2 to 12), and the median number of mitotic figures was 8 mitotic figures/10 hpfs (range, 0 to 34 mitotic figures/10 hpfs). Mitotic index was not correlated with the percentage of EGFR stain-positive cells or staining intensity. Of the 43 EGFR-immunoreactive SCCs, 38 had stain present primarily in the cytoplasm and 5 had stain equally distributed between the cytoplasm and cell membranes. Thirty-five of 46 (76%) SCCs were immunoreactive for HER2. Mitotic index was not correlated with the percentage of HER2 stain-positive cells or staining intensity. Of the 35 HER2-immunoreactive SCCs, the stain was present primarily in the cytoplasm and 7 had stain equally distributed between the cytoplasm and cell membranes. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that most periocular SCCs of horses expressed EGFR and HER2, which suggested that equine periocular SCCs might respond to treatment with EGFR inhibitors.
Spatial Learning and Wayfinding in an Immersive Environment: The Digital Fulldome

Previous work has examined whether immersive technologies can benefit learning in virtual environments, but the potential benefits of technology in this context are confounded by individual differences such as spatial ability. We assessed spatial knowledge acquisition in male and female participants using a technology not previously examined empirically: the digital fulldome. Our primary aim was to examine whether performance on a test of survey knowledge was better in a fulldome (N = 28, 12 males) relative to a large, flat screen display (N = 27, 13 males). Regression analysis showed that, compared to a flat screen display, males showed higher levels of performance on a test of survey knowledge after learning in the fulldome, but no benefit occurred for females. Furthermore, performance correlated with spatial visualization ability in male participants, but not in female participants. Thus, the digital fulldome is a potentially useful learning aid, capable of accommodating multiple users, but individual differences and use of strategy need to be considered.
Estimating the New Keynesian Phillips Curve for the UK: evidence from the inflation-indexed bonds market

Abstract This paper utilizes the information in the inflation-indexed bonds market to estimate the New Keynesian Phillips Curve for the UK using an unobserved component approach. The main advantage of this approach comes from using the Kalman filter to explicitly estimate the unobserved expected inflation from the observed break-even inflation rates – the yield difference between the inflation-indexed bonds and the nominal bonds. Our results show that the expected inflation estimated from the unobserved component model plays a significant role in explaining the inflation dynamics in the UK. The evidence also suggests that the estimated inflation expectations are better able to capture the evolution of actual inflation process as compared to the break-even inflation rate as a proxy for expected inflation.
Proangiogenic Function of CD40 Ligand-CD40 Interactions 12

Angiogenesis is a characteristic component of cell-mediated immune inflammation. However, little is known of the immunologic mediators of angiogenesis factor production. Interactions between CD40 ligand (CD40L) and CD40 have been shown to have pluripotent functions in inflammation, including the production of cytokines, chemokines, as well as the angiogenesis factor, vascular endothelial growth factor (VEGF), by endothelial cells. In this study we found that treatment of cultured human endothelial cells with an anti-CD40 Ab (to ligate CD40) resulted in the expression of several other angiogenesis factors, including fibroblast growth factor-2 and the receptors Flt-1 and Flt-4. To determine the proangiogenic effect of CD40L in vivo, human skin was allowed to engraft on SCID mice for 6 wk. These healed human skins express CD40 on resident endothelial cells and monocyte/macrophages, but not on CD20-expressing B cells. Skins were injected with saline, untransfected murine fibroblasts, or murine fibroblasts stably transfected with human CD40L. We found that the injection of CD40L-expressing cells, but not control cells, resulted in the in vivo expression of several angiogenesis factors (including VEGF and fibroblast growth factor) and a marked angiogenesis reaction. Mice treated with anti-VEGF failed to elicit an angiogenesis reaction in response to injection of CD40L-expressing cells, suggesting that the proangiogenic effect of CD40L in vivo is VEGF dependent. These observations imply that ligation of CD40 at a peripheral inflammatory site is of pathophysiological importance as a mediator of both angiogenesis and inflammation.
Overt and Relational Aggression in Girls With Attention Deficit Hyperactivity Disorder

We employed a multi-informant approach to examine attention deficit hyperactivity disorder (ADHD) subtype differences, as well as ADHD versus comparison group differences, in overt aggression, relational aggression, and peer regard related to such aggression. Participants included 228 girls (ages 6 to 12 years) diagnosed with either ADHD-Combined (ADHD-C; n = 93), ADHD-Inattentive (ADHD-I; n = 47), or nondiagnosed comparisons (n = 88) who attended research-based summer camp programs. Girls with ADHD-C exhibited higher rates of overt and relational aggression than did girls with ADHD-I, who in turn exhibited higher rates than comparison girls. For the ADHD-C subgroup, aggressive behavior was associated with both negative peer regard and lack of positive peer regard; for the ADHD-I subgroup, aggressive behavior was related to negative peer regard but not to positive peer regard. Controlling for subtype, relational aggression contributed incremental variance in peer regard over and above overt aggression, but effects for the latter were stronger. We discuss the importance of overt versus relational aggression for girls with ADHD as well as disparities in findings according to informant sources.
Networkers, fund hunters, intermediaries, or policy players? The activities of regions in Brussels

Abstract Regions started opening offices in Brussels in the mid-1980s. Today, well over half of Europe’s regions are present there. What do they do once they are in Brussels? Are they mainly networking, chasing funding, acting as intermediaries, monitoring legislation, or trying to influence the EU’s decision-making process? No study has analysed this question apart from the pioneering work by Marks et al. in 2002. This article breaks new ground by analysing both group-level and contextual factors in a series of multilevel models. Based on a survey of regional offices in Brussels, results indicate that contextual factors, such as levels of self-government back home, matter. However, group-level characteristics, such as an office’s longevity in Brussels, seem to affect a wider range of activities. Overall, older offices are more interested in the EU policy-making process and less interested in chasing funds or networking. Conversely, offices representing regions with weaker self-governing capacities rather conceive of their role as that of an intermediary, acting as an interface between the region and the EU institutions.
Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1

Dendritic cells (DCs) consist of various subsets that play crucial roles in linking innate and adaptive immunity. In the murine spleen, CD8α+ DCs exhibit a propensity to ingest dying/dead cells, produce proinflammatory cytokines, and cross-present Ags to generate CD8+ T cell responses. To track and ablate CD8α+ DCs in vivo, we generated XCR1-venus and XCR1-DTRvenus mice, in which genes for a fluorescent protein, venus, and a fusion protein consisting of diphtheria toxin receptor and venus were knocked into the gene locus of a chemokine receptor, XCR1, which is highly expressed in CD8α+ DCs. In both mice, venus+ cells were detected in the majority of CD8α+ DCs, but they were not detected in any other cells, including splenic macrophages. Venus+CD8α+ DCs were superior to venus−CD8α+ DCs with regard to their cytokine-producing ability in response to TLR stimuli. In other tissues, venus+ cells were found primarily in lymph node (LN)-resident CD8α+, LN migratory and peripheral CD103+ DCs, which are closely related to splenic CD8α+ DCs, although some thymic CD8α−CD11b− and LN CD103−CD11b− DCs were also venus+. In response to dsRNAs, diphtheria toxin–treated XCR1-DTR mice showed impaired CD8+ T cell responses, with retained cytokine and augmented CD4+ T cell responses. Furthermore, Listeria monocytogenes infection and anti–L. monocytogenes CD8+ T cell responses were defective in diphtheria toxin–treated XCR1-DTRvenus mice. Thus, XCR1-expressing DCs were required for dsRNA- or bacteria-induced CD8+ T cell responses. XCR1-venus and XCR1-DTRvenus mice should be useful for elucidating the functions and behavior of XCR1-expressing DCs, including CD8α+ and CD103+ DCs, in lymphoid and peripheral tissues.
We see ICT spillovers everywhere but in the econometric evidence: a reassessment

Using company-level data for the US we study the productivity effects of knowledge spillovers, induced by the diffusion of ICT in the markets where companies operate. We adopt multiple spillover proxies and account for firms' absorptive capacity and lagged effects. Our results show that intra-industry ICT spillovers have a contemporaneous negative effect while the impact of inter-industry spillovers is positive. The overall productivity effect of ICT is negative, except for those companies with a strong absorptive capacity. However, after a 5-year lag the overall spillover effect turns positive while the role of absorptive capacity diminishes as a consequence of decreasing learning costs and more accessible technology.
Gastrointestinal stem cells

Turnover of the epithelial cell lineages within the gastrointestinal tract is a constant process, occurring every 2–7 days under normal homeostasis and increasing after damage. This process is regulated by multipotent stem cells, which give rise to all gastrointestinal epithelial cell lineages and can regenerate whole intestinal crypts and gastric glands. The stem cells of the gastrointestinal tract are as yet undefined, although it is generally agreed that they are located within a ‘niche’ in the intestinal crypts and gastric glands. Studies of allophenic tetraparental chimeric mice and targeted stem cell mutations suggest that a single stem cell undergoes asymmetrical division to produce an identical daughter cell, and thus replicate itself, and a committed progenitor cell which further differentiates into an adult epithelial cell type. The discovery of stem cell plasticity in many tissues, including the ability of transplanted bone marrow to transdifferentiate into intestinal subepithelial myofibroblasts, provides a potential use of bone marrow cells to deliver therapeutic genes to damaged tissues, for example, in treatment of mesenchymal diseases in the gastrointestinal tract, such as fibrosis and Crohn's disease. Studies are beginning to identify the molecular pathways that regulate stem cell proliferation and differentiation into adult gastrointestinal cell lineages, such as the Wnt and Notch/Delta signalling pathways, and the importance of mesenchymal–epithelial interactions in normal gastrointestinal epithelium and in development and disease. Copyright © 2002 John Wiley & Sons, Ltd.
Computed Tomography Scans as an Objective Measure of Disease Severity in Chronic Rhinosinusitis

Objectives A truly objective method of measuring disease severity in chronic rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography (CT) scans of CRS patients using this novel objective 3D computerized system and compared results with a novel 2D computerized analysis of a single coronal slice through the osteomeatal complex (OMC) and subjective methods including Lund-Mackay and Zinreich’s modified Lund-Mackay. Study Design Prospective multicenter study. Setting Two academic tertiary referral centers. Subjects and Methods Forty-six adults with a diagnosis of CRS underwent CT examination and received an intramuscular triamcinolone injection, dosage weight dependent, followed by CT scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with all 4 scoring methods over 5 months. Results The Lin’s concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Posttreatment results demonstrated that both the OMC (0.824) and Zinreich’s (0.778) methods had strong agreement with the 3D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) had only moderate agreement. Conclusion Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich’s subjective method correlated well overall, but the Lund-Mackay method lagged behind in disease representation and sensitivity to change.
Effects of shoulder girdle dynamic stabilization exercise on hand muscle strength

BACKGROUND: Shoulder girdle stabilization influences hand strength but the effects of functional training remain unknown. OBJECTIVE: To determine the influence of shoulder girdle stabilization on hand muscle strength. METHODS: Handgrip strength (with hand in neutral position, supination, pronation) and tripod pinch strength were measured in 20 healthy volunteers (10 in training/control groups) weekly over six weeks. The training consisted of six specific Dynamic Neuromuscular Stabilization (DNS) exercises performed five times per week. The exercises were designed to obtain maximum joint stability within the shoulder. RESULTS: Using mixed effects models, the training group showed significant improvement relative to the control group on all measures of hand muscle strength ( p< 0.05). The gains were particularly pronounced in handgrip strength in the neutral position (dominant hand: Estimate = 0.26, standard error [SE] = 0.04, p< 0.001; non-dominant hand: Estimate = 0.23, SE = 0.03, p< 0.001). That is, the training group gained about 0.25 standard deviations over the control group per session for a total of 1.5 standard deviations (about 27 Newtons) across all sessions. CONCLUSIONS: Shoulder girdle exercises based on DNS may generate clinically significant gains in hand muscle strength.
Occupational Radon Exposure and Lung Cancer Mortality: Estimating Intervention Effects Using the Parametric g-Formula

Background: Traditional regression analysis techniques used to estimate associations between occupational radon exposure and lung cancer focus on estimating the effect of cumulative radon exposure on lung cancer. In contrast, public health interventions are typically based on regulating radon concentration rather than workers’ cumulative exposure. Estimating the effect of cumulative occupational exposure on lung cancer may be difficult in situations vulnerable to the healthy worker survivor bias. Methods: Workers in the Colorado Plateau Uranium Miners cohort (n = 4,134) entered the study between 1950 and 1964 and were followed for lung cancer mortality through 2005. We use the parametric g-formula to compare the observed lung cancer mortality to the potential lung cancer mortality had each of 3 policies to limit monthly radon exposure been in place throughout follow-up. Results: There were 617 lung cancer deaths over 135,275 person-years of follow-up. With no intervention on radon exposure, estimated lung cancer mortality by age 90 was 16%. Lung cancer mortality was reduced for all interventions considered, and larger reductions in lung cancer mortality were seen for interventions with lower monthly radon exposure limits. The most stringent guideline, the Mine Safety and Health Administration standard of 0.33 working-level months, reduced lung cancer mortality from 16% to 10% (risk ratio = 0.67 [95% confidence interval = 0.61 to 0.73]). Conclusions: This work illustrates the utility of the parametric g-formula for estimating the effects of policies regarding occupational exposures, particularly in situations vulnerable to the healthy worker survivor bias.
Inhibition by TNF‐alpha and IL‐4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells

In vivo, tracheal gland serous cells highly express the cystic fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the human CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in weak and transient gene expression.
Aggressive Tax Planning & the Ethical Tax Lawyer

Can a tax planner be both ethical and aggressive? When a client wants help with a transaction in which the lawyer thinks the tax benefits will probably not be sustained on the merits if challenged, what is the ethical response? How low should the tax adviser go? The rules of ethics and standards of tax practice generally do not answer these questions. And there is a dearth of guidance about what it means to behave ethically when making discretionary decisions about when and how to provide advice for aggressive tax planning. This article fills that gap and argues that a lawyer seeking to pursue a career as an ethical tax planner should identify and implement her philosophy of lawyering to help her make these difficult discretionary decisions in a principled way. Using, as an example, a U.S. multinational corporation that wants to invert and engage in other potentially aggressive cross-border tax reduction strategies that Congress and the Treasury have repeatedly tried to curtail, this article demonstrates that employing a philosophy of lawyering empowers a tax planner determine how (and whether) to assist this client. Ultimately, this article helps a tax planner operationalize, on an individual basis and in a way that aligns with her values, both the general and tax-specific rules of professional conduct so that she can answer the questions posed above.
Steroid‐refractory ulcerative colitis: Predictive factors of response to cyclosporine and validation in an independent cohort

Background: One‐third of patients with steroid‐refractory ulcerative colitis (UC) do not respond to cyclosporine and require colectomy. Since alternative pharmacological treatments for this condition are available, it is pertinent to identify factors that predict response. The objective of this study was to determine predictive factors of response prior to cyclosporine administration, with validation in an independent cohort. Methods: The 2 cohorts of patients were identified from prospectively established databases. All patients had received 1 mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The efficacy measure was need of early surgery (within 3 months). Results: From 1998 to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38 patients in the second institution (validation cohort). Eleven patients in the derivation cohort and 9 patients in the validation cohort underwent early colectomy. Univariate analysis in the derivation cohort demonstrated a significant association of colectomy with C‐reactive protein (P = 0.012) and the Ho index before initiation of cyclosporine (P = 0.013). Regression analysis showed that only the Ho index (P = 0.011) had an independent predictive value. The Ho index predicted need of colectomy, with an area under the characteristic receiver operating curve of 0.79 (95% confidence interval [CI], 0.59–0.99) in the derivation cohort and 0.74 (95% CI, 0.53–0.96) in the validation cohort. The cutoff point with the best sensitivity and specificity ratio was ≥5. Conclusions: The Ho‐based predictive score is a good predictor of response to cyclosporine and avoidance of colectomy, and may aid in the indication of this treatment for management of steroid‐resistant UC.