bluuebunny/crossref_metadata_2025_split huggingface dataset:
TBX20 Regulates Angiogenesis Through the Prokineticin 2–Prokineticin Receptor 1 Pathway
Authors: Meng Shu , Gu Qilin , Yang Xiaojie , Lv Jie , Owusu Iris , Matrone Gianfranco , Chen Kaifu , Cooke John P. , Fang Longhou 
Published: March 2018

Background:
Angiogenesis is integral for embryogenesis, and targeting angiogenesis improves the outcome of many pathological conditions in patients. TBX20 is a crucial transcription factor for embryonic development, and its deficiency is associated with congenital heart disease. However, the role of TBX20 in angiogenesis has not been described.

Methods:
Loss- and gain-of-function approaches were used to explore the role of TBX20 in angiogenesis both in vitro and in vivo. Angiogenesis gene array was used to identify key downstream targets of TBX20.

Results:

Unbiased gene array survey showed that
TBX20
knockdown profoundly reduced angiogenesis-associated
PROK2
(prokineticin 2) gene expression. Indeed, loss of TBX20 hindered endothelial cell migration and in vitro angiogenesis. In a murine angiogenesis model using subcutaneously implanted Matrigel plugs, we observed that TBX20 deficiency markedly reduced PROK2 expression and restricted intraplug angiogenesis. Furthermore, recombinant PROK2 administration enhanced angiogenesis and blood flow recovery in murine hind-limb ischemia. In zebrafish, transient knockdown of
tbx20
by morpholino antisense oligos or genetic disruption of
tbx20
by CRISPR/Cas9 impaired angiogenesis. Furthermore, loss of
prok2
or its cognate receptor
prokr1a
also limited angiogenesis. In contrast, overexpression of
prok2
or
prokr1a
rescued the impaired angiogenesis in
tbx20
-deficient animals.

Conclusions:
Our study identifies TBX20 as a novel transcription factor regulating angiogenesis through the PROK2–PROKR1 (prokineticin receptor 1) pathway in both development and disease and reveals a novel mode of angiogenic regulation whereby the TBX20-PROK2–PROKR1 signaling cascade may act as a “biological capacitor” to relay and sustain the proangiogenic effect of vascular endothelial growth factor. This pathway may be a therapeutic target in the treatment of diseases with dysregulated angiogenesis.
Associations Between Ambient Particle Radioactivity and Blood Pressure: The NAS (Normative Aging Study)
Authors: Nyhan Marguerite M. , Coull Brent A. , Blomberg Annelise J. , Vieira Carol L.Z. , Garshick Eric , Aba Abdulaziz , Vokonas Pantel , Gold Diane R. , Schwartz Joel , Koutrakis Petros 
Published: March 2018

Background

The cardiovascular effects of low‐level environmental radiation exposures are poorly understood. Although particulate matter (
PM
) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (
BP
), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether
BP
increased with higher exposures to radioactive components of ambient
PM
, herein referred to as particle radioactivity (
PR
).

Methods and Results

We performed a repeated‐measures analysis of 852 men to examine associations between
PR
exposure and
BP
using mixed‐effects regression models. As a surrogate for
PR
, we used gross β activity, measured by the US Environmental Protection Agency's radiation monitoring network. Higher
PR
exposure was associated with increases in both diastolic
BP
and systolic
BP
, for exposures from 1 to 28 days. An interquartile range increase in 28‐day
PR
exposure was associated with a 2.95–mm Hg increase in diastolic BP (95% confidence interval, 2.25–3.66;
P
<0.001) and a 3.94–mm Hg increase in systolic BP (95% confidence interval, 2.62–5.27;
P
<0.001). For models including both
PR
and
PM
≤2.5 µm, the
PR
‐
BP
associations remained stable and significant. For models including
PR
and black carbon or
PR
and particle number, the
PR
‐
BP
associations were attenuated; however, they remained significant for many exposure durations.

Conclusions

This is the first study to demonstrate the potential adverse effects of
PR
on both systolic and diastolic
BP
s. These were independent and similar in magnitude to those of PM ≤2.5 µm, black carbon, and particle number. Understanding the effects of particle‐bound radionuclide exposures on
BP
may have important implications for environmental and public health policy.
Gamete Donation: Are Children Entitled to Know Their Genetic Origins? A Comparison of Opposing Views. The Italian State of Affairs
Authors: Montanari Vergallo Gianluca , Marinelli Enrico , di Luca Natale Mario , Zaami Simona 
Published: March 2018

Abstract
Medically assisted fertilization techniques give rise to a wide array of issues, such as the rights to secrecy, partial anonymity or to the full disclosure of information about the donors’ identities. The authors espouse the right of donor-conceived children to know their biological origins, and delve into opposing views, either in favour of the gamete donors’ right to anonymity or against it. Be that as it may, the right to know one’s biological origins has been gaining a foothold as part of the broader right to personal identity. The latter is in fact codified and upheld in numerous international treaties and conventions as a fundamental human right. The authors expound upon the Italian legislation, which is designed to enforce total donor anonymity. Against that backdrop, the authors weigh the suitability of further regulating access to sensitive, identifying information about the procreation methods involved in each case.
On Some Shortcomings of Shannon Entropy as a Measure of Information Content in Indirect Measurements of Continuous Variables
Authors: Petty Grant W. 
Published: March 2018

AbstractShannon entropy has long been accepted as a primary basis for assessing the information content of sensor channels used for the remote sensing of atmospheric variables. It is not widely appreciated, however, that Shannon information content (SIC) can be misleading in retrieval problems involving nonlinear mappings between direct observations and retrieved variables and/or non-Gaussian prior and posterior PDFs. The potentially severe shortcomings of SIC are illustrated with simple experiments that reveal, for example, that a measurement can be judged to provide negative information even in cases in which the postretrieval PDF is undeniably improved over an informed prior based on climatology. Following previous authors’ writing mainly in the data assimilation and climate analysis literature, the Kullback–Leibler (KL) divergence, also commonly known as relative entropy, is shown to suffer from fewer obvious defects in this particular context. Yet, even KL divergence is blind to the expected magnitude of errors as typically measured by the error variance or root-mean-square error. Thus, neither information metric can necessarily be counted on to respond in a predictable way to changes in the precision or quality of a retrieved quantity.
James Michael Lee's Crusade for Empiricism
Authors: Newell Edward J. 
Published: March 2018

James Michael Lee advocated a social scientific “macrotheory” for religious and Christian education from the late 1960s until his death in 2004. Lee said that theology should no longer direct methods of education. Social scientific empirical results would provide firm ground for the teaching of faith and make a way past confessional educational expressions. However, empirical data are now recognized to arise from philosophical pre-commitments, especially since Thomas Kuhn. Lee's social scientific macrotheory is not neutral but comes from his understanding of “fact,” based in turn on a commitment to immanentism and a theology of faith. The article traces stated and unstated philosophical and theological commitments that give rise to Lee's macrotheory.
Spiritual Formation in Online Higher Education Communities: Nurturing Spirituality in Christian Higher Education Online Degree Programs
Authors: Maddix Mark A. , Estep James R. 
Published: March 2018

Spiritual formation is one of the recognized benchmarks of higher education that is Christian. A communal commitment to spiritual formation is indeed part of the Christian higher education community's DNA, and is in fact reflected in the criteria for accreditation in both the Association of Biblical Higher Education (ABHE) and the Association of Theological Schools (ATS). However, as many Christian institutions of higher education begin to engage in online instruction, even offering entire degree programs online, how can they affirm their campus's commitment to the spiritual formation of students? This article addresses the question of providing intentional Christian nurture toward spiritual formation in online degree programs. The aim of the article is to inform participants of the challenges and opportunities for student spiritual formation in online degree programs so as to better equip participants to develop Christian nurture initiatives for online students from an informed perspective. To do so the article includes two parts: (a) the development of a theoretical matrix for online spiritual formation, based principally on precedent literature and the experience of the two authors; and (b) a survey of actual Christian nurture and spiritual formation models specifically designed for online programs.
Generating and Facilitating Effective Online Learning through Discussion
Authors: Maddix Mark A. 
Published: March 2018

In Christian higher education, most teaching and learning has been confined to the traditional classroom. However, with the advent of computer technology many universities and seminaries are offering online courses and programs. These online courses provide facilitators and teachers with a different learning context. One of the most important social learning components of online learning is discussion forums. These forums provide a context for faculty-student and student-student interaction. For teachers facilitating discussion, this can become an overwhelming task, especially when there is too much or not enough student interaction. This article addresses such questions as: How can teachers ensure that discussion is contributing to learning. How much interaction is necessary and what constitutes effective interaction? How can we ensure that students engage in thoughtful discussion? This article explores how teachers can facilitate effective online learning through discussion. The article also presents a framework for effective online discussion called the Community Inquiry Model (Garrison & Anderson, 2011). The article provides guidelines for teachers to develop discussion board rubrics and effective faculty-student and student-student interaction in online courses. The article concludes by providing best practices of online discussion based on current research and personal experience in teaching online courses.
Tibiotalocalcaneal Arthrodesis With Bulk Talar Allograft for Treatment of Talar Osteonecrosis
Authors: DeFontes Kenneth W. , Vaughn Joshua , Smith Jeremy , Bluman Eric M. 
Published: March 2018

Talar body osteonecrosis can be a devastating, painful condition that is difficult to manage surgically when conservative treatments have failed. With early disease, nonoperative treatments can prolong the need for operative correction in the young patient. Later stage disease with extensive involvement may require a tibiotalocalcaneal (TTC) arthrodesis to retain functionality of the limb. This situation frequently requires a structural bone graft. Using the technique described in this article, the void resulting from collapse of the talar body is filled with talar allograft, which offers a more anatomic and structurally rigid construct than previously described methods using an allograft femoral head. We have found this technique to be more resilient and successful than other methods. Level of Evidence: Level V, expert opinion.
Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis
Authors: Siller Nelly , Kuhle Jens , Muthuraman Muthuraman , Barro Christian , Uphaus Timo , Groppa Sergiu , Kappos Ludwig , Zipp Frauke , Bittner Stefan 
Published: March 2018

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.
Use of computed tomography perfusion for acute stroke in routine clinical practice: Complex scenarios, mimics, and artifacts
Authors: Garcia-Esperon Carlos , Bivard Andrew , Levi Christopher , Parsons Mark 
Published: March 2018

Background Computed tomography perfusion is becoming widely accepted and used in acute stroke treatment. Computed tomography perfusion provides pathophysiological information needed in the acute decision making. Moreover, computed tomography perfusion shows excellent correlation with diffusion-weighted imaging and perfusion-weighted sequences to evaluate core and penumbra volumes. Multimodal computed tomography perfusion has practical advantages over magnetic resonance imaging, including availability, accessibility, and speed. Nevertheless, it bears some limitations, as the limited accuracy for small ischemic lesions or brainstem ischemia. Interpretation of the computed tomography perfusion maps can sometimes be difficult. The stroke neurologist faces complex or atypical cases of cerebral ischemia and stroke mimics, and needs to decide whether the “lesions” on computed tomography perfusion are real or artifact. Aims The purpose of this review is, based on clinical cases from a comprehensive stroke center, to describe the added value that computed tomography perfusion can provide to the stroke physician in the acute phase before a treatment decision is made.
Sex-Based Differences in Knee Kinetics With Anterior Cruciate Ligament Strain on Cadaveric Impact Simulations
Authors: Schilaty Nathan D. , Bates Nathaniel A. , Nagelli Christopher , Krych Aaron J. , Hewett Timothy E. 
Published: March 2018

Background: Females are at an increased risk of sustaining noncontact knee ligament injuries as compared with their male counterparts. The kinetics that load the anterior cruciate ligament (ACL) are still under dispute in the literature. Purpose/Hypothesis: The purpose of this study was to determine whether there are differences in knee kinetics between the sexes that lead to greater ACL strain in females when similar external loads are applied during a simulated drop vertical jump landing task. It was hypothesized that female limbs would demonstrate significant differences in knee abduction moment that predispose females to ACL injury when compared with males. Study Design: Controlled laboratory study. Methods: Motion analysis data of 67 athletes who performed a drop vertical jump were collected. The kinematic and kinetic data were used to categorize tertiles of relative risk, and these values were input into a cadaveric impact simulator to assess ligamentous loads during the simulated landing task. Uni- and multiaxial load cells and differential variable reluctance transducer strain sensors were utilized to collect kinetic data and maximum ACL strain for analysis. Conditions of external loads applied to the cadaveric limbs were systematically varied and randomized. Data were analyzed with 2-way repeated-measures analysis of variance and the Fisher exact test. Results: Five kinetic parameters were evaluated. Of the 5 kinetic variables, only knee abduction moment (KAM) demonstrated significant differences in females as compared with males ( F1,136 = 4.398, P = .038). When normalized to height and weight, this difference between males and females increased in significance ( F1,136 = 7.155, P = .008). Compared with males, females exhibited a 10.3-N·m increased knee abduction torque at 66 milliseconds postimpact and a 22.3-N·m increased abduction torque at 100 milliseconds postimpact. For loading condition, the condition of “maximum ACL strain” demonstrated a maximum difference of 54.3-N·m increased abduction torque and 74.5-N·m increased abduction torque at 66 milliseconds postimpact. Conclusion: Under the tested conditions, increased external loads led to increased medial knee translation force, knee abduction moment, and external knee moment. Females exhibited greater forces and moments at the knee, especially at KAM, when loaded in similar conditions. As these KAM loads are associated with increased load and strain on the ACL, the sex-based differences observed in the present study may account for a portion of the underlying mechanics that predispose females to ACL injury as compared with males in a controlled simulated athletic task. Clinical Relevance: KAM increases strain to the ACL under clinically representative loading. Additionally, this work establishes the biomechanical characteristics of knee loading between sexes.
Pattern of Opioid Analgesic Prescription for Adults by Dentists in Nova Scotia, Canada
Authors: Jimoh K.O. , Matthews D.C. , Brillant M. , Sketris I. 
Published: March 2018

Global consumption of prescription opioid analgesics has increased dramatically in the past 2 decades, outpacing that of illicit drugs in some countries. The increase has been partly ascribed to the widespread availability of prescription opioid analgesics and their subsequent nonmedical use, which may have contributed to the epidemic of opioid abuse, addiction, and overdose-related deaths. International studies report that dentists may be among the leading prescribers of opioid analgesics, thus adding to the societal impact of this epidemic. Between 2009 and 2011, dentists in the United States prescribed 8% to 12% of opioid analgesics dispensed. There is little information on the pattern of opioid analgesic prescription by dentists in Canada. The aim of this study was to examine the pattern of opioid analgesics prescription by dentists in Nova Scotia (NS), Canada. This retrospective observational study used the provincial prescription monitoring program’s record of oral opioid analgesics and combinations dispensed to persons 16 y and older at community pharmacies that were prescribed by dentists from January 2011 to December 2015. During the study period, more than 70% of licensed dentists in NS wrote a prescription for dispensed opioid analgesics, comprising about 17% of all opioid analgesic prescribers. However, dentists were responsible for less than 4% of all prescriptions for dispensed opioid analgesics, prescribing less than 0.5% of the total morphine milligram equivalent (MMEq) of opioid analgesics dispensed over the 5 y. There was a significant downward trend in total MMEq of dispensed opioid analgesics prescribed by dentists from about 2.23 million MMEq in 2011 to 1.93 million MMEq in 2015 (r = –0.97; P = 0.006). Opioid prescription is common among dentists, but their contribution to the overall availability of opioid analgesics is low. Furthermore, there has been a downward trend in total dispensed MMEq of opioid analgesics prescribed by dentists. Knowledge Transfer Statement: This study will serve to inform dentists and policy makers on the types and dosage of opioid analgesics being prescribed by dentists. The study may prompt dentists to reflect on and adjust their practice of opioid analgesic prescription in view of the current opioid analgesic epidemic.
How I treat the postthrombotic syndrome
Authors: Rabinovich Anat , Kahn Susan R. 
Published: March 2018

Abstract
The postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that imposes significant morbidity, reduces quality of life, and is costly. After DVT, 20% to 50% of patients will develop PTS, and up to 5% will develop severe PTS. The principal risk factors for PTS are anatomically extensive DVT, recurrent ipsilateral DVT, obesity, and older age. By preventing the initial DVT and DVT recurrence, primary and secondary prophylaxis of DVT will reduce occurrence of PTS. The effectiveness of elastic compression stockings (ECSs) for PTS prevention is controversial. Catheter-directed thrombolysis is not effective to prevent PTS overall but may prevent more severe forms of PTS and should be reserved for select patients with extensive thrombosis, recent symptoms onset, and low bleeding risk. For patients with established PTS, the cornerstone of management is ECS, exercise, and lifestyle modifications. Surgical or endovascular interventions may be considered in refractory cases. Because of a lack of effective therapies, new approaches to preventing and treating PTS are needed. This article uses a case-based approach to discuss risk factors for PTS after DVT, how to diagnose PTS, and available means to prevent and treat PTS, with a focus on new information in the field.
Epidemiology, clinical features, and outcome of HTLV-1–related ATLL in an area of prevalence in the United States
Authors: Malpica Luis , Pimentel Agustin , Reis Isildinha M. , Gotuzzo Eduardo , Lekakis Lazaros , Komanduri Krishna , Harrington Thomas , Barber Glen N. , Ramos Juan C. 
Published: March 2018

Key Points
ATLL presents more aggressively in US Afro-Caribbean than Japanese patients and continues to have a poor outcome despite modern therapies. AZT-IFN is a reasonable up-front option for aggressive, nonbulky, leukemic ATLL subtypes, resulting in long PFS after a complete response.
Bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis: a multicentre cohort study in Korea
Authors: Kim Cheon Tae , Kim Tae-Ok , Shin Hong-Joon , Ko Young Chun , Hun Choe Yeong , Kim Hak-Ryul , Kwon Yong-Soo 
Published: March 2018

Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment.This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for >1 month, combined with a World Health Organization-recommended regimen.Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38.5–61.0) years. 42 (68.9%) patients had fluoroquinolone-resistant MDR-TB and 16 (26.2%) had extensively drug-resistant TB. The median (IQR) duration of treatment with bedaquiline and/or delamanid was 168 (166.5–196.5) days, with 33 (54.1%) receiving linezolid for a median (IQR) of 673 (171–736) days. Of the 55 patients with positive sputum cultures at the start of bedaquiline and/or delamanid treatment, 39 (70.9%) achieved sputum culture conversion within a median of 119 days. Treatment was halted in four patients (6.6%) because of prolonged Fridericia's corrected QT interval.Bedaquiline and delamanid were effective and safe for treating MDR-TB, with initial evidence of sequential administration of these two drugs as a viable treatment strategy for patients when an adequate treatment regimen cannot be constructed.