bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Lean Six Sigma to Improve Pneumococcal Vaccination Rates in a Veterans Affairs Rheumatology Clinic
Authors: Wilson Jaime , Swee Melissa , Mosher Hilary , Scott-Cawiezell Jill , Levins Lori , Fort Krista , Kumar Bharat 
Published: August 2019

ABSTRACT
Pneumonia is a major cause of morbidity and mortality in the United States. Therefore, prevention of pneumococcal pneumonia by administering effective and well-tolerated vaccines is an important goal, especially in the immunocompromised patients who are at an increased risk of infections. At a large Midwestern Veterans Affairs Rheumatology Clinic, an internal audit revealed a baseline immunization rate of 3%. Through the Lean Six Sigma approach, the investigators sought to increase the rate to 70%. An interprofessional approach incorporating provider education, reinforcement at the point of care, and workflow simplification was sequentially implemented. Lean Six Sigma tools, including process mapping, voice of the customer, and statistical process control charts were utilized. These interventions increased the percentage of eligible patients receiving vaccinations from 3% (n = 19/687) to 23% (n = 11/48) and decreased the vaccine administration time from 15 to 7 minutes. No adverse reactions were reported. This was balanced by an increase in appointment time by 4 minutes in those who received vaccines. The Lean Six Sigma approach was critical to reducing waste and improving value for patients and providers by increasing pneumococcal vaccination rates among the immunocompromised veteran population in a Midwestern Veterans Affairs Rheumatology Clinic.
Strength in Differences? The Importance of Diversity to Students When Choosing a Physician Assistant Program
Authors: Yuen Cynthia X. 
Published: August 2019

Purpose
Physician assistant (PA) programs are the linchpin of endeavors to increase the diversity of the PA profession. Key to this role is understanding whether students from various backgrounds value certain program attributes differently. The current study investigated whether PA students' demographic characteristics were associated with their likelihood of having considered program diversity, and the importance they placed on program diversity when selecting a program to attend.

Methods
In 2017, 3882 recently matriculated PA students provided key demographic information (ie, gender, race, and ethnicity) and indicated whether they had considered student body and faculty diversity when choosing PA programs to attend. Those who had considered a factor then reported how important it was to them for their program to have that attribute. The current study investigated whether students' demographic characteristics were associated with their likelihood of considering PA program diversity and their subsequent ratings of the importance of program diversity.

Results
Female, Asian, and underrepresented racial and ethnic minority students, compared with male and non-Hispanic white students, were significantly more likely to consider program diversity when choosing PA programs to attend and rated program diversity as being more important.

Conclusions
Program diversity is a greater concern for female and racial and ethnic minority students when selecting PA programs to attend. Less diverse programs could potentially increase their appeal to minority students by highlighting opportunities to connect with communities of color outside of the PA program and by prioritizing the recruitment of minority faculty.
Defining Global Health Competencies for Entry-Level Physical Therapist Education
Authors: Ubani Nnedinma C. , Pechak Celia , Black Jill D. 
Published: August 2019

Introduction.
Health professions educators are advocating for curricular changes to better prepare graduates for contemporary practice in an increasingly complex and interdependent world. No framework for the integration of a global health perspective into physical therapist (PT) education exists. A previous study proposed 33 global health competencies (GHCs) for PT education; however, participants' comments suggested the need for additional revisions to ensure entry-level relevance to PT education. The purpose of this study was to delineate GHCs relevant to all entry-level PT education in the United States.

Methods.
Current full-time US-based PT faculty participated. The 2-phase nonexperimental study utilized focus group and Delphi survey methodologies. In phase 1, 4 participants in a focus group revised the 33 GHCs from the previous study. In phase 2, 19 participants were asked (via 3 rounds of an online Delphi survey) whether the revised competencies were relevant to all entry-level PT education. Competencies with at least 80% consensus within any round were deemed relevant.

Results.
In phase 1, participants made changes to 17 competencies, eliminated 2, and suggested 3 new ones, leaving 30 to advance. In phase 2, 6 competencies were rejected and 24 were accepted as relevant to entry-level PT education in the United States.

Discussion and Conclusion.
Participants readily accepted GHCs with content similar to current PT education accreditation standards, such as social determinants of health, cultural competency, and effective communication. Additional accepted GHCs pertained to strategies for low-resource settings, organizations and agreements, and public health concerns. The delineated GHCs may be used as a standardized framework to integrate a global health perspective into PT curricula.
Long noncoding RNAs in thyroid cancer
Authors: Sedaghati Mahsa , Kebebew Electron 
Published: August 2019

Purpose of review
Our understanding of the molecular pathology events involved in thyroid cancer initiation and progression and its subtypes has markedly improved as a result of multiomic studies. Recently, long noncoding RNA (lncRNA) have been shown to have a role in cancer initiation and progression and have also been studied in thyroid cancer.

Recent findings
lncRNA are dysregulated in thyroid cancer. lncRNA have tumor suppressive and oncogenic function in thyroid cancer cells and play a role in some of the established genetic drivers of thyroid cancer initiation and progression. Lastly, some lncRNA are associated with clinicopathologic features of thyroid cancer and circulating blood lncRNA could potentially detect the presence of thyroid cancer.

Summary
We highlight the possible clinical utility of analyzing lncRNAs as biomarkers for thyroid cancer diagnosis and prognosis and their association with common genetic changes associated with thyroid cancer.
Impact of acute-on-chronic liver failure on post-transplant survival and on kidney outcomes
Authors: Marciano Sebastián , Mauro Ezequiel , Giunta Diego , Torres María C. , Diaz Juan M. , Bermudez Carla , Gutierrez-Acevedo María N. , Narvaez Adrián , Ortíz Jorge , Dirchwolf Melisa , Pollarsky Florencia , Rojas-Saunero Liliana P. , Gadano Adrián 
Published: August 2019

Objectives
We aimed to evaluate the effect of acute-on-chronic liver failure (ACLF) on patients’ 1-year post-liver transplant (LT) survival. In addition, we evaluated the effect of ACLF on the development of post-LT chronic kidney disease (CKD) and early allograft dysfunction (EAD).

Patients and methods
A retrospective cohort of patients who underwent transplantation from 2010 to 2016 was studied. EASL-CLIF’s definition of ACLF was used. The risk of post-LT death, CKD, and EAD was estimated with regression models weighted by inverse probability weighting considering the recipients’ characteristics. Donor’s BMI and donor risk index were included in the models as well.

Results
A total of 185 patients were included: 125 (67.6%) without ACLF and 60 (32.4%) with ACLF. The 1-year post-LT survival rate was 91.2% [95% confidence interval (CI): 84.6–95.1%] in patients without ACLF versus 84.9% (95% CI: 73.1–91.9%) in patients with ACLF. Post-LT CKD occurred in 43 (38.7%) patients without ACLF versus 26 (52.0%) patients with ACLF. EAD occurred in 40 (32.3%) patients without ACLF versus 15 (28.8%) patients with ACLF. No effect of ACLF was found on survival (hazard ratio 1.75; 95% CI: 0.64–4.75, P = 0.272), CKD (odds ratio: 1.31; 95% CI: 0.60–2.86; P = 0.491), or EAD (odds ratio: 0.74; 95% CI: 0.38–1.66, P = 0.473).

Conclusion
In this study, which included mainly patients with grade 1 ACLF at the time of LT, its presence had no impact on post-LT survival or on the occurrence of CKD or EAD.
Role of Metoprolol Succinate in the Treatment of Heart Failure and Atrial Fibrillation: A Systematic Review
Authors: Vinereanu Dragos , Spinar Jindrich , Pathak Atul , Kozlowski Dariusz 
Published: August 2019

Background:
Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used since the 1970s.

Areas of Uncertainty:
Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited.

Data Sources:
We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed.

Results:
A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF.

Conclusions:
Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.
Hospital-Acquired Pressure Injuries in Children With Congenital Heart Disease: Prevalence and Associated Factors*
Authors: Kulik Lindyce A. , Hasbani Natalie R. , Stellar Judith J. , Quigley Sandy M. , Shelley Stacey S. , Wypij David , Curley Martha A. Q. 
Published: August 2019

Objectives:
To explore the prevalence, location, and clinical factors associated with hospital-acquired pressure injuries among pediatric patients with congenital heart disease.

Design:
Secondary analysis of data from a multicenter prospective cohort study of pediatric pressure injury risk, including patients with congenital heart disease.

Setting:
Eight acute care academic pediatric hospitals.

Patients:
Patients were preterm to 21 years old with congenital heart disease and on bed rest for at least 24 hours after hospital admission with a medical device attached to or traversing the skin or mucous membrane.

Interventions:
None.

Measurements and Main Results:
Patients were evaluated for a maximum of eight observations during a 4-week period to identify Braden QD risk and pressure injury development. Hospital-acquired pressure injuries were staged according to the National Pressure Ulcer Advisory Panel guidelines. Stepwise logistic regression was used to explore risk factors associated with hospital-acquired pressure injuries development, accounting for site as a cluster variable using generalized estimating equations. Overall, 279 pediatric cardiac patients provided 919 observations (median, 2 per patient [interquartile range, 2–5 per patient]). Thirty-eight hospital-acquired pressure injuries occurred in 27 patients (9.7%). Most injuries (28/38 [74%]) were related to medical devices. The most common medical devices that caused injury were oxygen saturation probes. The remaining hospital-acquired pressure injuries were immobility-related pressure injuries (10/38 [26%]) located primarily on the buttock, sacrum, or coccyx (5/10 [50%]). In multivariable analyses, being non-Hispanic white (odds ratio, 3.54; 95% CI, 2.15–5.84), experiencing operating room time greater than 4 hours (odds ratio, 2.91; 95% CI, 1.13–7.49), having oxygen saturation levels less than 85% (odds ratio, 2.65; 95% CI, 1.01–6.96), and having worse Braden QD scores (odds ratio, 1.25 per 1 point increase; 95% CI, 1.17–1.34) were significantly associated with hospital-acquired pressure injuries development.

Conclusions:
In this multicenter observational study of pediatric patients with congenital heart disease, we describe a hospital-acquired pressure injury prevalence of 9.7% with approximately 75% of injuries related to medical devices. These data can be used to inform practice and target interventions to decrease pressure injury risk and prevent pressure injuries in this vulnerable pediatric population.
Imiquimod Acts Synergistically with BMP9 through the Notch Pathway as an Osteoinductive Agent In Vitro
Authors: Alverdy Alexandria K. , Pakvasa Mikhail , Zhao Chen , Mostafa Sami , Liu Wei , Luo Wenping , Wolf Jennifer M. , Ameer Guillermo A. , He Tong-Chuan , Reid Russell R. 
Published: August 2019

Background:
Autologous bone grafts used for surgical reconstruction are limited by infection or insufficient supply of host material. Experimental agents that promote differentiation of stem cells into mature bone are currently being studied for future use in the repair of bone defects. The authors hypothesized that imiquimod, a synthetic immune response modifier, increases Notch pathway gene expression and acts synergistically with bone morphogenetic protein (BMP) 9 to induce differentiation of mesenchymal stem cells toward an osteogenic phenotype.

Methods:
Alkaline phosphatase activity was used to assess the osteogenic potential of cultured mouse immortalized multipotent adipose-derived cells (iMADs) treated with 0, 4, 6, and 8 μg/ml of imiquimod with and without BMP9. Adenoviral vectors expressing human BMP9 and a dominant-negative mutant of mouse Notch1 were used to assess BMP9 and Notch blockade on osteogenic activity, respectively. Expression of Notch signaling mediators and osteogenic markers were assayed by quantitative polymerase chain reaction. Alizarin red staining was used to assess the synergism between BMP9 and imiquimod.

Results:
Imiquimod exposure enhanced osteogenic differentiation of iMADs by 2.8-fold (p < 0.001) and potentiated BMP9-induced osteogenic differentiation of iMADs by 1.6-fold (p < 0.001), shown by increased alkaline phosphatase activity and augmented matrix mineralization. Quantitative-real time polymerase chain reaction analysis demonstrated that imiquimod induced the expression of downstream genes (p < 0.01) of the Notch signaling pathway Hey1, Hey2, and Hes1, by increases of 9.7-, 22-, and 2.7-fold, respectively.

Conclusions:
These findings identify a novel role for imiquimod to shift mesenchymal stem cells toward an osteogenic phenotype. Imiquimod may be useful clinically when scaffolds are applied to treat bone defects.
Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates
Authors: Safley Susan A. , Graham Melanie L. , Weegman Bradley P. , Einstein Samuel A. , Barber Graham F. , Janecek Jody J. , Mutch Lucas A. , Singh Amar , Ramachandran Sabarinathan , Garwood Michael , Sambanis Athanassios , Papas Klearchos K. , Hering Bernhard J. , Weber Collin J. 
Published: August 2019

Background.
We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes.

Methods.
Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem.

Results.
At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20+ B cells, CD4+ and CD8+ T cells, and CD14+ macrophages increased consistent with a mild foreign body reaction.

Conclusions.
The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.
DSA-FXM: Accelerated Donor-specific Flow Crossmatch Discriminating Class I and II Antibody Specifically and Only to Donor HLA for Determining True Incompatibility
Authors: Chen Ge , Lin Lingling , Tyan Dolly B. 
Published: August 2019

Background.
Worldwide, a final crossmatch is the gold standard for determining compatibility between patient and donor before solid organ transplantation and preventing hyperacute rejection. In the absence of autoantibodies, an incompatible crossmatch in a sensitized patient is attributed to mismatched donor HLA. However, current physical crossmatch methods cannot distinguish reactivity to HLA from other clinically irrelevant cell surface targets nor the class of HLA if it is the target. Result interpretation is difficult or impossible when autoantibodies, alloantibodies, or therapeutic antibodies coexist.

Methods.
Herein, we describe a unique donor-specific flow crossmatch (DSA-FXM) that distinguishes HLA class I or II donor-specific antibody bound to HLA antigens on the donor cell surface in their native conformation that is not impacted by rituximab, anti-thymocyte globulin (after absorption), or autoantibodies. It is HLA specific.

Results.
We compared the results of single-antigen antibody testing, autoreactive and alloreactive flow cytometry crossmatches (FXM) using traditional FXM and our DSA-FXM method from 94 patients (enriched for auto+/allo+ pairs; n = 64) against 110 donors (338 tests) and show that, in our cohort, positive traditional FXM results are not directed to donor HLA 60.25% of the time and negative traditional FXM results are missing HLA donor-specific antibody 36.2% of the time based on the DSA-FXM.

Conclusions.
We demonstrate that the DSA-FXM is able to define categorically distinct and clinically important HLA antibody profiles in half the time required for the standard FXM, potentially shortening cold ischemia time and providing clinicians with unambiguous essential information regarding HLA compatibility when time is critical.
Similar Cerebral Blood Flow and Autonomic Responses to Upright Tilt Test in Adult Patients With Different Hemodynamic Mechanisms Leading to Reflex Syncope
Authors: González-Hermosillo J. Antonio , Petersen Alvaro , Salas-Herrera Cecy , Brown-Escobar Christopher , Kostine Andrey , Sierra-Beltrán Manuel , Lerma Claudia 
Published: August 2019

Purpose:
Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope.

Methods:
The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt.

Results:
At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge.

Conclusions:
Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.
Hydrogen molecular ions: H
3
+
, H
5
+
and beyond
Authors: Tennyson Jonathan , Miller Steve 
Published: August 2019

Three decades after the spectroscopic detection of H
3
+
in space, the inspiring developments in physics, chemistry and astronomy of H

n

+
(
n
= 3, 5, 7) systems, which led to this Royal Society Discussion Meeting, are reviewed, the present state of the art as represented by the meeting surveyed and future lines of research considered.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
The motion and distribution of the gas in the central 300 pc of the galaxy as revealed by spectra of H
3
+
Authors: Geballe T. R. , Oka T. , Goto M. 
Published: August 2019

Spectroscopy of absorption lines of H
3
+
in the central molecular zone (CMZ) of the Galaxy show that a previously largely unknown component of the interstellar medium there, warm (
T
∼200 K) and diffuse (
n
≲ 10
2
cm
−3
) gas, makes up a large fraction of the volume of the CMZ, and that this gas is moving radially outward from the centre. These discoveries upend the generally accepted understanding that the interstellar environment of the CMZ comprises almost entirely an ultra-hot plasma and dense molecular clouds. The radial momentum associated with the diffuse gas in the CMZ exceeds that of the ejecta of thousands of core-collapse supernovae and implies some extraordinary past activity in the centre, possibly associated with the supermassive black hole, Sgr A*. We speculate that within approximately 10
6
years, gravity could halt the expansion of the diffuse gas and that contraction towards the centre could then commence.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.