bluuebunny/crossref_metadata_2025 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

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.

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’.
Photodissociation as a probe of the H
3
+
avoided crossing seam
Authors: Urbain X. , Dochain A. , Marion R. , Launoy T. , Loreau J.
Published: August 2019

Experiments are conducted to investigate the role of the avoided crossing seam in the photodissociation of H
3
+
. Three-dimensional imaging of dissociation products is used to determine the kinetic energy release and branching ratio among the fragmentation channels. Vibrational distributions are measured by dissociative charge transfer of H
2
+
products. It is found that the photodissociation of hot H
3
+
in the near-ultraviolet produces cold H
2
+
, but hot H
2
. Modelling the wavepacket dynamics along the repulsive potential energy surface accounts for the repopulation of the ground potential energy surface. The role of the avoided crossing seam is emphasized and its importance for the astrophysically relevant charge transfer reactions underlined.

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’.
Deuterated forms of H
3
+
and their importance in astrochemistry
Authors: Caselli P. , Sipilä O. , Harju J.
Published: August 2019

At the low temperatures (approx. 10 K) and high densities (approx. 100 000 H
2
molecules per cm
−3
) of molecular cloud cores and protostellar envelopes, a large amount of molecular species (in particular those containing C and O) freeze-out onto dust grain surfaces. It is in these regions that the deuteration of H
3
+
becomes very efficient, with a sharp abundance increase of H
2
D
+
and D
2
H
+
. The multi-deuterated forms of H
3
+
participate in an active chemistry: (i) their collision with neutral species produces deuterated molecules such as the commonly observed N
2
D
+
, DCO
+
and multi-deuterated NH
3
; (ii) their dissociative electronic recombination increases the D/H atomic ratio by several orders of magnitude above the D cosmic abundance, thus allowing deuteration of molecules (e.g. CH
3
OH and H
2
O) on the surface of dust grains. Deuterated molecules are the main diagnostic tools of dense and cold interstellar clouds, where the first steps toward star and protoplanetary disc formation take place. Recent observations of deuterated molecules are reviewed and discussed in view of astrochemical models inclusive of spin-state chemistry. We present a new comparison between models based on complete scrambling (to calculate branching ratio tables for reactions between chemical species that include protons and/or deuterons) and models based on non-scrambling (proton hop) methods, showing that the latter best agree with observations of NH
3
deuterated isotopologues and their different nuclear spin symmetry states.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Hydrogen molecular ions and the violent birth of the Solar System
Authors: Ceccarelli Cecilia , Favre Cecile , López-Sepulcre Ana , Fontani Francesco
Published: August 2019

Many pieces of evidence indicate that the Solar System youth was marked by violent processes: among others, high fluxes of energetic particles (greater than or equal to 10 MeV) are unambiguously recorded in meteoritic material, where an overabundance of the short-lived
10
Be products is measured. Several hypotheses have been proposed to explain from where these energetic particles originate, but there is no consensus yet, mostly because of the scarcity of complementary observational constraints. In general, the reconstruction of the past history of the Solar System is best obtained by simultaneously considering what we know of it and of similar systems nowadays in formation. However, when it comes to studying the presence of energetic particles in young forming stars, we encounter the classical problem of the impossibility of directly detecting them toward the emitting source (analogously to what happens to galactic cosmic rays). Yet, exploiting the fact that energetic particles, such as cosmic rays, create

H

3

+

and that an enhanced abundance of

H

3

+

causes dramatic changes on the overall gas chemical composition, we can indirectly estimate the flux of energetic particles. This contribution provides an overview of the search for solar-like protostars permeated by energetic particles and the discovery of a protocluster, OMC-2 FIR4, where the phenomenon is presently occurring.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Local-time averaged maps of H
3
+
emission, temperature and ion winds
Authors: Stallard Tom S. , Baines Kevin H. , Melin Henrik , Bradley Thomas J. , Moore Luke , O'Donoghue James , Miller Steve , Chowdhury Mohammad N. , Badman Sarah V. , Allison Hayley J. , Roussos Elias
Published: August 2019

We present Keck-NIRSPEC observations of Saturn's

H

3

+

aurora taken over a period of a month, in support of the Cassini mission's ‘Grand Finale’. These observations produce two-dimensional maps of Saturn's

H

3

+

temperature and ion winds for the first time. These maps show surprising complexity, with different morphologies seen in each night. The

H

3

+

ion winds reveal multiple arcs of 0.5–1 km s
−1
ion flows inside the main auroral emission. Although these arcs of flow occur in different locations each night, they show intricate structures, including mirrored flows on the dawn and dusk of the planet. These flows do not match with the predicted flows from models of either axisymmetric currents driven by the Solar Wind or outer magnetosphere, or the planetary periodic currents associated with Saturn's variable rotation rate. The average of the ion wind flows across all the nights reveals a single narrow and focused approximately 0.3 km s
−1
flow on the dawn side and broader and more extensive 1–2 km s
−1
sub-corotation, spilt into multiple arcs, on the dusk side. The temperature maps reveal sharp gradients in ionospheric temperatures, varying between 300 and 600 K across the auroral region. These temperature changes are localized, resulting in hot and cold spots across the auroral region. These appear to be somewhat stable over several nights, but change significantly over longer periods. The position of these temperature extremes is not well organized by the planetary period and there is no evidence for a thermospheric driver of the planetary period current system. Since no past magnetospheric or thermospheric models explain the rich complexity observed here, these measurements represent a fantastic new resource, revealing the complexity of the interaction between Saturn's thermosphere, ionosphere and magnetosphere.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
JUNO/JIRAM's view of Jupiter's H
3
+
emissions
Authors: Dinelli B. M. , Adriani A. , Mura A. , Altieri F. , Migliorini A. , Moriconi M. L.
Published: August 2019

The instrument JIRAM (Jovian Infrared Auroral Mapper), on board the NASA spacecraft Juno, is both an imager and a spectrometer. Two distinct detectors are used for imaging and spectroscopy. The imager acquires Jupiter images in two bands, one of which (L band, 3.3–3.6 μm) is devoted to monitor the H
3
+
emission. The spectrometer covers the spectral region from 2 to 5 μm (average spectral resolution 9 nm) with a 256 pixels slit that can observe the same scene of the L band imager with some delay. JIRAM scientific goals are the exploration of the Jovian aurorae and the planet's atmospheric structure, dynamics and composition. Starting early July 2016 Juno is orbiting around Jupiter. Since then, JIRAM has provided an unprecedented amount of measurements, monitoring both Jupiter's atmosphere and aurorae. In particular, the camera has monitored Jupiter's poles with very high spatial resolution, providing new insights in both its aurorae and the polar dynamic. The main findings obtained by the L imager are detailed pictures of Jupiter's aurorae showing an extremely complex morphology of the H
3
+
distribution in the main oval and in the moon's footprints. The spectrometer has enabled the measure the distribution of both H
3
+
concentration and temperature. The analysis of the north auroral region limb observations shows that the peak density of H
3
+
is above 750 km and that often it is anticorrelated to the temperature, confirming the infrared cooling effect of H
3
+
.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Why is the H
3
+
hot spot above Jupiter's Great Red Spot so hot?
Authors: Ray L. C. , Lorch C. T. S. , O'Donoghue J. , Yates J. N. , Badman S. V. , Smith C. G. A. , Stallard T. S.
Published: August 2019

Recent observations of Jupiter's Great Red Spot indicate that the thermosphere above the storm is hotter than its surroundings by more than 700 K. Possible suggested sources for this heating have thus far included atmospheric gravity waves and lightning-driven acoustic waves. Here, we propose that Joule heating, driven by Great Red Spot vorticity penetrating up into the lower stratosphere and coupling to the thermosphere, may contribute to the large observed temperatures. The strength of Joule heating will depend on the local inclination angle of the magnetic field and thus the observed emissions and inferred temperatures should vary with planetary longitude as the Great Red Spot tracks across the planet.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
The H
3
+
ionosphere of Uranus: decades-long cooling and local-time morphology
Authors: Melin Henrik , Fletcher L. N. , Stallard T. S. , Miller S. , Trafton L. M. , Moore L. , O'Donoghue J. , Vervack R. J. , Dello Russo N. , Lamy L. , Tao C. , Chowdhury M. N.
Published: August 2019

The upper atmosphere of Uranus has been observed to be slowly cooling between 1993 and 2011. New analysis of near-infrared observations of emission from H
3
+
obtained between 2012 and 2018 reveals that this cooling trend has continued, showing that the upper atmosphere has cooled for 27 years, longer than the length of a nominal season of 21 years. The new observations have offered greater spatial resolution and higher sensitivity than previous ones, enabling the characterization of the H
3
+
intensity as a function of local time. These profiles peak between 13 and 15 h local time, later than models suggest. The NASA Infrared Telescope Facility iSHELL instrument also provides the detection of a bright H
3
+
signal on 16 October 2016, rotating into view from the dawn sector. This feature is consistent with an auroral signal, but is the only of its kind present in this comprehensive dataset.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Non-adiabatic effects in the H
3
+
spectrum
Authors: Amaral Paulo H. R. , Stanke Monika , Adamowicz Ludwik , Diniz Leonardo G. , Mohallem José R. , Alijah Alexander
Published: August 2019

The effect of non-adiabatic coupling on the computed rovibrational energy levels amounts to about 2 cm
−1
for H
3
+
and must be included in high-accuracy calculations. Different strategies to obtain the corresponding energy shifts are reviewed in the article. A promising way is to introduce effective vibrational reduced masses that depend on the nuclear configuration. A new empirical method that uses the stockholder atoms-in-molecules approach to this effect is presented and applied to H
3
+
. Furthermore, a highly accurate potential energy surface for the D
3
+
isotopologue, which includes relativistic and leading quantum electrodynamic terms, is constructed and used to analyse the observed rovibrational frequencies for this molecule. Accurate band origins are obtained that improve existing data.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
PAAR proteins act as the ‘sorting hat’ of the type VI secretion system
Authors: Wood Thomas E. , Howard Sophie A. , Wettstadt Sarah , Filloux Alain
Published: August 2019

Bacteria exist in polymicrobial environments and compete to prevail in a niche. The type VI secretion system (T6SS) is a nanomachine employed by Gram-negative bacteria to deliver effector proteins into target cells. Consequently, T6SS-positive bacteria produce a wealth of antibacterial effector proteins to promote their survival among a prokaryotic community. These toxins are loaded onto the VgrG–PAAR spike and Hcp tube of the T6SS apparatus and recent work has started to document the specificity of effectors for certain spike components.

Pseudomonas aeruginosa

encodes several PAAR proteins, whose roles have been poorly investigated. Here we describe a phospholipase family antibacterial effector immunity pair from

Pseudomonas aeruginosa

and demonstrate that a specific PAAR protein is necessary for the delivery of the effector and its cognate VgrG. Furthermore, the PAAR protein appears to restrict the delivery of other phospholipase effectors that utilise distinct VgrG proteins. We provide further evidence for competition for PAAR protein recruitment to the T6SS apparatus, which determines the identities of the delivered effectors.
LTR_FINDER_parallel: parallelization of LTR_FINDER enabling rapid identification of long terminal repeat retrotransposons
Authors: Ou Shujun , Jiang Ning
Published: August 2019

Annotation of plant genomes is still a challenging task due to the abundance of repetitive sequences, especially long terminal repeat (LTR) retrotransposons. LTR_FINDER is a widely used program for identification of LTR retrotransposons but its application on large genomes is hindered by its single threaded processes. Here we report an accessory program that allows parallel operation of LTR_FINDER, resulting up to 8,500X faster identification of LTR elements. It takes only 72 minutes to process the 14.5 Gb bread wheat (Triticum aestivum) genome in comparison to 1.16 years required by the original sequential version.

Availability

LTR_FINDER_parallel is freely available at https://github.com/oushujun/LTR_FINDER_parallel.

Contact

jiangn@msu.edu
genepanel.iobio - an easy to use web tool for generating disease- and phenotype-associated gene lists
Authors: Ekawade Aditya , Velinder Matt , Ward Alistair , DiSera Tonya , Marth Gabor
Published: August 2019

A comprehensive list of candidate genes that succinctly describe the complete and objective phenotypic features of disease is critical when both ordering genetic testing and when triaging candidate variants in exome and genome sequencing studies. Great efforts have been made to curate gene:disease associations both in academic research and commercial gene testing settings. However, many of these valuable resources exist as islands and must be used independently, generating static, single-resource gene:disease association lists. To more effectively utilize these resources we created genepanel.iobio (https://genepanel.iobio.io), an easy to use, free and open-source web tool for generating disease- and phenotype-associated gene lists from multiple gene:disease association resources, including the NCBI Genetic Testing Registry (GTR), Phenolyzer, and the Human Phenotype Ontology (HPO). We demonstrate the utility of genepanel.iobio by applying it to complex, rare and undiagnosed disease cases which had reached a diagnostic conclusion. We find that genepanel.iobio is able to correctly prioritize the diagnostic variant in over half of these challenging cases. Importantly, each resource contributed diagnostic value, showing the benefits of this aggregate approach. We expect genepanel.iobio will improve the ease and diagnostic value of generating gene:disease association lists for genetic test ordering and whole genome or exome sequencing variant prioritization.
DeepC: Predicting chromatin interactions using megabase scaled deep neural networks and transfer learning
Authors: Schwessinger Ron , Gosden Matthew , Downes Damien , Brown Richard , Telenius Jelena , Teh Yee Whye , Lunter Gerton , Hughes Jim R.
Published: August 2019

Understanding 3D genome structure requires high throughput, genome-wide approaches. However, assays for all vs. all chromatin interaction mapping are expensive and time consuming, which severely restricts their usage for large-scale mutagenesis screens or for mapping the impact of sequence variants. Computational models sophisticated enough to grasp the determinants of chromatin folding provide a unique window into the functional determinants of 3D genome structure as well as the effects of genome variation.

A chromatin interaction predictor should work at the base pair level but also incorporate large-scale genomic context to simultaneously capture the large scale and intricate structures of chromatin architecture. Similarly, to be a flexible and generalisable approach it should also be applicable to data it has not been explicitly trained on. To develop a model with these properties, we designed a deep neuronal network (deepC) that utilizes transfer learning to accurately predict chromatin interactions from DNA sequence at megabase scale. The model generalizes well to unseen chromosomes and works across cell types, Hi-C data resolutions and a range of sequencing depths. DeepC integrates DNA sequence context on an unprecedented scale, bridging the different levels of resolution from base pairs to TADs. We demonstrate how this model allows us to investigate sequence determinants of chromatin folding at genome-wide scale and to predict the importance of regulatory elements and the impact of sequence variations.
Fronto-striatal oscillations predict vocal output in bats
Authors: Weineck Kristin , García-Rosales Francisco , Hechavarría Julio C.
Published: August 2019

The ability to vocalize is ubiquitous in vertebrates, but neural networks leading to vocalization production remain poorly understood. Here we performed simultaneous, large scale, neuronal recordings in the frontal cortex and dorsal striatum (caudate nucleus) during the production of echolocation and non-echolocation calls in bats. This approach allows to assess the general aspects underlying vocalization production in mammals and the unique evolutionary adaptations of bat echolocation. Our findings show that distinct intra-areal brain rhythms in the beta (12-30 Hz) and gamma (30-80 Hz) bands of the local field potential can be used to predict the bats’ vocal output and that phase locking between spikes and field potentials occurs prior vocalization production. Moreover, the fronto-striatal network is differentially coupled in the theta-band during the production of echolocation and non-echolocation calls. Overall, our results present evidence for fronto-striatal network oscillations in motor action prediction in mammals.
Comparative analysis of CreER transgenic mice for the study of brain macrophages – a case study
Authors: Chappell-Maor Louise , Kolesnikov Masha , Grozovski Jonathan , Kim Jung-Seok , Shemer Anat , Haimon Zhana , Boura-Halfon Sigalit , Masuda Takahiro , Prinz Marco , Jung Steffen
Published: August 2019

Conditional mutagenesis and fate mapping have contributed considerably to our understanding of physiology and pathology. Specifically, Cre recombinase-based approaches allow the definition of cell type-specific contributions to disease development and inter-cellular communication circuits in respective animals models. Here we compared Cx3cr1CreER and Sall1CreER transgenic mice and their use to decipher the brain macrophage compartment as a showcase to discuss recent technological advances. Specifically, we highlight the need to define the accuracy of Cre recombinase expression, as well as strengths and pitfalls of these particular systems that should be taken into consideration when applying these models.
Convolutional neural network model to predict causal risk factors that share complex regulatory features
Authors: Lee Taeyeop , Sung Min Kyung , Lee Seulkee , Yang Woojin , Oh Jaeho , Hwang Seongwon , Ban Hyo-Jeong , Choi Jung Kyoon
Published: August 2019

Major progress in disease genetics has been made through genome-wide association studies (GWASs). One of the key tasks for post-GWAS analyses is to identify causal noncoding variants with regulatory function. Here, on the basis of > 2,000 functional features, we developed a convolutional neural network framework for combinatorial, nonlinear modeling of complex patterns shared by risk variants scattered among multiple associated loci. When applied for major psychiatric disorders and autoimmune diseases, neural and immune features, respectively, exhibited high explanatory power while reflecting the pathophysiology of the relevant disease. The predicted causal variants were concentrated in active regulatory regions of relevant cell types and tended to be in physical contact with transcription factors while residing in evolutionarily conserved regions and resulting in expression changes of genes related to the given disease. We demonstrate some examples of novel candidate causal variants and associated genes. Our method is expected to contribute to the identification and functional interpretation of causal noncoding variants in post-GWAS analyses.
Deep mutational scanning comprehensively maps how Zika envelope protein mutations affect viral growth and antibody escape
Authors: Sourisseau Marion , Lawrence Daniel J.P. , Schwarz Megan C. , Storrs Carina H. , Veit Ethan C. , Bloom Jesse D. , Evans Matthew J.
Published: August 2019

Functional constraints on viral proteins are often assessed by examining sequence conservation among natural strains, but this approach is relatively ineffective for Zika virus because all known sequences are highly similar. Here we take an alternative approach to map functional constraints on Zika virus’s envelope (E) protein by using deep mutational scanning to measure how all amino-acid mutations to the protein affect viral growth in cell culture. The resulting sequence-function map is consistent with existing knowledge about E protein structure and function, but also provides insight into mutation-level constraints in many regions of the protein that have not been well characterized in prior functional work. In addition, we extend our approach to completely map how mutations affect viral neutralization by two monoclonal antibodies, thereby precisely defining their functional epitopes. Overall, our study provides a valuable resource for understanding the effects of mutations to this important viral protein, and also offers a roadmap for future work to map functional and antigenic selection to Zika virus at high resolution.

Importance

Zika virus has recently been shown to be associated with severe birth defects. The virus’s E protein mediates its ability to infect cells, and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino-acid mutations to E protein affected the virus’s ability to grow in cells in the lab and escape from several antibodies. The resulting maps relate changes in the E protein’s sequence to changes in viral function, and therefore provide a valuable complement to existing maps of the physical structure of the protein.
Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjærg syndrome
Authors: Kang Yilin , Anderson Alexander J. , De Souza David P. , Palmer Catherine S. , Fujihara Kenji M. , Stait Tegan , Frazier Ann E , Clemons Nicholas J. , Tull Dedreia , Thorburn David R , McConville Malcolm J. , Ryan Michael T. , Stroud David A. , Stojanovski Diana
Published: August 2019

Human Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.