bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking Social Cohesion to Task: Perceptions of Transgender Military Inclusion and Concepts of Cohesion
Authors: Spindel Jennifer , Ralston Robert
Published: October 2019

Recent political debates over the inclusion of transgender servicemembers in the US military center around the impact such inclusion will have on unit cohesion and effectiveness. Missing from the debate, however, are the perceptions of those who do the soldiering. What are their perceptions of cohesion? Do they, like political leaders and the general public, believe unit cohesion leads to military effectiveness? In other words, how much does the narrative at the elite level—that insists excluding minority groups is a military necessity—match the perceptions of those who serve? Drawing on an original survey of 151 current and former members of the US military, our results suggest that servicemembers’ perceptions mirror those in the general public: political ideology is correlated with beliefs that minority groups disrupt unit cohesion. We find that conservatives are more likely to believe that the inclusion of transgender soldiers will negatively impact cohesion and undermine unit effectiveness. Moreover, conservatives are more likely to endorse a conceptualization of cohesion that hinges on the social—“people like me” or “band of brothers”—dynamics of cohesion rather than more professional, task-oriented conceptions of cohesion. However, military experience affects these perceptions: respondents with combat experience, who held/hold a higher rank, and who are currently serving are more likely to endorse a task-based conception of cohesion that ties cohesion to professionalism and competence, rather than social identity.
Spinal subdural hygroma as a post-operative complication in revision spine fusion: a case report
Authors: Nentwig Michelle J , Whitaker Camden M , Yang Shang-You
Published: October 2019

Lumbar spine fusion has become a common and effective procedure in orthopedic practice, and a spinal subdural hygroma development is a rare complication following this procedure. We report here the case of a revision lumbar spine fusion at levels L4-5, L5-S1, where the patient subsequently developed cauda equina syndrome 2 days post-operatively. Magnetic resonance imaging (MRI) showed a subdural, extra-arachnoid fluid collection from T12-L2, cephalad to the site of spine fusion. It appears the first case reported a subdural hygroma developed cephalad to the site of spine fusion. When a patient complains of radicular pain along with urinary retention and neurologic deficits post-lumbar spine surgery, cauda equina syndrome possibly caused by subdural hygroma should be considered. This warrants immediate MRI and emergent reoperation to relieve the pressure on the spinal cord may be necessary.
Rhino–orbito–cerebral mucormycosis following penetrating keratoplasty
Authors: Raffa Lina H
Published: October 2019

Rhino–orbito–cerebral mucormycosis (ROCM) is a potentially devastating fungal infection with a significant fatality rate. Early diagnosis and prompt management are crucial to ensure a favorable outcome due to the recognized rapid progression. This case is a rare presentation of ROCM in a patient with uncontrolled diabetes following a corneal transplant. The procedure required early surgical resection in the first 30 hours of hospitalization. The patient received wide-spectrum antibiotics and antifungal treatment and underwent extensive debridement of the necrotic area. A high index of suspicion is needed to diagnose ROCM. Any diabetic patient with sinonasal disease and/or cranial nerve involvement, irrespective of their serum glucose or glycated hemoglobin levels, is a candidate for prompt evaluation to exclude mucormycosis. The rapid evolution of our case highlights the importance of treating ROCM promptly and aggressively.
A statistical view to study the aphorisms in Nahj al-Balaghah
Authors: Tian Yu , Pho Kim-Hung
Published: October 2019

Besides the Holly Quran, Nahj al-Balagha is the main source of literature in Arabian nations, especially for Shia as one of the main branches of the Muslims. Along with literary brilliance, the text of this book covers the broad topics. This research deals with the application of the statistical text and data analysis to extract knowledge from the aphorisms in Nahj al-Balaghah. First, we classify these aphorisms in seven topics. Then, the count of the aphorisms in each category is computed. Finally, the counts of the aphorisms of the categories are compared using the chi-square test and the cluster analysis.
Properties of jet and surrounding material of GW/GRB 170817A
Authors: Ziaeepour Houri
Published: October 2019

We use published data in radio, optical, and X-ray bands to analyse and model afterglows of GW/GRB 170817A. Our analysis is based on a phenomenological gamma-ray burst generator model, which we previously used to study the prompt gamma-ray emission of this important transient. We find a multicomponent model and a few of its variants that are consistent with broad-band ∼1 yr observations of afterglows, once the contribution of kilonova in optical/IR band is taken into account. Considering beaming and off-axis view of relativistic outflows, we interpret the components of the model as approximately presenting the profile of a relativistic structured jet with a rapidly declining Lorentz factor from our line of sight, where it had a Lorentz factor of $\mathcal {O}(100)$, to outer boundaries, where it became a mildly relativistic cocoon with a relative velocity to light of ∼0.4–0.97. Properties of the ultra-relativistic core of the jet obtained here are consistent with conclusions from analysis of the prompt gamma-ray emission. In particular, our results show that after prompt internal shocks the remnant of the jet retained in some extent its internal collimation and coherence. Slow rise of the afterglows can be associated to low density of circumburst material and low column density of the jet. The long distance of external shocks from the merger, which could have been in part responsible for extensive thinning of the jet through expansion and energy dissipation before occurrence of external shocks, is responsible for the peak of emission being at ≳110 d after the merger. We discuss implications of these observations for origin and properties of circumburst material around binary neutron stars. This analysis confirms our previous results showing that an outflow with a Lorentz factor of ∼2–5 cannot explain observed afterglows without an additional X-ray source or significant absorption of optical/IR photons.
MSDB: a comprehensive, annotated database of microsatellites
Authors: Avvaru Akshay Kumar , Sharma Deepak , Verma Archana , Mishra Rakesh K , Sowpati Divya Tej
Published: October 2019

Microsatellites are short tandem repeats of 1–6 nucleotide motifs, studied for their utility as genome markers and in forensics. Recent evidence points to the role of microsatellites in important regulatory functions, and their length polymorphisms at coding regions are linked to various neurodegenerative disorders in humans. Microsatellites show a taxon-specific enrichment in eukaryotic genomes, and their evolution remains poorly understood. Though other databases of microsatellites exist, they fall short on several fronts. MSDB (MicroSatellite DataBase) is a collection of >4 billion microsatellites from 37 680 genomes presented in a user-friendly web portal for easy, interactive analysis and visualization. This is by far the most comprehensive, annotated, updated database to access and analyze microsatellite data of multiple species. The features of MSDB enable users to explore the data as tables that can be filtered and exported, and also as interactive charts to view and compare the data of multiple species simultaneously. Its modularity and architecture permit seamless updates with new data, making it a powerful tool and useful resource to researchers working on this important class of DNA elements, particularly in context of their evolution and emerging roles in genome organization and gene regulation.
A novel and translational role for autophagy in antisense oligonucleotide trafficking and activity
Authors: Ochaba Joseph , Powers Andrew F , Tremble Kaitlyn A , Greenlee Sarah , Post Noah M , Matson John E , MacLeod A Robert , Guo Shuling , Aghajan Mariam
Published: October 2019

Endocytosis is a mechanism by which cells sense their environment and internalize various nutrients, growth factors and signaling molecules. This process initiates at the plasma membrane, converges with autophagy, and terminates at the lysosome. It is well-established that cellular uptake of antisense oligonucleotides (ASOs) proceeds through the endocytic pathway; however, only a small fraction escapes endosomal trafficking while the majority are rendered inactive in the lysosome. Since these pathways converge and share common molecular machinery, it is unclear if autophagy-related trafficking participates in ASO uptake or whether modulation of autophagy affects ASO activity and localization. To address these questions, we investigated the effects of autophagy modulation on ASO activity in cells and mice. We found that enhancing autophagy through small-molecule mTOR inhibition, serum-starvation/fasting, and ketogenic diet, increased ASO-mediated target reduction in vitro and in vivo. Additionally, autophagy activation enhanced the localization of ASOs into autophagosomes without altering intracellular concentrations or trafficking to other compartments. These results support a novel role for autophagy and the autophagosome as a previously unidentified compartment that participates in and contributes to enhanced ASO activity. Further, we demonstrate non-chemical methods to enhance autophagy and subsequent ASO activity using translatable approaches such as fasting or ketogenic diet.
Minimally Invasive Injection to the Phrenic Nerve in a Porcine Hemidiaphragmatic Paralysis Model: A Pilot Study
Authors: Texakalidis Pavlos , Tora Muhibullah S , Canute Skyler , Hardcastle Nathan , Poth Kelly , Donsante Anthony , Federici Thais , Javidfar Jeffrey , Boulis Nicholas M
Published: October 2019

BACKGROUND

Neurodegenerative diseases and spinal cord injury can affect respiratory function often through motor neuron loss innervating the diaphragm. To reinnervate this muscle, new motor neurons could be transplanted into the phrenic nerve (PN), allowing them to extend axons to the diaphragm. These neurons could then be driven by an optogenetics approach to regulate breathing. This type of approach has already been demonstrated in the peripheral nerves of mice. However, there is no established thoracoscopic approach to PN injection. Also, there is currently a lack of preclinical large animal models of diaphragmatic dysfunction in order to evaluate the efficacy of potential treatments.

OBJECTIVE

To evaluate the feasibility of thoracoscopic drug delivery into the PN and to assess the viability of hemidiaphragmatic paralysis in a porcine model.

METHODS

Two Landrace farm pigs underwent a novel procedure for thoracoscopic PN injections, including 1 nonsurvival and 1 survival surgery. Nonsurvival surgery involved bilateral PN injections and ligation. Survival surgery included a right PN injection and transection proximal to the injection site to induce hemidiaphragmatic paralysis.

RESULTS

PN injections were successfully performed in both procedures. The animal that underwent survival surgery recovered postoperatively with an established right hemidiaphragmatic paralysis. Over the 5-d postoperative period, the animal displayed stable vital signs and oxygenation saturation on room air with voluntary breathing.

CONCLUSION

Thoracoscopic targeting of the porcine PN is a feasible approach to administer therapeutic agents. A swine model of hemidiaphragmatic paralysis induced by unilateral PN ligation or transection may be potentially used to study diaphragmatic reinnervation following delivery of therapeutics.
Steering elementary steps towards efficient alkaline hydrogen evolution via size-dependent Ni/NiO nanoscale heterosurfaces
Authors: Zhao Lu , Zhang Yun , Zhao Zhonglong , Zhang Qing-Hua , Huang Lin-Bo , Gu Lin , Lu Gang , Hu Jin-Song , Wan Li-Jun
Published: October 2019

Alkaline hydrogen evolution reaction (HER), consisting of Volmer and Heyrovsky/Tafel steps, requires extra energy for water dissociation, leading to more sluggish kinetics than acidic HER. Despite the advances in electrocatalysts, how to combine active sites to synergistically promote both steps and understand the underlying mechanism remain largely unexplored. Here, Density Functional Theory (DFT) calculations predict that NiO accelerates the Volmer step while metallic Ni facilitates the Heyrovsky/Tafel step. A facile strategy is thus developed to control Ni/NiO heterosurfaces in uniform and well-dispersed Ni-based nanocrystals, targeting both reaction steps synergistically. By systematically modulating the surface composition, we find that steering the elementary steps through tuning the Ni/NiO ratio can significantly enhance alkaline HER activity, and Ni/NiO nanocrystals with a Ni/NiO ratio of 23.7% deliver the best activity, outperforming other state-of-the-art analogues. The results suggest that integrating bicomponent active sites for elementary steps is effective for promoting alkaline HER, but they have to be balanced.
Potential-tuned selective electrosynthesis of azoxy-, azo- and amino-aromatics over a CoP nanosheet cathode
Authors: Chong Xiaodan , Liu Cuibo , Huang Yi , Huang Chenqi , Zhang Bin
Published: October 2019

Azoxy-, azo- and amino-aromatics are among the most widely used building blocks in materials science pharmaceuticals and synthetic chemistry, but their controllable and green synthesis has not yet been well established. Herein, a facile potential-tuned electrosynthesis of azoxy-, azo- and amino-aromatics via aqueous selective reduction of nitroarene feedstocks over a CoP nanosheet cathode is developed. A series of azoxy-, azo- and amino-compounds with excellent selectivity, good functional group tolerance and high yields are produced by applying different bias input. The synthetically significant and challenging asymmetric azoxy-aromatics can be controllably synthesized in moderate to good yields. The use of water as the hydrogen source makes this strategy remarkably fascinating and promising. In addition, deuterated aromatic amines with a high deuterium content can be readily obtained by using D2O. By pairing with anodic oxidation of aliphatic amines to nitriles, synthetically useful building blocks can be simultaneously produced in a CoP||Ni2P two-electrode electrolyzer. Only 1.25 V is required to achieve a current density of 20 mA cm−2, which is much lower than that of overall water splitting (1.70 V). The paired oxidation and reduction reactions can also be driven using a 1.5 V battery to synthesize nitrile and azoxybenzene with good yields and selectivity, further emphasizing the flexibility and controllability of our method. This work paves the way for a promising approach to the green synthesis of valuable chemicals through potential-controlled electrosynthesis.
Encapsulating soluble active species into hollow crystalline porous capsules beyond integration of homogeneous and heterogeneous catalysis
Authors: Cai Guorui , Ding Meili , Wu Qianye , Jiang Hai-Long
Published: October 2019

Homogeneous molecular catalysts and heterogeneous catalysts possess complementary strengths, and are of great importance in laboratory/commercial procedures. While various porous hosts, such as polymers, carbons, silica, metal oxides and zeolites, have been used in an attempt to heterogenize homogeneous catalysts, realizing the integration of both functions at the expense of discounting their respective advantages, it remains a significant challenge to truly combine their intrinsic strengths in a single catalyst without compromise. Here, we describe a general template-assisted approach to incorporating soluble molecular catalysts into the hollow porous capsule, which prevents their leaching due to the absence of large intergranular space. In the resultant yolk (soluble)–shell (crystalline) capsules, the soluble yolks can perform their intrinsic activity in a mimetic homogeneous environment, and the crystalline porous shells endow the former with selective permeability, substrate enrichment, size-selective and heterogeneous cascade catalysis, beyond the integration of the respective advantages of homogeneous and heterogeneous catalysts.
Benchmarking HIV Quality Measures in the US OPERA HIV Cohort
Authors: Heglar Robert , Mood Rodney , Priest Julie L , Schulman Kathy L , Fusco Gregory P
Published: October 2019

Background

Quality measures are effective tools to improve patient outreach, retention in care, adherence, and outcomes. This study benchmarks National Quality Forum–endorsed HIV quality measures in a US clinical cohort.

Methods

This observational study utilized prospectively captured data from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) database over 2014−2016 to assess quality measure achievement among patients with HIV in terms of medical visit frequency (#2079), medical visit gaps (#2080), viral suppression (#2082), and antiretroviral therapy (ART) prescriptions (#2083). The proportion of patients meeting each measure was calculated. Generalized estimating equations assessed trends in measure achievement.

Results

The OPERA sample included 23 059−42 285 patients with similar demographics and characteristics across measurement periods. Overall, 62%−66% of patients met the visit frequency measure (#2079), 81%−85% had no gaps between visits (#2080), 71%−73% achieved viral suppression (#2082), and 92%−94% were prescribed ART (#2083). The adjusted odds of achieving viral suppression and being prescribed ART increased over time by 3% and 19%, respectively, despite a significant decline in patient engagement (16% for #2079, 25% for #2080). Patients <30 years of age were significantly less likely to meet all measures than older patients (P < .0001), with particularly low levels of engagement. Measure achievement also varied by gender, ethnicity, region, and select clinical characteristics.

Conclusions

Despite gains in the rate of ART prescription and viral suppression, there remains room for improvement in the care of patients with HIV. Strategies for quality improvement may be more effective if tailored by age group.
The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015–2017
Authors: Ellis Jayne , Bangdiwala Ananta S , Cresswell Fiona V , Rhein Joshua , Nuwagira Edwin , Ssebambulidde Kenneth , Tugume Lillian , Rajasingham Radha , Bridge Sarah C , Muzoora Conrad , Meya David B , Boulware David R
Published: October 2019

Background

Central nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%–25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving.

Methods

We prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures.

Results

We screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person.

Conclusions

Despite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics.
Formation of Spherical Palmelloid Colony with Enhanced Lipid Accumulation by Gel Encapsulation of Chlamydomonas debaryana NIES-2212
Authors: Yoshitomi Toru , Kaminaga Saeko , Sato Naoki , Toyoshima Masakazu , Moriyama Takashi , Yoshimoto Keitaro
Published: October 2019

Microalgae such as Chlamydomonas reinhardtii accumulate triacylglycerol (TAG), which is a potential source of biofuels, under stress conditions such as nitrogen deprivation, whereas Chlamydomonas debaryana NIES-2212 has previously been identified and characterized as one of the rare species of Chlamydomonas, which massively accumulates TAG in the stationary phase without external stress. As the high density of the cells in the stationary phase was supposed to act as a trigger for the accumulation of TAG in C. debaryana, in this study, C. debaryana was encapsulated in a Ca2+-alginate gel for the culture with high cell density. We discovered that the growth of the encapsulated cells resulted in the formation of spherical palmelloid colonies with high cell density, where daughter cells with truncated flagella remained wrapped within the mother cell walls. Interestingly, gel encapsulation markedly promoted proliferation of C. debaryana cells, and the encapsulated cells reached the stationary phase earlier than that of the free-living cells. Gel encapsulation also enhanced TAG accumulation. Gene expression analysis revealed that two genes of acyltransferases, DGAT1 and DGTT3, were upregulated in the stationary phase of free-living C. debaryana. In addition, the gene expression of these acyltransferases increased earlier in the encapsulated cells than that in the free-living cells. The enhanced production of TAG by alginate gel encapsulation was not found in C. reinhardtii which is known to use a different repertoire of acyltransferases in lipid accumulation.
Attempts to develop an enzyme converting DHIV to KIV
Authors: Oki Kenji , Lee Frederick S , Mayo Stephen L
Published: October 2019

Dihydroxy-acid dehydratase (DHAD) catalyzes the dehydration of R-2,3-dihydroxyisovalerate (DHIV) to 2-ketoisovalerate (KIV) using an Fe-S cluster as a cofactor, which is sensitive to oxidation and expensive to synthesize. In contrast, sugar acid dehydratases catalyze the same chemical reactions using a magnesium ion. Here, we attempted to substitute the high-cost DHAD with a cost-efficient engineered sugar acid dehydratase using computational protein design (CPD). First, we tried without success to modify the binding pocket of a sugar acid dehydratase to accommodate the smaller, more hydrophobic DHIV. Then, we used a chemically activated substrate analog to react with sugar acid dehydratases or other enolase superfamily enzymes. Mandelate racemase from Pseudomonas putida (PpManR) and the putative sugar acid dehydratase from Salmonella typhimurium (StPutD) showed beta-elimination activity towards chlorolactate (CLD). CPD combined with medium-throughput selection improved the PpManR kcat/KM for CLD by four-fold. However, these enzyme variants did not show dehydration activity towards DHIV. Lastly, assuming phosphorylation could also be a good activation mechanism, we found that mevalonate-3-kinase (M3K) from Picrophilus torridus (PtM3K) exhibited adenosine triphosphate (ATP) hydrolysis activity when mixed with DHIV, indicating phosphorylation activity towards DHIV. Engineering PpManR or StPutD to accept 3-phospho-DHIV as a substrate was performed, but no variants with the desired activity were obtained.
Serial Casting of the Ankle and Knee in a Child With Vascular Anomaly of the Calf Musculature: A Case Report
Authors: Peyton Colleen
Published: October 2019

Background and Purpose

Contracture and toe-walking in children due to vascular anomaly of the calf musculature is rarely described, and there is limited evidence regarding treatment. The purpose of this case is to describe the novel use of serial casting, combining the knee and ankle, to reduce contracture in a child with hemangioma of the calf.

Case Description

An 11-year-old girl received 12 casts of the ankle and knee, followed by custom orthotics, to address chronic contracture and gait impairments caused by a vascular anomaly in the posterior compartment of the lower extremity.

Outcomes

After casting, the patient had fully restored knee range of motion and improved ankle range of motion by 45 degrees. She received custom orthotics and maintained her range of motion 4 months after casting.

Discussion

Serial casting of the knee and ankle may be a useful alternative to surgical lengthenings in patients with chronic contractures caused by vascular anomalies of the lower extremity.
Inhibition of the negative effect of high glucose on osteogenic differentiation of bone marrow stromal cells by silicon ions from calcium silicate bioceramics
Authors: Dong Xixi , Wang Xiaoya , Xing Min , Zhao Cancan , Guo Bin , Cao Junkai , Chang Jiang
Published: October 2019

Human bone marrow stem cells (hBMSCs) are exploited for miscellaneous applications in bone tissue engineering where they are mainly used as seed cells. However, high glucose (HG) environment has negative impacts on the proliferation and osteogenic differentiation of hBMSCs, thus reducing the bone formation in diabetic patients. In our former research works, we discovered that silicon (Si) ions extracted from silicate-based bioceramics are able to stimulate the proliferation and osteogenic differentiation of hBMSCs under normal culture condition. This study aimed to investigate if Si ions could prevent HG-induced inhibition of proliferation and osteogenesis of hBMSCs. We found that 2.59 ppm concentration of Si ions promoted the proliferation of hBMSCs under HG condition. The results from alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time PCR analysis of osteogenic genes (BMP2, RUNX2, ALP, COL1 and OCN) demonstrated that the 15.92 ppm concentration of Si ions prevented HG-induced inhibition of the osteogenic differentiation of hBMSCs. Moreover, application of Si ions reduced the level of reactive oxygen species in HG-treated hBMSCs. In HG-treated hBMSCs following 15.92 ppm Si ions treatment, activation of BMP2/SMAD signaling pathway was detected, as indicated by the increased expression of BMP2 receptors and its downstream genes such as SMAD1, SMAD4 and SMAD5. Taken together, we provide evidence that the specific concentration of Si ions compensated HG-induced inhibition of proliferation and osteogenic differentiation of hBMSCs through antioxidant effect and modulation of BMP2/SMAD pathway. The results suggest that silicate-based bioceramics might be good scaffold biomaterials for bone engineering applications in diabetes patients.
P05 A national survey of clinical practice of corticosteroid use in newly diagnosed or flaring cases of juvenile idiopathic arthritis across the UK
Authors: Jones Ashley , Clayton Dannii , Nkhoma Gloria , Sherratt Frances , Peak Matthew , Ramanan Athimalaipet , Rooney Madeleine , Foster Helen , Stones Simon , McErlane Flora , Moitt Tracy , Roper Louise , Young Bridget , Beresford Michael , Baildam Eileen
Published: October 2019

Background

Background Corticosteroids (CS) are widely used for rapid-action or induction treatment in children and young people (CYP) with juvenile idiopathic arthritis (JIA). Given a lack of evidence base on CS induction regimen for CYP with JIA, and since criteria for choosing CS are based on healthcare professional (HCP) preference, further research is needed (1).

Methods

A national electronic survey was undertaken among HCPs across the UK as part of the Steroid Induction Regimen for Juvenile Idiopathic Arthritis (SIRJIA) study. We aimed to establish the opinions of HCPs current practice regarding the clinical criteria for commencing CS treatment

Results

A total of 39 (24%) responses were received from 162 HCPs. These included 22 (56%) NHS consultants, five (13%) grid trainees, eight (21%) clinical nurse specialists and four other HCPs (10%).

The most common treatments newly diagnosed JIA or a disease flare were intra-articular IACS or a combination of DMARDs and IAS (except for systemic JIA and oligoarticular JIA). The majority of HCPs 17 would treat new and flaring CYP the same with 53% choosing a different regime or not answering.

The key criteria HCPs used for commencing CS and choosing route of administration were rapid induction of remission (31 (89%)), high disease activity (31 (89%)), severity of systemic JIA (30 (86%)) and level of inflammation (28 (80%)), see Table 1. The main determinants of route of administration was disease severity disease subtype.

The majority of HCPs (52-72%) would consider entering CYP with JIA into a trial randomising to modes of administration.

P14 Table 1 Reasons of CS Choice Number N = 39 Percentage % High Disease Activity 35 89.7 Rapid induction of remission 34 87.18 Severity of Systemic JIA 34 87.18 Level of inflammation 32 82.5 Severe Uveitis 30 76.92 JIA subtype 27 68.21 Targeting Specific Joints 26 66.67 Level of Disability 18 46.15 Level of pain 16 41.03 Long-standing Disease 11 28.1 Patient reluctance to take DMARDS 8 20.5

Conclusion

The results from this national survey of clinical practice showed varying practices in the management of new CYP with JIA and those that are flaring. The majority of HCPs who completed this survey, indicated that they would be prepared to consider entering CYP into a trial that randomised to the four CS delivery methods.

Conflicts of Interest

The authors declare no conflicts of interest.
P18 Audit on pre-methotrexate screening in a paediatric rheumatology centre
Authors: Foster Rebecca , Deepak Samundeeswari , Warrier Kishore , Rangaraj Satyapal , Camina Nikki
Published: October 2019

Background

The BSPAR section council consensus-based guidance is the most widely used guideline on the use of methotrexate. This recommends that varicella immunity status is checked prior to commencing methotrexate and to consider immunisation if the child is non-immune. It also suggests considering checking measles status and testing for TB in high risk patients. We aim to evaluate our practice of screening paediatric rheumatological patients prior to commencing them on methotrexate. All patients in our centre have methotrexate teaching with a clinical nurse specialist prior to commencing treatment.

Methods

This study included paediatric patients who were prescribed methotrexate in all forms (subcutaneous, intravenous and orally) for rheumatological conditions and uveitis during a 2-year period (2016 – 2018) regardless of when it was first commenced. Digital health records were accessed to obtain the data retrospectively. Patients were excluded if they had been started on methotrexate prior to joining our centre, or were lost to follow up during the study period or if the required data was unavailable.

Results

123 patients were identified to have been prescribed methotrexate during the 2-year study period and 102 patients were included in the study. 28 patients were commenced on methotrexate during 2016 /17 and others were commenced anytime between 2008 -2015.

91 (89%) patients had their varicella status checked prior to commencing methotrexate and 7 patients were checked after treatment was commenced. It was not checked in 4 patients (1 sample rejected and not repeated). Of those checked 20 patients were non-immune and 16 were vaccinated. 57 patients had had measles serology checked, 31 of these prior to commencing methotrexate. 35 patients had TB Quantiferon checked prior to methotrexate being started and 39 after. There were no positive results and 6 (8%) indeterminate of which 5 were repeated and 4 were negative. Of the indeterminate results 4 samples were taken prior to commencing methotrexate and 2 after.

Conclusion

This study shows that local adherence to checking varicella status prior to commencing methotrexate and vaccinating non-immune patients is good. Routine practice for checking measles, hepatitis and TB is varied. The data was captured over a 2-year period but actually included practice of methotrexate commencement over 9 years and thus time span and change in doctors will have contributed to the variation in practice. We believe some results from outreach clinics were not captured. All four tests are often carried out if it is felt the patient is likely to go on to require biologics. An updated guideline would help streamline the pre-DMARD screening and may limit the number of unnecessary investigations.

Conflicts of Interest

The authors declare no conflicts of interest.
Farm-to-school education grants reach low-income children and encourage them to learn about fruits and vegetables
Authors: Rains Caroline B , Giombi Kristen C , Joshi Anupama
Published: October 2019

Oregon’s Farm to School Education Grant Program reached students in low-income districts, enabled districts to conduct farm to school educational activities, and allowed children to learn about local produce.
Environmental, social, and economic factors related to the intersection of food security, dietary quality, and obesity: an introduction to a special issue of the Translational Behavioral Medicine journal
Authors: Calloway Eric E , Parks Courtney A , Bowen Deborah J , Yaroch Amy L
Published: October 2019

People who live in low-income communities face many social, environmental, and economic barriers that make it difficult for them to access enough healthful foods on a regular basis.
The SNAP-Ed Evaluation Framework: demonstrating the impact of a national framework for obesity prevention in low-income populations
Authors: Naja-Riese Andy , Keller Kimberly J M , Bruno Pamela , Foerster Susan B , Puma Jini , Whetstone Lauren , MkNelly Barbara , Cullinen Kathleen , Jacobs Laurel , Sugerman Sharon
Published: October 2019

The SNAP-Ed Evaluation Framework offers a new suite of evaluation measures toward eliminating disparities that contribute to poor diet, physical inactivity, food insecurity and obesity.
Food insecurity and obesity: research gaps, opportunities, and challenges
Authors: Brown Alison G M , Esposito Layla E , Fisher Rachel A , Nicastro Holly L , Tabor Derrick C , Walker Jenelle R
Published: October 2019

While the link between food insecurity and obesity are well documented in the research literature, more research is needed to better understand underlying mechanisms, associated risks, effective strategies and interventions, and implementation science approaches to mitigate these public health concerns.
Functional analysis of drought and salt tolerance mechanisms of mulberry RACK1 gene
Authors: Liu Changying , Zhu Panpan , Fan Wei , Feng Yang , Kou Min , Hu Jie , Zhao Aichun
Published: October 2019

The receptor for activated C kinase 1 (RACK1) protein acts as a central hub for the integration of many physiological processes in eukaryotic organisms. Plant RACK1 is implicated in abiotic stress responses, but the underlying molecular mechanisms of stress adaptation remain largely unknown. Here, the overexpression of the mulberry (Morus alba L.) RACK1 gene in Arabidopsis decreased tolerance to drought and salt stresses and MaRACK1 overexpression changed expression levels of genes in response to stress and stimuli. We developed a simple and efficient transient transformation system in mulberry, and the mulberry seedlings transiently expressing MaRACK1 were hypersensitive to drought and salt stresses. The expression levels of guanine nucleotide-binding protein (G-protein) encoding genes in mulberry and Arabidopsis were not affected by MaRACK1 overexpression. The interactions between RACK1 and G-proteins were confirmed, and the RACK1 proteins from mulberry and Arabidopsis could not interact with their respective G-proteins, which indicated that RACK1 may regulate stress responses independently of G-proteins. Additionally, MaRACK1 may regulate drought and salt stress tolerances by interacting with a fructose 1, 6-bisphosphate aldolase. Our findings provide new insights into the mechanisms underlying RACK1 functions in abiotic stress responses and important information for their further characterization.
Estrogen‐related receptor β activation and isoform shifting by cdc2‐like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma
Authors: Tiek Deanna M. , Khatib Subreen A. , Trepicchio Colin J. , Heckler Mary M. , Divekar Shailaja D. , Sarkaria Jann N. , Glasgow Eric , Riggins Rebecca B.
Published: October 2019

Glioblastoma (GBM; grade 4 glioma) is a highly aggressive and incurable tumor. GBM has recently been characterized as highly dependent on alternative splicing, a critical driver of tumor heterogeneity and plasticity. Estrogen‐related receptor β (ERR‐β) is an orphan nuclear receptor expressed in the brain, where alternative splicing of the 3' end of the pre‐mRNA leads to the production of 3 validated ERR‐β protein products: ERR‐β short form (ERR‐βsf), ERR‐β2, and ERR‐β exon 10 deleted. Our prior studies have shown the ERR‐β2 isoform to play a role in G2/M cell cycle arrest and induction of apoptosis, in contrast to the function of the shorter ERR‐βsf isoform in senescence and G1 cell cycle arrest. In this study, we sought to better define the role of the proapoptotic ERR‐β2 isoform in GBM. We show that the ERR‐β2 isoform is located not only in the nucleus but also in the cytoplasm. ERR‐β2 suppresses GBM cell migration and interacts with the actin nucleation‐promoting factor cortactin, and an ERR‐β agonist is able to remodel the actin cytoskeleton and similarly suppress GBM cell migration. We further show that inhibition of the splicing regulatory cdc2‐like kinases in combination with an ERR‐β agonist shifts isoform expression in favor of ERR‐β2 and potentiates inhibition of growth and migration in GBM cells and intracranial tumors.—Tiek, D. M., Khatib, S. A., Trepicchio, C. J., Heckler, M. M., Divekar, S. D., Sarkaria, J. N., Glasgow, E., Riggins, R. B. Estrogen‐related receptor β activation and isoform shifting by cdc2‐like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma. FASEB J. 33, 13476–13491 (2019). www.fasebj.org
Precision medicine in atopic diseases
Authors: Cianferoni Antonella , Annesi-Maesano Isabella
Published: October 2019

Purpose of review

To analyze the status of precision medicine in atopic diseases.

Recent findings

Atopic diseases are increasingly recognized as heterogeneous in nature and they can be quite different in severity, response to therapy, triggers, genetic back ground, ancestral risk and type of inflammation. This significant variability in the landscape of atopic diseases is not reflected in the common treatment guidelines that follow ‘one fits all’ approach for their management. Such an approach is largely based on minimal ‘phenotype’ elements, such as severity of disease and response to therapy and does not reflect the information accumulate in the last 20 years about particular pathogenic pathways (endotypes) leading to disease (phenotypes) based on biomolecular analysis of the single individuals. Accumulating data have defined asthma allergic rhinitis, food allergy based on their endotypes and clinically relevant phenotypes. In general, atopic diseases can be largely classified as high or low Th2 inflammatory status, which may explain the severity and response to therapy.

Precision medicine is aiming to use known endotype phenotype to guide specific individualized treatment. The work aimed in deep characterization of diseases to guide the disease management is crucial in light of the availability of ever more precise treatment able to target specific pathways.
Mechanical Analysis of Notch-Free Pre-Bent Rods for Spinal Deformity Surgery
Authors: Yamada Katsuhisa , Sudo Hideki , Iwasaki Norimasa , Chiba Akihiko
Published: October 2019

Study Design.

Experimental study of spinal rod as per the American Society for Testing Materials (ASTM) F2193 methodology for static and dynamic four-point bending.

Objective.

The hypotheses underlying this study were that the notch-free, curved rod would have a significantly higher ultimate load and fatigue strength compared with conventional notched curved rods. This study aimed to analyze the mechanical properties of notch-free curved rods compared with conventional notched rods.

Summary of Background Data.

The goal of instrumented spinal fusion in the management of spinal deformities is to realign the spine and maintain the correction and stability in order to obtain arthrodesis. Although rod curvature could play an important role, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength.

Methods.

Commercially produced titanium alloy (ϕ6.0 mm) and cobalt chromium alloy (ϕ5.5 mm) spinal rods were assessed by four-point bending tests in accordance with the ASTM F2193.

Results.

Static four-point bending tests for the curved spinal rods showed that cobalt chromium alloy rods had significantly higher stiffness compared with titanium alloy rods. Notch-free cobalt chromium alloy rods had a significantly higher ultimate load than the conventional notched cobalt chromium alloy and titanium alloy rods. The dynamic four-point bending test showed that force/displacement at a minimum force at 2,500,000 cycles was larger in the notch-free cobalt chromium alloy rod than in the notched cobalt chromium alloy rod.

Conclusion.

The notch-free curved cobalt chromium alloy rod is likely to maintain its curvature after spinal deformity surgery with a decreased risk of breakage and could overcome the problems of the conventional notched rod such as breakage and spring-back.

Level of Evidence: N/A
Pronounced clinical response following the oncolytic vaccinia virus GL-ONC1 and chemotherapy in a heavily pretreated ovarian cancer patient
Authors: Mori Kristina M. , Giuliano Peter D. , Lopez Katrina L. , King Monica M. , Bohart Randy , Goldstein Bram H.
Published: October 2019

Heavily pretreated ovarian cancer patients become progressively chemoresistant, and thereafter, only scant treatments potentially accord reasonable, albeit limited clinical efficacy. We describe a case involving a 67-year-old ovarian cancer patient who underwent multiple lines of chemotherapy and presented with recurrent disease and a CA-125 of 4112 U/mL. Thenceforth, she was treated with GL-ONC1 oncolytic viral therapy that was administered laparoscopically in accordance with a clinical trial. The patient subsequently received chemotherapy and during the fourth cycle, her CA-125 decreased to 99 U/mL; moreover, a computed tomography scan of the pelvis exhibited significant disease reduction. Viral therapy hypothetically confers significant promise in the treatment of recurrent ovarian cancer, especially in patients who remain unresponsive to traditional medications.
A Matter of Comprehensive Informed Consent
Authors: Dalwadi Shraddha M. , Savjani Ricky R. , Bernicker Eric H. , Butler Edward B. , Teh Bin S. , Farach Andrew M.
Published: October 2019

Background:

Although lobectomy is the standard of care in stage I non–small cell lung cancer (NSCLC), medical comorbidities increase surgical risk in elderly patients. No population-based studies compare short-term mortality (STM) for surgery (STM-S), radiation (STM-R), and observation (STM-O) in elderly patients with stage I NSCLC.

Methods:

A total of 60,466 biopsy-proven stage I NSCLC cases diagnosed between 2004 and 2012 were retrieved from the Surveillance, Epidemiology, and End Results Program. Patient characteristics were compared using χ2 test. Age was divided into 5-year subsets (60 to 64 to 90+ y) for analysis. Similar to other series, STM was defined as death within 2 months of diagnosis. Univariate and multivariate analysis for STM was performed using odds ratio, Kaplan-Meier actuarial method, and Cox proportional hazard ratio.

Results:

In younger patients, STM-S rates are lower compared with STM-R (1.6% vs. 3.4% in patients 60 to 64 y, P<0.001). However, STM-S rates surpass STM-R with increasing age (up to 8.1% vs. 2.3% in patients 90+ y, P<0.001) becoming significant in the 75- to 79-year age group (4.7% vs. 2.2%, P<0.001). There is an inflection point in the 65- to 69-year age group where STM-S and STM-R rates are similar (2.6% vs. 3.0%, P=0.090). STM for observation reflected the poor health of this cohort with high STM rates in all age groups (19.5% for age 60 to 64 y to 25.3% for age 90+ y, P=0.005). Sex, race, Hispanic ethnicity, age group, and treatment were associated with higher STM on the multivariable analysis (all P<0.001).

Conclusion:

STM in elderly stage I NSCLC patients treated with surgery increases with advancing age but remains stable for patients receiving radiation. Given the success of stereotactic body radiation therapy, radiation should be considered for patients with high STM risk associated with surgery.
Reconstruction of Large Transmural Nasal Defects With a Nasolabial Turnover Interpolation Flap
Authors: Lane Joshua E. , Bob Hsia Ling-Lun , Merritt Bradley G.
Published: October 2019

BACKGROUND

Reconstruction of large nasal surgical defects often warrant the use of mucosal flaps to repair the inner lining. This often presents a challenge for surgical reconstruction.

OBJECTIVE

To describe a unique reconstructive option for the repair of large surgical wounds that necessitate mucosal nasal lining.

MATERIALS AND METHODS

This study is a retrospective review of 10 patients who underwent surgical reconstruction of large nasal and/or heminasal surgical defects following Mohs micrographic surgery. A nasolabial turnover interpolation flap was used to repair missing nasal mucosal lining, coupled with a cutaneous flap which typically involved a paramedian forehead flap. The duration of follow-up was 8 months. An aesthetic and functional surgical outcomes measure was used to assess the final repair.

RESULTS

Favorable aesthetic outcomes were obtained in all patients and without need of revision surgery by the use of a nasolabial turnover interpolation flap.

CONCLUSION

The nasolabial turnover interpolation flap offers a reliable and effective method of repair for large transmural nasal surgical wounds. We typically paired this nasal lining flap with a paramedian forehead flap with reliable and aesthetic outcomes. This technique is straightforward, reproducible, and with both good aesthetic and functional outcomes.