bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractMicroalgae 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

AbstractDihydroxy-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

Abstract

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

Abstract
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

Abstract

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

Abstract

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.
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

Abstract
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.
Precision medicine in atopic diseases
Authors: Cianferoni Antonella , Annesi-Maesano Isabella 
Published: October 2019

Purpose of reviewTo analyze the status of precision medicine in atopic diseases.Recent findingsAtopic 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.SummaryPrecision 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
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.