bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSP-17. Augmented Drug Delivery for Pediatric Diffuse Midline Glioma using Convection Enhanced Delivery
Authors: Souweidane Mark M 
Published: June 2022

Abstract
Convection enhanced delivery (CED), an alternative to systemic chemotherapy, spans nearly two decades of clinical experience. The application of CED in pediatric neuro-oncology has been mainly used in children with DMG. This exploratory period is highlighted by widely variable features including procedural technique, disease extent, device interface, infusion parameters, and therapeutic agent. This presentation is meant to critically assess if CED for DMG is a logical therapeutic strategy. Most convincing to the perpetuation of this platform is the reproducible demonstration of augmented drug delivery. Post-treatment ratios of intralesional to systemic drug concentrations consistently exceed 1000. CED in the brain stem satisfies a desirable goal of CNS drug delivery: achieving high target tissue drug concentrations while avoiding systemic exposure. Surgical targeting of the brain stem and cannula deployment are solidly established as safe and accurate. Catheter insertion complications such as clinically relevant hemorrhage, CNS infection, and neurological injury are exceptional. Likewise, targeting error is on a millimeter scale with infrequent need for catheter repositioning. The use of intrinsic MRI signals, direct drug labeling, and surrogate tracers have all been used for measuring distribution of the infusion. The experience using a radio-labelled theragnostic agent has provided detailed distribution and dosimetry information. Based on estimates of tumor and hence target volumes, a rationale goal is to reach volumes of distribution in the range of 15-25 cm3. Optimizing this goal has focused on surgical targeting, infusion duration, and multiple treatment plans. Computational predictive modeling is being employed as a preoperative adjunct for maximizing distribution. Experience in DMG thus far has been limited to feasibility and safety studies. There is a paucity of Phase 2 studies and hence outcome has not yet been rigorously tested. Anecdotal increase in survival and long-term survival has been reproducibly reported. Of particular interest are the occasional cases of children exhibiting late out-of-treatment field and even extra-CNS recurrence. Available data is convincing that CED should serve be further explored in future clinical trials designs for children with DMG. Important features of any Phase 2 study design however should include monitoring of drug distribution, measures of tumor coverage, early response monitoring techniques, and possibly combination with whole CNS axis treatment.
Management of neurofibromatosis type 1-associated plexiform neurofibromas
Authors: Fisher Michael J , Blakeley Jaishri O , Weiss Brian D , Dombi Eva , Ahlawat Shivani , Akshintala Srivandana , Belzberg Allan J , Bornhorst Miriam , Bredella Miriam A , Cai Wenli , Ferner Rosalie E , Gross Andrea M , Harris Gordon J , Listernick Robert , Ly Ina , Martin Staci , Mautner Victor F , Salamon Johannes M , Salerno Kilian E , Spinner Robert J , Staedtke Verena , Ullrich Nicole J , Upadhyaya Meena , Wolters Pamela L , Yohay Kaleb , Widemann Brigitte C 
Published: June 2022

Abstract
Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts.
Isotopic constraints confirm the significant role of microbial nitrogen oxides emissions from the land and ocean environment
Authors: Song Wei , Liu Xue-Yan , Houlton Benjamin Z , Liu Cong-Qiang 
Published: June 2022

Abstract
Nitrogen oxides (NOx, the sum of nitric oxide (NO) and N dioxide (NO2)) emissions and deposition have increased markedly over the past several decades, resulting in many adverse outcomes in both terrestrial and oceanic environments. However, because the microbial NOx emissions have been substantially underestimated on the land and unconstrained in the ocean, the global microbial NOx emissions and their importance relative to the known fossil-fuel NOx emissions remain unclear. Here we complied data on stable N isotopes of nitrate in atmospheric particulates over the land and ocean to ground-truth estimates of NOx emissions worldwide. By considering the N isotope effect of NOx transformations to particulate nitrate combined with dominant NOx emissions in the land (coal combustion, oil combustion, biomass burning and microbial N cycle) and ocean (oil combustion, microbial N cycle), we demonstrated that microbial NOx emissions account for 24 ± 4%, 58 ± 3% and 31 ± 12% in the land, ocean and global environment, respectively. Corresponding amounts of microbial NOx emissions in the land (13.6 ± 4.7 Tg N yr−1), ocean (8.8 ± 1.5 Tg N yr−1) and globe (22.5 ± 4.7 Tg N yr−1) are about 0.5, 1.4 and 0.6 times on average those of fossil-fuel NOx emissions in these sectors. Our findings provide empirical constraints on model predictions, revealing significant contributions of the microbial N cycle to regional NOx emissions into the atmospheric system, which is critical information for mitigating strategies, budgeting N deposition and evaluating the effects of atmospheric NOx loading on the world.
Cryptococcal and Histoplasma Antigen Screening Among People With Human Immunodeficiency Virus in Ghana and Comparative Analysis of OIDx Histoplasma Lateral Flow Assay and IMMY Histoplasma Enzyme Immunoassay
Authors: Ocansey Bright K , Otoo Benjamin , Asamoah Isabella , Ganu Vincent , Berko Kofi P , Oladele Oluwakemi , Amankwa Emmanuella A , Opoku-Asare Bismark , Agyei Martin , George Lawrence , Kotey Fleischer C N , Kosmidis Chris , Puplampu Peter , Opintan Japheth A , Denning David W 
Published: June 2022

Abstract

Background
Cryptococcal meningitis (CM) and disseminated histoplasmosis (DH) are common in people with human immunodeficiency virus (PWH) and diagnosed by detecting cryptococcal antigen (CrAg) and Histoplasma antigen (HistoAg), respectively. In Ghana, CM and DH are rarely suspected by clinicians due to limited epidemiological data.

Methods
This study was conducted among PWH in Ghana who are unwell. Sociodemographic and clinical data were collected by questionnaire. Serum and/or urine were screened for CrAg and HistoAg, using IMMY CrAg lateral flow assay (LFA) and IMMY Histoplasma enzyme immunoassay (EIA) kits, respectively, regardless of symptoms. Samples run with IMMY Histoplasma EIA were simultaneously run with Optimum Imaging Diagnostics (OIDx) Histoplasma LFA. Laboratory investigations were conducted by the research team, and diagnosis incorporating clinical assessment, screening, and confirmatory testing results and treatment decisions were made by the clinical team. Treatment and outcome information on CM and DH patients were evaluated.

Results
Overall, 150 participants were recruited. There were 73% (n = 109) females, and the age range was 18–62 years. The prevalence rates of CrAg and HistoAg were 2.7% (4 of 150) and 4.7% (5 of 107), respectively. The OIDx Histoplasma LFA showed a high concordance (98.4%) with the IMMY Histoplasma EIA. All antigen-positive cases by standard tests were diagnosed with CM and DH. Antifungal treatment was given in 5 patients and follow-up revealed 2 deaths and 3 recoveries.

Conclusions
Histoplasmosis among PWH may be more common than previously anticipated and may be more frequent than cryptococcosis in Ghana. The performance of the OIDx Histoplasma LFA should be further explored.
The relationship of the neutron skin thickness to the symmetry energy and its slope
Authors: Suzuki Toshio 
Published: June 2022

Abstract
The neutron skin thickness of asymmetric semi-infinite nuclear matter (δRM) is shown to be a function of the Coulomb energy (Vc), the asymmetry energy coefficient (J), the slope (L) of the asymmetry energy, and the incompressibility coefficient (K), in addition to the Fermi momentum (kF) and the asymmetry parameter (I = (N − Z)/A). The relational formula is derived on the basis of the Hugenholtz–Van Hove theorem in the mean-field (MF) approximation for nuclear matter. Using the formula as a guide, the neutron skin thickness (δR) in 208Pb is examined in the MF models. The apparently spurious linear correlation between L and δR appears through the model-dependent correlation of L with J that is included in the main components of the formula.
Global bifurcation of capillary-gravity dark solitary waves on the surface of a conducting fluid under normal electric fields
Authors: Doak A , Gao T , Vanden-Broeck J -M 
Published: June 2022

Summary
This article is concerned with capillary-gravity waves travelling on the interface of a dielectric gas and a conducting fluid under the effect of a vertical electric field. A boundary integral equation method is employed to compute fully nonlinear steady travelling wave solutions. The global bifurcation diagram of periodic waves, solitary waves, generalised solitary waves and dark solitary waves is presented and discussed in detail.
Dry matter and crude protein degradability of Napier grass (Pennisetum purpureum) silage is affected by fertilization with cow-dung bio-digester slurry and fermentable carbohydrate additives at ensiling
Authors: Rambau Mashudu D , Fushai Felix , Callaway Todd R , Baloyi Joseph J 
Published: June 2022

Abstract
Dry seasons pose a major nutritional constraint on ruminant livestock production in tropical regions, which justifies forage conservation to meet the dry season feed requirement. Napier grass is a tropical forage that is used for silage in South Africa. The present objective was to determine the effects of Napier grass fertilization with bio-digester slurry (BDS) and the inclusion of fermentable carbohydrate additives at ensiling on the chemical composition and ruminal degradability of Napier grass silage. Napier grass was established in 5 × 4 m plots, replicated three times in a completely randomized design, and irrigated weekly with either BDS or water. After 12 weeks, the Napier was cut and ensiled for 90 days in 1-liter glass jars in a 2 (BDS, water) × 4 (no-additive, molasses, brown sugar, and maize meal) factorial arrangement replicated three times. The nutrient composition was determined using standard protocols. The ruminal degradability of dry matter (DM) and crude protein (CP) was determined using the nylon bag technique. Fertilization with BDS increased (P &lt; 0.05) pH and CP and reduced (P &lt; 0.05) fat content of fresh-cut Napier. Additives increased (P &lt; 0.01) silage DM content and reduced (P &lt; 0.01) acid detergent fiber, neutral detergent fiber content. The BDS fertilization with molasses inclusion increased (P &lt; 0.05) silage DM relative to the no-additive and maize meal inclusion, and decreased (P &lt; 0.05) fat content compared to the no-fertilizer, added maize meal silage. Molasses increased silage water-soluble carbohydrate and decreased the NH3-N content (P &lt; 0.05) compared to the no-additive and maize meal treatments. For DM, the BDS fertilized, no additive silage had the least “a” fraction (P &lt; 0.01), while the no BDS, no-additive silage had the least “b” fraction (P &lt; 0.01), with least (P &lt; 0.01) potential degradability (PD) observed for the no BDS, no-additive treatment. Fertilization increased (P &lt; 0.01) effective degradability of DM at outflow rates k = 0.02, 0.05, 0.08, with same effect for molasses and maize meal inclusion. Relative to the control, molasses inclusion increased (P &lt; 0.01) PD of silage CP. In conclusion, our results suggested BDS fertilization of Napier grass ensiling with added readily fermentable carbohydrate substrate, particularly from molasses, induced changes in silage chemical and fermentation characteristics likely to promote better forage preservation and ruminal microbial function.
Water uptake patterns of tropical canopy trees in Borneo: species-specific and temporal variation and relationships with aboveground traits
Authors: Hiiragi Katsuura , Matsuo Naoko , Sakai Shoko , Kawahara Kazuma , Ichie Tomoaki , Kenzo Tanaka , Aurelia Dulce Chung , Kume Tomonori , Nakagawa Michiko 
Published: June 2022

Abstract
Root water uptake depth and its temporal variation are important determinants of tree mortality, resource partitioning and drought resistance; however, their effects on tropical trees remain poorly understood. In this study, we investigated interspecific differences in water uptake depth and its temporal variation using stable isotope analysis and examined the relationships between water uptake depth and aboveground traits in a humid aseasonal tropical rainforest in Borneo. Species-specific differences in water uptake depth were examined for six dominant dipterocarp species. Temporal variation in water uptake depth for various canopy trees was assessed in three periods with different soil moisture conditions. We then examined the relationships between water uptake depth and aboveground traits including wood density, maximum tree height, flowering frequency and growth rate. Dipterocarpus globosus appeared to be more reliant on deep water resources than the other dipterocarp species. Water uptake from the soil layers varied among the three sampling periods. Trees generally utilized deeper soil water during the second driest sampling period, when temperatures were lowest. During the driest and wettest sampling periods, species with higher flowering frequencies tended to preferentially uptake deep soil water. These results suggest that low temperature and soil moisture promote increased deep soil water uptake in the study region. Dynamic relationships between water uptake patterns and aboveground tree traits may be related to resource partitioning among co-existing species.
Diagnostic Utility of Cerebrospinal Fluid Procalcitonin in Neonatal Meningitis
Authors: Nagaraj Meghana , Bandiya Prathik , Jagannatha Bhavana , Shivanna Niranjan , Benakappa Naveen , Bandyopadhyay Tapas 
Published: June 2022

Abstract
We aimed to study the diagnostic utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in neonates with meningitis. All the neonates with sepsis who qualified for lumbar puncture were prospectively evaluated. The neonates were classified into Meningitis and No meningitis group based on predefined criteria. CSF PCT was estimated in these neonates along with cytological and biochemical parameters. A total of 113 neonates were included in the study with 29 in the meningitis group and 84 in the no meningitis group. The median PCT levels were higher in babies with meningitis as compared to those without meningitis [0.194 (0.034–0.534) in meningitis group vs. 0.012 (0.012–0.012) ng/ml in no meningitis group, p &lt; 0.001]. The area under curve for CSF PCT was 0.867 (0.77–0.95) and at a cut-off level of 0.120 ng/ml CSF PCT had a sensitivity of 83%, specificity of 84% and positive and negative predictive likelihood ratios of 5.35 and 0.20, respectively for the diagnosis of meningitis. CSF PCT has a good diagnostic accuracy similar to other parameters in the diagnosis of neonatal meningitis and can be considered as an additional diagnostic marker particularly when CSF culture is negative and cytochemical analysis is inconclusive.
Epidemiological inference from pathogen genomes: A review of phylodynamic models and applications
Authors: Featherstone Leo A , Zhang Joshua M , Vaughan Timothy G , Duchene Sebastian 
Published: June 2022

Abstract
Phylodynamics requires an interdisciplinary understanding of phylogenetics, epidemiology, and statistical inference. It has also experienced more intense application than ever before amid the SARS-CoV-2 pandemic. In light of this, we present a review of phylodynamic models beginning with foundational models and assumptions. Our target audience is public health researchers, epidemiologists, and biologists seeking a working knowledge of the links between epidemiology, evolutionary models, and resulting epidemiological inference. We discuss the assumptions linking evolutionary models of pathogen population size to epidemiological models of the infected population size. We then describe statistical inference for phylodynamic models and list how output parameters can be rearranged for epidemiological interpretation. We go on to cover more sophisticated models and finish by highlighting future directions.
Recombinant Human Nerve Growth Factor for Pediatric Neurotrophic Keratopathy
Authors: Niruthisard Duangratn , Fung Simon S. M. 
Published: June 2022

Abstract:
A 4-year-old boy presented with right neurotrophic corneal ulcer, lagophthalmos, and facial palsy 8 months after neurosurgery for synchronous brain tumors. Initial treatment with topical antibiotics, topical corticosteroids, lubrication, and lateral tarsorrhaphy successfully treated the corneal epithelial defect; however, the cornea continued to demonstrate diffuse epitheliopathy and a dense stromal opacity and remained insensate on Cochet–Bonnet esthesiometry. After a course of topical cenegermin, central corneal sensation normalized, and the corneal epitheliopathy was markedly improved. Two years after the completion of cenegermin, corneal sensation was maintained; there were no recurrences of epithelial defects, and the stromal opacity had markedly improved. In vivo confocal microscopy (IVCM) demonstrated the presence of subbasal corneal innervation. This report highlights the safety and prolonged effects of cenegermin for the treatment of pediatric iatrogenic neurotrophic keratopathy, as evidenced by the clinical course and IVCM.
Preferences for Risks and Benefits of Islet Cell Transplantation for Persons With Type 1 Diabetes With History of Episodes of Severe Hypoglycemia: A Discrete-Choice Experiment to Inform Regulatory Decisions
Authors: Wilson Leslie , Kwok Tiffany , Ma Yanlei , Wong Jenise , Ho Martin , Ionova Yelena , McGrath Maureen , Mueller Monica M. , Gitelman Stephen E. , Irony Telba 
Published: June 2022

Background.
The advisory panel for US Food and Drug Administration (FDA) recently endorsed pancreatic islet cell transplantation (ICT) therapy for suboptimally controlled type 1 diabetes (T1D), and FDA approval is under consideration. An important part of regulatory approval includes the patient perspective, through discrete choice. We developed a discrete-choice instrument and used it to determine how 90 people with T1D weigh the risks and benefits of ICT to inform regulatory decisions.

Methods.
Sawtooth software created a random, full-profile, balanced-overlap experimental design for a measure with 8 attributes of ICT risks/benefits, each with 3 to 5 levels. We asked 18 random task pairs, sociodemographics, diabetes management, and hypoglycemia questions. Analysis was performed using random parameters logistic regression technique.

Results.
The strongest preference was for avoiding the highest chance (15%) of serious procedure-related complications (β = −2.03, P < 0.001). The strongest positive preference was for gaining 5-y insulin independence (β = 1.75, P < 0.001). The desire for 5-y HbA1C-defined clinical treatment success was also strong (β = 1.39, P < 0.001). Subgroup analysis suggested strong gender differences with women showing much higher preferences for all benefits (68% higher for 5-y insulin independence), and men were generally more risk averse than women. Those with high versus low diabetes distress showed 3 times stronger preference for 5-y insulin independence but also twice preference to avoid risks of serious complications.

Conclusions.
Despite showing the most preference for avoiding serious ICT complications, people with T1D had a strong preference for achieving ICT benefits, especially insulin independence. We identified important attributes of ICT and demonstrated that patients are willing to make these trade-offs, showing support for the introduction of ICT.
Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by JAK inhibition
Authors: Chokesuwattanaskul Susama , Alarcon Michele Fresneda , Mangalakumaran Sangeetha , Grosman Rudi , Cross Andrew L , Chapman Elinor A , Mason David , Moots Robert J , Phelan Marie M , Wright Helen L 
Published: June 2022

AbstractNeutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function can be modulated by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors has been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n=6) and people with RA (n=7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h. Metabolites were extracted and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models showed a divergent metabolic pattern in RA neutrophils compared to HC at 0h (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p<0.05). Bacterial killing was not impaired by JAK inhibitors, indicating the effect of JAK inhibitors on neutrophils can inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.