bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts
Authors: Rifai Olivia M , O’Shaughnessy Judi , Dando Owen R , Munro Alison F , Sewell Michael D E , Abrahams Sharon , Waldron Fergal M , Sibley Christopher R , Gregory Jenna M 
Published: July 2023

Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. ALS is on a pathogenetic disease spectrum with frontotemporal dementia, referred to as ALS-frontotemporal spectrum disorder (ALS-FTSD). For mutations associated with ALS-FTSD, such as the C9orf72 hexanucleotide repeat expansion, the molecular factors associated with heterogeneity along this spectrum require further characterization.
Here, using a targeted NanoString molecular barcoding approach, we interrogate neuroinflammatory dysregulation and heterogeneity at the level of gene expression in post-mortem motor cortex tissue from a cohort of clinically heterogeneous C9-ALS-FTSD cases.
We identified 20 dysregulated genes in C9-ALS-FTSD, with enrichment of microglial and inflammatory response gene sets. Two genes with significant correlations to available clinical metrics were selected for validation: FKBP5, a correlate of cognitive function, and brain-derived neurotrophic factor (BDNF), a correlate of disease duration. FKBP5 and its signalling partner, NF-κB, appeared to have a cell type-specific staining distribution, with activated (i.e. nuclear) NF-κB immunoreactivity in C9-ALS-FTSD. Expression of BDNF, a correlate of disease duration, was confirmed to be higher in individuals with long compared to short disease duration using BaseScope™ in situ hybridization. Our analyses also revealed two distinct neuroinflammatory panel signatures (NPS), NPS1 and NPS2, delineated by the direction of expression of proinflammatory, axonal transport and synaptic signalling pathways. We compared NPS between C9-ALS-FTSD cases and those from sporadic ALS and SOD1-ALS cohorts and identified NPS1 and NPS2 across all cohorts. Moreover, a subset of NPS was also able to separate publicly available RNA sequencing data from independent C9-ALS and sporadic ALS cohorts into two inflammatory subgroups.
Importantly, NPS subgroups did not clearly segregate with available demographic, genetic, clinical or pathological features, highlighting the value of molecular stratification in clinical trials for inflammatory subgroup identification. Our findings thus underscore the importance of tailoring therapeutic approaches based on distinct molecular signatures that exist between and within ALS-FTSD cohorts.
Superior Accuracy of Aspergillus Plasma Cell-Free DNA Polymerase Chain Reaction Over Serum Galactomannan for the Diagnosis of Invasive Aspergillosis
Authors: Mah Jordan , Nicholas Veronica , Tayyar Ralph , Moreno Angel , Murugesan Kanagavel , Budvytiene Indre , Banaei Niaz 
Published: July 2023

Abstract

Background
Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice.

Methods
We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan.

Results
Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7–95.7) and 93.1% (121 of 130; 95% CI, 87.4–96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3–82.1) and 89.8% (53 of 59; 95% CI, 79.5–95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9–98.5) in patients with a new diagnosis of IA.

Conclusions
Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA.
Extracting IP parameters of rock samples using machine learning
Authors: He Ziang , Cai Hongzhu , Li Shuai , Xian Jinchi , Hu Xiangyun 
Published: July 2023

SUMMARY
The induced polarization (IP) phenomenon describes the variation of resistivity with frequency and this geophysical method has been widely used to classify rock properties. Various experimental models have been developed to describe the mechanism of IP effect. The model based on the generalized effective-medium theory of induced polarization (GEMTIP) is an extension of the classic Cole–Cole model by considering electromagnetic inductions. Compared to the Cole–Cole model, the GEMTIP model can effectively incorporate rock composition and morphology to provide a more precise complex resistivity response. However, adding one more grain type to the GEMTIP model will result in adding three more parameters to the inversion process. Even for the GEMTIP model with only three-phase spherical grains, seven parameters need to be inverted. In general, the inversion of GEMTIP model with more than three phases is characterized by high uncertainty. Traditional geophysical inversion methods such as global optimization and least-squares optimization have certain limitations in inverting IP parameters. The effectiveness of least-squares optimization algorithm depends on the setting of initial inversion parameters. Efficiently processing massive amounts of data is challenging for both least-squares optimization and global optimization algorithms. Considering the powerful search and generalization capabilities of neural network (NN), we develop a machine learning (ML) approach for efficient inversion of IP parameters based on long short-term memory (LSTM) networks with physical constraints. Compared with traditional methods, ML method can significantly reduce the computational cost and produce reliable inversion results. To validate the effectiveness of ML approach, we first conduct multiple synthetic model studies based on the Cole–Cole and the GEMTIP models, respectively. We then further demonstrate the effectiveness of NNs in recovering IP parameters from rock samples using measured data from man-made and field rock samples. The results show that the developed method can effectively obtain accurate inversion results based on Cole–Cole and GEMTIP models.
Context matters—the phased development of an adaptable food literacy intervention: Up for Cooking
Authors: Harms Lisa S E , van Assema Patricia , Gubbels Jessica S , Gerards Sanne M P L , Linssen Evelyne , Vonken Lieve , Bessems Kathelijne M H H 
Published: July 2023

Abstract
Adapting interventions to the context increases the impact and sustainability of interventions. Literature acknowledges the need to adapt existing interventions and that these adaptations should be clearly reported. However, little is known about how to incorporate adaptation from the beginning. This paper argues that interventions should be developed and adaptations should be made using an ongoing non-linear approach. An action-oriented research approach with feedback loops is proposed. We illustrate this with the development of a food literacy intervention ‘Up for Cooking’ (Dutch: Zin in Koken) and present lessons learned in developing, implementing and studying such adaptable interventions. Interventions should clearly define and differentiate the intervention function and form. Implementers, in turn, should be encouraged to tailor interventions within a form that fits with a specific context. Sufficient time, continuous adaptation based on co-creation, feedback loops and interdisciplinary collaboration are important prerequisites for the development of adaptable interventions.
A mixed-method study of perceptions of cigarette pack inserts among adult smokers from New York and South Carolina exposed as part of a randomized controlled trial
Authors: Hackworth Emily E , Budiongan Julia R , Lambert Victoria C , Kim Minji , Ferguson Stuart G , Niederdeppe Jeff , Hardin James , Thrasher James F 
Published: July 2023

Abstract
While many countries require prominent pictorial health warning labels (PHWLs) on the outside of cigarette packs to communicate the harms of smoking, there is evidence that cigarette pack inserts that contain efficacy messages may enhance the effectiveness of PHWLs. The US Food and Drug Administration (FDA) has regulatory authority to communicate with smokers through inserts. While current labeling regulations do not require inclusion of inserts, the FDA could implement them in the future. This study assesses US smokers’ perceptions of cigarette package inserts at the conclusion of a two-week randomized trial on cigarette labeling where half of participants were exposed to insert messages (two response-efficacy messages and two self-efficacy messages) in their packs. Participants (n = 359) completed a 30- to 60-min interview with both quantitative and qualitative assessments, including measures of recall and perceived message effectiveness (PME) for specific inserts. Correlates of recall and PME were estimated using mixed-effects regression models. Qualitative responses to PME items were analyzed using thematic analysis. Response-efficacy messages had higher PME and recall than self-efficacy messages. People had diverse responses to the inserts, including that they were positive, thought-provoking, and helpful. Reactions to and perceptions of the inserts indicate potential benefits of integrating efficacy messages into labeling policies.
Identifiability of causal effects in test-negative design studies
Authors: Shrier Ian , Stovitz Steven D , Textor Johannes 
Published: July 2023

Abstract
Causal directed acyclic graphs (DAGs) are often used to select variables in a regression model to identify causal effects. Outcome-based sampling studies, such as the ‘test-negative design’ used to assess vaccine effectiveness, present unique challenges that are not addressed by the common back-door criterion. Here we discuss intuitive, graphical approaches to explain why the common back-door criterion cannot be used for identification of population average causal effects with outcome-based sampling studies. We also describe graphical rules that can be used instead in outcome-based sampling studies when the objective is limited to determining if the causal odds ratio is identifiable, and illustrate recent changes to the free online software Dagitty which incorporate these principles.
L
2 norm error estimates of BDF methods up to fifth-order for the phase field crystal model
Authors: Liao Hong-lin , Kang Yuanyuan 
Published: July 2023

Abstract
The well-known backward difference formula (BDF) of the third, the fourth and the fifth orders are investigated for time integration of the phase field crystal model. By building up novel discrete gradient structures of the BDF-$\textrm{k}$ ($\textrm{k}=3,4,5$) formulas, we establish energy dissipation laws at the discrete levels and then obtain a priori solution estimates for the associated numerical schemes; however, we can not build any discrete energy dissipation law for the corresponding BDF-6 scheme because the BDF-6 formula itself does not have any discrete gradient structures. With the help of the discrete orthogonal convolution kernels and Young-type convolution inequalities, some concise $L^{2}$ norm error estimates (with respect to the starting data in the $L^{2}$ norm) are established via the discrete energy technique. To the best of our knowledge, this is the first time such type $L^{2}$ norm error estimates of non-A-stable BDF schemes are obtained for nonlinear parabolic equations. Numerical examples are presented to verify and support the theoretical analysis.
Integral Points on Varieties With Infinite Étale Fundamental Group
Authors: Achenjang Niven T , Morrow Jackson S 
Published: July 2023

Abstract
We study integral points on varieties with infinite étale fundamental groups. More precisely, for a number field $F$ and $X/F$ a smooth projective variety, we prove that for any geometrically Galois cover $\varphi \colon Y \to X$ of degree at least $2\dim (X)^{2}$, there exists an ample line bundle $\mathscr{L}$ on $Y$ such that for a general member $D$ of the complete linear system $|\mathscr{L}|$, $D$ is geometrically irreducible and any set of $\varphi (D)$-integral points on $X$ is finite. We apply this result to varieties with infinite étale fundamental group to give new examples of irreducible, ample divisors on varieties for which finiteness of integral points is provable.
Dynamic modelling predicts lactate and IL-1β as interventional targets in metabolic-inflammation-clock regulatory loop in glioma
Authors: Sharma Shalini , Gowda Pruthvi , Lathoria Kirti , Mitra Mithun K , Sen Ellora 
Published: July 2023

Abstract
In an attempt to understand the role of dysregulated circadian rhythm in glioma, our recent findings highlighted the existence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1β and circadian CLOCK. To further elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this lactate dehydrogenase A (LDHA)-IL-1β-CLOCK/BMAL1 circuit and predicts potential therapeutic targets. The model was calibrated on quantitative western blotting data in two glioma cell lines in response to either lactate inhibition or IL-1β stimulation. The calibrated model described the experimental data well and most of the parameters were identifiable, thus the model was predictive. Sensitivity analysis identified IL-1β and LDHA as potential intervention points. Mathematical models described here can be useful to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in designing effective therapeutic strategies. Our findings underscore the importance of including the circadian clock when developing pharmacological approaches that target aberrant tumour metabolism and inflammation.
Insight box The complex interplay of metabolism-inflammation-circadian rhythm in tumours is not well understood. Our recent findings provided evidence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1β and circadian CLOCK/BMAL1 in glioma. To elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this LDHA-IL-1β-CLOCK/BMAL1 circuit and integrates experimental data to predict potential therapeutic targets. The study employed a multi-start optimization strategy and profile likelihood estimations for parameter estimation and assessing identifiability. The simulations are in reasonable agreement with the experimental data. Sensitivity analysis found LDHA and IL-1β as potential therapeutic points. Mathematical models described here can provide insights to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in identifying effective therapeutic targets.
Trend, prevalence and predictors of successful vaginal birth after caesarean section in Ethiopia: a systematic review and meta-analysis
Authors: Balis Bikila , Bekele Habtamu , Hunde Aboma Diriba , Abdisa Lemesa , Lami Magarsa 
Published: July 2023

AbstractBackgroundVaginal birth after caesarean section (VBAC) is an alternative to a caesarean section (CS) in the absence of repeat or new indications for primary CS. There is a knowledge gap regarding the trend and successful VBAC in Ethiopia. Therefore this systematic review and meta-analysis aimed to assess the trend, pooled prevalence of successful VBAC and its predictors in Ethiopia.MethodsElectronic databases (SCOPUS, CINAHL, Embase, PubMed and Web of Science), Google Scholar and lists of references were used to search works of literature in Ethiopia. Stata version 14 was used for analysis and the odds ratios of the outcome variable were determined using the random effects model. Heterogeneity among the studies was assessed by computing values for I2 and p-values. Also, sensitivity analyses and funnel plots were done to assess the stability of pooled values to outliers and publication bias, respectively.ResultsA total of 12 studies with a sample size of 2080 were included in this study. The overall success rate of VBAC was 52% (95% confidence interval 42 to 65). Cervical dilatation ≥4 cm at admission, having a prior successful vaginal delivery and VBAC were the predictors of successful VBAC.ConclusionsMeta-analyses and sensitivity analyses showed the stability of the pooled odds ratios and the funnel plots did not show publication bias. The pooled prevalence of successful VBAC was relatively low compared with existing evidence. However, the rate was increasing over the last 3 decades, which implies it needs more strengthening and focus to decrease maternal morbidity and mortality by CS complications. Promoting VBAC by emphasizing factors favourable for its success during counselling mothers who previously delivered by CS to enhance the prevalence of VBAC.
Buttons, Devices, and Adults: How Preschool Children Designed an IoT Programming Tool
Authors: Silva Neto Benedito , Rodriguez Carla , Neris Vania 
Published: July 2023

Abstract
Preschool children may interact with the Internet of Things (IoT) devices and program the behavior of these products. However, not much is known about the children’s ideas for a software programming tool. This research aimed at investigating how children aged from 4 to 6 years perceive the programming of IoT devices and, from practice with them, build a prototype of a programming environment for them. To this end, three Participatory Design techniques were adapted and applied to (and with) 30 children. A final prototype was built and its usability was assessed with the participation of six children. Photos and videos collected during the empirical assessment were later analysed using the Content Analysis Method. During the design, children relied on buttons and explicitly represented the IoT devices and adults in the user interfaces. They also adopted a top-down approach to programming IoT devices. Lessons learned for the design of these solutions are discussed.
Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults
Authors: Chang Jack , Liu Jiajun , Alshaer Mohammad H , Venugopalan Veena , Maranchick Nicole , Peloquin Charles A , Rhodes Nathaniel J , Scheetz Marc H 
Published: July 2023

Abstract

Objective
To investigate and describe the variability in cefepime exposures among ‘real-world’, critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations.

Methods
A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2). Variability in the relationship between cefepime clearance and creatinine clearance (CrCL) was visualized, and a random, representative sample of 10 simulated patients was utilized to illustrate variability in cefepime exposures.

Results
A total of 75 adult medical ICU patients (52% female) and 98 serum cefepime samples were included in the study. Population parameter estimates for cefepime displayed a wide range of variation in Model 1 (CV: 45% to 95%), with low bias at the individual level at 0.226 mg/L but high bias in the population model 10.6 mg/L. Model 2 displayed similar fits, demonstrating that correcting for individual patient creatinine clearance slightly improves the bias of the population model (bias = 4.31 mg/L). Among 10 simulated patients that a clinician would deem similar from a dosing perspective (i.e. equivalent creatinine clearance), maximum concentrations after three simulated doses varied more than 8-fold from 41.2 to 339 mg/L at the 5th and 95th percentiles, and clearance profiles were highly different.

Conclusion
Creatinine clearance estimates alone are inadequate for predicting cefepime exposures. Wide variations in cefepime exposure exist among ICU patients, even for those with similar kidney function estimates. Current population adjustment schemes based solely on creatinine clearance will result in unintended high and low exposures leading to safety and efficacy concerns, respectively.
Augmented Renal Function in Burn Patients: Occurrence and Discordance With Commonly Used Methods to Assess Renal Function
Authors: Mueller Scott W , Blass Brittany , Molina Kyle C , Gibson Cameron , Krsak Martin , Kohler Amber D , Deeter Lyndsay , Stalilonis Jennifer , Wiktor Arek J 
Published: July 2023

Abstract
Augmented renal clearance (ARC) is defined by supraphysiologic renal function and is associated with drug failure due to subtherapeutic drug exposure. Burn patients are cited as being at high risk for ARC, yet rates of ARC have not been well described. This retrospective study described the prevalence and incidence of ARC, and compared 12-hour urine collection values (CrCl-12) vs. common estimates of renal function in assessed patients at an American Burn Association-verified burn center. All thermally injured burn patients with a CrCl-12 result were included. ARC was defined as a CrCl-12 &gt;130 ml/min. Cockcroft-Gault, modification of diet in renal disease (MDRD), and CKD-EPI-2021 estimates were calculated. Over 13 months, 163 CrCl-12 results were collected in 68 patients at a median of 9 days from admission with an average value of 160 ml/min. The median total body surface area (total body surface area [TBSA]%) was 17.25%. ARC prevalence was 70.6% with an incidence of 66.3% in all CrCl-12 assessments. Those with ARC were less likely to have heart failure, P = .007. Age, TBSA%, and trauma were not different between those with or without ARC. ARC incidences in those with TBSAs of ≥20%, &lt;20%, or &lt;10%, were 70.5%, 58.6%, and 76.7%, respectively. Agreement of Cockcroft-Gault, MDRD, and CKD-EPI-2021 to CrCl-12 was moderate to weak and frequently failed to identify ARC. ARC is common in burn patients, regardless of TBSA%. Widely accepted estimations of renal function may be incorrect resulting in under-dosing of medications. Additional research is required to identify burn patients at greatest risk for ARC and subsequent dosing strategies to maintain pharmacologic efficacy without unduetoxicity.