bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vote-processing rules for combining control recommendations from multiple models
Authors: Probert William J. M. , Nicol Sam , Ferrari Matthew J. , Li Shou-Li , Shea Katriona , Tildesley Michael J. , Runge Michael C. 
Published: August 2022

Mathematical modelling is used during disease outbreaks to compare control interventions. Using multiple models, the best method to combine model recommendations is unclear. Existing methods weight model projections, then rank control interventions using the combined projections, presuming model outputs are directly comparable. However, the way each model represents the epidemiological system will vary. We apply electoral vote-processing rules to combine model-generated rankings of interventions. Combining rankings of interventions, instead of combining model projections, avoids assuming that projections are comparable as all comparisons of projections are made within each model. We investigate four rules: First-past-the-post, Alternative Vote (AV), Coombs Method and Borda Count. We investigate rule sensitivity by including models that favour only one action or including those that rank interventions randomly. We investigate two case studies: the 2014 Ebola outbreak in West Africa (37 compartmental models) and a hypothetical foot-and-mouth disease outbreak in UK (four individual-based models). The Coombs Method was least susceptible to adding models that favoured a single action, Borda Count and AV were most susceptible to adding models that ranked interventions randomly. Each rule chose the same intervention as when ranking interventions by mean projections, suggesting that combining rankings provides similar recommendations with fewer assumptions about model comparability.This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
Technical challenges of modelling real-life epidemics and examples of overcoming these
Authors: Panovska-Griffiths J. , Waites W. , Ackland G. J. 
Published: August 2022

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of mathematical modelling in informing and advising policy decision-making. Effective practice of mathematical modelling has challenges. These can be around the technical modelling framework and how different techniques are combined, the appropriate use of mathematical formalisms or computational languages to accurately capture the intended mechanism or process being studied, in transparency and robustness of models and numerical code, in simulating the appropriate scenarios via explicitly identifying underlying assumptions about the process in nature and simplifying approximations to facilitate modelling, in correctly quantifying the uncertainty of the model parameters and projections, in taking into account the variable quality of data sources, and applying established software engineering practices to avoid duplication of effort and ensure reproducibility of numerical results. Via a collection of 16 technical papers, this special issue aims to address some of these challenges alongside showcasing the usefulness of modelling as applied in this pandemic.
This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
The cognitive basis of intracranial self-stimulation of midbrain dopamine neurons
Authors: Millard Samuel J. , Hoang Ivy B. , Greer Zara , O’Connor Shayna L. , Wassum Kate M. , James Morgan H. , Barker David J. , Sharpe Melissa J. 
Published: August 2022

AbstractRecently there has been a reckoning in the dopamine field. This has suggested that the dopamine prediction error may function as a teaching signal, without endowing preceding events with value. We studied the cognitive basis of intracranial self-stimulation (ICSS), a setting where dopamine appears to be valuable. Physiological frequencies seen during reinforcement learning did not support robust ICSS or promote behavior that would indicate the stimulation was represented as a meaningful reward in a specific or general sense. This was despite demonstrating that this same physiologically-relevant signal could function as a teaching signal. However, supraphysiological frequencies supported robust ICSS where the stimulation was represented as a specific sensory event, which acted as a goal to motivate behavior. This demonstrates that dopamine neurons only support ICSS at supraphysiological frequencies, and in a manner that does not reflect our subjective experience with endogenous firing of dopamine neurons during reinforcement learning.One sentence summaryDopamine neurons only support ICSS at supraphysiological frequencies and in a manner not reflecting dopamine’s role in learning.
Remote sensing-based forest modeling reveals positive effects of functional diversity on productivity at local spatial scale
Authors: Schneider Fabian D , Longo Marcos , Paul-Limoges Eugénie , Scholl Victoria M , Schmid Bernhard , Morsdorf Felix , Pavlick Ryan P , Schimel David S , Schaepman Michael E , Moorcroft Paul R 
Published: August 2022

SummaryForest biodiversity is critical for many ecosystem functions and services at plot scale, but it is uncertain how biodiversity influences ecosystem functioning across environmental gradients and contiguous larger areas. We used remote sensing and process-based terrestrial biosphere modeling to explore functional diversity–productivity relationships at multiple scales for a heterogeneous forest site in Switzerland.We ran the biosphere model with empirical data about forest structure and composition derived from ground-based surveys, airborne laser scanning and imaging spectroscopy for the years 2006–2015 at 10×10-m spatial resolution. We then related the model outputs forest productivity to functional diversity under observed and experimental model conditions.Functional diversity increased productivity significantly (p<0.001) across all simulations at 20×20-m to 30×30-m scale, but at 100×100-m scale positive relationships disappeared under homogeneous soil conditions.Whereas local functional diversity was an important driver of productivity, environmental context (especially soil depth, texture and water availability) underpinned the variation of productivity (and functional diversity) at larger spatial scales. Integration of remotely-sensed information on canopy composition and structure into terrestrial biosphere models helps fill the knowledge gap about how plant biodiversity affects carbon cycling and biosphere feedbacks onto climate over large contiguous areas.
The post-translational modification SUMO affects TDP-43 phase separation, compartmentalization, and aggregation in a zebrafish model
Authors: Maurel Cindy , Scherer Natalie M. , Hogan Alison , Vidal-Itriago Andres , Don Emily K. , Radford Rowan , Chapman Tyler , Cull Stephen , Vourc’h Patrick , Chung Roger , Lee Albert , Morsch Marco 
Published: August 2022

SUMMARYTDP-43 is a nuclear RNA-binding protein that can undergo liquid-liquid phase separation (LLPS) and forms pathological insoluble aggregates in frontotemporal dementia and amyotrophic lateral sclerosis (ALS). Perturbations of TDP-43 function are linked to mislocalization and neurodegeneration. By studying TDP-43 in vivo, we confirmed for the first time that TDP-43 undergoes LLPS and forms biomolecular condensates in spinal motor neurons (MNs). Importantly, we discovered that interfering with the K136 SUMOylation site of TDP-43 altered its phase separation behavior, reducing cytoplasmic mislocalization and aggregation. Introduction of the ALS-linked mutation G294V did not alter these LLPS characteristics, indicating that posttranslational modifications such as lysine-specific alterations can modulate TDP-43 pathogenesis through regulating phase separation. Altogether, our in vivo characterization of TDP-43 confirms the formation of dynamic nuclear TDP-43 condensates in zebrafish spinal neurons and establishes a critical platform to validate the molecular grammar of phase separation that underpins TDP-43 aggregation in ALS and other proteinopathies.
An evolutionarily conserved pacemaker role for HCN ion channels in smooth muscle
Authors: Yang Lei , Ricart Arbona Rodolfo J. , Smith Carl , Banks Kelly M. , Thomas V. Kaye , Palmer Lawrence , Evans Todd , Hurtado Romulo 
Published: August 2022

ABSTRACTAlthough HCN ion channels are well established to underlie cardiac pacemaker activity, their role in smooth muscle organs remains controversial. HCN expressing cells are localized to renal pelvic smooth muscle (RPSM) pacemaker tissues of the murine upper urinary tract and HCN channel conductance is required for peristalsis. To date, however, the Ih pacemaker current conducted by HCN channels has never been detected in these cells, raising questions on the identity of RPSM pacemakers. Indeed, the RPSM pacemaker mechanisms of the unique multicalyceal upper urinary tract exhibited by humans remains unknown. Here, we developed immunopanning purification protocols and demonstrate that 96% of isolated HCN+ cells exhibit Ih. Single molecule STORM to whole-tissue imaging showed HCN+ cells express single HCN channels on their plasma membrane and integrate into the muscular syncytium. By contrast, PDGFR-α+ cells exhibiting the morphology of ICC gut pacemakers were shown to be vascular mural cells. Translational studies in the homologous human and porcine multicalyceal upper urinary tracts showed that contractions and pacemaker depolarizations originate in proximal calyceal RPSM. Critically, HCN+ cells were shown to integrate into calyceal RPSM pacemaker tissues, and HCN channel block abolished electrical pacemaker activity and peristalsis of the multicalyceal upper urinary tract. Cumulatively, these studies demonstrate that HCN ion channels play a broad, evolutionarily conserved pacemaker role in both cardiac and smooth muscle organs and have implications for channelopathies as putative etiologies of smooth muscle disorders.
Morphological Differences in Isolated Brook Trout Populations in the Desolation Wilderness of the Sierra Nevada
Authors: Luby-Prikot Lukas , Bock Oliver , Martin Joseph 
Published: August 2022

abstractBrook trout (Salvelinus fontinalis) is an invasive species in the Desolation Wilderness of California. But it is unknown to what extent this species is evolving to adapt to isolated high altitude lakes. We quantified morphological differences between three brook trout populations in Desolation Wilderness that are in isolation and of common origin. We took standardized photos of fish, created geometric nets of each specimen using points located at known morphological features, and performed a Procrustes superimposition and principal component analysis to examine and cluster morphological variation between individuals. Together, our results show morphological differences between three Salvelinus fontinalis populations in independent environments. Our results suggest that invasive species introduced from one source can show physical variation generations after introduction, and thus deserve attention for adapting to and perhaps becoming an increasingly complex part of their ecosystem.
IgG derived dendritic cells can induce production of IL-17 by T cells in multiple sclerosis
Authors: Pournasrolla Nazanin , Ahmadi Ehsan , Siroos Seyedbahaadin , Nourizadeh Maryam , Harirchian Mohammad Hossein , Izad Maryam 
Published: August 2022

AbstractMultiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Myelin-autoreactive T cells have been implicated in the initiation of an inflammatory cascade. Dendritic cells (DC) are key modulators of this immuno-pathological cascade. The interaction between immune complexes (IC) and FcγRs results in activation of the immune system and induction of host inflammatory responses. Otherwise, monocytes differentiate into DCs after ligation of their FcγRs to IgG. We investigated circulating immune complexes levels (CIC) and differentiation of monocytes onto immature dendritic cell (iDC) via FcγR by Plate-bound human IgG in MS patients compared to healthy individuals. Our results showed that the concentration of CIC in patients with MS was significantly higher than healthy controls. Human IgG alone differentiate monocytes into DCs with a phenotype, including up-regulation of CD1b, CD86 and down-regulation of CD14. Also, the ability of LPS/MBP matured DCs in activation and cytokine production of autologous T cells was evaluated by MLR assay and ELISA. The level of IL-17 was significantly higher in MS patients when IgG derived DCs cocultured with T cells. Also, a correlation between IL-17 levels and circulating immune complexes level was observed in MS patients. Therefore, activation of FcγR on monocytes triggers differentiation into specialized iDC with the capacity to induce auto-reactive T cells that may contribute to the pathogenesis of MS.
Development and validation of glycolysis-cholesterol synthesis genes in lung adenocarcinoma
Authors: Qian Bao , Guo Yangjie , Jiang Jiuzhou 
Published: August 2022

AbstractBackgroundLung adenocarcinoma (LUAD) is the most common subtype of lung cancer which is one of the most dangerous malignant tumors affecting human health. The pathways of glycolysis and cholesterol production play an essential role in the metabolism of cancer. The mitochondrial pyruvate carrier (MPC) consists of MPC1 and MPC2, and impaired MPC function may induce a solid capacity for tumor proliferation, migration, and invasion.MethodsGenes positively and negatively correlated with MPC1/2 expression were identified by calculating Spearman correlation, then gene ontology (GO) analysis was conducted. Univariate cox regression, lasso regression, and multivariate cox regression analyses were performed to model predictive outcome events using differentially expressed genes. Thirteen prognostic genes were selected to construct a prognostic model.Results1359 and 2026 genes were positively and negatively associated with MPC1/2, respectively. The expression of MPC1 and MPC2 was significantly different. The prognostic model had great predictive performance in the test set.ConclusionsMPC1/2 genes were involved in a cellular network associated with the malignant development of LUAD. The prognostic model can provide an essential basis for physicians to predict the clinical outcomes of LUAD patients.
Minimal alveolar concentration of sevoflurane in combination with dexmedetomidine in patients with hysteroscopy: An up‐down sequential allocation study
Authors: Guo Yan‐Xia , Luo Kai , Jiang Ping‐Ping , Wang Dan , Wang Yi‐Zheng , Yang Xiao‐Lin 
Published: August 2022

AbstractBackgroundDexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end‐tidal concentration of sevoflurane when it is co‐administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery.MethodsOne‐hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, D1, D2, D3) and received a loading dose of dexmedetomidine (0, 0.6, 0.8 and 1.0 μg/kg) over 10 min before anaesthesia induction, respectively. Anaesthesia was induced in each patient with 5% sevoflurane in 100% oxygen via a facemask. A laryngeal mask (LMA) was inserted when the patient had lost consciousness and the BIS value decreased below 40. The response to cervical dilatation stimulus (movement vs non‐movement) by the insert of hysteroscope was recorded. The MAC of sevoflurane was measured by up and down sequential method of Dixon and Mood and centred isotonic regression analysis.ResultsThe calculated MAC of sevoflurane using up‐and‐down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, D1, D2 and D3, respectively.ConclusionsThe administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 μg/kg.
Inductive research in last‐mile delivery routing: Introducing the Re‐Gifting heuristic
Authors: Rose William J. , Bell John E. , Griffis Stanley E. 
Published: August 2022

AbstractThe last‐mile problem presents a daunting challenge for many logistics service providers, especially some 7000 small, localized operations for whom the cost of complex software solutions is often prohibitive. As a result, last‐mile dispatchers rely on simple heuristics to ensure adequate customer service at an acceptable cost. This research effort extends prior qualitative work by developing and testing a simple vehicle routing heuristic, based on behaviors observed in practice, that prioritizes customer service over cost against other simple vehicle routing heuristics across a variety of environments using simulation. The results support the inclusion of a customer service focus in vehicle routing and the addition of such heuristics to existing algorithm portfolios, specifically in urban areas with well‐developed highway systems.
Case‐only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD‐2353F22.1 implying the importance of periodontal wound healing for disease aetiology
Authors: Müller Ricarda , Freitag‐Wolf Sandra , Weiner January , Chopra Avneesh , Top Tugba , Dommisch Henrik , Schaefer Arne S. 
Published: August 2022

AbstractAimThe basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles.Materials and MethodsWe used the case‐only design and investigated single‐nucleotide polymorphism (SNPs) that showed associations in our recent genome‐wide association study (GWAS) and GWAS meta‐analysis with p < 5 × 10−6. CRISPR‐dCas9 gene activation followed by RNA‐sequencing and gene‐set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele‐specific effects on transcription factor binding.ResultsSNPs at the genes sialic acid binding Ig‐like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non‐coding RNA (lncRNA) CTD‐2353F22. Associated chromatin cis‐activated CTD‐2353F22.1 6.5‐fold (p = .003), indicating CTD‐2353F22.1 as target gene of this interaction. CTD‐2353F22.1 regulated GADD45A (padj < 4.9 × 10−11, log2 fold change (FC) = −0.55), THBS1, SERPINE1 and Tissue Factor F3 (padj < 5 × 10−7, log2 FC ≥ −0.35) and the gene set “angiogenesis” (area under the curve = 0.71, padj = 8.2 × 10−5). rs1122900 effect C‐allele decreased reporter gene activity (5.5‐fold, p = .0003) and PRDM14 binding (76%).ConclusionsCTD‐2353F22.1 mediates interaction of SIGLEC5 and PLG, together with genes that function in periodontal wound healing.
(Un)conditional consumer protections in high‐cost lending regulation: Impacts on local lending geographies
Authors: Bea Megan Doherty , Bley K. 
Published: August 2022

AbstractRegulation of small‐dollar lending in the United States is heterogeneous, leaving open the question about what policy designs work best for protecting consumers. We compare the effectiveness of regulations that include a consumer eligibility component and regulations that apply to all consumers, centering our analyses on communities with disproportionate exposure to high‐interest lending storefronts. Specifically, we compare how the Military Lending Act (MLA), which provided military‐specific protections, and statewide policies affected high‐cost lender activity in military communities in three states. We find that statewide regulations were effective in reducing the number of high‐cost lenders within local communities across states, including military communities, while the MLA had no impact on the number of lenders around military bases. Our findings have implications for how to regulate small‐dollar lending and protect consumers at increased risk of exposure to high‐cost lending, with specific attention to product alternatives and access to low‐cost financial services.
MRI of a middle ear cholesteatoma in a cat
Authors: Herberger Arielle , Hammond James , Miller Andrew , Olson Benjamin 
Published: August 2022

AbstractA 9‐year‐old Maine coon cat presented with right‐sided Horner and facial nerve paralysis. Magnetic resonance imaging (MRI) showed a heterogeneously contrast‐enhancing mass occupying the right dorsolateral compartment of the tympanic cavity and extending into the ventromedial compartment, which was expanded and fluid filled. A ventral bulla osteotomy was performed to debulk the soft tissue mass. Histopathology revealed a cholesteatoma. The cat showed slow improvement of clinical signs and was euthanized eleven months postoperatively for unrelated causes. The MRI characteristics of middle ear cholesteatoma in the present case varied from those described in humans and dogs.
Does the Use of Gelled Platelet-Rich Plasma during Fixation of Subacute Proximal Pole Scaphoid Fractures Help? – A Single Centre Experience
Authors: DE VITIS Rocco , PASSIATORE Marco , PERNA Andrea , CILLI Vitale , PONZO Ida , TACCARDO Giuseppe 
Published: August 2022

Background: Subacute proximal pole scaphoid fractures (1 month to 6 months) have a higher risk of non-union. The aim of the present retrospective analysis is to evaluate the efficacy of gelled platelet-rich plasma (GPRP) as additional treatment to antegrade headless screw fixation of proximal pole scaphoid fractures.Methods: Forty-one patients were divided into two groups based on surgical treatment received: screw fixation alone (group A) and screw fixation and GPRP application at the fracture site (group B). A short cast was maintained for 4 weeks after surgery. Outcome measures included time to union, need for additional procedures, time to return to work, disabilities of the arm, shoulder, and hand (DASH) questionnaire, Michigan Hand Questionnaire (MHQ) and Mayo wrist score (MWS).Time to union was determined by monthly radiographs and confirmed by a computerized tomographic (CT) scan done at 4 months.Results: Union was achieved in 85.7% of patients in group A and in 100% of patients in group B. Patients in group B showed a faster time to healing (2.3 ± 0.4 months vs 3.1 ± 0.7 months, p = 0.0001) and earlier return to work (10.4 ± 2.2 vs 15.1 ± 2.9, p = 0.0001). There were no significant differences in patient-rated outcomes scores between the two groups at final follow-up.Conclusions: Internal fixation alone is effective in treating subacute proximal pole scaphoid fractures. GPRP application improves bone healing and functional recovery.Level of Evidence: Level III (Therapeutic)