bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity and uncertainty in the Lee-Carter mortality model
Authors: Zuo Wenyun , Damle Anil , Tuljapurkar Shripad 
Published: February 2023

AbstractBACKGROUNDThe Lee-Carter model (LC) is widely used in research and applications for forecasting age specific mortality, and typically performs well regardless of the uncertainty and often the limited quality of mortality data.OBJECTIVEWhy dose LC perform well regardless of the uncertainty and the limited data quality?METHODSWe analyze the robustness of LC using sensitivity analyses based on matrix perturbation theory, coupled with simulations that examine the effect of unavoidable randomness in mortality data. The combined effects of sensitivity and uncertainty determine the robustness of LC.RESULTSWe find that the sensitivity of LC and the uncertainty of death rates both have nonuniform patterns across ages and years. The sensitivities are small in general, with largest sensitivities at both ends of the period. The uncertainty of death rates are high in young ages (5–19) and old ages (90+) with rising in young ages but dropping in old ages.CONCLUSIONSThe sensitivity and uncertainty analyses indicate that the randomness hardly interrupts the prediction of LC. The divergence of long term prediction in LC is likely due to structural changes in the age-year specific mortality, which is associated with the development of public health policy, medical innovations and chronic disasters.CONTRIBUTIONOur results reveal that LC is robust against random perturbation and sudden short term changes.
Linking Muscle Mechanics to the Metabolic Cost of Human Hopping
Authors: Jessup Luke N. , Kelly Luke A. , Cresswell Andrew G. , Lichtwark Glen A. 
Published: February 2023

AbstractMany models have been developed to predict metabolic energy expenditure based on biomechanical proxies of muscle function. However, current models may only perform well for select forms of locomotion, not only because the models are rarely rigorously tested across subtle and broad changes in locomotor task, but also because previous research has not adequately characterised different forms of locomotion to account for the potential variability in muscle function and thus metabolic energy expenditure. To help to address the latter point, the present study imposed frequency and height constraints to hopping and quantified gross metabolic power as well as the activation requirements of medial gastrocnemius, lateral gastrocnemius (GL), soleus (SOL), tibialis anterior, vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF), and the work requirements GL, SOL and VL. Gross metabolic power increased with a decrease in hop frequency and increase in hop height. There was no hop frequency or hop height effect on the mean electromyography (EMG) of ankle musculature, however, the mean EMG of VL and RF increased with a decrease in hop frequency and that of BF increased with an increase in hop height. With a reduction in hop frequency, GL, SOL and VL fascicle shortening, fascicle shortening velocity and fascicle to MTU shortening ratio increased, whereas with an increase in hop height, only SOL fascicle shortening velocity increased. Therefore, within the constraints that we imposed, decreases in hop frequency and increases in hop height resulted in increases in metabolic power that could be explained by increases in the activation requirements of knee musculature and/or increases in the work requirements of both knee and ankle musculature.Summary StatementThis study directly measures activation and work requirements of lower-limb musculature and whole-body metabolic energy requirements across a wide variety of human hopping conditions, helping to guide biomechanical models of energy expenditure.
Patient Registry of Upper Limb Outcomes (PRULO) A Protocol for an orthopaedic clinical quality registry to monitor treatment outcomes
Authors: Scholes Corey , Eng Kevin , Harrison-Brown Meredith , Ebrahimi Milad , Brown Graeme , Gill Stephen , Page Richard 
Published: February 2023

ABSTRACTIntroductionRegistries have been widely utilised to track clinical results in observational cohorts for quality improvement. They have been very successful in orthopaedics, particularly in the context of arthroplasties where they have guided and optimised implant choice, patient safety and identified underperforming implants. However, equivalent systems to monitor outcomes in soft-tissue disorders are lacking. This manuscript describes the protocols around design, ethics and implementation of a regional registry focusing on upper limb soft tissue orthopaedic conditions.Methods and analysisPRULO (Patient Registry of Upper Limb pathology Outcomes) is a multi-cohort, prospective observational, clinical quality registry collating clinical data and patient-reported outcomes for patients presenting to a specialist orthopaedic clinic with upper limb pathology. PRULO is currently a single-centre study involving three clinician investigators, which aims to determine what patient characteristics, pathology factors and treatment strategies are associated with treatment success within 2 years of surgical or non-surgical treatment of targeted pathology. PRULO captures patient reported outcomes (VAS, EQ5D-5L, QuickDASH, MODEMS-Expectations and Satisfaction, WORC, WOSI), clinical and radiological data. Data points are recorded at initial practice registration, after initial consultation, intraoperatively, as well as 3, 6, 12 and 24 months. Inclusion criteria are patients aged 16 and above offered treatment by speciality trained surgeons, for upper limb orthopaedic pathology. Patient subgroups (cohorts) will include shoulder conditions: conditions affecting predominantly the rotator cuff (tear, tendinopathy), conditions associated with glenohumeral instability, as well as all other conditions presenting in the shoulder elbow, hand and wrist, according to the surgeon-generated diagnosis.Ethics and disseminationEthical approval was obtained by the Barwon Health Research Ethics Committee (approval number 19/70).Trial RegistrationThe project was added as a trial to the Australia and New Zealand Clinical Trials Registry (ACTRN12619000770167) 23-May-2019.
Nearly half of adults with symptoms of sexually transmitted infections (STIs) did not seek clinical care: A population-based study of treatment-seeking behavior among adults in Rakai, Uganda
Authors: Ogale Yasmin P. , Kennedy Caitlin E. , Nalugoda Fred , Mpagazi Josephine , Jackson Jade C. , Galiwango Ronald , Ssekubugu Robert , Kigozi Godfrey , Denison Julie A. , Gaydos Charlotte A. , Kagaayi Joseph , Grabowski M. Kathryn 
Published: February 2023

AbstractUnderstanding treatment-seeking behavior is critical to the treatment and control of sexually transmitted infections (STIs), yet current data on STI treatment-seeking in low-resource settings is scarce. This study aims to describe STI treatment-seeking behavior and identify factors associated with seeking treatment at a clinic among adults with STI-related symptoms in rural Uganda. The STI prevalence study (STIPS) conducted a population-based survey and STI testing among all consenting adults aged 18–49 in two communities in rural south-central Uganda. Of 1,825 participants, 962 individuals self-reported STI symptoms in the past six months; we present descriptive data on treatment-seeking and STI prevalence among these individuals. We used multivariable Poisson regressions with robust variance to determine the sociodemographic and symptom-related factors independently associated with seeking STI treatment at a clinic and assessed the association with previous clinic treatment-seeking and current STI diagnosis. Forty-three percent of adults who reported STI-related symptoms in the past six months said they did not seek any treatment. Among those who did, 58% sought treatment at a private clinic, 28% at a government clinic, 9% at a pharmacy/drug store, 3% at a traditional healer, 2% at a market/shop, and 5% at another location. Among both men and women, having multiple STI related symptoms was positively associated with clinic treatment seeking (men=PRR: 1.73, 95%CI: 1.36-2.21; women=PR: 1.41, 95%CI: 1.12-1.78). Approximately one-third of men and women who reported previously seeking clinic treatment for their symptoms were diagnosed with a curable STI at the time of the survey. In this setting, nearly half of adults with STI-related symptoms are not seeking clinical care and many who report having sought treatment recent STI symptoms have curable STIs. Future studies should explore barriers to care-seeking and strategies to improve STI services.
Systematic identification of structure-specific protein–protein interactions
Authors: Holfeld Aleš , Schuster Dina , Sesterhenn Fabian , Stalder Patrick , Haenseler Walther , Barrio-Hernandez Inigo , Ghosh Dhiman , Vowles Jane , Cowley Sally A. , Nagel Luise , Khanppnavar Basavraj , Beltrao Pedro , Korkhov Volodymyr M. , Riek Roland , Souza Natalie de , Picotti Paola 
Published: February 2023

AbstractProtein–protein interactions (PPIs) mediate numerous essential functions and regulatory events in living organisms. The physical interactome of a protein can be abnormally altered in response to external and internal cues, thus modulating cell physiology and contributing to human disease. In particular, neurodegenerative diseases due to the accumulation of aberrantly folded and aggregated proteins may lead to alterations in protein interactomes. Identifying changes in the interactomes of normal and disease states of proteins could help to understand molecular disease mechanisms, but current interactomics methods are limited in the ability to pinpoint structure-specific PPIs and their interaction interfaces on a proteome-wide scale. Here, we adapted limited proteolysis–mass spectrometry (LiP–MS) to systematically identify putative structure-specific PPIs by probing protein structural alterations within cellular extracts upon treatment with specific structural states of a given protein. We demonstrate the feasibility of our method to detect well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and show that it pinpoints PPI interfaces. We then applied the LiP–MS approach to study the structure-specific interactors of the Parkinson’s disease hallmark protein alpha-synuclein (aSyn). We identified several previously known interactors of both aSyn monomer and amyloid fibrils and provide a resource of novel putative structure-specific interactors for further studies. This approach is applicable to identify structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound structural states of proteins.
Isolating objective and subjective filling-in using the Drift Diffusion Model
Authors: Dekel Ron , Sagi Dov , Zomet Ativ , Levi Dennis M. , Polat Uri 
Published: February 2023

AbstractSpatial context is known to influence the behavioral sensitivity (d’) and the decision criterion (c) for detection of low-contrast targets. Of interest here is the effect on the decision criterion. Polat and Sagi (2007) demonstrated that for a Gabor target positioned between two similar co-aligned high contrast flankers, observers’ reports of seeing the target (Hit and False-Alarm) decreased with increasing target-flankers distance. This effect was more pronounced when distance was randomized within testing blocks compared to when it was fixed. According to Signal-Detection-Theory (SDT), the latter result suggests that the decision-criterion is adjusted to a specific, distance-dependent combination of signal (S) and Noise (N) when the S and N statistics are fixed, but not when they vary across trials. However, SDT cannot differentiate between changes in the decision-bias (criterion-shift) and changes introduced by variations in S and N (signal-shift). To circumvent this limitation of SDT, we analyze reaction-time data (RT) within the framework of the Drift-Diffusion-Model (DDM). We performed an RT analysis of target-flanker interactions using data from Polat & Sagi (2007) and Zomet et al. (2008; 2016). The analysis revealed a stronger dependence on flankers for faster RTs and a weaker dependence for slower RTs. The results are explained by DDM, where an evidence accumulation process depends on the flankers via a change in the rate of the evidence (signal-shift), and on observers’ prior via a change in the starting point (criterion-shift), leading to RT-independent and RT-dependent effects, respectively. The RT-independent distance-dependent response-bias is attributed to the observers’ inability to learn multiple internal distributions required to accommodate the distance-dependent effects of the flankers on both the Signal and Noise.
Lung viral infection modelling in a bioengineered whole-organ
Authors: Tommasini Fabio , Benoist Thomas , Shibuya Soichi , Woodall Maximillian N.J. , Naldi Eleonora , Orr Jessica C. , Giobbe Giovanni Giuseppe , Maughan Elizabeth F. , Hynds Robert E. , Gjinovci Asllan , Hutchinson J. Ciaran , Arthurs Owen J. , Janes Sam M. , Elvassore Nicola , Smith Claire M. , Michielin Federica , Pellegata Alessandro Filippo , De Coppi Paolo 
Published: February 2023

AbstractLung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection with the engineered lung by infecting primary human airway epithelial cells. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral Remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.
Risk assessment during nest defense against three simulated predators by female northern house wrens (Troglodytes aedon)
Authors: Eggleston Ross C. , Fornara Josephina H. , Davis Kyle M. , Dong Jess , Reichard Dustin G. 
Published: February 2023

AbstractOffspring predation is one of the greatest obstacles to an organism’s reproductive success, but parents vary in the strength of their response to potential predators. One explanation for this variable investment is that defending current offspring has the potential to lower future reproductive success if the predator is also capable of injuring or killing the parent. Northern house wrens (Troglodytes aedon) are cavity-nesting songbirds that defend against multiple species of nest predators including small mammals, birds of prey, and snakes. Here, we used three different predator decoys: two nest predators - an eastern chipmunk (Tamias striatus) and an eastern ratsnake (Pantherophis alleghaniensis) - as well as a predator of both offspring and adults - a juvenile Cooper’s hawk (Accipiter cooperi) - to elicit nest defense and test whether females use risk assessment to modulate their antipredator behavior. We found that antipredator behaviors were not significantly different between the two nest predators, which posed a high risk to the nestlings, but lower risk to the parents as neither species frequently captures adult wrens outside the nest box. However, female wrens never dove at or attacked the Cooper’s hawk while they frequently attacked both the snake and chipmunk decoys. Neighboring house wrens from adjacent territories were also less likely to respond to the hawk, but more heterospecifics mobbed the hawk than the snake decoy. Collectively, these results show that risk assessment and the strength of the antipredator response varies substantially both within and among species. Female house wrens exhibit plasticity in their nest defense behavior, and they respond to different types of predators in a way that could maximize lifetime fitness while risking the loss of their current offspring.
Nociceptor neuroimmune interactomes reveal cell type- and injury-specific inflammatory pain pathways
Authors: Jain Aakanksha , Gyori Benjamin M. , Hakim Sara , Bunga Samuel , Taub Daniel G , Ruiz-Cantero Mari Carmen , Tong-Li Candace , Andrews Nicholas , Sorger Peter K , Woolf Clifford J 
Published: February 2023

AbstractInflammatory pain associated with tissue injury and infections, results from the heightened sensitivity of the peripheral terminals of nociceptor sensory neurons in response to exposure to inflammatory mediators. Targeting immune-derived inflammatory ligands, like prostaglandin E2, has been effective in alleviating inflammatory pain. However, the diversity of immune cells and the vast array of ligands they produce make it challenging to systematically map all neuroimmune pathways that contribute to inflammatory pain. Here, we constructed a comprehensive and updatable database of receptor-ligand pairs and complemented it with single-cell transcriptomics of immune cells and sensory neurons in three distinct inflammatory pain conditions, to generate injury-specific neuroimmune interactomes. We identified cell-type-specific neuroimmune axes that are common, as well as unique, to different injury types. This approach successfully predicts neuroimmune pathways with established roles in inflammatory pain as well as ones not previously described. We found that thrombospondin-1 produced by myeloid cells in all three conditions, is a negative regulator of nociceptor sensitization, revealing a non-canonical role of immune ligands as an endogenous reducer of peripheral sensitization. This computational platform lays the groundwork to identify novel mechanisms of immune-mediated peripheral sensitization and the specific disease contexts in which they act.
crossing3dforest: an R package for evaluating empty space structure in forest ecosystems
Authors: Puletti Nicola , Castronuovo Rossella , Ferrara Carlotta 
Published: February 2023

AbstractTraditionally, forest structure is mostly described by vegetative elements; however, the complementary empty space also contributes to the forest spatial structure.We developed an R package (crossing3dforest) to support the entire processing of Terrestrial Laser Scanning point clouds to quantify the size, shape, and connectivity of empty spaces within the mid and low strata of forest stands, using an approach based on the percolation theory. The package functions, which are designed for step-by-step single stand analysis, can be executed sequentially in a pipeline.A case study is presented to demonstrate thecrossing3dforestpotentials for characterising the forest empty space architecture. TLS point clouds collected in ten different pure beech (Fagus sylvatica L.) stands, representative of five distinct forest management regimes, were analysed and characterised.The adopted empty space approach can be integrated into forest structural analysis to identify animal-habitat associations and establish appropriate habitat structure for wildlife management.Graphical abstract
Stroke induces early recurrent vascular events by inflammasome-dependent atherosclerotic plaque rupture
Authors: Cao Jiayu , Roth Stefan , Zhang Sijia , Kopczak Anna , Georgakis Marios K. , Li Xinghai , Dutsch Alexander , Liman Thomas G , Endres Matthias , Brough David , Green Jack P. , Wernsdorf Saskia , Fürle Christina , Carofiglio Olga , Zhu Jie , Asare Yaw ,   DEMDAS Study Group, Dichgans Martin , Sager Hendrik B. , Große Gerrit M. , Liesz Arthur 
Published: February 2023

SummaryThe risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies. Risk is particularly high in patients with atherosclerosis, with more than 10% of patients experiencing early recurrent events. However, despite the enormous medical burden of this clinical phenomenon, the underlying mechanisms leading to increased vascular risk and recurrent stroke are largely unknown. Here, using a novel mouse model of stroke-induced recurrent ischemia, we show that stroke leads to activation of the AIM2 inflammasome in vulnerable atherosclerotic plaques via an increase of circulating cell-free DNA from the ischemic tissue. Enhanced plaque inflammation post-stroke results in plaque destabilization and atherothrombosis, finally leading to arterio-arterial embolism and recurrent stroke within days after the index stroke. We confirm key steps of plaque destabilization also after experimental myocardial infarction and in carotid artery plaque samples from patients with acute stroke. Neutralization of cell-free DNA by DNase treatment or inhibition of inflammasome activation reduced the rate of stroke recurrence after experimental stroke. Our findings present an explanation for the high recurrence rate after incident ischemic events in atherosclerotic patients. The detailed mechanisms uncovered here provide so far clinically uncharted therapeutic targets for which we show high efficacy to prevent recurrent events. Targeting DNA-mediated inflammasome activation after remote tissue injury represents a promising avenue for further clinical development in the prevention of early recurrent events.
Aromatic amino acids in the finger domain of the FMRFamide-gated Na+channel are involved in the FMRFamide recognition and the activation
Authors: Furukawa Yasuo , Tagashira Iori 
Published: February 2023

AbstractFMRFamide-gated Na+channel (FaNaC) is a member of the DEG/ENaC family and activated by a neuropeptide, FMRFamide. Structural information about the FMRFamide-dependent gating is, however, still elusive. Because two phenylalanines of FMRFamide are essential for the activation of FaNaC, we hypothesized that aromatic-aromatic interaction between FaNaC and FMRFamide is critical for FMRFamide recognition and/or the activation gating. Here, we focused on eight conserved aromatic residues in the finger domain of FaNaCs and tested our hypothesis by mutagenic analysis andin silicodocking simulations The mutation of conserved aromatic residues in the finger domain reduced the FMRFamide potency, the extent of which were dependent on the mutated position, suggesting that the conserved aromatic residues are more or less involved in the FMRFamide-dependent activation. The kinetics of the FMRFamide-gated currents were also modified substantially in some mutants. The docking simulations revealed the aromatic-aromatic interaction between some conserved aromatic residues in FaNaC and FMRFamide. Collectively, our results suggest that the conserved aromatic residues in the finger domain of FaNaC are important determinants of the ligand recognition and/or the activation gating in FaNaC.